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2,400 | 23,444,466 | All studies showed a significant bilateral benefit in localization over unilateral cochlear implantation .
Bilateral cochlear implants were beneficial for speech perception in noise under certain conditions and several self-reported measures .
Most speech perception in quiet outcomes did not show a bilateral benefit .
The current review provides additional evidence in favor of bilateral cochlear implantation , even in complex listening situations | OBJECTIVE Assessment of the clinical effectiveness of bilateral cochlear implantation compared with unilateral cochlear implantation or bimodal stimulation , in adults with severe-to-profound hearing loss .
In 2007 , the National Institute for Health and Clinical Excellence ( NICE ) in the U.K. conducted a systematic review on cochlear implantation . | Objective : To determine the efficacy of “ simultaneous ” bilateral cochlear implantation ( both implants placed during a single surgical procedure ) by comparing bilateral and unilateral implant use in a large number of adult subjects tested at multiple sites . Design : Prospect i ve study of 37 adults with postlinguistic onset of bilateral , severe to profound sensorineural hearing loss . Performance with the bilateral cochlear implants , using the same speech processor type and speech processing strategy , was compared with performance using the left implant alone and the right implant alone . Speech underst and ing in quiet ( CNCs and HINT sentences ) and in noise ( BKB-SIN Test ) were evaluated at several postactivation time intervals , with speech presented at 0 ° azimuth , and noise at either 0 ° , 90 ° right , or 90 ° left in the horizontal plane . APHAB question naire data were collected after each subject underwent a 3-wk “ bilateral deprivation ” period , during which they wore only the speech processor that produced the best score during unilateral testing , and also after a period of listening again with the bilateral implants . Results : By 6-mo postactivation , a significant advantage for speech underst and ing in quiet was found in the bilateral listening mode compared with either unilateral listening modes . For speech underst and ing in noise , the largest and most robust bilateral benefit was when the subject was able to take advantage of the head shadow effect ; i.e. , results were significantly better for bilateral listening compared with the unilateral condition when the ear opposite to the side of the noise was added to create the bilateral condition . This bilateral benefit was seen on at least one of the two unilateral ear comparisons for nearly all ( 32/34 ) subjects . Bilateral benefit was also found for a few subjects in spatial configurations that evaluated binaural redundancy and binaural squelch effects . A subgroup of subjects who had asymmetrical unilateral implant performances were , overall , similar in performance to subjects with symmetrical hearing . The question naire data indicated that bilateral users perceive their own performance to be better with bilateral cochlear implants than when using a single device . Conclusions : Findings with a large patient group are in agreement with previous reports on smaller groups , showing that , overall , bilateral implantation offers the majority of patients advantages when listening in simulated adverse conditions Objective : Compare results of cochlear implantation in younger and older adults in the domains of disability and h and icap , as well as in tests of word recognition and localization , across unilateral implant ( CI ) , bilateral ( CI + CI ) , and CI with an acoustic hearing aid in the nonimplanted ear ( CI + HA ) . Design : Three parts : retrospective ( postimplant only ) analysis ; prospect i ve ( preimplant versus postimplant ) ; correlation between age and benefit from CI versus CI + CI . Two age groups , older and younger than 60 years , for the first 2 analyses ; age is a continuous variable for the third analysis . Setting : Tertiary referral hospital clinic . Patients : Postlingually severely-to-profoundly hearing-impaired adults : Totals of 68 CI , 36 CI + CI , and 38 CI + HA in the retrospective part of the study ; totals of 30 CI , 18 CI + CI , and 16 CI + HA in the prospect i ve parts . Numbers vary from these totals on individual measures . Interventions : Patients receive either 1 or 2 cochlear implants ; some with 1 CI opt to retain a hearing aid in the nonimplanted ear . Outcome Measures : Principal measures : Hearing H and icap Inventory for the Elderly , Hearing H and icap Question naire , Speech , Spatial and Qualities of Hearing Scale , word recognition test , and soundfield localization test . The study is exploratory , but proceeding from a null hypothesis of no expected contrast as a function of patient age . Results : All patient groups show significant benefit after implantation . No significant age-related differences are observed in patients with unilateral implant , nor in CI + HA group . In the CI + CI group , the younger cohort showed very substantial increases in both performance and self-rated abilities ; the older cohort provides more mixed outcomes . Conclusion : Results for the CI group confirm and extend earlier research . The result for the younger group of CI + CI patients demonstrates the consistent incremental benefit obtained from a bilateral procedure . The mixed outcome observed in the older CI + CI group might be due to individual differences in interaction between effects of aging and the ability to integrate binaural cues Adult users of unilateral Nucleus CI24 cochlear implants with the SPEAK processing strategy were r and omised either to receive a second identical implant in the contralateral ear immediately , or to wait 12 months while they acted as controls for late-emerging benefits of the first implant . Twenty four subjects , twelve from each group , completed the study . Receipt of a second implant led to improvements in self-reported abilities in spatial hearing , quality of hearing , and hearing for speech , but to generally non-significant changes in measures of quality of life . Multivariate analyses showed that positive changes in quality of life were associated with improvements in hearing , but were offset by negative changes associated with worsening tinnitus . Even in a best-case scenario , in which no worsening of tinnitus was assumed to occur , the gain in quality of life was too small to achieve an acceptable cost-effectiveness ratio . The most promising strategies for improving the cost-effectiveness of bilateral implantation are to increase effectiveness through enhanced signal processing in binaural processors , and to reduce the cost of implant hardware Objective : Preliminary studies show that bilateral cochlear implantation improves speech-recognition ability in many subjects ; however , the magnitude of this improvement has been variable . The objective of our research was to explore means to better differentiate the binaural benefit that many patients who receive bilateral cochlear implants ( CIs ) describe . Hypothesis : Binaural improvements in speech-perception performance will be consistently evident across patients when they are tested in more challenging listening situations . Design : This was a prospect i ve clinical study . Speech-perception performance was compared between the unilateral and bilateral cochlear implant conditions . Because the purpose was to investigate testing parameters that would demonstrate binaural benefit , word- and sentence-recognition tests were administered under several stimulation conditions : with and without noise and at three presentation levels . In addition , all subjects completed the Abbreviated Profile of Hearing Aid Benefit as a measure of subjective benefit . Subjects were adult cochlear implant recipients . Three device manufacturers were represented ( Advanced Bionics Corporation , Cochlear Americas , and the Med-El Corporation ) ; three patients received simultaneous implantation , and the other four patients received sequential CIs . The setting was a comprehensive cochlear implant program/tertiary referral center . The main outcomes measures were speech-recognition scores in percent correct , mean score difference for unilateral versus bilateral conditions , and subjective benefit scores . Results : The most significant improvements in binaural cochlear implant use were found when subjects were tested with sentence material presented at 60 dB SPL with a + 8 dB signal-to-noise ratio . Six of seven subjects showed significant binaural improvement , with a mean improvement score of 12.43 % ( SD = 5.32 ) . All subjects preferred the binaural listening condition . Measured improvements in quality of life were seen . Conclusions : Preliminary study findings suggest that significant cochlear implant binaural benefit in speech perception may be observed when testing in more difficult listening situations ( i.e. , lower presentation levels and in noise ) . According to the outcome of our study , testing the binaural benefit of CIs requires consideration of suitable test material s and stimulation parameters Objective : The purpose of this 4-year longitudinal study was to assess the stability of the binaural benefits of head shadow , summation , and squelch for bilateral cochlear implant recipients and to quantify these benefits for the underst and ing of speech in noise . Design : This is a prospect i ve study of 9 patients who received simultaneous bilateral insertion of MED-EL COMBI + 40 cochlear implants in a single-stage operation at the University of North Carolina , Chapel Hill , NC . Each patient had postlingual deafness of short duration before insertion of the device . Each year , the patients were tested for word recognition using consonant-nucleus-consonant words in quiet and speech perception in noise using City University of New York sentences . These tests were administered using direct audio input to the implants . Head-related transfer functions were used to simulate speech in noise testing in a spatial environment . Speech was always presented at midline ( 0 ° ) , and the noise masker was presented at either side or midline ( −90 , 0 , + 90 degrees ) . Results : The binaural benefits of head shadow and summation effects developed early in the postoperative period and remained stable throughout the follow-up period . Squelch developed more slowly and was first demonstrated at 12 months after implantation but continued to increase beyond the first year of follow-up . Conclusion : Benefits of head shadow and summation emerge early and remain stable . However , squelch has the most protracted period of development , with increasing benefit after a year or more of implant experience . These data support the idea that binaural integration continues several years after insertion of bilateral cochlear implant devices The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s Objective : To evaluate the benefits of bilateral electrical stimulation for hearing-impaired adult subjects using the Nucleus 24 cochlear implant in a multicenter study , and to compare and quantify performance on speech perception measures in quiet and in noise and localization ability for unilateral and bilateral cochlear implant use . Design : Repeated single subject measures were carried out for each subject , with each subject serving as their own control . Assessment of unilateral and bilateral listening conditions for performance on tests of speech comprehension and sound localization were performed . Speech comprehension measures were performed in quiet at 0 degree azimuth and in the presence of background noise simultaneously presented from the same speaker and spatially separated by 90 degrees , at S+45 ° N45 ° and at S−45 ° N+45 ° . Test material s included Freiburger monosyllabic words , Oldenburger sentences , and the Hochmair-Schulz-Moser sentences . Tests of localization were performed in the horizontal plane with 12 speaker locations 30 degrees apart using a shortened sentence stimulus from the Hochmair-Schulz-Moser sentences at two possible presentation levels of 55 and 70 dB sound pressure level for assessment of directionality . The binaural advantage provided by bilateral stimulation was calculated with respect to each ear separately , classified as either the better or poorer performing ear for each speech material in quiet and in noise test conditions . For localization of sound , the binaural advantage was compared with left and right ears separately . Paired comparisons for performance data in all conditions were carried out by considering measurements for each subject in different conditions as paired observations and applying the Student ’s t test to determine the statistical difference between the data sets . Setting : Tertiary referral centers with a cochlear implant program . Patients : Thirty-seven profoundly hearing-impaired adults were enrolled in the study , 22 simultaneously and 15 sequentially bilaterally implanted . All patients received the Nucleus 24 cochlear implant and used the Nucleus SPrint or ESPrit 3 G speech processor , with the vast majority using the ACE speech coding strategy . Results : For spatially separated speech in noise conditions , an interaural performance advantage for the ear closest to the speech source ( i.e. , with a superior signal to noise ratio ) compared with that for the ear closest to the noise source ( i.e. , with an inferior signal to noise ratio ) is consistently demonstrated regardless of whether it is the better or poorer performing ear closest to the speech signal . This is referred to as a significant binaural head-shadow benefit , result ing in a mean improvement between −10 dB and −11.4 dB in the critical signal to noise ratio required for 50 % speech comprehension for the Olden-burger sentences and a mean improvement in the maximum score of 42 % to 55 % for the ear closest to the speech signal over the ear farthest away for the Hochmair-Schulz-Moser sentences . Bilateral stimulation is always observed to provide a performance advantage over the unilateral listening condition for either ear when ipsilateral to the noise source . In addition , as demonstrated by approximately half the subjects tested in noise with the Hochmair-Schulz-Moser sentences , a performance advantage of bilateral stimulation may be observed over the better ear alone when positioned ipsilateral to the speech signal , which is referred to as a binaural squelch effect . On average , for the group , this result ed in a statistically significant improvement in speech comprehension scores of 8 % in the bilateral listening condition compared with the scores for the better ear alone . Through assessment of comprehension of coincidental speech in noise and speech in quiet , a significant benefit of binaural redundancy was noted for the group for Oldenburger sentence scores in noise and in quiet compared with unilateral scores for either ear and for the Freiburger monosyllabic words in quiet in comparison with the better ear alone scores . Binaural stimulation also led to a significant improvement in localization ability over either monaural condition , with the root mean square degrees of error reduced by 38 degrees compared with that observed for unilateral stimulation . Conclusion : Similar to what has been observed for bilateral acoustic stimulation in the past , bilateral electrical stimulation provides the foundation for the potential advantages of the head-shadow effect , providing a binaural head-shadow benefit and binaural auditory processing such as binaural redundancy and binaural squelch effects , all of which combine to lead to improved speech comprehension over unilateral listening conditions . The combination of improved speech comprehension and improved localization ability made available through bilateral electrical stimulation provides the necessary foundation to further assist the hearing-impaired listener to better cope with communication in the everyday listening situation both in noise and in quiet |
2,401 | 28,981,654 | WIDER IMPLICATION S This comprehensive meta-regression analysis reports a significant decline in sperm counts ( as measured by SC and TSC ) between 1973 and 2011 , driven by a 50 - 60 % decline among men unselected by fertility from North America , Europe , Australia and New Zeal and . | BACKGROUND Reported declines in sperm counts remain controversial today and recent trends are unknown .
A definitive meta- analysis is critical given the predictive value of sperm count for fertility , morbidity and mortality .
OBJECTIVE AND RATIONALE To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration ( SC ) and total sperm count ( TSC ) , and their modification by fertility and geographic group . | Recent prospect i ve studies of male reproductive health have shown differences between several European countries . Our objective was to evaluate the current situation in the two Baltic States Estonia and Lithuania . In 1997 - 99 we investigated semen parameters , levels of reproductive hormones and general health factors of 196 men from the general population in Lithuania ; from Estonia , 79 men from the general population and 118 soldiers were investigated . Adjusted for interlaboratory differences and abstinence period , sperm concentration of Lithuanian and Estonian men from the general population s were shown to be 55 and 67 million/mL , respectively . The Estonian soldiers had the highest sperm concentration , 82 million/mL. The frequencies of morphologically normal spermatozoa were 6.2 , 7.7 and 9.6 % , respectively . In contrast to the semen qualities , highest Inhibin B levels were detected in the Lithuanians ( 233 pg/mL ) followed by Estonian men from the general population ( 220 pg/mL ) and Estonian soldiers ( 185 pg/mL ) . The soldiers had also the lowest level of testosterone and oestradiol . The sperm counts of the Estonian and Lithuanian men investigated here are higher than recently shown for Norwegian , Danish , Estonian and Finnish men . Comparisons should be cautiously drawn as the groups are not completely comparable . Still , even within the Baltic region , geographically close and sharing common recent social history , differences in semen quality and levels of reproductive hormones are apparent Semen analyses was carried out in a population of 1250 r and omly selected Libyan males . Two semen sample s collected from each volunteer were subjected to the routine analyses following the World Health Organization recommendations . The Libyan population had a higher percentage of men with sperm density in the range of 40 - 60 millions/ml . The percentage of men with sperm counts above 100 millions/ml is comparatively lower than that is reported by MacLeod and Gold ( 9 ) . The seminal plasma transferrin levels showed a positive correlation with sperm density and alpha-glucosidase activity with sperm motility Population studies have shown that a high proportion of Nordic men may have so poor semen quality that they can be classified as sub-fertile according to international st and ards . A question is whether the Nordic data are specific for the Nordic countries or they should be seen as an expression of a general trend in Europe . We therefore carried out a prospect i ve study of semen quality of young men raised in the former East Germany ( Leipzig ) and West Germany ( Hamburg ) . To enable inter-regional comparisons , we utilized a common European research protocol previously used in studies in the Nordic-Baltic region . Three hundred and thirty-four young men representative of the general population from Hamburg , and 457 from Leipzig delivered semen sample s , underwent physical examinations and provided information on life-style and reproductive health parameters . The study period in Hamburg was February 2003 - -July 2004 , and in Leipzig July 2003 - -April 2005 . No significant differences were observed in sperm concentration ( median 46 , 42 , and 44 million/mL for men from Hamburg , Leipzig and the combined Hamburg-Leipzig group respectively ) or total sperm count ( 154,141 and 149 million ) , whereas the differences for morphologically normal spermatozoa ( 9.4 and 8.4 % ) and motile spermatozoa ( 67 and 81 % ) were significantly different . Previously published studies have shown reduced fertility with decreasing sperm concentrations below 40 - 55 millions/mL and normal sperm morphology below 9 - 19 % . Thus , a large fraction of young German men seem to have impaired semen quality that may reduce their natural fertility . However , it remains to be investigated to what extent poor semen quality contributes to the low German fertility rates OBJECTIVE To determine the consequences of adjuvant testicular germ cell tumor treatment ( TGCT ) on sperm characteristics and sperm DNA , and to evaluate the predictors of sperm recovery . DESIGN Multicenter prospect i ve longitudinal study of patients analyzed before treatment and after 3 , 6 , 12 , and 24 months . SETTING University hospitals . PATIENT(S ) One hundred twenty-nine volunteer TGCT patients and a control group of 257 fertile men . INTERVENTION(S ) Routine semen analyses , sperm DNA , and chromatin assessment s. MAIN OUTCOME MEASURE(S ) Comparisons of mean sperm characteristics before and after treatment , with sperm recovery analyzed by the Kaplan-Meier method . RESULT ( S ) The quantitative and qualitative sperm characteristics decreased after treatment , with lowest values at 3 and 6 months and with variations according to treatment type . The mean total sperm count recovered to pretreatment values at 12 months after treatment after two or fewer bleomycin , etoposide , and cisplatin ( BEP ) cycles , but not after radiotherapy or more than two BEP cycles . Only the treatment modalities and pretreatment sperm production were related to recovery of the World Health Organization reference sperm values . An increased proportion of patients had elevated high sperm DNA stainability at 6 months after radiotherapy . CONCLUSION ( S ) Adjuvant treatments for testicular germ cell tumor have drastic effects on spermatogenesis and sperm chromatin quality . These new data on both the recovery period according to treatment modalities and the post-treatment chromatin status of sperm are useful tools for counseling patients wishing to conceive AIM To analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception . METHODS A nested case-control study was conducted , involving 43 subjects , who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate ( TU ) , defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis ( complete suppressors ) . Sperm density , serum testosterone , luteinizing hormone ( LH ) and follicle stimulating hormone ( FSH ) concentrations at the baseline and the suppression phase were compared between partial and complete suppressors . Polymorphisms of and rogen receptor ( AR ) and three single nucleotide variants and their haplotypes of FSH receptor ( FSHR ) genes determined by polymerase chain reaction ( PCR ) and DNA sequencing technique were compared between 29 partial and 34 complete suppressors . RESULTS Baseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors . Additionally , in a logistic regression analysis larger testis volume , higher serum FSH concentrations alone , or interaction of serum LH , FSH , testosterone and sperm concentrations were associated with degree of suppression . The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors . In cases with incomplete FSH suppression ( FSH 0.2 IU/L ) , the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats . CONCLUSION Partial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes STUDY QUESTION Are urinary phthalate concentrations associated with altered semen quality parameters among males recruited from the general population ? SUMMARY ANSWER Urinary levels of metabolites of phthalate diesters are associated with lower total sperm counts , larger sperm head sizes , and higher percentages of morphologically abnormal sperm . WHAT IS KNOWN ALREADY High dose experiments in rats implicate phthalates as anti- and rogens . Studies involving infertile men seeking care suggest that phthalates influence measures of semen quality raising concern about the implication s for men in the general population . STUDY DESIGN , SIZE , DURATION This prospect i ve cohort study comprised 501 male partners in couples discontinuing contraception to become pregnant , who were recruited from 16 US counties using population -based sampling frameworks from 2005 to 2009 . PARTICIPANTS / MATERIAL S , SETTING , METHODS Urine and semen sample s were obtained at baseline from 473 ( 94 % ) men , of whom 378 ( 80 % ) men provided a second sample the following month . Urine was analyzed for 14 monoester metabolites of phthalate diesters by high-performance liquid chromatography coupled to t and em mass spectrometry . Semen sample s were analyzed for 34 quality parameters categorized as general , motility , morphology , sperm head and sperm chromatin structure . MAIN RESULTS AND THE ROLE OF CHANCE Urinary mono-[2-(carboxymethyl ) hexyl ] phthalate ( MCMHP ) , mono-(2-ethyl-5-hydroxyhexyl ) phthalate ( MEHHP ) , mono-benzyl phthalate ( MBzP ) , and mono-isononyl phthalate ( MNP ) were significantly associated with lower total sperm counts and concentrations , larger sperm head sizes , higher proportions of megalo head sperm morphology , and /or other morphological changes . Urinary mono-methyl phthalate ( MMP ) and mono-cyclohexyl phthalate ( MCPP ) were significantly associated with lower sperm motility , and urine mono-2-ethylhexyl phthalate ( MEHP ) was significantly associated with higher sperm motility . LIMITATIONS , REASONS FOR CAUTION While adverse associations were observed , the implication s of the findings for couple fecundity and fertility remain to be established . Cautious interpretation is needed in light of reliance on a single measurement of phthalate measure and no correction for multiple comparisons Objectives Considerable interest and controversy over a possible decline in semen quality during the 20th century raised concern that semen quality could have reached a critically low level where it might affect human reproduction . The authors therefore initiated a study to assess reproductive health in men from the general population and to monitor changes in semen quality over time . Design Cross-sectional study of men from the general Danish population . Inclusion criteria were place of residence in the Copenhagen area , and both the man and his mother being born and raised in Denmark . Men with severe or chronic diseases were not included . Setting Danish one-centre study . Participants 4867 men , median age 19 years , included from 1996 to 2010 . Outcome measures Semen volume , sperm concentration , total sperm count , sperm motility and sperm morphology . Results Only 23 % of participants had optimal sperm concentration and sperm morphology . Comparing with historic data of men attending a Copenhagen infertility clinic in the 1940s and men who recently became fathers , these two groups had significantly better semen quality than our study group from the general population . Over the 15 years , median sperm concentration increased from 43 to 48 million/ml ( p=0.02 ) and total sperm count from 132 to 151 million ( p=0.001 ) . The median percentage of motile spermatozoa and abnormal spermatozoa were 68 % and 93 % , and did not change during the study period . Conclusions This large prospect i ve study of semen quality among young men of the general population showed an increasing trend in sperm concentration and total sperm count . However , only one in four men had optimal semen quality . In addition , one in four will most likely face a prolonged waiting time to pregnancy if they in the future want to father a child and another 15 % are at risk of the need of fertility treatment . Thus , reduced semen quality seems so frequent that it may impair the fertility rates and further increase the dem and for assisted reproduction Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin . The incidence of testis cancer has been shown to increase among Finnish men , whereas there is no recent publication describing temporal trends in semen quality . Therefore , we carried out a prospect i ve semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends . A total of 858 men were investigated in the semen quality study during 1998–2006 . Median sperm concentrations were 67 ( 95 % CI 57–80 ) million/mL , 60 ( 51–71 ) and 48 ( 39–60 ) for birth cohorts 1979–81 , 1982–83 and 1987 ; total sperm counts 227 ( 189–272 ) million , 202 ( 170–240 ) and 165 ( 132–207 ) ; total number of morphologically normal spermatozoa 18 ( 14–23 ) million , 15 ( 12–19 ) and 11 ( 8–15 ) . Men aged 10–59 years at the time of diagnosis with testicular cancer during 1954–2008 were included in the registry study , which confirmed the increasing incidence of testicular cancer in recent cohorts . These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and , as such , preventable . Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors OBJECTIVE To determine the frequency of sperm cells with fragmented DNA in semen sample s from men with genitourinary infection by Chlamydia trachomatis and Mycoplasma and the influence of antibiotic therapy , using the sperm chromatin dispersion test with the Halosperm kit . DESIGN Prospect i ve study . SETTING University-affiliated reproductive medicine center , medical genetics laboratory , and academic biology center . PATIENT(S ) One hundred forty-three male member of couples attending the and rology infertility center and a group of 50 fertile subjects . The effect of antibiotic treatment was evaluated in 95 male patients . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Classical semen analysis ( concentration , motility , morphology , and vitality ) , sperm DNA fragmentation , and clinical outcome . RESULT ( S ) The mean percentage of sperm cells with fragmented DNA was 35.2 % + /- 13.5 % , 3.2 times higher than in the control fertile group ( 10.8 % + /- 5.6 % ) . Concentration , morphology , and motility were also significantly affected but to a much lower degree . Sperm vitality was not significantly affected . After 3.8 + /- 2.2 months of antibiotic treatment , the mean frequency of spermatozoa with fragmented DNA decreased from 37.7 % + /- 13.6 % to 24.2 % + /- 11.2 % . Sperm concentration and motility were not significantly improved . In a group of 16 couples who attempted pregnancy during antibiotic treatment course , only 12.5 % achieved pregnancy . However , in a group of 14 couples who attempted pregnancy after finishing the antibiotic treatment , 85.7 % achieved it . The only significant differences found between groups was the rate of sperm DNA fragmentation and morphology . CONCLUSION ( S ) Patients with genitourinary infection by Chlamydia trachomatis and Mycoplasma have increased sperm DNA fragmentation in comparison with fertile controls . This increase is proportionally greater than the influence on classical semen parameters and could result in a decreased fertility potential . Antibiotic therapy appears to be important in providing a remedy for infection-induced high DNA fragmentation levels Aim . To determine stimulated serum anti-Müllerian hormone ( AMH ) levels in men with different causes of subfertility . Subjects and methods . We prospect ively studied 82 subfertile men and 31 controls . The subfertile men underwent a diagnostic procedure to identify the causes of subfertility . Study parameters included testicular volume , levels of follicle-stimulating hormone , luteinizing hormone , total testosterone , prolactin , inhibin B and AMH , and sperm parameters . Results . Clinical diagnoses in subfertile men were idiopathic non-obstructive azoospermia ( n = 26 , 32 % ) , idiopathic non-obstructive dyspermia ( n = 17 , 21 % ) , varicocele ( n = 16 , 20 % ) , cryptorchidism ( n = 10 , 12 % ) and other diagnoses ( n = 13 , 16 % ) . Serum AMH levels in subfertile men were 60 % lower than in controls [ median ( interquartile range ) 4.6 ( 3.6 ) vs. 11.6 ( 7.7 ) ng/ml , p < 0.001 ] , with no significant differences among the different groups of subfertile men . Conclusions . Serum AMH levels differentiate control from subfertile men but not men with different causes of subfertility OBJECTIVES : To confirm or refute the hypothesis that organic farmers have higher sperm concentrations than traditional farmers . METHODS : Traditional and organic farmers were selected r and omly from central registers , and 171 traditional farmers and 85 organic farmers delivered one semen sample before the start of the spraying season . The participation rate was 28.8 % among traditional farmers and 42.9 % among organic farmers . RESULTS : The median sperm concentration for traditional and organic farmers was 58 million/ml and 64 million/ml , respectively . After adjustment for several confounders , sperm concentration , total count , proportion of non-vital spermatozoa , sperm chromatin structure , and motility variables did not differ significantly between the two groups . The traditional farmers had a significantly lower proportion of normal spermatozoa , but this result was not confirmed in a second sample . Organic farmers had slightly higher inhibin B concentration and testosterone/sex hormone binding globulin ratio . CONCLUSION : Despite slight differences in concentrations of reproductive hormones , no significant differences in conventional measures of semen quality were found between organic and traditional farmers OBJECTIVE To assess the tumor necrosis factor (TNF)-α gene polymorphism relationship with seminal variables in fertile men ( N ) and those with asthenozoospermia ( A ) , asthenoteratozoospermia ( AT ) , and oligoasthenoteratozoospermia ( OAT ) . MATERIAL S AND METHODS A total of 50 infertile men without a female factor who were attending a fertility clinic and 48 fertile men were r and omly screened for semen analysis , analysis of the TNF-α promoter region for polymorphism , seminal caspase-9 , acrosin activity , α-glucosidase , and reproductive hormones . RESULTS The TNF-α GG genotype was present in 83.9 % , 72.7 % , 66.7 % , and 59.5 % , the TNF-α AA genotype in 3.2 % , 6.8 % , 10.4 % , and 11.9 % , and TNF-α AG genotype in 12.9 % , 20.5 % , 22.9 % , and 28.6 % in the N , A , AT , OAT groups , respectively . The occurrence of A allele was significantly greater among infertile patients than among fertile controls ( 21.6 % vs 9.7 % ; odds ratio 0.388 , 95 % confidence interval 0.2 to 0.75 , P = .005 ) . Men with the TNF-α AA genotype demonstrated a significant decrease in the sperm count , sperm motility , normal sperm morphology , acrosin activity , and seminal α-glucosidase and a significant increase in seminal caspase-9 compared with those with the TNF-α GG genotype . CONCLUSION This single nucleotide polymorphism in the TNF-α(-308 ) gene was associated with significantly increased seminal caspase-9 and a significantly decreased sperm count , sperm motility , normal sperm morphology , acrosin activity , and seminal α-glucosidase OBJECTIVE To examine the relationships between hormone profiles and semen analysis measures and fertility in the male partners of presumed normal couples . DESIGN Prospect i ve clinical study . SETTING S Healthy volunteers in an academic research environment . PATIENT(S ) One hundred forty-five reproductive age couples without known risk factors for infertility and who had discontinued contraception to achieve pregnancy completed this component of this study . Each couple was followed for < or = 12 menstrual cycles while they attempted to conceive . INTERVENTION(S ) Semen quality measures for the first ejaculates were obtained at the start of the study along with a single blood sample . Levels of FSH , bioactive FSH , inhibin B , LH , and T were measured for each man . MAIN OUTCOME MEASURE(S ) Semen analysis , FSH , inhibin B , LH , T , and clinical pregnancy . RESULTS Significant positive relationships were observed between the two measures of FSH as well as between both of the FSH measures and LH . Follicle-stimulating hormone as measured by RIA was significantly negatively correlated with inhibin B. Inhibin B showed a marginally significant negative correlation with LH , and LH and T had a marginally significant positive correlation . Inhibin B increased significantly , and both measures of FSH activity showed significant decreases , with increasing levels in several semen quality measures . There was no significant relationship between the measured hormones and the pregnant and nonpregnant groups or time to pregnancy . CONCLUSION ( S ) These results contribute additional information on the utility of reproductive hormone measurements for predicting semen quality in couples without known reduced fertility INTRODUCTION Recent studies have highlighted the influence of alpha1-adrenoceptor antagonists on ejaculatory function . AIM We evaluated the effect of a new , highly selective alpha1A-blocker , silodosin , on ejaculatory function of normal volunteers . METHODS The study included 15 healthy male urologists who voluntarily participated in the study . They took 4 mg of silodosin or a placebo twice daily for 3 days in a r and omized , double-blind crossover design . MAIN OUTCOME MEASURES We investigated the ejaculatory volume , sperm count in urine after ejaculation , and fructose concentration in seminal plasma before and after administration of the agents . RESULTS All volunteers on silodosin had a complete lack of ejaculation . Three days after completion of silodosin , the mean ejaculatory volume recovered to the baseline level . There was no sperm in urine after ejaculation under silodosin administration in any volunteer . CONCLUSIONS All volunteers on silodosin had anejaculation and did not show post-ejaculate sperm in their urine . The mechanism of ejaculatory dysfunction caused by silodosin is a loss of seminal emission The suppression of spermatogenesis by a combination of depot medroxyprogesterone acetate ( DMPA ) and testosterone enanthate ( TE ) was studied in Indonesian men . Twenty healthy , fertile volunteers were allocated r and omly to either of two treatments each consisting of four intramuscular injections at monthly intervals . Group I ( n = 10 men ) received 100 mg DMPA plus 100 mg TE monthly while group II ( n = 10 men ) received 200 mg DMPA plus 250 mg TE monthly . Sperm concentration was suppressed markedly , with all men attaining azoospermia between the third and fourth month after the start of treatment . There was no significant difference in the suppression of spermatogenesis between the two dosage regimens . The median time to reaching azoospermia was 2.5 months from the onset of injections and the median time to recovery of sperm in the ejaculate was 2.0 months after cessation of treatment . Both steroid regimens were equally effective in suppressing LH , FSH and testosterone levels . Testosterone levels returned to baseline by the fourth post-treatment month while LH and FSH demonstrated significant rebound above baseline levels from 3 to 5 months after cessation of treatment . No serious clinical side effects were observed . Weight gain and increases in libido were reported during treatment by most volunteers . A transient decrease in libido was noted in 5/20 ( 25 % ) men between 1 - 2 months after cessation of injections , presumably due to the prolonged effects of DMPA relative to TE . These results indicate that uniform induction of reversible azoospermia with minimal side effects can be achieved in a non-Caucasian population . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract . Various seminal variables were studied in two groups of infertile couples and in one fertile control group . Sperm morphology was emphasized . Patients with normal postcoital tests and sperm counts exceeding 5 mill/ml were selected and followed prospect ively . The two clinical groups could then be OBJECTIVE To determine if air conditioning might mitigate summer reductions in semen quality . DESIGN Prospect i ve study of semen quality in summer and winter . SETTING Normal human volunteers were studied in the setting of a fertility laboratory . PATIENTS , PARTICIPANTS Two groups of volunteers were selected from the vicinity of New Orleans : 64 men who worked indoors during the summer in air-conditioned environments and 76 others who worked outdoors . INTERVENTIONS None . MAIN OUTCOME MEASURES Parameters of manual semen analysis were examined for seasonal and group differences . RESULTS Remarkably similar reductions in semen quality during summer as compared with winter were observed in both indoor and outdoor workers , respectively , with regard to the following parameters of semen quality : 19 % and 19 % in sperm concentration , 25 % and 27 % in total sperm per ejaculate , 17 % and 20 % in motile sperm concentration , 13 % and 15 % in percent sperm with normal morphology , and 23 % and 23 % in concentration of morphologically normal motile sperm . CONCLUSIONS These findings do not support the hypothesis that the heat of the summer is detrimental to male reproductive capacity . The available evidence suggests instead a possible role of photoperiod in causing the seasonal changes in semen quality OBJECTIVE To compare the sperm suppression in Indonesian men achieved by combination treatment with either T enanthate or 19-nortestosterone ester ) with depot-medroxyprogesterone acetate ( depot-MPA ) . DESIGN Prospect i ve multicenter parallel group r and omized trial . SETTING Five centers in Faculties of Medicine in Indonesia . PARTICIPANTS Ninety-six normal healthy volunteers . INTERVENTIONS Seven weekly injections of T enanthate or 19-nortestosterone ester , 200 mg IM , followed by injections every 3 weeks to week 24 . In both groups 250 mg depot-MPA was injected IM at 0 , 6 , 12 , and 18 weeks . MAIN OUTCOME MEASURES Sperm suppression by semen analysis at 3-week intervals and clinical chemistry , hematology , and gonadotrophin hormones monitored at 6-week intervals . Recovery assessed monthly until return to normal sperm concentration ( > or = 20 x 10(6)/mL ) . RESULTS Eighty-seven of 90 men ( 96.7 % ) achieved consistent azoospermia ; 95.6 % ( 43/45 ) and 97.8 % ( 44/45 ) in the T and 19-nortestosterone groups , respectively . The remaining three men also suppressed to near azoospermic levels . Six of 96 men discontinued injections for failure to attend at the schedule time ( 3 ) and for medical reasons ( 3 ) . Plasma FSH and LH concentrations were suppressed during treatment and returned to baseline levels during the recovery period . Clinical chemistry and hematologic values remained in the normal ranges throughout . More men complained of loss of libido in the 19-nortestosterone group ( seven versus two , respectively ) . Median time to recover to normal sperm concentrations was 6.5 months . CONCLUSIONS The two treatments were equally effective in sperm suppression . The rates of azoospermia achieved were higher than in previous studies with non-Indonesian men BACKGROUND Data available over the past twenty years reveal that in approximately 30 % of cases of infertility , pathology is found in man alone , and in another 20 % both man and woman are abnormal . Therefore , the male factor is at least partly responsible in about 50 % of infertile couples . The longer a couple remains sub fertile , the worse is their chance for an effective cure . This study was planned to analyse the complete semen picture of infertile men for assigning the specific cause to male infertility related to concentration , motility and morphology and to know the distribution and pattern of male infertility in the various subclasses in Pakistani population . METHODS It was a prospect i ve descriptive analytical study conducted at Department of Reproductive Physiology/Health , Public Health Divisions , National Institute of Health ( NIH ) , Islamabad . One thous and five hundred twenty-one ( 1,521 ) infertile male patients , and 97 proven fathers , taken as a control . Conventional semen analysis was performed on all sample s. RESULTS Out of 1,521 infertile men , 13.3 % were azoospermic , 23.2 % oligozoospermic , 0.9 % polyzoospermic , 14.5 % normozoospermic , 35.2 % asthenozoospermic 10.5 % oligoasthenozoospermic and 2.4 % teratozoospermic . Sperm concentration and active motility of proven fathers , was significantly higher ( p<0.05 ) than the normal concentration group . Least liquefaction time was recorded in case of polyzoospermic subjects , and highest for azoospermic cases . Although , the liquefaction time of azoospermic and oligozoospermic subjects varied non-significantly ( p>0.05 ) with the proven fathers . Normal forms were significantly higher ( p<0.05 ) among the proven fathers and polyzoospermic cases , in comparison with the other groups . Head defects were more in teratozoospermic group , followed by oligoasthenozoospermic and oligozoospermic patients . Neck defects were more profound in oligoasthenozoospermic and oligozoospermic patients , while , tail defect showed significant increase in teratozoospermic and asthenozoospermic cases only . Head and neck defect varied significantly ( p<0.05 ) with proven fathers in all groups , while tail defect varied significantly ( p<0.05 ) in oligozoospermic , asthenozoospermic and teratozoospermic groups only when compared with proven fathers . CONCLUSIONS Complete semen analysis which provides important information about the quality and quantity of the sperm , should be performed before reaching a final conclusion OBJECTIVE To evaluate the effects of chronic alcoholism on the male fertility hormones and quality of semen . DESIGN Non-probability purposive clinical study . SETTING Addiction treatment center and an academic research environment . PATIENT(S ) Sixty-six alcoholics free from smoking and drug abuse who consumed a minimum of 180 mL of alcohol per day ( br and y and whisky , both 40%-50 % alcohol content ) for a minimum of 5 days per week for > or = 1 year were included . Thirty nonsmoking nonalcoholics were selected as controls . INTERVENTION(S ) Before starting the addiction treatment for alcoholics , venous blood and semen sample s were collected . MAIN OUTCOME MEASURE(S ) Complete blood counts , biochemical parameters , levels of the male fertility hormones FSH , LH , T , PRL , P , and E2 in blood , and semen parameters . RESULT ( S ) In alcoholics , FSH , LH , and E2 levels were significantly increased , and T and P levels were significantly decreased . No significant change was noted in PRL levels . Semen volume , sperm count , motility , and number of morphologically normal sperm were significantly decreased . CONCLUSION ( S ) Chronic alcohol consumption has a detrimental effect on male reproductive hormones and on semen quality |
2,402 | 28,086,761 | The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities , a lack of dopaminergic abnormalities , and significant decreases in grey matter compared to treatment-responsive patients .
Conclusions Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia . | Background Schizophrenia is a highly heterogeneous disorder , and around a third of patients are treatment-resistant .
The only evidence -based treatment for these patients is clozapine , an atypical antipsychotic with relatively weak dopamine antagonism .
It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes , which would have significant implication s for research and clinical practice .
If these subtypes could be distinguished at illness onset , this could represent a first step towards personalised medicine in psychiatry .
This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes . | R and omized controlled trials among patients with schizophrenia have shown that < 20 % improvement in the first two weeks of treatment predicts nonresponse after 12 weeks . The findings have been consistent for patients treated with both conventional ( 1 ) and second-generation antipsychotic ( AP ) drugs ( 2 ) . However , despite the lack of evidence regarding the length of time that clinicians should pursue one treatment regimen , most psychiatric textbooks and practice guidelines suggest that patients should be treated for at least four to six weeks with one AP ( 3 - 5 ) before switching to another ( 6 ) . Large pragmatic trials with chronic patients , such as the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) ( 7 ) , have found no benefit from switching AP drugs ( 8,9 ) . No studies have considered less chronic patients , such as patients with recent-onset schizophrenia ( i.e. , less than five years of illness duration ) . We investigated responses to APs and switching strategies in patients with recent-onset schizophrenia . We used the IPAP algorithm , which is a well-defined algorithm for treating schizophrenia ( 4,10 ) OBJECTIVE Clinical response to antipsychotic drug treatment is highly variable , yet prognostic biomarkers are lacking . The authors recently demonstrated that successful antipsychotic drug treatment alters resting-state functional connectivity of the striatum . The goal of the present study was to test whether intrinsic striatal connectivity patterns provide prognostic information and can serve as a potential biomarker of treatment response to antipsychotic drugs . METHOD The authors used resting-state functional MRI ( fMRI ) to develop a prognostic index in a discovery cohort of 41 first-episode schizophrenia patients , then tested this index in an independent cohort of 40 newly hospitalized chronic patients with acute psychosis . In the discovery cohort , patients underwent resting-state fMRI scanning at the initiation of r and omized controlled treatment with a second-generation antipsychotic . Whole-brain functional connectivity maps were generated for each subject from striatal seed regions . A stringent measure of clinical response was calculated that required sustained improvement over two consecutive study visits . Clinical response was entered into a survival analysis , and Cox regression was applied to the functional connectivity data . A striatal connectivity index was created , comprising functional connections of the striatum that predicted treatment response . This striatal connectivity index was tested on a generalizability cohort of patients with psychotic disorders who were hospitalized for an acute psychotic episode . RESULTS A total of 91 regions functionally connected with the striatum provided significant prognostic information . Connectivity in these regions was used to create a baseline striatal connectivity index that predicted response to antipsychotic treatment with high sensitivity and specificity in both the discovery and generalizability cohorts . CONCLUSIONS These results provide evidence that individual differences in striatal functional connectivity predict response to antipsychotic drug treatment in acutely psychotic patients . With further development , this has the potential to serve as a prognostic biomarker with clinical utility and to reduce the overall burden associated with psychotic illnesses In the present study , including 66 schizophrenic patients and 73 healthy controls , the effect of atypical antipsychotic treatment over a period of 14 weeks on psychotic symptoms and plasma levels of glutamate and monoaminergic metabolites was investigated . Treatment induced a modest reduction of psychotic symptoms in 42 % of the patients ( response criterion : Brief Psychiatric Rating Scale [ BPRS ] decrease > /=40 % ) . Poor response was associated with severity of psychopathology , age and duration of disease . Glutamate at baseline was significantly higher in patients as compared to controls ( p<0.01 ) . During treatment , a significant further increase of glutamate , not related to response , was observed . Glutamate levels correlated significantly with negative symptom scores at baseline and weeks 3 , 6 and 14 ( p<0.05 ) . At baseline , serotonin ( 5-HT ) in plasma and 5-HT in platelets were significantly lower in the poor responders as compared to controls ( p<0.05 ) and increased significantly during treatment ( p<0.05 ) . In the responders , treatment coincided with a decrease of 5-HT parameters . No differences in plasma levels of HVA , 5-HIAA and their ratio were observed between controls and response groups . The results of this study suggest an effect of atypical antipsychotics on glutamatergic neurotransmission and an association between lower pretreatment peripheral 5-HT parameters and response Schizophrenia is a heterogeneous clinical condition that may reflect a variety of biological processes . In particular , treatment-resistant ( TR ) schizophrenia may have a distinct neurobiological substrate . Within the context of clinical data , a simultaneous study with different imaging techniques could help to eluci date differences in cerebral substrates among schizophrenia patients with different responses to treatment . In the present work we used a set of biological data ( basal and longitudinal volumetry , and P300 event-related potential measurements ) to compare TR and treatment-responsive chronic schizophrenia patients with healthy controls . The TR patients showed higher baseline clinical scores , a more severe basal profile of brain alterations , as well as a different outcome as regards to volume deficits . These data support the notion that biological substrates vary among groups of different psychotic patients , even when they have the same diagnosis , and that those substrates may be related to the response to treatment Connecticut State Hospital 's entire resident population ( n = 1,300 ) was screened on an arbitrary target day to determine eligibility for clozapine . Sixty percent of 803 patients with schizophrenia or schizoaffective disorder diagnoses met Food and Drug Administration ( FDA ) - approved criteria for clozapine use as judged by review of past medication trial records and by the responsible physicians . Eighty-eight percent of these patients were medically cleared , and of those cleared , 63 percent agreed to clozapine treatment . Of the patients who began a clozapine trial , 76 percent were still taking the drug 12 months later . Preliminary findings from a r and omized trial of clozapine versus usual care ( n = 227 ) indicate that discharge rates associated with clozapine and usual care do not differ . Once discharged , however , patients assigned to clozapine are less likely to be readmitted . Hence , clozapine may be more cost-effective than usual care . However , before savings can be realized , State governments will have to make up-front investments of approximately $ 140 million simply to give patients hospitalized on a single day a year 's access to clozapine OBJECTIVE Early , effective treatment in first-episode schizophrenia is advocated , although evidence based on a systematic approach over multiple antipsychotic trials is lacking . Employing a naturalistic design , we examined response rates over 3 circumscribed antipsychotic trials . METHOD Between June 2003 and December 2008 , 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , following an algorithm that moved them through 2 antipsychotic trials , followed by a trial with clozapine . For the first 2 trials , treatment consisted of risperidone followed by olanzapine , or vice versa ; each trial consisted of 3 stages ( low- , full- , or high-dose ) lasting up to 4 weeks at each level and adjusted according to response/tolerability . Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 ( much improved ) or 1 ( very much improved ) and /or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6 . Data were analyzed retrospectively , and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003 . RESULTS In trial 1 , 74.5 % of individuals responded , with rates significantly higher for olanzapine ( 82.1 % , 115/140 ) versus risperidone ( 66.3 % , 69/104 ; P = .005 ) . With trial 2 , response rate dropped dramatically to 16.6 % but again was significantly higher for olanzapine ( 25.7 % , 9/35 ) compared to risperidone ( 4.0 % , 1/25 ; P = .04 ) . Response rate climbed above 70 % once more , specifically 75.0 % ( 21/28 ) , in those individuals who agreed to a third trial with clozapine . CONCLUSIONS Results confirm a high response rate ( 75 % ) to initial antipsychotic treatment in first-episode schizophrenia . A considerably lower response rate ( < 20 % ) occurs with a second antipsychotic trial . Results here were specific to olanzapine and risperidone , suggesting clinical differences ( ie , olanzapine more effective than risperidone ) . A subsequent trial with clozapine is clearly warranted , although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm The aim of this work was to compare achievements in milestones of community functioning in highly disabling psychiatric conditions , including treatment resistant schizophrenia ( TRS ) , schizophrenia ( responsive to antipsychotics ) , bipolar disorder , and anxiety/depressive diseases . Also , we investigated the predictors of community functioning outcomes across several domains . Among consecutive patients screened , 188 met inclusion criteria and 118 ultimately entered the study . Diagnosis of TRS was made by stringent criteria , including historic and perspective evaluations and excluding potential confounding factors . Achievements in functional milestones of everyday living were recorded . Performances in discrete cognitive tasks were assessed . The Positive and Negative Syndrome Scale , the Personal and Social Performance Scale , the Drug Attitude Inventory-10 , and the Quality of Life Enjoyment and Satisfaction Question naire were administered . TRS patients showed the highest impairment in community functioning among diagnostic groups . TRS was found to have more severe psychopathology , more impaired cognitive functioning , and poorer psychosocial adjustment compared to all the other groups . In the whole sample , the main predictors of community functioning were the diagnostic group ( with TRS diagnosis associated with worst functioning ) and achievements in the other functional milestones . In psychotic patients , however , the main predictors of community functioning were clinical and psychopathological variables . These results may support the hypothesis that TRS represents a separate schizophrenia subtype , with its own neurobiology , psychopathology and clinical course . Our results identify a group of modifiable predictors to be addressed to prevent community disability OBJECTIVE Clozapine is the only compound proven to be effective in the 20 % of schizophrenic patients refractory to treatment with conventional neuroleptics . Although its mechanism of action has not been eluci date d , clozapine appears , in contrast to most conventional neuroleptics , to be a potent serotonin ( 5-HT ) antagonist . This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it . METHOD The 5-HT receptor agonist m-chlorophenylpiperazine ( MCPP ) was used as a probe to examine 5-HT function . MCPP ( 0.35 mg/kg p.o . ) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients . ACTH , prolactin , body temperature , behavior , and MCPP blood level were measured . Patients were then treated with a conventional neuroleptic , and , having failed to respond to it , were treated with clozapine for 5 weeks ( up to 600 mg/day ) . RESULTS Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine . Moreover , the degree of improvement with clozapine , particularly the improvement in psychotic symptoms , was strongly correlated with the magnitude of MCPP-induced ACTH release . Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine . CONCLUSIONS Results of this study suggest that MCPP-induced ACTH release , and by inference 5-HT receptor function , may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug D-fenfluramine has been identified as a highly selective serotonin ( 5-HT ) releaser and re-uptake inhibitor . The objective of our study was to investigate prolactin response to D-fenfluramine challenge in non-medicated , first episode schizophrenics . We hypothesized that 5-HT reactivity can predict a response to the neuroleptic treatment . Twenty-three in patients , 11 males and 12 females , at the Prague Psychiatric Center participated in the study . Inclusion criteria were : ICD-10 diagnosis of schizophrenia , first episode or duration of illness shorter than 36 months . D-fenfluramine challenge test was performed before 4 weeks of the haloperidol treatment . During the test , prolactin plasma levels were measured . The Brief Psychiatric Rating Scale ( BPRS ) was administered before and after the treatment . A statistically significant negative correlation was found between prolactin response to the D-fenfluramine challenge and improvement of psychopathology measured by the change in total BPRS score ( p = 0.0004 ) , in positive ( p = 0.0403 ) , negative ( p = 0.0267 ) , and anxiety-depression symptoms of BPRS ( p = 0.0014 ) . Our data support the original hypothesis that there is a relationship between 5-HT system activity and treatment response . The higher responsiveness of the 5-HT system in first episode , non-medicated schizophrenics , was associated with a poorer treatment response to haloperidol , an antidopaminergic neuroleptic We report an association between HLA-A1 allele and a subgroup of schizophrenic patients refractory to conventional neuroleptic treatment but responsive to clozapine . The frequency of HLA-A1 was 58 % among the schizophrenic patients not responding to conventional treatment but responsive to clozapine but only 10.5 % among the patients responding to conventional neuroleptics . The HLA-A1 occurs in 20 % of the r and om Finnish population . Our results indicate that HLA-A1 defines a subgroup of schizophrenic patients with a selective response to neuroleptics BACKGROUND Brain-derived neurotrophic factor ( BDNF ) has extensive effects on the nervous system including cell survival , differentiation , neuronal growth and maintenance , as well as cell death . Moreover , it promotes synaptic plasticity and interacts with dopaminergic and serotonergic neurons , suggesting an important role on the alteration of brain function with antipsychotic medications and induced weight gain in schizophrenia patients . The differential effects of BDNF gene variants could lead to changes in brain circuitry that would in turn cause variable response to antipsychotic medication . Therefore , we hypothesized that genetic variation in this c and i date gene helps in explaining the inter-individual variation observed in antipsychotic drug treatment with respect to response and induced weight gain . METHOD We examined four single-nucleotide polymorphisms across the BDNF gene , including Val66Met ( rs6265 ) . Prospect i ve BPRS change scores and weight change after six weeks were obtained from a total of 257 schizophrenia patients of European ancestry . RESULTS The markers rs11030104 and Val66Met were associated with antipsychotic response ( P=0.04 ; 0.007 , respectively ) . On the other h and , marker rs1519480 was associated with weight gain ( P=0.04 ) . Moreover , a two-marker haplotype across rs6265 and rs1519480 was associated with weight change ( P=0.001 ) . Results with Val66Met in response , and results with rs6265-rs1519480 haplotypes remained significant at the modified Bonferroni corrected alpha of 0.017 . CONCLUSION BDNF genetic variants might play an important role in predicting antipsychotic response and antipsychotic-induced weight gain . However , replication in larger and independent sample s is required |
2,403 | 16,679,336 | Increased mortality associated with a diagnosis of type 2 diabetes at an older age is lower than that reported for the general older diabetic population | OBJECTIVES To review all published observational studies reporting on all-cause mortality in patients with type 2 diabetes to determine the degree of increased mortality when diagnosed at an older age . | UNLABELLED We have investigated the incidence of newly diagnosed Type 2 diabetes in the Poole area and extrapolated it to the rest of the UK . METHODS this prospect i ve observational study used a surveillance programme in primary and secondary care . We identified all cases of newly diagnosed Type 2 diabetes mellitus occurring from 1st May 1996 to 30th June 1998 through the normal health care process without any active screening in 186889 people registered with 24 primary care practice s in the Poole area . RESULTS the 1996 prevalence of diagnosed Type 2 diabetes in this population was 1.59 ( 95 % CI 1.53 - 1.65%)% . During the first 24 months of the study , 706 new cases of Type 2 diabetes mellitus , 382 men and 324 women , were identified . The crude annual incidence of newly diagnosed Type 2 diabetes , thus was 1.93/1000 ( 95 % CI 1.73 - 2.13 % ) and age/sex adjusted incidence was 1.67/1000 ( 95 % CI 1.49 - 1.84 % ) . The age-adjusted incidence was higher in men , 1.86/1000 ( 95 % CI 1.60 - 2.13 ) , than in women , 1.48/1000 ( 95 % CI 1.25 - 1.71 % ) , relative risk 1.26 ( 95 % CI 0.997 - 1.527 % ) , but this difference did not reach statistical significance . Mean HbA1c at diagnosis was 10.8 ( S.D. 2.9%)% . Men were younger at diagnosis than women ( mean age , 62.9 vs. 65.9 % , P<0.01 ) . CONCLUSION in UK , prior to the change in the WHO diagnostic criteria for diabetes , we estimate that over 98000 new cases of Type 2 diabetes were diagnosed each year CONTEXT Elderly persons and women were underrepresented in r and omized controlled trials ( RCTs ) prior to 1990 . Since then , efforts have been made to correct these biases , but their effect is unclear . OBJECTIVE To determine whether the percentage of elderly persons and women in published clinical trials of acute coronary syndromes has increased and how this enrollment compared with disease prevalence . DATA SOURCES The MEDLINE and Cochrane data bases were search ed for English- language articles from January 1966 to March 2000 regarding myocardial infa rct ion , unstable angina , or acute coronary syndromes . Additional data sources included meta-analyses , review articles , and cardiology textbooks . Estimates of community-based myocardial infa rct ion rates came from the National Registry of Myocardial Infa rct ion and the Worcester Heart Study . STUDY SELECTION Published RCTs of acute coronary syndrome patients were included and trials enrolling 50 patients or fewer , those without clinical end points , papers published in a language other than English , and unpublished manuscripts were excluded . Of 7645 studies identified , 593 RCTs were selected for review . DATA EXTRACTION The RCTs were abstract ed by 2 of the authors for year of publication , source of support ( ie , funding ) , pharmacotherapy , study phase , number of study sites , trial location , number of patients , mean age of the study population , and any age exclusion criteria for enrollment . DATA SYNTHESIS The number of published RCTs with explicit age exclusions has declined from 58 % during 1966 - 1990 to 40 % during 1991 - 2000 . Trial enrollment of patients aged 75 years or older increased from 2 % for studies published during 1966 - 1990 to 9 % during 1991 - 2000 , but remains well below their representation among all patients with myocardial infa rct ion ( 37 % ) in the United States . Enrollment of women has risen from 20 % for studies published between 1966 - 1990 to 25 % during 1991 - 2000 , but remains well below their proportion of all patients with myocardial infa rct ion ( 43 % ) in the United States . CONCLUSIONS Attempts at making cardiovascular RCTs more inclusive appear to have had limited success ; thus , women and elderly persons remain underrepresented in published trial literature relative to their disease prevalence . Because safety and efficacy can vary as a function of sex and age , these enrollment biases undermine efforts to provide evidence -based care to all cardiac patients Abstract Objectives : To identify all patients with diabetes in a community using electronic record linkage of multiple data sources and to compare this method of case ascertainment with registers of diabetic patients derived from primary care . Design : Electronic capture-recapture linkage of records included data on all patients attending hospital diabetes clinics , all encashed prescriptions for diabetes related drugs and monitoring equipment , all patients discharged from hospital , patients attending a mobile unit for eye screening , and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry data base . Diabetes registers from primary care were from a r and om sample of eight Tayside general practice s. A detailed manual study of relevant records for the 35 144 patients registered with these eight general practice s allowed for validation of the case ascertainment . Setting : Tayside region of Scotl and , population 391 274 on 1 January 1996 . Main outcome measures : Prevalence of diabetes ; population of patients identified by different data sources ; sensitivity and positive predictive value of ascertainment methods . Results : Electronic record linkage identified 7596 diabetic patients , giving a prevalence of known diabetes of 1.94 % ( 0.21 % insulin dependent diabetes , 1.73 % non-insulin dependent ) : 63 % of patients had attended hospital diabetes clinics , 68 % had encashed diabetes related prescriptions , 72 % had attended the mobile eye screening unit , and 48 % had biochemical results diagnostic of diabetes . A further 701 patients had isolated hyperglycaemia ( plasma glucose > 11.1 mmol/l ) but were not considered diabetic by general practitioners . Validation against the eight general practice s ( 636 diabetic patients ) showed electronic linkage to have a sensitivity of 0.96 and a positive predictive value of 0.95 for ascertainment of known diabetes . General practice lists had a sensitivity of 0.91 and a positive predictive value of 0.98 . Conclusions : Electronic record linkage was more sensitive than general practice registers in identifying diabetic subjects and identified an additional 0.18 % of the population with a history of hyperglycaemia who might warrant screening for undiagnosed diabetes . Key messages It has been recommended that regional registers of patients with diabetes are established in order to facilitate effective monitoring and treatment of diabetes In Tayside we created a diabetes register by record linkage of multiple data sources : all patients attending hospital diabetes clinics , all encashed prescriptions for diabetes related drugs and monitoring equipment , all patients discharged from hospital , patients attending a mobile unit for eye screening , and results for glycated haemoglobin and plasma glucose concentrations from the regional biochemistry data base This register identified 7596 patients with diabetes in Tayside , giving a prevalence of diabetes of 1.94 % Record linkage was more sensitive than general practice registers in ascertaining cases of known diabetes A unique patient identifier , the community health number , was fundamental for successful record In 1981 - 1982 , 5699 persons representing 92.9 % of the total population aged 60 - 74 years living in Fredericia , Denmark , were interviewed about a possible history of diabetes and had a fasting blood glucose measured . A total of 236 gave a positive history of diabetes ; 88 had one fasting blood glucose of 7 mmol/L or more . For each of these prob and s , an age- and gender-matched control person with normal fasting blood glucose and no history of diabetes was selected r and omly . Of the 236 , 91.5 % had NIDDM as judged by glucagon-stimulated C-peptide tests . At the end of December 1995 , the participants were traced through the National Register and their status ( alive or dead ) was determined . The date of death was confirmed . The median observation time from screening and inclusion in the study till death or the end of the observation period in December 1995 was 12.81 years , the maximum was 14.91 , and the 25th and 75th percentile values were 6.36 and 13.94 years , respectively . At the end of 1995 , 165 ( 74.4 % ) of 228 persons with known diabetes at the time of ascertainment had died opposed to 90 ( 40.4 % ) of the 223 nondiabetic control persons . The difference is statistically highly significant ( p < 0.00001 , log-rank test ) . Within the first 5 years of observation , 42.9 % of diabetic men died and only 22.5 % of non-diabetic men . This percentage of deaths in diabetic men was found already in the 60 - 64 year age interval ( 46.2 % ) . The mortality rate for the non-diabetic population seems to increase later . After 13 years of observation , 74 ( 81.3 % ) of 91 men with known diabetes had died , in the age-matched control men , 50 ( 56.2 % ) of 89 ( p = 0.00006 ) . Ninety-one ( 66.4 % ) of 137 diabetic women had died : 40 ( 29.9 % ) of 134 control women ( p < 0.00001 ) . The difference between mortality in diabetic men and women , and between nondiabetic men and women is highly significant ( p = 0.00285 and 0.00001 , respectively ) . The over-mortality of established diabetic persons decreases with age . In the age group 60 - 74 years , the over-mortality is about 2.5 without gender difference The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases . Therefore , we determined total and free testosterone , luteinizing hormone ( LH ) , and sex-hormone binding globulin ( SHBG ) in a cohort of r and omly selected men ( n = 659 ) at 67 years of age . These data were analyzed cross-sectionally in relation to blood glucose and serum insulin , which were measured while fasting and after an oral glucose tolerance test , in addition to plasma lipids and blood pressure . The data were also analyzed in relation to impaired glucose tolerance ( IGT ) and diabetes , which were discovered at examination or earlier diagnosis . Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics . Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values ; total testosterone and SHBG , with triglycerides ; and SHBG , with blood pressure ( from P < 0.05 to P < 0.01 ) . Men with IGT or newly diagnosed diabetes had higher BMI values ( 26.2 ± 0.31 and 27.0 ± 0.59 [ mean ± SE ] , respectively ) and waist circumference ( 99.0 ± 1.03 and 100.5 ± 1.57 ) than nondiabetic men ( BMI , 25.1 ± 0.14 ; waist circumference , 95.4 ± 0.47 ; P < 0.05 ) , indicating abdominal obesity . Such men and men with previously diagnosed diabetes had , in general , lower total and free testosterone and SHBG levels , while those for LH were not different . In multivariate analyses that included BMI , waist-to-hip ratio , total and free testosterone , and SHBG , the remaining independent predictors for the development of diabetes were low total testosterone ( P = 0.015 ) and , on the borderline , low SHBG ( P = 0.053 ) . In relation to nondiabetic men , the risk ratio for mortality , myocardial infa rct ion , and stroke increased gradually and significantly from 1.18 to 1.68 , from 1.51 to 1.78 , and from 1.72 to 2.46 in men with IGT , newly diagnosed diabetes , and previously known diabetes , respectively . It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes . Moreover , low testosterone levels independently predict the risk of developing diabetes . In different degrees of expression , the diabetic state predicts strongly ( and gradually mortality from ) myocardial infa rct ion and stroke . It has been suggested that a relative hypogonadism might be a primary event , because other studies have shown that testosterone deficiency is followed by insulin resistance , which is ameliorated by testosterone substitution . The data suggest that the relative hypogonadism involved might be of both central and peripheral origin The life expectancy of well controlled diabetics has been considered to be approximately that of the normal individual . A 20 year prospect i ve study of the mortality of diabetics who applied for life insurance to the Equitable Life Assurance Society did not confirm this . The study population comprised 10,538 individuals with an average exposure of 7.9 years . During the period of the study 1,478 deaths were recorded , giving a mortality ratio of 335 % . Mortality decreased with increasing age at diagnosis of diabetes . Mortality increased with increasing duration of the disease . Mortality was lowest in cases treated by diet only . Mortality in cases with poor control was two and one-half times that of cases with good control . Albuminuria on examination was an extremely unfavorable prognostic factor . Hypertension had a particularly adverse effect on the diabetic as compared to the non-diabetic , especially at ages under 40 Background : To present actual data to estimate prevalence , incidence and mortality of known type 2 diabetes mellitus in all age categories in The Netherl and s. Methods : Prospect i ve population -based study between 1998 and 2000 in The Netherl and s. Baseline population of 155,774 patients , registered with 61 general practitioners participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC)- study . Results : Age- and sex-adjusted prevalence of type 2 diabetes was 2.2 % at baseline and 2.9 % after 2 years of follow-up ; for women and men it was 3.1 and 2.7 % at follow-up , respectively . Patients aged > 70 years account for almost 50 % of all type 2 diabetes patients . Age- and sex-adjusted mean annual incidence per 10,000 over 3 years was 22.7 overall ; for women 23.1 and for men 22.2 . Incidence - even though high - decreases after the age of 70 years . The mortality rate was 47.9/1000 and st and ardised mortality ratio 1.40 . Based on these results , the estimated total number of subjects known with type 2 diabetes was 466,000 for The Netherl and s in 2000 ; the number of patients with newly diagnosed diabetes 36,000 . Conclusions : Prevalence and incidence rates exceed all estimates regarding known type 2 diabetes for The Netherl and s. Elderly patients , aged 70 years and over , account for 50 % of the type 2 diabetic population . These results are important for health-care planning OBJECTIVE To examine diabetes prevalence , incidence , and mortality from 1993 to 2001 among fee-for-service Medicare beneficiaries > or = 67 years of age . RESEARCH DESIGN AND METHODS This study was a retrospective analysis of a 5 % r and om sample of Medicare fee-for-service beneficiaries > or = 65 years of age in each year . RESULTS In 1993 , the prevalence of diabetes among those > or = 67 years of age was 145 cases per 1,000 individuals . By 2001 , it was 197/1,000 , an increase of 36.0 % . The 2001 prevalence among Hispanics ( 334/1,000 ) was significantly higher than among blacks ( 296/1,000 ) , Asians ( 243/1,000 ) , and whites ( 184/1,000 , P < 0.0001 ) . During the 7-year period the greatest increase in diabetes prevalence was among Asians ( 68.0 % ) . Between 1994 and 2001 , the annual rate of newly diagnosed elderly individuals with diabetes increased by 36.9 % . Hispanics had the greatest increase at 55.0 % . The mortality rate among individuals with diabetes decreased by approximately 5 % between 1994 and 2001 from 92.1/1,000 to 87.2/1,000 ( P < 0.001 ) , due to a 6 % decrease among whites . No decrease in mortality was seen among elderly individuals without diabetes , it was 55/1,000 in 1994 and 54/1,000 in 2001 . CONCLUSIONS The dramatic increase in the incidence and prevalence of diabetes likely reflect a combination of true increases , as well as changes in the diagnostic criteria and increased interest in diagnosing and appropriately treating diabetes in the elderly . Improved treatment may have had an impact on mortality rates among individuals with diabetes , although they could have been influenced by the duration of diabetes before diagnosis , which has likely decreased . Changes in incidence , prevalence , and mortality in elderly individuals with diabetes need to continue to be monitored To clarify the mortality and causes of death among Japanese diabetics , we started a prospect i ve follow-up study of 1,629 diabetics who had been registered at our Diabetes Center in 1976 . After registration , all patients were checked annually for four years and we confirmed that they were still alive by sending question naires or obtaining copies of their resident cards . After a four-year follow-up , only 3 had dropped out , 1,486 were alive and 140 had died . The follow-up rate therefore was 99.8 % . We obtained copies of the death certificates of all the deceased . It was shown that risk factors increasing the mortality ratio ( the ratio of observed deaths to expected deaths ) among Japanese diabetics were early onset of diabetes ( 0 - 29 years of age ) , treatment by insulin and the presence of diabetic retinopathy combined with proteinuria at registration . The most frequent cause of death among the 140 deceased cases was malignant neoplasm , the second ischemic heart disease and the third was cerebrovascular disease . Analysis of the underlying causes of death showed a significant increase in the death rate due to diabetes mellitus and ischemic heart disease among Japanese diabetics compared with the general population matched for sex and age The 5- to 6-year all-cause mortality is analyzed in 1323 newly diagnosed diabetic patients aged 40 years or over . The median age at diagnosis is lower for men ( 63.6 years ) than for women ( 67.5 years ) , but more men ( 24.7 % ) than women ( 20.0 % ) have died ( p = 0.04 ) . This male excess mortality can be attributed mainly to the 60- to 79-year-old men . With increasing diabetes duration , both male and female diabetic patients exhibit an increasing excess mortality in comparison with the Danish population . For men , this excess mortality becomes statistically significant 4 years after diagnosis for the 40- to 59-year-old patient and 6 years after diagnosis for the 60- to 79-year-old patient . For women and very old men , no statistically significant excess mortality is observed . After 2 - 4 years , however , there is a tendency for the survival curve of 40- to 79-year-old women to separate from that of the Danish female population to show an excess mortality . In this population -based study , the disadvantageous mortality experience of even newly diagnosed diabetic patients is clearly demonstrated |
2,404 | 25,404,399 | Rashes , nausea , itching , vomiting and abnormal results on liver function tests were not significantly increased .
INTERPRETATION Diarrhea was caused by use of amoxicillin-clavulanic acid , and c and idiasis was caused by both amoxicillin and amoxicillin-clavulanic acid . | BACKGROUND When prescribing antibiotics for common indications , clinicians need information about both harms and benefits , information that is currently available only from observational studies .
We quantified the common harms of the most frequently prescribed antibiotic , amoxicillin , from r and omized placebo-controlled trials . | One hundred and six third trimester pregnant women with prelabour rupture of membranes preterm were r and omised to either peroral amoxicillin 0.75 g 3 times daily ( n = 50 ) or placebo ( n = 56 ) in a blinded way . The patients were hospitalised in bed for 7 days unless contractions started and delivery ensued . Only 1 patient was discharged after 7 days of treatment , while the remaining ones delivered within 1 week after admission . The average rupture-to-expulsion interval was 68.4 h in the placebo group and 91.7 h in the amoxicillin group , implying a significantly prolonged stay by 43 % in the amoxicillin group ( p = 0.03 ) . The other outcome variables registered ( birth weight , stillbirth prevalence , vaginal haemorrhage and postpartum endometritis-myometritis ) did not differ significantly in the two treatment groups . There was a trend towards a longer duration of stay in the neonatal ward among newborns in the amoxicillin group suffering neonatal death ( p = 0.06 ) . It is concluded that antibiotic treatment of this group of women may be justified in setting s were sexually transmitted diseases and other genital infections are prevalent , whereas such treatment is less likely to have an effect when genital infection is rare BACKGROUND Severe acute malnutrition contributes to 1 million deaths among children annually . Adding routine antibiotic agents to nutritional therapy may increase recovery rates and decrease mortality among children with severe acute malnutrition treated in the community . METHODS In this r and omized , double-blind , placebo-controlled trial , we r and omly assigned Malawian children , 6 to 59 months of age , with severe acute malnutrition to receive amoxicillin , cefdinir , or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition . The primary outcomes were the rate of nutritional recovery and the mortality rate . RESULTS A total of 2767 children with severe acute malnutrition were enrolled . In the amoxicillin , cefdinir , and placebo groups , 88.7 % , 90.9 % , and 85.1 % of the children recovered , respectively ( relative risk of treatment failure with placebo vs. amoxicillin , 1.32 ; 95 % confidence interval [ CI ] , 1.04 to 1.68 ; relative risk with placebo vs. cefdinir , 1.64 ; 95 % CI , 1.27 to 2.11 ) . The mortality rates for the three groups were 4.8 % , 4.1 % , and 7.4 % , respectively ( relative risk of death with placebo vs. amoxicillin , 1.55 ; 95 % CI , 1.07 to 2.24 ; relative risk with placebo vs. cefdinir , 1.80 ; 95 % CI , 1.22 to 2.64 ) . Among children who recovered , the rate of weight gain was increased among those who received antibiotics . No interaction between type of severe acute malnutrition and intervention group was observed for either the rate of nutritional recovery or the mortality rate . CONCLUSIONS The addition of antibiotics to therapeutic regimens for uncomplicated severe acute malnutrition was associated with a significant improvement in recovery and mortality rates . ( Funded by the Hickey Family Foundation and others ; Clinical Trials.gov number , NCT01000298 . ) In a prospect i ve r and omised double-blind controlled trial that involved 73 patients with non-invasive wound infections receiving local wound treatment , the effect of adjuvant systemic antibiotic therapy was compared with that of a placebo . On inspection , more wounds were assessed as clinical ly clean after administration of an antibiotic than after the placebo was given although this difference was not statistically significant . Microbiological evaluation , however , showed a significantly higher cure of sepsis and elimination of individual organisms ( P less than 0.05 ) after antibiotic therapy . Furthermore , eradication of antibiotic-susceptible organisms was significantly greater than that of resistant organisms ( P less than 0.005 ) , indicating adequate penetration of antibiotic into the septic wound exu date . The results suggest that appropriate adjuvant systemic antibiotic therapy in the management of infected wounds promotes bacterial clearance and this may enhance healing of wounds Background For children at high risk of chronic suppurative otitis media ( CSOM ) , strategies to prevent acute otitis media with perforation ( AOMwiP ) may reduce progression to CSOM . Methods In a double blind study in northern Australia , 103 Aboriginal infants with first detection of OME were r and omised to receive either amoxicillin ( 50 mg/kg/d BD ) or placebo for 24 weeks , or until bilateral aerated middle ears were diagnosed at two successive monthly examinations ( success ) . St and ardised clinical assessment s and international st and ards for microbiology were used . Results Five of 52 infants in the amoxicillin group and none of 51 infants in the placebo group achieved success at the end of therapy ( Risk Difference = 9.6 % [ 95 % confidence interval 1.6,17.6 ] ) . Amoxicillin significantly reduced the proportion of children with i ) perforation at the end of therapy ( 27 % to 12 % RD = -16 % [ -31,-1 ] ) , ii ) recurrent perforation during therapy ( 18 % to 4 % RD = -14 % [ -25,-2 ] ) , and iii ) reduced the proportion of examinations with a diagnosis of perforation during therapy ( 20 % to 8 % adjusted risk ratio 0.36 [ 0.15,0.83 ] p = 0.017 ) . During therapy , the proportion of examinations with penicillin non-susceptible ( MIC > 0.1 microg/ml ) pneumococci was not significantly different between the amoxicillin group ( 34 % ) and the placebo group ( 40 % ) . Beta-lactamase positive non-capsular H. influenzae ( NCHi ) were uncommon during therapy but more frequent in the amoxicillin group ( 10 % ) than placebo ( 5 % ) . Conclusion Aboriginal infants receiving continuous amoxicillin had more normal ears , fewer perforations , and less pneumococcal carriage . There was no statistically significant increase in resistant pneumococci or NCHi in amoxicillin children compared to placebo children who received regular paediatric care and antibiotic treatment for symptomatic illnesses Background Despite guideline recommendations , there are no published r and omised controlled trial data on the efficacy of antibiotics for chronic wet cough in children . The majority of children with chronic wet cough have protracted bacterial bronchitis ( PBB ) , a recognised condition in multiple national guidelines . The authors conducted a parallel 1:1 placebo r and omised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough . Methods 50 children ( median age 1.9 years , IQR 0.9–5.1 ) with chronic ( > 3 weeks ) wet cough were r and omised to 2 weeks of twice daily oral amoxycillin clavulanate ( 22.5 mg/kg/dose ) or placebo . The primary outcome was ‘ cough resolution ’ defined as a > 75 % reduction in the vali date d verbal category descriptive cough score within 14 days of treatment compared with baseline scores , or cessation of cough for > 3 days . In selected children , flexible bronchoscopy and bronchoalveolar lavage ( BAL ) were undertaken at baseline . Results Cough resolution rates ( 48 % ) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo ( 16 % ) , p=0.016 . The observed difference between proportions was 0.32 ( 95 % CI 0.08 to 0.56 ) . Post treatment , median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 ( IQR 0.0–2.0 ) was significantly lower than in the placebo group , 2.25 ( IQR 1.15–2.9 ) ( p=0.02 ) . Pre-treatment BAL data were consistent with PBB in the majority of children , with no significant difference between groups . Conclusion A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough . BAL data support the diagnosis of PBB in the majority of these children . Clinical trial number ACTRN 12605000533695 Objective To determine the st and ard of reporting of harms-related data , in r and omised controlled trials ( RCTs ) according to the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement extension for harms . Design Systematic review . Data sources The Cochrane library , Ovid MEDLINE , Scopus and ISI Web of Knowledge were search ed for relevant literature . Eligibility criteria for selecting studies We included publications of studies that used the CONSORT harms extension to assess the reporting of harms in RCTs . Results We identified 7 studies which included between 10 and 205 RCTs . The clinical areas of the 7 studies were : hypertension ( 1 ) , urology ( 1 ) , epilepsy ( 1 ) , complimentary medicine ( 2 ) and two not restricted to a clinical topic . Quality of the 7 studies was assessed by a risk of bias tool and was found to be variable . Adherence to the CONSORT harms criteria reported in the 7 studies was inadequate and variable across the items in the checklist . Adverse events are poorly defined , with 6 studies failing to exceed 50 % adherence to the items in the checklist . Conclusions Readers of RCT publications need to be able to balance the trade-offs between benefits and harms of interventions . This systematic review suggests that this is compromised due to poor reporting of harms which is evident across a range of clinical areas . Improvements in quality could be achieved by wider adoption of the CONSORT harms criteria by journals reporting RCTs BACKGROUND Recommendations vary regarding immediate antimicrobial treatment versus watchful waiting for children younger than 2 years of age with acute otitis media . METHODS We r and omly assigned 291 children 6 to 23 months of age , with acute otitis media diagnosed with the use of stringent criteria , to receive amoxicillin-clavulanate or placebo for 10 days . We measured symptomatic response and rates of clinical failure . RESULTS Among the children who received amoxicillin-clavulanate , 35 % had initial resolution of symptoms by day 2 , 61 % by day 4 , and 80 % by day 7 ; among children who received placebo , 28 % had initial resolution of symptoms by day 2 , 54 % by day 4 , and 74 % by day 7 ( P=0.14 for the overall comparison ) . For sustained resolution of symptoms , the corresponding values were 20 % , 41 % , and 67 % with amoxicillin-clavulanate , as compared with 14 % , 36 % , and 53 % with placebo ( P=0.04 for the overall comparison ) . Mean symptom scores over the first 7 days were lower for the children treated with amoxicillin-clavulanate than for those who received placebo ( P=0.02 ) . The rate of clinical failure -- defined as the persistence of signs of acute infection on otoscopic examination -- was also lower among the children treated with amoxicillin-clavulanate than among those who received placebo : 4 % versus 23 % at or before the visit on day 4 or 5 ( P<0.001 ) and 16 % versus 51 % at or before the visit on day 10 to 12 ( P<0.001 ) . Mastoiditis developed in one child who received placebo . Diarrhea and diaper-area dermatitis were more common among children who received amoxicillin-clavulanate . There were no significant changes in either group in the rates of nasopharyngeal colonization with nonsusceptible Streptococcus pneumoniae . CONCLUSIONS Among children 6 to 23 months of age with acute otitis media , treatment with amoxicillin-clavulanate for 10 days tended to reduce the time to resolution of symptoms and reduced the overall symptom burden and the rate of persistent signs of acute infection on otoscopic examination . ( Funded by the National Institute of Allergy and Infectious Diseases ; Clinical Trials.gov number , NCT00377260 . ) BACKGROUND AND AIM Several studies have reported adjunctive benefits to scaling and root planing ( SRP ) of systemic amoxycillin and metronidazole in the treatment of periodontal diseases . To date no comparisons have been made of these antimicrobials alone or in combination . The aim of this study was to compare the adjunctive benefits to SRP of amoxycillin and metronidazole alone and combined . METHODS 66 subjects < 46 years of age with advanced chronic periodontal disease participated in this r and omised , double blind , 4 parallel treatment group design ed study . All subjects received quadrant SRP and then were prescribed amoxycillin capsules ( 250 mg ) and metronidazole tablets ( 200 mg ) ( AM ) or lactate capsules and metronidazole ( PM ) or amoxycillin and calcium lactate tablets ( AP ) or lactate and calcium lactate ( PP ) . All medication was 3 of each per day for 7 days . Subgingival plaque sample s were obtained and probing depth ( PD ) , loss of attachment ( LOA ) , bleeding on probing ( BOP ) , suppuration ( SUPP ) and plaque ( DEP ) were recorded pre-treatment , 1 , 3 and 6 months post-treatment . RESULTS Final group sizes were : AM=15 , PM=16 , AP=16 and PP=15 . PD improved in all groups . Treatment effects were highly significantly different and always greatest in the AM and least in the PP groups . Benefits of PM and AP over PP were also noted . LOA improved in all groups and showed the same highly significant treatment differences , again favouring AM . BOP improved in all groups , particularly in AM compared to the other groups . SUPP improved in all groups and was virtually eradicated in AM with differences among treatments highly significant . DEP changed little in any group and there were no significant differences among groups . Microbiological data showed significant differences in favour of AM compared to PP and PM for total aerobes and anaerobes at 1 month . P. intermedia counts were always lower in active groups compared to PP and reached significance for AM and AP at 1 month and AM and PM at 3 months . CONCLUSION The significant differences among treatment groups and the overall trend in the data , in line with other studies , support the considerable adjunctive benefits to SRP of amoxycillin and metronidazole combined in the treatment of advanced chronic periodontal disease OBJECTIVE The role of routine antimicrobial treatment of acute middle-ear infections is under debate , because the efficacy of antimicrobials in the resolution of middle-ear fluid has not been unambiguously proven . Acute tube otorrhea is regarded as evidence of acute otitis media , and for method ologic reasons it was chosen to provide objectivity for diagnostics and outcome assessment . The objective of this study was to assess whether amoxicillin-clavulanate accelerates the resolution of acute tube otorrhea . DESIGN AND SETTING R and omized , double-blind , placebo-controlled study in outpatient setting . PATIENTS Volunteer sample of basically healthy 6- to 72-month-old children with a tympanostomy tube . Eligibility required having acute tube otorrhea of < 48 hours ' of duration and no prior treatment within the last 2 weeks . The mean age of the participants was 25 months ; they had a history of 3 episodes of acute otitis media ( median ) , and 99 % had manifestations of a concomitant respiratory infection . Of 79 r and omized patients , 7 were withdrawn because of adverse events ; 66 patients completed the study . INTERVENTIONS Amoxicillin-clavulanate ( N = 34 ; 45 mg/kg/d ) or matching placebo ( N = 32 ) for 7 days and daily suction of middle-ear fluid through tympanostomy tube . MAIN OUTCOME MEASURES Duration of acute tube otorrhea and duration of bacterial growth in middle-ear fluid . RESULTS The median duration of tube otorrhea was significantly shorter in amoxicillin-clavulanate than in the placebo group ( 3 vs 8 days ) . At the end of the 7-day medication period , tube otorrhea was resolved in 28 of 34 children receiving amoxicillin-clavulanate compared with 13 of 32 children on placebo ( treatment-control difference 41 % ; 95 % confidence interval , 20%-63 % ; number needed to treat , 2.4 ) . The median duration of bacterial growth in middle-ear fluid was shorter in amoxicillin-clavulanate than in the placebo group ( 1 vs 8 days ) . CONCLUSIONS Oral antibiotic treatment significantly accelerates the resolution of acute tube otorrhea by reducing bacterial growth in middle-ear fluid BACKGROUND Lower-respiratory-tract infection is one of the most common acute illnesses managed in primary care . Few placebo-controlled studies of antibiotics have been done , and overall effectiveness ( particularly in subgroups such as older people ) is debated . We aim ed to compare the benefits and harms of amoxicillin for acute lower-respiratory-tract infection with those of placebo both overall and in patients aged 60 years or older . METHODS Patients older than 18 years with acute lower-respiratory-tract infections ( cough of ≤28 days ' duration ) in whom pneumonia was not suspected were r and omly assigned ( 1:1 ) to either amoxicillin ( 1 g three times daily for 7 days ) or placebo by computer-generated r and om numbers . Our primary outcome was duration of symptoms rated " moderately bad " or worse . Secondary outcomes were symptom severity in days 2 - 4 and new or worsening symptoms . Investigators and patients were masked to treatment allocation . This trial is registered with EudraCT ( 2007 - 001586 - 15 ) , UKCRN Portfolio ( ID 4175 ) , IS RCT N ( 52261229 ) , and FWO ( G.0274.08N ) . FINDINGS 1038 patients were assigned to the amoxicillin group and 1023 to the placebo group . Neither duration of symptoms rated " moderately bad " or worse ( hazard ratio 1.06 , 95 % CI 0.96 - 1.18 ; p=0.229 ) nor mean symptom severity ( 1.69 with placebo vs 1.62 with amoxicillin ; difference -0.07 [ 95 % CI -0.15 to 0.007 ] ; p=0.074 ) differed significantly between groups . New or worsening symptoms were significantly less common in the amoxicillin group than in the placebo group ( 162 [ 15.9 % ] of 1021 patients vs 194 [ 19.3 % ] of 1006 ; p=0.043 ; number needed to treat 30 ) . Cases of nausea , rash , or diarrhoea were significantly more common in the amoxicillin group than in the placebo group ( number needed to harm 21 , 95 % CI 11 - 174 ; p=0.025 ) , and one case of anaphylaxis was noted with amoxicillin . Two patients in the placebo group and one in the amoxicillin group needed to be admitted to hospital ; no study -related deaths were noted . We noted no evidence of selective benefit in patients aged 60 years or older ( n=595 ) . INTERPRETATION When pneumonia is not suspected clinical ly , amoxicillin provides little benefit for acute lower-respiratory-tract infection in primary care both overall and in patients aged 60 years or more , and causes slight harms . FUNDING European Commission Framework Programme 6 , UK National Institute for Health Research , Barcelona Ciberde Enfermedades Respiratorias , and Research Foundation Fl and ers OBJECTIVE --To examine the efficacy and safety of conservative management of mild otitis media ( " the acute red ear " ) in children . DESIGN --Double blind placebo controlled trial . SETTING --17 group general practice s ( 48 general practitioners ) in Southampton , Bristol , and Portsmouth . PATIENTS --232 children aged 3 - 10 years with acute earache and at least one abnormal eardrum ( 114 allocated to receive antibiotic , 118 placebo ) . INTERVENTIONS --Amoxycillin 125 mg three times a day for seven days or matching placebo ; 100 ml paracetamol 120 mg/5 ml . MAIN OUTCOME MEASURES --Diary records of pain and crying , use of analgesic , eardrum signs , failure of treatment , tympanometry at one and three months , recurrence rate , and ear , nose , and throat referral rate over one year . RESULTS --Treatment failure was eight times more likely in the placebo than the antibiotic group ( 14.4 % v 1.7 % , odds ratio 8.21 , 95 % confidence interval 1.94 to 34.7 ) . Children in the placebo group showed a significantly higher incidence of fever on the day after entry ( 20 % v 8 % , p less than 0.05 ) , mean analgesic consumption ( 0.36 ml/h v 0.21 ml/h , difference 0.14 , 95 % confidence interval 0.07 to 0.23 ; p = 0.0022 ) , mean duration of crying ( 1.44 days v 0.50 days , 0.94 ; 0.50 to 1.38 ; p less than 0.001 ) , and mean absence from school ( 1.96 days v 0.52 days , 1.45 ; 0.46 to 2.42 ; p = 0.0132 ) . Differences in recorded pain were not significant . The prevalence of middle ear effusion at one or three months , as defined by tympanometry , was not significantly different , nor was there any difference in recurrence rate or in ear , nose , and throat referral rate in the follow up year . No characteristics could be identified which predicted an adverse outcome . CONCLUSIONS --Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy Background : Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries . Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown . Design , setting and participants : R and omised , triple blind , placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi , Kenya , with acute bronchitis but without evidence of chronic lung disease . Main outcome measure : The primary study end point was clinical cure , as defined by a ⩾75 % reduction in a vali date d Acute Bronchitis Severity Score by 14 days ; analysis was by intention to treat with equivalence defined as ⩽8 % difference between study arms . Results : Clinical cure rates in the amoxicillin and placebo arms were 81.7 % and 84.0 % , respectively ( difference 2.3 % , 95 % CI −8.6 % to 4.0 % ) . Of 131 HIV infected subjects ( 19.8 % ) , cure rates for those r and omised to amoxicillin ( 77.2 % ) and placebo ( 83.8 % ) differed by 6.6 % ( 95 % CI −21.7 % to 8.6 % ) . Among HIV uninfected subjects , the difference in cure rates was 1.6 % ( 95 % CI −8.5 % to 5.3 % ) . Potential drug side effects were similar in the two arms . No subjects required hospitalisation or died . Conclusion : Antibiotic treatment of acute bronchitis is unhelpful , even in population s with a high prevalence of HIV infection Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms Objective : The objective of this study was to determine whether prophylactic treatment with oral broad-spectrum antimicrobial therapy improves pregnancy outcomes in twin gestations . Methods : Patients with twin gestations between 24 and 32 weeks were r and omized to receive amoxicillin/clavulanic acid or placebo . Those patients r and omized before 24 weeks received a 1-week course at 24 and at 28 weeks gestation . Those patients entered later than 24 weeks received a 1-week course either at 28 weeks or at enrollment ( up to 32 weeks ) . Other than antibiotic use , the management of the groups was identical and unchanged from the routine care of twin gestations . Results : Of 149 twin pregnancies enrolled , 76 were r and omized to the drug group and 73 to the placebo group . There was no significant difference in mean gestational age at delivery ( 35.9 vs. 35.7 weeks ) , birth weight ( 2,358 vs. 2,344 g ) , mean neonatal nursery stay ( 9.9 vs. 11.7 days ) , or respiratory distress syndrome ( 6/76 vs. 4/73 ) in the drug vs. placebo group , respectively . Conclusions : The addition of prophylactic oral broad-spectrum antimicrobial therapy to the st and ard antepartum management of twin gestations had no demonstrable effect on the gestational age at delivery , birth weight , or neonatal complications . There did not appear to be any beneficial effect of the prophylactic use of amoxicillin/clavulanic acid in this clinical setting A double-blind r and omized controlled trial of amoxycillin , co-trimoxazole , and placebo was conducted on 197 children presenting with presumed viral respiratory infections . Routine throat swabs were taken to exclude streptococcal diseases . The three disease categories studied -- nasopharyngitis , pharyngotonsillitis , and bronchitis ( including laryngotracheobronchitis)--showed a generally similar pattern of resolution irrespective of treatment . Nevertheless , seven out of 66 children receiving placebo were withdrawn from the trial with unremitting symptoms or complications thought to require antimicrobial treatment . Only two of 56 children receiving amoxycillin and none of 75 receiving co-trimoxazole were withdrawn . Three other children receiving amoxycillin and three receiving placebo were seen during the trial but further treatment was not thought to be necessary . Thus the return consultation rate in children receiving placebo therapy was 15 % compared with 4 % for those receiving antimicrobial treatment . Antimicrobial treatment was associated with less nasal discharge on the eighth day of treatment . Placebo treatment allowed an earlier return to normal activity . There was a high incidence of possible side effects on all regimens including placebo . It is concluded that the benefits of antimicrobial treatment in presumed viral respiratory infections are marginal , and they should not be routinely prescribed for these conditions BACKGROUND Sinusitis is the fifth most common reason for patients to visit primary care physicians , yet clinical outcomes relevant to patients are seldom studied . OBJECTIVE To determine whether patients with purulent rhinitis , " sinusitis-type symptoms , " improved with antibiotics . Second , to examine a clinical prediction rule to provide preliminary validation data . METHODS Prospect i ve clinical trial , with double-blinded placebo controlled r and omization . The setting was a suburb of Washington , DC , from Oct 1 , 2001 , to March 31 , 2003 . All participants were 18 years or older , presenting to a family practice clinic with a complaint of sinusitis and with pus in the nasal cavity , facial pressure , or nasal discharge lasting longer than 7 days . The main outcome measures were resolution of symptoms within a 14-day follow-up period and the time to improvement ( days ) . RESULTS After exclusion criteria , 135 patients were r and omized to either placebo ( n=68 ) or amoxicillin ( n=67 ) for 10 days . Intention-to-treat analyses showed that 32 ( 48 % ) of the amoxicillin group vs 25 ( 37 % ) of the placebo group ( P=.26 ) showed complete improvement by the end of the 2-week follow-up period ( relative risk=1.3 ; 95 % confidence interval [ CI ] , 0.87 - 1.94 ] ) . Although the rates of improvement were not statistically significantly different at the end of 2 weeks , the amoxicillin group improved significantly earlier , in the course of treatment , a median of 8 vs 12 days , than did the placebo group ( P=.039 ) . CONCLUSION For most patients with sinusitis-type complaints , no improvement was seen with anti-biotics over placebo . For those who did improve , data suggested there is a subgroup of patients who may benefit from antibiotics BACKGROUND Reports of clinical trials usually emphasize efficacy results , especially when results are statistically significant . Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed . Our aim was to describe the reporting of harm-related results from r and omized controlled trials ( RCTs ) . METHODS We search ed the MEDLINE data base for reports of RCTs published from January 1 , 2006 , through January 1 , 2007 , in 6 general medical journals with a high impact factor . Data were extracted by use of a st and ardized form to appraise the presentation of safety results in text and tables . RESULTS Adverse events were mentioned in 88.7 % of the 133 reports . No information on severe adverse events and withdrawal of patients owing to an adverse event was given in 27.1 % and 47.4 % of articles , respectively . Restrictions in the reporting of harm-related data were noted in 43 articles ( 32.3 % ) with a description of the most common adverse events only ( n = 17 ) , severe adverse events only ( n = 16 ) , statistically significant events only ( n = 5 ) , and a combination of restrictions ( n = 5 ) . The population considered for safety analysis was clearly reported in 65.6 % of articles . CONCLUSION Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs The purpose of the present investigation was to assess the effects of periodontal surgery and 4 systemically administered agents , Augmentin , tetracycline , ibuprofen or a placebo on clinical and microbiological parameters of periodontal disease . 98 subjects were monitored at 2-month intervals at 6 sites per tooth for clinical parameters . Subgingival plaque sample s were taken from the mesial surface of each tooth at each visit and evaluated for their content of 14 subgingival species using DNA probes and a colony lift method . 40 subjects who exhibited loss of attachment > 2.5 mm at 1 or more sites during longitudinal monitoring were treated using modified Widman flap surgery at sites with probing pocket depth > 4 mm , subgingival scaling at all other sites and were r and omly assigned 1 of the 4 agents . Treatment was completed within 30 days during which time the subject took the assigned agent . Overall , subjects exhibited a mean attachment level " gain " of 0.34 + /- 0.10 mm ( SEM ) and a mean pocket depth reduction of 0.62 + /- 0.09 mm 10 + /- 4 months post-therapy . However , certain subjects in each treatment group showed a poor response . Subjects receiving antibiotics exhibited significantly more attachment level " gain " ( 0.57 + /- 0.15 mm , SEM ) than subjects receiving either ibuprofen or a placebo ( 0.02 + /- 0.10 ) . The differences between Augmentin and tetracycline groups were not significant , nor were the differences between ibuprofen and placebo . 10 months post-therapy , there was a reduction in the number of sites colonized in any subject group by detectable levels ( 10(3 ) ) of P. gingivalis . Species showing similar reductions were B. forsythus , P. intermedia and P. micros . Subjects receiving systemically administered antibiotics had a significant increase in the proportion of sites colonized by C. ochracea coupled with a greater decrease in the number of sites colonized by P. gingivalis , B. forsythus , P. intermedia and P. micros post-therapy than subjects not receiving antibiotics . The results of this investigation indicate that adjunctive systemic antibiotics increase periodontal attachment " gain " and decrease the levels of some suspected periodontal pathogens in subjects with evidence of current disease progression OBJECTIVE To evaluate whether an outpatient antibiotic regimen decreased group B streptococcal ( GBS ) colonization to preclude the use of intrapartum antibiotics . METHODS A double-blind r and omized controlled trial evaluating prenatal oral amoxicillin versus placebo with the primary outcome of GBS colonization at the time of labor . RESULTS Of those patients receiving both amoxicillin and a repeat culture at the time of labor , 6 of the 14 ( 43 % ) tested positive for GBS colonization . Given persistent GBS colonization of 67 % ( 10/15 ) in the placebo group , treatment with amoxicillin did not significantly impact colonization at the time of delivery ( P=0.20 ) . CONCLUSION A regimen of outpatient amoxicillin was associated with persistent GBS colonization in 43 % of women at the time of labor . Oral prenatal antibiotic prophylaxis against GBS does not sufficiently reduce colonization to preclude intrapartum intravenous antibiotics The aim of the study was to evaluate whether a broad-spectrum penicillin , amoxicillin , was superior to placebo in resolving symptoms of acute exacerbations of chronic bronchitis in patients from general practice . 131 general practitioners included 278 patients over a period of 30 months . The patients were r and omly assigned to treatment with amoxicillin 750 mg b.i.d . or corresponding placebo for 7 days . Patients with pneumonia , a temperature above 38.5 degrees C or heart rate over 100 were excluded for safety reasons . The main effect parameter -- the doctors ' overall evaluation of the treatment -- did not demonstrate any statistically significant difference between amoxicillin or placebo , 63 % versus 64 % of the patients . Resolution of symptoms was obtained by 19 % ( 25/132 ) of the patients in the amoxicillin group compared with 10 % ( 13/136 ) of the patients in the placebo group , P = 0.03 . The present findings do not favour routine use of antibiotics in an attempt to improve the course of acute exacerbations as defined in this study in patients with chronic bronchitis PURPOSE To evaluate the efficacy of prophylactic antibiotics for dental implant placement . MATERIAL S AND METHODS Thirteen dentists working in private practice s agreed to participate in this trial , each centre providing 50 patients . One hour prior to implant placement , patients were r and omised to take orally 2 g amoxicillin or identical placebo tablets . Patients needing bone augmentation at implant placement were not included . Outcome measures were prosthesis and implant failures , adverse events and post-operative complications . Patients were seen 1 week , 2 weeks and 4 months post-operatively . RESULTS Two centres did not deliver any data , two centres did not manage to include the agreed quota of patients and three patients had to be excluded . Two-hundred and fifty-two patients were evaluated in the antibiotic group and 254 in the placebo group , and none dropped out at 4 months . Four prostheses and seven implants ( in five patients ) failed in the antibiotics group versus 10 prostheses and 13 implants ( in 12 patients ) in the placebo group . Eleven complications were reported in the antibiotic group versus 13 ( in 12 patients ) in the placebo group . No side effects were reported . There were no statistically significant differences for prosthesis failures , implant losses and complications . Patients receiving immediate post-extractive implants had an increased failure risk compared with patients receiving delayed implants ( 9 % versus 2 % ) . CONCLUSIONS No statistically significant differences were observed , although trends clearly favoured the antibiotic group . Immediate post-extractive implants were more likely to fail Background The study was design ed to assess the usefulness of postoperative antibiotics in patients undergoing endoscopic sinus surgery ( ESS ) . Methods The effects of antibiotics in the postoperative period of ESS patients were evaluated in a prospect i ve , r and omized , double-blind , placebo-controlled study . Fifty patients were treated with amoxicillin/clavulanate for 2 weeks after ESS , while the other half received placebo . Preoperatively , the symptom , endoscopic , and CT scores were recorded . In the postoperative period , symptom and endoscopic scores were recorded on the 5th , 12th , 21st , and 30th days . In estimating the length of the blood crust formation episode , a Kaplan-Meier plot was used . Results Seventy-five patients completed the study : forty in the antibiotic-treated group and thirty-five in the placebo group . On the 5th day , nasal obstruction and drainage were significantly better in the antibiotic-treated group . In addition , a statistically significant difference in the endoscopic scores was noted between the treatment and placebo groups on days 5 and 12 . Conclusion The use of an antibiotic ( amoxicillin/clavulanate ) in the postoperative period is able to improve the outcome in the early blood crust healing phase : nasal obstruction and drainage are reduced and the endoscopic score objective ly showed a faster recovery In a r and omized , prospect i ve , double-blind study infants and children with uncomplicated Salmonella gastroenteritis were treated with ampicillin ( 15 patients ) , amoxicillin ( 15 patients ) , or placebo ( 14 patients ) . The dosage of antibiotics was 100 mg/kg/day in four equally divided doses given for five days . There was no significant benefit from antibiotic therapy on the duration of diarrhea ( means 8.8 , 7.3 , and 7.2 days , respectively ) or on the duration of recovery of Salmonella from stool cultures ( means 41.3 , 37.0 , and 20.9 days , respectively ) . Bacteriologic relapse was not observed in placebo-treated patients but eight patients given ampicillin ( 53 % ) and eight given amoxicillin ( 53 % ) had relapse ( P = .003 ) . Salmonella isolated in relapse were still susceptible in vitro to the antibiotics . Of the 16 patients with bacteriologic relapse six ( 38 % ) had concomitant recurrence of diarrhea . It is concluded that ampicillin or amoxicillin therapy provides no benefit to patients with uncomplicated Salmonella gastroenteritis and substantially increases the risk of bacteriologic and symptomatic relapse To test the hypothesis that sub clinical enteric infection ( such as bacterial overgrowth ) , rice malabsorption , and growth faltering are causally linked , a field trial of low-dose , short-term , intermittent antibiotic treatment was carried out in 142 hydrogen-producing ( by lactulose breath hydrogen test ) Burmese village children aged 6 - 59 months . The children were r and omly allocated treatment with metronidazole ( 20 mg/kg or 5 mg/kg daily ) , amoxycillin ( 25 mg/kg daily ) , or placebo given 1 week per month for 6 months . A cooked rice meal breath hydrogen test was done to classify the children as rice absorbers ( RA ) or rice malabsorbers ( RM ) before treatment and monthly on the day before each cycle of treatment . There were no differences between the treatment groups , so they were considered together . Factorial analysis showed that antibiotic treatment did not significantly affect the proportion of RM children . The only significant difference between antibiotic-treated and placebo-treated children 's growth was in the subgroup of RM children aged 36 - 47 months ; the antibiotic-treated children had significantly greater linear growth . In other age groups antibiotic treatment had no effect on growth We r and omly assigned 45 adult patients with Campylobacter pylori-confirmed antral gastritis to 8 days of treatment with 1 g amoxycillin suspension twice a day , or placebo , according to a double-blind study design . At the end of therapy , 91 % of patients treated with amoxycillin demonstrated clearance of the organism from the antrum , compared with 16 % in the placebo group ( p less than 0.001 ) . Active antral gastritis resolved in 68 % of patients in the amoxycillin group versus only 9 % in the placebo group ( p less than 0.001 ) . No significant difference was observed when looking at the evolution of chronic only gastritis . No significant improvement was observed in the assessment of clinical symptoms and endoscopic appearance . Reappearance of C. pylori and significant worsening of the histological score of active gastritis was observed after 2 wk in all patients . In a second study phase , 18 patients initially not cleared of their bacteria received amoxycillin single blind for 14 days . Clearance of bacteria associated with improvement or resolution of active gastritis was observed in 72 % of the cases . In this subgroup , all patients investigated after 1 month were recolonized with C. pylori and , again , had histological active gastritis . We conclude that amoxycillin is effective in treating active antral gastritis associated with C. pylori , but not in preventing relapses , which occur in all cases within 1 month after therapy Postoperative infections in the oral region are usually caused by anaerobic bacteria . While some authors cl aim that routine antibiotic prophylaxis is necessary after third molar surgery , others do not recommend this practice . The major subject of controversy is what constitutes postoperative infection . Previous studies that have examined the benefit of routine antibiotic prophylaxis have used several clinical symptoms ( pain , swelling , and trismus ) as indicators of infection ; however , these clinical symptoms may be vague and unreliable , and can not be evaluated scientifically . As a result , their use has only sparked more debate in this area of research . The present study assessed the value of routine antibiotic prophylaxis in impacted m and ibular third molar surgery using acute-phase protein levels as potential indicators of early and late postoperative infection . Specifically , serum levels of C-reactive protein and alpha-1 antitrypsin were measured preoperatively and postoperatively in patients who received either prophylactic antibiotics or placebos . The results revealed no statistically significant difference between treated and control patients in terms of incidence of postoperative infection The purpose of this investigation was to evaluate the efficacy of amoxicillin for treatment of bacterial vaginosis during pregnancy . The diagnosis of bacterial vaginosis was established by clinical examination and microscopic examination of a Gram stain and saline preparation of vaginal secretions . In a double-blind , r and omized manner , 108 patients at 15 - 25 weeks ' gestation were assigned to treatment with oral amoxicillin , 500 mg three times daily for 14 days , or placebo . Patients were evaluated 2 weeks after treatment , at 34 - 36 weeks ' gestation , and at delivery . There were no significant differences between the two groups with respect to any clinical or microbiologic measure of treatment outcome . There were also no significant differences in the frequency of obstetric complications . We conclude that amoxicillin is not effective therapy for bacterial vaginosis in pregnant The adequacy of serum bactericidal activity after oral amoxycillin given as prophylaxis against infective endocarditis was studied using a double blind r and omised protocol in healthy volunteers having dentistry . One hour before their procedure 38 patients received 3 g amoxycillin syrup and 12 received matching placebo . Venous blood sample s were drawn before and one and nine hours after dosing and serum amoxycillin concentrations determined using a st and ard bioassay . Sample s containing amoxycillin had inhibitory titres measured against two reference isolates of viridans streptococci known to have caused infective endocarditis . The susceptibility to amoxycillin of one strain was high and the other low , respective minimal bactericidal and inhibitory concentrations being 0.08 and 0.04 mumol/l ( 0.03 and 0.015 microgram/ml ) and 2.74 and 1.37 mumol/l ( 1 and 0.5 microgram/ml ) . Amoxycillin was detected in only post-treatment sample s of patients given the active drug . There were no significant correlations between one or nine hour drug concentrations and age or physical characteristics , nor was there any relation to preceding food consumption . Correlations between drug concentrations at one and nine hours were weak ( r = 0.34 ; p less than 0.05 ) , but between corresponding drug concentrations and serum inhibitory titres there were consistent correlations ( r = 0.46 - 0.48 ; p less than 0.005 ) . Against the low susceptibility reference isolate bactericidal amoxycillin concentrations were encountered in only 20 of the 38 nine hour sample s ( 95 % confidence limits 34 % and 66 % ) . When repeat doses of amoxycillin are indicated after dentistry they should be given about four hours later , not eight hours later as commonly practised We performed a r and omized , double-blind , placebo-controlled study to determine whether acute otitis media could be prevented by antibiotic therapy initiated promptly after the appearance of symptoms of upper respiratory tract infection . One hundred four children aged 1 to 4 years received a 7-day course of either amoxicillin-clavulanate or placebo . Acute otitis media developed in 9 ( 18 % ) of the 50 children receiving amoxicillin clavulanate and in 12 ( 22 % ) of the 54 children receiving placebo ( p = 0.59 ) 52 children with severe cough persisting for more than 10 days were r and omized to treatment with amoxycillin/clavulanic acid or placebo in a prospect i ve double-blinded study . Clinical ly suspected cases of pertussis were excluded , yet 12 ( 23 % ) of the children had laboratory verified pertussis infection . The nasopharyngeal colonization showed a predominance of Moraxella catarrhalis which was isolated in 37 ( 71 % ) children . Streptococcus pneumoniae and Haemophilus influenzae were isolated in 11 ( 20 % ) and 16 ( 30 % ) children , respectively . The antibiotic-treated group had a significantly better recovery in both the pediatrician 's estimation ( p = 0.02 ) and the independent parental judgement ( p = 0.002 ) . These findings are consistent with the view that Moraxella catarrhalis could be directly involved in the pathogenesis of persistent cough in children The value of prophylactic antibiotics in the treatment of animal bites is uncertain . A prospect i ve double blind stratified trial was performed comparing a broad spectrum antibiotic amoxycillin/clavulanate with placebo in full thickness animal bite wounds in a series of 185 consecutive patients . In wounds less than 9 h old , no significant benefit was found with the antibiotic . In older wounds , presenting 9 - 24 h after injury , the infection rate was reduced significantly ( P = 0.023 ) , although the numbers were small . We recommend the use of such an antibiotic on wounds 9 - 24 h old and query its use in more recent injuries , unless tendons or joints are likely to be involved BACKGROUND Borrelia burgdorferi , which causes Lyme disease , is transmitted by deer ticks ( lxodes dammini ) in the northeastern and midwestern United States . Although deer-tick bites are common in areas in which the disease is endemic , there is uncertainty about how to manage the care of persons who are bitten . METHODS To assess the risk of infection with B. burgdorferi and the efficacy of prophylactic antimicrobial treatment after a deer-tick bite , we conducted a double-blind , placebo-controlled trial in an area of southeastern Connecticut in which Lyme disease is endemic . Children and adults who had been bitten by deer ticks were r and omly assigned to receive either amoxicillin or placebo for 10 days . Subjects were followed for one year for clinical manifestations of Lyme disease . Serum sample s obtained at enrollment and six weeks and three months later were tested for antibodies against B. burgdorferi . RESULTS Of the 387 subjects , 205 ( 53 percent ) were assigned to receive amoxicillin and 182 ( 47 percent ) to receive placebo . Of 344 deer ticks su bmi tted and analyzed by the polymerase chain reaction , 15 percent were infected with B. burgdorferi . Erythema migrans developed in two subjects , both of whom had received placebo . There were no asymptomatic seroconversions and no late manifestations of Lyme disease . The risk of infection with B. burgdorferi in the placebo-treated subjects was 1.2 percent ( 95 percent confidence interval , 0.1 to 4.1 percent ) , which was not significantly different ( P = 0.22 ) from the risk in the amoxicillin-treated subjects ( 0 percent ; 95 percent confidence interval , 0 to 1.5 percent ) . CONCLUSIONS Even in an area in which Lyme disease is endemic , the risk of infection with B. burgdorferi after a recognized deer-tick bite is so low that prophylactic antimicrobial treatment is not routinely indicated The aim of the present study was to investigate the clinical and microbiological effects of initial periodontal therapy in conjunction with systemic amoxicillin plus clavulanic acid in adult periodontitis patients using a double-blind , parallel-group , and placebo-controlled protocol . 21 patients with a clinical diagnosis of generalised adult periodontitis were recruited . Clinical measurements and microbiological assessment s were carried out at baseline , 3 , and 12 months post-treatment . Approximately 6 weeks after initial periodontal treatment ( 3 - 6 h ) , patients were r and omly assigned to receive coded study medication of 500 mg amoxicillin plus 125 mg clavulanic acid ( Augmentin ) or placebo , every 8 h for 10 days . Patients returned for follow-up visits 3 , 6 , 9 , and 12 months after completion of the medication . The mean plaque index ( PI ) at baseline was 1.1 for placebo group and 0.9 for the test group . At 3 months , the PI had dropped to 0.3 in both groups , and was maintained during the rest of the study . The changes in bleeding on probing ( BOP ) and gingival index ( GI ) in the course of the study were similar in both groups . The mean whole mouth probing pocket depth ( PPD ) in the placebo group was 3.8 mm at baseline and 3.9 mm in the test group . A mean reduction of 1.0 mm in the placebo group and 0.9 mm in the test group was observed during the first 3 months . No further reduction in PPD was noticed during the study period in either group . There was no statistically significant difference in the PPD reduction between the 2 groups . The change in clinical attachment level ( CAL ) from baseline to 3 months amounted to 0.5 mm in both groups . Between 3 and 12 months , the CAL changed in neither group . In both groups , treatment result ed in a decrease in the number of spirochetes and motile rods in positive patients , but no significant differences between either group were noted in any of the dark field microscopy observations . At baseline , 1 patient in the placebo group and 2 patients in the test group were culture positive for Actinobacillus actinomycetemcomitans ( Aa ) . After therapy , Aa was not detectable in the placebo group and 1 patient remained positive in the test group . In the placebo group , the number of patients positive for Porphyromonas gingivalis ( Pg ) decreased from 7 to 2 after therapy . In the test group , the 4 patients positive for Pg at baseline remained positive after therapy . In both groups , all subjects were positive for Prevotella intermedia ( Pi ) and Fusobacterium nucleatum ( Fn ) at baseline . At 12 months , all subjects had detectable subgingival Fn . 9 out of the 11 placebo and 8 of the 10 test patients remained positive for Pi . There were no differences in detection frequency of Peptostreptococcus micros ( Pm ) and Bacteroides forsythus ( Bf ) in both groups between baseline , 3 , and 12 months post-treatment . The findings demonstrated that , in comparison to placebo , systemic amoxicillin plus clavulanic acid provided no additional clinical and microbiological effects in the treatment of adult periodontitis patients BACKGROUND Upper-respiratory-tract infection is one of the main causes of overuse of antibiotics . We have found previously that bacteria such as Haemophilus influenzae , Moraxella catarrhalis , and Streptococcus pneumoniae can be isolated from the nasopharyngeal secretions of a substantial proportion of adults with upper-respiratory-tract infections . We have assessed the efficacy of co-amoxiclav in patients with common colds but no clinical signs of sinusitis or other indications for antibiotics . METHODS Between January , 1992 and March , 1994 , 314 patients who presented to our outpatient clinic with common colds were enrolled in the double-blind , placebo-controlled study . They were r and omly assigned 5 days ' treatment with co-amoxiclav ( 375 mg three times daily ) or identical placebo . Clinical examinations were done at enrolment and on day 5 - 7 to assess outcome ( cured , persistent symptoms , worse symptoms ) . Seven patients were excluded after r and omisation , seven did not have nasopharyngeal aspiration , and 12 did not return for followup assessment . FINDINGS Of 300 patients with nasopharyngeal aspirates , 72 had negative bacterial cultures , 167 had cultures positive only for bacteria unrelated to respiratory infections , and 61 had cultures positive for H influenzae , M catarrhalis , or S pneumoniae . At 5-day follow-up of these culture-positive patients , the distribution of outcome was significantly better among co-amoxiclav-treated ( n=30 ) than placebo-treated ( n=28 ) patients ( cured 27 vs 4 % ; persistent symptoms 70 vs 60 % ; worse symptoms 3 vs 36 % ; p=0.001 ) . Patients on co-amoxiclav also scored their symptoms significantly lower than patients on placebo ( p=0.008 ) . Among culture-negative patients ( n=230 ) , the outcome distribution did not differ between the treatment groups ( p=0.392 ) . INTERPRETATION The majority of patients with upper-respiratory-tract infection do not benefit from antibiotics and side-effects are frequent . However , for the subgroup whose nasopharyngeal secretions contain H influenzae , M catarrhalis , or S pneumoniae , antibiotics are clinical ly beneficial OBJECTIVES This trial compared the efficacy of amoxicillin prophylaxis with that of placebo for the management of recurrent middle ear effusion ( MEE ) in children . METHODS Children between 7 months and 12 years of age who were effusion-free at entry but had histories of chronic or recurrent MEE were r and omly assigned to receive either amoxicillin ( 20 mg/kg once daily ) or placebo for 1 year . They were examined monthly and when there were symptoms of ear , nose or throat disease . Acute otitis media ( AOM ) and new episodes of otitis media with effusion ( OME ) were treated with amoxicillin-clavulanate ; tympanocentesis was performed when possible for episodes of AOM . Throat cultures were obtained at entry ; 4 , 8 and 12 months after entry ; and with new episodes of AOM and OME . Tympanometry was performed at each visit and audiometry was performed at entry and 4 , 8 and 12 months after entry . RESULTS One hundred eleven children were entered in this study . The rates per person year of new episodes of disease in the amoxicillin and placebo groups , respectively , were : MEE , 1.81 vs. 3.18 ( P < 0.001 ) ; AOM , 0.28 vs. 1.04 ( P < 0.001 ) ; and OME , 1.53 vs. 2.15 ( P = 0.016 ) . Subjects in the amoxicillin group had less time with MEE than the placebo group ( 19.7 and 33.2 % , respectively ; P = 0.002 ) . Middle ear and throat cultures did not reveal any increase in beta-lactamase-producing organisms or in Streptococcus pneumoniae attributable to daily use of amoxicillin . CONCLUSIONS Amoxicillin prophylaxis lowered the rates of occurrence of MEE , AOM and OME and decreased the percentage of time with MEE . However , because of present day concerns regarding antibiotic resistance , management should be individualized Objective To evaluate the effectiveness and costs of a multifaceted flexible educational programme aim ed at reducing antibiotic dispensing at the practice level in primary care . Design R and omised controlled trial with general practice s as the unit of r and omisation and analysis . Clinicians and research ers were blinded to group allocation until after r and omisation . Setting 68 general practice s with about 480 000 patients in Wales , United Kingdom . Participants 34 practice s were r and omised to receive the educational programme and 34 practice s to be controls . 139 clinicians from the intervention practice s and 124 from control practice s had agreed to participate before r and omisation . Practice level data covering all the clinicians in the 68 practice s were analysed . Interventions Intervention practice s followed the Stemming the Tide of Antibiotic Resistance ( STAR ) educational programme , which included a practice based seminar reflecting on the practice s ’ own dispensing and resistance data , online educational elements , and practising consulting skills in routine care . Control practice s provided usual care . Main outcome measures Total numbers of oral antibiotic items dispensed for all causes per 1000 practice patients in the year after the intervention , adjusted for the previous year ’s dispensing . Secondary outcomes included reconsultations , admissions to hospital for selected causes , and costs . Results The rate of oral antibiotic dispensing ( items per 1000 registered patients ) decreased by 14.1 in the intervention group but increased by 12.1 in the control group , a net difference of 26.1 . After adjustment for baseline dispensing rate , this amounted to a 4.2 % ( 95 % confidence interval 0.6 % to 7.7 % ) reduction in total oral antibiotic dispensing for the year in the intervention group relative to the control group ( P=0.02 ) . Reductions were found for all classes of antibiotics other than penicillinase-resistant penicillins but were largest and significant individually for phenoxymethylpenicillins ( penicillin V ) ( 7.3 % , 0.4 % to 13.7 % ) and macrolides ( 7.7 % , 1.1 % to 13.8 % ) . There were no significant differences between intervention and control practice s in the number of admissions to hospital or in reconsultations for a respiratory tract infection within seven days of an index consultation . The mean cost of the programme was £ 2923 ( € 3491 , $ 4572 ) per practice ( SD £ 1187 ) . There was a 5.5 % reduction in the cost of dispensed antibiotics in the intervention group compared with the control group ( −0.4 % to 11.4 % ) , equivalent to a reduction of about £ 830 a year for an average intervention practice . Conclusion The STAR educational programme led to reductions in all cause oral antibiotic dispensing over the subsequent year with no significant change in admissions to hospital , reconsultations , or costs . Trial registration IS RCT No 63355948 |
2,405 | 26,535,507 | CONCLUSIONS The studies analyzed did not find evidence to suggest that the use of colloids is superior to crystalloids .
Crystalloids are the preferred therapeutic option because of their effectiveness , low cost , and wide availability .
Colloids may be the first choice in cases of malaria when the central nervous system is affected | AIM The goal of this study was to perform a systematic review of the literature assessing the use of colloids for the initial treatment of severe sepsis and septic shock in pediatric patients . | Background Children with severe malnutrition who develop shock have a high mortality . Contrary to contemporaneous paediatric practice , current guidelines recommend use of low dose hypotonic fluid resuscitation ( half-strength Darrows/5 % dextrose ( HSD/5D ) . We evaluated the safety and efficacy of this guideline compared to resuscitation with a st and ard isotonic solution . Methods A Phase II r and omised controlled , safety and efficacy trial in Kenyan children aged over 6 months with severe malnutrition and shock including children with severe dehydration/shock and presumptive septic shock ( non-diarrhoeal shock ) . Eligible children were r and omised to HSD/5D or Ringer 's Lactate ( RL ) . A maximum of two boluses of 15 ml/kg of HSD/5D were given over two hours ( as recommended by guidelines ) while those r and omised to RL received 10 ml/kg aliquots half hourly ( maximum 40 ml/kg ) . Primary endpoint was resolution of shock at 8 and 24 hours . Secondary outcomes included resolution of acidosis , adverse events and mortality . Results 61 children were enrolled : 41 had shock and severe dehydrating diarrhoea , 20 had presumptive septic shock ; 69 % had decompensated shock . By 8 hours response to volume resuscitation was poor with shock persisting in most children:-HSD/5D 15/22 ( 68 % ) and RL14/25 ( 52 % ) , p = 0.39 . Oliguria was more prevalent at 8 hours in the HSD/5D group , 9/22 ( 41 % ) , compared to RL-3/25 ( 12 % ) , p = 0.02 . Mortality was high , HSD/5D-15/26(58 % ) and RL 13/29(45 % ) ; p = 0.42 . Most deaths occurred within 48 hours of admission . Neither pulmonary oedema nor cardiogenic failure was detected . Conclusions Outcome was universally poor characterised by persistence of shock , oliguria and high case fatality . Isotonic fluid was associated with modest improvement in shock and survival when compared to HSD/5D but inconclusive due to the limitations of design and effectiveness of either resuscitation strategy . Although isotonic fluid resuscitation did not result in cardiogenic heart failure , as previously feared , we conclude that the modest volumes used and rate of infusion were insufficient to promptly correct shock . The adverse performance of the recommended fluid resuscitation guideline for severe malnutrition should prompt clinical investigation of isotonic fluids for resuscitation of compensated shock , defining rate and volumes required to inform future guidelines .Trial Registration The trial is registered as ISCRTN : Introduction Inadequate initial treatment and delayed hemodynamic stabilization ( HDS ) may be associated with increased risk of death in severe sepsis patients . Methods In order to compare the hemodynamic efficacy and safety of 6 % HES 130/0.4 and NaCl 0.9 % for HDS in patients with severe sepsis , we design ed a prospect i ve , multicenter , active-controlled , double-blind , r and omized study in intensive care units . Results 174 out of 196 patients reached HDS ( 88 and 86 patients for HES and NaCl , respectively ) . Significantly less HES was used to reach HDS vs. NaCl ( 1,379 ±886 ml in the HES group and 1,709 ±1,164 ml in the NaCl group ( mean difference = -331± 1,033 , 95 % CI -640 to -21 , P = 0.0185 ) . Time to reach HDS was 11.8 10.1 hours vs. 14.3 ±11.1 hours for HES and NaCl , respectively . Total quantity of study drug infused over four consecutive days , ICU and hospital LOS , and area under the curve of SOFA score were comparable . Acute renal failure occurred in 24 ( 24.5 % ) and 19 ( 20 % ) patients for HES and NaCl , respectively ( P = 0.454 ) . There was no difference between AKIN and RIFLE criteria among groups and no difference in mortality , coagulation , or pruritus up to 90 days after treatment initiation . Conclusion Significantly less volume was required to achieve HDS for HES vs. NaCl in the initial phase of fluid resuscitation in severe sepsis patients without any difference for adverse events in both groups . Clinical Trials.gov 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 Symptomatic severe malarial anaemia ( SMA ) has a high fatality rate of 30–40 % ; most deaths occur in children awaiting blood transfusion . Blood transfusion services in most of Africa are not capable of delivering adequate supplies of safe blood in a timely manner to critically ill children with SMA . Contrary to widely held belief , hypovolaemia , rather than heart failure , has emerged as a common complication in such children . We examined the safety of pre‐transfusion management ( PTM ) by volume expansion , aim ed at stabilizing children and obviating the urgency for blood transfusion . Kenyan children with severe falciparum anaemia ( haemoglobin < 5 g/dl ) and respiratory distress were r and omly assigned to 20 ml/kg of 4·5 % albumin or 0·9 % saline or maintenance only ( control ) while awaiting blood transfusion . PTM was apparently safe since it did not lead to the development of pulmonary oedema or other adverse events . There was no significant difference in the primary outcome [ mean percentage reduction in base excess between admission and 8 h ( 95 % confidence interval ) ] between the control group 42 % ( 19–66 % ) albumin group 44 % ( 32–57 % ) and saline group 36 % ( 16–57 % ) ; adjusted analysis of variance F = 0·31 , P = 0·7 . However , the number of children requiring emergency interventions was significantly greater in the control group , four of 18 ( 22 % ) than the saline group 0 of 20 ( P = 0·03 ) . We have established the safety of this PTM in children with SMA whilst awaiting blood transfusion at a hospital with an adequate blood‐banking program . The impact on mortality should be assessed where blood transfusion services are unable to supply emergency transfusions BACKGROUND The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in re source -limited setting s is not established . METHODS We r and omly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5 % albumin solution ( albumin-bolus group ) or 0.9 % saline solution ( saline-bolus group ) per kilogram of body weight or no bolus ( control group ) at the time of admission to a hospital in Ug and a , Kenya , or Tanzania ( stratum A ) ; children with severe hypotension were r and omly assigned to one of the bolus groups only ( stratum B ) . All children received appropriate antimicrobial treatment , intravenous maintenance fluids , and supportive care , according to guidelines . Children with malnutrition or gastroenteritis were excluded . The primary end point was 48-hour mortality ; secondary end points included pulmonary edema , increased intracranial pressure , and mortality or neurologic sequelae at 4 weeks . RESULTS The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled . Malaria status ( 57 % overall ) and clinical severity were similar across groups . The 48-hour mortality was 10.6 % ( 111 of 1050 children ) , 10.5 % ( 110 of 1047 children ) , and 7.3 % ( 76 of 1044 children ) in the albumin-bolus , saline-bolus , and control groups , respectively ( relative risk for saline bolus vs. control , 1.44 ; 95 % confidence interval [ CI ] , 1.09 to 1.90 ; P=0.01 ; relative risk for albumin bolus vs. saline bolus , 1.01 ; 95 % CI , 0.78 to 1.29 ; P=0.96 ; and relative risk for any bolus vs. control , 1.45 ; 95 % CI , 1.13 to 1.86 ; P=0.003 ) . The 4-week mortality was 12.2 % , 12.0 % , and 8.7 % in the three groups , respectively ( P=0.004 for the comparison of bolus with control ) . Neurologic sequelae occurred in 2.2 % , 1.9 % , and 2.0 % of the children in the respective groups ( P=0.92 ) , and pulmonary edema or increased intracranial pressure occurred in 2.6 % , 2.2 % , and 1.7 % ( P=0.17 ) , respectively . In stratum B , 69 % of the children ( 9 of 13 ) in the albumin-bolus group and 56 % ( 9 of 16 ) in the saline-bolus group died ( P=0.45 ) . The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria , coma , sepsis , acidosis , and severe anemia . CONCLUSIONS Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these re source -limited setting s in Africa . ( Funded by the Medical Research Council , United Kingdom ; FEAST Current Controlled Trials number , IS RCT N69856593 . ) BACKGROUND Metabolic acidosis is the best predictor of death in children with severe falciparum malaria ; however , its treatment presents a therapeutic dilemma , because acidosis and hypovolemia may coexist with coma , which can be associated with elevated intracranial pressure . We postulated that volume resuscitation with albumin might correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid . In an open-label , r and omized , controlled trial , we compared the safety of resuscitation with albumin to saline in Kenyan children with severe malaria . METHODS We r and omly assigned children with severe malaria and metabolic acidosis ( base deficit , > 8 mmol/L ) to receive fluid resuscitation with either 4.5 % albumin or normal saline . A control ( maintenance only ) group was only included for patients with a base deficit of < 15 mmol/L. The primary outcome measure was the percentage reduction in base deficit at 8 h. Secondary end points included death , the requirement for rescue therapies , and neurological sequelae in survivors . RESULTS Of 150 children recruited for the trial , 61 received saline , 56 received albumin , and 33 served as control subjects . There was no significant difference in the resolution of acidosis between the groups ; however , the mortality rate was significantly lower among patients who received albumin ( 3.6 % [ 2 of 56 patients ] ) than among those who received saline ( 18 % [ 11 of 61 ] ; relative risk , 5.5 ; 95 % confidence interval , 1.2 - 24.8 ; P=.013 ) . CONCLUSIONS In high-risk children with severe malaria and acidosis , fluid resuscitation with albumin may reduce mortality . Our study design did not enable us to determine whether saline administration is preferable to fluid restriction or whether saline administration is actually hazardous . Further studies are needed to confirm our findings before definitive treatment recommendations can be made Dengue hemorrhagic fever and dengue shock syndrome ( DSS ) are major causes of childhood morbidity and mortality in many tropical countries . Increased intravascular permeability leading to shock is the cardinal feature of DSS . Fluid resuscitation to counteract massive plasma leakage is the mainstay of treatment . A double-blind , r and omized trial comparing four intravenous-fluid regimens for acute resuscitation of 50 children with DSS was conducted . Colloids ( dextran 70 or the protein digest gelafundin 35,000 ) restored cardiac index and blood pressure and normalized hematocrit more rapidly than crystalloids ( Ringer 's lactate or 0.9%-weight/volume saline ) . Dextran 70 provided the most rapid normalization of the hematocrit and restoration of the cardiac index , without adverse effects , and may be the preferred solution for acute resuscitation in DSS . Further large-scale double-blind trials are required to provide an evidence -based approach to the management of DSS Objectives : A previous meta- analysis has shown a consistent survival benefit in children with severe malaria receiving human albumin solution compared to other resuscitation fluids . Human albumin solution is expensive and not readily available in Africa . We examined the safety and efficacy of the fluid resuscitation with two synthetic colloids , Dextran 70 and hydroxyethyl starch , to inform future trial design . Design : An open-label r and omized , controlled , phase II safety and efficacy trial . Setting : High-dependency unit , Kilifi District Hospital , Kenya . Patients : Children aged > 6 months with severe falciparum malaria and acidosis ( base deficit > 8 mmol ) . Interventions : Boluses ( 20–40 mL/kg ) of 6 % Dextran 70 and 6 % hydroxyethyl starch ( 130/0.4 ) . Measurements and Main Results : Primary end point : resolution of shock over 8 hrs . Secondary end points include resolution of acidosis , in-hospital mortality , and adverse events ( allergic reactions , pulmonary edema , and neurologic sequelae ) . A total of 79 children were enrolled : 39 received Dextran 70 and 40 received hydroxyethyl starch . No significant difference was observed in Dextran 70 and hydroxyethyl starch groups for shock resolution at 8 hrs : 23/37 ( 62 % ) and 25/39 ( 64 % ) , respectively ( p = .99 ) . Acidosis resolution and respiratory distress were marginally superior in the hydroxyethyl starch group : 3/39 ( 8 % ) remained acidotic at 8 hrs versus 10/37 ( 27 % ) in the Dextran 70 arm ( p = .05 ) . There were four deaths ( 5 % ) : two per arm , including three deaths in the coma subgroup ( 3/39 , 8 % ) . No other new adverse event was reported . Conclusions : Correction of shock by volume expansion with either Dextran 70 or hydroxyethyl starch in children with severe malaria acidosis is safe with low mortality , including the highest risk cases admitted in coma . Both solutions present an attractive and practical option for consideration in future volume resuscitation trials in severe malaria Dengue hemorrhagic fever is an important cause of morbidity among Asian children , and the more severe dengue shock syndrome ( DSS ) causes a significant number of childhood deaths . DSS is characterized by a massive increase in systemic capillary permeability with consequent hypovolemia . Fluid resuscitation is critical , but as yet there have been no large trials to determine the optimal fluid regimen . We undertook a r and omized blinded comparison of 4 fluids ( dextran , gelatin , lactated Ringer 's , and " normal " saline ) for initial resuscitation of 230 Vietnamese children with DSS . All the children survived , and there was no clear advantage to using any of the 4 fluids , but the longest recovery times occurred in the lactated Ringer 's group . The most significant factor determining clinical response was the pulse pressure at presentation . A comparison of the colloid and crystalloid groups suggested benefits in children presenting with lower pulse pressures who received one of the colloids . Further large-scale studies , stratified for admission pulse pressure , are indicated OBJECTIVE To compare the efficacy of crystalloid ( Normal saline ) and colloid ( polymer from de grade d Gelatin in saline Haemaccel ) intravenous fluid in restoration of circulating volume in children with septic shock . DESIGN Prospect i ve , r and omized , open-label trial . SETTING Pediatric Emergency and Intensive Care Unit of a tertiary care referral and teaching hospital . SUBJECTS AND INCLUSION CRITERIA : Sixty patients , between 1 month to 12 years of age , with septic shock , without clinical evidence of organ failure at admission or underlying immunodeficiency . INTERVENTION Resuscitation with normal saline or polymer from de grade d gelatin ( Haemaccel ) in the boluses rate of 20 mL/kg till hemodynamic stabilization or if central venous pressure ( CVP ) exceeded 10 mmHg ( fluid requirement beyond 40 mL/kg guided by BP and CVP ) . METHODS Hemodynamic parameters ( heart rate , capillary filling time , pulse volume , and blood pressure ) were recorded before and during resuscitation , and then 2 hourly for 12 hours . Central venous pressure line was placed within first hour , soon after starting fluids . Estimation of plasma volume and body water was done at the end of first hour of fluid resuscitation . OUTCOME MEASURES Hemodynamic stabilization ( heart rate , capillary refill time , systolic BP in normal range ) , plasma volume at the end of fluid resuscitation and incidence of organ dysfunction . RESULTS 31 patients were r and omized to normal saline and 29 to gelatin polymer . Both the groups were similar with respect to age , gender , primary diagnosis , initial hemodynamic parameters and PRISM score . Pneumonia ( n = 22 ; 36 % ) , gut-associated sepsis ( n = 13 ) , and dengue hemorrhagic fever ( n = 11 ) were the common primary diagnosis . Initial hemodynamic stabilization was achieved in all . The mean ( SD plasma volume ( saline--53.4 ( 2.0 mL/kg , gelatin polymer--53.2 ( 1.9 mL/kg ) , extracellular fluid volume , total body water and interstitial fluid volume at the end of first hour of resuscitation were similar . The requirement of inotropes , incidence of organ dysfunction and case fatality rate ( Saline--29 % , gelatin polymer--31 % ) , were similar in two groups . CONCLUSION Both normal saline and gelatin polymer solution were equally effective as resuscitation fluid with respect to restoration of plasma volume and hemodynamic stability . Normal saline upto 110 mL/kg , and gelatin polymer solution upto 70 mL/kg may be required in first hour for successful fluid resuscitation of septic shock in children BACKGROUND Volume replacement with hydroxyethyl starch ( HES ) , a synthetic colloid , is widely accepted in adults , but only few data exist regarding its use in children . The aim of this study was to assess the effect of a low molecular weight HES solution ( HES 70/0.5 ) compared with lactated Ringer 's solution ( LR ) on haemoglobin levels as an indirect measure of plasma expansion in infants and toddlers , and its perioperative safety . METHODS Sixty-four patients , aged 1 - 38 months , were allocated r and omly to receive 20 ml x kg-1 body weight of either HES 70/0.5 or LR during the first hour of urological surgery lasting > 2 h. Thereafter , only LR was infused to maintain haemodynamic stability . Intraoperative blood loss and administered fluid volumes were analysed . Haemoglobin levels were determined perioperatively and intraoperatively at completion of volume loading . Changes in body weight and the incidence of postoperative oedema were assessed 24 and 48 h after surgery . For the safety analysis , patients were monitored for 72 h. RESULTS Intraoperative haemoglobin levels decreased significantly more with HES 70/0.5 ( 30 + /- 10 g.l-1 ) compared with LR ( 21 + /- 12 g.l-1 ) ( P < 0.01 ) . The overall administered fluid volumes during surgery did not differ between groups . The postoperative changes in body weight and incidence of postoperative oedema did not differ between groups . No anaphylactoid reactions , pruritus or adverse effects were observed during the study period . CONCLUSIONS A larger decrease in haemoglobin levels in infants and toddlers after HES 70/0.5 ( 20 ml.kg-1 ) compared with LR indicates a more effective plasma expansion . HES might be considered as a volume exp and er in the paediatric population Objectives To examine whether hypovolemia is an important cause of the acidosis in children with severe malaria . Design Prospect i ve phase 1 study examining the safety of volume expansion using detailed hemodynamic monitoring . Setting High-dependency unit of Kilifi District Hospital on the coast of Kenya . Patients Kenyan children admitted with clinical features of severe malaria ( impaired consciousness or deep breathing ) complicated by acidosis ( base excess of less than −8 ) . Three groups were considered : severe malarial anemia plus acidosis if hemoglobin of < 5 mg/dL and base excess less than −8 ; moderate malaria acidosis if the base excess was between −8 and −15 ; severe malaria acidosis if the base excess was less than −15 . Interventions Patients received between 10 and 40 mL/kg of either 0.9 % normal saline or 4.5 % human albumin solution . Measurements and Main Results A total of 53 children were recruited , and all had evidence of compensated shock at admission , with tachycardia , tachypnea , and prolonged capillary refill time . Mean central venous pressure ( se ) at admission was 2.9 cm H2O ( 0.5 cm H2O ) ; in the severe malaria acidosis group , 44 % had hypotension ( systolic blood pressure of < 80 mm Hg ) . Improvements of hemodynamic indices and a reduction in acidosis followed administration of either saline or albumin . By 8 hrs , mean central venous pressure had increased to 7.5 cm H2O ( 0.5 cm H2O , F = 34.4 , p < .001 ) and was associated with a reduction in mean respiratory rate from 49 to 41 breaths/min ( 2 to 1 breaths/min , respectively ; F = 7.0 ; p = .009 ) , a reduction in tachycardia from 151 to 141 beats/min ( 5 to 3 beats/min , respectively ; F = 3.4 ; p = .06 ) , and a reduction in capillary refill time . No child developed evidence of the life threatening complications of pulmonary edema and increased intracranial pressure . Conclusions Volume depletion is present at admission in the majority of children with severe malaria complicated by acidosis . Volume expansion corrects the hemodynamic abnormalities and is associated with improved organ function and reduction in acidosis . Formal trials of volume expansion are needed to determine whether volume expansion will reduce mortality BACKGROUND Dengue shock syndrome is characterized by severe vascular leakage and disordered hemostasis and progresses to death in 1 to 5 percent of cases . Although volume replacement is recognized as the critical therapeutic intervention , World Health Organization management guidelines remain empirical rather than evidence -based . METHODS We performed a double-blind , r and omized comparison of three fluids for initial resuscitation of Vietnamese children with dengue shock syndrome . We r and omly assigned 383 children with moderately severe shock to receive Ringer 's lactate , 6 percent dextran 70 ( a colloid ) , or 6 percent hydroxyethyl starch ( a colloid ) and 129 children with severe shock to receive one of the colloids . The primary outcome measure was requirement for rescue colloid at any time after administration of the study fluid . RESULTS Only one patient died ( < 0.2 percent mortality ) . The primary outcome measure -- requirement for rescue colloid -- was similar for the different fluids in the two severity groups . The relative risk of requirement for rescue colloid was 1.08 ( 95 percent confidence interval , 0.78 to 1.47 ; P=0.65 ) among children with moderate shock who received Ringer 's lactate as compared with either of the colloid solutions , 1.13 ( 95 percent confidence interval , 0.74 to 1.74 ; P=0.59 ) among children who received dextran as compared with starch in the group with severe shock , and 0.88 ( 95 percent confidence interval , 0.66 to 1.17 ; P=0.38 ) among children who received dextran as compared with starch in the combined analysis . Although treatment with Ringer 's lactate result ed in less rapid improvement in the hematocrit and a marginally longer time to initial recovery than did treatment with either of the colloid solutions , there were no differences in all other measures of treatment response . Only minor differences in efficacy were detected between the two colloids , but significantly more recipients of dextran than of starch had adverse reactions . Bleeding manifestations , coagulation derangements , and severity of fluid overload were similar for all fluid-treatment groups . CONCLUSIONS Initial resuscitation with Ringer 's lactate is indicated for children with moderately severe dengue shock syndrome . Dextran 70 and 6 percent hydroxyethyl starch perform similarly in children with severe shock , but given the adverse reactions associated with the use of dextran , starch may be preferable for this group Objectives : Hydroxyethyl starch 200 is associated with renal impairment in sepsis , but hydroxyethyl starch 130/0.4 and gelatin are considered to be less harmful . We hypothesized that fluid therapy with only crystalloids would decrease the incidence of acute kidney injury . Design : Prospect i ve sequential comparison during intensive care unit stay . Setting : Surgical intensive care unit . Patients : Patients with severe sepsis . Interventions : Changes in st and ard fluid therapy , with predominantly 6 % hydroxyethyl starch from January 2005 to June 2005 , 4 % gelatin from January 2006 to June 2006 , and only crystalloids from September 2008 to June 2009 . Measurements and Main Results : Acute kidney injury was defined by the presence of at least one RIFLE class ; 118 patients received hydroxyethyl starch , 87 patients received gelatin , 141 patients received only crystalloids . Baseline serum creatinine values were similar . Patients received median cumulative doses of 46 ( interquartile range , 18–92 ) mL/kg hydroxyethyl starch and 43 ( interquartile range , 18–76 ) mL/kg gelatin . Total median fluid amounts were 649 ( interquartile range , 275–1098 ) mL/kg in the hydroxyethyl starch group , 525 ( 237–868 ) mL/kg in the gelatin group , and 355 ( 173–911 ) mL/kg in the crystalloid group . The difference was statistically significant for hydroxyethyl starch after adjustment for multiple testing . Mean daily fluid intake and fluid balance were higher on days 0 and 1 in the crystalloid group . Acute kidney injury occurred in 70 % of patients receiving hydroxyethyl starch ( adjusted p = .002 ) and in 68 % of patients receiving gelatin ( adjusted p = .025 ) vs. 47 % patients receiving crystalloids . Need for renal replacement therapy tended to be higher in the hydroxyethyl starch group ( 34 % ; adjusted p = .086 ) and in the gelatin group ( 34 % ; adjusted p = .162 ) in comparison to the crystalloid group ( 20 % ) . Intensive care unit and hospital mortality were similar in each group ( hydroxyethyl starch : 35 % and 43 % ; gelatin : 26 % and 31 % ; crystalloids : 30 % and 37 % ) . Conclusion : Fluid resuscitation with only crystalloids was equally effective , result ed in a more positive fluid balance only on the first 2 days , and was associated with a lesser incidence of acute kidney injury IMPORTANCE Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear . OBJECTIVE To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit ( ICU ) with hypovolemic shock . DESIGN , SETTING , AND PARTICIPANTS A multicenter , r and omized clinical trial stratified by case mix ( sepsis , trauma , or hypovolemic shock without sepsis or trauma ) . Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill ( CRISTAL ) trial was open label but outcome assessment was blinded to treatment assignment . Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France , Belgium , North Africa , and Canada ; follow-up ended in November 2012 . INTERVENTIONS Colloids ( n = 1414 ; gelatins , dextrans , hydroxyethyl starches , or 4 % or 20 % of albumin ) or crystalloids ( n = 1443 ; isotonic or hypertonic saline or Ringer lactate solution ) for all fluid interventions other than fluid maintenance throughout the ICU stay . MAIN OUTCOMES AND MEASURES The primary outcome was death within 28 days . Secondary outcomes included 90-day mortality ; and days alive and not receiving renal replacement therapy , mechanical ventilation , or vasopressor therapy . RESULTS Within 28 days , there were 359 deaths ( 25.4 % ) in colloids group vs 390 deaths ( 27.0 % ) in crystalloids group ( relative risk [ RR ] , 0.96 [ 95 % CI , 0.88 to 1.04 ] ; P = .26 ) . Within 90 days , there were 434 deaths ( 30.7 % ) in colloids group vs 493 deaths ( 34.2 % ) in crystalloids group ( RR , 0.92 [ 95 % CI , 0.86 to 0.99 ] ; P = .03 ) . Renal replacement therapy was used in 156 ( 11.0 % ) in colloids group vs 181 ( 12.5 % ) in crystalloids group ( RR , 0.93 [ 95 % CI , 0.83 to 1.03 ] ; P = .19 ) . There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days ( mean : 2.1 vs 1.8 days , respectively ; mean difference , 0.30 [ 95 % CI , 0.09 to 0.48 ] days ; P = .01 ) and by 28 days ( mean : 14.6 vs 13.5 days ; mean difference , 1.10 [ 95 % CI , 0.14 to 2.06 ] days ; P = .01 ) and alive without vasopressor therapy by 7 days ( mean : 5.0 vs 4.7 days ; mean difference , 0.30 [ 95 % CI , -0.03 to 0.50 ] days ; P = .04 ) and by 28 days ( mean : 16.2 vs 15.2 days ; mean difference , 1.04 [ 95 % CI , -0.04 to 2.10 ] days ; P = .03 ) . CONCLUSIONS AND RELEVANCE Among ICU patients with hypovolemia , the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality . Although 90-day mortality was lower among patients receiving colloids , this finding should be considered exploratory and requires further study before reaching conclusions about efficacy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00318942 |
2,406 | 25,084,804 | Findings amongst pre-schoolers ( 3–5 years ) were mixed , with the more successful interventions requiring high levels of parental engagement , use of behaviour change techniques , a focus on skill building and links to community re sources .
The findings from the growing body of intervention research focusing on obesity prevention amongst young children from socioeconomically disadvantaged families suggest intervention effects are modest but promising . | Background Children from disadvantaged families including those from low socioeconomic background s and Indigenous families have higher rates of obesity , making early intervention a priority .
The aim of this study was to systematic ally review the literature to examine the effectiveness of interventions to prevent obesity or improve obesity related behaviours in children 0 - 5 years from socioeconomically disadvantaged or Indigenous families . | Objective : To use an ecological systems approach to examine individual- , family- , community- and area-level risk factors for overweight ( including obesity ) in 3-year-old children . Methods : A prospect i ve nationally representative cohort study conducted in Engl and , Wales , Scotl and , Northern Irel and . Participants included 13 188 singleton children aged 3 years in the Millennium Cohort Study , born between 2000 and 2002 , who had complete height/weight data . The main outcome measure was childhood overweight ( including obesity ) defined by the International Obesity TaskForce cut-offs for body mass index . Results : 23.0 % of 3-year-old children were overweight or obese . In the fully adjusted model , primarily individual- and family-level factors were associated with early childhood overweight : birthweight z-score ( adjusted odds ratio , 1.36 , 95 % CI 1.30 to 1.42 ) , black ethnicity ( 1.41 , 1.11 to 1.80 ) ( compared with white ) , introduction to solid foods < 4 months ( 1.12 , 1.02 to 1.23 ) , lone motherhood ( 1.32 , 1.15 to 1.51 ) , smoking during pregnancy ( 1–9 cigarettes daily : 1.34 , 1.17 to 1.54 ; 10–19 : 1.49 , 1.26 to 1.75 ; 20 + : 1.34 , 1.05 to 1.70 ) , parental overweight ( both : 1.89 , 1.63 to 2.19 ; father only : 1.45 , 1.28 to 1.63 ; mother only : 1.37 , 1.18 to 1.58 ) , prepregnancy overweight ( 1.28 , 1.14 to 1.45 ) and maternal employment ⩾21 hours/week ( 1.23 , 1.10 to 1.37 ) ( compared with never worked ) . Breastfeeding ⩾4 months ( 0.86 , 0.76 to 0.97 ) ( compared with none ) and Indian ethnicity ( 0.63 , 0.42 to 0.94 ) were associated with a decreased risk of early childhood overweight . Children from Wales were also more likely to be overweight than children from Engl and . Conclusions : Most risk factors for early childhood overweight are modifiable or would allow at-risk groups to be identified . Policies and interventions should focus on parents and providing them with an environment to support healthy behaviours for themselves and their children STUDY OBJECTIVE : To see whether the community mothers ' programme , using lay volunteer mothers to deliver a childhood development programme , could be extended successfully to the travelling community in Irel and . DESIGN : This was a prospect i ve study of the travelling community ; comparisons were made with results of a previous r and omised trial of settled mothers . SETTING : A regional health authority in Irel and . PARTICIPANTS : These comprised 39 traveller and 127 settled intervention mother/ infant pairs ( r and omised controlled trial ( RCT ) intervention ) ; settled community mothers ; 105 settled control pairs ( RCT control ) . All mothers received st and ard support ; traveller and RCT intervention groups also received the services of a community mother . MAIN RESULTS : The travellers ' sociodemographic profile differed significantly from the other groups . At the end of the study , traveller and intervention children were exposed to more cognitive games and nursery rhymes . There were significant differences in the proportions who received all three shots of their primary immunisation schedule before 12 months of age and who received " three in one " vaccination , with traveller children doing least well . The diet of traveller children surpassed that of RCT controls in all food groups except fruit ; they were less likely to begin cows ' milk before 26 weeks of age . Traveller mothers ' diet was superior to that of RCT control and similar to RCT intervention mothers . Traveller and RCT intervention mothers were less likely to feel tired , feel miserable , and want to stay indoors than RCT control mothers . CONCLUSIONS : The results of the community mothers ' programme in the travelling community are encouraging ; poor immunisation uptake remains a challenge Food preferences are established in early childhood and track later in life . Therefore , it is important to promote healthy feeding practice s as early as possible . A r and omized field trial was conducted with 500 mother-child pairs from a low-income area of São Leopoldo , State of Rio Gr and e do Sul , Brazil , to evaluate the impact of a nutritional intervention in the first year of life on the dietary quality of 3- to 4-y-old children . Mother-child pairs were r and omized either to intervention and control groups and dietary counseling was provided for mothers in the intervention group during 10 home visits in the course of the first year of life . These visits were carried out by fieldworkers who counseled the mothers about the Ten Steps for Healthy Feeding from Birth to Two Years of Age , based on the WHO guidelines . Dietary intake was assessed at 3 - 4 y of age for 345 children using two 24-h food recalls . Overall diet quality was determined by the Healthy Eating Index . The prevalence of poor diet in the intervention group was lower compared with the control group [ relative risk ( RR ) = 0.30 ; 95 % CI = 0.13 - 0.71 ) . The number of children who achieved the 75th percentile for the vegetable and fruit component score was higher in the intervention than in control group ( RR = 1.95 ; 95 % CI = 1.31 - 2.89 and RR = 1.49 ; 95 % CI = 1.07 - 2.07 , respectively ) . Such data provide evidence that dietary counseling for mothers during the first year of life improves the overall dietary quality of children in a low-income population OBJECTIVES : Despite recent efforts to increase breastfeeding , young African American mothers continue to breastfeed at low rates , and commonly introduce complementary foods earlier than recommended . This study examines the effects of a community doula home visiting intervention on infant feeding practice s among young mothers . METHODS : Low-income , African American mothers ( n = 248 ) under age 22 years participated in a r and omized trial of a community doula intervention . Intervention-group mothers received services from paraprofessional doulas : specialized home visitors trained as childbirth educators and lactation counselors . Doulas provided home visits from pregnancy through 3 months postpartum , and support during childbirth . Control-group mothers received usual prenatal care . Data were obtained from medical records and maternal interviews at birth and 4 months postpartum . RESULTS : Intent-to-treat analyses showed that doula-group mothers attempted breastfeeding at a higher rate than control-group mothers ( 64 % vs 50 % ; P = .02 ) and were more likely to breastfeed longer than 6 weeks ( 29 % vs 17 % ; P = .04 ) , although few mothers still breastfed at 4 months . The intervention also impacted mothers ’ cereal/solid food introduction ( P = .008 ) : fewer doula-group mothers introduced complementary foods before 6 weeks of age ( 6 % vs 18 % ) , while more waited until at least 4 months ( 21 % vs 13 % ) compared with control-group mothers . CONCLUSIONS : Community doulas may be effective in helping young mothers meet breastfeeding and healthy feeding guidelines . The intervention ’s success may lie in the relationship that develops between doula and mother based on shared cultural background and months of prenatal home visiting , and the doula ’s presence at the birth , where she supports early breastfeeding experiences BACKGROUND The American Academy of Pediatrics , the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) , and the World Health Organization recommend that infants receive only breast milk or formula for the first 4 to 6 months of life , followed by the introduction of complementary foods . Despite these recommendations , many infants , particularly those with adolescent mothers , receive solid foods ( often cereal mixed with formula in a bottle ) and liquids other than formula or breast milk in the first few weeks of life . Decisions on early feeding are often guided by gr and mothers and influenced by beliefs that infants need complementary food to counteract signals of hunger , reduce crying , and sleep through the night . OBJECTIVE This investigation evaluated the efficacy of an intervention to delay the early introduction of complementary feeding among first-time , black , adolescent mothers living in multigenerational households . The intervention focused on reducing the cultural barriers to the acceptance of the recommendations of the American Academy of Pediatrics , WIC , and World Health Organization on complementary feeding by highlighting 3 topics : 1 ) recognition of infants ' cues ; 2 ) nonfood strategies for managing infant behavior ; and 3 ) mother-gr and mother negotiation strategies . The intervention was delivered through a mentorship model in which a videotape made by an advisory group of black adolescent mothers was incorporated into a home-visiting program and evaluated through a r and omized , controlled trial . METHODS One hundred eighty-one first-time , low-income , black mothers < 18 years old , living in multigenerational households were recruited from 3 urban hospitals . Infants were born at term , with birth weight appropriate for gestational age and no congenital problems . Shortly after delivery , mothers and gr and mothers completed a baseline assessment and mothers were r and omized into an intervention or control group . Intervention group mothers received home visitation every other week for 1 year . At 3 months , a subset of 121 adolescent mothers reported on their infant 's intake through a food frequency question naire . Mothers who fed their infant only breast milk , formula , or water were classified as optimal feeders . Mothers who provided complementary foods other than breast milk , formula , or water were classified as less optimal feeders . RESULTS Sixty-one percent of the infants received complementary foods before 3 months old . Multivariate hierarchical logistic regression was used to evaluate the determinants of being in the optimal versus less optimal feeders group . After controlling for infant age and family income , mothers of infants in the optimal feeders group were more likely to report accurate messages from WIC regarding the timing of complementary food and nearly 4 times more likely to be in the intervention group . The most common complementary food was cereal mixed with formula in the bottle . CONCLUSIONS The success of this relatively brief intervention demonstrates the importance of using ecological theory and ethnographic research to design interventions that enable participants to alter their behavior in the face of contradictory cultural norms . The intervention focused on interpreting infants ' cues , nonfood methods of managing infant behavior , and mother-gr and mother negotiations . It was delivered through methods that were familiar and acceptable to adolescent mothers-a mentorship model incorporating home visits and videotape . The skill-oriented aspects of the intervention delivered in a culturally sensitive context may have enabled the young mothers to follow the guidelines that they received from WIC and from their pediatricians . Strategies , such as those used in this intervention , may be effective in promoting other caregiving recommendations , thereby enabling providers to meet the increasing dem and s from parents for advice regarding children 's early growth and development OBJECTIVE : To test the effect of a culturally tailored , family-centered , short-term behavioral intervention on BMI in Latino-American preschool-aged children . METHODS : In a r and omized controlled trial , 54 parent – child dyads were allocated to the intervention and 52 dyads were allocated to an alternative school-readiness program as the control condition . Parent – child dyads were eligible if the parent self-defined Latino , was at least 18 years old , had a 2- to 6-year-old child not currently enrolled in another healthy lifestyle program , had a valid telephone number , and planned on remaining in the city for the next 6 months . The Salud Con La Familia ( Health with the Family ) program consisted of 12 weekly 90-minute skills-building sessions design ed to improve family nutritional habits and increase physical activity . Both programs were conducted in a community recreation center serving an urban neighborhood of mostly Spanish-speaking residents . RESULTS : Forty-two percent of participating preschool-aged children were overweight or obese . Controlling for child age , gender , and baseline BMI , the effect of the treatment condition on postintervention absolute BMI was B = –0.59 ( P < .001 ) . The intervention effect seemed to be strongest for obese children . CONCLUSIONS : A skills-building , culturally tailored intervention involving parent – child dyads changed short-term early growth patterns in these Latino-American preschool-aged children . Examining long-term effects would be a prudent next step Background Early childhood provides a window of opportunity for the promotion of physical activity . Given the limited effectiveness of interventions to date , new approaches are needed . Socio-ecological models suggest that involving parents as intervention targets may be effective in fostering healthier lifestyles in children . This study describes the effectiveness of a family-focused ‘ Active Play ’ intervention in decreasing sedentary time and increasing total physical activity in preschool children . MethodS eventy-seven families were recruited from 8 r and omly selected SureStart children ’s centres in the North West of Engl and . Centres were r and omly assigned to either an intervention ( n = 4 ) or a comparison group ( n = 4 ) . Parents and children in the intervention group received a 10-week active play programme delivered by trained active play professionals ; this included an activity and educational component . Families in the comparison group were asked to maintain their usual routine . Each participating parent and child wore a uni-axial accelerometer for 7 days at baseline and post-test . Week and weekend day sedentary time and total physical activity adjusted for child- and home- level covariates were analysed using multilevel analyses . Results Significant intervention effects were observed for sedentary time and physical activity for both week and weekend days . Children in the intervention group engaged in 1.5 % and 4.3 % less sedentary time during week and weekend days , respectively and 4.5 % and 13.1 % more physical activity during week and weekend days , respectively than children in the comparison group . Parent ’s participation in sport and their physical activity levels , child ’s sex , availability of media in the home and attendance at organised activities were significant predictors of sedentary time and physical activity in this age group . Conclusion A 10-week family focused active play intervention produced positive changes in sedentary time and total physical activity levels in preschool children . Specific covariates were identified as having a significant effect on the outcome measures . Moreover , children whose parents were active engaged in less sedentary time and more physical activity suggesting that parent ’s activity habits are mediators of physical activity engagement in this age group OBJECTIVE --To see whether non-professional volunteer community mothers could deliver a child development programme to disadvantaged first time mothers for children aged up to 1 year . DESIGN --R and omised controlled trial . SETTING --A regional health authority in Dublin . SUBJECTS--262 first time mothers who were delivered during six months in 1989 and who lived in a deprived area of Dublin ; 30 experienced mothers from the same community recruited as community mothers . INTERVENTIONS --All the first time mothers received st and ard support from the public health nurse . In addition , those in the intervention group received the services of a community mother , who was scheduled to visit monthly during the first year of the child 's life . RESULTS --232 ( 89 % ) first time mothers completed the study --127 in the intervention group , 105 controls . At the end of the study children in the intervention group were more likely to have received all of their primary immunisations , to be read to , and to be read to daily , played more cognitive games ; and were exposed to more nursery rhymes . They were less likely to begin cows ' milk before 26 weeks and to receive an inappropriate energy intake and inappropriate amounts of animal protein , non-animal protein , wholefoods , vegetables , fruit , and milk . Mothers in the intervention group also had a better diet than controls . At the end of the study they were less likely to be tired , feel miserable , and want to stay indoors ; had more positive feelings ; and were less likely to display negative feelings . CONCLUSION --Non-professionals can deliver a health promotion programme on child development effectively . Whether they can do so as effectively as professionals requires further study OBJECTIVE : To assess the impact of dietary counseling given to mothers during the first year of infants ’ lives on food consumption , nutritional status , and lipid profile of the children up to 7 to 8 years old . METHODS : The r and omized trial was conducted with 500 mothers who gave birth to full-term infants with birth weight ≥2500 g between October 2001 and June 2002 in São Leopoldo , Brazil . Mothers were r and omly assigned to intervention ( n = 200 ) and control groups ( n = 300 ) and those in the intervention group received counseling on breastfeeding and complementary feeding by 12 fieldworkers on 10 home visits during the first year of children ’s lives . Blinded fieldworkers assessed dietary and anthropometric data at 12 to 16 months , 3 to 4 years , and 7 to 8 years and lipid profiles at 3 to 4 years and 7 to 8 years old . The lipid profile was the primary outcome . RESULTS : Of the 500 recruited children , 397 underwent the 12- to 16-month , 354 the 3- to 4-year , and 315 the 7- to 8-year assessment . The energy-dense foods intake was significantly lower in the intervention group at 12 to 16 months and 3 to 4 years old . At 3 to 4 years , serum lipid levels did not differ between groups . At 7 to 8 years , high-density lipoprotein levels were 0.11 mmol/L higher ( 0.00 to 0.20 ) , and triglycerides concentration was 0.13 mmol/L lower ( −0.25 to −0.01 ) in intervention children but only among the girls . Overweight/obesity rates did not differ between groups . CONCLUSIONS : Dietary counseling for mothers during infancy decreased the energy-dense foods consumption and improved lipid profile The Gudaga Study is a prospect i ve , longitudinal birth cohort study of Australian urban Aboriginal children . Mothers of Aboriginal infants were recruited using a survey of all mothers admitted to the maternity ward of an outer urban hospital in Sydney . These data established initiation rates among Gudaga infants and those of non-Aboriginal infants born locally ( 64.7 % and 75.2 % , respectively ) and factors associated with breastfeeding . Older ( relative risk , 1.24 ; confidence interval , 1.01 - 1.44 ) , more educated ( relative risk , 1.30 ; confidence interval , 1.11 - 1.48 ) mothers who intended to breastfeed ( relative risk , 2.22 ; confidence interval , 2.12 - 2.3 ) were more likely to breastfeed . Smokers ( relative risk , 0.72 ) and mothers of Aboriginal infants ( relative risk , 0.78 ) were less likely to initiate breastfeeding . Breastfeeding rates for Gudaga infants dropped rapidly , with 26.3 % breastfeeding at 2 months . Local health services providers can benefit from such information as they target relevant prenatal , perinatal , and postnatal services for Aboriginal mothers and their infants Objective To test the effect of a multidimensional lifestyle intervention on aerobic fitness and adiposity in predominantly migrant preschool children . Design Cluster r and omised controlled single blinded trial ( Ballabeina study ) over one school year ; r and omisation was performed after stratification for linguistic region . Setting 40 preschool classes in areas with a high migrant population in the German and French speaking regions of Switzerl and . Participants 652 of the 727 preschool children had informed consent and were present for baseline measures ( mean age 5.1 years ( SD 0.7 ) , 72 % migrants of multicultural origins ) . No children withdrew , but 26 moved away . Intervention The multidimensional culturally tailored lifestyle intervention included a physical activity programme , lessons on nutrition , media use ( use of television and computers ) , and sleep and adaptation of the built environment of the preschool class . It lasted from August 2008 to June 2009 . Main outcome measures Primary outcomes were aerobic fitness ( 20 m shuttle run test ) and body mass index ( BMI ) . Secondary outcomes included motor agility , balance , percentage body fat , waist circumference , physical activity , eating habits , media use , sleep , psychological health , and cognitive abilities . Results Compared with controls , children in the intervention group had an increase in aerobic fitness at the end of the intervention ( adjusted mean difference : 0.32 stages ( 95 % confidence interval 0.07 to 0.57 ; P=0.01 ) but no difference in BMI ( −0.07 kg/m2 , −0.19 to 0.06 ; P=0.31 ) . Relative to controls , children in the intervention group had beneficial effects in motor agility ( −0.54 s , −0.90 to −0.17 ; P=0.004 ) , percentage body fat ( −1.1 % , −2.0 to −0.2 ; P=0.02 ) , and waist circumference ( −1.0 cm , −1.6 to −0.4 ; P=0.001 ) . There were also significant benefits in the intervention group in reported physical activity , media use , and eating habits , but not in the remaining secondary outcomes . Conclusions A multidimensional intervention increased aerobic fitness and reduced body fat but not BMI in predominantly migrant preschool children . Trial registration Clinical Trials NCT00674544 The preschool years offer an opportunity to interrupt the trajectory toward obesity in black children . The Hip-Hop to Health Jr. Obesity Prevention Effectiveness Trial was a group-r and omized controlled trial assessing the feasibility and effectiveness of a teacher-delivered weight control intervention for black preschool children . The 618 participating children were enrolled in 18 schools administered by the Chicago Public Schools . Children enrolled in the nine schools r and omized to the intervention group received a 14-week weight control intervention delivered by their classroom teachers . Children in the nine control schools received a general health intervention . Height and weight , physical activity , screen time , and diet data were collected at baseline and postintervention . At postintervention , children in the intervention schools engaged in more moderate-to-vigorous physical activity ( MVPA ) than children in the control schools ( difference between adjusted group means = 7.46 min/day , P = 0.02 ) . Also , children in the intervention group had less total screen time ( -27.8 min/day , P = 0.05 ) . There were no significant differences in BMI , BMI Z score , or dietary intake . It is feasible to adapt an obesity prevention program to be taught by classroom teachers . The intervention showed positive influences on physical activity and screen time , but not on diet . Measuring diet and physical activity in preschool children remains a challenge , and interventions delivered by classroom teachers require both intensive initial training and ongoing individualized supervision OBJECTIVE To determine whether maternal participation in an obesity prevention plus parenting support ( OPPS ) intervention would reduce the prevalence of obesity in high-risk Native-American children when compared with a parenting support (PS)-only intervention . RESEARCH METHODS AND PROCEDURES Forty-three mother/child pairs were recruited to participate . Mothers were 26.5 + /- 5 years old with a mean BMI of 29.9 + /- 3 kg/m(2 ) . Children ( 23 males ) were 22 + /- 8 months old with mean weight-for-height z ( WHZ ) scores of 0.73 + /- 1.4 . Mothers were r and omly assigned to a 16-week OPPS intervention or PS alone . The intervention was delivered one-on-one in homes by an indigenous peer educator . Baseline and week 16 assessment s included weight and height ( WHZ score and weight-for-height percentile for children ) , dietary intake ( 3-day food records ) , physical activity ( measured by accelerometers ) , parental feeding style ( Child Feeding Question naire ) , and maternal outcome expectations , self-efficacy , and intention to change diet and exercise behaviors . RESULTS Changes in WHZ scores showed a trend toward significance , with WHZ scores decreasing in the PS condition and increasing among the OPPS group ( -0.27 + /- 1.1 vs. 0.31 + /- 1.1 , p = 0.06 ) . Children in the OPPS condition also significantly decreased energy intake ( -316 + /- 835 kcal/d vs. 197 + /- 608 kcal/d , p < 0.05 ) . Scores on the restriction subscale of the Child Feeding Question naire decreased significantly in the OPPS condition ( -0.22+/- 0.42 vs. 0.08+/- 0.63 , p < 0.05 ) , indicating that mothers in the OPPS group were engaging in less restrictive child feeding practice s over time . DISCUSSION A home-visiting program focused on changing lifestyle behaviors and improving parenting skills showed promise for obesity prevention in high-risk Native-American children Excess weight gain in American Indian/Alaskan native ( AI/AN ) children is a public health concern . This study tested ( 1 ) the feasibility of delivering community-wide interventions , alone or in combination with family-based interventions , to promote breastfeeding and reduce the consumption of sugar-sweetened beverages ; and ( 2 ) whether these interventions decrease Body Mass Index ( BMI ) -Z scores in children 18–24 months of age . Three AI/AN tribes were r and omly assigned to two active interventions ; a community-wide intervention alone ( tribe A ; n = 63 families ) or community-wide intervention containing a family component ( tribes B and C ; n = 142 families ) . Tribal staff and the research team design ed community-tailored interventions and trained community health workers to deliver the family intervention through home visits . Feasibility and acceptability of the intervention and BMI -Z scores at 18–24 months were compared between tribe A and tribes B & C combined using a separate sample pretest , posttest design . Eighty-six percent of enrolled families completed the study . Breastfeeding initiation and 6-month duration increased 14 and 15 % , respectively , in all tribes compared to national rates for American Indians . Breastfeeding at 12 months was comparable to national data . Parents expressed confidence in their ability to curtail family consumption of sugar-sweetened beverages . Compared to a pretest sample of children of a similar age 2 years before the study begun , BMI -Z scores increased in all tribes . However , the increase was less in tribes B & C compared to tribe A ( −0.75 , P = 0.016 ) . Family , plus community-wide interventions to increase breastfeeding and curtail sugar-sweetened beverages attenuate BMI rise in AI/AN toddlers more than community-wide interventions alone OBJECTIVE : To evaluate the effect of 2 anticipatory guidance styles ( maternal focused [ MOMS ] and infant focused [ Ounce of Prevention ] ) directed at mothers of infants aged newborn to 6 months on their infant feeding behaviors at 1 year compared with routine advice as outlined in Bright Futures ( BF ) . METHODS : This is a cluster r and omized trial . A total of 292 mother/infant dyads were enrolled at their first well-child visit to 3 urban pediatric clinics in Columbus , Ohio . Intervention-specific brief advice and 1-page h and outs were given at each well visit . In addition to infant weights and lengths , surveys about eating habits and infant feeding practice s were completed at baseline and 12 months . RESULTS : Baseline data revealed a group with high rates of maternal overweight ( 62 % ) and obesogenic habits . At 12 months , the maternal-focused group gave their infants less juice ( 8.97 oz vs 14.37 oz , P < .05 ) , and more daily servings of fruit ( 1.40 vs 0.94 , P < .05 ) and vegetables ( 1.41 vs 1.03 , P < .05 ) compared with BF mothers . Ounce of Prevention mothers also gave less juice ( 9.3 oz , P < .05 ) and more fruit servings ( 1.26 P < .05 ) than BF . CONCLUSIONS : Brief specific interventions added to well-child care may affect obesogenic infant feeding behaviors of mothers and deserves further study as an inexpensive approach to preventing childhood obesity OBJECTIVE Overweight ( OW ) and low fit children represent cardiovascular high-risk groups . A multidimensional school-based lifestyle intervention performed in 652 preschoolers reduced skinfold thickness and waist circumference , and improved fitness , but did not affect BMI . The objective of this study is to examine whether the intervention was equally effective in OW ( ≥90th national percentile ) and /or low fit ( lowest sex- and age-adjusted quartile of aerobic fitness ) children compared to their normal weight and normal fit counterparts . DESIGN AND METHODS Cluster r and omized controlled single blinded trial , conducted in 2008/09 in 40 r and omly selected preschool classes in Switzerl and . The intervention included a playful physical activity program and lessons on nutrition , media use and sleeps . Primary outcomes were BMI and aerobic fitness ; secondary outcomes included sum of four skinfolds , waist circumference and motor agility . Modification of intervention effects by BMI -group and fitness-group was tested by interaction terms . RESULTS Compared to their counterparts , OW children ( n = 130 ) had more beneficial effects on waist circumference ( p for interaction = 0.001 ) and low fit children ( n = 154 ) more beneficial effects on all adiposity outcomes ( p for interaction ≤0.03 ) . The intervention effects on both fitness outcomes were not modified by BMI - or fitness-group ( all p for interaction ≥0.2 ) . Average intervention effect sizes for BMI were -0.12 , -0.05 , -0.26 and -0.02 kg/m(2 ) and for aerobic fitness were 0.40 , 0.30 , 0.12 and 0.36 stages for OW , normal weight , low fit and normal fit children , respectively . CONCLUSIONS This multidimensional intervention was equally and for some adiposity measures even more effective in high-risk preschoolers and represents a promising option for these children OBJECTIVE Hip-Hop to Health Jr. was a diet/physical activity intervention design ed to reduce gains in BMI ( kilograms per meter squared ) in preschool minority children . RESEARCH METHODS AND PROCEDURES Twelve predominantly Latino Head Start centers participated in a group-r and omized trial conducted between Fall 2001 and Winter 2003 . Six centers were r and omized to a culturally proficient 14-week ( three times weekly ) diet/physical activity intervention . Parents participated by completing weekly homework assignments . The children in the other six centers received a general health intervention that did not address either diet or physical activity . The primary outcome was change in BMI , and secondary outcomes were changes in dietary intake and physical activity . Measures were collected at baseline , post-intervention , and at Years 1 and 2 follow-up . RESULTS There were no significant differences between intervention and control schools in either primary or secondary outcomes at post-intervention , Year 1 , or Year 2 follow-ups . DISCUSSION When Hip-Hop to Health Jr. was conducted in predominantly black Head Start centers , it was effective in reducing subsequent increases in BMI in preschool children . In contrast , when the program was conducted in Latino centers , it was not effective . Although the intervention did not prevent excessive weight gain in Latino children , it was very well received . Future interventions with this population may require further cultural tailoring and a more robust parent intervention INTRODUCTION Although the disadvantages of introducing non-breast milk and the early introduction of complementary foods are known , such practice s are common worldwide . OBJECTIVE To evaluate the efficacy of counseling about breastfeeding and complementary feeding in preventing the introduction of non-breast milk and complementary foods in the first 6 months . METHODS This r and omized clinical trial enrolled 323 adolescent mothers and their newborns and 169 maternal gr and mothers ; 163 mothers and 88 gr and mothers received five counseling sessions on breastfeeding while in the hospital and at 7 , 15 , 30 , and 60 days , and one session on complementary feeding at 120 days . Data about infant feeding were collected monthly . The impact was evaluated by comparing the Kaplan-Meier survival curves for the time of introduction of non-breast milk and complementary foods of the control and intervention groups . Median time of introduction of milk was calculated in the two groups . RESULTS The survival curves showed that the intervention postponed the introduction of non-breast milk and complementary foods . At 4 months , 41 % ( 95 % CI , 32.8 - 49.2 ) of the infants in the control group received complementary foods in comparison to 22.8 % ( 95 % CI , 15.9 - 29.7 ) of the intervention group . Counseling postponed the introduction of non-breast milk , which occurred at 95 days ( 95 % CI , 8.7 - 111.3 ) in the control group and at 153 days ( 95 % CI , 114.6 - 191.4 ) in the intervention group . CONCLUSIONS Counseling sessions on infant 's first 4 months were an efficacious strategy to prevent the introduction of non-breast milk and complementary foods in the 6 months of life OBJECTIVE To evaluate the impact of a dietary counseling in reducing the intake of energy-dense foods by infants . DESIGN A r and omized controlled trial . SETTING AND PARTICIPANTS São Leopoldo , Brazil . Mothers and infants of a low-income-group population were r and omized into intervention ( n = 163 ) and received dietary counseling during 10 home visits , or control ( n = 234 ) groups . MAIN OUTCOMES MEASURES Child consumption of sugar-dense ( SD ) and lipid-dense ( LD ) foods at 12 to 16 months . ANALYSIS The effect of the intervention was expressed by relative risks and 95 % confidence intervals . Poisson regression analysis was used to determine the association between exclusive breastfeeding and the energy-dense foods intake . RESULTS A smaller proportion of infants from the intervention group consumed c and y , soft drinks , honey , cookies , chocolate , and salty snacks . In the intervention group , there was a reduction of 40 % and 50 % in the proportion of infants who consumed LD and SD foods , respectively . Being breastfed up to 6 months reduced the risk for consumption of LD and SD foods by 58 % and 67 % , respectively . CONCLUSIONS AND IMPLICATION S Dietary counseling to mothers may be effective in reducing the consumption of energy-dense foods among infants , and it is helpful in improving early dietary habits SamenvattingGewichtsproblemen bij kinderen vormen een snelgroeiend probleem , in het bijzonder bij gezinnen met lage inkomens . Eetgedrag ontwikkelt zich vroeg bij kinderen en wordt gevormd door gezinsleden . De dreumesperiode is een kritische periode om een begin te maken met gezonde eetgewoontes en het ontstaan van overgewicht te voorkomen OBJECTIVE To describe patterns of health-service use in the first 12 months of life . METHODS In this prospect i ve cohort study , 173 first-born infants and their families living in two middle socio-economic urban areas of Melbourne were enrolled consecutively when presenting for their initial maternal and child health nurse ( MCHN ) visit ( at approximately 4 weeks of age ) . Families kept a daily " health diary " for the entire 12-month period , recording use of all health services for their infant , and reasons for the contact . RESULTS There was an 87 % completion rate of diaries . The mean number of visits to any health service , including medical , hospitals , MCHN services , pharmacists , allied health services and naturopaths , was 35.7 ( 95 % CI 34.7 - 36.6 ) during the 12 months . Of these , 31 % ( mean 10.9 visits ) were visits to a general practitioner ( GP ) and 41.5 % ( mean 14.3 visits ) were visits to the MCHN . Infants ' visits to the MCHN were far more frequent in the first 6 months of life compared with the second 6 months ( 10.3 vs 3.6 , P < 0.001 ) . Rates of GP use were constant over the same periods ( 5.3 vs 5.7 , P = 0.8 ) . CONCLUSIONS In a universal health-care system , this high rate of health-service use equates to approximately one visit to a health service every 2 weeks in the first year of life . The majority of these visits appeared unrelated to illness . This previously undocumented data has implication s for future integrated service delivery , health-professional training and policy development for this age group OBJECTIVE Formula-fed infants gain weight faster than breastfed infants . This study evaluated whether encouraging formula-feeding caregivers to be sensitive to infant satiety cues would alter feeding practice s and reduce infant formula intake and weight gain . DESIGN Double-blind , r and omized educational intervention , with intake and growth measured before ( at 1 to 2 months ) and after ( 4 to 5 months ) the intervention . SETTING Women , Infants , and Children ( WIC ) clinics in Sacramento , California . PARTICIPANTS 836 caregivers of young infants were screened ; 214 were eligible , and 104 agreed to participate . INTERVENTION Intervention subjects received education promoting awareness of satiety cues and discouraging bottles containing more than 6 ounces before 4 months of age ; intervention and control groups received education regarding introduction and feeding of solid food after 4 months of age . MAIN OUTCOME MEASURES Formula intake ( mL/24 hours ) and weight gain ( g/week ) . ANALYSIS Differences between groups evaluated using 2-way analysis of covariance ( ANCOVA ) . RESULTS Sixty-one subjects completed baseline records , 44 attended class , and 38 completed the study . Despite a positive response to the educational intervention , there was no change in bottle-feeding behaviors ( formula intake at 4 to 5 months was more than 1100 mL/day in both groups ) . Infant growth in the intervention group was greater than in the control group ( P < .01 ) , contrary to the hypothesis . CONCLUSIONS AND IMPLICATION S The intervention improved knowledge of the key messages , but further research is needed to underst and barriers to modifying bottle-feeding behaviors OBJECTIVES This field study tested the feasibility and benefits of a program to promote 6 targeted parental behaviors to prevent obesity in children served by the Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) . METHODS Two WIC sites participated in a nonr and omized , controlled 1-year prospect i ve study to assess parents ' self-reported behavior changes . RESULTS Statistical analyses of preintervention and postintervention assessment s of parental behavior demonstrated significant changes in 2 behaviors : frequency of offering the child water and frequency of engaging in active play with the child . In both cases , the intervention proved effective in increasing the desired behavior . CONCLUSIONS The findings demonstrate the feasibility of changing parental behaviors through multidimensional education in a WIC clinic setting IMPORTANCE Racial/ethnic and socioeconomic disparities exist across risk factors for childhood obesity . OBJECTIVE To examine the effectiveness of a home-based intervention to improve household routines known to be associated with childhood obesity among a sample of low-income , racial/ethnic minority families with young children . DESIGN R and omized trial . SETTING The intervention was delivered in the families ' homes . PARTICIPANTS The study involved 121 families with children aged 2 to 5 years who had a television ( TV ) in the room where he or she slept ; 111 ( 92 % ) had 6-month outcome data ( 55 intervention and 56 control ) . The mean ( SD ) age of the children was 4.0 ( 1.1 ) years ; 45 % were overweight/obese . Fifty-two percent of the children were Hispanic , 34 % were black , and 14 % were white/other . Nearly 60 % of the families had household incomes of $ 20,000 or less . INTERVENTIONS The 6-month intervention promoted 4 household routines , family meals , adequate sleep , limiting TV time , and removing the TV from the child 's bedroom , using ( 1 ) motivational coaching at home and by phone , ( 2 ) mailed educational material s , and ( 3 ) text messages . Control subjects were mailed material s focused on child development . MAIN OUTCOMES AND MEASURES Change in parent report of frequency of family meals ( times/wk ) , child sleep duration ( hours/d ) , child weekday and weekend day TV viewing ( hours/d ) , and the presence of a TV in the room where the child slept from baseline to 6 months . A secondary outcome was change in age- and sex-adjusted body mass index ( calculated as weight in kilograms divided by height in meters squared ) . RESULTS Compared with control subjects , intervention participants had increased sleep duration ( 0.75 hours/d ; 95 % CI , 0.06 to 1.44 ; P = .03 ) , greater decreases in TV viewing on weekend days ( -1.06 hours/d ; 95 % CI , -1.97 to -0.15 ; P = .02 ) , and decreased body mass index ( -0.40 ; 95 % CI , -0.79 to 0.00 ; P = .05 ) . No significant intervention effect was found for the presence of a TV in the room where the child slept or family meal frequency . CONCLUSIONS AND RELEVANCE Our results suggest that promoting household routines , particularly increasing sleep duration and reducing TV viewing , may be an effective approach to reduce body mass index among low-income , racial/ethnic minority children . Longer-term studies are needed to determine maintenance of behavior change . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01565161 OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years BACKGROUND The Community Mothers Programme aims at using experienced volunteer mothers in disadvantaged areas to give support to first-time parents in rearing their children up to 1 year of age . The programme was evaluated by r and omized controlled trial in 1990 . METHODS Seven years later , trial participants were interviewed about child health , nutrition , cognitive stimulation , parenting skills , and maternal self-esteem . The aim of this study was to see whether the demonstrated benefits at 1 year of age of this programme could be sustained at age 8 . RESULTS One-third of the original group ( 38 intervention , 38 control ) , were contacted and interviewed . The risk for having an accident requiring a hospital visit was lower in the intervention group : relative risk ( RR ) 0.59 , 95 per cent confidence interval ( CI ) 0.31 - 1.11 . Intervention children were more likely to visit the library weekly : RR 1.58 , 95 per cent CI 1.10 - 2.26 . Intervention mothers were more likely to check homework every night : RR 1.23 , 95 per cent CI 1.05 - 1.43 ( p=0.006 ) ; and to disagree with the statement ' children should be smacked for persistently bad behaviour ' : RR 2.11 , 95 per cent CI 1.10 - 4.06 . They were more likely to disagree with the statement ' I do not have much to be proud of ' : RR 1.24 , 95 per cent CI 1.04 - 1.40 ; and to make a positive statement about motherhood than controls : RR 1.53 , 95 per cent CI 1.06 - 2.20 . Subsequent children of intervention mothers were more likely to have completed Haemophilus influenzae b : RR 1.26 , 95 per cent CI 1.06 - 1.51 ; and polio immunization : RR 1.19 , 95 per cent CI 1.02 - 1.40 . CONCLUSIONS The Community Mothers programme had sustained beneficial effects on parenting skills and maternal self-esteem 7 years later with benefit extending to subsequent children Background : To assess whether monthly home visits from trained volunteers could improve infant feeding practice s at age 12 months , a r and omised controlled trial was carried out in two disadvantaged inner city London boroughs . Methods : Women attending baby clinics with their infants ( 312 ) were r and omised to receive monthly home visits from trained volunteers over a 9-month period ( intervention group ) or st and ard professional care only ( control group ) . The primary outcome was vitamin C intakes from fruit . Secondary outcomes included selected macro and micro-nutrients , infant feeding habits , supine length and weight . Data were collected at baseline when infants were aged approximately 10 weeks , and subsequently when the child was 12 and 18 months old . Results : Two-hundred and twelve women ( 68 % ) completed the trial . At both follow-up points no significant differences were found between the groups for vitamin C intakes from fruit or other nutrients . At first follow-up , however , infants in the intervention group were significantly less likely to be given goats ’ or soya milks , and were more likely to have three solid meals per day . At the second follow-up , intervention group children were significantly less likely to be still using a bottle . At both follow-up points , intervention group children also consumed significantly more specific fruit and vegetables . Conclusions : Home visits from trained volunteers had no significant effect on nutrient intakes but did promote some other recommended infant feeding practice s. Trial registration : Current Controlled Trials IS RCT UNLABELLED BACKGROUND ; The increasing prevalence of overweight among children in the United States presents a national health priority . Higher rates of overweight/obesity among minority women place their children at increased risk . Although increased rates of overweight are observed in 4- to 5-year-old children , they are not observed in 2- to 3-year-old children . Therefore , early prevention efforts incorporating families are critical . METHODS The primary aim of Hip-Hop to Health Jr. is to alter the trajectory toward overweight/obesity among preschool African-American and Latino children . This 5-year r and omized intervention is conducted in 24 Head Start programs , where each site is r and omized to either a 14-week dietary/physical activity intervention or a general health intervention . RESULTS This paper presents the rationale and design of the study . Efficacy of the intervention will be determined by weight change for the children and parent/caretaker . Secondary measures include reductions in dietary fat and increases in fiber , fruit/vegetable intake , and physical activity . Baseline data will be presented in future papers . CONCLUSIONS The problem of overweight/obesity is epidemic in the United States . Behaviors related to diet and physical activity are established early in life and modeled by family members . Early intervention efforts addressing the child and family are needed to prevent obesity later in life . This paper describes a comprehensive , family-oriented obesity prevention program for minority preschool children In a 4-year follow-up of a r and omized controlled trial , this study aim ed to evaluate the longer-term effects of a peer-led infant feeding intervention that was delivered during the first year of life . The original intervention used monthly home visits from trained volunteers to improve infant feeding practice s among a sample of low-income mothers in two disadvantaged London boroughs . Outcome measures at follow-up included children 's eating and drinking habits , general and dental health , and BMI . Data were collected via structured face-to-face interviews and postal question naires . Of 212 women who completed the original trial , 101 took part in the follow-up ( 55 intervention , 46 control ) . Children 's mean age at follow-up was 4 years 7 months . There is little evidence that the intervention had an important effect on children 's current BMI , caries levels or consumption of fruit and vegetables . However , mothers from the intervention group had better nutritional knowledge and confidence . Intervention group children also consumed more pure fruit juice [ relative risk ( RR ) = 1.57 ; 95 % confidence interval ( CI ) 0.99 , 2.49 ] and were more likely to never drink squash ( RR = 1.76 ; 95 % CI 1.20 , 2.58 ) . The data suggest that the original peer support intervention had a small number of positive long-term effects BACKGROUND Latino preschool children in the United States are at high risk for obesity . The objective of this study was to measure over a one-year period whether a parent training based on social learning theory combined with evidence -based interventions to promote optimal nutrition and physical activity will reduce the upward trend of BMI z-scores in groups of 2–4 year old Latino children living in low-income households . METHODS Seven weekly classes with 2 booster classes were delivered to low-income Latino parents with 2–4 year old children . A r and omized controlled pilot study evaluated the effectiveness of the intervention that contrasts 61 children whose parents were r and omized to receive Parent Training ( PT ) with 60 Wait-list ( WL ) subjects . Forty subjects did not attend the one-year follow up assessment , result ing in 81 subjects who have measurements for both baseline and one-year follow up assessment s. To adjust for differential dropout rates and missing observations , imputation of missing data was done using a carefully constructed model that included relevant independent variables . RESULTS There were no significant subject differences between groups at baseline for family characteristics and BMI categories for child and parent . Children in the intervention group decreased their BMI z-scores significantly on average by .20 ( SE= .08 ) compared to children in the control group who increased z scores on average by .04 ( SE=.09 ) at one year ( P<.05 ) . CONCLUSIONS Parent training is effective to reduce the risk of overweight in preschool Latino children living in low-income households . The findings need to be examined in a larger sample of children Objective : Given the increasing prevalence of pediatric obesity , we evaluated two kindergarten-based strategies for reducing overweight in preschool children in the Haute-Garonne Department in France . Methods : Kindergartens ( n=79 ) were r and omly assigned to one of the two strategies and followed for 2 years . In the first group ( Epidémiologie et prévention de l’obésité infantile , EPIPOI-1 ) , parents and teachers received basic information on overweight and health , and children underwent screening to identify those with overweight ( body mass index ( BMI ) ⩾90th percentile ) or at risk for overweight ( BMI between 75 and 90th percentile ) , who were then followed up by their physicians . EPIPOI-2 children , in addition , received kindergarten-based education to promote healthy practice s related to nutrition , physical activity and sedentary behaviors . Data on control children from non-intervention kindergartens ( n=40 ) were retrieved from medical records at the Division of School Health . Results : At baseline , groups differed significantly on age and school area ( underprivileged/ not ) . Owing to a significant interaction between school area and group , analyses were stratified by school area . At baseline , groups did not differ on overweight prevalence and BMI z-scores for any school area . After intervention , prevalence of overweight , BMI z-score and change in BMI z-score were significantly lower in intervention groups compared with controls in underprivileged areas . Using multilevel analysis adjusted for potential confounders , a significant effect on overweight prevalence at the end of the study was noted for EPIPOI-1 in underprivileged areas only ( odds ratio and 95 % confidence interval : 0.18 ( 0.07–0.51 ) . In non-underprivileged areas , the gain in BMI z-score was lower in EPIPOI-2 group compared with control and EPIPOI-1 . Conclusion : Our results suggest that simple measures involving increasing awareness on overweight and health , and periodic monitoring of weight and height with follow-up care when indicated , could be useful to reduce overweight in young children from underprivileged areas . A reinforced strategy with an education component , in addition , may be indicated in children in non-underprivileged areas |
2,407 | 12,535,419 | There was no evidence from these studies that this increase in uptake of tests was related to informed decision making by consumers .
REVIEW ER 'S CONCLUSIONS Personalised risk communication ( as currently implemented in the included studies ) is associated with increased uptake of screening programmes , but this may not be interpretable as evidence of informed decision making by consumers | BACKGROUND There is a trend towards greater patient involvement in health care decisions .
Adequate discussion of the risks and benefits associated with different choices is often required if involvement is to be genuine and effective .
Achieving adequate involvement of consumers and informed decision making are now seen as important goals for any screening programme .
Individualised risk estimates have been shown to be effective methods of risk communication in general , but the effectiveness of different strategies has not previously been examined .
OBJECTIVES To assess the effects of different types of individualised risk communication for consumers making decisions about participating in screening . | BACKGROUND The North Carolina Native American Cervical Cancer Prevention Project was a 5-year , National Cancer Institute-funded trial of health education design ed to increase screening for cervical cancer among Native-American women in North Carolina . PURPOSE This study was conducted to evaluate the effectiveness of this education program in the Eastern-B and Cherokee target population . METHODS Cherokee tribal l and s were mapped and all households ( N = 2223 ) were listed to ensure maximum coverage of the eligible population ( women , aged 18 years and older , who were enrolled tribal members ) . Eligible women were identified by the use of a brief question naire administered to an adult member of the household . Of the 1279 households with eligible women , 1020 ( 79.8 % ) agreed to participate . The intervention was an individualized health education program delivered by female Cherokee lay health educators . The participants were r and omly assigned to receive or not to receive the intervention ( i.e. , to program and control groups , respectively ) by use of the Solomon Four-Group design . Data were collected in face-to-face interviews conducted in the participant 's home . Of the 996 women who were ultimately enrolled , 540 were r and omly assigned to receive a pretest ( preintervention ) interview that involved administration of a 96-item question naire design ed to collect data on knowledge , intentions , and behaviors related to cervical cancer ; of these 540 women , 263 were r and omly assigned to receive the education program . The remaining 456 women did not receive the pretest , but 218 were r and omly assigned to receive the education program . Six months after receiving the education program , the women in all four groups were administered a post-test that was identical to the pretest . Logistic regression was used to assess the effects of the pretest and the educational program . All P values result ed from two-sided statistical tests . RESULTS Eight hundred and fifteen ( 81.8 % ) of the 996 participants completed the post-test interview . The remaining 181 women who were lost to follow-up were evenly distributed among the four study groups . At the post-test , 282 ( 73.2 % ) of the 385 women who received the education program reported having had a Pap smear following the intervention , compared with 275 ( 64 % ) of the 430 control subjects . Women who received the education program were more likely to answer all knowledge items correctly on the post-test ( odds ratio [ OR ] = 2.18 , 95 % confidence interval [ CI ] = 1.08 - 4.39 ) and to report having obtained a Pap smear in the past year ( OR = 2.06 , 95 % CI = 1.14 - 3.72 ) than women in the control groups . CONCLUSION Women who received the education program exhibited a greater knowledge about cervical cancer prevention and were more likely to have reported having had a Pap smear within the past year than women who did not receive the program OBJECTIVES Message tailoring , based on individual needs and circumstances , is commonly used to enhance face-to-face patient counseling . Only recently has individual tailoring become feasible for printed messages . This study sought to determine whether printed tailored recommendations addressing women 's specific screening and risk status and perceptions about breast cancer and mammography are more effective than st and ardized printed recommendations . METHODS Computer-assisted telephone interviews were conducted with 435 women , aged 40 to 65 years , who had visited family practice groups within the previous 2 years . Subjects were r and omly allocated to receive individually tailored or st and ardized mammography recommendation letters mailed from physicians to patients ' homes . Follow-up interviews were conducted 8 months later . RESULTS Tailored letter recipients were more likely to remember and to have read more of their letters than st and ardized version recipients . After controlling for baseline status , tailored letter receipt was associated with more favorable follow-up mammography status for women with incomes below $ 26,000 and for Black women . CONCLUSIONS Tailored messages are a more effective medium for physicians ' mammography recommendations ; tailoring may be especially important for women of low socioeconomic status BACKGROUND Although rates of mammography screening among women in the general population have been increasing they still fall short of national goals . This study evaluated the effects on rates of participation in mammography screening of obtaining risk factor information and providing general or personalized risk information through direct mailed correspondence . METHODS Women enrollees in a health maintenance organization ( N = 2,076 ) , age 50 and above , were r and omized to one of the following four groups : ( a ) no risk factor question naire + generic invitation , ( b ) no risk factor question naire + general risk invitation , ( c ) risk factor question naire + general risk invitation , and ( d ) risk factor question naire + personal risk invitation . Computerized visit records were monitored for 12 months following a mailed invitation to assess whether a mammogram had been obtained . RESULTS Overall participation was 37.5 % and the rate of participation did not differ significantly across groups ( P = 0.26 ) . Participation was related to age ( P < 0.02 ) , with rates highest for women ages 60 - 69 years ( 42.7 % ) compared with those for women ages 50 - 59 ( 35.5 % ) and those age 70 + ( 33.7 % ) . Among women with a family history of breast cancer , the personalized risk invitation was associated with significantly higher participation compared with general risk invitation ( 66.7 versus 42.9 % , respectively ; P < 0.003 ) . CONCLUSIONS Women with a family history of breast cancer are more likely to obtain a mammogram if that fact is reinforced as a risk factor . Research on environmental barriers to mammography screening may suggest alternative strategies for increasing participation Colorectal cancer is second only to lung cancer as a cause of cancer death in the United States . Studies have shown that fecal occult blood ( FOB ) tests are effective in detecting colorectal cancer in its early stages . To increase the participation in the FOB test among the working population , a r and omized controlled trial was conducted . A total 278 federal employees 40 years or older in Washington State were r and omly divided into a intervention group which received a Colorectal Cancer Risk Appraisal and a control group which received a simple information letter . After three months a follow-up question naire was sent to all participants to measure the effectiveness of the intervention . As a result of the study , the intervention group had a 4.3 % higher compliance rate with the FOB test during the three month follow-up period ( p = .10 ) . The largest effect of the intervention was on the employees ' intention to get a FOB test within the next year ( 62.6 % in the intervention group vs. 36.2 % in the control group , OR = 3.18 , p less than .001 ) OBJECTIVES We evaluated the impact of individualized breast cancer risk counseling on mammography use among women at risk for breast cancer . METHODS Participants ( n = 508 ) were r and omized to the breast cancer risk counseling intervention or a general health education control intervention , and 85 % completed follow-up . RESULTS In multivariate modeling , a significant group-by-education interaction demonstrated that among less-educated participants , breast cancer risk counseling led to reduced mammography use . There was no intervention effect among the more-educated participants . CONCLUSIONS These results suggest that st and ard breast cancer risk counseling could have an adverse impact on the health behaviors of less-educated women Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with " decisional confidence , " and least with " desire to participate in health care de cisions " and " satisfaction with provider " The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64 Mammography has been found significantly to impact mortality in women ; however , compliance is still problematic . A theoretical model which combined Health Belief Model ( HBM ) constructs with stage of mammography adoption was used to investigate the effect of an individualized belief and /or informational intervention on mammography compliance . A control group and three intervention groups ( belief , information , and belief and information ) were used . A probability sample of 405 women ages 40–88 years without a prior history of breast cancer was r and omly assigned to groups . Subjects in the intervention group received individually tailored messages to alter beliefs or provider information related to mammography screening . Women in the combined belief/information group were over two times more likely to have been compliant with mammography 1 year postintervention than those in the control . In addition , groups who received the belief intervention had significantly more women that went from a lower to a higher stage of mammography adoption BACKGROUND Mammography is the primary method used for breast cancer screening . However , compliance with recommended screening practice s is still below acceptable levels . This study examined the cost-effectiveness of five combinations of physician recommendation and telephone or in-person individualized counseling strategies for increasing compliance with mammography . METHODS There were 808 participants who were r and omly assigned to one of six groups . A logistic regression model with compliance as the dependent variable and group as the independent variable was used to test for significant differences and a ratio of cost to improvement in mammogram compliance evaluated the cost-effectiveness . RESULTS Three of the interventions ( in-person , telephone plus letter , and in-person plus letter ) had significantly better compliance rates compared with the control , physician letter , or telephone alone . However , when considering costs , only one emerged as the superior strategy . The cost-effectiveness ratios for the five interventions show that telephone-plus-letter is the most cost-effective strategy , achieving a 35.6 % mammography compliance at a marginal cost of $ 0.78 per 1 % increase in women screened . CONCLUSIONS A tailored phone prompt and physician reminder is an effective and economical intervention to increase mammography . Future research should confirm this finding and address its applicability to practice Screening for colorectal cancer by testing for faecal occult blood ( FOBT ) is effective for early diagnosis , but the success of a screening programme also depends on compliance . The aims of this study were to assess the effect of health education on compliance and to assess any addition to general practitioner workload that result ed . Altogether 3860 patients were recruited and r and omly allocated to test or control group . The test group was further divided into subgroups , some of which received health education . Compliance with FOBT was 54.7 % ( 210/384 ) in the subgroup receiving only the doctor 's letter , which fell to 48.1 % ( 743/1544 ) in the group receiving health education . General practitioner consultation rates were similar in test and control groups BACKGROUND Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety . In response to the need to communicate more accurate risk information to these women , specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States . PURPOSE Our purpose was 1 ) to evaluate the impact of a st and ardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2 ) to identify women most and least likely to benefit from such counseling . METHODS This study is a prospect i ve r and omized trial comparing individualized breast cancer risk counseling to general health counseling ( control ) . We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative . Women with a personal history of cancer were excluded . Risk comprehension was assessed as the concordance between perceived " subjective " lifetime breast cancer risk and estimated " objective " lifetime risk . RESULTS The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension , compared with women in the control condition ( odds ratio [ OR ] = 3.5 ; 95 % confidence interval [ CI ] = 1.3 - 9.5 ; P = .01 ) . However , in both groups , about two thirds of women continued to overestimate their lifetime risks substantially following counseling . Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line ( P = .02 ) . In addition , white women were less likely to benefit than African-American women ( OR = 0.34 ; 95 % CI = 0.11 - 0.99 ; P = .05 ) . CONCLUSION Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed . IMPLICATION S Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene , BRCA1 ( and BRCA2 when that gene has also been cloned ) Health risk appraisal ( HRA ) remains one of the most widely used health promotion tools despite only equivocal evidence for its effectiveness . Theories of behavior change predict conventional HRA 's ineffectiveness because risk information alone is seldom sufficient to change complex behaviors . In this study , a r and omized trial compared the effects of feedback from an enhanced HRA with a typical HRA and a control group among adult patients from eight family medicine practice s. The enhanced HRA assessed behavior-specific psychosocial factors and provided patients with computer-generated , individually-tailored behavior change information in addition to typical HRA risk feedback . Changes in seven behaviors were assessed at a 6 month follow-up . Overall , patients receiving enhanced HRA feedback were 18 % more likely to change at least one risk behavior than were patients receiving typical HRA feedback or no feedback ( OR = 1.18 , 95 % CI = 1.00 , 1.39 ) . The enhanced HRA feedback appeared to promote changes in cholesterol screening , dietary fat consumption and physical activity , but not in smoking , seat belt use , mammography and Pap smears . We conclude that the addition of theory-based , individually-tailored behavior change information may improve the effectiveness of HRA BACKGROUND In response to the isolation of the BRCA1 gene , a breast-ovarian cancer-susceptibility gene , biotechnology companies are already marketing genetic tests to health care providers and to the public . Initial studies indicate interest in BRCA1 testing in the general public and in population s at high risk . However , the optimal strategies for educating and counseling individuals have yet to be determined . PURPOSE Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and /or ovarian cancer . METHODS A r and omized trial design was used to evaluate the effects of education only ( educational approach ) and education plus counseling ( counseling approach ) , as compared with a waiting-list ( control ) condition ( n = 400 for all groups combined ) . The educational approach review ed information about personal risk factors , inheritance of cancer susceptibility , the benefits , limitations , and risks of BRCA1 testing , and cancer screening and prevention options . The counseling approach included this information , as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing . Data on knowledge of inherited cancer and BRCA1 test characteristics , perceived risk , perceived benefits , limitations and risks of BRCA1 testing , and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up . Provision of a blood sample for future testing served as a proxy measure of intention to be tested ( in the education and counseling arms of the study ) . The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling ( for the blood sample outcome ) . All P values are for two-sided tests . RESULTS The educational and counseling approaches both led to significant increases in knowledge , relative to the control condition ( P < .001 for both ) . The counseling approach , but not the educational approach , was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing ( P < .01 ) and decreases in perceived benefits ( P < .05 ) . However , neither approach produced changes in intentions to have BRCA1 testing . Prior to and following both education only and education plus counseling , approximately one half of the participants stated that they intended to be tested ; after the session , 52 % provided a blood sample . CONCLUSIONS St and ard educational approaches may be equally effective as exp and ed counseling approaches in enhancing knowledge . Since knowledge is a key aspect of medical decision-making , st and ard education may be adequate in situations where genetic testing must be streamlined . On the other h and , it has been argued that optimal decision-making requires not only knowledge , but also a reasoned evaluation of the positive and negative consequences of alternate decisions . Although the counseling approach is more likely to achieve this goal , it may not diminish interest in testing , even among women at low to moderate risk . Future research should focus on the merits of these alternate approaches for subgroups of individuals with different background s who are being counseled in the variety of setting s where BRCA1 testing is likely to be offered The authors evaluated the impact of individualized breast cancer risk counseling ( BCRC ) on breast-cancer-specific distress and general distress in 239 women with a family history of breast cancer . Following a baseline assessment of demographics , risk factors , coping styles , and distress , participants were assigned r and omly to receive either BCRC or general health education ( GHE ; i.e. , control group ) . After controlling for education level , women who received BCRC had significantly less breast-cancer-specific distress at 3-month follow-up compared with women who received GHE . A significant Education Level x Treatment Group interaction indicated that the psychological benefits of BCRC were greater for women with less formal education . In both the BCRC and GHE groups , participants who had monitoring coping styles exhibited increases in general distress from baseline to follow-up This study was design ed to identify factors that predict adherence by African American men to prostate cancer education and early detection Abstract Objectives : To vali date a self administered postal question naire appraising risk of coronary heart disease . To determine whether use of this question naire increased the percentage of people at high risk of coronary heart disease and decreased the percentage of people at low risk who had their cholesterol concentration measured . Design : Validation was by review of medical records and clinical assessment . The question naire appraising risk of coronary heart disease encouraged those meeting criteria for cholesterol measurement to have a cholesterol test and was tested in a r and omised controlled trial . The intervention group was sent the risk appraisal question naire with a health question naire that determined risk of coronary heart disease without identifying the risk factors as related to coronary heart disease ; the control group was sent the health question naire alone . Setting : One capitation funded primary care practice in Canada with an enrolled patient population of about 12 000 . Subjects : R and om sample of 100 participants in the intervention and control groups were included in the validation exercise . 5686 contactable patients aged 20 to 69 years who on the basis of practice records had not had a cholesterol test performed during the preceding 5 years were included in the r and omised controlled trial . 2837 were in the intervention group and 2849 were in the control group . Main outcome measures : Sensitivity and specificity of assessment of risk of coronary heart disease with risk appraisal question naire . Rate of cholesterol testing during three months of follow up . Results : Sensitivity of question naire appraising coronary risk was 87.5 % ( 95 % confidence interval 73.2 % to 95.8 % ) and specificity 91.7 % ( 81.6 % to 97.2 % ) . Of the patients without pre-existing coronary heart disease who met predefined screening criteria based on risk , 45 out of 421 in the intervention group ( 10.7 % ) and 9 out of 504 in the control group ( 1.8 % ) had a cholesterol test performed during follow up ( P<0.0001 ) . Of the patients without a history of coronary heart disease who did not meet criteria for cholesterol testing , 30 out of 1128 in the intervention group ( 2.7 % ) and 18 out of 1099 in the control group ( 1.6 % ) had a cholesterol test ( P=0.175 ) . Of the patients with pre-existing coronary heart disease , 1 out of 15 in the intervention group ( 6.7 % ) and 1 out of 23 in the control group ( 4.3 % ) were tested during follow up ( P=0.851 , one tailed Fisher 's exact test ) . Conclusions : Although the question naire appraising coronary risk increased the percentage of people at high risk who obtained cholesterol testing , the effect was small . Most patients at risk who received the question naire did not respond by having a test . Key messages Of patients at high risk of coronary heart disease , 10.7 % who received a risk appraisal question naire with a general health question naire and 1.8 % of those who received the general health question naire alone had a cholesterol test within the following three months Of patients at low risk , 2.7 % of patients receiving the risk appraisal question naire and 1.6 % of control subjects had a cholesterol test Most patients at risk who received the risk appraisal question naire did not seek a test Further research is needed to identify factors contributing to low uptake of cholesterol testing among people at high risk of coronary heart disease even when encouragement is BACKGROUND Computers that collect data from patients and provide both patients and practitioners with printed feedback on a range of health risks are a tool for assisting general practitioners with preventive care . This study assessed the impact of computer-generated printed feedback on cervical screening among women who were underscreened for cervical cancer . METHOD Female attenders at two Australian general practice s were r and omly allocated to Experimental or Control groups . Women in both groups completed a health risk survey on a touch screen computer prior to their consultation . Those in the Experimental group received printed pages summarizing their results , including their eligibility for cervical screening and last Pap test , for themselves and their doctor . The number and proportion of underscreened women who had a Pap test in the 6 months after completing the computer survey , as determined by pathology records , were examined . RESULTS Of the 679 participants , 139 were classified as underscreened on the basis of self-report ( 74 Experimental , 65 Control ) and 272 on the basis of their pathology records ( 148 Experimental , 124 Control ) . Overall about one-third of women had a test in the 6-month period , and the differences between the groups were not significant for women overall ( 18 - 70 years ) or for women 18 - 49 years . Among women 50 - 70 who were underscreened based on self-report , those receiving the printout were more likely to have a Pap test in the next 6 months ( P < 0.05 ) . This pattern was also evident , but did not reach statistical significance , for older women who were underscreened based on pathology records . CONCLUSIONS We are unable to draw conclusions regarding the effectiveness of the computer system due to the modest proportions of women screened , the small numbers , and the fact that the computer survey may have created an intervention effect in the Control group . As the study suggests the computer system is acceptable to women and may be effective for encouraging screening among older women , further exploration of the system is desirable BACKGROUND Tailoring is a promising technique for encouraging greater performance of health-related behaviors . Tailored interventions are design ed to be more individualized to personal characteristics , in contrast to " st and ard " interventions where all participants receive the same material s. METHODS A total of N = 1864 women aged 40 - 74 were recruited from a staff model HMO and r and omly assigned to one of three intervention groups : ( a ) No Educational Material s , ( b ) St and ard Material s , and ( c ) Stage-Matched Material s. A provider-directed component was common across all three conditions . The St and ard and Stage-Matched groups each received two mailed educational packets after baseline and follow-up telephone interviews . The Stage-Matched intervention was based on the Transtheoretical Model of behavior change . RESULTS Analyses of n = 1397 women ( after all attrition ) showed that receipt of mammography after the baseline interview was higher for the Stage-Matched group ( 63.6 % ) than for the No Material s group ( 54.9 % ; OR = 1.43 , 95 % CI = 1.10 , 1.86 ) . The St and ard intervention group was intermediate ( 58 . 5 % ) . The St and ard group did not differ from the No Material s group , but did differ from the Stage-Matched group in multivariate analysis . CONCLUSIONS Stage-matched , tailored material s may be a means to encourage screening mammography . Such interventions can be implemented by telephone and mail BACKGROUND Telephone counseling and tailored print communications have emerged as promising methods for promoting mammography screening . However , there has been little research testing , within the same r and omized field trial , of the efficacy of these two methods compared to a high- quality usual care system for enhancing screening . This study addressed the question : Compared to usual care , is tailored telephone counseling more effective than tailored print material s for promoting mammography screening ? DESIGN Three-year r and omized field trial . PARTICIPANTS One thous and ninety-nine women aged 50 and older recruited from a health maintenance organization in North Carolina . INTERVENTION Women were r and omized to 1 of 3 groups : ( 1 ) usual care , ( 2 ) tailored print communications , and ( 3 ) tailored telephone counseling . MAIN OUTCOME Adherence to mammography screening based on self-reports obtained during 1995 , 1996 , and 1997 . RESULTS Compared to usual care alone , telephone counseling promoted a significantly higher proportion of women having mammograms on schedule ( 71 % vs 61 % ) than did tailored print ( 67 % vs 61 % ) but only after the first year of intervention ( during 1996 ) . Furthermore , compared to usual care , telephone counseling was more effective than tailored print material s at promoting being on schedule with screening during 1996 and 1997 among women who were off-schedule during the previous year . CONCLUSIONS The effects of the intervention were most pronounced after the first intervention . Compared to usual care , telephone counseling seemed particularly effective at promoting change among nonadherent women , the group for whom the intervention was developed . These results suggest that telephone counseling , rather than tailored print , might be the preferred first-line intervention for getting nonadherent women on schedule for mammography screening . Many questions would have to be answered about why the tailored print intervention was not more powerful . Nevertheless , it is clear that additional interventions will be needed to maintain women 's adherence to mammography . Medical Subject Headings ( MeSH ) : mammography screening , telephone counseling , tailored print communications , barriers This study compared the effects of theoretically driven interventions on compliance with mammography utilization . A 2 × 2 factorial design yielded groups : a control group , a belief intervention group , an informational intervention group , and a belief/informational intervention group . A probability sample of 301 women , age 35 and older , without a history of breast cancer were r and omly assigned to groups . Subjects in the intervention groups received individually tailored messages to alter beliefs or provider information related mammography screening . Belief messages were developed from Health Belief Model constructs . Belief interventions significantly influenced all belief variables except perceived susceptibility in the desired direction . Women in belief/informational intervention group were almost four times more likely than those in the control group to comply with mammography recommendations in the year following intervention ( odds ratio=3.75 ) . In addition , belief variables and intervention significantly predicted mammography compliance 1 year postintervention We tested the hypothesis that an education program addressing breast cancer screening schedules and modalities coupled with a breast cancer risk assessment provided by community pharmacists can increase women 's confidence in performing screening practice s endorsed by the American Cancer Society ( ACS ) . This r and omized , paired , pre-post study was conducted in six community pharmacies and two health-screening fairs ; subjects were 140 women over 18 years of age . The pharmacist-administered program used the Breast Cancer Risk- Assessment Tool ( Gail model ) software provided by the National Cancer Institute of the National Institutes of Health . In addition , pharmacists provided education and training on breast self-examination ( BSE ) , clinical breast examination ( CBE ) , and mammography . Adherence to ACS guidelines for monthly BSE increased from 31 % to 56 % ( p<0.001 ) for all women 6 months after the program . Performance of monthly BSE by women considered at high risk for developing breast cancer increased from 20 % to 60 % ( p<0.005 ) . The mean number of BSEs performed over 6 months increased from 2.69 to 4.09 ( p<0.001 ) . Women 's confidence performing correct BSE improved from 6.41 to 7.04 ( p<0.001 ) on a scale of 0 - 10 . Adherence to ACS guidelines for CBE and mammography did not reveal statistically significant improvements except for better adherence to CBE in women aged 40 - 49 years ( 81 % to 97 % , p<0.025 ) . The strength of the pharmacists ' intervention may not appear as manipulation of high-risk patients ' behavior but as improvement of self-directed behaviors , such as BSE , across all age groups We conducted a 4-year r and omized study in a community health center that serves primarily low income Blacks in Durham , North Carolina . Patients ( 1318 at baseline ) were assigned r and omly to one of three study groups : provider prompting intervention alone , provider prompting and tailored print material s or the previous group and tailored telephone counseling . The purpose of the study was to determine whether increasingly intensive , tailored print and telephone interventions also were increasingly effective in promoting adherence to mammograms , Pap tests and overall cancer screening compliance . Thus , the combination of tailored print interventions ( print and telephone ) should have been more effective than the provider prompting intervention alone , or the print intervention and prompting combination . This is one of the few studies to examine a measure of overall cancer screening compliance and to assess the benefit of combinations of tailored interventions in promoting adherence to cancer screening . Patients gave extremely high ratings to the interventions . At the bivariate level , we found a significant effect of the most intensive group ( provider prompting intervention , tailored print communications and tailored telephone counseling ) on Pap test compliance ( P = 0.05 ) and borderline significance at the multivariate level ( P = 0.06 ) as well on overall screening compliance ( P = 0.06 ) . There was not a significant effect on mammography , probably because a majority of the patients were receiving regular mammograms . We also found some important subgroup differences . For example , a larger proportion of women reported Pap tests in the tailored print and counseling group when they believed the material s were ' meant for me . ' These results show that a combination of tailored interventions may have potential for reaching the women who have too often been labeled the ' hard to reach . BACKGROUND We assessed the short-term impact of decision-making interventions on knowledge about mammography , accuracy of women 's breast cancer risk perceptions , attitudes toward mammography , satisfaction with decisions , and mammography use since the intervention . METHODS The study was conducted among women who were members of Blue Cross Blue Shield of North Carolina and were in their 40s or 50s at the time the study began in 1997 . Women were r and omly assigned to usual care ( UC ) , tailored print booklets ( TP ) alone , or TP plus telephone counseling ( TP+TC ) . RESULTS 12-month interviews were completed by 1127 women to assess short-term intervention effects . Generally , women who received TP+TC were significantly more knowledgeable about mammography and breast cancer risk and were more accurate in their breast cancer risk perceptions than women in the TP and UC groups . They also were more likely to have had a mammogram since the baseline interview . In multivariable analyses , we found significant benefits of the combination of TP+TC compared to TP and to UC for knowledge , accuracy of risk perceptions , and mammography use . DISCUSSION For complex decision-making tasks , such as women 's decisions about mammography in the face of controversy , the combination of TP and TC may be more effective than TP alone , and certainly more effective than UC . It is critical that investigators determine the topics for which TP is appropriate and the situations that require additional supportive interventions Objective To find out how presenting information about the benefits of screening for cancer in different ways affects an individual 's decision to accept or reject screening . Methods A telephone survey of the Wellington region , New Zeal and was carried out . Results A response rate of 75.6 % was obtained . Respondents were most likely to accept screening when the benefits of screening were presented as a relative risk reduction . They were most likely to reject screening when the benefits were presented as numbers needed to screen to save one life . Conclusions An individual 's decision about screening for cancer is affected by the way the benefits are framed . Health professionals must choose between framing the benefits of screening in the most positive light , to enhance participation rates , and presenting information in such a way as to reduce framing effects — for example , by expressing the benefits in a variety of forms . Clearly there may be a tension between these approaches ; the former is arguably manipulation , and the latter may enhance informed choice , but may also reduce participation rates in screening programmes BACKGROUND Breast cancer screening with mammography is an effective intervention for women aged 50 to 75 years but it is underused , especially by the urban poor . OBJECTIVE To improve mammography completion rates for urban women aged 52 to 77 years who had not had a mammogram in at least 2 years . METHODS We conducted a r and omized controlled trial of a case management intervention by culturally sensitive community health educators vs usual care in 6 primary care practice s supported by a computerized clinical information system . RESULTS Women in the intervention group were nearly 3 times as likely to receive a mammogram ( relative risk , 2.87 ; 95 % confidence interval , 1.75 - 4.73 ) . The benefit persisted when analyzed by age ; race , and prior screening behavior . This intervention was practice based , not dependent on visits , and enhanced the efficacy of an already successful computerized preventive care information system . CONCLUSIONS Personalized education and case management are successful in enhancing compliance with breast cancer screening among historically noncompliant vulnerable urban women . This intervention , when combined with a preventive care information system , has the potential to achieve Healthy People 2000 objectives for breast cancer screening Clinical practice frequently generates questions that are not easily answered by r and omized trials . On conventional hierarchies of evidence , ' weaker ' study design s are often more feasible . Also , much research is not well design ed . Yet we still need to make best use of the available evidence . Systematic review s must therefore address the danger of underestimating the evidence from relevant literature if it includes only that of a certain method ological quality . This would run the risk of missing or distorting the true message that the review is trying to identify . We propose a classification of research which does not reject studies on the basis of design alone , but recognizes the importance of assessing the message or ' signal ' within each piece of research . It explicitly introduces judgement into the appraisal and synthesis of evidence , and affords more flexibility in attaching weight to evidence that might otherwise be lost . It includes an assessment of method ological quality , balancing this against the weight of its message , rather than rejecting studies which are below a certain threshold for quality . Fundamentally flawed research will still be rejected , but more commonly papers can still be used , tempering the importance that we attach to their signal by the amount of ' noise ' around that signal . The balance of these two elements may be termed the ' signal to noise ratio ' BACKGROUND Evidence indicates that although first-degree relatives of breast cancer cases are at increased risk of developing the disease themselves , they may be underutilizing screening mammography . Therefore , interventions to increase the use of mammography in this group are urgently needed . METHODS A r and omized two-group design was used to evaluate an intervention to increase mammography use among women ( N = 901 ) with at least one first-degree relative with breast cancer . A statewide cancer registry was used to obtain a r and om sample of breast cancer cases who identified eligible relatives . The mailed intervention consisted of personalized risk notification and other theoretically driven material s tailored for high-risk women . RESULTS An overall significant intervention effect was observed ( 8 % intervention group advantage ) in mammography at post-test . There was an interaction of the intervention with age such that there was no effect among women < 50 years of age and a fairly large ( 20 % advantage ) effect among women 50 + and 65 + . Health insurance , education , and having had a mammogram in the year before baseline assessment were positive predictors of mammography at post-test . Perceived risk , calculated risk , and relationship to index cancer case were not associated with mammography receipt . CONCLUSION The intervention was successful in increasing mammography rates among high-risk women 50 + years of age . Further work is needed to determine why it was ineffective among younger women |
2,408 | 20,615,496 | RESULTS There was no statistically significant effect on antidepressant response .
No significant effect on remission rate was seen for SS versus LL and SS/SL versus LL .
The 5-HTTLPR biallelic short/long polymorphism by itself does not seem to usefully predict antidepressant response | BACKGROUND The serotonin transporter gene-linked polymorphic region ( 5-HTTLPR ) has been proposed as a predictor of antidepressant response .
Insertion or deletion of a 44-base pair-long region gives rise to short " S " and long " L " forms of the promoter region , the " S " form being associated with reduced serotonin transporter expression . | BACKGROUND Although clinicians frequently add a second medication to an initial , ineffective antidepressant drug , no r and omized controlled trial has compared the efficacy of this approach . METHODS We r and omly assigned 565 adult out patients who had nonpsychotic major depressive disorder without remission despite a mean of 11.9 weeks of citalopram therapy ( mean final dose , 55 mg per day ) to receive sustained-release bupropion ( at a dose of up to 400 mg per day ) as augmentation and 286 to receive buspirone ( at a dose of up to 60 mg per day ) as augmentation . The primary outcome of remission of symptoms was defined as a score of 7 or less on the 17-item Hamilton Rating Scale for Depression ( HRSD-17 ) at the end of this study ; scores were obtained over the telephone by raters blinded to treatment assignment . The 16-item Quick Inventory of Depressive Symptomatology -- Self-Report ( QIDS-SR-16 ) was used to determine the secondary outcomes of remission ( defined as a score of less than 6 at the end of this study ) and response ( a reduction in baseline scores of 50 percent or more ) . RESULTS The sustained-release bupropion group and the buspirone group had similar rates of HRSD-17 remission ( 29.7 percent and 30.1 percent , respectively ) , QIDS-SR-16 remission ( 39.0 percent and 32.9 percent ) , and QIDS-SR-16 response ( 31.8 percent and 26.9 percent ) . Sustained-release bupropion , however , was associated with a greater reduction ( from baseline to the end of this study ) in QIDS-SR-16 scores than was buspirone ( 25.3 percent vs. 17.1 percent , P<0.04 ) , a lower QIDS-SR-16 score at the end of this study ( 8.0 vs. 9.1 , P<0.02 ) , and a lower dropout rate due to intolerance ( 12.5 percent vs. 20.6 percent , P<0.009 ) . CONCLUSIONS Augmentation of citalopram with either sustained-release bupropion or buspirone appears to be useful in actual clinical setting s. Augmentation with sustained-release bupropion does have certain advantages , including a greater reduction in the number and severity of symptoms and fewer side effects and adverse events . ( Clinical Trials.gov number , NCT00021528 . ) Depression with psychotic features has been shown to respond to selective serotonin reuptake inhibitors ( SSRIs ) . The serotonin transporter ( 5-HTT ) is a prime target for SSRIs . A functional polymorphism within the promoter region of the 5-HTT gene , leading to different transcriptional efficiency , was recently reported . We tested the hypothesis that allelic variation of the 5-HTT promoter could be related to the antidepressant response to fluvoxamine and /or augmentation with pindolol ( a serotonin autoreceptors antagonist ) which has been suggested as an augmentation therapy for nonresponders . One hundred and two in patients with major depression with psychotic features were r and omly assigned to treatment with a fixed dose of fluvoxamine and either placebo or pindolol for 6 weeks . Depression severity was assessed once a week using the Hamilton Depression Rating Scale . Allelic variation in each subject was determined using a PCR-based method . Data were analyzed with a three-way repeated measures analysis of variance . Both homozygotes for the long variant ( l/l ) of the 5-HTT promoter and heterozygotes ( l/s ) showed a better response to fluvoxamine than homozygotes for the short variant ( s/s ) . In the group treated with fluvoxamine plus pindolol all the genotypes acted like l/l treated with fluvoxamine alone . Fluvoxamine efficacy in delusional depression seems to be related to allelic variation within the promoter of the 5-HTT gene . Even though other factors may be implicated , genotyping at 5-HTT promoter may represent a promising tool to individualize the pharmacological treatment of depression In the context of a long term follow-up study , we analysed the possible implication of the 5-HTTLPR polymorphism at the serotonin transporter gene in clinical response and remission of major depressive patients treated with citalopram . The sample consisted of 131 patients , all of Spanish origin , diagnosed according to DSM-IV criteria . A 21-item Hamilton Depression Rating Scale ( HDRS ) was used to evaluate severity of the symptoms during the follow-up and to determine clinical response and remission condition of the patients at 4th and 12th week , respectively . Our results showed that S/S genotype of the 5-HTTLPR polymorphism was associated with the non-Remission condition at 12th week ( χ2 = 8.7 , P = 0.013 ) . Moreover , homozygous for the allele S presented three times more risk for non reaching remission of depressive episode after citalopram treatment than patients with any other 5-HTTLPR genotype combination ( χ2 : 7.29 , P = 0.006 ; OR = 3.23 [ 95%CI : 1.24–8.5 ] ) . In conclusion , our results show that genetic variation of serotonin transporter is involved in clinical remission of major depressive episodes after twelve weeks of citalopram treatment We examined allelic polymorphisms of the serotonin transporter ( 5-HTT ) gene and antidepressant response to 6 weeks ' treatment with the selective serotonin reuptake inhibitor ( SSRI ) drugs fluoxetine or paroxetine . We genotyped 120 patients and 252 normal controls , using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene . Diagnosis of depression was not associated with 5-HTT polymorphisms . Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others ( p < 0.0001 , p = 0.0074 , respectively ) . Lack of the I/I allele form in intron 2 most powerfully predicted non-response ( 83.3 % ) . Response to SSRI drugs is related to allelic variation in the 5-HTT gene in depressed Korean patients BACKGROUND Episodes of depression are the most frequent cause of disability among patients with bipolar disorder . The effectiveness and safety of st and ard antidepressant agents for depressive episodes associated with bipolar disorder ( bipolar depression ) have not been well studied . Our study was design ed to determine whether adjunctive antidepressant therapy reduces symptoms of bipolar depression without increasing the risk of mania . METHODS In this double-blind , placebo-controlled study , we r and omly assigned subjects with bipolar depression to receive up to 26 weeks of treatment with a mood stabilizer plus adjunctive antidepressant therapy or a mood stabilizer plus a matching placebo , under conditions generalizable to routine clinical care . A st and ardized clinical monitoring form adapted from the mood-disorder modules of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders , fourth edition , was used at all follow-up visits . The primary outcome was the percentage of subjects in each treatment group meeting the criterion for a durable recovery ( 8 consecutive weeks of euthymia ) . Secondary effectiveness outcomes and rates of treatment-emergent affective switch ( a switch to mania or hypomania early in the course of treatment ) were also examined . RESULTS Forty-two of the 179 subjects ( 23.5 % ) receiving a mood stabilizer plus adjunctive antidepressant therapy had a durable recovery , as did 51 of the 187 subjects ( 27.3 % ) receiving a mood stabilizer plus a matching placebo ( P=0.40 ) . Modest nonsignificant trends favoring the group receiving a mood stabilizer plus placebo were observed across the secondary outcomes . Rates of treatment-emergent affective switch were similar in the two groups . CONCLUSIONS The use of adjunctive , st and ard antidepressant medication , as compared with the use of mood stabilizers , was not associated with increased efficacy or with increased risk of treatment-emergent affective switch . Longer-term outcome studies are needed to fully assess the benefits and risks of antidepressant therapy for bipolar disorder . ( Clinical Trials.gov number , NCT00012558 [ Clinical Trials.gov ] . ) Serotonin systems appear to play a key role in the pathogenesis of major depression and the therapeutic mechanisms of antidepressants . The firing rate of dorsal raphe serotonergic neurons is controlled by somatodendritic 5-hydroxytryptamine 1A ( HTR1A ) autoreceptors , and desensitization of these receptors is implicated in the antidepressant mechanism of selective serotonin reuptake inhibitors . We tested whether a functional polymorphism ( C-1019 G ) in the promoter region of the HTR1A gene and serotonin-related genetic variants are related to fluoxetine antidepressant effect . We genotyped the HTR1A C-1019 G polymorphism as well as polymorphisms in the serotonin transporter gene-linked polymorphic region ( SERTPR ) , variable-number t and em-repeat polymorphisms in intron 2 ( STin2 ) of the serotonin transporter gene , serotonin 2A receptor ( T102C ) , tryptophan hydroxylase ( A218C ) , and G-protein beta3 subunit ( C825 T ) in 224 Chinese patients from southern Taiwan with major depression , who accepted 4-week fluoxetine treatment and therapeutic evaluation . Our results demonstrated that the HTR1A −1019C/C carriers ( P=0.009 ) and SERTPR l/l carriers ( P<0.001 ) showed a better response to fluoxetine , while other polymorphisms were not associated with fluoxetine therapeutic response . The major limitation of this study is the lack of a placebo control . Future prospect i ve study with placebo control may help to predict and individualize antidepressant treatment BACKGROUND It has been recently reported that the short variant of the serotonin transporter ( 5-HTT ) gene-linked functional polymorphic region ( 5-HTTLPR ) influences the antidepressant response to certain selective serotonin reuptake inhibitors . The aim of the present study was to test this finding in a sample of major and bipolar depressives , with or without psychotic features . METHODS One hundred fifty-five in patients were treated with fluvoxamine 300 mg and either placebo or pindolol in a double-blind design for 6 weeks . The severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression . Allelic variation of 5-HTTLPR in each subject was determined using a polymerase chain reaction-based technique . RESULTS 5-HTTLPR short variant was associated with a poor response to fluvoxamine treatment , independently from the recorded clinical variables . More specifically , the diagnosis , the presence of psychotic features , and the severity of depressive symptomatology did not influence this association . Conversely , pindolol augmentation may ameliorate the rate of response in 5-HTTLPR short variant subjects , thus reducing the difference in the response rate among the genotype variants . CONCLUSIONS If confirmed , these results may improve patient care by helping the clinician to individualize treatment according to the patient 's genetic 5-HTTLPR pattern Several studies and meta-analyses have implicated a polymorphism in the promoter region of the serotonin transporter ( 5-HTT ) gene , 5-HTTLPR in treatment outcomes of selective serotonin re-uptake inhibitors in patients with major depression . In this study we investigated the impact of 5-HTTLPR and a functional SNP rs25531 on the treatment outcomes to escitalopram in depressive patients . The study sample consisted of 135 out patients with major depressive disorder ( mean age 31.1+/-11.6 years , 68 % females ) treated with escitalopram 10 - 20 mg/day for 12 weeks . There were no significant associations between 5-HTT promoter region polymorphisms and response rate or mean change of depressive symptoms during escitalopram treatment . However we showed that patients carrying S allele of 5-HTTLPR may have increased risk for some side effects , including headache , induced by escitalopram medication The relationship of the serotonin transporter gene promoter region polymorphism ( 5-HTTLPR ) to antidepressant response was examined in 95 elderly patients receiving a protocol ized treatment for depression with paroxetine or nortriptyline . Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations . Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele . There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression ( HRSD ) scores or anxiety symptoms . During acute treatment with paroxetine , mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele , despite equivalent paroxetine concentrations . Onset of response to nortriptyline was not affected . Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor Rationale A common polymorphism ( 5HTTLPR ) within the promoter region of the serotonin transporter gene ( LSC6A4 ) has been shown to influence response time as well as overall response to selective serotonin reuptake inhibitors ( SSRIs ) in subjects with major depressive disorder . We hypothesized that a similar effect in response time to sertraline would be observed and that no effect on response time would be seen in a placebo arm . Objectives We tested the hypothesis that subjects homozygous for the long allele at the 5HTTLPR polymorphism would respond more rapidly to sertraline than subjects carrying one or two copies of the short allele . Methods HAM-D and CGI-I responses to sertraline and placebo were measured weekly in the context of an 8-week , placebo-controlled study in elderly depressed subjects . Genotyping of the 5HTTLPR polymorphism was performed to test for correlations with response at each week in the sertraline and placebo groups ( n=206 ) . Results Subjects homozygous for the long allele of 5HTTLPR showed a significant increase in response at week 1 and week 2 , as assessed by the CGI-I scale compared with subjects carrying one or two copies of the short allele ( P=0.01 at both weeks ) . No significant difference was observed in the placebo group . Conclusions These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs Depressive disorders account for a large and increasing global burden of disease . Although the condition of many patients improves with medication , only a minority experience full remission , and patients whose condition responds to one medication may not have a response to others . Individual variation in antidepressant treatment outcome is , at present , unpredictable but may have a partial genetic basis . We search ed for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression ( STAR*D ) study and were prospect ively assessed . In a split- sample design , a selection of 68 c and i date genes was genotyped , with 768 single-nucleotide-polymorphism markers chosen to detect common genetic variation . We detected significant and reproducible association between treatment outcome and a marker in HTR2A ( P range 1 x 10(-6 ) to 3.7 x 10(-5 ) in the total sample ) . Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample . HTR2A encodes the serotonin 2A receptor , which is downregulated by citalopram . Participants who were homozygous for the A allele had an 18 % reduction in absolute risk of having no response to treatment , compared with those homozygous for the other allele . The A allele was over six times more frequent in white than in black participants , and treatment was less effective among black participants . The A allele may contribute to racial differences in outcomes of antidepressant treatment . Taken together with prior neurobiological findings , these new genetic data make a compelling case for a key role of HTR2A in the mechanism of antidepressant action In this study , we tested the influence of the serotonin type 2A , 3A and 3B receptor genes ( HTR2A , HTR3A , HTR3B ) in addition to a polymorphism in the promoter region of the serotonin transporter ( SERTPR ) , and investigated the different characteristics of clinical responses to paroxetine and fluvoxamine . A total of 100 Japanese patients affected by major recurrent depression were enrolled in a r and omized 6-week study . The clinical response was evaluated using the Hamilton Rating Scale for Depression ( HAM-D ) , and adverse drug reactions were assessed at each visit . Patients with the l allele of SERTPR showed a better response to SSRIs than s/s genotype carriers ( p = 0.015–0.042 ) , more significantly to fluvoxamine . The –1438G/G genotype of HTR2A was associated with a good response to SSRIs ( p = 0.010–0.039 ) , especially to fluvoxamine , and significantly with severe nausea in paroxetine-treated patients ( p = 0.013 ) . The 178C/C genotype of the HTR3A was associated with an antidepressant response ( p = 0.022–0.042 ) , and more significantly in paroxetine-treated patients ( p = 0.002–0.042 ) . These effects were independent of one another . We replicated the finding that the SERPTR polymorphism was associated with a response to SSRIs . We additionally found that HTR2A and HTR3A polymorphisms are associated with the efficacy , and the HTR2A polymorphism is also associated with adverse drug reactions . Furthermore , the effects of these polymorphisms varied from one SSRI to another and thus may depend on the characteristics of each SSRI The aim of this pilot study was to examine the relationship between clinical response , adverse effects , sertraline ( SERT ) plasma concentrations and the genetic polymorphism of the serotonin transporter gene-linked polymorphic region ( 5HTTLPR ) in 2 ethnic patient groups . The study involved 45 patients in a clinical trial who received a fixed dose regimen of 50 mg SERT for one week , then a variable-dose regimen for a further 6 weeks for major depressive disorder . At weeks 1 and 6 , the following assessment s were completed : Hamilton Depression Rating Scale ( HDRS ) , Clinical Global Impression ( CGI ) , drug adverse reaction scale and measurement of plasma SERT levels . Genomic analysis for the long and short allele variants of the 5HTTLPR polymorphism was also carried out . Caucasian subjects had a higher rate of l/l genotype while Chinese subjects had higher frequencies of l/s and s/s genotypes . Comparison of the subjects with the 5HTTLPR s/s genotype and those with the l/l and l/s genotypes found no significant differences in the HDRS scores , CGI scores , response rates , adverse effects and SERT plasma concentrations at week 6 BACKGROUND We previously reported the association between some genetic factors and short-term antidepressant outcome . In the present paper we investigated the same gene variants in a prospect i ve 6-months naturalistic follow-up . METHODS The sample included 185 in patients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospect ively followed for 6 months after their recovery . All the patients were undertaking continuation therapy . The functional polymorphism in the upstream regulatory region of the serotonin transporter gene ( SERTPR ) , the tryptophan hydroxylase A218C substitution , a VNTR polymorphism located 1.2 kb upstream of the monoamine oxidase-A coding sequences , the CLOCK gene T3111C and the PER3exon15 gene T1940 G substitutions were analysed , using PCR-based techniques . RESULTS No association was found between clinical variables and relapses ; subjects showing TT genotype at CLOCK gene tended to relapse within 6 months after recovery more than TC and CC subjects taken together . A non-significant tendency of SERTPR*s/s subjects to a minor frequency of relapse was also observed . CONCLUSION Some subjects showing remission after acute treatment relapsed within 6 months , despite undertaking a maintenance treatment ; the causes could be heterogeneous , but CLOCK gene variants may influence the outcome In 169 depressed patients r and omized to treatment with either fluoxetine or nortriptyline , we examined whether polymorphisms of the serotonin transporter and the G protein beta3 subunit influenced response to these antidepressants . For depressed patients under the age of 25 yr the T allele of the G protein beta3 subunit was associated with a markedly poorer response to nortriptyline , while serotonin transporter polymorphisms did not predict antidepressant response . However , in patients 25 yr or older , the G protein beta3 polymorphisms did not predict antidepressant response , while the s , s genotype of the serotonin transporter was associated with a poorer response to both fluoxetine and nortriptyline . These differential pharmacogenetic predictors of antidepressant response by age , may provide clues to underst and ing the discontinuities in pharmacological responsiveness of child/adolescent and adult depressive disorders Finding predictors of the response to antidepressant therapy is a major goal of molecular psychiatry . The genes encoding the serotonin ( SERT ) and dopamine ( DAT1 ) transporters are among the possible c and i date genes modulating an individual 's antidepressant response . In a naturalistic prospect i ve cohort study with a total of 190 fully assessed patients , improvement of depression symptoms during the 3 weeks following initiation of antidepressant therapy was recorded using the 21-item Hamilton Depression Rating Scale ( HDRS ) . The SLC6A3 3′ UTR 40-bp variable number of t and em repeats ( VNTR ) and the SLC6A4 5′ 44-bp insertion/deletion polymorphism were analyzed by polymerase chain reaction . There was a significantly smaller number of rapid responders among homozygous carriers of the DAT1 9-repeat allele ( 9/9 ) than among heterozygous ( 9/10 ) and homozygous ( 10/10 ) carriers of the 10-repeat allele ( 19 versus 37 versus 52 % , respectively , P=0.0037 ) . Median decline in HDRS score was 35 , 40 , and 52 % in patients with the 9/9 , 9/10 , and 10/10 genotypes , respectively ( P=0.013 ) . The effect was found in all classes of medications ( selective serotonin reuptake inhibitors ( SSRIs ) , tricyclics , mirtazapine , venlafaxine ) and statistically significant also within the subgroup of patients having received SSRIs . The serotonin promoter insertion/deletion genotype had no effect in the entire study group , but there was an insignificant trend of better response in the l/l and l/s carriers who received SSRIs or mirtazapine . In conclusion , the dopamine transporter VNTR polymorphism influenced rapid response to antidepressant therapy . Compared with homozygous carriers of the 10-repeat allele , carriers of the 9/10 genotype had an odds ratio ( OR ) calculated by logistic regression analysis of 1.6 ( 95 % CI 0.8–3.2 ) and carriers of the 9/9 genotype had an OR of 6.0 ( 1.5–24.4 ) for no or poor response . Further studies are required to confirm this clinical association and to eluci date the underlying mechanisms Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants , and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene ( 5-HTTLPR ) . Mirtazapine has a dual-action profile , combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes . The goal of this study was to eluci date whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder ( MDD ) . One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment . The severity of depression was assessed with the 21-item Hamilton Depression Rating scale , and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction . Our results showed that responses at the 2nd and 4th weeks were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers . These results support our hypothesis that the response to noradrenergic and specific serotonergic antidepressants is significantly associated with the 5-HTTLPR polymorphism |
2,409 | 10,796,636 | There was no difference in forced expiratory volume .
In a second study , compared to placebo , recombinant human DNase showed no difference in forced expiratory volume or forced vital capacity .
Adverse effects , including influenza-like symptoms , were more common in the group receiving recombinant human DNase .
REVIEW ER 'S CONCLUSIONS There is not enough evidence to evaluate the routine use of mucolytics for bronchiectasis .
High doses of bromhexine coupled with antibiotics may help with sputum production and clearance | BACKGROUND Bronchiectasis is usually characterised by the production of large quantities of sputum that patients frequently have difficulty in expectorating .
Mucolytic agents target hyper-secretion or changed physiochemical properties of sputum to make it easier to clear .
One drug , recombinant human DNase , breaks down the DNA that is released at the site of infection by neutrophils .
OBJECTIVES The objective of this review was to assess the effects of ingested or inhaled mucolytics in patients with bronchiectasis . | It has previously been shown that unproductive coughing in both healthy subjects and patients with airways obstruction is not effective in clearing lung secretions . This study investigates the regional mucus transport in a group of subjects with airways obstruction who failed to expectorate following instructed cough and forced expiration technique . Fourteen patients ( mean + /- SEM age : 68 + /- 2 years ) with airways obstruction ( mean + /- SEM percent predicted . FEV1 : 54 + /- 5 ; daily wet weight sputum : 9.1 + /- 2.0 g ) took part in the study which was a r and omized , three-way crossover within-patient design . Each patient underwent three treatment maneuvers : control , cough ( 30 coughs over a 10-min period ) , and forced expiration ( 30 forced expirations over a 10-min period ) . An objective radioaerosol technique was used to monitor regional mucus movement within the lungs of the patients . The lungs were divided arbitrarily into four regions of interest : tracheal , inner , intermediate , and outer . Peak expiratory flow rate during cough and forced expiration was measured at the mouth . There was no correlation between the radioaerosol clearance from all regions and ( 1 ) mean peak flow during cough and forced expiration , and ( 2 ) mean 24-h sputum production prior to the study day . There were no differences in regional radioaerosol clearance between cough and forced expiration . However , both cough and forced expiration result ed in significant clearance compared with control for all regions with the exception of the forced expiration in the outer region . To our knowledge , this study is the first to demonstrate that unproductive cough and forced expiration result in movement of secretions proximally from all regions of the lung in patients with airways obstruction Eight patients with Young 's syndrome were treated with four " mucoregulatory " agents for eight weeks in a r and omised , open crossover study . There was no improvement in tracheobronchial clearance , pulmonary function , or sperm count The effectiveness of bromhexine in the treatment of patients with bronchiectasis , in a stage of clinical exacerbation , was assessed in a double-blind , placebo-controlled trial involving 88 in- patients . Bronchiectasis was diagnosed by bronchography and /or CT scan . Bromhexine or matched placebo was administered as 30-mg capsules three times daily per os . Ceftazidine , 1 g i.m . , was given to all patients once a day for the first week only . Bromhexine seemed to improve the clinical picture , with significantly positive trends for expectoration , quantity of sputum and auscultatory findings . It also increased the FEV1 and was well-tolerated . Both patients and investigators judged it efficacious BACKGROUND --In vitro studies have suggested that both the viscoelastic properties of lung secretions and the peak flow attained during simulated cough influence clearance . This study examines the possible association of the viscoelastic properties of sputum and maximum expiratory flow with measured effectiveness of mucus clearance induced by instructed cough and by forced expiration technique ( FET ) in patients with airways obstruction . METHODS --Nineteen patients ( 11 men and eight women ) of mean ( SE ) age , % predicted FEV1 , and daily sputum wet weight of 64 ( 2 ) years , 52 (6)% , and 37.5 ( 7.9 ) g respectively participated in the study . Mucus movement from proximal and peripheral lung regions was measured by an objective non-invasive radioaerosol technique . Each patient underwent three assessment s : control , cough , and FET . During cough and FET , maximum expiratory flow was measured at the mouth level . Apparent viscosity and elasticity of the expectorated sputum sample s were measured with a viscometer . RESULTS --Compared with the control run ( mean ( SE ) clearance : 16 (3)% ) there was an increase in clearance from the whole lung during cough ( 44 (5)% ) and FET ( 42 (5)% ) , and also an enhanced clearance of inhaled , deposited radioaerosol from the trachea , inner and intermediate regions of the lungs , but not from the outer region . There were , however , no differences in regional clearance between cough and FET . Neither regional nor total clearance correlated with maximum expiratory flow , apparent viscosity , elasticity , or daily sputum wet weight . CONCLUSIONS --These results confirm that cough and FET both promote effective clearance but suggest that , unlike in vitro studies , sputum production and viscoelasticity , as well as maximum expiratory flow , provide no guide to clearance efficacy in humans The authors report the results of a study design ed to evaluate the possible increase of penetration into bronchial secretions of antibiotics when combined with a fluidifying agent : bromhexine . The study was carried out in a double-blind experiment : erythromycin in 22 patients ( group I ) or amoxycillin in 26 patients ( group II ) were administered orally ; in both groups several patients were given a placebo , instead of bromhexine . Antibiotics were administered at the usual dosage : 0.5 g X 2 for erythromycin ( 3 days ) ; 1 g X 2 for amoxycillin ( 7 days ) ; with the latter , two different doses of bromhexine were administered simultaneously : 48 mg/day and 96 mg/day in ten and eight patients respectively . Sample s of bronchial secretions were collected by means of fibreoptic bronchoscopy at the second hour for erythromycin and for amoxycillin ; simultaneous serum sample s were also collected . The results of the study showed in both groups a significant increase of the ratios between bronchial levels and simultaneous serum concentrations when combined with bromhexine ; in patients receiving amoxycillin with 96 mg of bromhexine the percentage penetration was noticeably higher ( 7.5 % ) than in those treated with 48 mg bromhexine ( 4.3 % ) . These results confirm the efficacy of bromhexine as a drug able to disrupt mucopolysaccharides of bronchial secretions and , as a result , to increase the bronchial penetration of antimicrobial drugs as evaluated on the basis of percentage penetration ratio The effect of peroral N-acetylcysteine ( NAC ) in patients with cystic fibrosis ( CF ) and primary ciliary dyskinesia ( PCD ) was investigated . 41 CF patients and 13 PCD patients completed the study which was a double-blind , placebo-controlled , cross-over trial . The patients received either NAC or placebo for two periods of three months followed by a three month follow-up period . Active treatment consisted of NAC , either 200 mg x 3 daily ( patients weighing less than 30 kg ) or 400 mg x 2 daily ( greater than 30 kg ) . The effect was evaluated in terms of a subjective clinical score , weight , sputum bacteriology , blood leucocyte count , sedimentation rate , titres of specific antimicrobial antibodies , lung function parameters and measurement of the ciliary function . No effect was seen in PCD patients , but in CF patients an improved lung function was seen in the period when the patients suffer most from lower airway infections We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase ( rhDNase ) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis . All were in a stable clinical state at the commencement of the study , and they received ( 1 ) rhDNase 2.5 mg twice daily , ( 2 ) rhDNase once daily , or ( 3 ) placebo ( excipient only ) inhalation . The outcome measures were spirometry , subjective quality of life/dyspnea , and safety . We also measured the ciliary transportability of the sputum expectorated before and after the treatment period , using the mucus-depleted bovine trachea . The drug was well tolerated , but it produced no significant change in any of the outcome variables or in sputum transportability . When the drug was incubated with bronchiectatic sputum in vitro , a fall in transportability was observed . We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population , which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design Bromhexeine has been widely used as an adjunct in the management of lower respiratory infections and is useful in altering the physical characteristics of sputum . Its effect on the sputum penetration of an antibiotic has been sparsely studied . The present study highlights the improvement in sputum amoxycillin ( amoxy ) levels when a combination tablet , amoxy 500 mg plus bromhexeine 8 mg , is administered as compared to plain amoxy 500 mg . Sputum amoxy levels were significantly higher in the combination group ( 0.674 + /- 0.588 micrograms ml-1 ) as compared to 0.272 + /- 0.19 micrograms ml-1 in the amoxy group ( P = 0.028 ) . The clinical responses assessed by the physician as well as the patient were significantly better in the amoxy plus bromhexeine group as compared to the amoxy group . The radiological and bacteriological responses were similar in both groups . There was no increase in the side-effects due to bromhexeine and , overall , its use can be recommended in the treatment of acute lower respiratory infections STUDY OBJECTIVE To study the safety and efficacy of aerosolized recombinant human DNase I in the treatment of idiopathic bronchiectasis . DESIGN Double-blind , r and omized , placebo-controlled , multicenter study . POPULATION S Three hundred forty-nine adult out patients in stable condition with idiopathic bronchiectasis from 23 centers in North America , Great Britain , and Irel and . INTERVENTIONS AND MEASUREMENTS Study patients received aerosolized rhDNase or placebo twice daily for 24 weeks . Primary end points were incidence of pulmonary exacerbations and mean percent change in FEV1 from baseline over the treatment period . RESULTS Pulmonary exacerbations were more frequent and FEV1 decline was greater in patients who received rhDNase compared with placebo during this 24-week trial . CONCLUSIONS rhDNase was ineffective and potentially harmful in this group of adult out patients in stable condition with idiopathic bronchiectasis . This contrasts with previously published results that demonstrated efficacy of rhDNase in patients with cystic fibrosis bronchiectasis Summary : A double-blind crossover clinical trial design ed to evaluate the mucolytic activity of bromhexine hydrochloride on sputum was completed by 15 patients with chronic lung disease . All the subjects chosen were troubled by production of tenacious mucoid or mucopurulent sputum at the beginning of the trial . Each subject received 16 mg of bromhexine by mouth , three times daily and identical appearance placebo tablets , for an equal number of weeks , in r and om sequence . Twenty-four-hour sputum production was collected for each subject throughout the trial . Viscosity of sputum was evaluated with a Wells-Brookfield Micro-Viscometer Model RVT , study ing the highest viscosity sample produced per 24-hour period . In eight patients some significant decrease in sputum viscosity was observed during bromhexine therapy . In one patient a significant decrease in sputum viscosity was observed while he was receiving the placebo . The mean sputum viscosity for all 15 patients considered as a group was significantly lower during bromhexine therapy than during the placebo therapy . It is concluded from the results obtained that bromhexine has a demonstrable mucolytic effect on tenacious sputum and consequently may play a useful role in the management of patients with chronic lung disease involving the production of high viscosity bronchial secretions BACKGROUND The synthetic mucolytic neltene-xine is an amide derivative of ambroxol and thiophencarboxylic acid . The aim of this open , r and omised , controlled study versus sobrerol was to evaluate the efficacy and tolerability of neltenexine ( oral granules in sachets ) as compared with sobrerol ( oral granules in sachets ) , administered to patients with obstructive airways disease . METHODS Thirty male and female patients were recruited . The exclusion criteria were allergy to neltenexine or sobrerol , an assessed diagnosis of severe bronchospasm requiring beta2-agonists , corticosteroids or aminophylline , pregnant or nursing women , cystic fibrosis , active tuberculosis or an assessed diagnosis of bronchiectasis . No infections of other organs ( such as urinary tract infections ) were present at baseline . Concomitant treatment with antitussives or other mucolytic agents was not allowed during the course of the study . Fifteen patients were r and omised to treatment with neltenexine , 1 sachet thrice daily for 20 days orally ( neltenexine group ) and 15 patients to treatment with sobrerol , 1 sachet thrice daily for 20 days orally ( sobrerol group ) . The efficacy parameters were : sputum characteristics and volume , difficulty in expectorating , cough , dyspnoea , pulmonary auscultation . Tolerability was monitored and adverse events were reported . RESULTS The study highlighted that neltenexine has a good efficacy in the treatment of patients with obstructive airways disease entailing significant impairment of clinical parameters . CONCLUSIONS Neltenexine can be an effective therapeutic alternative to sobrerol Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment . Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance ( MCC ) in asthmatic and in healthy subjects ( Daviskas , E. , S. D. And erson , J. D. Brannan , H. K. Chan , S. Eberl , and G. Bautovich . 1997 . Inhalation of dry-powder mannitol increases mucociliary clearance . Eur . Respir . J. 10:2449 - 2454 ) . In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis . Eleven patients 40 to 62 yr of age inhaled mannitol ( approximately 300 mg ) from a Dinkihaler . MCC was measured over 90 min , in the supine position , on three occasions involving : mannitol or control or baseline , using a radioaerosol technique . On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol . Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung , central , and intermediate region . Mean ( + /- SEM ) clearance with mannitol was 34.0 + /- 5.0 % versus 17.4 + /- 3.8 % with control and 11.7 + /- 4.4 % with baseline in the whole right lung ( p < 0.0001 ) . The mean number of coughs induced by mannitol was 49 + /- 11 . In conclusion , inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis The clinical effect and utility of sfericase was compared with an inactive placebo by a double-blind method in three groups of a total 109 patients suffering from chronic respiratory diseases who had complained of difficult expectoration of sputum . A significantly greater improvement of expectoration was obtained in Group A-1 ( 6 tablets/day ) . Also in group A-1 , more cases showed subjective and objective improvement , i.e. , improvement in expectoration , reduction in coughs , decrease in the amount of sputum , and disappearance of râles . However , the sputum and its degree of purulency remained unchanged in most cases in all three groups . Side effects were few . The clinical efficacy of sfericase in the group with 2 tablets , 3X/day ( total daily dose of 6 tablets ) was shown to be significantly superior to the other two groups . This dosage was established as the optimal dose for treating difficulty in expectoration Primary ciliary dyskinesia ( PCD ) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance . Because patients with PCD use cough clearance as an airway defense mechanism , we tested the hypothesis that aerosolized uridine-5'-triphosphate ( UTP ) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells . We measured clearance during cough in 12 patients with PCD ( ages 14 to 71 yr , FEV1 43 % to 89 % predicted ) in a double blind , r and omized , crossover study after aerosolization of a single dose of UTP ( 5 mg/ml , 3.5 ml ) or vehicle ( 0.12 % saline , 3.5 ml ) . Clearance during cough ( whole lung ) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min . Safety parameters were recorded during and after drug delivery . Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle ( from 0 to 60 min : 0.40 + /- 0.07%/min [ UTP ] versus 0.26 + /- 0 . 04%/min [ vehicle ] [ mean + /- SEM ] , p = 0.01 ) , and from 0 to 120 min : 0.38 + /- 0.05%/min [ UTP ] versus 0.25 + /- 0.04%/ min [ vehicle ] , p = 0 . 02 ) . Aerosolized UTP is safe , with no serious adverse effects . Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP |
2,410 | 17,579,229 | In areas in which 1 of 4 treatments with sulfadoxine-pyrimethamine fail in children by day 14 , the 2-dose IPT with sulfadoxine-pyrimethamine regimen continues to provide substantial benefit to HIV-negative semi-immune pregnant women .
However , more frequent dosing is required in HIV-positive women not using cotrimoxazole prophylaxis for opportunistic infections | CONTEXT In malaria-endemic regions , strategies to control malaria during pregnancy rely on case management of malaria illness and anemia , and preventive measures such as insecticide-treated nets and intermittent preventive therapy ( IPT ) .
OBJECTIVE To determine the effect of increasing resistance to sulfadoxine-pyrimethamine on the efficacy of IPT during pregnancy in Africa . | Pyrimethamine-sulfadoxine , the first choice for uncomplicated falciparum malaria in Africa , exerts strong selection pressure for resistance because of its slow elimination . It is likely that resistance will emerge rapidly , and there is no widely affordable replacement . Chlorproguanil-dapsone is cheap , rapidly eliminated , more potent than pyrimethamine-sulfadoxine , and could be introduced in the near future to delay the onset of antifolate resistance and as " salvage therapy " for pyrimethamine-sulfadoxine failure . A total of 448 children were r and omly allocated ( double blind ) to either a single dose of pyrimethamine-sulfadoxine or to one of two chlorproguanil-dapsone regimens : a single dose or three doses at 24-h intervals . Reinfections are clinical ly indistinguishable from recrudescence and are more likely after treatment with rapidly eliminated drugs ; we measured the incidence of parasitemia in 205 initially aparasitemic children to allow comparison with the three treatment groups . The patients and a community surveillance group were followed up for 28 days . At the study end point , 31.2 % ( 95 % confidence interval , 24.9 - 38.0 ) of the community surveillance group subjects were parasitemic , compared with subjects in the treatment groups , whose rates of parasitemia were 40.8 % ( 32.9 - 49.0 ; relative risk [ RR ] , 1.31 [ 0.99 - 1.73 ] ) after triple-dose chlorproguanil-dapsone , 19.7 % ( 13.5 - 27.2 ; RR , 0.63 [ 0.43 - 0.93 ] ) after pyrimethamine-sulfadoxine , and 65.6 % ( 57.5 - 73.0 ; RR , 2.10 [ 1.66 - 2.65 ] ) after single-dose chlorproguanil-dapsone . Pyrimethamine-sulfadoxine and triple-dose chlorproguanil-dapsone were effective treatments . Pyrimethamine-sulfadoxine provided chemoprophylaxis during follow-up because of its slow elimination . Triple-dose chlorproguanil-dapsone should now be developed in an attempt to reduce the rate of emergence of antifolate resistance in Africa and for affordable salvage therapy in cases of pyrimethamine-sulfadoxine failure BACKGROUND In areas of endemic transmission , malaria in pregnancy is associated with severe maternal anaemia and low-birthweight babies . We studied the efficacy of intermittent treatment doses of sulphadoxine-pyrimethamine in preventing malaria and severe anaemia in pregnancy in a double-blind placebo-controlled trial among primigravid women living in Kilifi District , Kenya . METHODS Between January , 1996 , and April , 1997 , 1264 primigravid women were recruited when they attended for antenatal care , and r and omly assigned sulphadoxine-pyrimethamine ( 640 ) or placebo ( 624 ) . Women received one , two , or three doses of study medication depending on the duration of gestation at enrolment . Primary outcome measures were severe anaemia ( haemoglobin < 8 g/dL ) and malaria parasitaemia , assessed at 34 weeks of gestation . Analyses were based on intention to treat among women who had study blood tests at 34 weeks . FINDINGS 30 ( 5.3 % ) of 567 women in the sulphadoxine-pyrimethamine group and 199 ( 35.3 % ) of 564 in the placebo group had peripheral parasitaemia ( protective efficacy 85 % [ 95 % CI 78 - 90 ] , p<0.0001 ) . 82 ( 14.5 % ) and 134 ( 23.7 % ) had severe anaemia ( protective efficacy 39 % [ 22 - 52 ] , p<0.0001 ) . Even women who booked late and received only one dose of sulphadoxine-pyrimethamine benefited significantly from the intervention . The effects were seen both in women who owned insecticide-treated bednets and in women who did not . INTERPRETATION Intermittent presumptive treatment with sulphadoxine-pyrimethamine is an effective , practicable strategy to decrease the risk of severe anaemia in primigravidae living in malarious areas Objectives : In the Gambia , the combination of chloroquine ( CQ ) and sulphadoxine-pyrimethamine ( SP ) has replaced CQ monotherapy for treatment of malaria caused by Plasmodium falciparum . We measured the efficacy of the combination CQ/SP , and the prevalence of parasites carrying alleles associated with resistance to CQ or SP . Design : We conducted a single-blind , r and omised , controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone . Setting : The study took place in the town of Farafenni and surrounding villages in the Gambia . Participants : Participants were children aged 12 mo to 10 y presenting as out patients with uncomplicated P. falciparum malaria . Interventions : 500 children were r and omised to receive CQ , SP , or CQ/SP as supervised treatment and actively followed over 28 d. Outcome Measures : Primary outcome was parasitaemia at any time during follow-up . Secondary outcomes were PCR-confirmed recrudescent infections among treatment failures , and clinical failure requiring rescue medication by day 28 . Pretreatment parasite isolates from 161 patients were tested for the presence of resistance-associated genetic markers . Results : The prevalence of parasitological failure by day 28 for the CQ group was 60.3 % , compared to 17.6 % for SP ( odds ratio [ OR ] , 0.106 ; 95 % confidence interval [ CI ] , 0.057–0.194 ; p < 0.001 ) and 13.9 % for CQ/SP ( OR versus CQ , 0.140 ; 95 % CI , 0.078–0.250 ; p < 0.001 ) . There was no difference between the SP and CQ/SP groups ( OR , 1.324 ; 95 % CI , 0.705–2.50 ) . The projected prevalence of PCR-corrected treatment failure was 30.2 , 6.06 , and 3.94 % in the CQ , SP , and CQ/SP groups , respectively . The pfdhfr-triple mutant and pfdhps-437 G mutation were common , with prevalences of 67.4 and 51.2 % , respectively . Pretreatment carriage of pfdhps-437 G and of multidrug-resistant parasite genotypes was associated with treatment failure in the SP group , but not in the CQ or CQ/SP groups . Conclusions : The combination of CQ/SP was an efficacious treatment for uncomplicated malaria in Gambian children in this study , but the frequent occurrence of multidrug-resistant parasites suggests that this observed efficacy is not sustainable Whether and when to replace chloroquine with other antimalarial drugs is an urgent public health question in much of Africa , where Plasmodium falciparum , which is increasingly resistant to chloroquine , continues to kill millions each year . Antimalarial drug efficacy has traditionally been measured as parasitologic resistance , but recent guidelines use both clinical and parasitologic criteria to monitor therapeutic efficacy . To assess the new efficacy protocol , we measured parasitologic and therapeutic outcomes in 514 patients treated with chloroquine for uncomplicated P. falciparum malaria in Mali . There was a general agreement between parasitologic and therapeutic outcomes at two sites , with 13 - 17 % parasitologic resistance rates and 10 - 15 % treatment failure rates . However , the new protocol overestimated early treatment failure rates ( 21 - 71 % of cases classified as early treatment failure had sensitive or RI parasitologic responses ) , particularly where resistance was rare , and missed low-level parasitologic resistance . Modifications of the protocol for monitoring antimalarial therapeutic efficacy are recommended Malarial infection during pregnancy increases the risks of severe sequelae for the pregnant woman and the risk of delivering a low birthweight baby . The aim of this intervention study was to reduce significantly the prevalence of malaria parasitaemia in adolescent parturients in Matola and Boane in Mozambique . The study was focused upon the most malaria-vulnerable group , adolescent nulliparous and primiparous women . After completing the usual antenatal clinic and giving informed consent , 600 pregnant women were r and omly chosen in a double blind manner to one of two regimens comparing the prevailing routine ( placebo ) for malaria prevention with a two dose regimen of sulphadoxine-pyrimethamine ( SP ) . The first dose was given at enrollment with a second dose at the beginning of the third trimester . At delivery maternal and placental malaria parasitaemia as well as birthweight and gestational duration were analysed . At booking the prevalence of malaria parasitaemia was 35.3 % in the placebo group and 30.6 % in the SP group . At the second dose , the prevalence of malaria parasitaemia in the placebo group and SP group was 19.7 % and 8.7 % , respectively . This implies a relative risk ( RR ) of 2.24 with 95 % CI ( 1.34 , 3.75 ) . The corresponding figures at delivery were 13.6 % and 6.3 % with an RR of 2.22 ( 1.07 , 4.60 ) and in placenta 13.3 % and 2.4 % with an RR of 4.87 ( 1.58 , 15.0 ) . Newborns with malaria within 7 days were significantly more frequent in the placebo group , 6.4 % and 0.7 % respectively , with an RR of 6.55 ( 1.20 , 35.7 ) . Almost all ( approximately 98 % ) of the women studied had Plasmodium falciparum , the remainder had P. malariae and P. ovale . The mean birthweight in the SP group was 3077 g and in the placebo group 2926 g. The estimated mean difference between the two groups was 151 g with 95 % CI ( 51 , 252 ) . The mean placental weight in the placebo group was 596 and 645 g in the SP group , implying a difference of 49 g with a 95 % CI ( 11 , 88 ) . The mean gestational duration was 6.1 days longer in the SP group , 95 % CI ( 1.5 , 10.6 ) . In the placebo group there were two cases of urticaria and one case of nausea ; in the SP group there was one case of vomiting . No newborn showed any sign of serious SP side-effect . Two doses of SP were enough to significantly reduce the prevalence of peripheral and placental malaria parasitaemia among young nulliparous and primiparous pregnant women in Matola and Boane BACKGROUND Malaria during pregnancy contributes to maternal anemia and low birth weight . In East Africa , several studies have demonstrated that intermittent preventive treatment ( IPT ) with sulfadoxine-pyrimethamine ( SP ) is more efficacious than weekly chloroquine ( CQ ) chemoprophylaxis in preventing these adverse consequences . To our knowledge , there are no published trials evaluating IPT in West Africa . METHODS We undertook a r and omized controlled trial of weekly CQ chemoprophylaxis , 2-dose IPT with CQ , and 2-dose IPT with SP ; 1163 women were enrolled . RESULTS In multivariate analyses , when compared with weekly CQ , IPT/SP was associated with a reduction in third-trimester anemia ( adjusted odds ratio [ AOR ] , 0.49 ; P<.001 ) , placental parasitemia ( AOR , 0.69 ; P=.04 ) , and low birth weight ( < 2500 g ) ( AOR , 0.69 ; P=.04 ) . The prevalence of placental infection remained unexpectedly high , even in the IPT/SP group ( 24.5 % ) , possibly because of the intensity of seasonal transmission . There were no significant differences in stillbirths , spontaneous abortions , or neonatal deaths among the 3 groups . CONCLUSIONS In Mali , IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy . These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy . In intensely seasonal transmission setting s in Mali , > 2 doses may be required to prevent placental reinfection prior to delivery To define an effective and deliverable antimalarial regimen for use during pregnancy , pregnant women at highest risk of malaria ( those in their first or second pregnancy ) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and /or sulfadoxine-pyrimethamine ( SP ) . Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis ( CQ/CQ ) for at least 45 days prior to delivery , 32 % had placental malaria infection , compared with 26 % of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis ( SP/CQ ) , and only 9 % of 71 pregnant women who received a two-dose SP regimen ( SP/SP ; given once during the second trimester and repeated at the beginning of the third trimester ) ( P = 0.006 , by chi-square test ) . During the peak transmission season from April to July , 47 % of the women who received CQ/CQ had placental malaria infection at delivery , as compared with 37 % of the women who received SP/CQ , and 10 % of women who received SP/SP ( P = 0.004 , by chi-square test ) . Among women in their first or second pregnancy , two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery Chloroquine-resistant malaria is a major public health threat in sub-Saharan Africa . While a few countries have already replaced chloroquine as the first-line therapy for uncomplicated malaria or are in the process of doing so , other countries are faced with the complicated task of assessing the current status of drug resistance , making national policy-level decisions about whether to replace chloroquine or not , and initiating a monitoring system to track changes in the efficacy of malaria therapy . There is currently no st and ardized approach for collecting and interpreting data on therapy efficacy . There is also no agreement as to how much chloroquine resistance or treatment failure is acceptable and how much warrants a change in treatment policy . Using data collected in 10 sites in eastern and southern Africa between 1990 and 1996 , we have assessed the therapeutic response to chloroquine and investigated predictors of clinical success or failure . Based on these experiences and analyses , a st and ardized protocol for in vivo studies of the efficacy of malaria therapy and for approaches to design ing monitoring systems are proposed . The process of making policy-level decisions based on data collected by these systems is also discussed Plasmodium falciparum has developed resistance to almost all routinely used antimalarial drugs . Sulfadoxine-pyrimethamine ( SP ) has replaced chloroquine as first-line treatment of uncomplicated malaria infection in Kenya but resistance to SP is already reported . The addition of artemisinin derivatives to SP may delay the development of drug resistance , improve cure rates , and reduce transmission . The efficacy and safety of artesunate plus SP in the treatment of uncomplicated P. falciparum malaria was evaluated in a r and omized trial of 600 children at Siaya District Hospital , western Kenya between October 1999 and March 2000 . Children aged < 5 years were r and omly assigned to receive SP alone ( 1.25 mg/kg based on pyrimethamine ) , or in combination with artesunate ( 4 mg/kg/d ) for either 1 or 3 d. Parasitological failure by days 14 and 28 ( polymerase chain reaction [PCR]-corrected for new infections ) were the primary endpoints . Treatment failure rates by day 14 were 25.5 % in the SP alone group , 16.2 % ( risk difference [delta]-9.3 % , 95 % CI -17.3 to -1.2 % , P= 0.027 ) in the 1-dose artesunate group , and 9.4 % ( delta-16.2 % , 95 % CI -23.6 to -8.7 % , P < 0.001 ) in the 3-dose artesunate group . Corresponding rates by day 28 were 46.0 % in the SP alone group , 38.2 % ( delta-7.8 % , 95 % CI -17.7 to 2.1 % , P= 0.16 ) in the 1-dose artesunate group , and 26.0 % ( delta-20.0 % , 95 % CI -29.4 to -10.6 % , P < 0.001 ) in the 3-dose artesunate group . The artesunate and SP combination was well tolerated . There were no serious drug-related adverse events . Parasite clearance and gametocyte carriage were reduced significantly in both combination groups compared with SP alone . Three days of artesunate were required to reduce significantly the risk of treatment failure by day 28 . However , the high background rate of parasitological failure with SP may make this combination unsuitable for widespread use in Kenya To compare the effects of intermittent treatment with sulfadoxine-pyrimethamine ( SP ) given during the second and third trimester of pregnancy , the use of insecticide-treated nets ( ITN ) , or the combination of both on haemoglobin ( Hb ) levels during pregnancy , a r and omized , placebo-controlled intervention trial was conducted in a malaria-endemic area of western Kenya from July 1997 to September 1999 . Primigravidae and secundigravidae were enrolled into the study and r and omized into 4 intervention groups : ( i ) ITNs and SP , ( ii ) ITNs and placebo SP , ( iii ) SP alone , and ( iv ) placebo SP . All groups were offered case management and iron and folic acid supplementation . Seven hundred and fifty-two women were followed until delivery ( 53.2 % were primigravidae and 46.8 % secundigravidae ) . Among primigravidae in all the groups there was a significant improvement in Hb levels at delivery ( 107.6 g/L ) compared with recruitment ( 101.9 g/L ) ( P < 0.006 ) with the greatest improvement in the combination ITNs + SP group . The protective efficacy of ITNs + SP on anaemia was 55.8 % ( 95 % CI 30.6 - 71.8 ) , of SP alone 50.9 % ( 95 % CI 22.2 - 69.0 ) , and of ITNs 41.6 % ( 95 % CI 9.8 - 62.3 ) . Among secundigravidae , Hb levels were slightly lower at delivery compared with recruitment ( P = 0.03 ) . It was concluded that malaria is a major cause of anaemia in primigravidae but that other causes play a more significant role in secundigravidae , and that intermittent treatment with SP or use of ITNs benefits primigravidae more than secundigravidae Abstract Objective To measure the efficacy of sulfadoxine-pyrimethamine treatment of falciparum malaria in Malawi from 1998 to 2002 , after a change from chloroquine to sulfadoxine-pyrimethamine as first line treatment in that country in 1993 . Design Prospect i ve open label drug efficacy study . Setting Health centre in large peri-urban township adjacent to Blantyre , Malawi . Participants People presenting to a health centre with uncomplicated Plasmodium falciparum malaria . Main outcome measures Therapeutic efficacy and parasitological resistance to st and ard sulfadoxine-pyrimethamine treatment at 14 days and 28 days of follow up . Results Therapeutic efficacy remained stable , with adequate clinical response rates of 80 % or higher throughout the five years of the study . Analysis of follow up to 28 days showed modest but significant trends towards diminishing clinical and parasitological efficacy over time within the study period . Conclusion Contrary to expectations , sulfadoxine-pyrimethamine has retained good efficacy after 10 years as the first line antimalarial drug in Malawi . African countries with very low chloroquine efficacy , high sulfadoxine-pyrimethamine efficacy , and no other immediately available alternatives may benefit from interim use of sulfadoxine-pyrimethamine while awaiting implementation of combination antimalarial treatments In March 1993 , sulphadoxine/pyrimethamine ( SP ) replaced chloroquine as the first line drug for malaria treatment in Malawi . Since then , the Ministry of Health has been receiving anecdotal and written reports of SP treatment failures in children . To determine whether treatment failure with SP was a widespread problem , children < 5 years of age with axillary temperature > 38.0 degrees C and parasite density > 2000/mm3 attending the outpatient clinics of the Mangochi and Karonga District Hospitals were enrolled in the study with parental consent . These were then followed for 28 days or until they failed clinical ly . Of 159 patients enrolled , 145 ( 91.2 % ) were followed for 28 days or until clinical failure . Of these , none had RII resistance and 3 ( 1.9 % ) had RIII resistance : 2/69 ( 2.9 % ) in Mangochi and 1/76 ( 1.3 % ) in Karonga ; 142/145 ( 97.9 % ) exhibited RI/sensitive patterns . Of those followed to day 28 or to clinical failure , 77.1 % had parasite clearance by day 3 and 98.6 % had parasite clearance by day 7 . Of those with temperature readings ( n = 140 ) , 129 ( 92.1 % ) clinical ly improved on day 3 and 98.6 % improved by day 7 . Other indicators of clinical improvement ( from day 0 to day 3 ) included , reported increased level of activity in 136 ( 97.1 % ) of the children , and mother 's impression of child 's improvement in 113 ( 80.7 % ) . Of the 14 patients not followed to day 28 or to clinical failure , 11 were lost to follow-up by day 7 . No allergic skin reactions were noted , and no deaths were observed . These data show that after one year of widespread use of SP in Malawi , Plasmodium falciparum parasite resistance remains very low , and therefore contradicts reports of widespread parasite resistance to SP Sulphadoxine/pyrimethamine ( SP ) has become the first-line treatment of uncomplicated malaria in a number of African countries . Molecular surveillance of resistance-mediating mutations in Plasmodium falciparum dihydrofolate reductase ( dhfr ) and dihydropteroate synthase ( dhps ) has been proposed as a means of predicting SP treatment outcomes , but optimal methods of surveillance in different population s have not been well established . To investigate the relationship between molecular markers of SP resistance , host immunity , and response to therapy , we evaluated the association between the presence of five key dhfr and dhps mutations at enrollment and clinical outcome in children and adults treated with SP for uncomplicated malaria in Kampala , Ug and a. Clinical treatment failure was 11 % at 14 days , increasing to 30 % at 28 days , after excluding new infections . Outcomes varied markedly based on the number of dhfr and dhps mutations and on the age of treated subjects . All infections with less than two dhfr/dhps mutations were successfully treated . Treatment failure associated with any two , three , or four dhfr/dhps mutations occurred in nine of 24 ( 38 % ) children up to 5 years , but not in older patients ( 0/20 ) . In the presence of all five mutations , treatment failure occurred equally in children aged 5 years or younger [ 7/16 ( 44 % ) ] and in older patients [ 8/16 ( 50 % ) ] . Our results showed that age , a surrogate marker of antimalarial immunity , had a major impact on the relationship between polymorphisms in SP target enzymes and treatment outcomes . The use of molecular markers of SP resistance to predict treatment failure rates should take age into account BACKGROUND Intermittent preventive treatment during pregnancy ( IPTp ) with sulfadoxine-pyrimethamine ( SP ) decreases placental malaria parasitemia and associated maternal anemia , premature delivery , and low birth weight . However , the optimal regimen in the setting of a high prevalence of human immunodeficiency virus ( HIV ) infection remains unclear . METHODS In Malawi , where the efficacy of SP for the treatment of malaria in children is decreasing , we conducted a r and omized , nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women . RESULTS Of HIV-positive women , 7.8 % who received monthly SP had placental malaria , compared with 21.5 % of those who received 2-dose SP ( relative risk [ RR ] , 0.36 [ 95 % confidence interval { CI } , 0.17 - 0.79 ] ) . Of HIV-negative women , 2.3 % who received monthly SP and 6.3 % who received 2-dose SP had placental malaria ( RR , 0.37 [ 95 % CI , 0.11 - 1.19 ] ) . Less than 1 % of women reported adverse drug reactions , with no increase in HIV-positive women or those who received monthly SP . CONCLUSIONS In HIV-positive pregnant women , monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria . The study also demonstrates the continued efficacy of SP for the prevention of placental malaria , even in the face of its decreasing efficacy for the treatment of malaria in children . In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection , monthly SP IPTp should be adopted Sulfadoxine-pyrimethamine ( SP ) and co-trimoxazole were both effective in reducing fever , clearing parasitaemia and improving anaemia in children aged < 5 years with uncomplicated malaria in 2 Kenyan endemic sites , Oyugis in the west and Tiwi on the coast . We compared the efficacy of these 2 regimens ( in May-July 1998 ) by evaluating clinical and parasitological responses over 14 days . The combined incidence of parasitological failure for the combined sites for co-trimoxazole was 14/123 ( 11 % ) and for SP 23/145 ( 16 % ) ( RR 0.72 , 95 % confidence interval [ CI ] 0.31 - 1.46 , P = 0.289 ) . The 14-day clinical failure rate for the combined sites for co-trimoxazole was 4/123 ( 3.3 % ) , and for SP 8/145 ( 5.5 % ) , ( RR 1.69 , 95 % CI 0.91 - 3.15 , P = 0.129 ) . The results indicate that the risk of treatment failure for the 2 regimens was similar . The antimalarial use of co-trimoxazole in uncomplicated malaria needs further investigation , since the 10 - 12-h elimination half-life of both components should reduce selective pressure for resistance . In addition , use of a 2-day high-dose course , tested previously , requires further study to demonstrate its efficacy This paper reports a two-phase study in Manhiça district , Mozambique : first we assessed the clinical efficacy and parasitological response of Plasmodium falciparum to chloroquine ( CQ ) , sulphadoxine-pyrimethamine ( SP ) and amodiaquine ( AQ ) , then we tested the safety and efficacy in the treatment of uncomplicated malaria , of three combinations : AQ + SP , artesunate ( AR ) + SP and AQ + AR . Based on the WHO ( 1996 , WHO/MAL/96.1077 ) in vivo protocol , we conducted two open , r and omized , clinical trials . Children aged 6 - 59 months with axillary body temperature > or = 37.5 degrees C and non-complicated malaria were r and omly allocated to treatment groups and followed up for 21 days ( first and second trial ) and 28 days ( first trial ) . The therapeutic efficacy of AQ ( 91.6 % ) was better than that of SP ( 82.7 % ) and CQ ( 47.1 % ) . After 14 days , 69 % of the strains were parasitologically resistant to CQ , 21.4 % to SP and 26 % to AQ . Co-administration of AQ + SP , AR + SP and AQ + AR was safe and had 100 % clinical efficacy at 14-day follow-up . The combination therapies affected rapid fever clearance time and reduced the incidence of gametocytaemia during follow-up |
2,411 | 28,645,491 | In UCC and RCC , there was no conclusive association between programmed cell death receptor lig and 1 ( PD-L1 ) expression in tumor tissue and clinical outcome during pembrolizumab and nivolumab treatment , respectively .
In metastatic UCC and RCC , pembrolizumab and nivolumab have superior efficacy and safety to second-line chemotherapy and everolimus , respectively .
No beneficial effect of ipilimumab was observed in prostate cancer patients .
PD-L1 expression status is currently not suitable as a predictive marker for treatment outcome .
In second-line setting , pembrolizumab and nivolumab are safe and confer survival benefit in advanced urothelial cell and renal cell cancer , respectively | CONTEXT In patients with advanced and metastatic urological cancers , clinical outcome may be improved by immune checkpoint inhibitors ( ICIs ) .
OBJECTIVE To systematic ally review relevant literature on efficacy and safety of ICIs in patients with advanced and metastatic urothelial cell cancer ( UCC ) , renal cell cancer ( RCC ) , and prostate cancer .
PATIENT SUMMARY Immune checkpoint inhibitors are able to reactivate the immune system against tumor cells . | BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 . Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer . Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) BACKGROUND Enzalutamide ( formerly called MDV3100 ) targets multiple steps in the and rogen-receptor-signaling pathway , the major driver of prostate-cancer growth . We aim ed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy . METHODS In our phase 3 , double-blind , placebo-controlled trial , we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity . We r and omly assigned them , in a 2:1 ratio , to receive oral enzalutamide at a dose of 160 mg per day ( 800 patients ) or placebo ( 399 patients ) . The primary end point was overall survival . RESULTS The study was stopped after a planned interim analysis at the time of 520 deaths . The median overall survival was 18.4 months ( 95 % confidence interval [ CI ] , 17.3 to not yet reached ) in the enzalutamide group versus 13.6 months ( 95 % CI , 11.3 to 15.8 ) in the placebo group ( hazard ratio for death in the enzalutamide group , 0.63 ; 95 % CI , 0.53 to 0.75 ; P<0.001 ) . The superiority of enzalutamide over placebo was shown with respect to all secondary end points : the proportion of patients with a reduction in the prostate-specific antigen ( PSA ) level by 50 % or more ( 54 % vs. 2 % , P<0.001 ) , the soft-tissue response rate ( 29 % vs. 4 % , P<0.001 ) , the quality -of-life response rate ( 43 % vs. 18 % , P<0.001 ) , the time to PSA progression ( 8.3 vs. 3.0 months ; hazard ratio , 0.25 ; P<0.001 ) , radiographic progression-free survival ( 8.3 vs. 2.9 months ; hazard ratio , 0.40 ; P<0.001 ) , and the time to the first skeletal-related event ( 16.7 vs. 13.3 months ; hazard ratio , 0.69 ; P<0.001 ) . Rates of fatigue , diarrhea , and hot flashes were higher in the enzalutamide group . Seizures were reported in five patients ( 0.6 % ) receiving enzalutamide . CONCLUSIONS Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy . ( Funded by Medivation and Astellas Pharma Global Development ; AFFIRM Clinical Trials.gov number , NCT00974311 . ) BACKGROUND Cabozantinib is an oral inhibitor of tyrosine kinases including MET , VEGFR , and AXL . The r and omised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment . Here , we report the final overall survival results from this study based on an unplanned second interim analysis . METHODS In this open-label , r and omised phase 3 trial , we r and omly assigned ( 1:1 ) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma , measurable disease , and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day . R and omisation was done with an interactive voice and web response system . Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors . The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 r and omly assigned patients and has been previously reported . Secondary endpoints were overall survival and objective response in all r and omly assigned patients assessed by intention-to-treat . Safety was assessed per protocol in all patients who received at least one dose of study drug . The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation . This trial is registered with Clinical Trials.gov , number NCT01865747 . FINDINGS Between Aug 8 , 2013 , and Nov 24 , 2014 , 658 patients were r and omly assigned to receive cabozantinib ( n=330 ) or everolimus ( n=328 ) . The median duration of follow-up for overall survival and safety was 18·7 months ( IQR 16·1 - 21·1 ) in the cabozantinib group and 18·8 months ( 16·0 - 21·2 ) in the everolimus group . Median overall survival was 21·4 months ( 95 % CI 18·7-not estimable ) with cabozantinib and 16·5 months ( 14·7 - 18·8 ) with everolimus ( hazard ratio [ HR ] 0·66 [ 95 % CI 0·53 - 0·83 ] ; p=0·00026 ) . Cabozantinib treatment also result ed in improved progression-free survival ( HR 0·51 [ 95 % CI 0·41 - 0·62 ] ; p<0·0001 ) and objective response ( 17 % [ 13 - 22 ] with cabozantinib vs 3 % [ 2 - 6 ] with everolimus ; p<0·0001 ) per independent radiology review among all r and omised patients . The most common grade 3 or 4 adverse events were hypertension ( 49 [ 15 % ] in the cabozantinib group vs 12 [ 4 % ] in the everolimus group ) , diarrhoea ( 43 [ 13 % ] vs 7 [ 2 % ] ) , fatigue ( 36 [ 11 % ] vs 24 [ 7 % ] ) , palmar-plantar erythrodysaesthesia syndrome ( 27 [ 8 % ] vs 3 [ 1 % ] ) , anaemia ( 19 [ 6 % ] vs 53 [ 17 % ] ) , hyperglycaemia ( 3 [ 1 % ] vs 16 [ 5 % ] ) , and hypomagnesaemia ( 16 [ 5 % ] vs none ) . Serious adverse events grade 3 or worse occurred in 130 ( 39 % ) patients in the cabozantinib group and in 129 ( 40 % ) in the everolimus group . One treatment-related death occurred in the cabozantinib group ( death ; not otherwise specified ) and two occurred in the everolimus group ( one aspergillus infection and one pneumonia aspiration ) . INTERPRETATION Treatment with cabozantinib increased overall survival , delayed disease progression , and improved the objective response compared with everolimus . Based on these results , cabozantinib should be considered as a new st and ard-of-care treatment option for previously treated patients with advanced renal cell carcinoma . Patients should be monitored for adverse events that might require dose modifications . FUNDING Exelixis BACKGROUND In the phase 3 CheckMate 025 study , previously treated patients with advanced renal cell carcinoma who were r and omly assigned to nivolumab had an overall survival benefit compared with those assigned to everolimus . We aim ed to compare health-related quality of life ( HRQoL ) between treatment groups in this trial . METHODS CheckMate 025 was an open-label study done at 146 oncology centres in 24 countries . Patients were r and omly assigned to treatment between Oct 22 , 2012 , and March 11 , 2014 . Patients with advanced renal cell carcinoma were r and omly assigned ( 1:1 , block size of four ) to receive nivolumab every 2 weeks or everolimus once per day . The study was stopped early at the planned interim analysis in July , 2015 , because the study met its primary endpoint . A protocol amendment permitted patients in the everolimus group to cross over to nivolumab treatment . All patients not on active study therapy are being followed up for survival . At the interim analysis , HRQoL was assessed with the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease Related Symptoms ( FKSI-DRS ) and European Quality of Life (EuroQol)-5 Dimensions ( EQ-5D ) question naires . Prespecified endpoints were to assess , in each treatment group , disease-related symptom progression rate based on the FKSI-DRS and changes in reported global health outcomes based on the EQ-5D . Other endpoints were post hoc . We calculated the proportion of FKSI-DRS question naires completed using the number of patients with non-missing data at baseline and at least one post-baseline visit . We defined FKSI-DRS completion as completion of five or more of the nine items in the question naire ; otherwise data were treated as missing . FKSI-DRS symptom index score was prorated for missing items . We made no adjustments for missing EQ-5D data . We used descriptive statistics and multivariate analyses , including mixed-effects model repeated- measures , for between group comparisons . Analyses were powered according to the original study protocol , and we analysed FKSI-DRS and EQ-5D data for all patients who underwent r and omisation and had a baseline assessment and at least one post-baseline assessment . CheckMate 025 is registered with Clinical Trials.gov , number NCT01668784 . FINDINGS HRQoL data were collected at baseline for 362 ( 88 % ) of 410 patients in the nivolumab group and 344 ( 84 % ) of 411 patients in the everolimus group . The mean difference in FKSI-DRS scores between the nivolumab and everolimus groups was 1·6 ( 95 % CI 1·4 - 1·9 ; p<0·0001 ) with descriptive statistics and 1·7 ( 1·2 - 2·1 ; p<0·0001 ) with mixed-effects model repeated- measures analysis . In terms of FKSI-DRS score , more patients had a clinical ly meaningful ( ie , an increase of at least 2 points from baseline ) HRQoL improvement with nivolumab ( 200 [ 55 % ] of 361 patients ) versus everolimus ( 126 [ 37 % ] of 343 patients ; p<0·0001 ) . Median time to HRQoL improvement was shorter in patients given nivolumab ( 4·7 months , 95 % CI 3·7 - 7·5 ) than in patients given everolimus ( median not reached , NE-NE ) . INTERPRETATION Nivolumab was associated with HRQoL improvement compared with everolimus in previously treated patients with advanced renal cell carcinoma . FUNDING Bristol-Myers Squibb While programmed cell death 1 ( PD-1 ) inhibitors have shown clear anti-tumor efficacy in several solid tumors , prior results in men with metastatic castration resistant prostate cancer ( mCRPC ) showed no evidence of activity . Here we report unexpected antitumor activity seen in mCRPC patients treated with the anti-PD-1 antibody pembrolizumab . Patients with evidence of progression on enzalutamide were treated with pembrolizumab 200 mg IV every 3 weeks for 4 doses ; pembrolizumab was added to st and ard dose enzalutamide . Three of the first ten patients enrolled in this ongoing phase II trial experienced rapid prostate specific antigen ( PSA ) reductions to ≤ 0.2 ng/ml . Two of these three patients had measurable disease upon study entry ; both achieved a partial response . There were three patients with significant immune-related adverse events . One had grade 2 myositis , one had grade 3 hypothyroidism , and one had grade 2 hypothyroidism . None of these patients had a response . Two of the three responders had a baseline tumor biopsy . Immunohistochemistry from those biopsies showed the presence of CD3 + , CD8 + , and CD163 + leukocyte infiltrates and PD-L1 expression . Genetic analysis of the two responders revealed markers of microsatellite instability in one . The surprising and robust responses seen in this study should lead to re-examination of PD-1 inhibition in prostate cancer Purpose : While immune checkpoint inhibitors are disrupting the management of patients with cancer , anecdotal occurrences of rapid progression ( i.e. , hyperprogressive disease or HPD ) under these agents have been described , suggesting potentially deleterious effects of these drugs . The prevalence , the natural history , and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown . Experimental Design : Medical records from all patients ( N = 218 ) prospect ively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed . The tumor growth rate ( TGR ) prior ( “ REFERENCE ” ; REF ) and upon ( “ EXPERIMENTAL ” ; EXP ) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth . Associations between TGR , clinicopathologic characteristics , and overall survival ( OS ) were computed . Results : HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods . Of 131 evaluable patients , 12 patients ( 9 % ) were considered as having HPD . HPD was not associated with higher tumor burden at baseline , nor with any specific tumor type . At progression , patients with HPD had a lower rate of new lesions than patients with disease progression without HPD ( P < 0.05 ) . HPD is associated with a higher age ( P < 0.05 ) and a worse outcome ( overall survival ) . Interestingly , REF TGR ( before treatment ) was inversely correlated with response to anti-PD-1/PD-L1 ( P < 0.05 ) therapy . Conclusions : A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1 . This observation raises some concerns about treating elderly patients ( > 65 years old ) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon . Clin Cancer Res ; 23(8 ) ; 1920–8 . © 2016 AACR . See related commentary by Sharon , p. BACKGROUND Sipuleucel-T , an autologous active cellular immunotherapy , has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer . METHODS In this double-blind , placebo-controlled , multicenter phase 3 trial , we r and omly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T ( 341 patients ) or placebo ( 171 patients ) administered intravenously every 2 weeks , for a total of three infusions . The primary end point was overall survival , analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen ( PSA ) and lactate dehydrogenase . RESULTS In the sipuleucel-T group , there was a relative reduction of 22 % in the risk of death as compared with the placebo group ( hazard ratio , 0.78 ; 95 % confidence interval [ CI ] , 0.61 to 0.98 ; P=0.03 ) . This reduction represented a 4.1-month improvement in median survival ( 25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group ) . The 36-month survival probability was 31.7 % in the sipuleucel-T group versus 23.0 % in the placebo group . The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test ( hazard ratio , 0.77 ; 95 % CI , 0.61 to 0.97 ; P=0.02 ) and after adjustment for use of docetaxel after the study therapy ( hazard ratio , 0.78 ; 95 % CI , 0.62 to 0.98 ; P=0.03 ) . The time to objective disease progression was similar in the two study groups . Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills , fever , and headache . CONCLUSIONS The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer . No effect on the time to disease progression was observed . ( Funded by Dendreon ; Clinical Trials.gov number , NCT00065442 . PURPOSE To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma ( TCC ) of the urothelium treated with gemcitabine/cisplatin ( GC ) or methotrexate/vinblastine/doxorubicin/cisplatin ( MVAC ) . PATIENTS AND METHODS Efficacy data from a large r and omized phase III study of GC versus MVAC were up date d. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival . RESULTS A total of 405 patients were r and omly assigned : 203 to the GC arm and 202 to the MVAC arm . At the time of analysis , 347 patients had died ( GC arm , 176 patients ; MVAC arm , 171 patients ) . Overall survival was similar in both arms ( hazard ratio [ HR ] , 1.09 ; 95 % CI , 0.88 to 1.34 ; P = .66 ) with a median survival of 14.0 months for GC and 15.2 months for MVAC . The 5-year overall survival rates were 13.0 % and 15.3 % , respectively ( P = .53 ) . The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC , with an HR of 1.09 . The 5-year progression-free survival rates were 9.8 % and 11.3 % , respectively ( P = .63 ) . Significant prognostic factors favoring overall survival included performance score ( > 70 ) , TNM staging ( M0 v M1 ) , low/normal alkaline phosphatase level , number of disease sites ( < or= three ) , and the absence of visceral metastases . By adjusting for these prognostic factors , the HR was 0.99 for overall survival and 1.01 for progression-free survival . The 5-year overall survival rates for patients with and without visceral metastases were 6.8 % and 20.9 % , respectively . CONCLUSION Long-term overall and progression-free survival after treatment with GC or MVAC are similar . These results strengthen the role of GC as a st and ard of care in patients with locally advanced or metastatic TCC This paper is an overview of the new response evaluation criteria in solid tumours : revised RECIST guideline ( version 1 . 1 ) , with a focus on up date d contents PURPOSE This is the first r and omized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ( " unfit " ) for cisplatin chemotherapy . PATIENTS AND METHODS The primary objective of the phase III part of this study was to compare the overall survival ( OS ) of chemotherapy-naive patients with measurable disease and an impaired renal function ( glomerular filtration rate < 60 but > 30 mL/min ) and /or performance score of 2 who were r and omly assigned to receive either gemcitabine/carboplatin ( GC ) or methotrexate/carboplatin/vinblastine ( M-CAVI ) . To detect an increase of 50 % in median survival with GC compared with M-CAVI ( 13.5 v 9 months ) based on a two-sided log-rank test at error rates α = .05 and β = .20 , 225 patients were required . Secondary end points were overall response rate ( ORR ) , progression-free survival ( PFS ) , toxicity , and quality of life . RESULTS In all , 238 patients were r and omly assigned by 29 institutions over a period of 7 years . The median follow-up was 4.5 years . Best ORRs were 41.2 % ( 36.1 % confirmed response ) for patients receiving GC versus 30.3 % ( 21.0 % confirmed response ) for patients receiving M-CAVI ( P = .08 ) . Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm ( P = .64 ) . There was no difference in PFS ( P = .78 ) between the two arms . Severe acute toxicity ( death , grade 4 thrombocytopenia with bleeding , grade 3 or 4 renal toxicity , neutropenic fever , or mucositis ) was observed in 9.3 % of patients receiving GC and 21.2 % of patients receiving M-CAVI . CONCLUSION There were no significant differences in efficacy between the two treatment groups . The incidence of severe acute toxicities was higher for those receiving M-CAVI BACKGROUND Programmed death 1 ( PD-1 ) protein , a T-cell coinhibitory receptor , and one of its lig and s , PD-L1 , play a pivotal role in the ability of tumor cells to evade the host 's immune system . Blockade of interactions between PD-1 and PD-L1 enhances immune function in vitro and mediates antitumor activity in pre clinical models . METHODS In this multicenter phase 1 trial , we administered intravenous anti-PD-L1 antibody ( at escalating doses ranging from 0.3 to 10 mg per kilogram of body weight ) to patients with selected advanced cancers . Anti-PD-L1 antibody was administered every 14 days in 6-week cycles for up to 16 cycles or until the patient had a complete response or confirmed disease progression . RESULTS As of February 24 , 2012 , a total of 207 patients --75 with non-small-cell lung cancer , 55 with melanoma , 18 with colorectal cancer , 17 with renal-cell cancer , 17 with ovarian cancer , 14 with pancreatic cancer , 7 with gastric cancer , and 4 with breast cancer -- had received anti-PD-L1 antibody . The median duration of therapy was 12 weeks ( range , 2 to 111 ) . Grade 3 or 4 toxic effects that investigators considered to be related to treatment occurred in 9 % of patients . Among patients with a response that could be evaluated , an objective response ( a complete or partial response ) was observed in 9 of 52 patients with melanoma , 2 of 17 with renal-cell cancer , 5 of 49 with non-small-cell lung cancer , and 1 of 17 with ovarian cancer . Responses lasted for 1 year or more in 8 of 16 patients with at least 1 year of follow-up . CONCLUSIONS Antibody-mediated blockade of PD-L1 induced durable tumor regression ( objective response rate of 6 to 17 % ) and prolonged stabilization of disease ( rates of 12 to 41 % at 24 weeks ) in patients with advanced cancers , including non-small-cell lung cancer , melanoma , and renal-cell cancer . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00729664 . ) 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 . |
2,412 | 27,103,604 | The appropriate selection of motion tasks is an integral factor in dynamic stability testing as it evokes different kinematic outcomes in relation to the different stages of ACLR recovery .
Stair negotiation and l and ing tasks are best performed during the early stages of recovery , and l and ing and pivoting are recommended 6 months after ACLR surgery . | PURPOSE To examine the different motion tasks and the protocol s used to objective ly quantify dynamic stability in terms of knee kinematics at different stages of anterior cruciate ligament reconstruction ( ACLR ) recovery . | Background The effectiveness of anterior cruciate ligament reconstruction for restoring normal knee kinematics is largely unknown , particularly during sports movements generating large , rapidly applied forces . Hypothesis Under dynamic in vivo loading , significant differences in 3-dimensional kinematics exist between anterior cruciate ligament-reconstructed knees and the contralateral , uninjured knees . Study Design Prospect i ve , in vivo laboratory study . Methods Kinematics of anterior cruciate ligament-reconstructed and contralateral ( uninjured ) knees were evaluated for 6 subjects during downhill running 4 to 12 months after anterior cruciate ligament reconstruction , using a 250 frame/s stereoradiographic system . Anatomical reference axes were determined from computed tomography scans . Kinematic differences between the uninjured and reconstructed limbs were evaluated with a repeated- measures analysis of variance . Results Anterior tibial translation was similar for the reconstructed and uninjured limbs . However , reconstructed knees were more externally rotated on average by 3.8 ± 2.3 ° across all subjects and time points ( P = .0011 ) . Reconstructed knees were also more adducted , by an average of 2.8 ± 1.6 ° ( P = .0091 ) . Although differences were small , they were consistent in all subjects . Conclusions Anterior cruciate ligament reconstruction failed to restore normal rotational knee kinematics during dynamic loading . Clinical Relevance Although further study is required , these abnormal motions may contribute to long-term joint degeneration associated with anterior cruciate ligament injury/reconstruction Anterior cruciate ligament ( ACL ) injury can result in failure to return to pre-injury activity levels and future osteoarthritis predisposition . Single leg hop is used in late rehabilitation to evaluate recovery and inform treatment but biomechanical underst and ing of this activity is insufficient . This study investigated single leg hop for distance aim ing to evaluate if ACL patients had recovered : ( 1 ) l and ing strategies and ( 2 ) medio-lateral knee control . We hypothesized that patients with reconstructive surgery ( ACLR ) would have more similar l and ing strategies and knee control to healthy controls than patients treated conservatively ( ACLD ) . 16 ACLD and 23 ACLR subjects were compared to 20 healthy controls ( CONT ) . Kinematic and ground reaction force data were collected while subjects hopped their maximum distance . The main output parameters were hop distance , peak knee flexor angles and extensor moments and Fluency ( a measure introduced to represent medio-lateral knee control ) . Statistical differences between ACL and control groups were analyzed using a general linear model univariate analysis , with COM velocity prior to l and ing as covariate . Hop distance was the smallest for ACLD and largest for CONT ( p<0.001 ; ACLD 57.1±14.1 ; ACLR 75.1±17.8 ; CONT 77.7±14.07 % height ) . ACLR used a similar kinematic strategy to CONT , but had a reduced peak knee extensor moment ( p<0.001 ; ACLD 0.32±0.14 ; ACLR 0.31±0.16 ; CONT 0.42±0.13 BW.height ) . Fluency was reduced in both ACLD and ACLR ( p=0.006 ; ACLD 0.13±0.34 ; ACLR 0.14±0.34 ; CONT 0.17±0.41 s ) . Clinical practice uses hopping distance to evaluate ACL patients ' recovery . This study demonstrated that aspects such as movement strategies and knee control need to be evaluated Functional dynamic tests are increasingly used in rehabilitation after injuries of the lower extremities . In these tests quantitative measures ( e.g. time , height , distance ) are mainly used as parameters , whereas the quality of the neuromuscular performance is poorly evaluated . In the present study the neuromuscular performance of leg muscles in different motor tasks was investigated 10 - 16 months after ACL-reconstruction . In 39 subjects with arthroscopically assisted ACL-reconstruction and 20 controls , isometric knee extensor strength , thigh circumference , knee stability , subjective knee function and the neuromuscular performance ( by kinematic data and EMG ) during three dynamic tests ( stair descending , one-legged drop jump , one-legged cyclic hops ) were measured . During the strength measurements a superimposed twitch technique was used for the detection of neuromuscular inhibition . The results demonstrate a significantly reduced Lysholm-Score and a distinct strength deficit , but no neuromuscular inhibition and no differences in knee stability in the operated leg . Besides reduced motor abilities of the injured leg , significant differences of the neuromuscular performance could be detected . It was evident that different test conditions revealed different persisting changes of the neuromuscular performance , which could not be detected by kinematic parameters alone Purpose The effect of double-bundle ACL reconstruction on knee kinematics has recently been studied by several authors under controlled laboratory conditions however little evidence has been derived from dynamic in vivo evaluations . This study hypothesized that tibial rotation during pivoting motor tasks would be better restored after double-bundle ACL reconstructions when compared with single-bundle procedures . Methods Twenty patients with a chronic ACL rupture were r and omly assigned to receive a single- or double-bundle ACL reconstruction . Both knees were evaluated pre-operatively by kinematic 3-D gait analysis while performing low- and high-dem and motor tasks , including pivoting . At 6 months post-operatively , measurements were repeated in 16 patients . Ten healthy , sex- and age-matched subjects with no history of lower limb pathology formed the control group . The tibial rotational excursion was set as the dependent variable . Results The results indicate that at 6 months after surgery both “ anatomic ” single- and double-bundle ACL reconstruction are able to restore tibial rotational excursion when compared with the contralateral knees and with control knees from uninjured subjects . Chronic ACL-deficient patients show an increase in tibial rotation in both knees during high-dem and pivoting tasks . Conclusions Both “ anatomic ” single- and double-bundle ACL reconstruction adequately restore tibial rotational excursion in a human , “ in vivo ” kinematic model . As knee stability measurements by in vivo kinematic 3-D analysis more accurately represent actual knee loading during activities , the results of this study might better correlate with functional outcome after ACL reconstructions compared with static knee stability tests or ex vivo laboratory experiments . In such , the results of this dynamic study do not support the theoretical advantage of a double-bundle ACL reconstruction over an “ anatomic ” single-bundle ACL reconstruction . Level of evidence II Background : The restoration of knee rotational stability after anatomic double-bundle anterior cruciate ligament ( ACL ) reconstruction has been demonstrated in the cadaveric model and with passive stress tests on humans but not yet with dynamic functional biomechanical tests performed by human participants . Purpose : To prospect ively investigate the range of tibial rotation of ACL-deficient and ACL-reconstructed knees during a pivoting task . The authors hypothesized that there would be a significant increase in tibial internal rotation in the ACL-deficient knee compared with the contralateral knee and that the increased rotation would return to normal after anatomic double-bundle ACL reconstruction . Study Design : Case series ; Level of evidence , 4 . Methods : Ten men with unilateral ACL injury performed a high-dem and jump-l and ing and pivoting task before and after ACL reconstruction with mean follow-up of 11 months . The range of tibial rotation of the injured , reconstructed , and intact knees during the pivoting movement was measured by an optical motion analysis system . Paired t tests were performed to investigate any significant difference between the 2 limbs preoperatively and postoperatively and within the injured limb before and after the surgical treatment . Statistical significance was set at P < .05 . Results : The range of tibial rotation was higher in the ACL-deficient knee ( 12.6 ° ± 4.5 ° ) than in the intact knee ( 7.9 ° ± 3.1 ° ) preoperatively ( P < .05 ) . The increased rotation was reduced in the reconstructed knee ( 8.9 ° ± 3.0 ° ) after ACL reconstruction versus the intact knee postoperatively ( 8.2 ° ± 2.6 ° ) ( P < .05 ) . There was no significant difference in the tibial rotation between the intact knee and the reconstructed knee postoperatively ( P > .05 ) . Conclusion : As assessed with a dynamic functional pivoting movement , the anatomic double-bundle ACL reconstruction successfully restores knee rotational stability from an impaired level The relationships between extrinsic forces acting at the knee and knee kinematics were examined with the purpose of identifying specific phases of the walking cycle that could cause abnormal kinematics in the anterior cruciate ligament ( ACL ) deficient knee . Intersegmental forces and moments in directions that would produce anterior-posterior ( AP ) translation , internal-external ( IE ) rotation and flexion-extension ( FE ) at the knee were compared with the respective translation and rotations of the tibia relative to the femur during four selected phases ( heel strike , weight acceptance , terminal extension and swing ) of the walking cycle . The kinematic changes associated with loss of the ACL occurred primarily during the terminal portion of swing phase of the walking cycle where , for the ACL deficient knee , the tibia had reduced external rotation and anterior translation as the knee extended prior to heel strike . The kinematic changes during swing phase were associated with a rotational offset relative to the contralateral knee in the average position of the tibia towards internal rotation . The offset was maintained through the entire gait cycle . The abnormal offsets in the rotational position were correlated with the magnitude of the flexion moment ( balanced by a net quadriceps moment ) during weight acceptance . These results suggest that adaptations to the patterns of muscle firing during walking can compensate for kinematic changes associated with the loss of the ACL . The altered rotational position would cause changes in tibiofemoral contact during walking that could cause the type of degenerative changes reported in the meniscus and the articular cartilage following ACL injury Purpose The purpose of this study was to test whether rotational knee kinematics during dynamic pivoting activities are predictive of subjective functional outcome ( IKDC , Lysholm ) , objective laxity scores ( KT max ) , and activity levels ( Tegner ) in patients after anterior cruciate ligament reconstruction ( ACLR ) . Methods Thirty-one patients with single-bundle ACLR were evaluated prospect ively with 3D-motion analysis during ( 1 ) descending a stairway and pivoting and ( 2 ) l and ing from a jump and pivoting . The side-to-side difference of tibial rotation range of motion ( SSDTR ) between the ACLR and the contralateral intact knee was calculated for the pivoting phase of each task . Linear regression models were applied with SSDTR , for each task predictors of the subjective IKDC score , Lysholm score , anterior tibial translation , and Tegner activity level . Results SSDTR for descending and l and ing were predictive of the IKDC subjective score ( R2 = 0.46 , p < 0.001 and R2 = 0.40 , p < 0.001 , respectively ) with “ medium ” effect sizes and of the Lysholm score ( R2 = 0.13 , p < 0.05 and R2 = 0.09 , n.s . ) with “ small ” to “ none ” effect sizes . SSDTR was not predictive of anterior translation or Tegner activity level ( n.s . ) . Conclusions Restoring rotational kinematics during dynamic pivoting activities after ACLR is predictive of functional outcome . The ability of the athlete after ACLR to control tibial rotation during pivoting activities may be predictive of functional outcome .Level of evidence Case series study . Level IV UNLABELLED The patellar and semitendinosus tendon autograft are the two most common techniques that orthopedic surgeons use to reconstruct the anterior cruciate ligament ( ACL ) . It has not been established , however , whether either of these techniques provides a greater functional advantage to the patient . PURPOSE To identify patients ' functional capabilities after reconstruction of the ACL with a patellar or semitendinosus tendon autograft . METHODS Forty male soccer players volunteered for the study and were assigned to three homogeneous groups : individuals who had patellar tendon reconstruction ( N = 15 ) , individuals who had semitendinosus tendon reconstruction ( N = 15 ) , and a control group ( N = 10 ) . All patients had undergone surgery 2 yr before this study and received the same rehabilitation training . The testing procedures included measurement of thigh circumference , maximal isometric strength of quadriceps and hamstrings , two- and one-legged jump , squat and gait analysis . Kinetic , kinematic , and electromyographic data were collected . RESULTS The patellar tendon group exhibited lower ( P < 0.05 ) coactivation of the agonist and antagonist muscles around the knee joint during the squat movement and lower stabilization- and l and ing degrees during the jumps . Furthermore , the patellar tendon group had a shorter stance phase and reached the first vertical maximum later with the impaired leg while walking ( 720.2 + /- 15.6 ms vs 740.3 + /- 14.3 ms , and 24.3 + /- 0.64 % vs 22.9 + /- 0.74 % of stance phase ) , which was not observed in the semitendinosus tendon and control groups . CONCLUSION Functional performance is compromised in patients who undergo a patellar tendon graft compared with a semitendinosus graft , possibly due to an altered activation of the quadriceps and hamstring muscles OBJECTIVE Knee surgery may alter the neuromuscular response to unexpected perturbations during functional , dynamic tasks . Long latency reflexes ( LLR ) follow a transcortical pathway and appear to be modifiable by task dem and s , potentially giving them a role in neuromuscular performance . We examined LLRs of the quadriceps and hamstrings in response to unexpected perturbations in individuals with a repaired anterior cruciate ligament ( ACLR ) during a weight-bearing task . We also investigated the anticipatory and volitional muscle activity that preceded and followed the LLR to quantify possible reflex adaptations associated with surgical repair . METHODS Twelve females with ACLR and 12 healthy female controls performed a single leg squat maneuver , tracking a sinusoidal target . R and om perturbations at the start of the flexion phase yielded tracking errors ( " overshoot errors " ) and triggered compensatory reflex activity . RESULTS ACLR subjects demonstrated greater overshoot error and knee velocity during unexpected perturbations , increased LLR responses , and reduced absolute anticipatory , short-latency reflex , and voluntary quadriceps activity . CONCLUSIONS ACLR subjects showed impaired response to perturbation and a distinct EMG profile during a dynamic single leg weight-bearing task . Future research will determine the cause of neural adaptations in those with ACLR . SIGNIFICANCE Neuromuscular adaptations may be a viable target for post-ACL injury rehabilitation interventions We investigated whether preoperative perturbation training would help anterior cruciate ligament ( ACL ) deficient individuals who complain of knee instability ( " non-copers " ) regain quadriceps strength and walk normally after ACL reconstruction . Nineteen non-copers with acute ACL injury were r and omly assigned into a perturbation group ( PERT ) or a strengthening group ( STR ) . The PERT group received specialized neuromuscular training and progressive quadriceps strength training , whereas the STR group received progressive quadriceps strength training only . We compared quadriceps strength indexes and knee excursions during the mid-stance phase of gait preoperatively to data collected 6 months after ACL reconstruction . Analyses of Variance with repeated measures ( time/limb ) were conducted to compare quadriceps strength index values over time ( time x group ) and differences in knee excursions in limbs between groups over time ( limb x time x group ) . If significance was found , post hoc analyses were performed using paired and independent t-tests . Quadriceps strength indexes before intervention ( Pert : 87.2 % ; Str : 75.8 % ) improved 6 months after ACL reconstruction in both groups ( Pert : 97.1 % ; Str : 94.4 % ) . Non-copers who received perturbation training preoperatively had no differences in knee excursions between their limbs 6 months after ACL reconstruction ( p = 0.14 ) , whereas those who received just strength training continued to have smaller knee excursions during the mid-stance phase of gait ( p = 0.007 ) . Non-copers strength and knee excursions were more symmetrical 6 months postoperatively in the group that received perturbation training and progressive quadriceps strength training than the group who received strength training alone OBJECTIVE To determine biomechanical differences during single limb l and ing performed with and without shoe wear in anterior cruciate ligament reconstruction subjects . DESIGN Barefoot and shod conditions were compared for both operated and contralateral limbs . BACKGROUND Biomechanical analysis has been used to better underst and the functional changes associated with anterior cruciate ligament reconstruction . However , no studies have investigated whether routine testing of patients should be performed barefoot or shod . METHODS A three-dimensional motion analysis and force plate system were used to obtain kinematic and kinetic data from eight anterior cruciate ligament reconstruction subjects during single-limb l and ings from a 15 cm vertical height . RESULTS Peak knee flexion angles and moments were significantly reduced during barefoot testing in all eight subjects for the operated limb only ( p < 0.01 ) . The differences were however small ; mean angular difference 3 degrees and mean moment difference 0.2 Nm/kg . Knee flexion angles at initial contact and peak vertical ground-reaction forces were not affected by shoe wear . CONCLUSIONS These results show that shoe wear does affect some biomechanical variables on l and ing but not so as to affect comparisons between operated and contralateral limbs . RELEVANCE Given the comparable results between conditions , biomechanical testing following anterior cruciate ligament reconstruction can be performed either barefoot or shod . Testing subjects barefoot has the advantage of easier marker placement , and alleviates the need for shoe wear st and ardization Background Athletes who return to sport participation after anterior cruciate ligament reconstruction ( ACLR ) have a higher risk of a second anterior cruciate ligament injury ( either reinjury or contralateral injury ) compared with non — anterior cruciate ligament— injured athletes . Hypotheses Prospect i ve measures of neuromuscular control and postural stability after ACLR will predict relative increased risk for a second anterior cruciate ligament injury . Study Design Cohort study ( prognosis ) ; Level of evidence , 2 . Methods Fifty-six athletes underwent a prospect i ve biomechanical screening after ACLR using 3-dimensional motion analysis during a drop vertical jump maneuver and postural stability assessment before return to pivoting and cutting sports . After the initial test session , each subject was followed for 12 months for occurrence of a second anterior cruciate ligament injury . Lower extremity joint kinematics , kinetics , and postural stability were assessed and analyzed . Analysis of variance and logistic regression were used to identify predictors of a second anterior cruciate ligament injury . Results Thirteen athletes suffered a subsequent second anterior cruciate ligament injury . Transverse plane hip kinetics and frontal plane knee kinematics during l and ing , sagittal plane knee moments at l and ing , and deficits in postural stability predicted a second injury in this population ( C statistic = 0.94 ) with excellent sensitivity ( 0.92 ) and specificity ( 0.88 ) . Specific predictive parameters included an increase in total frontal plane ( valgus ) movement , greater asymmetry in internal knee extensor moment at initial contact , and a deficit in single-leg postural stability of the involved limb , as measured by the Biodex stability system . Hip rotation moment independently predicted second anterior cruciate ligament injury ( C = 0.81 ) with high sensitivity ( 0.77 ) and specificity ( 0.81 ) . Conclusion Altered neuromuscular control of the hip and knee during a dynamic l and ing task and postural stability deficits after ACLR are predictors of a second anterior cruciate ligament injury after an athlete is released to return to sport Background : The posterior cruciate ligament ( PCL ) index quantifies the curvature of the PCL seen on magnetic resonance imaging ( MRI ) that is caused by a change in tibiofemoral alignment in the anterior cruciate ligament (ACL)–deficient knee . It has been proposed that the PCL index may be useful in assessing the success of ACL reconstruction ( ACLR ) . Hypothesis/ Purpose : The purpose of this study was to test if the PCL index is predictive of in vivo rotational kinematics and joint laxity measures in knees of patients after single-bundle ACLR . The hypothesis was that the PCL index is predictive of rotational knee kinematics and objective laxity scores . Study Design : Controlled laboratory study . Methods : At a mean of 18.1 months postoperatively , the PCL index was defined on MRI in 16 patients prospect ively followed up after anatomic single-bundle ACLR and in 16 matched controls . The patients were evaluated with 3-dimensional motion analysis during ( 1 ) descending and pivoting as well as ( 2 ) l and ing and pivoting tasks . The side-to-side difference in tibial rotation range of motion between the reconstructed knee and the contralateral intact knee was calculated . The side-to-side difference in anterior tibial translation was measured with a KT-1000 arthrometer . Linear regression models were used with the PCL index as a predictor of the side-to-side difference in tibial rotation for each task and the side-to-side difference in anterior tibial translation . Results : The PCL index of the reconstructed knees was significantly lower compared with that of the control knees ( P < .001 ) . The index was predictive of the side-to-side difference in tibial rotation during both tasks ( R2 = 0.472 and 0.477 , P = .003 ) , with a lower index being indicative of increased rotational laxity . It was not predictive of anterior tibial translation ( at 134 N : R2 = 0.13 , P = .17 ; at maximum force : R2 = 0.009 , P = .726 ) . Conclusion : The PCL index after anatomic single-bundle ACLR using a bone – patellar tendon – bone graft is predictive of rotational kinematics during in vivo dynamic pivoting activities . The results show that the PCL index is correlated with the postoperative ability to control rotational kinematics of the knee joint . Clinical Relevance : This study provides evidence regarding the interplay between restoration of the native ACL ’s anatomy and the PCL ’s appearance and suggests that the effective restoration of tibiofemoral alignment after ACLR that is reflected in the PCL index translates into better functional outcomes as measured by tibial rotation during pivoting activities BACKGROUND While traditional surgical repair of the anterior cruciate ligament is able to restore anterior-posterior knee stability , laxity in the transverse plane remains . Double-bundle reconstruction has demonstrated greater rotational restraint than the single-bundle technique under passive loading conditions ; however , no comparison has been made under physiological weight-bearing conditions . The purpose of this study was to determine differences in rotational knee kinematics during a dynamic task in patients who had received either a single- or double-bundle reconstruction . METHODS Twenty-two patients exhibiting isolated anterior cruciate ligament rupture were r and omly allocated either a single or double-bundle reconstruction . Three-dimensional knee kinematics were measured during a dynamic cutting activity prior to and following surgery . Functional range of rotation was compared between groups pre- and post-operatively and kinematics were assessed against uninjured control subjects . FINDINGS No difference in overall range of rotation was found under physiological loading conditions . However , a significant interaction of the midpoint of the range of movement was observed ; a greater external rotational shift in the single-bundle group followed reconstruction , while the kinematics of the double-bundle patient group shifted closer to those of the control group . INTERPRETATION The double-bundle reconstruction demonstrated superior outcome in rotational kinematics to the single-bundle technique |
2,413 | 10,068,430 | Because research ers believe that 70 % of disease is preventable ( 6 , 7 ) , effective implementation of preventive care guidelines can lead to even greater improvements in patient care than the introduction of some new technologies .
Additional benefits , including reductions in mortality , morbidity , and suffering , could accrue from increasing the rates of provision of other recommended preventive care procedures ( 1 , 7 ) . | During the past decade , an increasing number of preventive care and other guidelines have been published in articles and textbooks and on the Internet ( 1 - 4 ) .
However , with the proliferation of this new and potentially important information , practitioners may become increasingly bewildered in their attempts to sort through the vast number of guidelines and decide which are most appropriate for their patients .
The accelerated pace of development has led to an abundance of guidelines created by different organizations with different methods and different objectives ( 1 - 4 ) .
The quality and rigor of the guidelines vary widely .
To address the propagation of preventive care and other guidelines , compendiums have been assembled to organize and integrate existing guideline information into a single source .
I describe 1 ) the rationale for continued attention to preventive care guidelines , 2 ) recent efforts to organize existing guidelines , 3 ) currently available compendiums of preventive care guidelines , 4 ) how the compendiums may be used in day-to-day practice , and 5 ) how this information may be used to improve the provision of preventive care .
Rationale for Continued Focus on Preventive Care Guidelines Despite the plethora of preventive care guidelines , significant gaps remain between appropriate levels of preventive care and levels of preventive care documented in clinical practice ( 5 , 6 ) .
Moreover , missed opportunities to provide preventive care can cause substantial human consequences ( 5 , 6 ) .
Until these gaps are closed , health care professionals will continue to consider how preventive care guidelines can be more effectively translated into clinical practice .
Recent Efforts To Organize and Integrate Guidelines Guideline development can create new knowledge by systematic ally evaluating and integrating primary research studies with expert interpretation to develop specific recommendations ( 9 , 10 ) .
Because many clinicians can not stay current with all published literature on preventive care , guidelines may integrate and codify existing information into a more digestible format .
Many health care organizations have developed practice guidelines , including preventive care guidelines , leading to a virtual explosion in the amount of guidelines available .
As a result , the challenge of having the most recent information about preventive care guidelines has become daunting ; efforts are under way to organize and integrate existing guidelines and make them more accessible , usable , and comprehensible .
Although practice guidelines organize and integrate available primary research and opinion into codified recommendations , practice guideline compendiums may organize and integrate different sources of practice guidelines .
The Clinical Practice Guidelines Directory ( www.ama-assn.org ) serves as a repository of guidelines on more than 2000 topics from more than 90 organizations .
Clinician 's H and book of Preventive Services The Clinician 's H and book of Preventive Services has recently published a second edition of preventive care guidelines to serve as a comprehensive re source for practitioners and students interested in preventive medicine .
The Agency for Health Care Policy and Research , in partnership with the American Association of Health Plans and the American Medical Association , has invited developers of practice guidelines , including professional societies , to su bmi t guidelines for possible inclusion in the National Guideline Clearinghouse .
The answers may relate to the care of an individual patient ( should I order mammography for this 47-year-old woman without a family history of breast cancer ? )
The following hypothetical situation addresses the use of a preventive care guideline compendium to research a question that is relevant to the care of a population of patients .
You are a primary care physician and belong to an independent practice association ( IPA ) . | OBJECTIVE To assess the impact of diverse continuing medical education ( CME ) interventions on physician performance and health care outcomes . DATA SOURCES Using continuing medical education and related phrases , we performed regular search es of the indexed literature ( MEDLINE , Social Science Index , the National Technical Information Service , and Educational Research Information Clearinghouse ) from 1975 through 1991 . In addition , for these years , we used manual search es , key informants , and requests to authors to locate other indexed articles and the nonindexed literature of adult and continuing professional education . STUDY SELECTION From the result ing data base we selected studies that met the following criteria : r and omized controlled trials ; educational programs , activities , or other interventions ; studies that included 50 % or more physicians ; follow-up assessment s of at least 75 % of study subjects ; and objective assessment s of either physician performance or health care outcomes . DATA EXTRACTION Studies were review ed for data related to physician specialty and setting . Continuing medical education interventions were classified by their mode(s ) of activity as being predisposing , enabling , or facilitating . Using the statistical tests supplied by the original investigators , physician performance outcomes and patient outcomes were classified as positive , negative , or inconclusive . DATA SYNTHESIS We located 777 CME studies , of which 50 met all criteria . Thirty-two of these analyzed physician performance ; seven evaluated patient outcomes ; 11 examined both measures . The majority of the 43 studies of physician performance showed positive results in some important measures of re source utilization , counseling strategies , and preventive medicine . Of the 18 studies of health care outcomes , eight demonstrated positive changes in patients ' health care outcomes . CONCLUSION Broadly defined CME interventions using practice -enabling or reinforcing strategies consistently improve physician performance and , in some instances , health care outcomes Computers are steadily being incorporated in clinical practice . We conducted a nonr and omised , controlled , prospect i ve trial of electronic messages design ed to enhance adherence to clinical practice guidelines . We studied 126 physicians and nurse practitioners who used electronic medical records when caring for 349 patients with HIV infection in a primary care practice . We analysed the response times of clinicians to the situations that triggered alerts and reminders , the number of ambulatory visits , and hospitalisation . The median response times to 303 alerts in the intervention group and 388 alerts in the control group were 11 and 52 days ( p < 0.0001 ) , respectively . The median response time to 432 reminders in the intervention group was 114 days and that for 360 reminders in the control group was over 500 days ( p < 0.0001 ) . There was no effect on visits to the primary care practice . There was , however , a significant increase in the rate of visits outside the primary care practice ( p = 0.02 ) , which is explained by the increased frequency of visits to ophthalmologists . There were no differences in admission rates ( p = 0.47 ) , in admissions for pneumocystosis ( p = 0.09 ) , in visits to the emergency ward ( p = 0.24 ) , or in survival ( p = 0.19 ) . We conclude that the electronic medical record was effective in helping clinicians adhere to practice guidelines 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 A r and omized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section . The guideline recommended clinical actions to increase trial of labor and vaginal birth rates . Charts for all 3552 cases in the study groups were audited . After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group , but rates were 46 % and 85 % higher , respectively , among physicians educated by an opinion leader . Duration of hospital stay was lower in the opinion leader education group than in the other two groups . The overall cesarean section rate was reduced only in the opinion leader education group . There were no adverse clinical outcomes attributable to the interventions . The use of opinion leaders improved the quality of care Currently , considerable enthusiasm exists for practice guideline development . However , little is known about their real effect , and substantial doubt exists about whether guidelines can actually decrease health care costs and improve quality of care [ 1 , 2 ] . Physicians have expressed reservations about practice guidelines , including concerns that they may be misapplied or even abused [ 3 ] , and the specter of cookbook medicine is often raised [ 2 ] . Because few controlled interventional trials using guidelines have been done , little is known about their actual performance in clinical practice and their acceptance by physicians . In addition , some have recommended that practice guidelines be used to certify and license physicians and to make decisions about which medical services to fund [ 1 ] . Thus , it is important to underst and physicians ' responses to guidelines and how to judge their usefulness in clinical practice . We hypothesized that the reasons for the failure of physicians to comply with the recommendations of a length-of-hospitalization practice guideline could be multifactorial . Noncompliance of physicians could be related to physician attitudes toward the guideline leading to rejection , to limitations of the guideline itself or its implementation strategy , to inefficiencies in the hospital or health care delivery system , or to differences in the patient 's clinical status . Although these and other factors might all contribute to apparent noncompliance of physicians , improvement in guideline performance and in physician compliance would be dependent on addressing the true causes rather than on simply assuming that the reason is physician resistance . We retrospectively analyzed the results from a successfully implemented practice guideline that sought to reduce hospital length of stay for patients admitted with chest pain [ 4 ] in order to determine the ways in which that effort might have been improved . The guideline recommended a 2-day length of hospital stay for carefully selected low-risk patients with chest pain . The guideline had previously been vali date d and shown to be relatively safe [ 5 ] . Attending physicians were given risk information concurrently by utilization-management nurses through the placement of letters on the chart and by telephone calls from utilization-management physician advisors . In a controlled interventional trial [ 4 ] , the guideline decreased length of stay and hospital costs and did not have an adverse effect on patient morbidity , mortality , health status , or satisfaction . The statistically significant total reductions in length of stay and total cost reductions of approximately $ 1397 per low-risk patient were achieved by improving physician compliance with the guideline from 50 % during control months to 69 % during intervention months . We determined the reasons why the remaining 31 % of low-risk patients were not discharged at hospital day 2 according to the chest pain guideline recommendations and why patients who were truly at high risk were misclassified as being at low risk . Methods Study Design The study was a retrospective analysis of a prospect i ve , controlled interventional trial [ 4 ] . Institutional Characteristics The study was done at Cedars-Sinai Medical Center , a large university-affiliated community teaching hospital in Los Angeles . Most patients were cared for by private practitioners . Although a coronary care unit director , cardiology faculty , cardiology fellows , medical housestaff , and medical students participated in the clinical care of many of the study patients , private practitioners had the ultimate responsibility for patient care decisions for most study patients , including the decision to discharge a patient from the hospital . Patient Population The prospect i ve , controlled interventional trial was done between 1 September 1991 and 31 August 1992 . Physicians were informed of risk information and guideline recommendations on an alternating month basis . The retrospective analysis done for the current study included patients from all interventional months ( October 1991 , December 1991 , February 1992 , April 1992 , June 1992 , and August 1992 ) . Patients were eligible for enrollment in the study if they were at least 30 years of age , presented with a chief symptom of chest pain , and were admitted to a monitored bed in the cardiac intensive care unit or the cardiac observation unit . Patients were enrolled in the study if they were concurrently classified as being at low risk for in-hospital complications according to our previously described practice guideline [ 4 ] or if they were identified through our hospital information system for retrospective review of all eligible patients admitted during intervention months . The guideline prescribed a 2-day length of hospital stay for patients classified as being at low risk . Noncompliance of physicians with the guideline was defined as a 3-day or greater length of stay . Analysis was by intention to treat . Intervention Before the study , all attending physicians received a letter describing the study and information about the chest pain practice guideline . The guideline [ 4 ] recommended a 2-day length of stay for patients hospitalized with chest pain who had none of the following conditions 24 hours after hospitalization : 1 ) acute myocardial infa rct ion ; 2 ) recurrent chest pain ; 3 ) previous cardiac intervention ; 4 ) planned cardiac intervention ; 5 ) previous complication ; 6 ) ongoing intervention ; or 7 ) unstable comorbid condition . All seven elements describing low-risk status were explicitly defined . Physicians caring for patients classified as low-risk received concurrent , personalized , written , and physician-to-physician feedback over the telephone about the guideline recommendations . Both types of feedback were delivered to physicians using the following structured format : Your patient ( Patient Name ) may be at low-risk for serious in-hospital complications . In fact , approximately 98 % of patients similar to your patient suffered no serious in-hospital complications after 2 days of hospitalization . If your patient continues to have an uncomplicated hospital course without chest pain , please consider whether a 2 day length of stay is appropriate for your patient . If further diagnostic testing is absolutely required prior to discharge , please let me know if we can help facilitate any test for you . Only you as the primary physician can determine the most appropriate length of stay for your patient . Thank you . No incentives were added or disincentives removed to enhance physician compliance with the guidelines . Specifically , no financial incentives were offered for complying with guideline recommendations , nor were any sanctions used against physicians who rejected the guidelines . Inclusion Criteria All patients eligible for enrollment in the study during intervention months who were classified at 24 hours as being at low risk by either concurrent utilization-management review or by retrospective review who were discharged 3 or more days after admission ( our definition of noncompliance of physicians ) were included in the analysis . Sources of Information Decisions about the possible cause or causes of noncompliance of physicians were based on review of the medical records and on the utilization-management physician-to-physician interaction sheets . Analytic Framework Patients were retrospectively assigned by an experienced research nurse to one of the following five general categories of physician noncompliance on the basis of a structured explicit review of medical records and of the utilization-management physician-to-physician interaction sheets ( the combination was considered the criterion st and ard ) . 1 . Noncompliance of Physicians Based on Guideline Implementation Problems a ) False-positive result : those patients misclassified as being at low risk during concurrent utilization-management review who after structured explicit review ( the criterion st and ard ) were considered high risk and , therefore , should not have been discharged according to the guideline 's recommendation . b ) False-negative result : 1 ) those patients falsely classified as being at high risk and , therefore , the physician was not contacted ; or 2 ) those patients not identified by utilization-management nurses as being at low risk but , instead , were identified retrospectively using the hospital information system and from retrospective structured explicit review ( that is , patients not enrolled in the study despite meeting eligibility requirements ) . 2 . Noncompliance of Physicians Based on Health Care System Inefficiencies Patients correctly categorized as being at low risk whose physician agreed to discharge them but because of health care system inefficiency were not discharged before day 3 . The delay tool [ 6 ] was used for the abstract ion and categorization of inefficiency . Examples of delays included waiting for tests , procedures , or results ; social issues ( for example , waiting for nursing home placement ) ; waiting for consultation ; and patient refusal . 3 . Noncompliance of Physicians Based on Changes in Patient Clinical Status between 24 and 48 Hours Patients correctly classified at 24 hours as being at low risk but who between 24 and 48 hours either had a complication , an intervention planned ( for example , cardiac catheterization ) , or an unstable comorbid condition . These events caused the patient to be reclassified as being at high risk on retrospective review ; therefore , physician noncompliance was based on a changing medical condition rather than on physician , guideline , or hospital issues . 4 . Physician Noncompliance Based on Physician Refusal To Discharge This category was assigned if the following four conditions were met : a ) The patient was truly at low risk and did not change status between 24 and 48 hours . b ) Discharge was not delayed secondary to possible hospital inefficiencies . c ) The physician 's refusal to discharge was documented on the utilization-management , OBJECTIVE : To measure primary care physicians ’ familiarity with , attitudes toward , and confidence in preventive care practice guidelines for the elderly and to determine whether their attitudes are associated with implementation of guidelines into clinical practice . DESIGN : A self-administered survey of physicians employed by a health maintenance organization ( HMO ) and of patients cared for by those physicians . Medical records were also review ed to assess compliance with practice guidelines . SETTING : An HMO in Southern California . PARTICIPANTS : Forty-eight primary care physicians completed the survey ( 100 % response rate ) . The medical records of 3,249 r and omly selected elderly patients ( 65 to 75 years old ) were studied . Of these patients , 2,799 completed a preventive care survey ( response rate 86.1%).MEASUREMENT AND RESULTS : Most HMO primary care physicians agreed or strongly agreed that guidelines will improve quality of medical care ( 88 % ) and that guidelines have caused them to change their care of patients ( 73 % ) . Although the physicians ’ general attitudes about guidelines did not often correlate with their use of preventive care guidelines , the physicians who stated that practice guidelines had changed their practice s were more likely to offer their patients clinical breast examinations ( 75.9 % vs 67.2 % , p=0.04 ) and to counsel their patients to exercise ( 70 % vs 58 % , p=0.01 ) than were the physicians who did not . There was a significant association between physicians ’ support for and adoption of specific practice guidelines regarding mammography ( r=0.34 , p=0.02 ) and immunizations against influenza ( r=0.42 , p<0.005 ) , pneumococcal pneumonia ( r=0.47 , p<0.001 ) , and tetanus ( r= 0.31 , p=0.03 ) . CONCLUSIONS : Physicians employed by an HMO were familiar with and hopeful about the role of guidelines for improving patient care . Physicians ’ attitudes toward specific preventive care guidelines and admission that guidelines had caused them to change their practice did at times , but not always , correlate with their implementation of guidelines into clinical practice |
2,414 | 27,541,335 | Therefore , we were unable to assess the effect of intravenous heparin on all-cause mortality and incidence of general arterial disease , for example , cardiovascular , cerebral , pulmonary and renal pathologies in rAAA management in people undergoing an emergency repair . | BACKGROUND There have been enormous advances in the screening , diagnosis , intervention and overall prognosis of abdominal aortic aneurysms ( AAAs ) in the last decade , but despite these , ruptured AAAs ( rAAAs ) still cause around 3500 to 6000 deaths in Engl and and Wales each year .
Open repair remains st and ard treatment for rAAA in most centres but increasingly endovascular aneurysm repair ( EVAR ) is being adopted .
This has a 30-day postoperative mortality of 40 % .
This has remained static despite surgical , anaesthetic and critical care advances .
One significant change to current practice for elective repairs of AAAs , as opposed to emergency repairs of rAAAs , has been the introduction of intravenous heparin .
This provides a protective effect against cardiac and thrombotic disease in the postoperative period .
This practice has not gained widespread acceptance for emergency repairs of rAAA even though a reduction in mortality and morbidity has been demonstrated in elective repairs .
OBJECTIVES The primary objective was to assess the effect of intravenous heparin on all-cause mortality in ruptured abdominal aortic aneurysm ( rAAA ) management in people undergoing an emergency repair .
The secondary objectives were to assess the effect of intravenous heparin in rAAA management on the incidence of general arterial disease , for example , cardiovascular , cerebral , pulmonary and renal pathologies , in people undergoing emergency repair . | Heparin anticoagulation during cardiovascular surgical procedures remains poorly investigated and understood . The objective of this investigation was to assess the effectiveness of three methods of heparin administration . Heparin sulfate ( 75 IU/kg ) administered to patients undergoing aortoiliac surgery was r and omised to one of three methods : Group I ( n = 9 ) heparin was injected into a central venous line 5 minutes before infrarenal aortic clamping ; Group II ( n = 9 ) heparin was injected into the distal aneurysm immediately after infrarenal aortic clamping ; and Group III ( n = 8) heparin was injected into a central venous line immediately after infrarenal aortic clamping . Blood sample s were analysed for anticoagulant activity from both the upper and lower extremities at 5 , 15 , 30 , 60 , and 120 minutes after heparin administration . Anticoagulation , as measured by aPTT , antifactor Xa levels , and ACT , was achieved in all three groups by 5 minutes , but initially with lower heparin activity ( measured as antifactor Xa ) in the upper extremity ( Group II ) and lower extremity ( Group III ) , respectively . These differences were also evident in ACT and aPTT determinations . Intravenous heparin administration prior to aortic cross-clamping achieves excellent anticoagulation ( anti-factor Xa approximately 1 U/ml ) in both upper and lower extremities after 5 minutes . With regional administration , rapid heparin redistribution occurs , but it takes longer to achieve the same level of anticoagulation distant from the site of administration . Nevertheless , from a practical perspective the method of administration does not appear to have a great influence on the eventual achievement of adequate anticoagulation Perioperative hemorrhage is one of the principal causes of death in patients with ruptured abdominal aortic aneurysm ( AAA ) . This study examines perioperative coagulation and fibrinolysis in patients undergoing ruptured AAA repair complicated by coagulopathy . Eight patients ( 8 men of median age 74 , range 69 - 87 , years ) who developed clinical and laboratory evidence of coagulopathy during attempted repair of ruptured infrarenal AAA were prospect ively studied . Platelet count , fibrinogen , clotting times , prothrombin fragment ( PF ) 1 + 2 , and tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor ( PAI ) activities were measured preoperatively , immediately before , and 5 min and 24 hr after aortic declamping . Six patients died , three intraoperatively , one within 24 hr , and two in the late postoperative period . All patients had thrombocytopenia and prolonged clotting times intraoperatively with evidence of increased thrombin generation ( as demonstrated by elevated PF 1 + 2 ) . Five patients had increased systemic fibrinolysis ( as demonstrated by elevated t-PA activity ) preoperatively and /or before aortic declamping and all of these patients died . Three patients had perioperative inhibition of systemic fibrinolysis ( as demonstrated by elevated PAI activity ) and two survived . These data demonstrate that coagulopathy in ruptured AAA repair may be associated with a hyperfibrinolytic state . Further research is required to determine if ( a ) a causal relationship exists between hyperfibrinolysis and coagulopathy and ( b ) whether antifibrinolytic agents can improve outcome if targeted at this group of patients BACKGROUND ruptured abdominal aortic aneurysm ( AAA ) is associated with inhibition of systemic fibrinolysis . Hypofibrinolysis is a risk factor for ischaemic myocardial injury , one of the commonest complications of ruptured AAA repair . Cardiac troponin I ( cTnI ) is one of the most sensitive and specific marker of myocardial injury currently available . OBJECTIVE To examine , for the first time , the relationship between fibrinolytic activity and myocardial injury in patients operated for ruptured AAA . METHODS Twenty patients ( 18 men and 2 women of median age 74 , range 65 - 86 years ) undergoing repair of ruptured AAA were prospect ively studied . Plasma tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor ( PAI-1 ) activity were measured pre-operatively , immediately before and five minutes following aortic clamp release . Serum cTnI was measured pre-operatively , 6 and 24 h following clamp release . Results cTnI was detectable at one or more sample points in 13 ( 65 % ) patients , and in 7 out of 8 patients who suffered major cardiac complications . There was a significant negative correlation between pre-operative t-PA activity and cTnI before operation ( r = -0.55 , p = 0.01 ) and 6 h ( r = -0.51 , p = 0.02 ) after clamp release . There was a significant positive correlation between pre-operative PAI activity and cTnI before operation ( r = + 0.50 , p = 0.03 ) , 6 h ( r = + 0.47 , p = 0.04 ) and 24 h ( r = + 0.50 , p = 0.03 ) after clamp release . There was no correlation between pre- and intra-operative hypotension or blood transfusion requirement and cTnI release . CONCLUSIONS Hypofibrinolysis during ruptured AAA repair is associated with the development of peri-operative myocardial injury . The causal mechanisms underlying this state are not clear but treatment of this prothrombotic/hypofibrinolytic diathesis may help to limit myocardial cell necrosis BACKGROUND Outcome after operative repair of ruptured abdominal aortic aneurysm ( AAA ) has traditionally been assessed in terms of survival . This study examines the functional outcome of patients who survive operation . METHODS Consecutive patients who survived open repair over an 18-month period were entered into a prospect i ve case-control study . Age- and sex-matched controls were identified from patients undergoing elective AAA repair . The Short Form-36 health survey was administered to both groups of patients at 6 months after operation . Results were compared with the expected scores for an age- and sex-matched normal UK population . RESULTS Fifty-seven patients underwent open repair of a ruptured AAA , and 30 survived ; no patient was lost to follow-up . There were no significant differences in quality of life between patients who had an emergency repair and those who had an elective repair . Both of these groups had poorer health-related quality of life outcomes than the matched normal population . Surprisingly , compared with the normal population , patients after elective repair had poorer outcomes in more health domains than patients who survived emergency operation . CONCLUSIONS Survivors of ruptured AAA repair have a good functional outcome within 6 months of operation OBJECTIVES The primary aim of this prospect i ve multi-centre study involving patients undergoing elective abdominal aortic aneurysm ( AAA ) surgery was to investigate the relationship between intraoperative intravenous heparinisation , blood loss during surgery and thrombotic complications . METHODS Two hundred and eighty-four patients were r and omised to receive intravenous heparin ( n = 145 ) or no heparin ( n = 139 ) . Groups were evenly matched for age , sex , weight , aneurysm size , haemoglobin concentration , platelet counts and distal occlusive disease measured by ankle/brachial systolic pressure . RESULTS There were no statistically significant differences in blood loss ( median 1400 ml vs. 1500 ml ; z = 0.02 , p = 0.98 , 95 % C.I. = -200 to 200 ) , blood transfused ( 4.0 units vs. 4.0 units ; z = 1.09 , p = 0.28 , 95 % C.I. = -1 to 0 ) or distal thrombosis between the two groups . However , analysis of the clinical outcome revealed that 5.7 % of the non-heparin group but only 1.4 % of the heparinised patients suffered a fatal perioperative myocardial infa rct ion ( MI ) ; p < 0.05 . All MI , including non fatal events , affected 8.5 % and 2 % respectively ( p = 0.02 ) . CONCLUSIONS Heparin does not increase blood loss or the need for blood transfusion during surgery . Heparin is not necessary to prevent distal thrombosis when the aorta is cross clamped . The results of the study are consistent with the known mechanisms leading to intraoperative MI and strategies for its prevention . Intravenous heparin , given before aortic cross clamping , is an important prophylaxic against perioperative MI in relation to AAA surgery Elective surgery of abdominal aortic aneurysm ( AAA ) sometimes leads to excessive bleeding and disseminated intravascular coagulation ( DIC ) , even in patients with normal preoperative coagulation parameters . Coagulation screen , performed routinely before surgery is of limited value in the assessment of compensated activation of the haemostatic system . In this study , we used a number of additional tests ( D-dimer , prothrombin fragment 1 + 2 , antithrombin , and activation of fibrinolysis in the platelet poor plasma ) for the diagnosis of compensated activation of the haemostatic system in AAA- patients . D-dimer and marker of thrombin generation ( prothrombin fragment 1 + 2 ) positively correlated with each other ( r = 0.768 , P < 0.001 ) . Out of 71 AAA patients , 15 patients had normal global coagulation times , but those with a D- dimer concentration above 3000 ng/ml were selected for preoperative low molecular weight heparin ( LMWH ) treatment . Administration of LMWH diminished coagulation abnormalities ( D-dimer and prothrombin fragment 1 + 2 decreased significantly ) and result ed in the increase of platelet number and fibrinogen concentration , indicating their previous consumption . Despite differences in aneurysm diameters between the groups of 15 LMWH treated patients ( mean 70.9 + /- 16 mm ) and the reference group of 20 untreated AAA patients ( mean 52.3 + /- 8.0 mm ) , intraoperative parameters ( operation time , blood loss and transfusion dem and s ) were similar The aim of this study was to investigate whether intravenous heparin administration was associated with a reduction in perioperative mortality and late distal thrombectomy in patients with ruptured abdominal aortic aneuryms ( AAAs ) . One hundred thirty-one patients had repair of ruptured AAA between January 1999 and January 2004 . Sixty-three received heparin according to the consultant 's preference at the time of the operation . Data were prospect ively collected , and multivariate analysis was performed for independent predictive factors . Thirty-day mortality was 29 % . Patients receiving heparin had lower perioperative mortality ( 16 % vs 42 % ; p = .001 ) . Heparin administration was not associated with increased hemorrhage or transfusion . Multivariate analysis confirmed that heparin administration was independently predictive of survival ( p = .036 ) . Other factors found to reduce survival were age ( p = .023 ) , smoking ( p = .042 ) , and systolic blood pressure ( < 100 mmHg ) at presentation ( p = .045 ) . Fewer patients had thrombectomy after heparin ( 8 % vs 12 % ) , but this was not statistically significant . Perioperative complications were similar in both groups . The administration of systemic heparin before the clamp is applied to leaking aneurysms does not appear to increase hemorrhage and subsequent mortality and may reduce the need for early thrombectomy Large abdominal aortic aneurysms ( AAAs ) are associated with coagulation abnormalities , which are significantly reduced by low molecular weight heparin ( LMWH ) . Considering anti-inflammatory properties of heparin we verified , whether LMWH influences MMP-2/-9 in AAA patients . The study involved 26 AAA individuals , 10 patients with coagulation abnormalities received LMWH and 16 were a control group . The plasma activity of MMP-2/-9 was measured using zymography . We found that , in addition to the reduction of coagulation abnormalities , LMWH treatment was associated with the decreased MMP-9 but not MMP-2 activity . Therefore , LMWH use could be considered as a valuable pretreatment before an elective aneurysm repair |
2,415 | 31,874,870 | Conclusions The results of this meta‐ analysis indicate that blood circulating vitamin D level is associated with decreased risk of colorectal cancer in Asian countries .
The dose-response meta- analysis shows that the strength of this association among the Asian population is similar to that among the Western population .
Our study suggests that the Asian population should improve nutritional status and maintain a higher level of blood circulating vitamin | Objectives To assess the association between blood circulating vitamin D levels and colorectal cancer risk in the Asian population .
Design This is a systematic review and dose-response meta- analysis of observational studies that investigated the relationship between blood circulating vitamin D levels and colorectal cancer risk in the Asian population . | Background There is clear evidence that nutrition and lifestyle can modify colorectal cancer risk . However , it is not clear if those factors can affect colorectal cancer treatment , recurrence , survival and quality of life . This paper describes the background and design of the “ COlorectal cancer : Longitudinal , Observational study on Nutritional and lifestyle factors that may influence colorectal tumour recurrence , survival and quality of life ” – COLON – study . The main aim of this study is to assess associations of diet and other lifestyle factors , with colorectal cancer recurrence , survival and quality of life . We extensively investigate diet and lifestyle of colorectal cancer patients at diagnosis and during the following years ; this design paper focusses on the initial exposures of interest : diet and dietary supplement use , body composition , nutrient status ( e.g. vitamin D ) , and composition of the gut microbiota . Methods / Design The COLON study is a multi-centre prospect i ve cohort study among at least 1,000 incident colorectal cancer patients recruited from 11 hospitals in the Netherl and s. Patients with colorectal cancer are invited upon diagnosis . Upon recruitment , after 6 months , 2 years and 5 years , patients fill out food-frequency question naires ; question naires about dietary supplement use , physical activity , weight , height , and quality of life ; and donate blood sample s. Diagnostic CT-scans are collected to assess cross-sectional areas of skeletal muscle , subcutaneous fat , visceral fat and intermuscular fat , and to assess muscle attenuation . Blood sample s are biobanked to facilitate future analyse of biomarkers , nutrients , DNA etc . Analysis of serum 25-hydroxy vitamin D levels , and analysis of metabolomic profiles are scheduled . A subgroup of patients with colon cancer is asked to provide faecal sample s before and at several time points after colon resection to study changes in gut microbiota during treatment . For all patients , information on vital status is retrieved by linkage with national registries . Information on clinical characteristics is gathered from linkage with the Netherl and s Cancer Registry and with hospital data bases . Hazards ratios will be calculated for dietary and lifestyle factors at diagnosis in relation to recurrence and survival . Repeated measures analyses will be performed to assess changes over time in dietary and other factors in relation to recurrence and survival We investigated the association between plasma 25(OH)D and the subsequent colorectal cancer incidence risk by a nested case – control study in The Japan Public Health Center-based Prospect i ve Study , covering 375 newly diagnosed cases of colorectal cancer from 38 373 study subjects during a 11.5-year follow-up after blood collection . Two controls were matched per case on sex , age , study area , date of blood draw , and fasting time . In a conditional logistic regression model with matched pairs adjusted for smoking , alcohol consumption , body mass index , physical exercise , vitamin supplement use , and family history of colorectal cancer , plasma 25(OH)D was not significantly associated with colorectal cancer in men or in women . However , the lowest category of plasma 25(OH)D was associated with an elevated risk of rectal cancer in both men ( odds ratio ( OR ) , 4.6 ; 95 % confidence interval ( CI ) , 1.0–20 ) and women ( OR , 2.7 , 95 % CI , 0.94–7.6 ) , compared with the combined category of the other quartiles . Our results suggest that a low level of plasma 25(OH)D may increase the risk of rectal cancer Objective To examine the association between pre-diagnostic circulating vitamin D concentration , dietary intake of vitamin D and calcium , and the risk of colorectal cancer in European population s. Design Nested case-control study . Setting The study was conducted within the EPIC study , a cohort of more than 520 000 participants from 10 western European countries . Participants 1248 cases of incident colorectal cancer , which developed after enrolment into the cohort , were matched to 1248 controls Main outcome measures Circulating vitamin D concentration ( 25-hydroxy-vitamin-D , 25-(OH)D ) was measured by enzyme immunoassay . Dietary and lifestyle data were obtained from question naires . Incidence rate ratios and 95 % confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models , with adjustment for potential dietary and other confounders . Results 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer ( P for trend < 0.001 ) . Compared with a pre-defined mid-level concentration of 25-(OH)D ( 50.0 - 75.0 nmol/l ) , lower levels were associated with higher colorectal cancer risk ( < 25.0 nmol/l : incidence rate ratio 1.32 ( 95 % confidence interval 0.87 to 2.01 ) ; 25.0 - 49.9 nmol/l : 1.28 ( 1.05 to 1.56 ) , and higher concentrations associated with lower risk ( 75.0 - 99.9 nmol/l : 0.88 ( 0.68 to 1.13 ) ; ≥100.0 nmol/l : 0.77 ( 0.56 to 1.06 ) ) . In analyses by quintile of 25-(OH)D concentration , patients in the highest quintile had a 40 % lower risk of colorectal cancer than did those in the lowest quintile ( P<0.001 ) . Subgroup analyses showed a strong association for colon but not rectal cancer ( P for heterogeneity=0.048 ) . Greater dietary intake of calcium was associated with a lower colorectal cancer risk . Dietary vitamin D was not associated with disease risk . Findings did not vary by sex and were not altered by corrections for season or month of blood donation . Conclusions The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European population s. Further r and omised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer Abstract Objective To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study . Design Nested case-cohort study within the Japan Public Health Center-based Prospect i ve Study cohort . Setting Nine public health centre areas across Japan . Participants 3301 incident cases of cancer and 4044 r and omly selected subcohort participants . Exposure Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay . Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts . Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration , with the lowest quarter as the reference . Main outcome measure Incidence of overall or site specific cancer . Results Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer , with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 ( 95 % confidence interval 0.70 to 0.94 ) , 0.75 ( 0.65 to 0.87 ) , and 0.78 ( 0.67 to 0.91 ) , respectively ( P for trend=0.001 ) . Among the findings for cancers at specific sites , an inverse association was found for liver cancer , with corresponding hazard ratios of 0.70 ( 0.44 to 1.13 ) , 0.65 ( 0.40 to 1.06 ) , and 0.45 ( 0.26 to 0.79 ) ( P for trend=0.006 ) . A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios . Conclusions In this large prospect i ve study , higher vitamin D concentration was associated with lower risk of total cancer . These findings support the hypothesis that vitamin D has protective effects against cancers at many sites BACKGROUND Numerous observational studies have found supplemental calcium and vitamin D to be associated with reduced risk of common cancers . However , interventional studies to test this effect are lacking . OBJECTIVE The purpose of this analysis was to determine the efficacy of calcium alone and calcium plus vitamin D in reducing incident cancer risk of all types . DESIGN This was a 4-y , population -based , double-blind , r and omized placebo-controlled trial . The primary outcome was fracture incidence , and the principal secondary outcome was cancer incidence . The subjects were 1179 community-dwelling women r and omly selected from the population of healthy postmenopausal women aged > 55 y in a 9-county rural area of Nebraska centered at latitude 41.4 degrees N. Subjects were r and omly assigned to receive 1400 - 1500 mg supplemental calcium/d alone ( Ca-only ) , supplemental calcium plus 1100 IU vitamin D3/d ( Ca + D ) , or placebo . RESULTS When analyzed by intention to treat , cancer incidence was lower in the Ca + D women than in the placebo control subjects ( P < 0.03 ) . With the use of logistic regression , the unadjusted relative risks ( RR ) of incident cancer in the Ca + D and Ca-only groups were 0.402 ( P = 0.01 ) and 0.532 ( P = 0.06 ) , respectively . When analysis was confined to cancers diagnosed after the first 12 mo , RR for the Ca + D group fell to 0.232 ( CI : 0.09 , 0.60 ; P < 0.005 ) but did not change significantly for the Ca-only group . In multiple logistic regression models , both treatment and serum 25-hydroxyvitamin D concentrations were significant , independent predictors of cancer risk . CONCLUSIONS Improving calcium and vitamin D nutritional status substantially reduces all-cancer risk in postmenopausal women . This trial was registered at clinical trials.gov as NCT00352170 BACKGROUND Calcium and vitamin D both appear to have antineoplastic effects in the large bowel . Although these nutrients are inter-related metabolically in bone and in the normal intestine , their potential interactions in large-bowel carcinogenesis are not well understood . METHODS We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center , placebo-controlled r and omized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence . Serum levels of 25-hydroxy [ 25-(OH ) ] vitamin D and 1,25-dihydroxy [ 1,25-(OH)2 ] vitamin D levels were determined , and the Taq I and Fok I polymorphisms in the vitamin D receptor ( VDR ) gene were analyzed by polymerase chain reaction . Risk ratios ( RRs ) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups . Associations of VDR polymorphisms with recurrence risk were also evaluated . All statistical tests were two-sided . RESULTS Among subjects with baseline 25-(OH ) vitamin D levels at or below the median ( 29.1 ng/mL ) , calcium supplementation was not associated with adenoma recurrence , whereas among those with levels above the median , calcium supplementation was associated with a reduced risk ( RR = 0.71 , 95 % confidence interval [ CI ] = 0.57 to 0.89 , P for interaction = .012 ) . Conversely , serum 25-(OH ) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements ( RR per 12 ng/mL increase of vitamin D = 0.88 , 95 % CI = 0.77 to 0.99 , P for interaction = .006 ) . VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium . CONCLUSIONS Calcium supplementation and vitamin D status appear to act largely together , not separately , to reduce the risk of colorectal adenoma recurrence . VDR genotype does not appear to be associated with risk CONTEXT We wanted to investigate vitamin D in low-risk prostate cancer . OBJECTIVES The objective of the study was to determine whether vitamin D(3 ) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen ( PSA ) or in the rate of progression . DESIGN In this open-label clinical trial ( Investigational New Drug 77,839 ) , subjects were followed up until repeat biopsy . SETTING All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center , both in Charleston , SC . PATIENTS AND OTHER PARTICIPANTS All subjects had a diagnosis of low-risk prostate cancer . Fifty-two subjects were enrolled in the study , 48 completed 1 yr of supplementation , and 44 could be analyzed for both safety and efficacy objectives . INTERVENTION The intervention included vitamin D(3 ) soft gels ( 4000 IU ) . MAIN OUTCOME MEASURES Adverse events were monitored throughout the study . PSA serum levels were measured at entry and every 2 months for 1 yr . Biopsy procedures were performed before enrollment ( for eligibility ) and after 1 yr of supplementation . RESULTS No adverse events associated with vitamin D(3 ) supplementation were observed . No significant changes in PSA levels were observed . However , 24 of 44 subjects ( 55 % ) showed a decrease in the number of positive cores or decrease in Gleason score ; five subjects ( 11 % ) showed no change ; 15 subjects ( 34 % ) showed an increase in the number of positive cores or Gleason score . CONCLUSION Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3 ) supplementation at 4000 IU/d Objective : Calcium , vitamin D , and dairy product intake may reduce the risk of colorectal cancer . We therefore examined the association between these factors and risk of colorectal cancer in a large prospect i ve cohort of United States men and women . Methods : Participants in the Cancer Prevention Study II Nutrition Cohort completed a detailed question naire on diet , medical history , and lifestyle in 1992–93 . After excluding participants with a history of cancer or incomplete dietary information , 60,866 men and 66,883 women remained for analysis . During follow-up through 31 August 1997 we documented 421 and 262 cases of incident colorectal cancers among men and women , respectively . Multivariate-adjusted rate ratios ( RR ) were calculated using Cox proportional hazards models . Results : Total calcium intake ( from diet and supplements ) was associated with marginally lower colorectal cancer risk in men and women ( RR = 0.87 , 95 % CI 0.67–1.12 , highest vs lowest quintiles , p trend = 0.02 ) . The association was strongest for calcium from supplements ( RR = 0.69 , 95 % CI 0.49–0.96 for ≥500 mg/day vs none ) . Total vitamin D intake ( from diet and multivitamins ) was also inversely associated with risk of colorectal cancer , particularly among men ( RR = 0.71 , 95 % CI 0.51–0.98 , p trend = 0.02 ) . Dairy product intake was not related to overall risk . Conclusions : Our results support the hypothesis that calcium modestly reduces risk of colorectal cancer . Vitamin D was associated with reduced risk of colorectal cancer only in men Vitamin D is associated with decreased risks of various cancers , including colon cancer . The vitamin D receptor ( VDR ) is a transcription factor , which plays an important role in cellular differentiation and inhibition of proliferation . A link between VDR and the RAS – mitogen-activated protein kinase ( MAPK ) or phosphatidylinositol 3-kinase (PI3K)–AKT pathway has been suggested . However , the prognostic role of VDR expression or its relationship with PIK3CA or KRAS mutation remains uncertain . Among 619 colorectal cancers in two prospect i ve cohort studies , 233 ( 38 % ) tumors showed VDR overexpression by immunohistochemistry . We analyzed for PIK3CA and KRAS mutations and LINE-1 methylation by Pyrosequencing , microsatellite instability ( MSI ) , and DNA methylation ( epigenetic changes ) in eight CpG isl and methylator phenotype (CIMP)–specific promoters [ CACNA1 G , CDKN2A ( p16 ) , CRABP1 , IGF2 , MLH1 , NEUROG1 , RUNX3 , and SOCS1 ] by MethyLight ( real-time PCR ) . VDR overexpression was significantly associated with KRAS mutation ( odds ratio , 1.55 ; 95 % confidence interval , 1.11 - 2.16 ) and PIK3CA mutation ( odds ratio , 2.17 ; 95 % confidence interval , 1.36 - 3.47 ) , both of which persisted in multivariate logistic regression analysis . VDR was not independently associated with body mass index , family history of colorectal cancer , tumor location ( colon versus rectum ) , stage , tumor grade , signet ring cells , CIMP , MSI , LINE-1 hypomethylation , BRAF , p53 , p21 , β-catenin , or cyclooxygenase-2 . VDR expression was not significantly related with patient survival , prognosis , or clinical outcome . In conclusion , VDR overexpression in colorectal cancer is independently associated with PIK3CA and KRAS mutations . Our data support potential interactions between the VDR , RAS – MAPK and PI3K – AKT pathways , and possible influence by KRAS or PIK3CA mutation on therapy or chemoprevention targeting VDR . ( Cancer Epidemiol Biomarkers Prev 2009;18(10):2765–72 BACKGROUND Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials . However , r and omized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking . METHODS We conducted a r and omized , double-blind , placebo-controlled trial involving 36,282 postmenopausal women from 40 Women 's Health Initiative centers : 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [ corrected ] twice daily ( 1000 mg of elemental calcium and 400 IU of vitamin D3 ) and 18,106 received a matching placebo for an average of 7.0 years . The incidence of pathologically confirmed colorectal cancer was the design ated secondary outcome . Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study . RESULTS The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo ( 168 and 154 cases ; hazard ratio , 1.08 ; 95 percent confidence interval , 0.86 to 1.34 ; P=0.51 ) , and the tumor characteristics were similar in the two groups . The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups . There were no significant treatment interactions with baseline characteristics . CONCLUSIONS Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women . The long latency associated with the development of colorectal cancer , along with the seven-year duration of the trial , may have contributed to this null finding . Ongoing follow-up will assess the longer-term effect of this intervention . ( Clinical Trials.gov number , NCT00000611 . ) Although calcium and vitamin-D intake were consistently shown to be inversely associated with colorectal cancer risk in several large prospect i ve studies and protective against adenoma and cancer in multiple r and omized trials , the Women 's Health Initiative ( WHI ) of calcium and low-dose vitamin-D supplementation trial found no overall effects on colorectal cancer . However , the previous report did not recognize an important biologic interaction with estrogen therapy . We investigated the treatment interaction of estrogen with calcium and vitamin-D on risk of colorectal cancer via a re analysis of primary data results from the WHI calcium and vitamin-D supplementation trial ( 1,000 mg elemental calcium , 400 IU of vitamin-D3 , or placebo ) , reanalyzing results from women concurrently r and omized to estrogen interventions and placebo . Results indicate that concurrent estrogen therapy was a strong effect modifier of calcium and vitamin-D supplementation on colorectal cancer risk . While calcium plus vitamin-D supplementation among women concurrently assigned to estrogen therapies suggested increased risk ( Hazard Ratio = 1.50 , 95 % CI : 0.96 - 2.33 ) , among women concurrently assigned to placebos arms of the estrogen trials , calcium plus vitamin-D indicated suggestive benefits ( HR = 0.71 , 95 % CI : 0.46 - 1.09 ) ( p-for-estrogen-interaction = 0.018 ) . Consistent interaction was also found by reported estrogen use ( p interaction = 0.037 ) . Results indicate contrasting effects of calcium and vitamin-D by concurrent estrogen therapy on colorectal cancer risk . Although further clinical and mechanistic studies are warranted , the potential clinical implication s of the apparent interaction of estrogen therapy with calcium and vitamin-D supplementation should be recognized . Important biological mechanisms related to the key membrane receptor megalin and estrogen-dependent protein calbindin are discussed Observational data on the association between circulating 25(OH)D and colorectal cancer risk are limited in women . To determine whether prediagnostic levels of 25(OH)D were associated with risk of incident colorectal cancer in the Women 's Health Study ( WHS ) , we conducted a nested case – control study using 274 colorectal cases and 274 controls . Each case was matched to a control by age , ethnicity , fasting status at the time of blood collection , time of day when blood was drawn , and month of blood draw . Conditional logistic regression was used to estimate the OR and 95 % confidence interval ( CI ) for colorectal cancer by 25(OH)D quartiles . Mean plasma 25(OH)D was lower in cases versus controls ( 21.9 vs. 23.9 ng/mL , P = 0.01 ) . In multivariable-adjusted logistic regression models , plasma 25(OH)D was significantly and inversely associated with odds of colorectal cancer ( quartile 4 [ Q4 ] vs. quartile 1 [ Q1 ] : OR , 0.45 ; 95 % CI , 0.25–0.81 ; Ptrend 0.02 ) . In addition , we observed a somewhat lower risk of colorectal cancer-related mortality after adjustment for matching variables , r and omization treatment and other risk factors ( Q4:Q1 OR , 0.40 ; 95 % CI , 0.17–0.97 ; Ptrend 0.05 ) . In this cohort of healthy women , we found a significant inverse association between prediagnostic 25(OH)D levels and risk of incident colorectal cancer , and a borderline significant inverse association between prediagnostic 25(OH)D levels and colorectal cancer-related mortality . These results support a possible association between plasma 25(OH)D and risk of colorectal cancer in women . Cancer Prev Res ; 8(8 ) ; 675–82 . © 2015 AACR . See related commentary by Demetrius Albanes , p. BACKGROUND Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis , but evidence is inconclusive . Circulating 25-hydroxyvitamin D ( 25(OH)D ) concentrations that minimize risk are unknown . Current Institute of Medicine ( IOM ) vitamin D guidance is based solely on bone health . METHODS We pooled participant-level data from 17 cohorts , comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations . For 30.1 % of participants , 25(OH)D was newly measured . Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations . Study -specific relative risks ( RRs ) for prediagnostic season-st and ardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using r and om effects models . RESULTS Compared with the lower range of sufficiency for bone health ( 50-<62.5 nmol/L ) , deficient 25(OH)D ( < 30 nmol/L ) was associated with 31 % higher colorectal cancer risk ( RR = 1.31 , 95 % confidence interval [ CI ] = 1.05 to 1.62 ) ; 25(OH)D above sufficiency ( 75-<87.5 and 87.5-<100 nmol/L ) was associated with 19 % ( RR = 0.81 , 95 % CI = 0.67 to 0.99 ) and 27 % ( RR = 0.73 , 95 % CI = 0.59 to 0.91 ) lower risk , respectively . At 25(OH)D of 100 nmol/L or greater , risk did not continue to decline and was not statistically significantly reduced ( RR = 0.91 , 95 % CI = 0.67 to 1.24 , 3.5 % of control participants ) . Associations were minimally affected when adjusting for body mass index , physical activity , or other risk factors . For each 25 nmol/L increment in circulating 25(OH)D , colorectal cancer risk was 19 % lower in women ( RR = 0.81 , 95 % CI = 0.75 to 0.87 ) and 7 % lower in men ( RR = 0.93 , 95 % CI = 0.86 to 1.00 ) ( two-sided Pheterogeneity by sex = .008 ) . Associations were inverse in all subgroups , including colorectal subsite , geographic region , and season of blood collection . CONCLUSIONS Higher circulating 25(OH)D was related to a statistically significant , substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men . Optimal 25(OH)D concentrations for colorectal cancer risk reduction , 75 - 100 nmol/L , appear higher than current IOM recommendations Background : The role of vitamin D in cancer risk remains controversial , and limited data exist on associations between vitamin D and subtypes of specific cancers . We investigated associations between circulating 25-hydroxyvitamin D ( 25(OH)D ) and risk of colorectal , breast , and prostate cancers , including subtypes . Methods : A case – cohort study within the Melbourne Collaborative Cohort Study included 547 colorectal , 634 breast , and 824 prostate cancers , and a sex-stratified r and om sample of participants ( n = 2,996 ) . Concentration of 25(OH)D in baseline-dried blood spots was measured using LC-MS/MS . Cox regression yielded adjusted HRs and 95 % confidence intervals ( CI ) for each cancer in relation to plasma-equivalent 25(OH)D concentration . Associations by stage and BRAF/KRAS status for colorectal cancer , estrogen receptor status for breast cancer , and aggressiveness for prostate cancer were examined in competing risks models . Results : 25(OH)D concentrations were inversely associated with risk of colorectal cancer [ highest vs. lowest 25(OH)D quintile : HR , 0.71 ; 95 % confidence interval ( CI ) , 0.51–0.98 ] , which was limited to women ( HR , 0.52 ; 95 % CI , 0.33–0.82 ) . Circulating 25(OH)D was also inversely associated with BRAF V600E – positive colorectal cancer ( per 25 nmol/L increment : HR , 0.71 ; 95 % CI , 0.50–1.01 ) . There were no inverse associations with breast cancer ( HR , 0.98 ; 95 % CI , 0.70–1.36 ) or prostate cancer ( HR , 1.11 ; 95 % CI , 0.82–1.48 ) . Conclusions : Circulating 25(OH)D concentration was inversely associated with colorectal cancer risk for women , but not with risk of breast cancer or prostate cancer . Impact : Vitamin D might play a role in preventing colorectal cancer . Further studies are required to confirm whether vitamin D is associated with specific tumor subtypes BACKGROUND & AIMS To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population . METHODS We undertook a population -based prospect i ve study in a population from southern Spain . The first phase of the study ( 1996 - 1998 ) included 1226 individuals . Of this original cohort , 988 persons were reassessed in 2002 - 2004 and 961 in 2005 - 2007 . Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002 - 2004 and an oral glucose tolerance test was done in three time points . RESULTS The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL ( percentile 25 ) was 12.4 % vs 4.7 % in subjects with levels > 18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [ OR = 0.17 ( 0.05 - 0.61 ) ] . None of the subjects with levels higher than 30 ng/mL developed diabetes . CONCLUSION In this prospect i ve study , we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain |
2,416 | 25,741,193 | Conclusion Some US indices , such as HV , exhibited an increased accuracy for diagnosing PH .
These indices may be useful in clinical practice for the detection of significant PH | Objective Studies have presented conflicting results regarding the accuracy of ultrasonography ( US ) for diagnosing portal hypertension ( PH ) .
We sought to identify evidence in the literature regarding the accuracy of US for assessing PH in patients with liver cirrhosis . | Background / Aims We compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system ( USSS ) combining six representative sonographic indices with that of liver stiffness measurement ( LSM ) by transient elastography , and prospect ively investigated the correlation between the USSS score and LSM in predicting cirrhosis . Methods Two hundred and thirty patients with chronic liver diseases ( 187 men , 43 women ; age , 50.4±9.5 y , mean±SD ) were enrolled in this prospect i ve study . The USSS produces a combined score for nodularity of the liver surface and edge , parenchyma echogenicity , presence of right-lobe atrophy , spleen size , splenic vein diameter , and abnormality of the hepatic vein waveform . The correlations of the USSS score and LSM with that of a pathological liver biopsy ( METAVIR scoring system : F0-F4 ) were evaluated . Results The mean USSS score and LSM were 7.2 and 38.0 kPa , respectively , in patients with histologically overt cirrhosis ( F4 , P=0.017 ) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis ( F0-F3 ) ( P=0.025 ) . The areas under the receiver operating characteristic ( ROC ) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729 , respectively . On the basis of ROC curves , criteria of USSS ≥6 : LSM ≥17.4 had a sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of 89.2%:77.6 % , 69.4%:61.4 % , 86.5%:83.7 % , 74.6%:51.9 % and 0.83:0.73 , respectively , in predicting F4 . Conclusions The results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis BACKGROUND / AIM The study was design ed to assess to what extent portal hemodynamic parameters obtained by duplex Doppler ultrasonography may be substituted for the measurement of hepatic venous pressure gradient in evaluating the severity of portal hypertension and the response to medical treatment with beta-blockers or beta-blockers plus nitrates in patients with cirrhosis and portal hypertension . METHODS In 39 of these patients hepatic venous pressure gradient was determined by hepatic vein catheterization , and portal blood flow velocity and the congestion index of the portal vein were measured by duplex Doppler ultrasonography . In 19 of these patients the changes in hepatic venous pressure gradient and in Doppler parameters were also assessed after chronic administration of nadolol . In 11 of the 19 patients the changes after chronic administration of nadolol plus isosorbide-5-mononitrate were also measured . RESULTS In the whole series , no significant correlation was found between hepatic venous pressure gradient and duplex Doppler parameters , but , when the 12 patients with a patent para-umbilical vein were excluded , significant linear correlations were found between hepatic venous pressure gradient and portal blood velocity ( r=-0.39 ; p=0.05 ) or congestion index ( r=0.37 ; p=0.05 ) . Considering together the changes induced by nadolol and nadolol plus isosorbide-5-mononitrate , no correlation was apparent between changes in duplex Doppler parameters and in hepatic venous pressure gradient . Agreement between hepatic venous pressure gradient and duplex Doppler parameters in defining good and poor responders was insufficient . CONCLUSIONS These data suggest that portal blood velocity and the congestion index of the portal vein are related to portal hypertension in patients without a patent para-umbilical vein , but are of limited value in discriminating good responders from poor responders to medical treatment for portal hypertension Background The effect of an angiotensin II blockade in lowering the portal pressure in patients with liver cirrhosis and portal hypertension is controversial . This prospect i ve study was undertaken to evaluate the portal hypotensive effect of captopril compared to that of propranolol , and to determine the factors that contribute to a successful reduction in the portal pressure after longterm captopril administration in patients with liver cirrhosis . Methods The hepatic venous pressure gradient ( HVPG ) and portal venous velocity ( PVV ) were measured both before and 3 months after initiation of the administration of captopril ( n = 29 ) or propranolol ( n = 29 ) in cirrhotic patients with a variceal bleeding episode . Patients who showed a reduction in the HVPG of more than 20 % of the baseline were defined as being responders . Results At 3 months , the mean reduction in the HVPG after captopril was less than that after propranolol ( −3.0 ± 9.3 % vs −28.5 % ± 4.1 % ; P ≪ 0.05 ) . However , of the 29 patients receiving captopril , 9 were classified as being responders . On multivariate analysis with parameters including age , cause , Child-Pugh score , HVPG , and PVV , only low PVV was found to be a significant independent factor for responders ( PVV ≪ 12 cm/s ; odds ratio [ OR ] , 12.2 ; 95 % confidence interval [ CI ] , 1.47–102.40 ) in the captopril group . Conclusions Longterm captopril administration reduces the portal pressure effectively in cirrhotic patients with a low PVV . This suggests that the reduction in portal pressure after captopril administration is a result of improved portal venous outflow brought about by a decrease in the intrahepatic vascular resistance . When the PVV is below 12 cm/s , a captopril trial might be useful in preventing variceal bleeding in portal hypertensive patients The drugs currently under investigation in the prevention of recurrent gastrointestinal bleeding in cirrhosis are likely to decrease the portal pressure by means of a primary reduction of portal blood flow . The hemodynamic effects of β‐blocking agents and vasodilatory drugs were noninvasively measured in eight patients with cirrhosis by means of pulsed echo‐doppler equipment . Portal caliber , blood velocity and flow were recorded hourly after a single dose of propranolol ( 40 mg p.o . ) or atenolol ( 100 mg p.o . ) , and every 5 min after treatment with isosorbide dinitrate ( 5 mg sublingually ) . The drugs were administered at r and om with an interval of 2 days or more . The portal caliber decreased after atenolol , but did not change after propranolol and isosorbide . The blood velocity decreased by 29 ± 2 % 3 hr after propranolol , by 26 ± 2 % 3 hr after atenolol and by 31 ± 3 % 15 min after isosorbide . The portal blood flow decreased by 0.29 ± 0.03 liters per min after propranolol , by 0.34 ± 0.06 after atenolol and by 0.26 ± 0.03 after isosorbide , without any difference among the various treatments . β‐blockers and vasodilatory drugs have comparable effects on portal blood flow . β1‐selective and nonselective β‐blockers are similarly effective in keeping with the hypothesis that changes in portal blood flow are mainly due to the block of β1‐receptors BACKGROUND : Octreotide and terlipressin are widely used in acute variceal hemorrhage to reduce the bleeding rate . They purportedly act by mesenteric arterial vasoconstriction , thus reducing portal venous flow ( PVF ) and portal pressure . Little is known about the immediate-early hemodynamic effects of these drugs . AIM : To compare the acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis . PATIENTS : Forty-two cirrhotic patients with a history of variceal bleeding were r and omized to receive either octreotide 100 μg intravenous bolus followed by a continuous infusion at 250 μg/h ( n = 21 ) , or terlipressin 2 mg intravenous bolus ( n = 21 ) . METHODS : Mean arterial pressure ( MAP ) , heart rate ( HR ) , hepatic venous pressure gradient ( HVPG ) , and PVF , assessed by duplex Doppler ultrasonography , were measured before and at 1 , 5 , 10 , 15 , 20 , and 25 min after the start of drug administration . RESULTS : Octreotide markedly decreased HVPG ( −44.5 ± 17.8 % ) and PVF ( −30.6 ± 13.6 % ) compared to the baseline at 1 min ( p < 0.05 ) . Thereafter , both variables rapidly returned toward the baseline , and by 5 min , no significant differences in HVPG ( −7.1 ± 28.9 % ) and PVF ( 10.2 ± 26.2 % ) were noted . A similar transient effect on MAP and HR was observed . Terlipressin significantly decreased HVPG ( −18.3 ± 11.9 % ) and PVF ( −32.6 ± 10.5 % ) at 1 min ( p < 0.05 ) and sustained these effects at all time points . The effects on arterial pressure and HR were also sustained . CONCLUSIONS : Octreotide only transiently reduced portal pressure and flow , whereas the effects of terlipressin were sustained . These results suggest that terlipressin may have more sustained hemodynamic effects in patients with bleeding varices BACKGROUND / AIMS This prospect i ve study aim ed to determine if Doppler ultrasonography can be representative of hepatic venous pressure gradient ( HVPG ) in assessing the severity of portal hypertension and response to drug reducing portal pressure . METHODS The HVPG and the parameters of Doppler ultrasonography including portal venous velocity ( PVV ) and splenic venous velocity , the pulsatility and resistive index of hepatic , splenic and renal arteries were measured in 105 patients with liver cirrhosis . In 31 patients the changes of hepatic venous pressure gradient and portal venous velocity after administration of terlipressin were evaluated . The patients who showed a reduction in HVPG of more than 20 % of the baseline were defined as responders to terlipressin . RESULTS Any Doppler ultrasonographic parameters did not correlate with HVPG . Both HVPG and PVV showed a highly significant reduction after the administration of terlipressin(-28.3 + /- 3.9 % , -31.2 + /- 2.2 % respectively ) . However , PVV decreased significantly not only in responders(31.7 + /- 2.4 % ) but also in nonresponders(29.5 + /- 6.1 % ) . CONCLUSION Doppler ultrasonography can not be representative of HVPG in assessing the severity of portal hypertension and response to drug reducing portal pressure in liver cirrhosis BACKGROUND AND AIMS Our aim was to identify predictors of clinical decompensation ( defined as the development of ascites , variceal hemorrhage [ VH ] , or hepatic encephalopathy [ HE ] ) in patients with compensated cirrhosis and with portal hypertension as determined by the hepatic venous pressure gradient ( HVPG ) . METHODS We analyzed 213 patients with compensated cirrhosis and portal hypertension but without varices included in a trial evaluating the use of beta-blockers in preventing varices . All had baseline laboratory tests and HVPG . Patients were followed prospect ively every 3 months until development of varices or VH or end of study . To have complete information , until study termination , about clinical decompensation , medical record review was done . Patients who underwent liver transplantation without decompensation were censored at transplantation . Cox regression models were developed to identify predictors of clinical decompensation . Receiver operating characteristic ( ROC ) curves were constructed to evaluate diagnostic capacity of HVPG . RESULTS Median follow-up time of 51.1 months . Sixty-two ( 29 % ) of 213 patients developed decompensation : 46 ( 21.6 % ) ascites , 6 ( 3 % ) VH , 17 ( 8 % ) HE . Ten patients received a transplant and 12 died without clinical decompensation . Median HVPG at baseline was 11 mm Hg ( range , 6 - 25 mm Hg ) . On multivariate analysis , 3 predictors of decompensation were identified : HVPG ( hazard ratio [ HR ] , 1.11 ; 95 % confidence interval [ CI ] , 1.05 - 1.17 ) , model of end-stage liver disease ( MELD ) ( HR , 1.15 ; 95 % CI , 1.03 - 1.29 ) , and albumin ( HR , 0.37 ; 95 % CI , 0.22 - 0.62 ) . Diagnostic capacity of HVPG was greater than for MELD or Child-Pugh score . CONCLUSIONS HVPG , MELD , and albumin independently predict clinical decompensation in patients with compensated cirrhosis . Patients with an HVPG < 10 mm Hg have a 90 % probability of not developing clinical decompensation in a median follow-up of 4 years Background and aims : A reliable non-invasive assessment of the severity of diffuse liver disease is much needed . We investigated the utility of hepatic vein transit times ( HVTT ) for grading and staging diffuse liver disease in a cohort of patients with hepatitis C virus ( HCV ) infection using an ultrasound microbubble contrast agent as a tracer . Material s and methods : Eighty five untreated patients with biopsy proven HCV induced liver disease were studied prospect ively . All were HCV RNA positive on polymerase chain reaction testing . Based on their histological fibrosis ( F ) and necroinflammatory ( NI ) scores , untreated patients were divided into mild hepatitis ( F ⩽2/6 , NI ⩽3/18 ) , moderate/severe hepatitis ( 3 ⩽F < 6 or NI ⩾4 ) , and cirrhosis ( F = 6/6 ) groups . In addition , 20 age matched healthy volunteers were studied . After an overnight fast , a bolus of contrast agent ( Levovist ) was injected into an antecubital vein and spectral Doppler signals were recorded from both the right and middle hepatic veins for analysis . HVTTs were calculated as the time from injection to a sustained rise in Doppler signal > 10 % above baseline . The Doppler signals from the carotid artery were also measured in 60 patients and carotid delay times ( CDT ) calculated as the difference between carotid and hepatic vein arrival times . The earliest HVTT in each patient was used for analysis . Results : Mean ( SEM ) HVTT for the control , mild hepatitis , moderate/severe hepatitis , and cirrhosis groups showed a monotonic decrease of 38.1 ( 2.8 ) , 38.8 ( 2.4 ) , 26.0 ( 2.4 ) , and 15.8 ( 0.8 ) seconds , respectively . Mean ( SEM ) CDT for the control , mild hepatitis , moderate/severe hepatitis , and cirrhosis patients again showed progressive shortening of 30.3 ( 2.6 ) , 25.9 ( 2.6 ) , 14.8 ( 2.1 ) , and 5.6 ( 1.2 ) seconds , respectively . There were significant differences between the groups for HVTT ( ANOVA , p<0.001 ) and CDT ( ANOVA , p<0.001 ) . There was 100 % sensitivity and 80 % specificity for diagnosing cirrhosis and 95 % sensitivity and 86 % specificity for differentiating mild hepatitis from more severe liver disease . Conclusion : We have shown , for the first time , that HVTT using an ultrasound microbubble contrast agent can assess HCV related liver disease with clear differentiation between mild hepatitis and cirrhosis . There were significant differences between these two groups and the moderate/severe hepatitis group . CDT offers no additional benefit or greater differentiation than HVTT and can be omitted , thus simplifying this technique . HVTT may complement liver biopsy and may also be a useful alternative for assessment of liver disease in patients who have contraindications to biopsy PURPOSE To prospect ively evaluate , in patients with liver cirrhosis , the correlation between the renovascular impedance measured by using color flow and pulsed wave Doppler ultrasonography ( US ) and the portal pressure measured by using the hepatic venous pressure gradient ( HVPG ) . MATERIAL S AND METHODS The study was approved by the senior staff committee ( comparable to institutional review board ) of the university hospital , and written informed consent was obtained from all patients . Thirty-one patients with cirrhosis ( 22 men , nine women ; mean age , 57.6 years + /- 8.8 [ st and ard deviation ] ) and esophageal varices were consecutively enrolled in the study . Having fasted , the patients underwent color flow and pulsed wave Doppler US of the right interlobar renal artery ( RRA ) and the left interlobar renal artery ( LRA ) . The resistance index ( RI ) and pulsatility index ( PI ) were determined . On the same day , with fluoroscopic guidance , a 5-F balloon-tipped catheter was advanced , via the right basilic vein , into the right hepatic vein ; HVPG was calculated as the difference between the wedged and free hepatic pressures . All measurements were performed in triplicate , and permanent tracings were recorded . Correlations were made by using the Pearson test . The positive predictive value of renovascular impedance for detection of severe portal hypertension was determined . RESULTS Mean RI and PI values were 0.67 + /- 0.07 and 1.21 + /- 0.25 , respectively , for the RRA , and 0.68 + /- 0.07 and 1.24 + /- 0.26 , respectively , for the LRA . All patients had portal hypertension ( mean HVPG , 19.3 mm Hg + /- 4.7 ; range , 11.5 - 33.5 mm Hg ) . Neither portal pressure nor renal impedance correlated with Child-Pugh score for cirrhosis . Renal artery impedance indexes correlated with the HVPG ( for RRA RI : R = 0.424 , P = .03 ; for RRA PI : R = 0.402 , P = .04 ; for LRA RI : R = 0.352 , P = .05 ; for LRA PI : R = 0.393 , P = .02 ) . A higher-than-normal renal impedance had a high positive predictive value ( RRA RI and PI , 100 % ; LRA RI , 92 % ; LRA PI , 84 % ) for the detection of severe portal hypertension . CONCLUSION Renovascular impedance had a direct correlation with HVPG AIM To assess the role of echo-Doppler ultrasonography in postpr and ial hyperemia in cirrhotic patients by comparing the results with the hepatic vein catheterization technique . METHODS Patients with cirrhosis , admitted to the portal hemodynamic laboratory were included into the study . After an overnight fast , echo-Doppler ultrasonography ( basal and 30 min after a st and ard meal ) and hemodynamic studies by hepatic vein catheterization ( basal , 15 min and 30 min after a st and ard meal ) were performed . Ensure Plus ( Abbot Laboratories , North Chicago , IL ) was used as the st and ard liquid meal . Correlation analysis of the echo-Doppler and hepatic vein catheterization measurements were done for the basal and postpr and ial periods . RESULTS Eleven patients with cirrhosis ( 5 Child A , 4 Child B , 2 Child C ) were enrolled into the study . After the st and ard meal , 8 of the 11 patients showed postpr and ial hyperemia with increase in portal blood flow , portal blood velocity and hepatic venous pressure gradient . Hepatic venous pressure gradient in the postpr and ial period correlated positively with postpr and ial portal blood velocity ( r = 0.8 , P < 0.05 ) and correlated inversely with postpr and ial superior mesenteric artery pulsatility index ( r = -1 , P < 0.01 ) . CONCLUSION Postpr and ial hyperemia can be efficiently measured by echo-Doppler ultrasonography and the results are comparable to those obtained with the hemodynamic studies OBJECTIVE : The aim of this prospect i ve study was to compare noninvasive Doppler sonography and invasive measurement of the hepatic venous pressure gradient ( HVPG ) to determine the acute portal hemodynamic response to propranolol in patients with liver cirrhosis . METHODS : In a blinded study design , portal vein velocity ( PVV ) and HVPG were simultaneously assessed in 11 cirrhotic patients for 4 h after oral ingestion of 40 mg propranolol . RESULTS : Both HVPG ( 17.2%± 4.3 % , p < 0.0001 ) and PVV ( 15.6%± 2.1 % , p < 0.0002 ) showed a highly significant reduction during the study period versus baseline . Based on HVPG measurements , four patients ( 36 % ) were classified as nonresponders . These patients had a significantly lower PVV reduction compared to the responders ( responders : 18.8%± 2.0 % vs nonresponders : 10.0%± 2.1 % , p < 0.05 ) . Nonresponders were identified by Doppler sonography with a sensitivity of 1.0 , specificity of 0.86 , and positive predictive value of 0.9 when a threshold of 20 % PVV reduction 120 min after drug intake was applied . CONCLUSIONS : Doppler sonography is a useful tool for assessment of the acute portal hemodynamic effect of propranolol . To distinguish portal hemodynamic nonresponders from responders to propranolol , PVV measurements should be carried out 2 h after drug administration , and PVV reduction should be not < 20 % in propranolol responders Background Portal hypertensive gastropathy ( PHG ) is a common endoscopic finding in patients with cirrhosis . However , the relationship between PHG and portal hypertension is controversial . Furthermore , nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis . Methods The hepatic venous pressure gradient ( HVPG ) , endoscopic PHG grade , Child – Pugh score , and model for end-stage liver disease ( MELD ) score were assessed at baseline and were followed prospect ively in 331 cirrhotic patients ( 284 males , 85.8 % ; mean age , 52.16 ± 9.05 years ) from January 2001 to April 2009 . The relationship between PHG with HVPG and survival was investigated . Results The HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG ( absent , 4.9 ± 1.7 mmHg ; mild , 10.7 ± 4.1 mmHg ; severe , 15.6 ± 4.6 mmHg ; P < 0.001 ) . During follow-up , 28 patients ( 8.5 % ) died from liver-related disease . In the Cox regression analysis , severe PHG ( none and mild vs. severe ) ( hazard ratio 1.153 , 95 % confidence interval : 1.048–1.269 ) showed a significantly high relative risk of mortality , and in the Kaplan – Meier analysis , severe PHG showed a significantly shorter expected survival time than none or mild PHG ( median survival time , 77.6 ± 9.6 months in severe PHG ; log-rank test , P = 0.030 ) . Conclusions PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis PURPOSE To evaluate the correlation between hepatic vein pressure gradient measurement and Doppler ultrasonography ( DUS ) in patients with chronic liver disease ( CLD ) . PATIENTS AND METHODS Sixty-six patients with fibrotic to cirrhotic hepatitis C virus-related CLD , were consecutively included upon referral to our haemodynamic laboratory . Superior mesenteric artery pulsatility index ( SMA-PI ) , right interlobar renal and intraparenchymal splenic artery resistance indices , were determined , followed by hepatic venous pressure gradient ( HVPG ) measurement . RESULTS A correlation was found between HVPG and intraparenchymal splenic artery resistance index ( SA-RI ) ( r=0.50 , P<0.0001 ) , SMA-PI ( r=-0,48 , P<0.0001 ) , right interlobar renal artery resistance index ( RRA-RI ) ( r=0.51 , P<0.0001 ) in the whole patient population . However , dividing patients according to the presence/absence of severe portal hypertension ( i.e. HVPG > or = 12 mmHg ) , a correlation between HVPG and intraparenchymal SA-RI ( r=0.70 , P<0.0001 ) , SMA-PI ( r=-0.49 , P=0.02 ) , RRA-RI ( r=0.66 , P=0.0002 ) was observed only for HVPG values < 12 mmHg . HVPG but not DUS correlated with the presence of esophageal varices ( P<0.0001 ) . CONCLUSIONS Superior mesenteric artery pulsatility index , intraparenchymal splenic and right interlobar renal artery resistance indices do not adequately predict severe portal hypertension PURPOSE To prospect ively evaluate both the correlation between abnormal Doppler ultrasonography ( US ) hepatic vein waveforms and the hepatic venous pressure gradient ( HVPG ) and the response to drug treatment in patients with cirrhosis . MATERIAL S AND METHODS Ethics committee approval and informed consent of patients and control subjects were obtained . In 78 patients with cirrhosis ( 70 men , eight women ; mean age , 49.4 years + /- 9.7 [ st and ard deviation ] ) and a history of variceal bleeding , both the hepatic vein waveform -- as measured with Doppler US-- and the HVPG were measured , and the relationship between them was analyzed . Hepatic vein Doppler waveforms were classified as triphasic , biphasic , or monophasic . Severe portal hypertension was defined as an HVPG of more than 15 mm Hg . In a subgroup of 21 patients , changes in hepatic vein waveform and HVPG were evaluated after intravenous administration of 2 mg of terlipressin . Statistical analyses were performed with Spearman rank correlation , logistic regression analysis , and cross tabulation . RESULTS Abnormal hepatic vein waveforms were seen in 72 patients ( 92 % ) . Forty-four patients ( 56 % ) had biphasic waveforms , 28 ( 36 % ) had monophasic waveforms , and six ( 8 % ) had triphasic waveforms . A positive correlation was found between the extent of abnormalities in hepatic vein waveforms and the increase in HVPG ( P < .05 ) . Monophasic waveforms were associated with severe portal hypertension , with a sensitivity of 74 % and a specificity of 95 % . Twenty patients in the terlipressin subgroup had abnormal baseline waveforms ; the baseline waveform improved in 18 patients in association with the HVPG reduction after injection of terlipressin . CONCLUSION Doppler US hepatic vein waveform assessment is useful in the noninvasive evaluation of the severity of portal hypertension and the response to vasoactive drugs in patients with portal hypertension and variceal bleeding The possibility of estimating portal hypertension combining splenic Doppler pulsatility index ( PI ) , which has been shown strictly to be related to portal resistance , and portal blood flow ( PBF ) was evaluated . Hepatic venous pressure gradient , and splanchnic Doppler parameters were measured in 40 cirrhotic patients . A formula to assess the severity of portal hypertension from Doppler parameters was calculated in a training group of 19 patients , and then this formula was tested to prospect ively predict the degree of portal pressure in 21 further patients . In the training group , the regression of portal resistance over splenic PI was calculated and individual values of estimated portal resistance were obtained for every patient of the test group . From them and from observed values of PBF , an estimated value of portal pressure was calculated . The following formula was obtained [ ( 0.066*splenic PI -0.044)*PBF ] . In the second group , predicted and observed portal pressure were well correlated ( r = 0.71 , p = .0003 ) . A good accuracy for the prediction of mild or severe portal hypertension was obtained BACKGROUND AND AIMS Alterations in the Doppler hepatic vein ( HV ) waveform are associated with cirrhosis and portal hypertension . We prospect ively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index ( DI ) and the hepatic venous pressure gradient ( HVPG ) and response to propranolol in patients with cirrhosis . MATERIAL AND METHODS In 76 patients with cirrhosis ( 69 men and seven women ) , both DI of Doppler HV waveform and HVPG were measured , and the relationship between them was analysed . DI was calculated by the minimum velocity/maximum velocity of the HV waveform . An HVPG>12 mmHg was defined as severe portal hypertension . In a subgroup of 19 patients receiving propranolol , changes in both DI and HVPG were evaluated after propranolol administration for 3 months . One author ( S. K. B. ) performed all DI of Doppler HV waveform studies . RESULTS Abnormal HV waveforms were seen in 66 of 76 patients ( 86.8 % ) . DI significantly correlated with the grade of HVPG , i.e. with higher HVPG increased DI was observed ( P<0.01 ) . By logistic regression analysis , DI>0.6 was significantly more likely to be severe portal hypertension ( odds ratio : 14.19 , 95 % confidence interval : 4.07 - 49.55 ) . Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9 % and a specificity of 81.8 % for the presence of severe portal hypertension . In 19 patients of the propranolol subgroup , change of DI following propranolol treatment also significantly correlated with that of HVPG ( P<0.01 ) . CONCLUSIONS Damping index of the HV waveform by Doppler ultrasonography might be a non-invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis |
2,417 | 24,572,322 | Our overall results suggest that the laser stapedotomy had significantly better hearing results than non-laser stapedotomy . | OBJECTIVE To compare and evaluate the hearing outcome and complications of otosclerosis treated with the laser or non-laser stapedotomy using meta- analysis . | BACKGROUND Otosclerosis is a progressive osteo-destructive disorder of the bony labyrinth in which the fixation of the stapes causes the hearing loss . The aim of this study was the postoperative determination of parameters of the effect of surgical intervention on hearing and the incidence of complications and , on the basis of the differences in the examined parameters of the study , the estimation of the efficacy of the two mentioned surgical techniques in the treatment of otosclerosis . METHODS In our research 40 patients with conductive hearing loss caused by otosclerosis underwent surgery with CO2 laser . Functional results were compared postoperatively with the results of 40 patients operated by the classical technique without the use of CO2 laser . The research was accomplished as a prospect i ve comparative study . RESULTS The air-bone interval ( gap ) as the difference between the rim of air and bone conductivity for separate frequencies did not significantly differ between the control and the experimental group . Both methods were effective in closing the air-bone gap with the rates of closure to within 10 dB in 82.6 % and 75.3 % for the laser and drill , respectively . The incidence of tinnitus was significantly lower in patients who underwent surgery with CO2 laser . The frequency of intraoperative and postoperative complications was significantly lower in the laser group . Differences were statistically significant for all parameters ( p < 0.05 ) . CONCLUSION On the basis of the degree of postoperative hearing improvement , tinnitus and the incidence of complications it can be concluded that the use of CO2 laser during inverse stapedoplasty represents an effective and safe method , justifying the promotion of its use in the surgical management of otosclerosis OBJECTIVE To compare three stapedotomy modalities used to fenestrate the stapes footplate in patients with primary otosclerosis . MATERIAL S The non-r and omized and unblinded one-center study included 48 patients with primary otosclerosis who underwent stapes surgery between May 2008 and April 2009 . The patients were divided into three groups ( single shot and two-shot CO(2 ) laser stapedotomy , perforator ) depending on the modality used for stapedotomy . Bone conduction ( BC ) and air conduction ( AC ) thresholds , air-bone gap ( ABG ) , and the difference between mean pre-operative and 2- to 3-week post-operative BC thresholds were analyzed . RESULTS The temporary BC deterioration was most pronounced at 6 and 8kHz after 2-shot laser stapedotomy . A significant drop in AC or BC was not found in any of our 48 patients . Age , high-dose cortisone therapy , and ' preoperative hearing ' did not influence the post-operative hearing results . CONCLUSION Even though the number of patients presented here was small and statistical analysis was limited , the study showed a trend toward worse BC thresholds at 6 and 8kHz after a second shot CO(2 ) application . Whenever possible , treatment should avoid a second laser shot on the already opened inner ear with the laser parameters used for the initial shot OBJECTIVE The aim of this study was to present our experiences and results of stapedotomy performed with and without the piezoelectric device . DESIGN The article evaluates and compares the use of the piezoelectric device in performing primary stapedotomy in patients affected by otosclerosis with the traditional method of microdrilling . SETTING The study was conducted with 100 patients in the Department of Otolaryngology of the University of Genoa ( Italy ) , between January 2007 and January 2008 . METHODS A prospect i ve , r and omized , controlled trial was undertaken on 100 stapedotomy patients performed using the piezoelectric device ( 50 patients ) or the microdrill ( 50 patients ) . MAIN OUTCOME MEASURES Before surgery and at 1 and 12 months afterward , all patients underwent the following : otomicroscopic evaluation of the external and middle ear , pure-tone audiometry , tympanometry , transient evoked otoacoustic emissions , distortion product otoacoustic emissions , and auditory brainstem response . RESULTS All patients treated with the piezoelectric device had an air-bone gap reduction , with a closure of the air-bone gap within 10 dB ; 44 ( 88 % ) patients who underwent traditional surgery had an air-bone gap reduction , with a closure of the air-bone gap within 10 dB. CONCLUSION All of our postoperative data confirm the safety of the device on the anatomic structures of the middle and inner ear and demonstrate the efficacy of the piezoelectric device in terms of safety , cutting precision , and protection of anatomic structures and its applicability to stapedotomy The early and long-term hearing results of 1,681 primary otosclerosis operations performed by the same surgeon , Jean Marquet , were review ed retrospectively and analyzed with very strict statistical st and ards . Significantly better short- and long-term results were achieved with the stapedotomy technique compared to total stapedectomy , mainly at the higher frequencies ( 4 and 8 kHz ) important for speech discrimination . Whatever technique was used to open the footplate ( micropick , microdrill , or laser ) , no statistical audiometric difference could be found . The results were equal whether or not the stapedial tendon was preserved . Perioperative problems like pronounced oozing , difficult anatomic relationships , and accidental perilymph aspiration could affect hearing at higher frequencies . The calibrated hole technique was equally as good as conventional oval window sealing in sealing of the fenestra to prevent fistula . The stapedotomy technique was found the safest , having fewer complications Objective : To valuate the influence of the color of footplate in the choice of the type of perforator . Study Design : Prospect i ve study . Level of Evidence 1b . Setting s : Single hospital study in Avellino , Italy . Subjects and Methods : From the first of September 2008 to the 30th of June 2009 , we considered 83 patients affected by otosclerosis . Patients were divided into 2 groups under footplate perforator used . In the group A , manual perforators ( the more traumatic drills ) were used . In group B , CO2 laser ( the less traumatic drill ) was used . The 2 groups under the color of visible portion of the footplate before removing the stapes superstructure were divided in 2 subgroups . Group IA includes 33 blue footplates and Group IIA 10 white footplates . Group IB includes 30 blue footplates and Group IIB 10 white footplates . We estimated whether there is statistical correlation between type of perforator , incidence of footplate complications , and color of footplate . Results : In group IA , we had 0 complications . In group IB , we had 0 complications . In group IIA , we had 7 complications . In group IIB , we had 2 complications . Comparison of incidence of footplate complications showed no statistical significance between group IA and IB and statistical significance between group IIA and IIB . Conclusion : The footplate color is important in the choice of the type of perforator Objective : To assess whether the incidence of complications of stapes surgery depended on the sequence of surgical steps and CO2 laser use in stapes surgery . Study Design and Setting : Retrospective and prospect i ve analysis of 420 consecutive stapedotomies was set in tertiary referral University Hospital . Patients : 376 patients with otosclerosis in whom 420 primary stapedotomies were performed . Intervention : Stapedotomy under local anesthesia using manual perforators and CO2 laser . Main Outcome Measure : The incidence of incus subluxation , floating footplate during stapedotomy . Results : Comparison of the incidence of incus luxation in groups with the piston inserted after removal of the stapes arch , and groups with the piston inserted on the intact ossicular chain showed statistical significance . In the group where perforation of the footplate was performed after removal of the stapes arch floating footplate occurred more often than in groups with reversed sequence of steps . Conclusion : Perforation of the footplate before removal of stapes arch reduces the risk of floating footplate , and placing the prosthesis on the incus before removal of stapes arch reduces the risk of subluxation of the incus . CO2 laser stapedotomy with reversed sequence of steps was the safest method of stapes surgery Thirty-four ears with conductive hearing loss due to otosclerosis were operated upon using the laser stapedotomy technique . Audiological results were compared with the results of 316 non-laser stapedotomies . The post-operative air-bone gap , calculated as the difference between the post-operative air and bone conduction levels , was smaller with the laser stapedotomy group . Also , the bone conduction showed significant improvement with the use of laser . Significant sensorineural hearing loss was not found in any of the laser-treated patients . According to our results , we concluded that laser is of benefit in stapes surgery for improving the hearing results and minimizing the inner ear trauma |
2,418 | 19,390,962 | Multiple fertility-related information needs specific to this group regarding menstrual changes and potential infertility attitudes to , and actual decisions made regarding , pregnancy breastfeeding and contraception emerged .
Information on fertility-related decisions was rated as important , and the preferred methods for obtaining this information was consultation with a specialist or a decision aid early in the treatment plan .
There is limited research about fertility-related needs , and even less on contraceptive preferences and the attitudes of health care providers towards fertility-related issues .
Young women with early breast cancer have specific fertility- and menopause-related needs and concerns , which are commonly not adequately addressed or discussed prior to commencing adjuvant therapy | Breast cancer is the most commonly diagnosed type of cancer in reproductive aged women .
Adjuvant systemic therapy is recommended in most women and has been demonstrated to reduce the risk of recurrence and increase survival .
However , there may be a negative impact of adjuvant systemic therapy on fertility as well as on subsequent quality of life .
There are a number of fertility preservation options currently available and relevant information regarding these options should be provided prior to commencing adjuvant treatment .
The aim of the review is to identify the fertility-related needs , concerns and preferences of young women with early breast cancer . | A prospect i ve study was conducted with early breast cancer patients who had either been offered , or not been offered , a choice of surgery for treatment . The choice involved mastectomy or wide excision plus radiotherapy . Available evidence suggests that the medical outcome between these two options is similar ; this study was design ed to investigate selected psychosocial outcomes . It was found that whether or not patients were given a choice was of greater relevance to psychosocial outcomes that was the type of operation performed . Providing a choice led to improved reported adjustments with respect to the ability to undertake work , attitudes towards the future , beliefs about coping , and in physical and psychological functioning PURPOSE To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer . METHODS An expert panel and a writing committee were formed . The questions to be addressed by the guideline were determined , and a systematic review of the literature from 1987 to 2005 was performed , and included a search of online data bases and consultation with content experts . RESULTS The literature review found many cohort studies , case series , and case reports , but relatively few r and omized or definitive trials examining the success and impact of fertility preservation methods in people with cancer . Fertility preservation methods are used infrequently in people with cancer . RECOMMENDATIONS As part of education and informed consent before cancer therapy , oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists . Clinician judgment should be employed in the timing of raising this issue , but discussion at the earliest possible opportunity is encouraged . Sperm and embryo cryopreservation are considered st and ard practice and are widely available ; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise . CONCLUSION Fertility preservation is often possible in people undergoing treatment for cancer . To preserve the full range of options , fertility preservation approaches should be considered as early as possible during treatment planning PURPOSE To study the sexual effects of the 2-year adjuvant goserelin ( Zoladex [ Zeneca AB , Södertälje , Sweden ] ) alone , tamoxifen alone , and Zoladex and tamoxifen in combination ( ZT ) versus no adjuvant endocrine therapy among premenopausal breast cancer patients with or without chemotherapy in a controlled clinical trial ( a European multicenter trial : Zoladex in Premenopausal Breast Cancer Patients ) . PATIENTS AND METHODS This prospect i ve study examined several aspects of sexuality through the use of self-administered question naires , which were completed by patients at seven points of assessment for 3 years after r and omization . RESULTS Patients treated with chemotherapy had a higher level of sexual dysfunction than did patients who received no systemic treatment . The addition of endocrine treatment did not alter this result . In contrast , among patients who did not receive chemotherapy , Zoladex and ZT produced a significantly higher level of dysfunction from 1 to 2 years after inclusion , as compared with those who received no endocrine treatment . Tamoxifen alone did not produce side effects . After termination of endocrine treatment , sexual dysfunction began to diminish . Those with chemotherapy had high and frequently increasing levels of dysfunction even after 2 to 3 years of independent of endocrine treatment . Zoladex had a negative effect on sexual fear , which was reduced by the addition of tamoxifen . CONCLUSION Zoladex increased sexual dysfunction during treatment among patients without chemotherapy , but the disturbances of sexual functioning were reversible . The use of adjuvant chemotherapy was associated with continued sexual problems , even at 3 years after r and omization Patient autonomy and participation in treatment decision making have been encouraged in recent years . However , patients and physicians frequently disagree with regard to the patient 's needs and perceptions of their illness . To the authors ' knowledge to date only limited research has assessed physicians ' perceptions of patients ' decision‐making preferences . The purpose of the current prospect i ve study was to determine the agreement between patient decision‐making preferences and physician perceptions of those preferences PURPOSE Young women who undergo chemotherapy for breast cancer face serious consequences to their reproductive health . Research in this area has previously focused on men , or on childhood cancer survivors . We sought to explore self-report of reproductive health counseling in young women undergoing chemotherapy for breast cancer . PATIENTS AND METHODS A total of 166 premenopausal women aged < or = 50 years were recruited from oncology offices in academic and private practice s in four northeastern states , as part of a r and omized controlled clinical trial aim ed at stress reduction . Women were asked a variety of questions regarding diagnosis and treatment , including whether they received any counseling regarding early menopause and fertility issues . RESULTS Sixty-eight percent and 34 % of women reported recalling a discussion with a physician regarding early menopause or fertility , respectively . In multivariate analysis , hormonal therapy and early stage of disease were associated with significantly increased odds of recall of a discussion regarding menopause . Difficulty communicating with medical team was associated with increased odds of recalling a discussion regarding fertility , whereas older age and anxiety in medical situations were associated with decreased odds . CONCLUSION Many women fail to recall discussion s regarding the reproductive health impact of chemotherapy . Demographic , psychological , and disease-related variables are related to recalling such discussion s. Counseling about premature menopause and fertility changes is an overlooked aspect of preparation for adjuvant chemotherapy in young premenopausal women with breast cancer . Future research should explore this issue further |
2,419 | 27,572,719 | End-diastolic interventricular septal thickness showed a small decrease in the smaller of the two included studies .
There were no deaths related to the treatment with antioxidants .
A single study of idebenone provided low- quality evidence for a decrease in LVM , which is of uncertain clinical significance but of potential importance that needs to be clarified .
According to low- quality evidence , serious and non-serious adverse events were rare in both antioxidant and placebo groups . | BACKGROUND Friedreich ataxia is a rare inherited autosomal recessive neurological disorder , characterised initially by unsteadiness in st and ing and walking , slowly progressing to wheelchair dependency usually in the late teens or early twenties .
It is associated with slurred speech , scoliosis , and pes cavus .
Heart abnormalities cause premature death in 60 % of people with the disorder .
There is no easily defined clinical or biochemical marker and no known treatment .
This is the second up date of a review first published in 2009 and previously up date d in 2012 .
OBJECTIVES To assess the effects of pharmacological treatments for Friedreich ataxia . | BACKGROUND Erythropoietin ( EPO ) derivatives have been found to increase frataxin levels in Friedreich 's ataxia ( FRDA ) in vitro . This multicenter , double-blind , placebo-controlled , phase II clinical trial aim ed to evaluate the safety and tolerability of Lu AA24493 ( carbamylated EPO ; CEPO ) . METHODS Thirty-six ambulatory FRDA patients harboring > 400 GAA repeats were 2:1 r and omly assigned to either CEPO in a fixed dose ( 325 µg thrice-weekly ) or placebo . Safety and tolerability were assessed up to 103 days after baseline . Secondary outcome measures of efficacy ( exploration of biomarkers and ataxia ratings ) were performed up to 43 days after baseline . RESULTS All patients received six doses of study medication . Adverse events were equally distributed between CEPO and placebo . There was no evidence for immunogenicity of CEPO after multiple dosing . Biomarkers , such as frataxin , or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo . CONCLUSION CEPO was safe and well tolerated in a 2-week treatment phase . Secondary outcome measures remained without apparent difference between CEPO and placebo BACKGROUND AND PURPOSE A pilot study of high dose coenzyme Q(10 ) ( CoQ(10))/vitamin E therapy in Friedreich 's ataxia ( FRDA ) patients result ed in significant clinical improvements in most patients . This study investigated the potential for this treatment to modify clinical progression in FRDA in a r and omized double blind trial . METHODS Fifty FRDA patients were r and omly divided into high or low dose CoQ(10)/ vitamin E groups . The change in International Co-operative Ataxia Ratings Scale ( ICARS ) was assessed over 2 years as the primary end-point . A post hoc analysis was made using cross-sectional data . RESULTS At baseline serum CoQ(10 ) and vitamin E levels were significantly decreased in the FRDA patients ( P < 0.001 ) . During the trial CoQ(10 ) and vitamin E levels significantly increased in both groups ( P < 0.01 ) . The primary and secondary end-points were not significantly different between the therapy groups . When compared to cross-sectional data 49 % of all patients demonstrated improved ICARS scores . This responder group had significantly lower baseline serum CoQ(10 ) levels . CONCLUSIONS A high proportion of FRDA patients have a decreased serum CoQ(10 ) level which was the best predictor of a positive clinical response to CoQ(10)/vitamin E therapy . Low and high dose CoQ(10)/vitamin E therapies were equally effective in improving ICARS scores Background : Friedreich ’s ataxia ( FRDA ) , the most common genetic cause of ataxia , is characterised by progressive neurodegeneration and cardiomyopathy . Initial treatments are likely to slow progression rather than reverse morbidity . An appropriate and sensitive scale to measure disease progress is critical to detect the benefit of treatments . Objective : To compare the Friedreich Ataxia Rating Scale ( FARS ) with other scales proposed as outcome measures for FRDA . Methods : 76 participants were assessed with the FARS and the International Cooperative Ataxia Rating Scale ( ICARS ) and 72 of these participants were also assessed with the Functional Independence Measure and the Modified Barthel Index . 43 participants had repeat measures at an interval of 12 months . Sensitivity and responsiveness were assessed using the effect size for each measure and the sample size required for a placebo-controlled clinical trial . Results : The FARS showed a high correlation with the other three measures . A significant change in the score over 12 months was detected by the FARS , the International Cooperative Ataxia Rating Scale and the Functional Independence Measure . The FARS had the greatest effect size and requires fewer patients for an equivalently powered study . Conclusions : Of the scales assessed , the FARS is the best to use in clinical trials of FRDA . This is based on effect size , and power calculations that show that fewer participants are required to demonstrate the same effect of an intervention . Further work is required to develop more sensitive and responsive instruments Background — This cross-sectional study provides a practical approach for the clinical assessment of Friedreich ataxia ( FA ) cardiomyopathy ( FA-CM ) . Methods and Results — A comprehensive cardiac assessment , including st and ard echocardiography , color Doppler myocardial imaging , cardiac magnetic resonance imaging , ECG , and exercise stress testing , was performed in 205 FA patients . To assess myocardial hypertrophy in FA-CM , the end-diastolic interventricular septal wall thickness ( IVSTd ) was found to be the best echocardiographic parameter compared with cardiac magnetic resonance imaging – determined left ventricular mass . With the use of this parameter , 4 groups of patients with FA-CM could be defined . Patients with normal values for IVSTd ( 31.7 % ) were classified as having no FA-CM . Patients with an IVSTd exceeding the predicted normal IVSTd were classified as having mild FA-CM ( 40 % ) if IVSTd exceeded the normal value by < 18 % or as having intermediate FA-CM ( 16.1 % ) if IVSTd exceeded the normal value by ≥18 % . Patients with ejection fraction < 50 % were classified as having severe FA-CM ( 12.2 % ) . In addition to increased myocardial mass , severe FA-CM was further characterized by dilatation of the left ventricle , reduced systolic strain rate of the posterior wall , and ECG abnormalities . Regional myocardial function correlated negatively with FA-CM groups . Younger patients had a tendency for more advanced FA-CM . Importantly , no clear correlation was found between FA-CM groups and neurological function . Conclusions — We provide and describe a readily applicable clinical grouping of the cardiomyopathy associated with FA based on echocardiographic IVSTd and ejection fraction data . Because no distinct interrelations between FA-CM and neurological status could be determined , regular follow-up of potential cardiac involvement in FA patients is essential in clinical practice . Clinical Trial Registration — https://www . clinical trials.gov . Unique identifier : NCT00905268 Genetic disorders of iron metabolism and chronic inflammation often evoke local iron accumulation . In Friedreich ataxia , decreased iron-sulphur cluster and heme formation leads to mitochondrial iron accumulation and ensuing oxidative damage that primarily affects sensory neurons , the myocardium , and endocrine gl and s. We assessed the possibility of reducing brain iron accumulation in Friedreich ataxia patients with a membrane-permeant chelator capable of shuttling chelated iron from cells to transferrin , using regimens suitable for patients with no systemic iron overload . Brain magnetic resonance imaging ( MRI ) of Friedreich ataxia patients compared with age-matched controls revealed smaller and irregularly shaped dentate nuclei with significantly ( P < .027 ) higher H-relaxation rates R2 * , indicating regional iron accumulation . A 6-month treatment with 20 to 30 mg/kg/d deferiprone of 9 adolescent patients with no overt cardiomyopathy reduced R2 * from 18.3 s(-1 ) ( + /- 1.6 s(-1 ) ) to 15.7 s(-1 ) ( + /- 0.7 s(-1 ) ; P < .002 ) , specifically in dentate nuclei and proportionally to the initial R2 * ( r = 0.90 ) . Chelator treatment caused no apparent hematologic or neurologic side effects while reducing neuropathy and ataxic gait in the youngest patients . To our knowledge , this is the first clinical demonstration of chelation removing labile iron accumulated in a specific brain area implicated in a neurodegenerative disease . The use of moderate chelation for relocating iron from areas of deposition to areas of deprivation has clinical implication s for various neurodegenerative and hematologic disorders OBJECTIVE To assess the efficacy of idebenone on neurological function in patients with Friedreich ataxia . DESIGN R and omized , double-blind , placebo-controlled intervention trial . SETTING Children 's Hospital of Philadelphia and the University of California at Los Angeles . PARTICIPANTS Seventy ambulatory pediatric patients ( age , 8 - 18 years ) with a baseline International Cooperative Ataxia Rating Scale ( ICARS ) score of 10 to 54 . INTERVENTIONS Participants were r and omized into 1 of 3 treatment arms : 450 or 900 mg of idebenone per day ( in those with a body weight < or = or > 45 kg , respectively ; n = 22 ) ; 1350 or 2250 mg of idebenone per day ( n = 24 ) ; or placebo ( n = 24 ) . MAIN OUTCOME MEASURES Mean change from baseline to week 24 in ICARS score was the primary efficacy variable . Mean change in Friedreich Ataxia Rating Scale ( FARS ) score , performance measures , and activities of daily living were the secondary efficacy variables . RESULTS Patients who received idebenone improved by 2.5 points on mean ICARS score compared with baseline , while patients in the placebo group improved by 1.3 points . Patients who took idebenone also improved by 1.6 points on the FARS , while patients taking placebo declined by 0.6 points . For both end points , the difference between the idebenone and placebo groups was not statistically different . CONCLUSIONS Idebenone did not significantly alter neurological function in Friedreich ataxia during the 6-month study . Larger studies of longer duration may be needed to assess the therapeutic potential of drug c and i date s on neurological function in Friedreich ataxia . Trial Registration clinical trials.gov Identifier : NCT00537680 Fast breath-hold cardiovascular magnetic resonance ( CMR ) shows excellent results for inter study reproducibility of left ventricular ( LV ) volumes , ejection fraction , and mass , which are thought to be superior to results of 2-dimensional echocardiography . However , there is no direct comparison of the inter study reproducibility of both methods in the same subjects . A total of 60 subjects ( normal volunteers [ n = 20 ] , or patients with heart failure [ n = 20 ] or LV hypertrophy [ n = 20 ] ) underwent 2 CMRs and 2 echocardiographic studies for assessment of LV volumes , function , and mass . The inter study reproducibility coefficient of variability was superior for CMR in all groups for all parameters . Statistical significance was reached for end-systolic volume ( 4.4 % to 9.2 % vs 13.7 % to 20.3 % , p < 0.001 ) , ejection fraction ( 2.4 % to 7.3 % vs 8.6 % to 19.4 % , p < 0.001 ) , and mass ( 2.8 % to 4.8 % vs 11.6 % to 15.7 % p < 0.001 ) , with a trend for end-diastolic volume ( 2.9 % to 4.9 % vs 5.5 % to 10.5 % , p = 0.17 ) . The superior inter study reproducibility result ed in considerably lower calculated sample sizes ( reductions of 55 % to 93 % ) required by CMR compared with echocardiography to show clinical ly relevant changes in LV dimensions and function . Thus , CMR has excellent inter study reproducibility in normal , dilated , and hypertrophic hearts , and is superior to 2-dimensional echocardiography BACKGROUND Antioxidant therapy is a new therapeutical approach for patients with Friedreich ataxia . AIMS To assess the effectiveness of long-term idebenone treatment in Friedreich ataxia patients . METHODS An open-labelled prospect i ve study . Ten paediatric patients ( age range 8 - 18 years ) and 14 adults ( age range 18 - 46 years ) with genetic diagnosis of Friedreich ataxia were treated with idebenone ( 5 - 20mg/kg/day ) for 3 - 5 years . Neurological evolution was evaluated using the International Cooperative Ataxia Rating Scale ( ICARS ) , and cardiological outcomes using echocardiography . RESULTS In paediatric patients , no significant differences were observed in ICARS scores and echocardiographic measurements when comparing baseline status and after 5 years of follow-up . Concerning adult cases , ICARS scores showed a significant increase in neurological dysfunctions during 3 years of therapy ( Wilcoxon test , p=0.005 ) , while echocardiographic measurements remained unchanged . CONCLUSIONS Our results indicate that longer-term idebenone treatment prevented progression of cardiomyopathy in both paediatric and adult patients , whereas its stabilizing effect on neurological dysfunction was present only in the paediatric population , mainly before puberty . This suggests that the age at which idebenone treatment is initiated may be an important factor in the effectiveness of the therapy To determine the role of recombinant human erythropoietin as a possible treatment option in Friedreich 's ataxia , we performed an open‐label clinical pilot study . Primary outcome measure was the change of frataxin levels at week 8 versus baseline . Twelve Friedreich 's ataxia patients received 5,000 units recombinant human erythropoietin three times weekly subcutaneously . Frataxin levels were measured in isolated lymphocytes by enzyme‐linked immunosorbent assay . In addition , urinary 8‐hydroxydeoxyguanosine and serum peroxides , were measured . Treatment with recombinant human erythropoietin showed a persistent and significant increase in frataxin levels after 8 weeks ( p < 0.01 ) . All patients showed a reduction of oxidative stress markers . Ann Neurol The objective of the study was to test the efficacy , safety and tolerability of triple therapy with deferiprone , idebenone and riboflavin in Friedreich 's ataxia ( FRDA ) patients in a clinical pilot study BACKGROUND Friedreich 's ataxia ( FA ) is a progressive , multisystem , degenerative disorder caused by a reduction in frataxin . Loss of frataxin results in mitochondrial dysfunction and oxidative damage in patients and model systems . Previous studies have indicated that the antioxidant idebenone ( 5 mg/kg daily ) reduces cardiac hypertrophy , but definite improvement in neurological function has not been shown . METHODS 48 genetically confirmed FA patients , aged 9 - 17 years , were enrolled in a 6-month , r and omised , double-blind , placebo-controlled study . The patients received placebo or one of three doses of idebenone ( approximately 5 mg/kg , 15 mg/kg , and 45 mg/kg ) , stratified by body weight . The primary endpoint was change from baseline in urinary 8-hydroxy-2'-deoxyguanosine ( 8OH2'dG ) , a marker of oxidative DNA damage . Secondary endpoints included changes in the international cooperative ataxia rating scale ( ICARS ) , the FA rating scale ( FARS ) , and a survey of activities of daily living ( ADL ) . This study is registered with Clinical Trials.gov , number NCT00229632 . FINDINGS Idebenone was generally well tolerated with similar numbers of adverse events in each group . One child receiving high-dose idebenone developed neutropenia after 6 months , which resolved after discontinuation of treatment . 8OH2'dG concentrations were not increased , and did not significantly change with idebenone treatment . Whereas an overall analysis did not show a significant difference in ICARS , FARS , or ADL total scores , there were indications of a dose-dependent response in the ICARS score . A second , pre-specified analysis , excluding patients who required wheelchair assistance , showed a significant improvement in ICARS ( Bonferroni p=0.03 ) and suggested a dose-related response in ICARS , FARS , and ADL scores . INTERPRETATION Treatment with higher doses of idebenone was generally well tolerated and associated with improvement in neurological function and ADL in patients with FA . The degree of improvement correlated with the dose of idebenone , suggesting that higher doses may be necessary to have a beneficial effect on neurological function BACKGROUND Antioxidant therapy has been applied to Friedreich 's ataxia patients . We assessed the effect of idebenone treatment in patients with Friedreich 's ataxia . METHODS DESIGN open-label trial . Nine Friedreich 's ataxia patients ( age range 11 - 19 years ) were treated with idebenone ( 5 mg/kg/day ) . Patients were evaluated before the start of the therapy and throughout one year of treatment by International Cooperative Ataxia Rating Scales ( ICARS ) scores , neurophysiological investigations and echocardiographic measurements . Serum idebenone concentrations were measured by HPLC with electrochemical detection . The number of GAA repeats at the frataxin gene was analyzed by PCR . RESULTS Serum idebenone concentrations ranged between 0.04 - 0.37 micro mol/L. Significantly positive correlation was observed between idebenone values and the percentage of difference between the ICARS scores before and 12 months after the start of the therapy ( r = 0.883 ; p = 0.002 ) . Significant reduction was observed comparing the ICARS scores in baseline conditions and after 3 months of treatment ( p = 0.017 ) . No differences were observed in echocardiographic measurements after the start of the therapy . CONCLUSIONS Cerebellar improvement was notable in mild patients after the first 3 months of therapy . Idebenone treatment at early stages of the disease seems to reduce the progression of cerebellar manifestations . Further blind trials with a greater number of patients and higher doses are needed to fully assess the therapeutic potential of idebenone in Friedreich 's ataxia Summary .Impaired oxidative phosphorylation is a crucial factor in the pathogenesis of Friedreich ’s ataxia ( FA ) . L-carnitine and creatine are natural compounds that can enhance cellular energy transduction . We performed a placebo-controlled triple-phase crossover trial of L-carnitine ( 3 g/d ) and creatine ( 6.75 g/d ) in 16 patients with genetically confirmed FA . Primary outcome measures were mitochondrial ATP production measured as phosphocreatine recovery by 31Phosphorus magnetic resonance spectroscopy , neurological deficits assessed by the international co-operative ataxia rating scale and cardiac hypertrophy in echocardiography . After 4 months on L-carnitine phosphocreatine recovery was improved compared to baseline ( p < 0.03 , t-test ) but comparison to placebo and creatine effects did not reach significance ( p = 0.06 , F-test ) . Ataxia rating scale and echocardiographic parameters remained unchanged . Creatine had no effect in FA patients . L-carnitine is a promising substance for the treatment of FA patients , and larger trials are warranted Friedreich ataxia ( FRDA ) is an autosomal recessive inherited neurodegenerative disorder leading to reduced expression of the mitochondrial protein frataxin . Previous studies showed frataxin upregulation in FRDA following treatment with recombinant human erythropoietin ( rhuEPO ) . Dose – response interactions between frataxin and rhuEPO have not been studied until to date . We administered escalating rhuEPO single doses ( 5,000 , 10,000 and 30,000 IU ) in monthly intervals to five adult FRDA patients . Measurements of frataxin , serum erythropoietin levels , iron metabolism and mitochondrial function were carried out . Clinical outcome was assessed using the “ Scale for the assessment and rating of ataxia ” . We found maximal erythropoietin serum concentrations 24 h after rhuEPO application which is comparable to healthy subjects . Frataxin levels increased significantly over 3 months , while ataxia rating did not reveal clinical improvement . All FRDA patients had considerable ferritin decrease . NADH/NAD ratio , an indicator of mitochondrial function , increased following rhuEPO treatment . In addition to frataxin upregulation in response to continuous low-dose rhuEPO application shown in previous studies , our results indicate for a long-lasting frataxin increase after single high-dose rhuEPO administration . To detect frataxin-derived neuroprotective effects result ing in clinical ly relevant improvement , well- design ed studies with extended time frame are required BACKGROUND Friedreich ataxia ( FA ) is the most frequent autosomal recessive cerebellar ataxia . Although the phenotype is well known , disease progression has not been evaluated in a prospect i ve manner . OBJECTIVE To perform a long-term prospect i ve follow-up of neurological , cardiological , and oculomotor function in patients with FA ( FA patients ) . DESIGN In this open-labeled prospect i ve survey , we examined 104 FA patients every 6 months during a median period of 5 years ( range , 6 months to 7 years ) , with a systematic st and ardized protocol . Data are reported as mean + /- SD . SETTING Neurological examinations were performed at the Federation of Neurology and the Department of Genetics of the Salpêtrière Hospital , Paris , France . Cardiological follow-up was performed at the Department of Cardiology ; oculomotor examinations were performed at the Institut National de la Santé et de la Récherche Médicale Unit 679 , at the same hospital . Patients We studied 104 FA patients with a confirmed molecular diagnosis . None were receiving antioxidant therapy at baseline ; 88 accepted treatment with the coenzyme Q(10 ) analogue idebenone ( 5 mg/kg per day ) . Sixteen preferred not to be treated . INTERVENTIONS Neurological status was evaluated with the International Cooperative Ataxia Rating Scale ( ICARS ) and a quantitative writing test . Cardiological evaluations included echocardiography , electrocardiography , and Holter monitoring . Oculomotor function was evaluated by electro-oculography to determine the frequency of square wave jerks . RESULTS The total ICARS score worsened during follow-up , whether or not the patients were treated with idebenone ( 1.93 + /- 0.25 and 4.43 + /- 1.56 points per year , respectively ) . The total ICARS score increased faster in patients with onset before age 15 years compared with the others ( 2.6 + /- 0.4 [ n = 51 ] vs 1.1 + /- 0.3 [ n = 37 ] ; P = .05 ) . The posture subscore increased faster in patients able to st and at baseline , who also had shorter disease duration s than patients unable to st and ( 1.25 + /- 0.12 vs 0.47 + /- 0.22 point per year ; P<.001 ) . Neurological progression was underestimated , however , by the ICARS scores , which reached a plateau in patients with long disease duration s. Oculomotor function slightly deteriorated ( 0.09 + /- 0.02 Hz per year ; P<.001 ) . Left ventricular mass index decreased ( -4.1 + /- 1.5 g/m(2 ) per year ; P = .008 ) , as did ejection fraction ( -1.32 % + /- 0.29 % per year ; P<.001 ) . CONCLUSIONS The neurological condition of FA patients deteriorated slowly over time , even with idebenone treatment . Although cardiac hypertrophy decreased under treatment , cardiac function did not improve . The ICARS scale is not appropriate to evaluate the progression of FA in patients with long disease duration s. Additional quantitative measures may improve the reliability of this scale Background : Friedreich 's ataxia encodes a protein of unknown function , frataxin . The loss of frataxin is caused by a large GAA trinucleotide expansion in the first intron of the gene , result ing in deficiency of a Krebs cycle enzyme , aconitase , and of three mitochondrial respiratory chain complexes ( I – III ) . This causes oxidative stress . Idebenone , a short chain quinone acting as an antioxidant , has been shown to protect heart muscle against oxidative stress in some patients . Objective : To assess the efficiency of idebenone on cardiac hypertrophy in Friedreich 's ataxia . Design : Prospect i ve , open trial . Setting : Tertiary care centre . Methods : Idebenone ( 5 mg/kg/day ) was given orally to 38 patients with Friedreich 's ataxia aged 4–22 years ( 20 males , 18 females ) . Cardiac ultrasound indices were recorded before and after idebenone treatment . Results : After six months , cardiac ultrasound indicated a reduction in left ventricular mass of more than 20 % in about half the patients ( p < 0.001 ) . The shortening fraction was initially reduced in six of the 38 patients ( by between 11–26 % ) and it improved in five of these . In one patient , the shortening fraction only responded to 10 mg/kg/day of idebenone . No correlation was found between responsiveness to idebenone and age , sex , initial ultrasound indices , or the number of GAA repeats in the frataxin gene . Conclusions : Idebenone is effective at controlling cardiac hypertrophy in Friedreich 's ataxia . As the drug has no serious side effects , there is a good case for giving it continuously in a dose of 5–10 mg/kg/day in patients with Friedreich 's ataxia at the onset of hypertrophic cardiomyopathy The authors report 1-year prospect i ve data on eight patients with Friedreich ataxia . Idebenone did not halt the progression of ataxia . At the end of therapy , cardiac ultrasound demonstrated significant reduction of cardiac hypertrophy in six of eight patients . Cardiac strain and strain rate imaging showed that the reduction of hypertrophy is preceded by an early and linear improvement in cardiac function . Idebenone reduced erythrocyte protoporphyrin IX levels in five of six patients with elevated baseline levels ; however , changes did not consistently relate to cardiac improvement We conducted a 6‐month , r and omized , double‐blind , placebo‐controlled study to assess safety , tolerability , and efficacy of deferiprone in Friedreich ataxia ( FRDA ) BACKGROUND Friedreich ataxia ( FRDA ) is commonly associated with hypertrophic cardiomyopathy , but little is known about its frequency , severity , or treatment . In this 6-month r and omized , double-blind , controlled study , we sought to determine whether idebenone improves cardiac measures in FRDA . METHODS Seventy pediatric subjects were treated either with idebenone ( 450/900 mg/d or 1,350/2,250 mg/d ) or with placebo . Electrocardiograms ( ECGs ) were assessed at each visit , and echocardiograms , at baseline and week 24 . RESULTS We found ECG abnormalities in 90 % of the subjects . On echocardiogram , 81.4 % of the total cohort had left ventricular ( LV ) hypertrophy , as measured by increased LV mass index-Dubois , and the mean ejection fraction ( EF ) was 56.9 % . In linear regression models , longer PR intervals at baseline were marginally associated with longer GAA repeat length ( P = .011 ) . Similarly , GAA repeat length did not clearly predict baseline EF ( P = .086 ) and LV mass by M-mode ( P = .045 ) . Left ventricular mass index , posterior wall thickness , EF , and ECG parameters were not significantly improved by treatment with idebenone . Some changes in echocardiographic parameters during the treatment phase correlated with baseline status but not with treatment group . CONCLUSIONS Idebenone did not decrease LV hypertrophy or improve cardiac function in subjects with FRDA . The present study does not provide evidence of benefit in this cohort over a 6-month treatment period Objective of the study was to test the efficacy , safety , and tolerability of two single doses of Epoetin alfa in patients with Friedreich 's ataxia . Ten patients were treated subcutaneously with 600 IU/kg for the first dose , and 3 months later with 1200 IU/kg . Epoetin alfa had no acute effect on frataxin , whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose ( + 35 % ; P < 0.05 ) , and up to 6 months after the second dose ( + 54 % ; P < 0.001 ) . The treatment was well tolerated and did not affect hematocrit , cardiac function , and neurological scale . Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted . In addition , no hemoglobin increase was observed , and none of our patients required phlebotomy , indicating lack of erythropoietic effect of single high dose of erythropoietin The authors carried out a 1-year , r and omized , placebo-controlled trial of idebenone in 29 patients with Friedreich ataxia . They found significant reductions of interventricular septal thickness and left ventricular mass in the idebenone group vs the placebo group , with no improvement in other heart ultrasound measures or neurologic condition . The absolute cardiac changes were modest , but the findings suggest that larger trials should assess whether idebenone reduces ventricular hypertrophy in patients with Friedreich ataxia To investigate whether a histone deacetylase inhibitor ( HDACi ) would be effective in an in vitro model for the neurodegenerative disease Friedreich ataxia ( FRDA ) and to evaluate safety and surrogate markers of efficacy in a phase I clinical trial in patients |
2,420 | 27,920,977 | Conclusion This review provides evidence for alterations in the biochemical profile of the brain in patients with CLBP , which suggests that biochemical changes may play a significant role in the development and pathophysiology of CLBP and shed light on the development of new treatments for CLBP | Background Low back pain is a highly prevalent health problem around the world , affecting 50 % to 85 % of people at some point in life .
The purpose of this systematic review is to summarize the previous proton magnetic resonance spectroscopy studies on brain chemical changes in patients with chronic low back pain ( CLBP ) . | Summary . The neurobiology of the interaction between pain and anxiety is unknown . The present study examined interrelationships between : regional brain chemistry ( as identified by in vivo proton magnetic resonance spectroscopy [ 1H-MRS ] in dorsolateral prefrontal cortex [ DLPFC ] , orbitofrontal cortex [ OFC ] , cingulate and thalamus ) , pain ( as measured by short form of the McGill Pain Question naire [ SF-MPQ ] ) , and anxiety ( measured by the State-Trait Anxiety Inventory ) in chronic low back pain ( CLBP ) patients , and contrasted to the relationship between brain chemistry and anxiety in sex and age-matched normal subjects . The results show that brain chemistry depends on a 3-way interaction of brain regions examined , subject groups ( normal vs. CLBP ) , and anxiety levels ( high vs. low ) . The concentration of N-Acetyl aspartate ( the largest peak in 1H-MRS ) in OFC could distinguish between anxiety levels and between subject groups . Chemical-perceptual relationships were analyzed by calculating correlations between regional chemicals and perceptual measures of pain and anxiety . To isolate pain from anxiety , these maps were subdivided based on anxiety and , in the CLBP patients along anxiety-more-related vs. anxiety-less-related pain descriptors and along sensory vs. affective pain descriptors . There was a precise relationship between perception and brain chemistry . The chemical-perceptual network best related to pain in CLBP patients was comprised of the DLPFC and OFC ; the chemical-anxiety network was best related to the OFC chemistry in normals and to all four regions studied in CLBP patients ; and the cingulate was best related to the affective component of pain . We conclude that the chemical-perceptual mapping differentiates between closely related perceptual states of pain and anxiety in chronic pain and provides a brain regional-chemical-perceptual description of the long-term reorganization that occurs with chronic pain Functional neuroimaging studies in humans have shown that nociceptive stimuli elicit activity in a wide network of cortical areas commonly labeled as the " pain matrix " and thought to be preferentially involved in the perception of pain . Despite the fact that this " pain matrix " has been used extensively to build models of where and how nociception is processed in the human brain , convincing experimental evidence demonstrating that this network is specifically related to nociception is lacking . The aim of the present study was to determine whether there is at least a subset of the " pain matrix " that responds uniquely to nociceptive somatosensory stimulation . In a first experiment , we compared the fMRI brain responses elicited by a r and om sequence of brief nociceptive somatosensory , non-nociceptive somatosensory , auditory and visual stimuli , all presented within a similar attentional context . We found that the fMRI responses triggered by nociceptive stimuli can be largely explained by a combination of ( 1 ) multimodal neural activities ( i.e. , activities elicited by all stimuli regardless of sensory modality ) and ( 2 ) somatosensory-specific but not nociceptive-specific neural activities ( i.e. , activities elicited by both nociceptive and non-nociceptive somatosensory stimuli ) . The magnitude of multimodal activities correlated significantly with the perceived saliency of the stimulus . In a second experiment , we compared these multimodal activities to the fMRI responses elicited by auditory stimuli presented using an oddball paradigm . We found that the spatial distribution of the responses elicited by novel non-target and novel target auditory stimuli resembled closely that of the multimodal responses identified in the first experiment . Taken together , these findings suggest that the largest part of the fMRI responses elicited by phasic nociceptive stimuli reflects non nociceptive-specific cognitive processes It is well known that multiple sclerosis ( MS ) pathogenesis continues even during periods of clinical silence . To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate ( NAA ) , creatine ( Cr ) , and choline ( Cho ) in the normal-appearing white matter ( NAWM ) between relapsing-remitting ( RR ) MS patients and controls . Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3 ) volume-of-interest ( VOI ) , centered on the corpus callosum of 11 MS patients and 9 matched controls . Gray/white-matter/cerebral-spinal-fluid ( CSF ) volumes were obtained from MRI segmentation . Patients ' average VOI tissue volume ( V(T ) ) , 410.8 + /- 24.0 cm(3 ) , and metabolite levels , NAA = 6.33 + /- 0.70 , Cr = 4.67 + /- 0.52 , Cho = 1.40 + /- 0.17 mM , were different from the controls by -8 % , -9 % , + 22 % and + 32 % . The Cho level was the only single metric differentiating patients from controls at 100 % specificity and > 90 % sensitivity . Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation , gliosis , or de- and remyelination in the NAWM . Both metabolites are potential prognostic indicators of current disease activity , preceding NAA decline and atrophy Quantitative single-voxel , short echo-time ( TE ) MR spectroscopy ( MRS ) was used to determine metabolite concentrations in the cerebral normal-appearing white matter ( NAWM ) of 76 patients with multiple sclerosis ( MS ) , and the WM of 25 controls . In NAWM of all MS disease types ( primary progressive , relapsing-remitting , and secondary progressive ) , the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine ( tCr ) was decreased compared to controls . Remarkably , this was entirely due to an increase of tCr in MS patients , whereas there was no difference in tNAA . Separate quantification of the two tNAA components yielded no significant difference in NAA ( N-acetyl-aspartate ) , while the concentration of NAAG ( N-acetyl-aspartyl-glutamate ) was slightly-but significantly-elevated in MS patients . Myo-inositol ( Ins ) was strongly increased in MS patients , and choline-containing compounds ( Cho ) were mildly increased . There were no metabolite differences between disease types , and no correlations with disability scores . The results are supported by measures of spectral quality , which were identical for patients and controls . In conclusion , MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers ( increase of Ins and tCr ) without evidence of axonal dysfunction ( normal NAA ) . Further studies should eluci date the mechanism underlying increased NAAG in MS NAWM Study Design . Cost of illness study alongside a r and omized controlled trial . Objective . To describe the costs of care for patients with low back pain ( 1 ) and to identify patient characteristics as predictors for high health care cost during a 1-year follow-up ( 2 ) . Summary of Background Data . Low back pain ( LBP ) is one of the leading causes of high health care costs in industrialized countries ( Life time prevalence , 70 % ) . A lot of research has been done to improve primary health care and patients ′ prognosis . However , the cost of health care does not necessarily follow changes in patient outcomes . Methods . General practitioners ( n = 126 ) recruited 1378 patients consulting for LBP . Sociodemographic data , pain characteristics , and LBP-related cost data were collected by interview at baseline and after 6 and 12 months . Costs were evaluated from the societal perspective . Predictors of high cost during the subsequent year were studied using logistic regression analysis . Results . Mean direct and indirect costs for LBP care are about twice as high for patients with chronic LBP compared to acutely ill patients . Indirect costs account for more than 52 % to 54 % of total costs . About 25 % of direct costs refer to therapeutic procedures and hospital or rehabilitational care . Patients with high disability and limitations in daily living show a 2- to 5-fold change for subsequent high health care costs . Depression seems to be highly relevant for direct health care utilization . Conclusion . Interventions design ed to reduce high health care costs for LBP should focus on patients with severe LBP and depressive comorbidity . Our results add to the economic underst and ing of LBP care and may give guidance for future actions on health care improvement and cost reduction & NA ; Although chronic back pain is one of the most frequent reasons for permanent impairment in people under 65 , the neurobiological mechanisms of chronification remain vague . Evidence suggests that cortical reorganisation , so‐called functional plasticity , may play a role in chronic back pain patients . In the search for the structural counterpart of such functional changes in the CNS , we examined 18 patients suffering from chronic back pain with voxel‐based morphometry and compared them to 18 sex and age matched healthy controls . We found a significant decrease of gray matter in the brainstem and the somatosensory cortex . Correlation analysis of pain unpleasantness and the intensity of pain on the day of scanning revealed a strong negative correlation ( i.e. a decrease in gray matter with increasing unpleasantness/increasing intensity of pain ) in these areas . Additionally , we found a significant increase in gray matter bilaterally in the basal ganglia and the left thalamus . These data support the hypothesis that ongoing nociception is associated with cortical and subcortical reorganisation on a structural level , which may play an important role in the process of the chronification of pain |
2,421 | 27,345,006 | There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and /or ICSI treatment | Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction .
However , the impact of sperm DNA damage on assisted reproduction outcomes remains controversial . | OBJECTIVE To examine the effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility . Prospect i ve study . SETTING S Infertility clinic at a tertiary care academic institution . PATIENT(S ) Ninety-two infertile men with normal female partners . Sixteen fertile donors served as the control group . INTERVENTION(S ) St and ard semen analysis and assessment of levels of seminal oxidative stress . Assisted reproductive techniques in 33 of the 92 patients ( IUI [ n = 19 ] , IVF [ n = 10 ] , and intracytoplasmic sperm injection [ n = 4 ] ) . MAIN OUTCOME MEASURE(S ) Sperm DNA damage by sperm chromatin structure assay . Results were expressed as DNA fragmentation index . RESULT ( S ) Patients were classified as having either idiopathic ( n = 23 ) or male factor infertility ( n = 69 ) . Patients with idiopathic and male factor infertility had significantly higher DNA fragmentation index and oxidative stress compared with the case of fertile donors . A clinical pregnancy was achieved in 9 ( 27 % ) of 33 patients with assisted reproductive techniques . Significantly higher DNA fragmentation index and oxidative stress were found in men who failed to initiate a pregnancy after assisted reproductive techniques ( n = 24 ) , compared with the cases of those who succeeded and of the fertile donors . DNA fragmentation index was correlated positively with oxidative stress ( r = 0.27 ) , and negatively with fertilization ( r = -0.70 ) and embryo quality ( r = -0.70 ) . CONCLUSION ( S ) Sperm DNA damage is significantly increased in men with idiopathic and male factor infertility and in men who failed to initiate a pregnancy after assisted reproductive techniques . Such an increase may be related to high levels of seminal oxidative stress OBJECTIVE To determine the level of DNA damage , both fragmentation and oxidative , in the sperm population used for intrauterine insemination ( IUI ) and intracytoplasmic sperm injection ( ICSI ) and its impact on fertilization and clinical pregnancy rates . DESIGN A prospect i ve clinical study . SETTING A tertiary care fertility clinic . PATIENT(S ) Couples undergoing ICSI ( n = 48 ) and couples undergoing IUI cycles ( n = 53 ) . INTERVENTION(S ) Assessment of both sperm DNA fragmentation using the TUNEL assay and oxidative DNA damage using the biomarker 8-hydroxy-2'-deoxyguanosine ( 8-OHdG ) in the sample s prepared and used for insemination . MAIN OUTCOME MEASURE(S ) Achievement of a clinical pregnancy . RESULT ( S ) Sperm DNA fragmentation and 8-OHdG were highly correlated ( r = 0.55 ) and 8-OHdG was significantly lower in those who achieved a clinical pregnancy after IUI ( 8.9 % vs. 20.2 % ) . A threshold value of 11.5 % 8-OHdG was identified as a useful predictor of IUI success . No differences were found in sperm DNA fragmentation or 8-OHdG between pregnant and nonpregnant couples in ICSI cycles . CONCLUSION ( S ) 8-Hydroxy-2'-deoxyguanosine , a biomarker of oxidative DNA damage highly correlated with sperm DNA fragmentation , in human sperm DNA has significant value in predicting the chance of a clinical pregnancy after IUI but not ICSI in assisted reproductive technology A prospect i ve study was performed to assess the impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes . The study population included 178 couples ( 62 cycles of IVF , 116 of intracytoplasmic sperm injection ( ICSI ) ) with own ( n=77 ) and donor ( n=101 ) oocytes . DNA fragmentation was evaluated by TdT ( terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay . Correlation between DNA damage to oocyte fertilization , embryo quality and clinical pregnancy , implantation and miscarriage rates was evaluated . DNA fragmentation was not related to fertilization rates in either IVF ( r=0.08 ) or ICSI ( r=-0.04 ) cycles . DNA fragmentation was similar in patients with < 50 % embryo utilization rate compared with ≥50 % , in cancelled and in embryo transfer cycles and in miscarriages and in successful deliveries . Moreover , DNA fragmentation was similar in pregnant and non-pregnant women as well as in IVF with own or donor oocytes . In the multivariable analysis , the odds ratio of DNA after controlling by age was 1.0 . Using a 36 % sperm fragmentation threshold , results did not vary . It is concluded that DNA damage was not related to outcomes of IVF or ICSI with own or donor oocytes OBJECTIVE To examine sperm DNA fragmentation in semen used for assisted reproduction procedures to establish this factor 's prognostic role in fertilization rate , embryo development , pregnancy rate , and outcome . DESIGN Prospect i ve study . SETTING Department of Medicine and Biology of Reproduction of the Edouard Herriot Hospital in Lyon , France . PATIENT(S ) 322 couples , divided into 88 cycles of in vitro fertilization ( IVF ) or 234 cycles of intracytoplasmic sperm injection ( ICSI ) . INTERVENTION(S ) Sperm DNA fragmentation was detected in sperm obtained 2 to 5 months before the ART procedure . MAIN OUTCOME MEASURE(S ) Sperm DNA fragmentation was measured with the terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling ( TUNEL ) technique . RESULT ( S ) There was a negative statistical correlation between the rate of fragmentation and the semen characteristics . A statistically significant negative relationship was found for sperm DNA fragmentation and fertilization when ICSI and IVF were compared . With ICSI , a statistically significant negative relationship was found between fertilization rate and percentage of sperm DNA fragmentation ( DNA fragmentation index , or DFI ) . The risk of nontransfer due to blocked embryo development increased when the DFI exceeded 15 % ( 18.2 % for ICSI vs 4.2 % for IVF ) with an odds ratio of 5.05 . The miscarriage risk increased fourfold when the DFI exceeded 15 % ( 37.5 % for ICSI vs 8.8 % for IVF ) . CONCLUSION ( S ) Sperm DNA fragmentation measured 2 to 5 months before the assisted reproduction procedure was a prognostic indicator of the fertilization , pregnancy , and miscarriage rates and the pregnancy outcome Background Sperm DNA damage is associated with male infertility but whether normozoospermic infertile men also have DNA damage is unknown . Objective To evaluate sperm DNA and chromatin integrity in men with mild male factor infertility . Design , setting and participants Prospect i ve study of 102 consecutive men ( 78 normozoospermic , 15 asthenozoospermic , 9 oligozoospermic ) enrolled for intrauterine insemination ( IUI ) and 15 fertile controls . Outcome measurements and statistical analysis St and ard semen parameters and sperm chromatin and DNA integrity were assessed and compared between groups . Sperm chromatin quality was assessed by ( 1 ) aniline blue staining ( AB is specific to histone lysines ) , ( 2 ) iodoacetamide fluorescein fluorescence ( IAF targets free protamine sulfhydryl groups ) and ( 3 ) sperm chromatin structure assay ( SCSA ) with the results expressed as % DNA fragmentation index ( % DFI ) . Results and limitations The mean ( ±SD ) percentage of spermatozoa with positive IAF fluorescence was significantly higher in the IUI population compared to fertile controls ( 17 % ± 10 % vs. 8 % ± 6 % , P = 0.0011 ) and also in the normozoospermic subset ( n = 78 ) compared to controls ( 16 % ± 9 % vs. 8 % ± 6 % , P < 0.0001 , ANOVA ) . We also observed a trend toward lower % progressive motility , and higher % AB staining and % DFI in the IUI group compared to controls . We observed significant relationships between sperm % DFI and progressive motility ( r = −0.40 , P < 0.0001 ) and between positive AB staining and IAF fluorescence ( r = 0.58 , P < 0.0001 ) . Conclusions The data indicate that sperm chromatin integrity may be abnormal in men enrolled in IUI treatment cycles , despite the fact that most of these men are normozoospermic BACKGROUND We aim ed to investigate whether sperm DNA quality may predict intrauterine insemination ( IUI ) outcome . METHODS The study was design ed in a prospect i ve cohort fashion , at a tertiary centre for reproductive medicine . A total of 119 patients underwent 154 cycles of IUI . Parameters related to demography , cycle management and semen sample used for IUI were evaluated . Conventional semen parameters , morphology ( strict criteria ) , sperm DNA fragmentation and stability [ evaluated by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling ( TUNEL ) and acridine orange staining under both acid and acid + heat denaturing conditions respectively ] were measured . The main outcome measure was clinical pregnancy , defined as ultrasonographic visualization of intrauterine gestational sac(s ) . RESULTS Logistic regression analyses were done on six sets of data , including all cycles combined , cycles with washed sample s , first cycle of each couple , first cycle of each couple with washed sample s , cycles stimulated with gonadotrophins and finally gonadotrophin-stimulated cycles with washed sample s. The number of pre-ovulatory follicles on day of hCG , the age of the woman and the percentage of sperm with acid- + heat-resistant DNA were the parameters that predicted IUI outcome in most of these data subsets . For the gonadotrophin-stimulated cycles , age of the man appeared as a predictor as opposed to that of the woman ; and for the cycles within this subgroup , where the semen sample was washed , sperm DNA fragmentation and age of the man were the only two parameters to predict IUI outcome . No sample s with > 12 % of sperm having DNA fragmentation result ed in pregnancy . CONCLUSIONS The number of follicles , age of the woman/man and sperm DNA quality may predict IUI outcome OBJECTIVES To st and ardize the TUNEL assay by establishing inter- and intraobserver variability , interassay variability , cutoff values , sensitivity and specificity of the assay , and study ing the distribution of the DNA damage in a population of infertile men referred to a clinical and rology laboratory . METHODS Seminal ejaculates from 25 healthy male volunteers ( controls ) and 194 infertile men ( with male factor infertility ) referred to an and rology laboratory were examined for DNA damage by TUNEL assay using flow cytometric analysis . RESULTS Both the inter- and intraobserver variability and interassay variability was small ( < 10 % ) . DNA damage in the controls was 11.9 ± 6.8 % vs. 29.5 ± 18.7 % in patients ( P < .001 ) . The cut-off value of 19.25 % maximized the observed sensitivity ( 64.9 % ) and specificity ( 100 % ) of the assay . The distribution of DNA damage in the patients was as follows : 14.9 % ( 29 of 194 ) with DNA damage between 0 % and 10 % ; 22.7 % ( 44 of 194 ) between 10 % and 20 % ; 8.8 % ( 17 of 194 ) between 20 % and 30 % ; and 17.5 % ( 34 of 194 ) between 30 % and 40 % . Finally , 27.3 % ( 53 of 194 ) had TUNEL values > 40 % . CONCLUSIONS We report a detailed st and ardization of the TUNEL assay for clinical use , as well as reference ranges for DNA damage in normal healthy donors and infertile men . A cut-off of 19.25 % with observed 100 % specificity established in our program can differentiate infertile men with DNA damage from healthy men . This test can be offered to infertile patients who are idiopathic , have severe oxidative stress-related abnormal semen quality , and contribute to the infertility problem of the couple who are considering assisted reproductive techniques BACKGROUND St and ard semen parameters have proven poor at predicting the outcomes of IVF treatment cycles . As recent studies suggest that the male genome may play an important role in early embryogenesis , this study attempts to correlate the level of sperm DNA damage in fresh semen and prepared sperm with the outcomes of conventional IVF treatment cycles . METHODS Forty patients embarking on IVF treatment were recruited into this prospect i ve observational study . Both fresh semen and PureSperm-prepared sperm were processed using a modified comet assay 3 - 6 months prior to the patients ' IVF treatment cycles . Comet head DNA ( mean and integrated head density ) and tail DNA parameters ( length and moment ) were measured separately . RESULTS Significant correlations between total sperm concentration and between comet length , moment , mean head density with embryo quality were detected in fresh semen and prepared sperm . Surprisingly , no significant correlations between head and tail parameters were detected . CONCLUSIONS Comet head and tail DNA parameters appear to be potentially useful as predictors of embryo quality and IVF outcomes , especially in couples with unexplained subfertility . The lack of correlation between head and tail parameters may be due to a different mechanism of DNA damage within these two compartments To determine predictive values of routine semen analysis , sperm morphology evaluation using strict criteria and DNA status for in-vitro fertilization ( IVF ) , 66 consecutive couples undergoing IVF in a university hospital IVF programme were prospect ively investigated . Semen sample s from 66 men were evaluated by routine semen analysis , morphology evaluation using strict criteria and acridine orange staining for determination of DNA status . A new technique is described for acridine orange scoring which consisted of evaluation of two smears per case , with and without heat treatment . Resistance to heat-provoked denaturation was determined by the difference between two evaluations . A logistic regression model was built and receiver operating characteristic curves were constructed to determine the threshold values and to compare diagnostic properties . Morphology evaluation using strict criteria and concentration of progressively motile spermatozoa were found to be the principal parameters determining the sperm fertilizing capacity in vitro . The logistic regression model composed of morphology evaluation using strict criteria and acridine orange score had a powerful diagnostic capability for prediction of fertilization in vitro OBJECTIVE To assess the value of sperm DNA fragmentation , measured by the sperm chromatin dispersion ( SCD ) test , in predicting fertilization rate , embryo quality , and pregnancy outcome . DESIGN Prospect i ve study . SETTING Four French infertility centers , from January to August 2005 . PATIENT(S ) Six hundred twenty-two couples participating in their first IVF or ICSI program . INTERVENTION(S ) Analysis of DNA fragmentation by the sperm chromatin dispersion test in sperm sample s used for IVF or ICSI . MAIN OUTCOME MEASURE(S ) Correlations and associations between sperm parameters , sperm DNA integrity , and pregnancy outcomes . RESULT ( S ) A statistically significant correlation was observed between sperm DNA fragmentation rate and the following sperm characteristics : sperm motility , morphology , and concentration . We found a statistically significant relationship between sperm DNA fragmentation rate and fertilization rate , and we were able to suggest a threshold sperm DNA fragmentation rate of 18 % , above which fragmentation rate was predictive of fertilization rate . Regarding embryo quality , we observed a relationship between sperm DNA fragmentation and embryo quality . No significant relationship was found between sperm DNA fragmentation rate and clinical pregnancies or births . CONCLUSION ( S ) The results of this study confirm the utility of the sperm chromatin dispersion test for assessment of DNA fragmentation OBJECTIVE To evaluate DNA fragmentation in morphologically normal sperm recovered from the same sample used for intracytoplasmic sperm injection ( ICSI ) and to correlate DNA damage with embryo quality and pregnancy outcome . DESIGN Prospect i ve study . SETTING Academic center . PATIENT(S ) 36 infertile men participating in the ICSI program . INTERVENTION(S ) Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-fluorescein nick end labeling ( TUNEL ) assay and morphologic assessment by phase contrast . MAIN OUTCOME MEASURE(S ) Simultaneous assessment of sperm morphology and DNA fragmentation by TUNEL assay was performed in the same cell , then the percentage of normal sperm with fragmented DNA ( normal SFD ) was correlated with embryo quality and pregnancy outcomes . RESULT ( S ) A highly statistically significant negative correlation was found between the percentage of normal SFD and embryo quality . This association was confirmed for the transferred embryos and for the total embryo cohort . The receiver operating characteristics curve analysis demonstrated that the percentage of normal SFD and embryo quality were statistically significant predictors of pregnancy . When the percentage of normal SFD was < or=17.6 % , the likelihood of pregnancy was 3.5 times higher . No correlation was found between the percentage of total sperm with fragmented DNA ( morphologically normal and abnormal ) and ICSI outcomes . CONCLUSION ( S ) The DNA fragmentation of morphologically normal sperm negatively impacts embryo quality and probability of pregnancy in ICSI cycles OBJECTIVE To evaluate the influence of DNA fragmentation , DNA methylation , and protamine deficiency as indicators of chromatin status on assisted reproductive technology outcome , and also to assess the relation between these parameters . DESIGN Prospect i ve study . SETTING Royan Institute and Isfahan Fertility and Infertility Center . PATIENT(S ) Semen sample s from 92 infertile couples undergoing intracytoplasmic sperm injection ( ICSI ) and IVF were assessed during this study . INTERVENTION(S ) Semen analysis was carried out according to World Health Organization criteria . Protamine deficiency , DNA methylation , and DNA fragmentation were assessed by chromomycin A3 ( CMA3 ) , immunostaining , and sperm chromatin dispersion , respectively . MAIN OUTCOME MEASURE(S ) Chromomycin A3 positivity , DNA methylation , DNA fragmentation and assisted reproductive technology outcome . RESULT ( S ) Chromomycin A3 positivity shows a significant correlation with DNA fragmentation and fertilization rate . Furthermore , unlike in IVF patients , DNA fragmentation showed a significant negative correlation with fertilization rate in ICSI . A significant negative correlation was observed between DNA methylation and DNA fragmentation . In addition , no correlation was found between fertilization rate and DNA methylation in both IVF and ICSI patients . CONCLUSION ( S ) The results reveal that in ICSI procedure DNA fragmentation , and CMA3 positivity affect the fertilization rate , whereas none of these parameters affect postfertilization development . Furthermore , both CMA3 positivity and DNA methylation affect DNA fragmentation , independently of each other . Thus , it can be concluded that these parameters may play an early role in initiation of development OBJECTIVE To investigate sperm DNA damage in relation to fertilization and pregnancy . DESIGN Prospect i ve study . SETTING The Institute of Reproductive Medicine , Giessen , Germany . PATIENT(S ) Semen collected from 249 patients attending the IVF program . MAIN OUTCOME MEASURE(S ) The percentage of terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling- ( TUNEL- ) , Fas- , and annexin-V-positive sperm and the proportion of green-fluorescing sperm in the acridine orange stain was determined and correlated with sperm concentration , motility , fertilization , and pregnancy . RESULT ( S ) Significant correlations with the concentration of motile sperm were only found for the acridine orange stain ( before and after sperm separation ) and for the TUNEL assay ( after sperm separation ) . Moreover , patients whose sperm had a high percentage of DNA fragmentations showed significantly lower pregnancy rates ( TUNEL assay : 19.05 % vs. 34.65 % ; acridine orange stain : 24.58 % vs. 37.93 % ) . The apoptosis parameters ( annexin V binding and Fas expression ) showed no statistically significant differences . CONCLUSIONS Our data clearly demonstrate that DNA fragmentation , as determined by the TUNEL assay , is predictive for pregnancy in IVF . This implies that spermatozoa with DNA fragmentation can still fertilize an oocyte but that when paternal genes are " switched on , " further embryonic development stops , result ing in failed pregnancy . It seems that , at least in the patients we analyzed , apoptosis in the sperm does not play a role for fertilization . This would imply that DNA fragmentation in human spermatozoa is caused by external factors , such as reactive oxygen species , rather than by apoptosis BACKGROUND Sperm DNA integrity is essential for the accurate transmission of genetic information . The clinical significance of this assessment lies in its association with not only natural conception rates , but also the success of assisted reproduction technology ( ART ) . It has been reported that sperm chromatin structure assay ( SCSA ) identified thresholds for negative pregnancy outcome after ART when the DNA fragmentation index ( DFI ) , previously known as COMPalphat , was > 30 % . METHODS In a prospect i ve clinical study , we examined 34 male infertile patients , the husb and s of women undergoing conventional IVF or ICSI . SCSA and ART were carried out on semen aliquots taken from the same ejaculate . Fertilization rate , embryo quality and pregnancy rates were correlated to SCSA parameters , DFI and highly DNA stainable ( HDS ) cells . RESULTS No differences were seen in SCSA parameter values between patients initiating pregnancies and not doing so in either ICSI or conventional IVF . Pregnancies and normal delivery were obtained even with high levels of DFI . CONCLUSIONS There is still controversy over whether analytical techniques currently in use are able to identify the level of damage to spermatozoa . Large-scale studies should be conducted in different clinical setting s to determine the effects of sperm DNA damage on the outcome of ART OBJECTIVE To determine the diagnostic value of the following sperm function tests in predicting the fertilizing ability of spermatozoa in conventional in vitro fertilization ( IVF ) and intracytoplasmic sperm injection ( ICSI ) : hyaluronan-binding assay ( HBA ) , DNA fragmentation ( Halosperm ) , and hyperactivity . DESIGN Prospect i ve study . SETTING University medical center . PATIENT(S ) 133 couples undergoing infertility treatment with IVF/ICSI . INTERVENTION(S ) Analysis of sperm DNA fragmentation , hyaluronan-binding ability , and hyperactivation on washed semen sample s used for the insemination of oocytes . MAIN OUTCOME MEASURE(S ) Correlation between the results of sperm function tests and the fertilization rate ( FR ) or embryo quality ( EQ ) after IVF and ICSI . Comparison of the sperm DNA fragmentation , hyperactivation , and hyaluronan binding ability between cycles with less than 50 % ( group 1 ) and more than 50 % ( group 2 ) of oocytes fertilized after IVF . RESULT ( S ) Both FR and EQ in IVF cycles negatively correlated with sperm DNA fragmentation . Furthermore , a positive correlation was observed between FR and hyaluronan-binding ability or induced hyperactivity . The semen sample s from the IVF cycles with low FR ( group 1 ) were characterized by statistically significantly higher sperm DNA fragmentation and lower hyaluronan-binding ability in comparison with semen sample s from the group with high levels of fertilization ( group 2 ) . In ICSI cycles , no relationship was found between sperm function tests and FR or EQ . CONCLUSION ( S ) The Halosperm test , the HBA test , and induced hyperactivity are useful in predicting the ability of spermatozoa to fertilize oocytes in IVF and are helpful in distinguishing semen sample s suitable for IVF or ICSI The prediction of human fertilization is an important aspect of research protocol s dealing with male fertility . Sperm DNA has been reported to be an indicator of human sperm fertility potential . The Acridine Orange test for evaluation of sperm DNA has been employed during the present study to determine its relationship with human sperm morphology and fertilization in vitro . Seventy-six patients from the in-vitro fertilization ( IVF ) and /or gamete intra-Fallopian transfer ( GIFT ) programme were r and omly selected for the study . All patients had a routine semen analysis , sperm DNA evaluation and underwent st and ard IVF procedures at the time of the study . The results indicated a moderate positive correlation ( r = 0.38 , P = 0.0006 ) between results of the Acridine Orange test and normal sperm morphology . Patients with an Acridine Orange test value exceeding 24 % had significantly higher oocyte fertilization rates than patients with lower values , for metaphase I ( 74 versus 51 % , P = 0.0008 ) and for metaphase II oocytes ( 88 versus 60 % , P = 0.0001 ) . Sperm morphology , however , proved to be a more significant predictor of fertilization in vitro compared to the Acridine Orange test Sperm DNA fragmentation ( SDF ) has been proposed to be one of the main markers regarding male infertility . A prospect i ve study was performed to assess primarily whether sperm DNA damage has any impact on embryological data and secondarily on pregnancy rates . This prospect i ve study evaluated the sperm DNA damage in fresh ejaculated sperm sample s from couples undergoing IVF/ICSI treatments , using the improved SCD method , known as Halosperm ® . The results were evaluated by performing statistical analysis with the statistical package of SPSS v17 . A total of 156 fresh semen sample s derived from 156 couples undergoing 156 IVF/ICSI cycles . From the 156 couples , 139 finally reached the embryo transfer ( ET ) procedure . Overall , SDF did not correlate with embryological data , while ongoing pregnancy rate/ET was 21.6 % . SDF only correlated with sperm characteristics . After the categorisation of SDF ( ≤35 % and > 35 % ) , according to the specific references of the method used , embryological data were comparable as also ongoing pregnancy rates . Using the SCD method , sperm DNA damage is associated neither with embryological data nor to pregnancy rates . However , we should not rule out the fact that extremely high DNA damages are associated with total pregnancy failure In the human , male ageing results in reproductive hormonal and cellular changes that can influence semen quality ( volume , motility , concentration and morphology ) and ultimately result in a reduced fertilising capacity and a longer ‘ time to pregnancy ’ for ageing men as well as an increased risk for miscarriage . This prospect i ve cohort study of 278 patients undergoing a first in vitro fertilisation or intracytoplasmic sperm injection treatment was undertaken to examine whether patient ’s age was reflected in sperm motility , concentration , morphology as well as in DNA fragmentation ( DFI ) and immature chromatin ( unprocessed nuclear proteins and /or poorly condensed chromatin ) as measured by the sperm chromatin structure assay . This study also investigated the possible influence of male age ( after correcting for female age ) on their fertilising capacity , on obtaining a pregnancy and a healthy baby at home . Logistic regression analysis did not reveal any male age‐related influences on sperm parameters like concentration , motility or morphology . No significant male age‐related increase in DFI or immature chromatin was demonstrable for these patients . Elevated male age , after correcting for female age , was not related to lower fertilisation rates or significant decreases in the chance for a healthy baby at home Functional sperm tests such as the sperm chromatin structure assay ( SCSA ) , chromomycin A3 staining ( CMA(3 ) ) and hyaluronic acid binding assay ( HBA ) have been suggested as predictive tests of fertility in vitro . This study aim ed to define the clinical role of these functional parameters in assisted reproduction in a prospect i ve cohort study . Conventional sperm diagnosis ( motility , morphology and concentration ) as well as SCSA , CMA(3 ) and HBA tests were performed on 205 semen sample s [ 74 IVF , 94 ICSI and 37 combined IVF/intracytoplasmic sperm injection ( ICSI ) ] . Main outcome parameters were fertilization rate , clinical pregnancy rate and take-home baby rate . The study showed that each of the three functional sperm tests was related to one or more conventional and one or more functional sperm tests , indicating that spermatozoa from patients with abnormal conventional semen parameters have a higher likelihood for multiple functional abnormalities . Only SCSA and CMA(3 ) staining were shown to have a limited predictive value when IVF or combined IVF/ICSI was applied . The proposed threshold value of < or=15 % for predicting good fertilization rates and obtaining a pregnancy in IVF could only be confirmed for percent HDS ( high DNA stainability in SCSA ) . ICSI outcome was not influenced by any of the conventional or functional sperm parameters PURPOSE We prospect ively evaluated changes in sperm chromatin structure in infertile patients before and after surgical repair of varicocele , and the impact on the pregnancy rate . MATERIAL S AND METHODS Included in the study were 49 men with at least a 1-year history of infertility , a palpable varicocele and oligospermia . World Health Organization semen analysis and sperm DNA damage expressed as the DNA fragmentation index using the sperm chromatin structure assay were assessed preoperatively and postoperatively . Pregnancy ( spontaneous and after assisted reproductive technique ) was recorded 2 years after surgery . RESULTS Mean sperm count , sperm concentration and sperm progressive motility improved significantly after varicocelectomy from 18.3 × 10(6 ) to 44.4 × 10(6 ) , 4.8 × 10(6)/ml to 14.3 × 10(6)/ml and 16.7 % to 26.6 % , respectively ( p < 0.001 ) . The DNA fragmentation index decreased significantly after surgery from 35.2 % to 30.2 % ( p = 0.019 ) . When the definition of greater than 50 % improvement in sperm concentration after varicocelectomy was applied , 31 of 49 patients ( 63 % ) responded to varicocelectomy . After varicocelectomy 37 % of the couples conceived spontaneously and 24 % achieved pregnancy with assisted reproductive technique . The mean postoperative DNA fragmentation index was significantly higher in couples who did not conceive spontaneously or with assisted reproductive technique ( p = 0.033 ) . CONCLUSIONS After varicocelectomy sperm parameters significantly improved and sperm DNA fragmentation was significantly decreased . Low DNA fragmentation index values are associated with a higher pregnancy rate ( spontaneous and with assisted reproductive technique ) . We suggest that varicocelectomy should be considered in infertile men with palpable varicocele , abnormal semen analysis and no major female factors OBJECTIVE To investigate the influence of human sperm nuclear chromatin on fertilization . DESIGN Prospect i ve study . SETTING Assisted reproductive technology unit at a university teaching hospital . PATIENT(S ) Fifty men starting an IVF-ET program . INTERVENTION(S ) Epifluorescent microscopic observation of human-ejaculated sperm nuclei stained with diamide-acridine orange . Sodium dodecyl sulfate-polyacrylamide gel electrophoresis ( SDS-PAGE ) analysis of extracted sperm nucleoproteins . MAIN OUTCOME MEASURE(S ) Usefulness of diamide-acridine orange in analysis of human sperm nuclear chromatin and fertilization ability . RESULT ( S ) There was no correlation between the semen parameters and the diamide-acridine orange observation . A positive correlation was observed between the fertilization rate after conventional IVF and the green-type increase ratio ( percentage of green-pattern sperm after diamide-acridine orange staining/percentage of green-pattern sperm after acridine orange staining ) . Furthermore , it was suggested by SDS-PAGE that structural differences were noticed between the fertile men and the men with sperm immaturity diagnosed after diamide-acridine orange staining . CONCLUSION ( S ) Diamide-acridine orange staining was a more precise method for detecting chromatin abnormalities in human-ejaculated sperm and evaluating fertilization ability than acridine orange staining alone . This method can be used as a diagnostic tool to assess the fertilization ability of human-ejaculated spermatozoa before IVF procedures OBJECTIVE To determine whether the extent of ongoing apoptotic cell death measured as the presence of DNA str and breaks in spermatozoa affects embryo development to the blastocyst stage in IVF . DESIGN A prospect i ve comparative study . SETTING A university IVF clinic and a private IVF clinic . PATIENT(S ) Men ( n = 49 ) undergoing infertility treatment with IVF . INTERVENTION(S ) After density gradient centrifugation preparation , part of the sperm sample was used for infertility treatment , and the rest was fixed in paraformaldehyde . Str and breaks in DNA that are indicative of apoptosis were detected by the in situ DNA nick end labeling ( TUNEL ) technique . A total of 15,000 spermatozoa from each sample were evaluated for TUNEL reactivity by flow cytometry . MAIN OUTCOME MEASURE(S ) Percentage of ejaculated spermatozoa with DNA str and breaks indicative of apoptosis , blastocyst development rate , and pregnancy rate . RESULT ( S ) Blastocyst development showed a significant negative correlation with percentage TUNEL positivity in spermatozoa . When 20 % was used as a cutoff for TUNEL positivity in sperm sample s , the percentage of blastocyst development was 50 % higher in the < 20 % TUNEL-positivity group ( n = 27 ) compared with those with > /=20 % TUNEL positivity ( n = 22 ; 44.7 % blastocyst development vs. 29.8 % ) . Clinical pregnancy rates in these two groups were 52 % vs. 44 % , respectively . CONCLUSION ( S ) The extent of nuclear DNA fragmentation in prepared ejaculated spermatozoa used in IVF negatively correlates with blastocyst development . A larger series of patients needs to be assessed to determine whether this paternal effect on blastocyst development may also affect pregnancy outcome The assessment of male infertility is largely based around the examination of a freshly produced ejaculate by a trained technician according to laboratory methods agreed by the World Health Organization . Although many suggestions have been made to improve this approach , the basic techniques of semen analysis established in the 1950s are still being used . Although several putative tests of sperm function have been developed ( e.g. the measurement of sperm hyperactivation , sperm acrosomal status , or sperm penetration through mucus or binding to zona pellucida ) , none have made it into routine clinical practice . Recently , several ' new ' tests of sperm function and sperm selection have been developed . These include the use of microfluidic chambers , electrophoresis , the binding of sperm to hyaluronic acid , and high magnification sperm selection . R and omised-controlled trials are needed to evaluate these as a replacement or addition to routine semen analysis or current sperm preparation methods OBJECTIVE To quantify the effect of sperm DNA fragmentation ( SDF ) on reproductive outcome by evaluating the most statistically significant bias factors using logistic regression . DESIGN Prospect i ve blind observational cohort study . SETTING University affiliated private IVF unit . PATIENT(S ) Two hundred ten male partners of couples undergoing in vitro fertilization ( IVF ) or first intracytoplasmic sperm injection ( ICSI ) cycles with fresh or thawed sperm with the women 's own or donated oocytes . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) SDF determined before and after swim-up ( n=420 ) , odds ratio calculated of the effect of an increase of one unit of SDF on pregnancy , and stratified regression analysis performed to evaluate the confusion effect of oocyte quality , sperm origin , and the fertilization procedure . RESULT ( S ) The effect of SDF on pregnancy was not affected by sperm origin ( fresh or thawed ) or fertilization procedure when measured both before and after swim-up . When oocytes from infertile patients were employed , SDF had a statistically significant negative impact on chance of pregnancy . For every 10 % increase in SDF , the probability of not achieving pregnancy increased by 1.31 . When donated oocytes were employed , SDF did not have a statistically significant effect . CONCLUSION ( S ) The effect of SDF on the probability of pregnancy can be calculated independent of the fertilization procedure or sperm origin . Oocyte quality conditions the extent of the negative impact of SDF on pregnancy ; this can be overcome when good quality oocytes are employed OBJECTIVE To determine the relationship between sperm chromatin structure assay ( SCSA ) parameters ( DNA fragmentation index [ DFI ] and high DNA stainability [ HDS ] ) , and conventional IVF and IVF/intracytoplasmic sperm injection ( ICSI ) outcomes . DESIGN Retrospective review and prospect i ve study . SETTING Private IVF clinic . PATIENT(S ) Two hundred forty-nine couples undergoing first IVF and /or ICSI cycle . INTERVENTION(S ) IVF , ICSI , blastocyst culture . MAIN OUTCOME MEASURE(S ) DFI , HDS , conventional semen parameters , IVF , ICSI . RESULT ( S ) IVF and ICSI fertilization rates were not statistically different between high- and low-DFI groups . More men with > or = 15 % HDS had lower ( < 25 % and < 50 % ) IVF fertilization rates . High DNA stainability was not related to ICSI fertilization rates . High DNA stainability did not affect blastocyst rates or pregnancy outcomes . Men with > or = 30 % DFI were at risk for low blastocyst rates ( < 30 % ) and no ongoing pregnancies . Men with > or = 30 % DFI had more male factors . World Health Organization thresholds were not predictive of ongoing pregnancy . CONCLUSION ( S ) The relationship between HDS and poor IVF fertilization rates provides preliminary evidence that ICSI may be indicated in men with > or = 15 % HDS . Men with high levels of DNA fragmentation ( > or = 30 % DFI ) were at greater risk for low blastocyst rates and failure to initiate an ongoing pregnancy . The SCSA provides valuable prognostic information to physicians counseling couples before IVF and /or ICSI cycles OBJECTIVE To look for correlations between acridine orange ( AO ) staining and semen parameters before and after sperm separation procedures and to assess whether the AO test predicts fertilization or pregnancy outcomes after st and ard IVF and intracytoplasmic sperm injection . DESIGN Prospect i ve study that simultaneously assesses sperm morphology and nuclear protein maturity on a cell-by-cell basis before and after preparative procedures . SETTING University teaching hospital . PATIENT(S ) Men ( n = 140 ) undergoing diagnostic semen analysis . MAIN OUTCOME MEASURE(S ) Acridine orange fluorescence of sperm nuclei , semen parameters , IVF outcome . RESULT ( S ) In unprocessed sample s , 90 % of sperm with normal heads displayed green fluorescence ( mature nuclear protein ) ; significantly lower percentages of green fluorescence were observed in sperm with abnormal heads . The percentage of mature normal sperm in the specimen correlated with motility . Sperm maturity after swim-up or Percoll gradient was significantly improved for sperm with normal or abnormal heads . The percentage of mature normal sperm correlated with motility after either Percoll or swim-up . Neither the percentages of mature nuclei nor mature normal nuclei correlated with fertilization or pregnancy outcome . CONCLUSION ( S ) Nuclear protein maturation correlates with sperm motility and morphology . Because morphologically normal and motile sperm are more mature , separation procedures should generate a population of sperm with the highest fertilization capacity . Acridine orange staining , however , did not predict fertilization efficiency or pregnancy outcome in IVF cycles OBJECTIVE To test the hypothesis that couples with sperm chromatin structure assay ( SCSA ) DNA fragmentation index ( DFI ) values > 27 % would not achieve pregnancy with assisted reproductive techniques ( ART ) and to investigate how DFI and high DNA stainability ( HDS ) , as measured by the SCSA , affect fertilization , cleavage , implantation , and pregnancy rates in IVF cycles . DESIGN Prospect i ve clinical study . SETTING Academic human reproduction laboratory . PATIENT(S ) One hundred couples undergoing IVF with conventional insemination or intracytoplasmic sperm injection . INTERVENTION(S ) Testing with SCSA was performed by SCSA Diagnostics ( Brookings , South Dakota ) on a semen aliquot taken from ejaculate used for ART . MAIN OUTCOME MEASURE(S ) Relating total DFI and HDS to conventional semen parameters and cycle-specific outcomes after ART . RESULT ( S ) Nine of nineteen couples achieved clinical pregnancy when DFI was > or = 27 % , and 2 of 22 couples achieved clinical pregnancy when DFI was < or = 9 % . One of nine couples achieved clinical pregnancy with HDS > 17 % . The DFI was negatively correlated with sperm density ( r = -0.23 , P<.03 ) and motility ( r = -0.55 , P<.00 ) , and HDS was negatively correlated with sperm density ( r = -0.37 , P<.00 ) . CONCLUSION ( S ) Sperm chromatin structure assay failed to identify elevated DFI thresholds for negative pregnancy outcome after ART . Patients with low DFI ( < or = 9 % ) were least likely to become pregnant , which is also contradictory to SCSA marketing , which states that DFIs of < or = 15 % have excellent fertility potential . Patients with HDS > or = 17 % had low pregnancy rates , indicating decreased fertility potential , which deserves further investigation . Larger studies are necessary to confirm that low DFI is associated with decreased fertility and , if proved , might redefine the use of the SCSA in evaluating infertility OBJECTIVE To study the correlation between sperm DNA fragmentation index ( DFI ) , age of male , various parameters of sperm , rates of fertilization , high quality embryo and pregnancy and implantation rates . METHODS One hundred and eleven infertile couples were selected r and omly , and DFI was tested by flow cytometry for the sperm used for IVF . The patients were divided into different groups according to the DFI scores . The results of each group were analyzed . RESULTS The IVF normal fertilization was significantly lower in couples with sperm DFI over 10 % ( 60.5 % ) than that in couples with DFI below 10 % ( 70.1 % ) ( P<0.05 ) . Significantly positive correlation was found between DFI and the age of male ( r=0.624 , P<0.05 ) . DFI was also significantly negatively correlated with the percentage of linearly progressive sperm ( r=-0.360 , P<0.05 ) . There was no significant correlation between the rates of high quality cleaved embryos , pregnancy and implantation rate and sperm DFI . CONCLUSION DFI scores are increased with male 's age , and it can influence the sperm motility . DFI=10 % can be considered as a critical point which can be used to estimate the clinical fertility rate of IVF . But it could not provide relative information about the rates of high quality embryos and pregnancy for infertile couples undergoing IVF procedure OBJECTIVE Potential reparation of sperm DNA fragmentation in the oocyte may disturb any relationship between DNA-damaged sperm and the implantation ability of result ing embryos . To rule out this factor , we analyzed the consequences of sperm DNA fragmentation on IVF-ET outcome in women with healthy ovarian function . DESIGN Prospect i ve study . SETTING Teaching hospital , France . PATIENT(S ) All 117 women were < 38 years old , who combined normal serum day-3 FSH and inhibin B levels with an adequate response to controlled ovarian hyperstimulation . INTERVENTION(S ) The DNA fragmentation rate was determined in the raw sperm used for conventional IVF by flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay . Cycles were sorted into two groups according to whether DNA fragmentation exceeded ( high fragmentation [ HF ] , n = 52 ) or did not exceed ( low fragmentation [ LF ] , n = 65 ) the 50th percentile of values ( 35 % ) . MAIN OUTCOME MEASURE(S ) D2 embryo quality and implantation and ongoing pregnancy rates . RESULT ( S ) Patients ' characteristics , raw semen parameters , fertilization rates , and embryology data were similar in HF and LF groups . Clinical ( 37.5 % vs. 62.5 % ) and ongoing ( 23.5 % vs. 57.8 % ) pregnancy rates per ET and implantation rates ( 24.5 % vs. 42.4 % ) were lower in the HF group than in the LF group . CONCLUSION ( S ) High sperm DNA fragmentation spares fertilization and top embryo morphology rates but is associated with decreased IVF-ET outcome |
2,422 | 24,846,507 | CONCLUSIONS CABG for patients with diabetes mellitus and LM and /or MVD had advantages over PCI-DES in all-cause death , nonfatal MI , and repeat revascularization , but the substantial disadvantage in nonfatal stroke .
The high-selected patients ( RCTs ) risked a higher mortality than the real-world patients ( OCTs ) | BACKGROUND With advances in theinterventional field , the choice between coronary artery bypass grafting ( CABG ) and percutaneous coronary intervention with drug-eluting stents ( PCI-DES ) for the diabetic subset with left main ( LM ) and /or multivessel disease ( MVD ) remains consistently controversial . | BACKGROUND This retrospective study of prospect ively collected data compared coronary artery bypass graft ( CABG ) surgery to drug-eluting stenting ( DES ) in diabetic patients with multivessel coronary artery disease ( CAD ) . Prior r and omized trials and clinical studies have suggested that CABG may be the preferred revascularization strategy in diabetic patients with multivessel CAD . Data are limited regarding the impact of DES vs. CABG on clinical outcomes . METHODS We included 205 consecutive diabetic patients who underwent either CABG ( n=103 ) or DES ( n=102 ) . The primary clinical end points were freedom from major adverse cardiac events ( MACE ) at 30 days and 1 year . RESULTS Baseline characteristics were similar between both groups . At 1 year , the mortality rate was similar in the CABG and DES group ( 8 % vs. 10 % , p=0.6 ) but the MACE rate was lower in the CABG group ( 12 % vs. 27 % , p=0.006 ) due to less repeat revascularization with CABG ( 3 % vs. 20 % , p<0.001 ) . Stroke occurred only in the CABG group ( 4 % vs. 0 % , p=0.04 ) . Angiographically-documented stent thrombosis after DES occurred in 3 % . Presentation with acute myocardial infa rct ion ( hazard ratio [ HR ] , 2.26 , 95 % CI , 1.13 to 4.55 ) and DES ( HR , 2.4 , 95 % CI , 1.23 to 4.77 ) were positive independent predictors , whereas therapy with a statin was a negative independent predictor of MACE ( HR , 0.40 , 95 % CI , 0.21 to 0.76 ) . CONCLUSIONS Bypass surgery was associated with less MACE primarily due to the higher repeat revascularization rate with DES and is therefore superior to DES despite more extensive CAD in CABG patients BACKGROUND In some r and omized trials comparing revascularization strategies for patients with diabetes , coronary-artery bypass grafting ( CABG ) has had a better outcome than percutaneous coronary intervention ( PCI ) . We sought to discover whether aggressive medical therapy and the use of drug-eluting stents could alter the revascularization approach for patients with diabetes and multivessel coronary artery disease . METHODS In this r and omized trial , we assigned patients with diabetes and multivessel coronary artery disease to undergo either PCI with drug-eluting stents or CABG . The patients were followed for a minimum of 2 years ( median among survivors , 3.8 years ) . All patients were prescribed currently recommended medical therapies for the control of low-density lipoprotein cholesterol , systolic blood pressure , and glycated hemoglobin . The primary outcome measure was a composite of death from any cause , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS From 2005 through 2010 , we enrolled 1900 patients at 140 international centers . The patients ' mean age was 63.1±9.1 years , 29 % were women , and 83 % had three-vessel disease . The primary outcome occurred more frequently in the PCI group ( P=0.005 ) , with 5-year rates of 26.6 % in the PCI group and 18.7 % in the CABG group . The benefit of CABG was driven by differences in rates of both myocardial infa rct ion ( P<0.001 ) and death from any cause ( P=0.049 ) . Stroke was more frequent in the CABG group , with 5-year rates of 2.4 % in the PCI group and 5.2 % in the CABG group ( P=0.03 ) . CONCLUSIONS For patients with diabetes and advanced coronary artery disease , CABG was superior to PCI in that it significantly reduced rates of death and myocardial infa rct ion , with a higher rate of stroke . ( Funded by the National Heart , Lung , and Blood Institute and others ; FREEDOM Clinical Trials.gov number , NCT00086450 . ) Objectives : To explore the clinical performance of a strategy of revascularization by percutaneous coronary intervention ( PCI ) with drug‐eluting stent ( DES ) in diabetic patients with multivessel disease ( MVD ) compared with coronary artery bypass graft ( CABG ) , when it is based on clinical judgment . Background : Diabetes mellitus ( DM ) is a major risk factor for poor outcome after PCI . However , PCI may result in better outcome if the choice of revascularization ( PCI versus CABG ) is based on the physician decision , rather than r and omization . Limited experiences have compared revascularization by DES‐PCI versus CABG in DM patients with MVD . Methods : From August 2004 to August 2005 , 220 consecutive DM patients with MVD underwent DES‐PCI ( 93 ) or CABG ( 127 ) at our Institution . The type of revascularization was dependent on patient and /or physician choice . Major adverse cardiac and cerebrovascular events ( MACCE ) included death , myocardial infa rct ion , repeat coronary revascularization , and stroke . Results : Compared with PCI patients , CABG patients had higher prevalence of 3‐vessel disease ( P < 0.001 ) , significant LAD involvement ( P < 0.001 ) , presence of total occlusions ( P = 0.04 ) , collateral circulation ( P < 0.001 ) . At 2‐year follow‐up , MACCE were not different between CABG group and DES‐PCI group ( OR 1.2 ; P = 0.6 ) and , only when the clinical judgment on the revascularization choice was excluded at propensity analysis , DES‐PCI increased the risk of 24‐month MACCE in total population ( OR 1.8 ; P = 0.04 ) . Conclusions : For patients with DM and MVD , a clinical judgment‐based revascularization by DES‐PCI is not associated with worse 2‐year outcome compared with CABG . © 2008 Wiley‐Liss , Background —Diabetes portends an adverse prognosis in patients undergoing percutaneous coronary intervention ( PCI ) . Whether improvements in current clinical practice ( stents , IIb/IIIa antagonists ) have result ed in substantial improvement of these outcomes remains an issue . The aim of this study was to determine the influence of diabetes on 9-month outcomes of patients undergoing PCI in the current era . Methods and Results —The 11 482 patients enrolled in the Prevention of REStenosis with Tranilast and its Outcomes ( PRESTO ) Trial were stratified according to the presence ( n=2694 ) or absence ( n=8798 ) of diabetes . Diabetic patients were older ; were more likely to be female ; had a higher proportion of congestive failure , hypertension , prior CABG , and unstable angina ; and had higher body mass index and lower ejection fraction than nondiabetic patients ( P < 0.01 for all comparisons ) . The degree of multivessel disease was similar between the two groups . American College of Cardiology/American Heart Association type C lesions were more common in diabetic patients ( 17 % versus 15 % , P < 0.01 ) . Angiographic and procedural success rates and in-hospital events were similar between the two groups . The primary end point of death , myocardial infa rct ion , or target vessel revascularization ( TVR ) was analyzed as time-to-first event within 9 months of the index PCI . After adjusting for certain baseline characteristics , diabetes was independently associated with death at 9 months ( relative risk [ RR ] , 1.87 ; 95 % CI , 1.31 to 2.68 , P < 0.01 ) and with an increased likelihood of TVR ( RR , 1.27 ; 95 % CI , 1.14 to 1.42 , P < 0.01 ) , as well as the composite end point of death/myocardial infa rct ion/TVR ( RR , 1.26 ; 95 % CI , 1.13 to 1.40 , P < 0.01 ) . Conclusions —Despite advances in interventional techniques , diabetes remains a significant independent predictor of adverse events in the intermediate term after PCI Background — Advances in coronary artery bypass grafting ( CABG ) surgery and percutaneous coronary intervention ( PCI ) with drug-eluting stents have dramatically improved results of these procedures . The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospect i ve , r and omized data reflecting current practice . This study represents a “ real-world ” evaluation of current technology in the treatment of multivessel coronary artery disease . Methods and Results — A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified . Of these , 1080 patients were treated for 2-vessel disease ( 196 CABG and 884 PCI ) and 600 for 3-vessel disease ( 505 CABG and 95 PCI ) . One-year mortality , cerebrovascular events , Q-wave myocardial infa rct ion , target vessel failure , and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts . Outcomes were adjusted for baseline covariates and reported as hazard ratios . The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease ( 9.7 % CABG versus 21.2 % PCI ; P<0.001 ) and 3-vessel disease ( 10.8 % CABG versus 28.4 % PCI ; P<0.001 ) . Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel ( hazard ratio 2.29 ; 95 % CI 1.39 to 3.76 ; P=0.01 ) and 3-vessel disease ( hazard ratio 2.90 ; 95 % CI 1.76 to 4.78 ; P<0.001 ) . Adjusted outcomes for the nondiabetic sub population demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel ( hazard ratio 1.77 ; 95 % CI 0.96 to 3.25 ; P=0.07 ) and 3-vessel disease ( hazard ratio 1.70 ; 95 % CI 0.77 to 3.61 ; P=0.19 ) . Conclusions — Compared with PCI with drug-eluting stents , CABG result ed in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease , primarily in those with underlying diabetes . Coronary artery bypass surgery may be the preferred revascularization strategy in diabetic patients with multivessel coronary artery disease OBJECTIVES This prespecified subgroup analysis examined the effect of diabetes on left main coronary disease ( LM ) and /or three-vessel disease ( 3VD ) in patients treated with percutaneous coronary intervention ( PCI ) or coronary artery bypass grafting ( CABG ) in the SYNTAX trial . METHODS Patients ( n = 1800 ) with LM and /or 3VD were r and omized to receive either PCI with TAXUS Express paclitaxel-eluting stents or CABG . Five-year outcomes in subgroups with ( n = 452 ) or without ( n = 1348 ) diabetes were examined : major adverse cardiac or cerebrovascular events ( MACCE ) , the composite safety end-point of all-cause death/stroke/myocardial infa rct ion ( MI ) and individual MACCE components death , stroke , MI and repeat revascularization . Event rates were estimated with Kaplan-Meier analyses . RESULTS In diabetic patients , 5-year rates were significantly higher for PCI vs CABG for MACCE ( PCI : 46.5 % vs CABG : 29.0 % ; P < 0.001 ) and repeat revascularization ( PCI : 35.3 % vs CABG : 14.6 % ; P < 0.001 ) . There was no difference in the composite of all-cause death/stroke/MI ( PCI : 23.9 % vs CABG : 19.1 % ; P = 0.26 ) or individual components all-cause death ( PCI : 19.5 % vs CABG : 12.9 % ; P = 0.065 ) , stroke ( PCI : 3.0 % vs CABG : 4.7 % ; P = 0.34 ) or MI ( PCI : 9.0 % vs CABG : 5.4 % ; P = 0.20 ) . In non-diabetic patients , rates with PCI were also higher for MACCE ( PCI : 34.1 % vs CABG : 26.3 % ; P = 0.002 ) and repeat revascularization ( PCI : 22.8 % vs CABG : 13.4 % ; P < 0.001 ) , but not for the composite end-point of all-cause death/stroke/MI ( PCI : 19.8 % vs CABG : 15.9 % ; P = 0.069 ) . There were no differences in all-cause death ( PCI : 12.0 % vs CABG : 10.9 % ; P = 0.48 ) or stroke ( PCI : 2.2 % vs CABG : 3.5 % ; P = 0.15 ) , but rates of MI ( PCI : 9.9 % vs CABG : 3.4 % ; P < 0.001 ) were significantly increased in the PCI arm in non-diabetic patients . CONCLUSIONS In both diabetic and non-diabetic patients , PCI result ed in higher rates of MACCE and repeat revascularization at 5 years . Although PCI is a potential treatment option in patients with less-complex lesions , CABG should be the revascularization option of choice for patients with more-complex anatomic disease , especially with concurrent diabetes Background —Early clinical studies demonstrated the feasibility of local paclitaxel delivery in reducing restenosis after treatment of de novo coronary lesions in small patient population s. Methods and Results —We conducted a r and omized , double-blind trial of 536 patients at 38 medical centers evaluating slow-release ( SR ) and moderate-release ( MR ) formulations of a polymer-based paclitaxel-eluting stent ( TAXUS ) for revascularization of single , primary lesions in native coronary arteries . Cohort I compared TAXUS-SR with control stents , and Cohort II compared TAXUS-MR with a second control group . The primary end point was 6-month percent in-stent net volume obstruction measured by intravascular ultrasound . Secondary end points were 6-month angiographic restenosis and 6- and 12-month incidence of major adverse cardiac events , a composite of cardiac death , myocardial infa rct ion , and repeat revascularization . At 6 months , percent net volume obstruction within the stent was significantly lower for TAXUS stents ( 7.9 % SR and 7.8 % MR ) than for respective controls ( 23.2 % and 20.5 % ; P < 0.0001 for both ) . This corresponded with a reduction in angiographic restenosis from 17.9 % to 2.3 % in the SR cohort ( P < 0.0001 ) and from 20.2 % to 4.7 % in the MR cohort ( P = 0.0002 ) . The incidence of major adverse cardiac events at 12 months was significantly lower ( P = 0.0192 ) in the TAXUS-SR ( 10.9 % ) and TAXUS-MR ( 9.9 % ) groups than in controls ( 22.0 % and 21.4 % , respectively ) , predominantly because of a significant reduction in repeat revascularization of the target lesion in TAXUS-treated patients . Conclusions —Compared with a bare metal stent , paclitaxel-eluting stents reduced in-stent neointimal formation and restenosis and improved 12-month clinical outcome of patients with single de novo coronary lesions Background —R and omized clinical trials have shown that a sirolimus-eluting stent significantly reduces restenosis after percutaneous coronary revascularization . Diabetic patients are known to have a higher risk of restenosis compared with nondiabetic patients . The purpose of this analysis was to determine the impact of sirolimus-eluting stents on outcomes of diabetic compared with nondiabetic patients . Methods and Results —The SIRIUS ( SIRolImUS-coated Bx Velocity balloon-exp and able stent in the treatment of patients with de novo coronary artery lesions ) trial is a r and omized , double-blind study that compared sirolimus-eluting and bare metal stent implantation in 1058 patients with de novo native coronary artery lesions . Diabetes mellitus was present in 279 ( 26 % ) patients ( diabetes mellitus group , 131 patients received sirolimus-eluting stents and 148 patients received bare metal stents ) and was absent in 778 patients ( no – diabetes mellitus group , 402 patients received sirolimus-eluting stents and 376 patients received bare metal stents ) . At 270 days , target lesion revascularization was reduced in diabetic patients from 22.3 % with bare metal stents to 6.9 % with sirolimus-eluting stents ( P < 0.001 ) and in nondiabetic patients from 14.1 % to 2.99 % ( P < 0.001 ) , respectively . Major adverse cardiac events were reduced in diabetic patients from 25 % with bare metal stents to 9.2 % with sirolimus-eluting stents ( P < 0.001 ) and from 16.5 % to 6.5 % ( P < 0.001 ) in nondiabetic patients , respectively . Conclusions —Implantation of sirolimus-eluting stents compared with bare metal stents in de novo coronary lesions reduces major adverse cardiac events in patients with and without diabetes mellitus . However , among patients receiving sirolimus-eluting stents , there remains a trend toward a higher frequency of repeat intervention in diabetic patients compared with nondiabetic patients , particularly in the insulin-requiring patients Background —The TAXUS NIRx stent ( Boston Scientific Corp ) provides local delivery of paclitaxel via a slow-release polymer coating . The TAXUS I trial was the first in-human experience evaluating safety and feasibility of the TAXUS NIRx stent system compared with bare NIR stents ( control ) ( Boston Scientific Corp ) for treatment of coronary lesions . Methods and Results —The TAXUS I trial was a prospect i ve , double-blind , three-center study r and omizing 61 patients with de novo or restenotic lesions ( ≤12 mm ) to receive a TAXUS ( n=31 ) versus control ( n=30 ) stent ( diameter 3.0 or 3.5 mm ) . Demographics , lesion characteristics , clinical outcomes were comparable between the groups . The 30-day major adverse cardiac event ( MACE ) rate was 0 % in both groups ( P = NS ) . No stent thromboses were reported at 1 , 6 , 9 , or 12 months . At 12 months , the MACE rate was 3 % ( 1 event ) in the TAXUS group and 10 % ( 4 events in 3 patients ) in the control group ( P = NS ) . Six-month angiographic restenosis rates were 0 % for TAXUS versus 10 % for control ( P = NS ) patients . There were significant improvements in minimal lumen diameter ( 2.60±0.49 versus 2.19±0.65 mm ) , diameter stenosis ( 13.56±11.77 versus 27.23±16.69 ) , and late lumen loss ( 0.36±0.48 versus 0.71±0.48 mm ) in the TAXUS group ( all P < 0.01 ) . No evidence of edge restenosis was seen in either group . Intravascular ultrasound analysis showed significant improvements in normalized neointimal hyperplasia in the TAXUS ( 14.8 mm3 ) group compared with the control group ( 21.6 mm3 ) ( P < 0.05 ) . Conclusions —In this feasibility trial , the TAXUS slow-release stent was well tolerated and showed promise for treatment of coronary lesions , with significant reductions in angiographic and intravascular ultrasound measures of restenosis BACKGROUND We report the 5-year results of the SYNTAX trial , which compared coronary artery bypass graft surgery ( CABG ) with percutaneous coronary intervention ( PCI ) for the treatment of patients with left main coronary disease or three-vessel disease , to confirm findings at 1 and 3 years . METHODS The r and omised , clinical SYNTAX trial with nested registries took place in 85 centres in the USA and Europe . A cardiac surgeon and interventional cardiologist at each centre assessed consecutive patients with de-novo three-vessel disease or left main coronary disease to determine suitability for study treatments . Eligible patients suitable for either treatment were r and omly assigned ( 1:1 ) by an interactive voice response system to either PCI with a first-generation paclitaxel-eluting stent or to CABG . Patients suitable for only one treatment option were entered into either the PCI-only or CABG-only registries . We analysed a composite rate of major adverse cardiac and cerebrovascular events ( MACCE ) at 5-year follow-up by Kaplan-Meier analysis on an intention-to-treat basis . This study is registered with Clinical Trials.gov , number NCT00114972 . FINDINGS 1800 patients were r and omly assigned to CABG ( n=897 ) or PCI ( n=903 ) . More patients who were assigned to CABG withdrew consent than did those assigned to PCI ( 50 vs 11 ) . After 5 years ' follow-up , Kaplan-Meier estimates of MACCE were 26·9 % in the CABG group and 37·3 % in the PCI group ( p<0·0001 ) . Estimates of myocardial infa rct ion ( 3·8 % in the CABG group vs 9·7 % in the PCI group ; p<0·0001 ) and repeat revascularisation ( 13·7%vs 25·9 % ; p<0·0001 ) were significantly increased with PCI versus CABG . All-cause death ( 11·4 % in the CABG group vs 13·9 % in the PCI group ; p=0·10 ) and stroke ( 3·7%vs 2·4 % ; p=0·09 ) were not significantly different between groups . 28·6 % of patients in the CABG group with low SYNTAX scores had MACCE versus 32·1 % of patients in the PCI group ( p=0·43 ) and 31·0 % in the CABG group with left main coronary disease had MACCE versus 36·9 % in the PCI group ( p=0·12 ) ; however , in patients with intermediate or high SYNTAX scores , MACCE was significantly increased with PCI ( intermediate score , 25·8 % of the CABG group vs 36·0 % of the PCI group ; p=0·008 ; high score , 26·8%vs 44·0 % ; p<0·0001 ) . INTERPRETATION CABG should remain the st and ard of care for patients with complex lesions ( high or intermediate SYNTAX scores ) . For patients with less complex disease ( low SYNTAX scores ) or left main coronary disease ( low or intermediate SYNTAX scores ) , PCI is an acceptable alternative . All patients with complex multivessel coronary artery disease should be review ed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment . FUNDING Boston Scientific OBJECTIVES We compared the 5-year outcomes of diabetic patients with multivessel disease treated with sirolimus-eluting stents ( SES ) , bare-metal stents ( BMS ) , and coronary artery bypass graft surgery ( CABG ) enrolled in the ARTS ( Arterial Revascularization Therapy Study ) I and II studies . BACKGROUND Diabetes is an established risk factor for major adverse cardiac events after revascularization . Recent trials suggest that revascularization with drug-eluting stents has equivalent safety to CABG up to 2 years . METHODS The ARTS I and II studies included 367 diabetic patients ( SES : 159 , CABG : 96 , and BMS : 112 ) compared with respect to 5-year clinical outcomes . RESULTS The rate of major adverse cardiovascular and cerebrovascular events was significantly higher in patients treated with BMS ( BMS 53.6 % vs. CABG 23.4 % vs. SES 40.5 % ; log-rank , p < 0.01 for SES vs. BMS and SES vs. CABG ) . There was no significant difference in mortality among all 3 groups . There was , however , a statistically significant difference in the myocardial infa rct ion rate between BMS and CABG arms ( BMS 11.0 % , CABG 5.2 % , SES 4.8 % , p = 0.04 for SES vs. BMS and p = 0.76 for SES vs. CABG ) . The rate of repeat revascularization was significantly lower in patients treated with CABG compared with SES ( SES 33.2 % vs. CABG 10.7 % , p < 0.001 ) . Revascularization rate of patients treated with SES at 5 years approached that of patients treated with BMS although remained significantly lower . This " catch-up " phenomenon was not apparent in the nondiabetic population . CONCLUSIONS At 5-year follow-up , CABG has comparable safety and superior efficacy compared with BMS and SES in the treatment of diabetic patients with multivessel disease OBJECTIVES We sought to determine the safety and efficacy of polymer-regulated site-specific delivery of paclitaxel in patients with diabetes mellitus undergoing stent implantation . BACKGROUND Percutaneous coronary intervention in patients with diabetes is associated with high rates of restenosis and repeat revascularization due to excessive neointimal proliferation , a process that may be blunted with the site-specific delivery of paclitaxel . METHODS In the TAXUS-IV trial , 1,314 patients were prospect ively r and omized to the slow rate-release polymer-based paclitaxel-eluting TAXUS stent or the bare-metal EXPRESS stent ( Boston Scientific Corp. , Natick , Massachusetts ) . Medically treated diabetes was present in 318 patients ( 24 % ) , 105 of whom required insulin . RESULTS Among patients with diabetes , the TAXUS stent , compared to the bare-metal stent , reduced the rate of 9-month binary angiographic restenosis by 81 % ( 6.4 % vs. 34.5 % , p < 0.0001 ) , and reduced the 12-month rates of target lesion revascularization by 65 % ( 7.4 % vs. 20.9 % , p = 0.0008 ) , target vessel revascularization by 53 % ( 11.3 % vs. 24 % , p < 0.004 ) , and composite major adverse cardiac events by 44 % ( 15.6 % vs. 27.7 % , p = 0.01 ) . The one-year rates of cardiac death ( 1.9 % vs. 2.5 % ) , myocardial infa rct ion ( 3.2 % vs. 6.4 % ) , and subacute thrombosis ( 0.6 % vs. 1.2 % ) were comparable between the paclitaxel-eluting and control stents , respectively . In the insulin-requiring subgroup , the TAXUS stent reduced angiographic restenosis by 82 % ( 7.7 % vs. 42.9 % , p = 0.0065 ) , and reduced the one-year rate of target lesion revascularization by 68 % ( 6.2 % vs. 19.4 % , p = 0.07 ) , a relative reduction similar to patients without diabetes . CONCLUSIONS The site-specific delivery of paclitaxel after coronary stent implantation is highly effective in reducing clinical and angiographic restenosis in patients with diabetes mellitus BACKGROUND There are few data to compare the long-term efficacy of sirolimus-eluting stent ( SES ) and off-pump coronary artery bypass grafting ( OPCAB ) for diabetic patients with multivessel disease ( MVD ) . METHODS AND RESULTS In a single-center non-r and omized registry , 208 diabetic patients with MVD were examined ( SES group : n=92 , OPCAB group : n=116 ) . The occurrence of major adverse cardiac and cerebrovascular events ( MACCE , defined as all-cause death , non-fatal myocardial infa rct ion , cerebrovascular event , and repeat revascularization ) was compared between the 2 groups . Fasting blood glucose level , type of diabetic treatment and the prevalence of diabetic major vascular complications were similar between groups . The SES group had a significantly higher prevalence of 2-vessel disease and a significantly lower prevalence of 3-vessel disease compared with the OPCAB group . During the follow-up period ( mean : 42+/-8 months ) , the rate of revascularization was significantly higher in the SES group than the OPCAB group ( 21 % vs 6.9 % , P=0.003 ) . On the other h and , there was a significant higher occurrence of cerebrovascular events in the OPCAB group . Finally , the cumulative MACCE was similar between the 2 groups ( 27 % vs 23 % , P=0.492 ) . CONCLUSIONS At the 3-year clinical follow-up , the prevalence of MACCE in diabetic patients with MVD was comparable between the SES and the OPCAB groups BACKGROUND The study compares five-year clinical outcomes of CABG vs PCI in a real world population of diabetic patients with multivessel coronary disease since it is not clear whether to prefer surgical or percutaneous revascularization . METHODS Between July 2002 and December 2008 , 2885 multivessel coronary diabetic patients underwent revascularization ( 1466 CABG and 1419 PCI ) at hospitals in Emilia-Romagna Region , Italy and were followed for 1827 ± 617 days by record linkage of two clinical registries with the regional administrative data base of hospital admissions and the mortality registry . Five-year incidences of MACCE ( mortality , acute myocardial infa rct ion [ AMI ] , stroke , and repeat revascularization [ TVR ] ) were assessed with Kaplan-Meier estimates , Cox proportional hazards regression and cumulative incidence functions of death and TVR , to evaluate the competing risk of AMI on death and TVR . The same analyses were applied to the propensity score matched subgroup of patients undergoing CABG or PCI with DES and with complete revascularization . RESULTS PCI had higher mortality for all causes ( HR : 1.8 , 95 % CI 1.4 - 2.2 p<0.0001 ) , AMI ( HR : 3.3 , 95 % CI 2.4 - 4.6 p<0.0001 ) and TVR ( HR : 4.5 , 95 % CI 3.4 - 6.1 p<0.0001 ) . No significant differences emerged for stroke ( HR : 0.8 , 95 % CI 0.5 - 1.2 p=0.26 ) . The higher incidence of AMI caused higher mortality in PCI group . Results did not change comparing CABG with PCI patients receiving complete revascularization or DES only . CONCLUSIONS Diabetics show a higher incidence of MACCE with PCI than with CABG : thus diabetes and its degree of control should be considered when choosing the type of revascularization 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 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 OBJECTIVES The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention ( PCI ) with stenting against coronary artery bypass grafting ( CABG ) in patients with diabetes and symptomatic multivessel coronary artery disease . BACKGROUND CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease , but with advances in PCI , there is uncertainty whether CABG remains the preferred method of revascularization . METHODS The primary outcome was a composite of all-cause mortality , myocardial infa rct ion ( MI ) , and stroke , and the main secondary outcome included the addition of repeat revascularization to the primary outcome events . A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were r and omized to PCI plus stenting ( and routine abciximab ) or CABG . The primary comparison used a noninferiority method with the upper boundary of the 95 % confidence interval ( CI ) not to exceed 1.3 to declare PCI noninferior . Bare-metal stents were used initially , but a switch to Cypher ( sirolimus drug-eluting ) stents ( Cordis , Johnson & Johnson , Bridgewater , New Jersey ) was made when these became available . RESULTS At 1 year of follow-up , the composite rate of death , MI , and stroke was 10.5 % in the CABG group and 13.0 % in the PCI group ( hazard ratio [ HR ] : 1.25 , 95 % CI : 0.75 to 2.09 ; p=0.39 ) , all-cause mortality rates were 3.2 % and 3.2 % , and the rates of death , MI , stroke , or repeat revascularization were 11.3 % and 19.3 % ( HR : 1.77 , 95 % CI : 1.11 to 2.82 ; p=0.02 ) , respectively . When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents ( 69 % of patients ) , the primary outcome rates were 12.4 % and 11.6 % ( HR : 0.93 , 95 % CI : 0.51 to 1.71 ; p=0.82 ) , respectively . CONCLUSIONS The CARDia ( Coronary Artery Revascularization in Diabetes ) trial is the first r and omized trial of coronary revascularization in diabetic patients , but the 1-year results did not show that PCI is noninferior to CABG . However , the CARDia trial did show that multivessel PCI is feasible in patients with diabetes , but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies . ( The Coronary Artery Revascularisation in Diabetes trial ; IS RCT N19872154 ) OBJECTIVES This study sought to determine the optimal coronary revascularization strategy in patients with diabetes with severe coronary disease . BACKGROUND Although subgroup analyses from large trials , data bases , and meta-analyses have found better survival for patients with diabetes with complex coronary artery disease when treated with surgery , a r and omized trial comparing interventions exclusively with drug-eluting stents and surgery in patients with diabetes with high-risk coronary artery disease has not yet been reported . METHODS In a prospect i ve , multicenter study , 198 eligible patients with diabetes with severe coronary artery disease were r and omly assigned to either coronary artery bypass grafting ( CABG ) ( n = 97 ) or percutaneous coronary intervention ( PCI ) with drug-eluting stents ( n = 101 ) and followed for at least 2 years . The primary outcome measure was a composite of nonfatal myocardial infa rct ion or death . Secondary outcome measures included all-cause mortality , cardiac mortality , nonfatal myocardial infa rct ion , and stroke . RESULTS The study was stopped because of slow recruitment after enrolling only 25 % of the intended sample size , leaving it severely underpowered for the primary composite endpoint of death plus nonfatal myocardial infa rct ion ( hazard ratio : 0.89 ; 95 % confidence interval : 0.47 to 1.71 ) . However , after a mean follow-up period of 2 years , all-cause mortality was 5.0 % for CABG and 21 % for PCI ( hazard ratio : 0.30 ; 95 % confidence interval : 0.11 to 0.80 ) , while the risk for nonfatal myocardial infa rct ion was 15 % for CABG and 6.2 % for PCI ( hazard ratio : 3.32 ; 95 % confidence interval : 1.07 to 10.30 ) . CONCLUSIONS This study was severely underpowered for its primary endpoint , and therefore no firm conclusions about the comparative effectiveness of CABG and PCI are possible . There were interesting differences in the components of the primary endpoint . However , the confidence intervals are very large , and the findings must be viewed as hypothesis generating only . ( Coronary Artery Revascularization in Diabetes ; NCT00326196 ) |
2,423 | 26,908,962 | Kangaroo mother care was applied in different ways in different context s. The studies show that there are several barriers to implementing kangaroo mother care , including the need for time , social support , medical care and family acceptance .
Barriers within health systems included organization , financing and service delivery .
In the broad context , cultural norms influenced perceptions and the success of adoption .
CONCLUSION Kangaroo mother care is a complex intervention that is behaviour driven and includes multiple elements . | null | null |
2,424 | 27,875,387 | High and intermediate-IL-2 dosage showed no CR difference , while low-dose IL-2 showed a nonstatistical trend toward an increased CR rate .
The significance is that , contrary to popular belief , the data demonstrated that CR rates were similar for intermediate versus high-IL-2 dosing | Interleukin-2 ( IL-2 ) , initially used in 1986 , can induce clinical regression — complete responses ( CR ) and partial responses ( PR ) of metastatic malignant melanoma .
IL-2 has been used alone or in combination , and in different dosage schedules , as an immunotherapeutic agent for melanoma treatment .
This meta- analysis aim ed to document and evaluate the spectrum of reported clinical response rates from the combined experience of almost 30 years of IL-2 clinical usage . | BACKGROUND High dose interleukin-2 therapy , administered in bolus , is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma . OBJECTIVES To present our experience using this mode of therapy in 21 patients with metastatic melanoma . MATERIAL S AND METHODS The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years ( range 29 - 63 ) . Their metastatic disease was present in all extracranial sites , dermal and sub-dermal metastases being the most common ( 15 patients had at least one site , in addition to other locations of metastases ) . Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site . Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between . Radiological and physical evaluation was performed 6 - 8 weeks after the first course . If a response was achieved a second course of therapy was given . Patients received up to 14 planned doses of IL-2 in each week , 720,000 IU/kg of IL-2 per dose i.v . in 15 minutes . All treatments were given in the surgical ward , and only one patient was hospitalized in the intensive care unit . RESULTS Of the 21 patients , one had a complete response that has lasted for 17 months and 5 patients had a partial response ( range 3 months to 3 years ) . One patient died during treatment , and one patient who refused further treatment because of no response died a few days after completion of treatment . Prior to therapy three of the responders had received autologous vaccines with good immunological response ( P = 0.115 ) . Toxic side effects were significant , but they were treated successfully with no residual damage . CONCLUSIONS High dose IL-2 can be administered safely in a surgical department . The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients . To improve response rates , a combination of autologous vaccines prior to high dose IL-2 may be recommended Objective : To evaluate the activity of interleukin-2 ( IL-2 ) in combination with allogeneic large multivalent immunogen ( LMI ) vaccine , prepared by immobilizing SK23-CD80 + melanoma cell line plasma membrane on 5-&mgr;m-diameter silica beads , in patients with melanoma . Methods : Twenty-one patients with metastatic melanoma were r and omly assigned to an IL-2 alone control group or an IL-2 plus LMI vaccine treatment group . The primary objective was to evaluate the progression-free survival ( PFS ) of each group . Secondary clinical objectives included median overall survival ( OS ) and 1- and 2-year rates of OS . Results : Treatment was very well tolerated . Median PFS was no different between the treatment arm ( 2.20 mo ) and control arm ( 1.95 mo ) . Median OS was also similar for the treatment arm ( 11.89 mo ) and control arm ( 9.97 mo ) . Conclusions : This study failed to demonstrate that allogeneic LMI vaccine and low-dose IL-2 improved survival in patients with melanoma as compared with low-dose IL-2 alone Thus far , peptide vaccines used to stimulate tumor-specific immune responses in patients with melanoma have been largely unsuccessful . Granulocyte-macrophage colony-stimulating factor and interleukin-2 are immune-potentiating cytokines that have improved vaccine responses in pre clinical models . We hypothesized that higher doses of granulocyte-macrophage colony-stimulating factor and addition of low-dose interleukin-2 might augment responses to vaccine antigens . Patients with resected stage II , III , or IV melanoma were treated with vaccines containing three melanoma-associated peptides [ MART-1a , gp100(207–217 ) , and survivin ] , along with 300 or 500 mcg granulocyte-macrophage colony-stimulating factor in Montanide ISA . Cohorts of patients received low-dose subcutaneous interleukin-2 on days 7–20 after vaccination . Induction of a response was defined as either doubling of cytotoxic T lymphocyte frequency from baseline or increase in frequency from undetectable ( < 0.05 % ) to detectable . Leukocyte subsets and plasma cytokines were analyzed before and after vaccination . Cytotoxic T lymphocyte responses to MART-1a , gp100(207–217 ) , and survivin were induced in 11 , 16 , and 14 of 19 patients , respectively . Responses were not higher in patients receiving 500 mcg granulocyte-macrophage colony-stimulating factor or low-dose interleukin-2 than in patients receiving 300 mcg granulocyte-macrophage colony-stimulating factor only . Interleukin-2 treatment ( in nine patients ) led to increases in natural killer cells and T regulatory cells compared with no interleukin-2 treatment ( nine patients ) . Multiple plasma cytokines were transiently induced during vaccination . Neither increasing the dose of granulocyte-macrophage colony-stimulating factor nor addition of low-dose interleukin-2 result ed in an increase in the frequency of vaccine-specific cytotoxic T lymphocytes to a melanoma peptide vaccine . The increase in T regulatory cells associated with interleukin-2 treatment suggests that interleukin-2 may be immunosuppressive in this setting PURPOSE To compare the response rate , survival , and toxicity of treatment with high-dose intravenous ( IV ) bolus interleukin-2 ( IL-2 ) plus interferon alfa-2a ( IFN-alpha ) with high-dose IL-2 alone in patients with advanced melanoma in a r and omized phase III trial design . PATIENTS AND METHODS Eighty-five patients with advanced melanoma were r and omly assigned to receive IL-2 6 X 10(6 ) U/m2 per dose every 8 hours as tolerated for a maximum of 14 doses on days 1 through 5 and 15 through 19 , or IL-2 4.5 X 10(6 ) U/m2 per dose , plus IFN-alpha 3 X 10(6 ) U/m2 using an identical schedule . A planned interim analysis was performed after 85 patients were entered , which forms the basis for this report . RESULTS Partial response ( PR ) occurred in two of 44 patients ( 5 % ; 95 % confidence interval , 1 % to 15 % ) receiving IL-2 alone , compared with four of 41 patients ( 10 % ; 95 % confidence interval , 3 % to 23 % ) receiving IL-2/IFN-alpha ( P = .30 ) . There were no complete responses ( CRs ) . The median duration of response was 11.5 months ( range , 2.0 to 15.7 + ) . There was no significant difference in the median survival duration for patients receiving IL-2 alone ( 10.2 months ) compared with patients receiving IL-2/IFN-alpha ( 9.7 months ) . The median and mean number of doses of IL-2 were equivalent in both groups , as was toxicity . There were three treatment-related deaths , two in the IL-2-alone arm and one in the IL-2/IFN-alpha arm . The trial was terminated after the first interim analysis based on predefined early-stopping rules , which included termination if the response rate in the IL-2/IFN-alpha arm was less than 25 % . CONCLUSION Using the preparation , dose , and schedule of IL-2 in our trial , IFN-alpha failed to enhance significantly the response rate to high-dose IL-2 in the treatment of patients with advanced melanoma BACKGROUND Treatment using interleukin-2 ( IL-2 ) alone or in conjunction with lymphokine-activated killer ( LAK ) cells has been shown to mediate disease regression in selected patients with advanced cancer . PURPOSE This prospect i ve r and omized trial was design ed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and survival rates , compared with those for IL-2 alone , in patients with advanced cancer . METHODS The 181 patients who had metastatic cancer that had failed to respond to st and ard therapy or who had disease for which no effective therapy existed received treatment with high-dose IL-2 alone or with LAK cells plus IL-2 . Both treatment groups were to receive the same dose of IL-2 administered according to the same schedule . IL-2 doses were omitted depending on the tolerance of the patient . Of the 181 patients , 97 had renal cell cancer and 54 had melanoma . RESULTS Median potential follow-up was 63.2 months . There were 10 complete responses among the 85 assessable patients who received IL-2 plus LAK cells , compared with four among the 79 who received IL-2 alone . There were 14 and 12 partial responses , respectively . Complete response continues in seven patients at 50 - 66 months . The 36-month actuarial survival with IL-2 plus LAK cells was 31 % , compared with 17 % with IL-2 alone ( two-sided P value [ P2 ] = .089 ) . A trend toward improved survival was seen for patients with melanoma who received IL-2 plus LAK cells , compared with those who received IL-2 alone ( 24-month survival : 32 % versus 15 % ; 48-month survival : 18 % versus 4 % ; P2 = .064 [ corrected ] ) . None of 26 patients with melanoma who received IL-2 alone are alive ; five of 28 who received IL-2 plus LAK cells are alive , and three continue in complete response . No difference in survival was seen in patients with renal cell cancer in the two treatment groups . There were six treatment-related deaths ( 3.3 % ) ; three were due to myocardial infa rct ion . Other toxic effects resolved by discontinuation of IL-2 . Many toxic effects were related to increased vascular permeability induced by IL-2 . CONCLUSIONS Some patients with metastatic cancer have prolonged remission when they are treated with high-dose IL-2 alone or in conjunction with LAK cells . Our results suggest a trend toward increased survival when IL-2 is given with LAK cells in patients with melanoma , but no trend was observed for patients with renal cell cancer . IMPLICATION S As these studies continue , efforts are underway to develop improved immunotherapies using tumor-infiltrating lymphocytes ( TIL ) and gene-modified TIL BACKGROUND Objective tumor response is a common endpoint in daily practice as well as in clinical trials to evaluate the efficacy of anti-cancer agents . Traditionally , the st and ard World Health Organization ( WHO ) criteria has been adopted in these context s. However , the recent development of new classes of anti-cancer agents and progress in imaging technology have required new methodology to evaluate response to treatment . Recently , the Response Evaluation Criteria in Solid Tumors Group ( RECIST ) proposed new guidelines using unidimensional measurement . Theoretically , the simple sum of the maximum diameters of individual tumors is more linearly related to cell kill than is the sum of the bidimensional products . To vali date these new guidelines , we have compared the st and ard WHO response criteria with the new RECIST guidelines in the same patient population . METHODS Data from 79 patients enrolled in eight prospect i ve phase II studies at Samsung Medical Center were retrospectively re-analyzed to determine the concordance between the two response criteria . The two response criteria were applied separately , and the results were compared using the kappa statistic to test concordance for overall response rate . RESULTS The overall response rate according to the WHO criteria was 31.6 % . Using the RECIST criteria , nine patients were reclassified and the overall response rate was 30.4 % . There was excellent agreement between the unidimensional and bidimensional criteria in 23 of 25 responses ( 92 % ) . The kappa statistic for concordance for overall response was 0.91 . CONCLUSIONS We conclude that the new RECIST guidelines are comparable to the old response criteria in evaluating response in solid tumors . Moreover , the new guidelines are just as simple and reproducible in the measurement of response in daily practice as they are in clinical trials Tumour-infiltrating lymphocytes ( TIL ) were isolated and exp and ed from small tumour biopsy sample s of twenty-eight patients ( thirteen with malignant melanoma , seven with renal cell carcinoma , and eight with non-small-cell lung cancer ) . The patients were treated with autologous exp and ed TIL ( about 10(10 ) ) and continuous infusions of recombinant human interleukin-2(1 - 3 x 10(6 ) U/m2 per 24 h ) . 29 % of the patients with renal cell cancer and 23 % of those with melanoma achieved objective tumour responses lasting 3 - 14 months . Toxic side-effects were limited , and no patient required intensive-care monitoring . Adoptive immunotherapy with TIL and interleukin-2 may be an effective systemic approach to the treatment of some patients with malignant melanoma and renal cell carcinoma BACKGROUND The safety and efficacy of immunotherapy with histamine dihydrochloride ( HDC ) , interleukin-2 ( IL-2 ) and interferon-alpha2b ( IFN ) compared with dacarbazine ( DTIC ) in adult patients with stage IV melanoma was evaluated . PATIENTS AND METHODS Two hundred and forty-one patients were r and omized to either receive repeated 4-week cycles of IFN [ 3 MIU , s.c . , once daily for 7 days ] , IL-2 ( 2.4 MIU/m(2 ) , s.c . , twice a day for 5 days ) and HDC ( 1 mg , s.c . , twice a day for 5 days ) or DTIC 850 mg/m(2 ) i.v . every 3 weeks . The primary endpoint was overall survival . RESULTS Median survival was longer for patients receiving HDC/IL-2/IFN ( 271 days ) than for patients receiving DTIC ( 231 days ) , but this did not achieve statistical significance . Four patients receiving HDC/IL-2/IFN and nine receiving DTIC experienced at least one grade 4 adverse event . Striking differences in overall survival were observed between countries participating in the study . CONCLUSION Treatment with HDC/IL-2/IFN was safely administered on an outpatient basis , but this immunotherapeutic regimen did not improve upon the response rate and overall survival seen with DTIC |
2,425 | 21,311,394 | In all the studies , surgery showed better results for pain , disability , and quality of life , although not for walking ability .
Results of surgery were similar among patients with and without spondylolisthesis , and slightly better among those with neurogenic claudication than among those without it .
In patients with symptomatic LSS , the implantation of a specific type of device or decompressive surgery , with or without fusion , is more effective than continued conservative treatment when the latter has failed for 3 to 6 months | OBJECTIVE To compare the effectiveness of surgery versus conservative treatment on pain , disability , and loss of quality of life caused by symptomatic lumbar spinal stenosis ( LSS ) .
SUMMARY OF BACKGROUND DATA LSS is the most common reason for spine surgery in persons older than 65 years in the United States . | Study Design . Single blind r and omized study . Objectives . To compare the effectiveness of lumbar instrumented fusion with cognitive intervention and exercises in patients with chronic low back pain and disc degeneration . Summary of Background Data . To the authors ’ best knowledge , only one r and omized study has evaluated the effectiveness of lumbar fusion . The Swedish Lumbar Spine Study reported that lumbar fusion was better than continuing physiotherapy and care by the family physician . Patients and Methods . Sixty-four patients aged 25–60 years with low back pain lasting longer than 1 year and evidence of disc degeneration at L4–L5 and /or L5–S1 at radiographic examination were r and omized to either lumbar fusion with posterior transpedicular screws and postoperative physiotherapy , or cognitive intervention and exercises . The cognitive intervention consisted of a lecture to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The main outcome measure was the Oswestry Disability Index . Results . At the 1-year follow-up visit , 97 % of the patients , including 6 patients who had either not attended treatment or changed groups , were examined . The Oswestry Disability Index was significantly reduced from 41 to 26 after surgery , compared with 42 to 30 after cognitive intervention and exercises . The mean difference between groups was 2.3 ( −6.7 to 11.4 ) ( P = 0.33 ) . Improvements inback pain , use of analgesics , emotional distress , life satisfaction , and return to work were not different . Fear-avoidance beliefs and fingertip-floor distance were reduced more after nonoperative treatment , and lower limb pain was reduced more after surgery . The success rateaccording to an independent observer was 70 % after surgery and 76 % after cognitive intervention and exercises . The early complication rate in the surgical group was 18 % . Conclusion . The main outcome measure showed equal improvement in patients with chronic low back pain and disc degeneration r and omized to cognitive intervention and exercises , or lumbar fusion BACKGROUND Management of degenerative spondylolisthesis with spinal stenosis is controversial . Surgery is widely used , but its effectiveness in comparison with that of nonsurgical treatment has not been demonstrated in controlled trials . METHODS Surgical c and i date s from 13 centers in 11 U.S. states who had at least 12 weeks of symptoms and image-confirmed degenerative spondylolisthesis were offered enrollment in a r and omized cohort or an observational cohort . Treatment was st and ard decompressive laminectomy ( with or without fusion ) or usual nonsurgical care . The primary outcome measures were the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) bodily pain and physical function scores ( 100-point scales , with higher scores indicating less severe symptoms ) and the modified Oswestry Disability Index ( 100-point scale , with lower scores indicating less severe symptoms ) at 6 weeks , 3 months , 6 months , 1 year , and 2 years . RESULTS We enrolled 304 patients in the r and omized cohort and 303 in the observational cohort . The baseline characteristics of the two cohorts were similar . The one-year crossover rates were high in the r and omized cohort ( approximately 40 % in each direction ) but moderate in the observational cohort ( 17 % crossover to surgery and 3 % crossover to nonsurgical care ) . The intention-to-treat analysis for the r and omized cohort showed no statistically significant effects for the primary outcomes . The as-treated analysis for both cohorts combined showed a significant advantage for surgery at 3 months that increased at 1 year and diminished only slightly at 2 years . The treatment effects at 2 years were 18.1 for bodily pain ( 95 % confidence interval [ CI ] , 14.5 to 21.7 ) , 18.3 for physical function ( 95 % CI , 14.6 to 21.9 ) , and -16.7 for the Oswestry Disability Index ( 95 % CI , -19.5 to -13.9 ) . There was little evidence of harm from either treatment . CONCLUSIONS In nonr and omized as-treated comparisons with careful control for potentially confounding baseline factors , patients with degenerative spondylolisthesis and spinal stenosis treated surgically showed substantially greater improvement in pain and function during a period of 2 years than patients treated nonsurgically . ( Clinical Trials.gov number , NCT00000409 [ Clinical Trials.gov ] . ) Abstract . The reported complication rates after various surgical techniques used to create a lumbar fusion vary within wide ranges . In a previous paper , the Swedish Lumbar Spine Study Group have reported on the clinical outcome of lumbar spine fusion for chronic low back pain in a comparably homogeneous patient population where there were no significant differences between baseline sociodemographic , clinical and para clinical characteristics . In this report we compared the complication rates of the surgical procedures used in that study and analyzed the association between complications and baseline variables , and between outcome results and complications . A multicenter r and omized study was conducted where 211 patients aged 25–65 were treated with lumbar fusion according to three different surgical techniques : noninstrumented posterolateral fusion ( PLF , n=71 ) , instrumented posterolateral fusion ( VSP , n=68 ) , and in the third procedure we added an interbody fusion with solid autogenous bone grafts ( " 360 " , n=72 ) . We categorized complications as : early/late , major/minor . The association between complications and sociodemographic characteristics ( age , gender , comorbidity , previous surgery , smoking ) , and technical variables ( surgical technique , levels fused , hospital category ) was analyzed . The association between outcome variables ( patient global assessment , pain , disability , depressive symptoms ) and complications was analyzed . A literature review was conducted . There was no mortality . There was no significant difference in clinical outcome between the surgical groups after 2 years , although the power to detect such a difference was low . The total complication rate after 2 years in the PLF group was 12 % , compared with 22 % in the VSP group , and 40 % in the " 360 " group ( P=0.0003 ) . After exclusion of complications , there was still no difference in outcome between the groups . The odds ratio ( confidence intervals ) of having a complication was 5.3 ( 2.2–12.7 ) when " 360 " was used compared with PLF , and 2.4 ( 1.1–5.3 ) for " 360 " compared with VSP . There was no association between clinical outcome and complications on a group level . The reintervention rate was 6 % in the PLF group , 22 % in the VSP , and 17 % in the " 360 " group ( P=0.020 ) . The odds ratio ( confidence intervals ) of having a reintervention was 4.0 ( 1.3–11.9 ) when instrumentation was used compared with non-instrumented fusion . In this prospect i ve r and omized study comparing three lumbar fusion techniques in a comparably homogeneous patient population , complications increased significantly with increasing technicality of the surgical procedure . Even though we did not find a significant association between clinical outcome and complications after 2 years , the increased morbidity inflicted on an individual patient was not negligible . In this light , and as no fusion technique produced superior clinical outcome irrespective of whether complications were included or excluded in the analyses , the patient and the treating physician should carefully discuss the possible advantages and drawbacks of the different surgical options before making a decision . In order to make valid comparisons of both complication and reintervention rates after lumbar fusion , there is a need for a consensus in the spinal society regarding the definition of these entities Background Decompressive laminotomy is the st and ard surgical procedure in the treatment of patients with canal stenosis related intermittent neurogenic claudication . New techniques , such as interspinous process implants , cl aim a shorter hospital stay , less post-operative pain and equal long-term functional outcome . A comparative ( cost- ) effectiveness study has not been performed yet . This protocol describes the design of a r and omized controlled trial ( RCT ) on ( cost- ) effectiveness of the use of interspinous process implants versus conventional decompression surgery in patients with lumbar spinal stenosis . Methods / Design Patients ( age 40 - 85 ) presenting with intermittent neurogenic claudication due to lumbar spinal stenosis lasting more than 3 months refractory to conservative treatment , are included . R and omization into interspinous implant surgery versus bony decompression surgery will take place in the operating room after induction of anesthesia . The primary outcome measure is the functional assessment of the patient measured by the Zurich Claudication Question naire ( ZCQ ) , at 8 weeks and 1 year after surgery . Other outcome parameters include perceived recovery , leg and back pain , incidence of re-operations , complications , quality of life , medical consumption , absenteeism and costs . The study is a r and omized multi-institutional trial , in which two surgical techniques are compared in a parallel group design . Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 1 year . Discussion Currently decompressive laminotomy is the golden st and ard in the surgical treatment of lumbar spinal stenosis . Whether surgery with interspinous implants is a reasonable alternative can be determined by this trial . Trial registerDutch Trial register number : We prospect ively evaluated the results of decompression of the spine , with and without arthrodesis , for the treatment of lumbar spinal stenosis without instability in forty-five patients ( twenty-one men and twenty-four women ) who had been managed between November 1989 and November 1990 . The average age at the time of the operation was sixty-seven years ( range , forty-eight to eighty-seven years ) . The patients were r and omly assigned to one of three treatment groups ( fifteen patients in each group ) according to when they were admitted to the hospital . Group I was treated with decompression with laminotomy and medial facetectomy ; Group II , with decompression and arthrodesis of the most stenotic segment ; and Group III , with decompression and arthrodesis of all of the decompressed vertebral segments . All of the operations were performed by the same surgeon . The average duration of follow-up was twenty-eight months ( range , twenty-four to thirty-two months ) . All three groups had a significant improvement in the distance that the patients were able to walk at the time of the latest follow-up examination compared with before the operation ( p < 0.001 for Group I , p < 0.002 for Group II , and p < 0.005 for Group III ) . With the numbers available , there were no significant differences in the results among the three groups with regard to the relief of pain ( p = 0.25 for Group I compared with Group II , p = 0.36 for Group II compared with Group III , and p = 0.92 for Group I compared with Group III ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks , but the optimal timing of surgery is not known . METHODS We r and omly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed . The primary outcomes were the score on the Rol and Disability Question naire , the score on the visual-analogue scale for leg pain , and the patient 's report of perceived recovery during the first year after r and omization . Repeated- measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups . RESULTS Of 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiskectomy after a mean of 2.2 weeks . Of 142 patients design ated for conservative treatment , 55 ( 39 % ) were treated surgically after a mean of 18.7 weeks . There was no significant overall difference in disability scores during the first year ( P=0.13 ) . Relief of leg pain was faster for patients assigned to early surgery ( P<0.001 ) . Patients assigned to early surgery also reported a faster rate of perceived recovery ( hazard ratio , 1.97 ; 95 % confidence interval , 1.72 to 2.22 ; P<0.001 ) . In both groups , however , the probability of perceived recovery after 1 year of follow-up was 95 % . CONCLUSIONS The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment with eventual surgery if needed , but the rates of pain relief and of perceived recovery were faster for those assigned to early surgery . ( Current Controlled Trials number , IS RCT N26872154 [ controlled-trials.com ] . ) Summary of Background Data . The Spine Patient Outcomes Research Trial ( SPORT ) was design ed to assess the relative efficacy and cost-effectiveness of surgical and nonsurgical approaches to the treatment of common conditions associated with low back and leg pain . Objectives . To describe the rationale and design of the SPORT project and to discuss its strengths and limitations . Study Design . Descriptive . Methods . First , the authors explain the rationale for embarking on SPORT , i.e. , deficiencies in the existing scientific knowledge base for treatment of these conditions . Second , the authors describe the design of SPORT , including topics such as specific aims , participating sites , study population , recruitment and enrollment , study interventions , follow-up , outcomes , statistical analysis , and study governance and organization . Finally , issues that complicate the performance of r and omized trials in surgery as they relate to the design and conduct of SPORT are discussed . Results . The SPORT project is being conducted at 11 clinical centers around the United States . It involves the simultaneous conduct of three multicenter , r and omized , controlled clinical trials . The study includes patients with the three most common diagnoses for which spine surgery is performed : intervertebral disc herniation , spinal stenosis , and degenerative spondylolisthesis , and it compares the most commonly used st and ard surgical and nonsurgical treatments for patients with these diagnoses . By the end of enrollment the authors anticipate a total of 500 patients with intervertebral disc herniation , 370 patients with spinal stenosis , and 300 patients with degenerative spondylolisthesis in the r and omized trials . Patients who meet the eligibility criteria but decline to be r and omized are invited to participate in an observational cohort study . Patients are being followed for a minimum of 24 months with visits scheduled at 6 weeks and at 3 , 6 , 12 , and 24 months . Conclusions . The results of this study will provide high- quality scientific evidence to aid clinical decision-making and improve treatment outcomes for these common , costly , and , in some instances , debilitating conditions Study Design This paper describes the background and factors that led to the development and implementation of the Maine Lumbar Spine Study , a prospect i ve cohort study of patients undergoing surgical and non‐surgical treatment of herniated lumbar disc with sciatica and symptomatic spinal stenosis . Objectives To define the factors leading to the study and the methods of design ing and implementing a community‐based effectiveness study to evaluate the outcomes of herniated lumbar intervertebral disc and spinal stenosis . Summary of Background Data Variations in the utilization of surgery for these conditions and physicians ' uncertainty regarding the best way to manage them result ed in support of a community‐based study of the effectiveness of treatment alternatives . Methods A prospect i ve cohort design was used . Methods of patient enrollment , data collection , management , and analysis are described . An innovative method of ascertaining the representativeness of the enrolled versus nonenrolled patient population is presented . Results The importance of developing community‐based networks of physicians is discussed . Conclusions These networks play an important role in analyzing practice pattern variations and in stimulating and participating in effectiveness research . Because effectiveness studies must be conducted at the community level , mechanisms must be developed with which to support and implement these efforts Abstract Objectives To assess the clinical effectiveness of surgical stabilisation ( spinal fusion ) compared with intensive rehabilitation for patients with chronic low back pain . Design Multicentre r and omised controlled trial . Setting 15 secondary care orthopaedic and rehabilitation centres across the United Kingdom . Participants 349 participants aged 18 - 55 with chronic low back pain of at least one year 's duration who were considered c and i date s for spinal fusion . Intervention Lumbar spine fusion or an intensive rehabilitation programme based on principles of cognitive behaviour therapy . Main outcome measure The primary outcomes were the Oswestry disability index and the shuttle walking test measured at baseline and two years after r and omisation . The SF-36 instrument was used as a secondary outcome measure . Results 176 participants were assigned to surgery and 173 to rehabilitation . 284 ( 81 % ) provided follow-up data at 24 months . The mean Oswestry disability index changed favourably from 46.5 ( SD 14.6 ) to 34.0 ( SD 21.1 ) in the surgery group and from 44.8 ( SD14.8 ) to 36.1 ( SD 20.6 ) in the rehabilitation group . The estimated mean difference between the groups was –4.1 ( 95 % confidence interval –8.1 to –0.1 , P = 0.045 ) in favour of surgery . No significant differences between the treatment groups were observed in the shuttle walking test or any of the other outcome measures . Conclusions Both groups reported reductions in disability during two years of follow-up , possibly unrelated to the interventions . The statistical difference between treatment groups in one of the two primary outcome measures was marginal and only just reached the predefined minimal clinical difference , and the potential risk and additional cost of surgery also need to be considered . No clear evidence emerged that primary spinal fusion surgery was any more beneficial than intensive rehabilitation OBJECT This study was conducted to compare the quality of life ( QOL ) in patients with neurogenic intermittent claudication ( NIC ) secondary to lumbar spinal stenosis ( LSS ) . Using the 36-Item Short Form ( SF-36 ) question naire , the authors compared the results obtained in patients treated with the X STOP Interspinous Process Decompression ( IPD ) System with those obtained in patients who underwent nonoperative therapies . METHODS Patients with LSS were enrolled in a prospect i ve 2-year multicenter study and r and omized either to the X STOP or nonoperative group . The SF-36 survey was used to assess the QOL before treatment and at 6 weeks , 6 months , 1 year , and 2 years posttreatment . An analysis of variance was used to compare individual pre- and posttreatment mean SF-36 domain scores between the two groups and within each treatment group . At all posttreatment time points , the authors observed the following : ( 1 ) mean domain scores in X STOP-treated patients were significantly greater than those in patients treated nonoperatively , with the exception of the mean General Health ( GH ) , Role Emotional , and Mental Component Summary scores at 2 years ; and ( 2 ) mean posttreatment domain scores documented in X STOP-treated patients were significantly greater than mean pretreatment scores , with the exception of mean GH scores at 6 , 12 , and 24 months . CONCLUSIONS The results of this study demonstrate that the X STOP device is significantly more effective than nonoperative therapy in improving the QOL in patients with LSS . The results are comparable with those reported in other studies involving traditional decompressive techniques for LSS and suggest that the X STOP implant can provide an effective treatment compared with nonoperative and conventional surgical therapies Study Design . A prospect i ve observational cohort study . Objective . To assess long-term outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically . Summary of Background Data . The relative benefit of various treatments for lumbar spinal stenosis is uncertain . Surgical treatment has been associated with short-term improvement , but recurrence of symptoms has been documented . Few studies have compared long-term outcomes of surgical and nonsurgical treatments . Methods . Patients recruited from the practice s of orthopaedic surgeons , neurosurgeons , and occupational medicine physicians throughout Maine had baseline interviews with follow-up question naires mailed at regular intervals over 10 years . Clinical data were obtained at baseline from a physician question naire . Most patients initially undergoing surgery had a laminectomy without fusion performed . Outcomes including patient-reported symptoms of leg and back pain , functional status , and satisfaction were assessed at 8- to 10-year follow-up . Primary analyses were based on initial treatment received with secondary analyses examining actual treatment received by 10 years . Results . Of 148 eligible consenting patients initially enrolled , 105 were alive after 10 years ( 67.7 % survival rate ) . Among surviving patients , long-term follow-up between 8 and 10 years was available for 97 of 123 ( 79 % ) patients ( including 11 patients who died before the 10-year follow-up but completed a 8 or 9 year survey ) ; 56 of 63 ( 89 % ) initially treated surgically and 41 of 60 ( 68 % ) initially treated nonsurgically . Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically . Outcomes at 1 and 4 years favored initial surgical treatment . After 8 to 10 years , a similar percentage of surgical and nonsurgical patients reported that their low back pain was improved(53 % vs. 50 % , P = 0.8 ) , their predominant symptom ( either back or leg pain ) was improved ( 54 % vs. 42 % , P = 0.3 ) , and they were satisfied with their current status ( 55 % vs. 49 % , P = 0.5 ) . These treatment group findings persisted after adjustment for other determinants of outcome in multivariate models . However , patients initially treated surgically reported less severe leg pain symptoms and greater improvement in back-specific functional status after 8 to 10 years than nonsurgically treated patients . By 10 years , 23 % of surgical patients had undergone at least one additional lumbar spine operation , and 39 % of nonsurgical patients had at least one lumbar spine operation . Patients undergoing subsequent surgical procedures had worse outcomes than those continuing with their initial treatment . Outcomes according to actual treatment received at 10 years did not differ because individuals undergoing additional surgical procedures had worse outcomes than those continuing with their initial treatment . Conclusions . Among patients with lumbar spinal stenosis completing 8- to 10-year follow-up , low back pain relief , predominant symptom improvement , and satisfaction with the current state were similar in patients initially treated surgically or nonsurgically . However , leg pain relief and greater back-related functional status continued to favor those initially receiving surgical treatment . These results support a shared decision-making approach among physicians and patients when considering treatment options for lumbar spinal stenosis BACKGROUND The management of degenerative spondylolisthesis associated with spinal stenosis remains controversial . Surgery is widely used and has recently been shown to be more effective than nonoperative treatment when the results were followed over two years . Questions remain regarding the long-term effects of surgical treatment compared with those of nonoperative treatment . METHODS Surgical c and i date s from thirteen centers with symptoms of at least twelve weeks ' duration as well as confirmatory imaging showing degenerative spondylolisthesis with spinal stenosis were offered enrollment in a r and omized cohort or observational cohort . Treatment consisted of st and ard decompressive laminectomy ( with or without fusion ) or usual nonoperative care . Primary outcome measures were the Short Form-36 ( SF-36 ) bodily pain and physical function scores and the modified Oswestry Disability Index at six weeks , three months , six months , and yearly up to four years . RESULTS In the r and omized cohort ( 304 patients enrolled ) , 66 % of those r and omized to receive surgery received it by four years whereas 54 % of those r and omized to receive nonoperative care received surgery by four years . In the observational cohort ( 303 patients enrolled ) , 97 % of those who chose surgery received it whereas 33 % of those who chose nonoperative care eventually received surgery . The intent-to-treat analysis of the r and omized cohort , which was limited by nonadherence to the assigned treatment , showed no significant differences in treatment outcomes between the operative and nonoperative groups at three or four years . An as-treated analysis combining the r and omized and observational cohorts that adjusted for potential confounders demonstrated that the clinical ly relevant advantages of surgery that had been previously reported through two years were maintained at four years , with treatment effects of 15.3 ( 95 % confidence interval , 11 to 19.7 ) for bodily pain , 18.9 ( 95 % confidence interval , 14.8 to 23 ) for physical function , and -14.3 ( 95 % confidence interval , -17.5 to -11.1 ) for the Oswestry Disability Index . Early advantages ( at two years ) of surgical treatment in terms of the secondary measures of bothersomeness of back and leg symptoms , overall satisfaction with current symptoms , and self-rated progress were also maintained at four years . CONCLUSIONS Compared with patients who are treated nonoperatively , patients in whom degenerative spondylolisthesis and associated spinal stenosis are treated surgically maintain substantially greater pain relief and improvement in function for four years Patients suffering from neurogenic intermittent claudication secondary to lumbar spinal stenosis have historically been limited to a choice between a decompressive laminectomy with or without fusion or a regimen of non-operative therapies . The X STOP Interspinous Process Distraction System ( St. Francis Medical Technologies , Concord , Calif. ) , a new interspinous implant for patients whose symptoms are exacerbated in extension and relieved in flexion , has been available in Europe since June 2002 . This study reports the results from a prospect i ve , r and omized trial of the X STOP conducted at nine centers in the U.S. Two hundred patients were enrolled in the study and 191 were treated ; 100 received the X STOP and 91 received non-operative therapy ( NON OP ) as a control . The Zurich Claudication Question naire ( ZCQ ) was the primary outcomes measurement . Vali date d for lumbar spinal stenosis patients , the ZCQ measures physical function , symptom severity , and patient satisfaction . Patients completed the ZCQ upon enrollment and at follow-up periods of 6 weeks , 6 months , and 1 year . Using the ZCQ criteria , at 6 weeks the success rate was 52 % for X STOP patients and 10 % for NON OP patients . At 6 months , the success rates were 52 and 9 % , respectively , and at 1 year , 59 and 12 % . The results of this prospect i ve study indicate that the X STOP offers a significant improvement over non-operative therapies at 1 year with a success rate comparable to published reports for decompressive laminectomy , but with considerably lower morbidity STUDY DESIGN A prospect i ve r and omized study was performed . OBJECTIVE To determine whether posterolateral fusion in patients with adult isthmic spondylolisthesis results in an improved outcome compared with an exercise program . SUMMARY OF BACKGROUND DATA In spondylolisthesis , satisfactory results have been reported with both surgical and conservative management . The evidence for treatment efficacy , however , is weak because prospect i ve r and omized studies are lacking . METHODS In this study , 111 patients were r and omly allocated to an exercise program ( n = 34 ) or posterolateral fusion with or without transpedicular fixation ( n = 77 ) . The inclusion criteria were lumbar isthmic spondylolisthesis of any grade , at least 1 year of low back pain or sciatica , and a severely restricted functional ability in individuals 18 to 55 years of age . Pain and functional disability were quantified before treatment and at 1- and 2-year follow-up assessment s by visual analog scales ( VAS ) . RESULTS The 2-year follow-up rate was 93 % . The functional outcome , as assessed by the Disability Rating Index and the pain reduction , was better in the surgically treated group than in the exercise group at both the 1- and 2-year follow-up assessment s ( P < 0.01 ) . In the longitudinal analysis , the mean Disability Rating Index and pain improved in the surgical group ( P < 0.0001 ) . In the exercise group , the Disability Rating Index did not change at all , whereas the pain decreased slightly ( P < 0.02 ) . CONCLUSIONS Surgical management of adult isthmic spondylolisthesis improves function and relieves pain more efficiently than an exercise program Study Design . A prospect i ve r and omized clinical study . Objectives . To evaluate supplementary pedicle screw fixation ( Cotrel‐Dubousset ) in posterolateral lumbar spinal fusion . Summary of Background Data . The rationale behind lumbar fusion is to eliminate pathologic motion to relieve pain . To improve fusion rates and to allow reduction , a rigid transpedicular screw fixation may be beneficial , but the positive effect of this may be counter‐balanced by an increase in complications . Methods . The inclusion criteria were severe , chronic low back pain from spondylolisthesis Grade s 1 and 2 or from primary or secondary degenerative segmental instability . One hundred thirty patients were r and omly allocated to receive no instrumentation ( n = 66 ) or Cotrel‐Dubousset instrumentation ( n = 64 ) in posterolateral lumbar fusion . Variables were registered at the time of surgery and at 1 and 2 years after surgery . Results . Follow‐up was achieved in 97.7 % of the patients . Fusion rates deduced from plain radiographs were not significantly different between instrumented and noninstrumented groups . The functional outcome assessed by the Dallas Pain Question naire improved significantly in both groups , and there were no significant differences in results between the two groups , except for significantly better ( P < 0.05 ) functional outcome in relation to daily activities in the instrumented group when neural decompression had been performed . The global patients ' satisfaction was 82 % in the instrumented group versus 74 % in the noninstrumented group ( not significant ) . Fixation of instrumentation increased operation time , blood loss , and early reoperation rate significantly . Patients experienced only a few minor postoperative complications ; none were major . Two infections appeared in the Cotrel‐Dubousset group . Significant symptoms from misplacement of pedicle screws were seen in 4.8 % of the instrumented patients . Conclusions . Lumbar posterolateral fusion with pedicle screw fixation increases the operation time , blood loss , and reoperation rate , and leads to a significant risk of nerve injury . The functional outcome improves significantly with high patient satisfaction , with or without instrumentation . No significant differences were observed between the two groups in functional outcome and fusion rate . The only gain in functional outcome from instrumentation was found in the daily activity category in patients with supplementary neural decompression . The results of this study do not justify the general use of pedicle screw fixation alone as an adjunct to posterolateral lumbar fusion STUDY DESIGN A cohort of 100 patients with symptomatic lumbar spinal stenosis , characterized in a previous article , were given surgical or conservative treatment and followed for 10 years . OBJECTIVES To identify the short- and long-term results after surgical and conservative treatment , and to determine whether clinical or radiologic predictors for the treatment result can be defined . SUMMARY OF BACKGROUND DATA Surgical decompression has been considered the rational treatment . However , clinical experience indicates that many patients do well with conservative treatment . METHODS In this study , 19 patients with severe symptoms were selected for surgical treatment and 50 patients with moderate symptoms for conservative treatment , whereas 31 patients were r and omized between the conservative ( n = 18 ) and surgical ( n = 13 ) treatment groups . Pain was decisive for the choice of treatment group . All patients were observed for 10 years by clinical evaluation and question naires . The results , evaluated by patient and physician , were rated as excellent , fair , unchanged , or worse . RESULTS After a period of 3 months , relief of pain had occurred in most patients . Some had relief earlier , whereas for others it took 1 year . After a period of 4 years , excellent or fair results were found in half of the patients selected for conservative treatment , and in four fifths of the patients selected for surgery . Patients with an unsatisfactory result from conservative treatment were offered delayed surgery after 3 to 27 months ( median , 3.5 months ) . The treatment result of delayed surgery was essentially similar to that of the initial group . The treatment result for the patients r and omized for surgical treatment was considerably better than for the patients r and omized for conservative treatment . Clinical ly significant deterioration of symptoms during the final 6 years of the follow-up period was not observed . Patients with multilevel afflictions , surgically treated or not , did not have a poorer outcome than those with single-level afflictions . Clinical or radiologic predictors for the final outcome were not found . There were no dropouts , except for 14 deaths . CONCLUSIONS The outcome was most favorable for surgical treatment . However , an initial conservative approach seems advisable for many patients because those with an unsatisfactory result can be treated surgically later with a good outcome Study Design . A r and omized controlled multicenter study with a 2-year follow-up by an independent observer . Objectives . To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain ( CLBP ) . Summary of Background Data . The reported results after fusion surgery on patients with CLBP vary considerably , and the evidence of treatment efficacy is weak in the absence of r and omized controlled studies . Patients and Methods . A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were r and omized blindly into four treatment groups . Patients aged 25–65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4–L5 , L5-S1 , or both were eligible to participate in the study . The surgical group ( n=222 ) included three different fusion techniques , not analyzed separately in this study . Patients in the nonsurgical group ( n=72 ) were treated with different kinds of physical therapy . The surgical group comprised 49.5 % men , and the mean age was 43 years . The corresponding figures for the nonsurgical group were 48.6 % and 44 years . The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years , respectively . The Visual Analogue Scale ( VAS ) was used to measure pain . The Oswestry Low Back Pain Question naire , the Million Score and the General Function Score ( GFS ) were used to measure disability . The Zung Depression Scale was used to measure depressive symptoms . The overall result was assessed by the patient and by an independent observer . Records from the Swedish Social Insurance were used to evaluate work disability . Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle . Results . At the 2-year follow-up 289 of 294 ( 98 % ) patients , including 25 who had changed groups , were examined . Back pain was reduced in the surgical group by 33 % ( 64 to 43 ) , compared with 7 % ( 63 to 58 ) in the nonsurgical group ( P = 0.0002 ) . Pain improved most during the first 6 months and then gradually deteriorated . Disability according to Oswestry was reduced by 25 % ( 47 to 36 ) compared with 6 % ( 48 to 46 ) among nonsurgical patients ( P = 0.015 ) , according to Million by 28 % ( 64 to 46 ) compared with 8 % ( 66 to 60 ) ( P = 0.004 ) , and accordingtoGFS by 31 % ( 49 to 34 ) compared with 4 % ( 48 to 46 ) ( P = 0.005 ) . The depressive symptoms , according to Zung , were reduced by 20 % ( 39 to 31 ) in the surgical group compared with 7 % ( 39 to 36 ) in the nonsurgical group ( P = 0.123 ) . In the surgical group 63 % ( 122/195 ) rated themselves as “ much better ” or “ better ” compared with 29 % ( 18/62 ) in the nonsurgical group ( P < 0.0001 ) . The “ net back to work rate ” was significantly in favor of surgical treatment , or 36 % vs. 13 % ( P = 0.002 ) . The early complication rate in the surgical group was 17 % . Conclusion . Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment Study Design . A r and omized controlled trial . Objectives . To assess the effectiveness of decompressive surgery as compared with nonoperative measures in the treatment of patients with lumbar spinal stenosis . Summary of Background Data . No previous r and omized trial has assessed the effectiveness of surgery in comparison with conservative treatment for spinal stenosis . Methods . Four university hospitals agreed on the classification of the disease , inclusion and exclusion criteria , radiographic routines , surgical principles , nonoperative treatment options , and follow-up protocol s. A total of 94 patients were r and omized into a surgical or nonoperative treatment group : 50 and 44 patients , respectively . Surgery comprised undercutting laminectomy of the stenotic segments in 10 patients augmented with transpedicular fusion . The primary outcome was based on assessment of functional disability using the Oswestry Disability Index ( scale , 0–100 ) . Data on the intensity of leg and back pain ( scales , 0–10 ) , as well as self-reported and measured walking ability were compiled at r and omization and at follow-up examinations at 6 , 12 , and 24 months . Results . Both treatment groups showed improvement during follow-up . At 1 year , the mean difference in favor of surgery was 11.3 in disability ( 95 % confidence interval [ CI ] , 4.3–18.4 ) , 1.7 in leg pain ( 95 % CI , 0.4–3.0 ) , and 2.3(95 % CI , 1.1–3.6 ) in back pain . At the 2-year follow-up , the mean differences were slightly less : 7.8 in disability ( 95 % CI , 0.8–14.9 ) 1.5 in leg pain ( 95 % CI , 0.3–2.8 ) , and 2.1 in back pain ( 95 % CI , 1.0–3.3 ) . Walking ability , either reported or measured , did not differ between the two treatment groups . Conclusions . Although patients improved over the 2-year follow-up regardless of initial treatment , those undergoing decompressive surgery reported greater improvement regarding leg pain , back pain , and overall disability . The relative benefit of initial surgical treatment diminished over time , but outcomes of surgery remained favorable at 2 years . Longer follow-up is needed to determine if these differences persist Study Design . A r and omized , controlled , prospect i ve multicenter trial comparing the outcomes of neurogenic intermittent claudication ( NIC ) patients treated with the interspinous process decompression system ( X STOP ) with patients treated nonoperatively . Objective . To determine the safety and efficacy of the X STOP interspinous implant . Summary of Background Data . Patients suffering from NIC secondary to lumbar spinal stenosis have been limited to a choice between nonoperative therapies and decompressive surgical procedures , with or without fusion . The X STOP was developed to provide an alternative therapeutic treatment . Methods . 191 patients were treated , 100 in the X STOP group and 91 in the control group . The primary outcomes measure was the Zurich Claudication Question naire , a patient-completed , vali date d instrument for NIC . Results . At every follow-up visit , X STOP patients had significantly better outcomes in each domain of the Zurich Claudication Question naire . At 2 years , the X STOP patients improved by 45.4 % over the mean baseline Symptom Severity score compared with 7.4 % in the control group ; the mean improvement in the Physical Function domain was 44.3 % in the X STOP group and −0.4 % in the control group . In the X STOP group , 73.1 % patients were satisfied with their treatment compared with 35.9 % of control patients . Conclusions . The X STOP provides a conservative yet effective treatment for patients suffering from lumbar spinal stenosis . In the continuum of treatment options , the X STOP offers an attractive alternative to both conservative care and decompressive surgery Abstract The effectiveness of lumbar fusion for chronic low back pain after surgery for disc herniation has not been evaluated in a r and omized controlled trial . The aim of the present study was to compare the effectiveness of lumbar fusion with posterior transpedicular screws and cognitive intervention and exercises . Sixty patients aged 25–60 years with low back pain lasting longer than 1 year after previous surgery for disc herniation were r and omly allocated to the two treatment groups . Experienced back surgeons performed transpedicular fusion . Cognitive intervention consisted of a lecture intended to give the patient an underst and ing that ordinary physical activity would not harm the disc and a recommendation to use the back and bend it . This was reinforced by three daily physical exercise sessions for 3 weeks . The primary outcome measure was the Oswestry Disability Index ( ODI ) . Outcome data were analyzed on an intention‐to‐treat basis . Ninety‐seven percent of the patients , including seven of eight patients who had either not attended treatment ( n = 5 ) or changed groups ( n = 2 ) , completed 1‐year follow‐up . ODI was significantly improved from 47 to 38 after fusion and from 45 to 32 after cognitive intervention and exercises . The mean difference between treatments after adjustment for gender was −7.3 ( 95 % CI −17.3 to 2.7 , p = 0.15 ) . The success rate was 50 % in the fusion group and 48 % in the cognitive intervention/exercise group . For patients with chronic low back pain after previous surgery for disc herniation , lumbar fusion failed to show any benefit over cognitive intervention and exercises Study Design The Maine Lumbar Spine Study is a prospect i ve cohort study of patients recruited from the practice s of orthopedic surgeons , neurosurgeons , and occupational medicine physicians throughout Maine . Objective To assess 1‐year outcomes of patients with sciatica believed to be due to a herniated lumbar disc treated surgically or nonsurgically . Summary of Background Data Lumbar spine surgery rates vary by geographic region and may reflect uncertainty about optimal clinical use . Methods Eligible consenting patients participated in a baseline interview performed by study personnel and then were mailed follow‐up question naires at 3 , 6 , and 12 months . Clinical data were obtained from a physician question naire . Outcomes included patient‐reported symptoms of leg and back pain , functional status , disability , quality of life , and satisfaction with care . Results Five hundred seven patients with sciatica , 275 treated surgically and 232 treated nonsurgically initially , were enrolled . Surgically treated patients , on average , had more severe symptoms and had more severe physical and imaging findings than nonsurgically treated patients at entry . Although few surgically treated patients had mild symptoms and few nonsurgically treated patients had severe symptoms , about half in each treatment group had symptoms that fell into a moderate category . At the 1‐year evaluation , improvement in symptoms , functional status , and disability were found in both treatment groups . However , surgically treated patients reported significantly greater improvement . For the predominant symptom , either back or leg pain , 71 % of surgically treated and 43 % of nonsurgically treated patients reported definite improvement ( P < 0.001 ) . This effect was even greater after adjustment for differences between treatment groups at entry ( relative odds of definite improvement , 4.3 ; P < 0.001 ) . For patients with moderate symptoms and abnormal physical examination findings , surgical treatment also result ed in greater improvement than nonsurgical treatment . However , there was little difference in the employment or workers ' compensation status of patients treated surgically versus nonsurgically ( 5 % vs. 7 % unemployed at 1‐year follow‐up if employed at entry [ P = 0.68 ] ; 46 % vs. 55 % receiving workers ' compensation at 1‐year follow‐up if receiving it at entry [ P = 0.30 ] for surgical and nonsurgical management , respectively ) . For patients with mild symptoms , the benefits of surgical and nonsurgical treatment were similar . Conclusions Although surgically treated patients were on average more symptomatic at entry , there was substantial overlap in symptoms between surgically treated and nonsurgically treated patients . Surgically treated patients with sciatica reported substantially greater improvement at 1‐year follow‐up . However , employment and compensation outcomes were similar between the two treatment groups , and surgery appeared to provide little advantage for the subset of patients with mild symptoms . These results should be interpreted cautiously , because surgical treatment was not assigned r and omly . Long‐term follow‐up will determine if these differences persist Study Design . Clinical trial subgroup analysis . Objective . To compare outcomes of different fusion techniques treating degenerative spondylolisthesis ( DS ) . Summary of Background Data . Surgery has been shown to be more effective than nonoperative treatment out to 4 years . Questions remain regarding the differential effect of fusion technique . Methods . Surgical c and i date s from 13 centers in 11 states with at least 12 weeks of symptoms and confirmatory imaging showing stenosis and DS were studied . In addition to st and ard decompressive laminectomy , 1 of 3 fusion techniques was employed at the surgeon ’s discretion : posterolateral in situ fusion ( PLF ) ; posterolateral instrumented fusion with pedicle screws ( PPS ) ; or PPS plus interbody fusion ( 360 ° ) . Main outcome measures were the SF-36 bodily pain ( BP ) and physical function ( PF ) scales and the modified Oswestry Disability Index ( ODI ) assessed at 6 weeks , 3 months , 6 months , and yearly to 4 years . The as-treated analysis combined the r and omized and observational cohorts using mixed longitudinal models adjusting for potential confounders . Results . Of 380 surgical patients , 21 % ( N = 80 ) received a PLF ; 56 % ( N = 213 ) received a PPS ; 17 % ( N = 63 ) received a 360 ° ; and 6 % ( N = 23 ) had decompression only without fusion . Early outcomes varied , favoring PLF compared to PPS at 6 weeks ( PF : 12.73 vs. 6.22 , P < 0.020 ) and 3 months ( PF : 25.24 vs.18.95 , P < 0.025 ) and PPS compared to 360 ° at 6 weeks ( ODI : −14.46 vs. −9.30 , P < 0.03 ) and 3 months ( ODI : −22.30 vs. −16.78 , P < 0.02 ) . At 2 years , 360 ° had better outcomes : BP : 39.08 versus 29.17 PLF , P < 0.011 ; and versus 29.13 PPS , P < 0.002 ; PF : 31.93 versus 23.27 PLF , P < 0.021 ; and versus 25.29 PPS , P < 0.036 . However , these differences were not maintained at 3- and 4-year follow-up , when there were no statistically significant differences between the 3 fusion groups . Conclusion . In patients with DS and associated spinal stenosis , no consistent differences in clinical outcomes were seen among fusion groups over 4 years Study Design A prospect i ve cohort study of patients with lumbar spinal stenosis recruited from the practice s of orthopedic surgeons and neurosurgeons throughout Maine . Objective To assess 1‐year outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically . Summary of Background Data No r and omized trials and few nonexperimental studies have compared surgical and nonsurgical treatment of patients with lumbar spinal stenosis . The authors ' goal was to assess 1‐year outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically . Methods Eligible , consenting patients participated in baseline interviews and were then mailed follow‐up question naires at 3 , 6 , and 12 months . Clinical data were obtained from a physician question naire . Outcomes included patient‐reported symptoms of leg and back pain , functional status , disability , and satisfaction with care . Results One hundred forty‐eight patients with lumbar spinal stenosis were enrolled , of whom 81 were treated surgically and 67 treated nonsurgically . On average , patients in the surgical group had more severe imaging findings and symptoms and worse functional status than patients in the nonsurgical group at entry . Few patients with mild symptoms were treated surgically , and few patients with severe symptoms were treated nonsurgically . However , of the patients with moderate symptoms , a similar percent were treated surgically or nonsurgically . One year after study entry , 28 % of nonsurgically and 55 % of surgically treated patients reported definite improvement in their predominant symptoms ( P = 0.003 ) . For patients with moderate symptoms , outcomes for surgically treated patients were also improved compared with those of nonsurgically treated patients . Surgicla treatment remained a significant determinant of 1‐year outcome , even after adjustment for differences between treatment groups at entry ( P = 0.05 ) . The maximal benefit of surgery was observed by the time of the first follow‐up evaluation , which was at 3 months . Although few nonsurgically treated patients experienced a worsening of their condition , there was little improvement in symptoms and functional status compared with study entry . Conclusions At a 1‐year evaluation of patient‐reported outcomes , patients with severe lumbar spinal stenosis who were treated surgically had greater improvement than patients treated nonsurgically . Comparisons of outcomes by treatment received must be made cautiously because of differences in baseline characteristics . A determination of whether the outcomes observed persist requires long‐term follow‐up STUDY DESIGN A prospect i ve cohort study of patients with lumbar spinal stenosis recruited from the practice s of orthopedic surgeons and neurosurgeons throughout Maine . OBJECTIVE To assess 4-year outcomes for patients with lumbar spinal stenosis treated surgically or nonsurgically . SUMMARY OF BACKGROUND DATA Surgery for lumbar spinal stenosis has increased dramatically despite the lack of r and omized trials comparing surgical with nonsurgical treatments . Long-term evaluation of surgical series has documented deterioration in initial symptomatic improvement , but few studies have compared long-term outcomes of surgical and nonsurgical treatment . METHODS Eligible , consenting patients had baseline interviews with mailed follow-up question naires at 3 , 6 , and 12 months , then annually thereafter . Clinical data were obtained at baseline from a physician question naire . Outcomes included patient-reported symptoms of leg and back pain , functional status , and satisfaction . RESULTS Of 148 patients with lumbar spinal stenosis initially enrolled , 4-year outcomes were available on 119 patients ( 80.4 % ) : 67 of 81 ( 83 % ) treated surgically and 52 of 67 ( 78 % ) treated nonsurgically . The surgically treated patients had more severe symptoms and worse functional status at baseline and better outcomes at 4-year evaluation than the nonsurgically treated patients . After 4 years , 70 % of the surgically treated and 52 % of the nonsurgically treated patients reported that their predominant symptom , either leg or back pain , was better ( P = 0.05 ) . Satisfaction of patients with their current state at 4 years was reported by 63 % of the surgically treated and 42 % of the nonsurgically treated patients ( P = 0.04 ) . Surgical treatment remained a significant determinant of 4-year satisfaction , even after adjustment for other independent predictors ( P = 0.001 ) . For the nonsurgically treated patients , there was no significant change in outcomes over 4 years , whereas the initial improvement seen in the surgically treated patients modestly decreased over the subsequent 4 years . CONCLUSIONS For the patients with severe lumbar spinal stenosis , surgical treatment was associated with greater improvement in patient-reported outcomes than nonsurgical treatment at 4-year evaluation , even after adjustment for differences in baseline characteristics among treatment groups . The relative benefit of surgery declined over time but remained superior to nonsurgical treatment . Outcomes for the nonsurgically treated patients improved modestly and remained stable over 4 years . Determining whether outcomes continue to converge will require longer-term evaluation Study Design . A sub analysis study . Objective . The purpose of this study was to determine the impact of multilevel lumbar stenosis with or without degenerative spondylolisthesis compared to single level disease on patients ' baseline symptoms and clinical outcomes over time . Summary of Background Data . Previous studies have demonstrated better clinical outcomes with surgery than nonoperative treatment in patients with spinal stenosis with or without degenerative spondylolisthesis . However , the impact of multilevel stenosis has not been studied in these patients . Methods . The results from a multicenter r and omized and observational study , the Spine Patient Outcomes Research Trial ( SPORT ) comparing surgical versus nonoperative treatment for spinal stenosis with or without spondylolisthesis , were analyzed . The primary outcomes measures were the Bodily Pain and Physical Function scales of the Medical Outcomes Study 36-item Short-Form General Health Survey ( SF-36 ) and the modified Oswestry Disability Index at 6 weeks , 3 months , 6 months , 1 year , and 2 years . Secondary outcome measures included the stenosis bothersomeness index , leg pain bothersomeness , low back pain bothersomeness , and patient satisfaction . Results . In this sub analysis of SPORT data , multilevel spinal stenosis did not demonstrate worse baseline symptoms or worse treatment outcomes in isolated spinal stenosis ; however , if concomitant degenerative spondylolisthesis existed , patients with only single level stenosis tended to improve more than those with multilevel stenosis , particularly after surgery . Conclusion . Patients with spinal stenosis without associated degenerative spondylolisthesis or scoliosis can be managed nonoperatively irrespective of the number of levels involved . If surgery is performed , the number of levels treated does not predict outcome . In contrast , patients with concomitant degenerative spondylolisthesis and single level stenosis do better surgically than those with additional levels of stenosis . This study emphasizes the importance of shared decision-making between the physician and patient when considering treatment for spinal stenosis Study Design A prospect i ve , r and omized study of patients with symptomatic lumbar spinal stensosis . Objectives Evaluation of clinical and radiologic characteristics and relationship Summary of Background Data The diagnosis of lumbar spinal stenosis is frequently used and represents a wide variety of patients with more or less well defined spinal disorders . Methods One hundred patients who met inclusion criterie were consecutively salacted from a neurology department and examined clinical ly and radiologically with plain radiography , myelography , and computed tomographic imaging . Results Duration of complaints was long , and multilevel , bilateral afflictions were common . The dominating symptoms were sciatica , neurogenic claudication , and low back pain . The clinical findings were modest . Narrowness in the spinal canal was demonstrated radiologically with signs of compression on nerve roots , central ly and /or laterally . The radiologic findings were more extensive than expected from the clinical symptom and signs . In most patients the sagittal diameter of the spinal canal increased on flexion and decreased on extension of the spine . An exception was demonstrated in 33 patients where extension increased the diameter , usually at one level . Radiologic subgroups stenosis were found , but their clinical relationship could hardly be identified . No definite association between the degree of narrowing and clinical symptoms was found . Conclusions A clinical picture is demonstrated in 100 patients with symptomatic lumbar spinal stenosis . Different types of stenosis are found radiologically , but their clinical relationships are not identified . The radiologic changes were more extensive than expected from the clinical picture , and the degree of narrowing did not correspond to the degree of clinical affiliction BACKGROUND Today there is some evidence -based medicine support for a positive short-term treatment effect of fusion in chronic low back pain in spondylolisthesis and in nonspecific degenerative lumbar spine disorders . The long-term effect is , however , unknown . PURPOSE To determine the long-term outcome of lumbar fusion in adult isthmic spondylolisthesis . STUDY DESIGN Prospect i ve , r and omized controlled study comparing a 1-year exercise program with instrumented and non-instrumented posterolateral fusion with average long-term follow-up of 9 years ( range , 5 - 13 ) . PATIENT SAMPLE 111 patients aged 18 to 55 years with adult lumbar isthmic spondylolisthesis at L5 or L4 level of all degrees , and at least 1-year 's duration of severe lumbar pain with or without sciatica . OUTCOME MEASURES Pain and functional disability was quantified by pain ( VAS ) , the Disability Rating Index ( DRI ) , the Oswestry Disability Index ( ODI ) work status , and global assessment of outcome by the patient into much better , better , unchanged or worse . Quality of life was assessed by the SF-36 . METHODS The patients were r and omly allocated to treatment with 1 ) a 1-year exercise program ( n=34 ) , 2 ) posterolateral fusion without pedicle screw instrumentation ( n=37 ) , or 3 ) posterolateral fusion with pedicle screw instrumentation ( n=40 ) . Long-term follow-up was obtained in 101 ( 91 % ) patients . Nine patients in the exercise group were eventually operated on . RESULTS Longitudinal analysis : At long-term follow-up pain and functional disability were significantly better than before treatment in both surgical groups . No significant differences were observed between instrumented and non-instrumented patients in any variable studied . In the exercise group the pain was significantly reduced but not the functional disability . Compared with the 2-year follow-up a significant increase in functional disability was observed , as measured by the DRI , but not the ODI , in the surgical group at long term . In the exercise group no significant changes were observed between the 2-year and the long-term follow-up . Cross-sectional analysis : Between the surgical and conservative group no significant differences were observed in any outcome measurement at long-term follow-up except for global assessment , which was significantly better for surgical patients . Of surgical patients 76 % classified the overall outcome as much better or better compared with 50 % of conservatively treated patients ( p=0.015 ) . Quality of life as estimated by the SF-36 at long term was not different between treatment groups in any of the eight domains studied but was considerably lower than for the normal population . CONCLUSIONS Posterolateral fusion in adult lumbar isthmic spondylolisthesis results ina modestly improved long-term outcome compared with a 1-year exercise program . Although the results show that some of the previously reported short-term improvement is lost at long term , patients with fusion still classify their global outcome as clearly better than conservatively treated patients . Furthermore , because the long-term outcome of the patients conservatively treated most likely reflects the natural course , one can also conclude that no considerable spontaneous improvement should be expected over time in adult patients with symptomatic isthmic spondylolisthesis . Substantial pain , functional disability and a reduced quality of life will in most patients most likely remain unaltered over many years Regional variations in lumbar spinal fusion rates suggest a poor consensus on surgical indications . Therefore , complications , costs , and reoperation rates were compared for elderly patients undergoing surgery with or without spinal fusion . Subjects were Medicare recipients who underwent surgery in 1985 , with 4 years of subsequent follow-up . There were 27,111 eligible patients , of whom 5.6 % had fusions . Mean age was 72 years . Patients undergoing fusion had a complication rate 1.9 times greater than those who had surgery without fusion . The blood transfusion rate was 5.8 times greater , nursing home placement rate 2.2 times greater , and hospital charges 1.5 times higher ( all P < 0.0005 ) . Six-week mortality was 2.0 times greater for patients undergoing fusions ( P = 0.025 ) . Reoperation rates at 4 years were no lower for patients who had fusion surgery and results were similar in most diagnostic subgroups . Indications for fusion among older patients require better definition , preferably based on outcomes from prospect i ve controlled studies BACKGROUND Surgery for spinal stenosis is widely performed , but its effectiveness as compared with nonsurgical treatment has not been shown in controlled trials . METHODS Surgical c and i date s with a history of at least 12 weeks of symptoms and spinal stenosis without spondylolisthesis ( as confirmed on imaging ) were enrolled in either a r and omized cohort or an observational cohort at 13 U.S. spine clinics . Treatment was decompressive surgery or usual nonsurgical care . The primary outcomes were measures of bodily pain and physical function on the Medical Outcomes Study 36-item Short-Form General Health Survey ( SF-36 ) and the modified Oswestry Disability Index at 6 weeks , 3 months , 6 months , and 1 and 2 years . RESULTS A total of 289 patients were enrolled in the r and omized cohort , and 365 patients were enrolled in the observational cohort . At 2 years , 67 % of patients who were r and omly assigned to surgery had undergone surgery , whereas 43 % of those who were r and omly assigned to receive nonsurgical care had also undergone surgery . Despite the high level of nonadherence , the intention-to-treat analysis of the r and omized cohort showed a significant treatment effect favoring surgery on the SF-36 scale for bodily pain , with a mean difference in change from baseline of 7.8 ( 95 % confidence interval , 1.5 to 14.1 ) ; however , there was no significant difference in scores on physical function or on the Oswestry Disability Index . The as-treated analysis , which combined both cohorts and was adjusted for potential confounders , showed a significant advantage for surgery by 3 months for all primary outcomes ; these changes remained significant at 2 years . CONCLUSIONS In the combined as-treated analysis , patients who underwent surgery showed significantly more improvement in all primary outcomes than did patients who were treated nonsurgically . ( Clinical Trials.gov number , NCT00000411 [ Clinical Trials.gov ] . ) Study Design . Prospect i ve r and omized controlled trial . Objective . To assess effectiveness of microdiscectomy in lumbar disc herniation patients with 6 to 12 weeks of symptoms but no absolute indication for surgery . Summary of Background Data . There is limited evidence in favor of discectomy for prolonged symptoms of lumbar disc herniation . However , only one r and omized trial has directly compared discectomy with conservative treatment . Methods . Fifty-six patients ( age range , 20–50 years ) with a lumbar disc herniation , clinical findings of nerve root compression , and radicular pain lasting 6 to 12 weeks were r and omized to microdiscectomy or conservative management . Fifty patients ( 89 % ) were available at the 2-year follow-up . Leg pain intensity was the primary outcome measure . Results . There were no clinical ly significant differences between the groups in leg or back pain intensity , subjective disability , or health-related quality of life over the 2-year follow-up , although discectomy seemed to be associated with a more rapid initial recovery . In a subgroup analysis , discectomy was superior to conservative treatment when the herniation was at L4–L5 . Conclusions . Lumbar microdiscectomy offered only modest short-term benefits in patients with sciatica due to disc extrusion or sequester . Spinal level of the herniation may be an important factor modifying effectiveness of surgery , but this hypothesis needs verification Study Design . Cohort study . Objectives . To estimate the Minimal Clinical ly Important Change ( MCIC ) of the pain intensity numerical rating scale ( PI-NRS ) , the Quebec Back Pain Disability Scale ( QBPDS ) , and the Euroqol ( EQ ) in patients with low back pain . Summary of Background Data . MCIC can provide valuable information for research ers , healthcare providers , and policymakers . Methods . Data from a r and omized controlled trial with 442 patients with low back pain were used . The MCIC was estimated over a 12-week period , and three different methods were used : 1 ) mean change scores , 2 ) minimal detectable change , and 3 ) optimal cutoff point in receiver operant curves . The global perceived effect scale ( GPE ) was used as an external criterion . The effect of initial scores on the MCIC was also assessed . Results . The MCIC of the PI-NRS ranged from 3.5 to 4.7 points in (sub)acute patients and 2.5 to 4.5 points in chronic patients with low back pain . The MCIC of the QBPDS was estimated between 17.5 to 32.9 points and 8.5 to 24.6 points for (sub)acute and chronic patients with low back pain . The MCIC for the EQ ranged from 0.07 to 0.58 in (sub)acute patients and 0.09 to 0.28 in patients with chronic low back pain . Conclusion . Reporting the percentage of patients who have made a MCIC adds to the interpretability of study results . We present a range of MCIC values and advocate the choice of a single MCIC value according to the specific context OBJECTIVES To assess the relative effect of initial surgical and nonsurgical treatment on longitudinal outcomes of patients with lumbar spinal stenosis over a 10-year follow-up period . DESIGN A prospect i ve observational cohort study . SETTING Enrollment from community-based specialist practice s throughout Maine . PARTICIPANTS One hundred forty-four patients with lumbar spinal stenosis who had at least one follow-up : 77 initially treated surgically and 67 initially treated nonsurgically . INTERVENTION Initial surgical or nonsurgical treatment . MEASUREMENTS Clinical data were obtained at baseline and outcomes followed at regular intervals over 10 years with mailed question naires including patient-reported symptoms of back pain , leg symptoms , back-specific functional status , and satisfaction . Longitudinal data were analyzed using general linear mixed models . In addition to treatment ( initial surgical or nonsurgical care ) , time period , and the interaction between treatment and time , the models included baseline score , patient age and sex , and a time-varying general health status score . The effects of these covariates in explaining differences between treatment groups were also examined . The effect of subsequent surgical procedures was assessed using different analysis strategies . RESULTS The 10-year rate of subsequent surgical procedures was 23 % and 38 % for patients initially treated surgically and nonsurgically , respectively , and the overall 10-year survival rate was 69 % . Patients undergoing initial surgical treatment had worse baseline symptoms and functional status than those initially treated nonsurgically . For all outcomes and at each time point , surgically treated patients reported greater improvement in symptoms and functional status and higher satisfaction scores , indicative of better outcomes , than nonsurgically treated patients . However , the relative magnitude of the benefit diminished over time such that the relative differences for low back pain and satisfaction were no longer significant over long-term follow-up ( both P=.08 for treatment effect between 5 and 10 years after controlling for covariates ) . Regardless of initial treatment received , patients undergoing subsequent surgical procedures reported less improvement in outcomes over time than patients who did not undergo subsequent procedures , but the relative differences between treatment groups were similar in analyses that controlled for outcomes after subsequent procedures . CONCLUSION After controlling for covariates , patients initially treated surgically demonstrated better outcomes on all measures than those initially treated nonsurgically . Although outcomes of initial surgical treatment remained superior over time , the relative benefit of surgery diminished in later years , especially for low back pain and satisfaction . Patients undergoing subsequent surgery had worse outcomes regardless of initial treatment received , but excluding them did not change overall treatment group comparisons . The analytical methods described may be helpful in the design and analysis of future studies comparing treatment outcomes for patients with lumbar spinal stenosis Study Design . Prospect i ve cohort study . Objective . To create and vali date an index describing the extent of spine surgical intervention to allow fair comparisons of complication rates among patients treated by different surgeons , devices , or hospitals . Summary of Background Data . Safety comparisons in spine surgery are limited by lack of methods that adjust for important variations in the surgical “ case-mix . ” Among other factors , the magnitude of an operation is likely to have a substantial influence on the likelihood of complications . Methods . We created a spine surgery invasiveness index defined as the sum , across all vertebral levels , of 6 possible interventions on each operated vertebra : anterior decompression , anterior fusion , anterior instrumentation , posterior decompression , posterior fusion , and posterior instrumentation . We assessed the validity of this index by examining its association with blood loss and surgery duration in 1723 spine surgeries , adjusting for important factors including age , gender , body mass index , diagnosis , neurologic deficit , revision surgery , and vertebral level of surgery . Results . Blood loss increased by 11.5 % and surgery duration increased by 12.8 minutes for each unit increase in the invasiveness index . The invasiveness index explained 44 % of the variation in blood loss and 52 % of the variation in surgery duration . For specific surgical components , blood loss increased by 9.4 % and surgery duration by 11.4 minutes for each vertebral level of anterior decompression , 19.4 % and 33.8 minutes for each segment of anterior instrumentation , 12.9 % and 22.7 minutes for each level of posterior decompression , and 25.1 % and 18.8 minutes for each segment of posterior instrumentation . Conclusion . An “ invasiveness ” index based on the number of vertebrae decompressed , fused , or instrumented showed the expected associations with both blood loss and surgery duration . This quantitative description of surgery invasiveness may be useful to adjust for surgical variations when making safety comparisons in spine surgery OBJECT Interspinous process decompression ( IPD ) theoretically relieves narrowing of the spinal canal and neural foramen in extension and thus reduces the symptoms of neurogenic intermittent claudication ( NIC ) . The purpose of this study was to compare the efficacy of IPD with nonoperative treatment in patients with NIC secondary to degenerative spondylolisthesis . METHODS The authors conducted a r and omized controlled study in patients with NIC ; they compared the results obtained in patients treated with the X STOP IPD device with those acquired in patients treated nonoperatively . The X STOP implant is a titanium alloy device that is placed between the spinous processes to reduce the canal and foraminal narrowing that occurs in extension . In a cohort of 75 patients with degenerative spondylolisthesis , 42 underwent surgical treatment in which the X STOP IPD device was placed and 33 control individuals were treated nonoperatively . Patients underwent serial follow-up evaluations . The Zurich Claudication Question naire ( ZCQ ) , 36-Item Short Form Health Survey ( SF-36 ) , and radiographic assessment were used to determine outcomes . Two-year follow-up data were obtained in 70 of 75 patients . Statistically significant improvement in ZCQ and SF-36 scores was seen in X STOP device-treated patients but not in the nonoperative control patients at all postoperative intervals . Overall clinical success occurred in 63.4 % of X STOP device-treated patients and only 12.9 % of controls . Spondylolisthesis and kyphosis were unaltered . CONCLUSIONS The X STOP device was more effective than nonoperative treatment in the management of NIC secondary to degenerative lumbar spondylolisthesis The authors performed single- or multiple-level unilateral laminectomy to treat lumbar spinal stenosis in patients with mild to moderate leg pain and compared the results with those from patients treated with conservative therapy in a prospect i ve study . This decompression technique produced a 68 % rate of improvement compared with a 33 % rate for conservatively treated patients . The surgical group exhibited significant and sustained improvement , whereas the functional and clinical status of the conservatively managed group had returned to baseline during the same period . The preoperative dural sac cross-sectional area at the level of the most stenosis was 70.76 + /- 28.2 mm(2 ) for the surgical group , whereas on postoperative scans it was 108.12 + /- 31.5 mm(2 ) , with an average correction rate of 65 % . Neither new degenerative spondylolisthesis nor any evidence of instability was detected in any patient during the study Fifty patients who had spinal stenosis associated with degenerative lumbar spondylolisthesis were prospect ively studied clinical ly and radiographically to determine if concomitant intertransverse-process arthrodesis provided better results than decompressive laminectomy alone . There were thirty-six women and fourteen men . The mean age of the twenty-five patients who had had an arthrodesis was 63.5 years and that of the twenty-five patients who had not had an arthrodesis , sixty-five years . The level of the operation was between the fourth and fifth lumbar vertebrae in forty-one patients and between the third and fourth lumbar vertebrae in nine patients . The patients were followed for a mean of three years ( range , 2.4 to four years ) . In the patients who had had a concomitant arthrodesis , the results were significantly better with respect to relief of pain in the back and lower limbs |
2,426 | 26,130,030 | Directly addressing tobacco was not a significant moderator affecting tobacco use outcomes . | This meta- analysis synthesizes studies of brief interventions ( BIs ) that targeted alcohol consumption and reported both alcohol and tobacco outcomes .
It examines whether BIs reduce alcohol and tobacco use for adolescents and young adults among interventions that ( 1 ) directly targeted tobacco and alcohol use , or ( 2 ) did not target tobacco use but measured it as a secondary outcome . | Background Epidemiologic data indicate most adolescents and adults experience multiple , simultaneous risk behaviors . Purpose The purpose of this study is to examine the efficacy of a brief image-based multiple-behavior intervention ( MBI ) for college students . Methods A total of 303 college students were r and omly assigned to : ( 1 ) a brief MBI or ( 2 ) a st and ard care control , with a 3-month postintervention follow-up . Results Omnibus treatment by time multivariate analysis of variance interactions were significant for three of six behavior groupings , with improvements for college students receiving the brief MBI on alcohol consumption behaviors , F(6 , 261 ) = 2.73 , p = 0.01 , marijuana-use behaviors , F(4 , 278 ) = 3.18 , p = 0.01 , and health-related quality of life , F(5 , 277 ) = 2.80 , p = 0.02 , but not cigarette use , exercise , and nutrition behaviors . Participants receiving the brief MBI also got more sleep , F(1 , 281 ) = 9.49 , p = 0.00 , than those in the st and ard care control . Conclusions A brief image-based multiple-behavior intervention may be useful in influencing a number of critical health habits and health-related quality -of-life indicators of college students The authors evaluated the efficacy of a brief image-based prevention intervention and assessed current drug use as a moderator of intervention effects . In a clinical trial , 416 high school-age adolescents were r and omized to either the brief intervention or usual care control , with data collected at baseline and 3-month follow-up . The brief intervention consisted of a tailored in-person communication and a series of parent/guardian print material s based on the behavior-image model . Health behavior goal setting increased for participants receiving the brief intervention , with an effect size in the small range ( d = 0.33 ) . Overall effect sizes for cigarette smoking frequency and quantity and alcohol use frequency and quantity were small ( ds = 0.16 - 0.21 ) and in favor of the brief intervention . However , adolescents reporting current substance use who received the brief intervention reduced their frequency and heavy use of alcohol , frequency and quantity of cigarette smoking , and reported fewer alcohol/drug problems , with larger effects ranging from small to approaching medium in size ( ds = 0.32 - 0.43 , ps < .01 ) . This study suggests that brief image-based messages may increase health behavior goal setting and reduce substance use , particularly among drug-using older adolescents This study evaluated the efficacy of a brief integrative multiple behavior intervention and assessed risk factors as mediators of behavioral outcomes among older adolescents . A r and omized controlled trial was conducted with participants r and omly assigned to either a brief intervention or st and ard care control with 3-month follow-up . A total of 479 students attending two public high schools participated . Participants receiving the intervention showed a significant reduction in quantity × frequency of alcohol use , and increases in fruit and vegetable consumption and frequency of relaxation activities , compared to those receiving the control , P ’s = .01 . No effects were found on cigarette and marijuana use , exercise and sleep . Effect sizes were small with alcohol use cessation effects reaching medium size . Intervention effects were mediated by changes in peer influenceability for alcohol use , and self-efficacy and self-image for health promoting behaviors . Findings suggest that the brief intervention result ed in health risk and promoting behavior improvements for adolescents , with outcomes mediated by several risk factors BACKGROUND The prevention of initiation of tobacco , alcohol and drug use is a major societal challenge , for which the existing research literature is generally disappointing . This study aim ed to test the effectiveness of adaptation of Motivational Interviewing ( MI ) for universal prevention purpose s , i.e. to prevent initiation of new substance use among non-users , and to reduce risks among existing users . METHODS Cluster r and omised trial with 416 students aged 16 - 19 years old recruited in 12 London Further Education colleges without regard to substance use status . Individualised MI was compared with st and ard practice classroom-delivered Drug Awareness intervention , both delivered over the course of one lesson . Prevalence , initiation and cessation rates for the 3 target behaviours of cigarette smoking , alcohol consumption and cannabis use , along with reductions in use and harm indicators after both 3 and 12 months were assessed . RESULTS This adaptation of MI was not demonstrated to be effective in either intention-to-treat or sub-group analyses for any outcome . Unexpected lower levels of cannabis initiation and prevalence were found in the Drug Awareness control condition . CONCLUSIONS This particular adaptation of MI is ineffective as a universal drug prevention intervention and does not merit further study BACKGROUND Heavy drinking is one of the leading causes of morbidity and mortality in young men . Brief motivational intervention ( BMI ) has shown promising results for young people , but has never been tested in young men in the community who volunteered to receive an intervention . METHODS We evaluated the effectiveness of BMI in reducing alcohol use among heavy episodic users and in maintaining low-risk drinking among nonheavy episodic users . Participants were French-speaking young men attending the m and atory Swiss army conscription process . They were offered the opportunity to receive a 20-minute BMI , and those interested were r and omized into an intervention group ( BMI immediately ) or into a control group ( BMI after the 6-month follow-up assessment , in a waiting list design ) . Analyses were conducted separately for heavy and nonheavy episodic users ( separated using baseline heavy episodic use frequency ) as the hypotheses tested were different between both groups ( primary vs. secondary prevention intervention ) . RESULTS From a pool of 6,085 young men invited to receive BMI , 727 ( 11.9 % ) showed up and 572 were included in the study ( after exclusions related to organizational aspects of the conscription process ) . Among nonheavy episodic users , there was a protective effect of BMI on weekly alcohol use ( p < 0.05 ) . Among heavy episodic users , there were no significant effects of BMI . CONCLUSIONS About 12 % of young men were interested in addressing their drinking within the BMI framework , suggesting that there is some need for easily accessible alcohol intervention . The present intervention did have a preventive effect among low-risk young drinkers in helping them maintain their patterns of alcohol use . An explanation for the lack of effectiveness among heavy episodic users might be that those individuals interested in BMI had patterns of more severe alcohol use , thereby making change more difficult AIM To test whether beneficial effects of a single session of Motivational Interviewing ( MI ) on alcohol , tobacco and illicit drug use apparent after 3 months were maintained until 12 months . DESIGN Cluster r and omized trial , allocating 200 young people in the natural groups in which they were recruited to either MI ( n = 105 ) or to an assessment -only control condition ( n = 95 ) . SETTING Ten further education colleges across inner London . PARTICIPANTS Two hundred young people who were current users of illegal drugs ( age range 16 - 20 years ) with whom contact was established through peers trained for the project . INTERVENTION The intervention was adapted from MI in the form of a topic-based 1-hour single-session discussion . MEASUREMENTS Changes in cigarette , alcohol , cannabis and other drug use and perceptions of risk and harm between the time of recruitment and follow-up interviews after 3 and 12 months . FINDINGS A satisfactory follow-up rate ( 81 % ) was achieved . After 12 months , 3-month differences between MI and assessment -only groups have disappeared almost entirely . Unexpected improvements by the assessment -only control group on a number of outcomes suggest the possibility of reactivity to the research assessment at 3-month follow-up . CONCLUSION In the terms of the original experiment , there is little evidence of enduring intervention effectiveness shown by between-group differences after 12 months . Deterioration of effect is the most probable explanation , although reactivity to 3-month assessment , a late Hawthorne effect , can not be ruled out AIMS We examined the alcohol-tobacco relationship using two prospect i ve , ethnically diverse sample s. Trajectories of alcohol and tobacco use are portrayed overall and by sex and ethnicity . Using prospect i ve analyses , we examine directional influences between alcohol and tobacco use , and we characterize initiation versus persistence of drinking and smoking as a function of use of the other substance . DESIGN , SETTING Data were from the National Longitudinal Study of Adolescent Health ( AddHealth ) and the Adolescent Health Risk Study ( AHRS ) . Follow-up intervals for AddHealth and AHRS were 1 and 5 years , respectively . PARTICIPANTS AddHealth respondents ( n = 4831 ) were on average 14.8 years old ( 48 % male , 23 % black , 61 % white ) and AHRS respondents ( n = 1814 ) were on average 16.7 years old ( 47 % male , 44 % black , 49 % white ) . MEASUREMENTS Two alcohol consumption variables and two smoking variables were used : drinking frequency and heavy drinking frequency , and regular ( current ) smoking and daily number of cigarettes . FINDINGS Alcohol and tobacco use exhibited monotonic increases over adolescence and young adulthood . Men and white respondents reported more use than women and black respondents . Alcohol and tobacco were moderately associated at both times . Analyses revealed that prior alcohol use predicted tobacco use more strongly than the converse . Initiation of smoking was a function of prior drinking ; to a lesser extent , initiation of drinking was a function of prior smoking . Persistence of smoking was a function of prior drinking and persistence of drinking was a function of prior smoking . CONCLUSIONS Provisional support exists for the cl aim that alcohol use predicts tobacco use more strongly than the converse . For both drinking and smoking , onset and persistence are predicted by prior use of the other substance , and these associations were robust across sex and ethnicity OBJECTIVE To examine the effectiveness of a brief , school-based intervention for preventing alcohol use . DESIGN AND SETTING R and omized , control trial assigning inner-city public school students to an intervention program or a comparison program . PARTICIPANTS Sixth , seventh , and eighth grade students in Jacksonville , Fla ( N=104 ) . INTERVENTIONS Students assigned to the intervention program were given a self-instructional module and corresponding audiotape , a health consultation with a physician or nurse , and a follow-up consultation with a trained peer health model . MAIN OUTCOME MEASURES Alcohol consumption during the month after the intervention and students ' assessment s of the interventions were measured . RESULTS Students ' t tests showed participants were more satisfied with physician or nurse consultations than with peer consultations or the self-instructional module and audiotapes ( P=.05 ) . Analysis of covariance tests showed significant main effects for 30-day quantity of alcohol use ( F=5.15 , P=.02 ) , with intervention students reporting less alcohol consumption at follow-up than comparison students , and for 30-day frequency of alcohol use ( F=5.92,P=.01 ) with intervention students again showing less frequent use at follow-up . CONCLUSIONS A multicomponent , school-based intervention using print and audiotape media , brief physician or nurse consultations , and follow-up peer contacts holds promise in altering short-term alcohol use and selected behavioral factors among inner-city youth The primary purpose of this study was to test the efficacy of a brief , multi-health behavior intervention integrating physical activity and alcohol use prevention messages for high school-aged adolescents . A total of 604 participants , 335 9th and 269 11th grade students from a suburban high school in northeast Florida participated in this study . A r and omized control trial was conducted with participants r and omly assigned within grade levels to receive either a brief consultation and prescription with a mailed reinforcing follow-up flyer ( Project SPORT ) or a minimal intervention control consisting of a wellness brochure provided in school and a pamphlet about teen health and fitness mailed to the home . Differences between intervention groups were evaluated with a series of MANCOVA tests . Project SPORT participants demonstrated significant positive effects at 3-months postintervention for alcohol consumption , alcohol initiation behaviors , alcohol use risk and protective factors , drug use behaviors , and exercise habits , and at 12-months for alcohol use risk and protective factors , cigarette use , and cigarette initiation ( p 's < 0.05 ) . A post hoc analysis examining interactions between past 30-day use of marijuana and /or cigarettes by treatment group indicates significant positive effects for drug using adolescents who received Project SPORT on alcohol consumption , drug use behaviors , and drug use initiation at 3-months , and for drug use behaviors and exercise habits at 12-months ( p 's < 0.05 ) . A brief , 12-min one-on-one consultation integrating alcohol avoidance messages within those promoting fitness and other positive health behaviors holds promise for influencing adolescent alcohol and cigarette use and other health behaviors at posttreatment and 1 year later . Long-term sustained effects for cigarette and marijuana use , and both vigorous and moderate physical activity , were found among adolescents using marijuana and /or cigarettes prior to intervention AIM To test whether a single session of Motivational Interviewing ( MI ) focussing on drinking alcohol , and cigarette and cannabis smoking , would successfully lead to reductions in use or problems . METHODS Naturalistic quasi-experimental study , in 162 young people ( mean age 17 years ) who were daily cigarette smokers , weekly drinkers or weekly cannabis smokers , comparing 59 receiving MI with 103 non-intervention assessment -only controls . MI was delivered in a single session by youth workers or by the first author . Assessment was made of changes in self-reported cigarette , alcohol , cannabis use and related indicators of risk and problems between recruitment and after 3 months by self-completion question naire . RESULTS 87 % of subjects ( 141 of 162 ) were followed up . The most substantial evidence of benefit was achieved in relation to alcohol consumption , with those receiving MI drinking on average two days per month less than controls after 3 months . Weaker evidence s of impact on cigarette smoking , and no evidence of impact on cannabis use , were obtained . CONCLUSIONS Evidence of effectiveness for the delivery of MI by youth workers in routine conditions has been identified . However , the extent of benefit is much more modest than previously identified in efficacy studies This study explored secondary effects of a multisite r and omized alcohol prevention trial on tobacco , marijuana , and other illicit drug use among a sample of incoming college students who participated in high school athletics . Students ( n = 1,275 ) completed a series of Web-administered measures at baseline during the summer before starting college and 10 months later . Students were r and omized to one of four conditions : a parent-delivered intervention , a brief motivation enhancement intervention ( Brief Alcohol Screening and Intervention for College Students [ BASICS ] ) , a condition combining the parent intervention and BASICS , and assessment -only control . A series of analyses of variance evaluating drug use outcomes at the 10-month follow-up assessment revealed significant reductions in marijuana use among students who received the combined intervention compared to the BASICS-only and control groups . No other significant differences between treatment conditions were found for tobacco or other illicit drug use . Our findings suggest the potential utility of targeting both alcohol and marijuana use when developing peer- and parent-based interventions for students transitioning to college . Clinical implication s and future research directions are considered CONTEXT Adults aged 18 to 24 years , many of whom are in college , represent the youngest legal targets for tobacco industry marketing . Cigarette smoking has been described among college students , but little is known about non-cigarette tobacco use by college students or cigar use by adults of any age . OBJECTIVES To assess the prevalence of all forms of tobacco use ( cigarettes , cigars , pipes , and smokeless tobacco ) among US college students and to identify student- and college-level factors associated with use of each product . DESIGN The Harvard College Alcohol Survey , a self-administered survey conducted in 1999 . SETTING One hundred nineteen nationally representative US 4-year colleges . SUBJECTS A total of 14,138 r and omly selected students ( 60 % response rate ) . MAIN OUTCOME MEASURES Self-report of current ( in the past 30 days ) , past-year , and lifetime use of cigarettes , cigars , pipes , smokeless tobacco , and all tobacco products . RESULTS Nearly half ( 45.7 % ) of respondents had used a tobacco product in the past year and one third ( 32.9 % ) currently used tobacco . Cigarettes accounted for most of the tobacco use ( 28.5 % current prevalence ) , but cigar use was also substantial ( 37.1 % lifetime prevalence , 23.0 % past-year prevalence , and 8.5 % current prevalence ) and combinations of the 2 were common . Total tobacco use was higher in men than in women ( 37 . 9 % vs 29.7 % ; P<.001 ) , despite nearly identical current cigarette smoking rates between the sexes ( 28.5 % for women vs 28.4 % for men ) , because of greater use of cigars ( current prevalence , 15.7 % vs 3.9 % ; P<.001 ) and smokeless tobacco ( current prevalence , 8.7 % vs 0.4 % ; P<. 001 ) by men . Tobacco use was significantly higher among white students ( P<.001 ) , users of other substances ( alcohol and marijuana ) ( P<.001 ) , and students whose priorities were social rather than educational or athletic ( P<.05 ) . Among students who had used both cigars and cigarettes , only 8.9 % smoked cigars at an earlier age than they had smoked cigarettes . CONCLUSION Our study indicates that tobacco use is common among college students and is not limited to cigarettes . College appears to be a time when many students are trying a range of tobacco products and are in danger of developing lifelong nicotine dependence . National efforts to monitor and reduce tobacco use of all types should exp and to focus on college students and other young adults . JAMA . 2000;284:699 - Objectives To show the effectiveness of a brief group alcohol intervention . Aims of the intervention were to reduce the frequency of heavy drinking occasions , maximum number of drinks on an occasion and overall weekly consumption . Methods A cluster quasi-r and omized control trial ( intervention n = 338 ; control n = 330 ) among 16- to 18-year-old secondary school students in the Swiss Canton of Zürich . Groups homogeneous for heavy drinking occasions ( 5+/4 + drinks for men/women ) consisted of those having medium risk ( 3–4 ) or high risk ( 5 + ) occasions in the past 30 days . Groups of 8–10 individuals received two 45-min sessions based on motivational interviewing techniques . Results Borderline significant beneficial effects ( p < 0.10 ) on heavy drinking occasions and alcohol volume were found 6 months later for the medium-risk group only , but not for the high-risk group . None of the effects remained significant after Bonferroni corrections . Conclusions Group intervention was ineffective for all at-risk users . The heaviest drinkers may need more intensive treatment . Alternative explanations were iatrogenic effects among the heaviest drinkers , assessment reactivity , or reduction of social desirability bias at follow-up through peer feedback OBJECTIVES There is considerable variability in progression from smoking initiation to established smoking . This paper addresses the extent to which different patterns of adolescent smoking , including periods of cessation , predict smoking status in young adults . STUDY DESIGN Ten-year , eight-wave prospect i ve cohort study of a state-wide community sample in Victoria , Australia . METHODS Participants were 1520 students from 44 secondary schools , initially aged 14 to 15 years . Adolescent smoking and quitting patterns were assessed during Waves 1 - 6 with self-reported frequency of use and a 7-day retrospective diary . The Fagerstrom Test for Nicotine Dependence ( ND ) was used to assess ND at the age of 24 years ( Wave 8) . RESULTS The prevalence of ND in young adults was 16.9 % for all adolescent smokers , with prevalence rates of 6.8 % and 26.7 % for adolescent non-daily and daily adolescent smokers , respectively . Maximum smoking levels , onset of daily smoking , duration of smoking , escalation time and duration of cessation during adolescence predicted later ND . Daily smokers who ceased smoking for at least two waves ( > or = 12 months ) had a level of risk similar to adolescents who had never smoked . CONCLUSIONS Quitting smoking as an adolescent substantially alters the risk for later ND . For adolescents who become daily smokers , quitting for 12 months should be the aim in tobacco control and clinical interventions OBJECTIVE The current study is a multisite r and omized alcohol prevention trial to evaluate the efficacy of both a parenting h and book intervention and the Brief Alcohol Screening and Intervention for College Students ( BASICS ) intervention , alone and in combination , in reducing alcohol use and consequences among a high-risk population of matriculating college students ( i.e. , former high school athletes ) . METHOD Students ( n = 1,275 ) completed a series of Web-administered measures at baseline ( in the summer before starting college ) and follow-up ( after 10 months ) . Students were r and omized to one of four conditions : parent intervention only , BASICS only , combined ( parent and BASICS ) , and assessment -only control . Intervention efficacy was tested on a number of outcome measures , including peak blood alcohol concentration , weekly and weekend drinking , and negative consequences . Hypothesized mediators and moderators of intervention effect were tested . RESULTS The overall results revealed that the combined-intervention group had significantly lower alcohol consumption , high-risk drinking , and consequences at 10-month follow-up , compared with the control group , with changes in descriptive and injunctive peer norms mediating intervention effects . CONCLUSIONS The findings of the present study suggest that the parent intervention delivered to students before they begin college serves to enhance the efficacy of the BASICS intervention , potentially priming students to respond to the subsequent BASICS session OBJECTIVES This study examined long-term response to an individual preventive intervention for high-risk college drinkers relative to the natural history of college drinking . METHODS A single-session , individualized preventive intervention was evaluated within a r and omized controlled trial with college freshmen who reported drinking heavily while in high school . An additional group r and omly selected from the entire screening pool provided a normative comparison . Participant self-report was assessed annually for 4 years . RESULTS High-risk controls showed secular trends for reduced drinking quantity and negative consequences without changes in drinking frequency . Those receiving the brief preventive intervention reported significant additional reductions , particularly with respect to negative consequences . Categorical individual change analyses show that remission is normative , and they suggest that participants receiving the brief intervention are more likely to improve and less likely to worsen regarding negative drinking consequences . CONCLUSIONS Brief individual preventive interventions for high-risk college drinkers can achieve long-term benefits even in the context of maturational trends OBJECTIVES The purpose of this study was to evaluate a brief smoking cessation intervention for women 15 to 35 years of age attending Planned Parenthood clinics . METHODS Female smokers ( n = 1154 ) were r and omly assigned either to advice only or to a brief intervention that involved a 9-minute video , 12 to 15 minutes of behavioral counseling , clinician advice to quit , and follow-up telephone calls . RESULTS Seventy-six percent of those eligible participated . Results revealed a clear , short-term intervention effect at the 6-week follow-up ( 7-day self-reported abstinence : 10.2 % vs 6.9 % for advice only , P < .05 ) and a more ambiguous effect at 6 months ( 30-day biochemically vali date d abstinence : 6.4 % vs 3.8 % , NS ) . CONCLUSIONS This brief , clinic-based intervention appears to be effective in reaching and enhancing cessation among female smokers , a traditionally underserved population Objective . The purpose of this study was to compare the effects of a single drug , i.e. , alcohol , against a multiple drug preventive intervention . Methods . A controlled trial was conducted with 448 8th grade students ( mean age = 13 years old ) from an inner-city middle school ( n = 216 ) and a rural junior high school ( n = 232 ) in 2000–2001 . Students were r and omized within school , and 3-month post-intervention follow-up data were collected . Results . Two risk/protective factors were found to differ significantly in favor of youth receiving the single drug alcohol intervention ( p 's = 0.03 ) , while the frequency of alcohol use and two additional risk/protective factors approached significance ( p 's < 0.10 ) . Conclusion . These findings support the potential efficacy of a brief , single drug preventive intervention over a brief , multi-drug intervention in producing short-term alcohol outcomes for adolescents , and indicate differential effects of interventions for subgroups of substance using youth AIM To test the effectiveness of motivational interviewing ( MI ) in comparison with drug information and advice in opportunistically securing reductions in drug-related risk among young cannabis users not seeking help . DESIGN R and omized controlled trial . SETTING Eleven London Further Education colleges . PARTICIPANTS A total of 326 students aged 16 - 19 years who smoked cannabis weekly or more frequently . INTERVENTIONS Participants were r and omized to a single-session intervention of MI or drug information and advice-giving . MEASUREMENTS Cannabis use , cigarette smoking and alcohol consumption and harm outcomes were assessed after both 3 and 6 months . FINDINGS No differences were found between MI and drug information and advice , although MI fidelity was not high . There were wide-ranging individual practitioner effects on observed outcomes and a practitioner-intervention interaction was detected in relation to cannabis cessation after 3 months . Change over time was more pronounced for cannabis use than for other drug use . CONCLUSIONS Further study of the nature and consequences of MI fidelity , and individual practitioner effects more generally , is needed . Advice may be an effective brief intervention with young cannabis users in its own right and should be evaluated further in trials OBJECTIVE This study examined whether 3-month outcomes of a brief image-based multiple behavior intervention on health habits and health-related quality of life of college students were sustained at 12-month follow-up without further intervention . METHODS A r and omized control trial was conducted with 303 undergraduates attending a public university in southeastern US . Participants were r and omized to receive either a brief intervention or usual care control , with baseline , 3-month , and 12-month data collected during fall of 2007 . RESULTS A significant omnibus MANOVA interaction effect was found for health-related quality of life , p=0.01 , with univariate interaction effects showing fewer days of poor spiritual health , social health , and restricted recent activity , p's<0.05 , for those receiving the brief intervention . Significant group by time interaction effects were found for driving after drinking , p=0.04 , and moderate exercise , p=0.04 , in favor of the brief intervention . Effect sizes typically increased over time and were small except for moderate size effects for social health-related quality of life . CONCLUSION This study found that 3-month outcomes from a brief image-based multiple behavior intervention for college students were partially sustained at 12-month follow-up BACKGROUND Brief motivational intervention ( BMI ) is one of the few effective strategies targeting alcohol consumption , but has not been tested in young men in the community . We evaluated the efficacy of BMI in reducing alcohol use and related problems among binge drinkers and in maintaining low-risk drinking among non-bingers . METHODS A r and om sample of a census of men included during army conscription ( which is m and atory for 20-year-old males in Switzerl and ) was r and omized to receive a single face-to-face BMI session ( N=199 ) or no intervention ( N=219 ) . A six-month follow-up rate was obtained for 88.7 % of the subjects . RESULTS Among binge drinkers , there was 20 % less drinking in the BMI group versus the control group ( incidence rate ratio=0.80 , confidence interval 0.66 - 0.98 , p=0.03 ) ; the BMI group showed a weekly reduction of 1.5 drinks compared to an increase of 0.8 drinks weekly in the control group . Among subjects who experienced one or more alcohol-related consequences over the last 12 months , there was 19 % less drinking in the BMI group compared to the control group ( incidence rate ratio=0.81 , confidence interval 0.67 - 0.97 , p=0.04 ) . Among non-bingers , BMI did not contribute to the maintenance of low-risk drinking . CONCLUSION BMI reduced the alcohol use of binge drinkers , particularly among those who experienced certain alcohol-related adverse consequences . No preventive effect of BMI was observed among non-bingers . BMI is a plausible secondary preventive option for young binge drinkers |
2,427 | 25,891,319 | The proposed time schedule of investigations as well as the amount and type of investigation were different according to specific neurological lesions .
They depend on the dysfunctional pattern of the lower urinary tract ( LUT ) and its risk profile .
The goal of neuro-urological management is the best possible preservation of upper urinary tract ( UUT ) and LUT function in relation to the individual neurological disorder . | OBJECTIVES To systematic ally review the long-term urological follow-up strategies for patients with neurogenic lower urinary tract dysfunction ( NLUTD ) , focusing on three main groups of neurological diseases : ( i ) spinal cord injuries , ( ii ) spinal dysraphism , and ( iii ) multiple sclerosis . | Study Design . Multicenter , double-blind , placebo-controlled , parallel-group study . Objective . To assess the effect of the oral phosphodiesterase type-5 inhibitor , vardenafil , on ejaculation rates and self-confidence in men with spinal cord injury ( SCI ) . Summary of Background Data . Spinal comm and of male sexual functions is often seriously impaired by traumatic spinal cord injury ( SCI ) . A high proportion of men with SCI can not ejaculate during sexual intercourse . SCI-related ejaculatory disorders are often responsible for male infertility . Sexual dysfunction associated with SCI can also affect men 's self-confidence . Methods . In this 12-week study , 418 men aged ≥18 years with erectile dysfunction > 6 months result ing from a traumatic SCI were r and omized to vardenafil ( n = 207 ) or placebo ( n = 211 ) 10 mg for 4 weeks , then maintained or titrated to 5 or 20 mg at weeks 4 and 8 . Assessment s included questions of the International Index of Erectile Function ( IIEF ) about ejaculation success and orgasmic perception ; the Global Confidence Question ; and quality -of-life scales to measure psychological well-being , self-esteem , depression , and mental health status . Results . Overall per patient ejaculation success rates were significantly greater with vardenafil than placebo over 12 weeks of treatment ( 19 % vs. 10 % ; P < 0.001 ) . At last observation carried forward , the IIEF “ orgasmic function ” score increased from 2.9 at baseline to 4.0 for vardenafil and from 3.0 at baseline to 3.4 for placebo . Sixteen percent of men receiving vardenafil and 8 % receiving placebo felt orgasm “ almost always ” or “ always ” at weeks 8–12 , compared with 4 % and 6 % , respectively , at baseline . Significant improvements in confidence scores were observed with vardenafil compared with placebo ( P < 0.0001 ) . There were no clinical ly significant differences between vardenafil and placebo in the quality -of-life measures at the study endpoint , but these had been in the normal range at baseline . Conclusion . Vardenafil significantly improved ejaculation and self-confidence in men with erectile dysfunction due to SCI Fourteen male patients suffering from Parkinson 's disease , each of whom had been treated with L-DOPA , and in whom additional treatment with oral dopamine agonist ( DA ) was needed , were followed for a period of one year . Pergolide mesylate ( Permax ) was given to each patient , and titrated to a total daily dose of 3 mg . All of the patients were taking L-DOPA . The assessment s performed before the start of pergolide treatment consisted of neurological examination , unified Parkinson 's disease rating scale ( UPDRS ) III and IV subscales scoring , mini mental state examination ( MMSE ) scoring , the neuropsychological examination including Zung scale scoring , biochemical and hematological examinations including prolactine serum levels ; and a sexological examination during which the patients filled-in the international index of erectile function ( IIEF ) question naire . These examinations were repeated during the control assessment s at months 1 , 3 , 6 and 12 . ANOVA , non-parametric Friedmann 's ANOVA and Tukey post hoc tests were used for the statistical analysis . There were statistically significant differences between the values of UPDRS III motor subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3 , 6 and 12 . Pergolide mesylate , when added to L-DOPA , significantly improved all sexual functions in younger male Parkinsonian patients who were still interested in sexual activities . The treatment with pergolide in these cases might be more beneficial than with short-acting PDE-5 inhibitor sildenafile . Nevertheless , the relationship between pergolide treatment and incidence of restrictive valvular heart disease must be considered Bladder augmentation has revolutionized the care of children with neurogenic bladder but it is associated with certain short- and long-term complications . Using the combination of gastric and ileal segments to balance effects of these segments might be a solution for complications . A total of 39 female Spraque-Dawley rats r and omly divided into four groups : ileocystoplasty ( 11 ) , gastrocystoplasty ( 9 ) , ileogastrocystoplasty ( 11 ) and control ( 8) . Serum/urine electrolytes and pH values , and serum creatinine levels and urine mucus concentration were measured . Kruskal – Wallis non-parametric variance analysis was performed to compare the groups and p < 0.05 was accepted as significant . Metabolic alkalosis with significantly lower urine pH was observed in gastrocystoplasty group . Gastroileal group showed similar results with the ileal group in all parameters . No stone formation was detected in the sham and gastric cystoplasty groups . Metaplastic and hyperplastic changes were observed in all segments surrounding urothelium . In conclusion , combination of gastric and ileal segments does not significantly reduce the rate of metabolic impairments , stone and mucus formation . Besides it is not associated with significant improvement in histological outcome since urine is still in contact with the gastrointestinal mucosa Background Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction , but its value in patients with a neurological cause is unclear . Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction , the number of investigated patients is low and there is a lack of r and omized controlled trials . Methods and design This study is a prospect i ve , r and omized , placebo-controlled , double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerl and . Patients with refractory neurogenic lower urinary tract dysfunction are enrolled . After minimally invasive bilateral tined lead placement into the sacral foramina S3 and /or S4 , patients undergo prolonged sacral neuromodulation testing for 3–6 weeks . In case of successful ( defined as improvement of at least 50 % in key bladder diary variables ( i.e. number of voids and /or number of leakages , post void residual ) compared to baseline values ) prolonged sacral neuromodulation testing , the neuromodulator is implanted in the upper buttock . After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation , the patients are r and omized in a 1:1 allocation in sacral neuromodulation ON or OFF . At the end of the 2 months double-blind sacral neuromodulation phase , the patients have a neuro-urological re-evaluation , unblinding takes place , and the neuromodulator is turned ON in all patients . The primary outcome measure is success of sacral neuromodulation , secondary outcome measures are adverse events , urodynamic parameters , question naires , and costs of sacral neuromodulation . Discussion It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction . If this type of treatment is effective in the neurological population , it would revolutionize the management of neurogenic lower urinary tract dysfunction . Trial registration Trial registration number : http://www . clinical trials.gov ; Identifier : NCT02165774 PURPOSE We assessed the tolerability , safety and efficacy of sildenafil for the treatment of women with sexual dysfunction secondary to multiple sclerosis , as well as the role of somatosensory evoked potential neurophysiological testing . MATERIAL S AND METHODS We performed a double-blind , r and omized , placebo controlled , crossover study investigating the effects of sildenafil in women with multiple sclerosis and sexual dysfunction . Assessment s were done by vali date d question naires . Pudendal and tibial evoked potentials were also recorded . RESULTS A total of 19 women completed the 2 arms of the double-blind phase and 12 completed the optional open label extension phase . Statistically significant improvement following sildenafil was only reported in the lubrication domain of sexual function during the double-blind phase . There was no overall change in quality of life after sildenafil . There was a significant correlation between the latency of tibial and pudendal evoked potentials . CONCLUSIONS Sildenafil only appeared to produce limited benefit in certain individuals with female sexual dysfunction . Some measure of the extent of neurological deficit in these patients could be ascertained from the latency of tibial evoked potentials , which correlated with pudendal evoked potentials . However , it could not predict the extent of sexual dysfunction . Sildenafil is unlikely to help all patients with neurogenic female sexual dysfunction OBJECTIVE To determine the efficacy and safety of tadalafil when taken on dem and by men with erectile dysfunction ( ED ) secondary to traumatic spinal cord injury ( SCI ) . DESIGN AND SETTING Multicenter , r and omized , double-blind , placebo-controlled , flexible dose-titration , parallel-group study in clinical practice s in Europe . Patients Enrolled patients had ED secondary to SCI ( all spinal levels ) and sustained 6 months or longer before visit 1 . INTERVENTIONS After a 4-week run-in period , patients were r and omly assigned to tadalafil , 10 mg , ( n = 142 ) or placebo ( n = 44 ) for a 12-week , on-dem and treatment period with assessment s at 4-week intervals . The dose of tadalafil was maintained or titrated ( 10 or 20 mg ) at 4 and 8 weeks . MAIN OUTCOME MEASURES Efficacy was measured using the International Index of Erectile Function ( IIEF ) , Sexual Encounter Profile ( SEP ) , and Global Assessment Question ( GAQ ) . Treatment-emergent adverse events and vital signs were collected at each visit . RESULTS Mean age was 38 years . Mean baseline IIEF erectile function domain score was 13.4 , and following 12 weeks of treatment , 22.6 for tadalafil and 13.6 for placebo ( P < .001 ) . After treatment , the tadalafil group compared with the placebo group was significantly greater ( P < .001 ) in mean per-patient percentage of successful penetration attempts ( SEP question 2 ; 75.4 % vs 41.1 % ) and intercourse attempts ( SEP question 3 ; 47.6 % vs 16.8 % ) ; percentage of improved erections ( GAQ question 1 ; 84.6 % vs 19.5 % ) ; and ejaculatory frequency ( IIEF question 9 ; P = .03 ) . The 2 most common treatment-emergent adverse events in the tadalafil group compared with placebo were headache ( 8.5 % vs 4.5 % ) and urinary tract infection ( 7.7 % vs 6.8 % ) . CONCLUSIONS Tadalafil ( 10 mg and 20 mg ) improved erectile function and was well tolerated by men with ED secondary to traumatic SCI OBJECTIVE To assess the course of sexual function in epilepsy patients treated with lamotrigine . MATERIAL AND METHODS This open study included 141 patients treated with lamotrigine for a period of 8 months : 79 patients initiated treatment with lamotrigine monotherapy , and 62 were switched to lamotrigine because of lack of efficacy or adverse events to a previous antiepileptic drug ( AED ) . Patients were assessed at baseline and after 4 and 8 months of treatment . In the baseline and final visits the Changes in Sexual Functioning Question naire ( CSFQ ) was applied . Analysis was performed in an intent-to-treat population . RESULTS In women who started treatment with lamotrigine , a significant improvement was observed , both in total CSFQ score ( increase of 5.39 + /- 6.95 points ; p < 0.05 ) , and in the five dimensions of the scale ( desire/frequency , desire/interest , pleasure , arousal/excitement and orgasm ) . In men , a significant improvement was only observed in the pleasure dimension . In the group of patients in whom a previous AED was substituted by lamotrigine , significant improvement was recorded in the dimensions of pleasure and orgasm in men and desire/frequency in women , whilst in women the desire/interest dimension showed a decrease . CONCLUSIONS In this observational study , an improvement in sexual dysfunction was observed in association with lamotrigine . This could have been the result of improvement of the epilepsy , changes in quality of life , elimination of side effects from other AEDs , or a mood-stabilizing effect of lamotrigine INTRODUCTION Lower urinary tract symptoms ( LUTS ) have a profound impact on physical , social , and sexual well-being . Sacral neuromodulation ( SNM ) may have a positive effect on sexuality , though few studies have so far evaluated its impact on female sexual function . AIM To prospect ively assess changes in sexual function , clinical outcome and quality of life after SNM in female patients with overactive bladder ( OAB ) and their possible correlation with improvement in urinary symptoms and quality of life indexes . MAIN OUTCOME MEASURES Correlations between differences in Female Sexual Function Index ( FSFI ) scores and in clinical outcome and correlations between differences in FSFI , SF36 , and IQoL scores were evaluated by Spearman 's coefficient . Comparison between preoperative , midterm follow-up ( MFU ) , and last follow-up ( FFU ) visits were performed by generalized linear model ( GLM ) for repeated measurements . METHODS Between May 2003 and December 2008 , 30 consecutive female patients ( median age 53 years , range 35 - 79 ) with OAB underwent the two-stage procedure of SNM . Only 16 ( 53 % ) patients were considered eligible ; these completed a bladder diary , the FSFI , the Status of Health question naire ( SF36 ) and the Incontinence Quality of Life Index ( IQoL ) before implantation and on follow-up examinations . RESULTS The results were analyzed before implantation , on MFU ( median MFU 22.5 months ) and on FFU ( median FFU period 36.3 months ) . Regarding sexuality , the mean improvement in the total FSFI score was 27.9 % on MFU and 29.3 % on FFU . Only four patients ( 25 % ) showed a > 50 % improvement in global FSFI score on MFU , and 3 ( 25 % ) on FFU . A significant correlation was found between clinical improvement and improvement in sexual function . No significant correlation was found between differences in FSFI and quality of life indexes ( IQoL and SF36 ) . CONCLUSION Our results demonstrate that improvement in the quality of sexual function in female patients with OAB correlates with improvement in urinary symptoms OBJECTIVES To assess the efficacy and safety of sildenafil citrate ( Viagra ) in men with erectile dysfunction and parkinsonism due either to Parkinson 's disease or multiple system atrophy . METHODS Twenty four patients with erectile disease were recruited , 12 with Parkinson 's disease and 12 with multiple system atrophy , into a r and omised , double blind , placebo controlled , crossover study of sildenafil citrate . The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability . The international index of erectile function question naire ( IIEF ) was used to assess treatment efficacy and a quality of life question naire to assess the effect of treatment on sex life and whole life . Criteria for entry included a definite neurological diagnosis and a st and ing systolic blood pressure of 90–180 mm Hg and diastolic blood pressure of 50–110 mm Hg , on treatment if necessary . Blood pressure was taken at r and omisation ( visit 2 ) and crossover ( visit 5 ) lying , sitting , and st and ing , before and 1 hour after taking the study medication in hospital . RESULTS Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement , as demonstrated in question naire responses , in ability to achieve and maintain an erection and improvement in quality of sex life . In Parkinson 's disease there was minimal change in blood pressure between active and placebo medication . In multiple system atrophy , six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication . Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension . However , the blood pressures in all three had been within the inclusion criterion for the study protocol . Despite a significant postural fall in blood pressure after sildenafil , all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication . CONCLUSIONS Sidenafil citrate ( 50 mg ) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson 's disease or multiple system atrophy ; however , it may unmask or exacerbate hypotension in multiple system atrophy . As Parkinson 's disease may be diagnostically difficult to distinguish from multiple system atrophy , especially in the early stages , we recommend measurement of lying and st and ing blood pressure before prescribing sildenafil to men with parkinsonism . Furthermore , such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension Study design : A multi-center longitudinal study . Objectives : To estimate the current trend in the incidence of first kidney stone among persons with spinal cord injury ( SCI ) and to delineate the potential contributing factors . Setting : Twenty-one Model SCI Care Systems throughout the United States . Methods : A longitudinal cohort of 8314 subjects enrolled in the National SCI Data base between 1986 and 1999 was used to estimate and compare the incidence of first kidney stone with a previous report of 5850 SCI patients injured between 1973 and 1982 . A Cox regression analysis was performed to identify risk factors for stones , including age , race , gender , severity of injury , and method of urinary drainage . These variables have been routinely collected , on a yearly basis , by the collaborating SCI centers . Results : During the 12 years , 6 months of case ascertainment , 286 incident stone cases were documented . The risk was greatest during the first 3 months after injury ( 31 cases per 1000 person-years ) , quickly decreasing and leveling off later ( eight cases per 1000 person-years ) . It was estimated that within 10 years after injury , 7 % of persons with SCI would develop their first kidney stone . There was no evidence that the risk has changed over the past 25 years ( P=0.96 ) . During the first year post injury only , a significantly increased risk of stones was observed in Caucasians and persons aged 45 years or older . A positive association of the severity of injury and requiring instrumentation for bladder emptying with kidney stones was found after the first year post injury . The type of urinary drainage , including indwelling , intermittent , and condom catheterization , had no significant differential effect on stone formation at either risk period . Conclusions : The highest risk of kidney stones is within the first few months post injury . Little progress has been made in reducing this risk . Although inability to control bladder function is an important risk factor after the first year post injury , for those who need bladder management , the type of urinary drainage does not appear to be an important factor in determining risk To investigate a possible correlation between sexual hormonal status and the presence of female sexual dysfunction ( FSD ) using the Female Sexual Function Index ( FSFI ) in females with spinal cord injuries ( SCI ) , we selected 39 SCI fertile-aged women . At visit 1 , we assessed the presence of FSD using the FSFI , and all individuals were su bmi tted to a blood hormone evaluation on the third day of their menstrual cycle . The levels of serum follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , prolactin ( PRL ) , thyroid-stimulating hormone ( TSH ) , cortisol , dehydroepi and rosterone sulphate ( DHEA-S ) , and rostenedione , 17[alpha]-hydroxyprogesterone ; total and free testosterone , 17beta-estradiol , inhibin , sex hormone-binding globulin ( SHBG ) , and thyroid hormones ( fT3 and fT4 ) were checked . Progesterone was measured on the 20th to 21st day after the menstrual cycle . In patients with amenorrhea , we tested all the hormones using 1 r and om blood test . After a 3-month period , the tests were repeated . Overall , 23/39 ( 58.9 % ) patients continued to manifest at least one sexual dysfunction . These patients reached a median score of 19.52 . All but 6 patients ( 15.3 % ) consistently showed hormonal values within the normal range . Of the 6 patients with abnormal hormonal alterations , 5 showed at least one sexual dysfunction , 2 had low levels of total testosterone , 1 had a low level of free testosterone , 1 suffered from hypothyroidism , 1 presented with low levels of cortisol , and 1 showed hypoprogesterone . There was no significant correlation between abnormal hormonal status and the presence of a specific sexual dysfunction , as assessed with the FSFI Objective : Identifying and effectively treating erectile dysfunction ( ED ) can result in an improvement of the quality of life ( QoL ) in men with multiple sclerosis ( MS ) . Methods : This r and omised , double blind ( DB ) , placebo controlled , flexible dose study with an open label extension ( OLE ) assessed efficacy , QoL , and safety of sildenafil citrate in men with MS and ED . Overall , 217 men received sildenafil ( 25–100 mg ; n = 104 ) or placebo ( n = 113 ) for 12 weeks . Efficacy was assessed by the International Index of Erectile Function ( IIEF ) question naire that includes questions on achieving ( Q3 ) and maintaining ( Q4 ) an erection as well as a global efficacy question ( GEQ ) . QoL was also assessed . Results : After 12 weeks , patients receiving sildenafil had higher mean scores for IIEF Q3 and Q4 compared with those receiving placebo ( p<0.0001 ) , and 89 % ( 92/103 ) reported improved erections compared with 24 % ( 27/112 ) of patients receiving placebo ( p<0.0001 ) . At the end of the OLE phase , 95 % of men reported improved erections . Patients receiving placebo during the DB phase showed a nearly fourfold increase in improved erections ( 97 % v 26 % ) . Men receiving sildenafil also showed improvements in five of the eight general QoL questions compared with men receiving placebo ( p<0.05 ) . The total mean score for the QoL question naire improved by 43 % for the sildenafil group versus 13 % for the placebo group ( p<0.0001 ) . Treatment related AEs were predominantly mild in nature , and no patient discontinued due to an AE . Conclusion : Sildenafil treatment for ED in men with MS was effective and well tolerated , and result ed in significant improvements in both general and disease specific QoL variables Study design : A r and omized , blinded , crossover clinical trial comparing sildenafil versus tadalafil for erectile dysfunction ( ED ) in male spinal cord-injured ( SCI ) patients . Objectives : To compare the safety , time/ duration effectiveness , and the impact on the quality of life ( QoL ) of tadalafil 10 mg versus sildenafil 50 mg . Setting : Neurourology Section , Careggi Hospital , Florence , Italy . Methods : During a screening ( visit 1 ) , a diary card was distributed , in which the subjects assessed , after each attempt at intercourse the quality of their erection , responding ( Yes/No ) to both Sexual Encounter Profile Questions 2 ( SEP2 ) and 3 ( SEP3 ) . The subjects made at least four attempts at intercourse . At visit 2 , 15 patients ( group 1 ) were assigned sildenafil and 15 ( group 2 ) started with tadalafil . Responses to baseline International Index of Erectile Function 5 items ( IIEF-5 ) , Questions 13–14 ( IIEF 15 items ) and SEP diary were recorded . Patients attempted intercourse on four separate occasions : within 4 h of taking the first tablet , within 12 h for the second tablet , 24 h for the third , and the fourth from 24 to 36 h. At visit 3 , the investigators evaluated the effectiveness with the same measures used at baseline . After a wash-out period , at visit 4 , Group 1 was given tadalafil , and Group 2 was given sildenafil . Patients were required to observe the same criteria in taking the four tablets as in visit 2 . After 4 weeks ( visit 5 ) , we evaluated the patients as we did in visit 3 . Results : Overall , 28 patients completed the study . No subjects discontinued the drugs due to drawbacks . Tadalafil allowed a majority of men in this trial to achieve both normal sexual functioning up to 24 h postdosing compared to sildenafil ( P<0.01 ) and improved overall sex life satisfaction as well as sexual relations with partner . Conclusion : Based on these data , tadalafil may have the potential to become an important treatment option for ED in SCI patients .Sponsorship : This study was not sponsored Study design : Two r and omized , double-blind , placebo-controlled trials . Objective : To evaluate the efficacy and safety of fampridine sustained-release tablets ( fampridine-SR ) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury ( SCI ) . Setting : United States and Canada . Methods : Patients with incomplete chronic SCI were r and omized to twice daily fampridine-SR 25 mg or placebo , with a 2-week single-blind placebo run-in , a 2-week titration , 12 weeks of stable dosing , 2 weeks of downward titration and 2 weeks of untreated follow-up . Co- primary end points were the change from baseline , averaged over the double-blind treatment period , for Ashworth score ( bilateral knee flexors and extensors ) and a 7-point Subject Global Impression of treatment ( SGI ; 1 , terrible ; 7 , delighted ) . Secondary end points were : Penn Spasm Frequency Scale ; the motor/sensory score from the International St and ards for Neurological Classification of SCI ; Clinician ’s Global Impression of Change of neurological status ; and the International Index of Erectile Function ( men ) or the Female Sexual Function Index ( women ) . Results : The population s were 212 and 203 patients in the two studies , respectively . Changes from baseline in Ashworth score were −0.15 ( placebo ) and −0.19 ( fampridine-SR ) in the first study , and −0.16 ( placebo ) and −0.28 ( fampridine-SR ) in the second study . The between-treatment difference was not significant for either the Ashworth score or the SGI and , with few exceptions , neither were the secondary end points . Fampridine-SR was generally well tolerated ; treatment-emergent adverse events ( TEAEs ) and serious TEAEs were reported with similar frequency between treatments . Conclusion : Fampridine-SR was well tolerated . No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI Study design : A prospect i ve study . Objectives : To investigate the risk factors predicting upper urinary tract ( UUT ) deterioration in patients with spinal cord injury ( SCI ) . Setting : Beijing , China . Methods : We review ed the medical records and UUT imaging studies of 112 patients , with a mean follow-up of 2 years . Variables evaluated for possible influence on UUTs included patient age , gender and educational background ; injury level and completeness ; bladder management method ; and the presence of adverse outcomes such as recurrent urinary tract infections and bladder stones . Video urodynamic data were also review ed . Total renal function was assessed by serum creatinine . UUT abnormalities were assessed by renal ultrasound or magnetic resonance imaging . Results : Lumbosacral spinal cord lesions likely contribute to UUT deterioration . UUT abnormalities were present in 23 patients ( 65.7 % ) in a spontaneous voiding group , 10 patients ( 20 % ) in a clean intermittent catheterization group , 15 patients ( 78.9 % ) in an indwelling urethral catheterization group and 7 patients ( 87.5 % ) in a suprapubic Foley catheterization group ( P<0.001 ) . When dividing bladder management method into two groups , catheter-free ( spontaneous and intermittent voiding ) and indwelling catheter ( urethral and suprapubic catheterization ) , there was UUT dysfunction in 33 patients ( 38.3 % ) and 22 patients ( 81.5 % ) , respectively ( P<0.001 ) . Conclusions : Lumbosacral SCI and chronic indwelling urethral and suprapubic catheterization were predictors of UUT deterioration Study design : Double-blind , placebo-controlled , flexible-dose study . Objective : To evaluate the efficacy , safety and tolerability of oral sildenafil in women with female sexual arousal disorder as a result of SCI ( paraplegia/tetraplegia ) . Setting : The study was conducted at clinical practice sites in North America ( n = 23 ) , 11 European countries ( n = 23 ) , Australia ( n = 4 ) and South Africa ( n = 2 ) . Methods : 129 women were r and omized and treated with sildenafil or matching placebo . A 4-week baseline period was followed by 12 weeks of treatment , which could be increased from 50 to 100 mg or decreased to 25 mg once during the treatment period , depending on efficacy and tolerability . By use of an event log , sexual activity was monitored between screening and the end of treatment . The Sexual Function Question naire , the Sexual Quality of Life Question naire – Female , a global efficacy question and Sexual Distress Question were also assessed . Results : Sildenafil-treated women and placebo-treated women had an increase in their percentage of sexual activities throughout the course of the study , with no statistically significant difference between groups in the percentage of successful sexual activities at end of treatment versus baseline . There were also no statistically significant differences between sildenafil- and placebo-treated women on the aforementioned measures . The most common adverse events included headache and vasodilatation . Conclusion : The results of this study are similar to other reports regarding a lack of clinical ly meaningful benefit of sildenafil in other population s of women . Sponsorship : This study was sponsored by Pfizer AIM This U.S. multicenter open-label study used a noninferiority trial design to assess the efficacy of tadalafil 20 mg to treat erectile dysfunction ( ED ) in the black American and Hispanic groups compared with a reference group of Caucasians . A secondary objective was to demonstrate the efficacy and safety of tadalafil 20 mg in various population s of men with ED . METHODS A total of 1,911 patients with ED were enrolled into eight predefined groups : ( 1 - 3 ) Caucasian ( Reference group ) , Black American , or Hispanic patients , < or = 65 years of age with no diabetes mellitus or depression ; ( 4 ) patients with depression , < or = 65 years of age , no diabetes ; ( 5 ) patients with diabetes , < or = 65 years of age , no depression ; ( 6 ) patients > 65 years of age , no diabetes or depression ; ( 7 ) patients who met enrollment criteria but were not included in any other group ; and ( 8) patients with ED due to traumatic spinal cord injury . The study had a 4-week run-in period , followed by a 12-week treatment period with tadalafil taken as needed , up to one dose/day , prior to sexual activity . Change from baseline to endpoint in the Erectile Function ( EF ) domain of the International Index of Erectile Function ( IIEF ) was used to determine noninferiority of groups 2 and 3 from group 1 . Secondary efficacy measures included other IIEF domains and Sexual Encounter Profile ( SEP ) . RESULTS Noninferiority analyses based on the EF domain score showed that tadalafil was as efficacious in the Hispanic and Black American groups as in the Reference group . Patients in each of the eight groups had a significant change from baseline ( P < 0.001 ) in the IIEF EF domain score and positive responses to SEP Questions 1 - 5 . The most common treatment-emergent adverse events reported by patients in all eight groups were headache , nasal congestion , dyspepsia , flushing , and back pain . CONCLUSION Tadalafil 20 mg was as efficacious in the Hispanic and black American groups as in the Caucasian/Reference group . Tadalafil was efficacious and well tolerated in each of the groups studied in this trial INTRODUCTION Data are sparse concerning the effects of phosphodiesterase type 5 ( PDE5 ) inhibitors for erectile dysfunction ( ED ) in subjects with multiple sclerosis ( MS ) . AIM To evaluate the efficacy and safety of tadalafil use in subjects with ED because of MS . METHODS Ninety-six MS patients with ED after a 4-week treatment-free period were given tadalafil 10 mg . All patients were re-evaluated after 4 weeks . Those with a score lower than 26 on the International Index of Erectile Function ( IIEF-15 ) and with less than 75 % of total successful sexual attempts assessed by the Sexual Encounter Profile Questions 2 and 3 ( SEP2 - 3 ) had their dosage of tadalafil increased to 20 mg , whereas responding subjects continued with 10 mg . Subsequently , all patients had a final follow-up visit after 8 weeks . MAIN OUTCOME MEASURES SEP2 - 3 , IIEF-15 question naire . The Life Satisfaction Checklist ( LSC ) question naire composed of eight questions was used prior to starting tadalafil and at the end of the 12-week treatment . RESULTS Ninety-two subjects completed the study . Seventy-two responded , 30 of whom used 10 mg . Two subjects discontinued the therapy because of moderate side effects : one suffered from headache and one from tachycardia . Responding patients reached a significant statistical improvement in all follow-ups compared with baseline on the erectile domain and overall sexual satisfaction scores of the IIEF-15 using the Wilcoxon test P < 0.01 . Furthermore , they showed statistical improvement through the Wilcoxon test P < 0.01 on the sexual life , family life , and partner relationship questions of the LSC compared with baseline . CONCLUSION Tadalafil is an effective and safe treatment for males with MS suffering from ED . Further studies are needed on MS patients to evaluate the efficacy and safety of long-term use , and to detect predictable parameters for the success of PDE5 inhibitors Abstract Objectives : Approximately one third to one half of the penis is embedded in the pelvis and can be felt through the scrotum and in the perineum . The main arteries and nerves enter the penis through this perineal part of the penis , which seems to represent a highly sensitive area . We investigated the hypothesis that percutaneous perineal stimulation evokes erection in patients with neurogenic erectile dysfunction . Methods : Percutaneous electrostimulation of the perineum ( PESP ) with synchronous intracorporeal pressure ( ICP ) recording was performed in 28 healthy volunteers ( age 36.3 ± 7.4 y ) and 18 patients ( age 36.6 ± 6.8 y ) with complete neurogenic erectile dysfunction ( NED ) . Current was delivered in a sine wave summation fashion . Average maximal voltages and number of stimulations delivered per session were 15 to 18 volts and 15 to 25 stimulations , respectively . Results : PESP of healthy volunteers effected an ICP increase ( P < 0.0001 ) , which returned to the basal value upon stimulation cessation . The latent period recorded was 2.5 ± 0.2 seconds . Results were reproducible on repeated PESP in the same subject but with an increase of the latent period . Patients with NED recorded an ICP increase that was lower ( P < 0.05 ) and a latent period that was longer ( P < 0.0001 ) than those of healthy volunteers . Conclusion : PESP effected ICP increase in the healthy volunteers and patients with NED . The ICP was significantly higher and latent period shorter in the healthy volunteers than in the NED patients . PESP may be of value in the treatment of patients with NED , provided that further studies are performed to reproduce these results Abstract Background / objective : To show the efficacy , safety , and tolerability of sildenafil in men with erectile dysfunction ( ED ) associated with complete or incomplete spinal cord injury ( SCI ) and to assess its effects on quality of life ( Qol ) using the Life-Satisfaction Check List . Methods : This was a placebo-controlled , multicenter , r and omized , double-blind , flexible-dose , 2-way crossover study with a 2-week washout period between each phase . Patients with ED attributable to SCI(Sexual Health Inventory-Male score ≤21 ) received 50 to 100 mg sildenafil ( n = 24 ) or placebo ( n = 26 ) . Results : Compared with placebo , sildenafil produced higher levels of successful sexual stimulation , intercourse success , satisfaction with sexual life and sexual relationship , erectile function , overall sexual satisfaction , and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score , with no clinical ly relevant effects onvital signs . Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI , producing significant improvements , compared with placebo , in a number of measures only in patients with incomplete SCI . All patients who expressed a preference selected sildenafil over placebo , although the drug had no effect on patient Qol . Sildenafil was well tolerated , with a profile comparable to that of placebo . Conclusions : Compared with placebo , treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI , especially in those with incomplete injury , and was theagent of choice in those who expressed a preference Objective : To assess the efficacy and tolerability of vardenafil in men with erectile dysfunction ( ED ) due to traumatic spinal cord injury ( SCI ) . Methods : In this multicenter , double-blind , placebo-controlled , parallel-group 12-week study , 418 men aged 18 years and older with ED for more than 6 months consequent to SCI were r and omized to vardenafil ( n = 207 ) or placebo ( n = 211 ) ( 10 mg for 4 weeks , then maintained or titrated to 5 or 20 mg at weeks 4 and 8) . Efficacy assessment s included the erectile function ( EF ) domain score of the International Index of Erectile Function question naire and diary questions regarding penetration , maintenance of erection to completion of intercourse , and ejaculation . Results : Baseline patient characteristics were similar in the vardenafil ( mean age 40 years ) and placebo ( mean age 39 years ) groups . Mean baseline EF domain scores were 11.6 in the vardenafil group and 12.1 ( moderate ED ) in the placebo group . EF domain score in the vardenafil group improved to 22.0 ( mild ED ) at last observation carried forward vs 13.5 in the placebo group ( p < 0.001 ) . Over 12 weeks of treatment , mean per-patient penetration ( 76 % vs 41 % ) , maintenance ( 59 % vs 22 % ) , and ejaculation ( 19 % vs 10 % ) success rates were significantly greater vs placebo ( all p < 0.001 ) . The most frequently reported drug-related adverse events were headache ( vardenafil 15 % , placebo 4 % ) , flushing ( vardenafil 6 % , placebo 0 % ) , nasal congestion ( vardenafil 5 % , placebo 0 % ) , and dyspepsia ( vardenafil 4 % , placebo 0 % ) . Conclusion : Vardenafil significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury Study design : Open , before – after study . Objective : To assess the efficacy and safety of phosphodiesterase type 5 ( PDE5 ) inhibitors for erectile dysfunction ( ED ) in spinal cord-injured ( SCI ) patients . Setting : Home- and clinic-based assessment s in the outpatient department at the Centre Bouffard Vercelli , Cerbère France . Methods : Clinic trials with Sildenafil ( Viagra ® ) on 120 patients , Tadalafil ( Cialis ® ) on 54 patients and Vardenafil ( Levitra ® ) on 66 patients were performed . Flexible doses of PDE5 inhibitors were given depending on efficacy and tolerability , from 50 to 100 mg for Sildenafil , and from 10 to 20 mg for Vardenafil and Tadalafil . Each trial was performed after a week 's interval . The efficacy was self-assessed by the patients on a six-point quantitative scale assessment . The response to treatment was assessed at home in 90 patients ( 57 patients on Sildenafil , 12 patients on Vardenafil and 21 patients on Tadalafil ) using the International Index of Erectile Function ( IIEF ) . Results : In clinic trials , PDE5 inhibitors were effective ( rigidity enough for penetration ) in 85 % of the patients on Sildenafil , 74 % of the patients on Vardenafil and 72 % of the patients on Tadalafil . The mean duration of erection was 34 , 28 and 26 min , respectively . Adverse effects were mild , usually attenuated with continued dosing . More than 70 % of the patients on Vardenafil and Tadalafil required higher doses of 20 mg , whereas 50 mg of Sildenafil was effective in 55 % of the patients . Two-thirds of our patients on Tadalafil reported a duration of action longer than 24 h. The presence of an upper motor neuron lesion was significantly associated with therapeutic success , lower motor neuron lesions and cauda equina patients were poor responders . Other variables such as completeness of lesion had no impact . In the follow-up visits , the IIEF global scores and three IIEF domains ( erectile function , intercourse satisfaction and overall satisfaction ) were significantly improved in all patients . Patients on Sildenafil showed a significant improvement of orgasmic function , ejaculation ( Question 9 ) and orgasm ( Question 10 ) . Conclusion : Sildenafil , Vardenafil and Tadalafil are all effective and well-tolerated treatments for ED in SCI patients . Although no statistical analysis could be applied on these data , these results might indicate that Sildenafil is more effective in treating ED . Clinic trials are important for proper dose titration and appropriate education of the patients Parkinson 's disease ( PD ) is one of the most commonly occurring neurodegenerative disorders , with lifetime incidence between 1 and 2 % among people older than 65 years . ED is one of the more disabling and poorly addressed aspects of PD . The purpose of this study was to assess the efficacy and safety of sildenafil citrate in Parkinson-emergent ED . Sexual function of participants was assessed using responses to the 15- question International Index of Erectile Function ( IIEF ) , Sexual Encounter Profile ( SEP ) diary questions 2 and 3 , Erectile Dysfunction Inventory of Treatment Satisfaction ( EDITS ) question naire and a Global Efficacy Question ‘ Has the treatment you have been taking over the study period improved your erections ? ’ This r and omized , double-blind , placebo-controlled study , comprised a screening period of at least 1 month , a placebo-lead in period of 1 week and treatment period . Two hundred thirty-six patients entered the trial . These patients had mild-to-moderate PD ( stages I – III Hoehn – Yahr ) and were experiencing Parkinson-emergent neurogenic ED . They were r and omized to receive 100 mg sildenafil on dem and 1 h before sexual activity ( group 1 , n=118 ) , or similar regimen of placebo ( group 2 , n=118 ) . Patients were instructed to use at least 24 doses/attempts at home . At the end of the trial , differences between sildenafil and placebo groups were significant for the IIEF erectile function ( EF ) score ( 22.6±4.6 vs 14.8±4.2 , P=0.01 ) , for percent Global Efficacy Question ‘ Yes ’ responses ( 68.1±4.6 vs 12.2±3.2 , P=0.001 ) , for SEP2 ‘ Yes ’ responses ( 68.1±4.2 vs 32.5±2.2 , P=0.003 ) , for SEP3 ‘ Yes ’ responses ( 75.9±5.4 vs 33.5±4.4 , P=0.004 ) and for mean EDITS score ( 69.8±4.2 vs 13.0±2.7 , P=0.004 ) . A normal EF domain score ( ⩾26 ) at end point was achieved by 56.9 and 8.7 % of the patients in the sildenafil and placebo groups , respectively ( P=0.001 ) . Sildenafil can be considered as an effective treatment in patients with Parkinson-emergent ED Regulatory T cells ( Tregs ) play a key role in cancer immune escape . We identified target antigens of spontaneous tumor-specific T cell responses in urothelial carcinoma ( UC ) and evaluated their modulation by treatment and Treg . We determined Treg target antigens in UC . Fifty-six UC and 13 control patients were prospect ively enrolled . Blood was drawn before and after routine treatment . Changes in Treg frequency were measured by fluorescence cytometry and the T effector cell ( Teff ) response against a set of nine tumor-associated antigens ( TAAs ) was monitored with an interferon-gamma ELISpot . Antigen specificity of Treg was determined by their increased capacity to inhibit after TAA-specific activation the proliferation of an autologous T cell population . The highest difference in the overall response rate for the total T cell population was observed for epidermal growth factor receptor ( EGFR ) ( UC : 23 % and controls : 0 % ) . After depleting Treg , also new york esophageal (NYES)O1 ( 19 and 0 % ) and MUC20 ( 27 and 0 % ) were more frequently recognized in UC patients . In metastasized patients , the TAA-directed T cell response was augmented by Treg depletion . Tumor resection seemed to diminish Treg suppression of TAA-specific immunity , whereas chemotherapy had no effect . We demonstrated the existence of TAA-specific Treg in UC , which share antigen specificities with Teff . The coexistence of TAA-specific Treg and Teff was very rare . Treg frequencies in the peripheral blood were not changed by therapy . In summary , we identified potentially immunologically relevant TAA in UC . TAA-specific T cell responses against these antigens are suppressed by Treg . We identified TAA-specific Treg in UC patients , which do not cooccur with TAA-specific Teff Background Urinary tract symptoms are an underestimated problem in multiple sclerosis ( MS ) . Objective Hundred urodynamics of MS patients have been evaluated prospect ively . Design , setting and participants In an inpatient rehabilitation , all persons with MS who also suffered from urinary tract symptoms received a voiding diary , post-void sonography and an urodynamic examination according to International Continence-Society-St and ard . Results and limitations Between 10/2009 and 3/2011 , 100 patients ( 79 women ; 21 men ; mean EDSS , 4.52 ± 2.26 ) were examined who had primary progressive MS ( 9 × ) , relapsing – remitting MS ( 41 × ) , secondary progressive MS ( 43 × ) and CIS ( 1 × ) . The mean duration of MS was 10.26 ± 10.09 years and mean duration of LUTS , 6.9 ± 7.75 years . Urodynamic testing showed normal findings in 22 patients , detrusor overactivity in 7 , increased bladder sensation without detrusor overactivity in 21 , detrusor – sphincter dyssynergia in 26 , detrusor hypocontractility in 12 , detrusor acontractility in 4 and unclear diagnosis in 8 patients . Statistically significant risk factors for pathological urodynamic findings were as follows : wheelchair dependency , use of more than one incontinence pad per day and a MS type other than relapsing – remitting . Conclusions The urodynamic investigation at h and showed urinary tract dysfunction in 78 of 100 MS patients with lower urinary tract symptoms ( LUTS ) . The long latency between the occurrence of MS and /or the beginning of LUTS and the first neuro-urological evaluation indicates a deficit in treatment . Beyond national guidelines , all MS patients should at regular intervals be question ed about LUTS and receive urodynamic assessment especially according to the presented risk profile AIM Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction ( ED ) . Efficacy of vardenafil has been demonstrated in various ED population s , but that in Japanese patients with spinal cord injury ( SCI ) has not been assessed . METHODS This was an open-label , multicenter , flexible dose , 12-week study in patients with ED due to SCI . Following a 4-week observation period , patients received vardenafil 10 mg for 4 weeks , and based on efficacy , tolerability and patient preference , doses for the remaining 8 weeks were decided by investigators . The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function . RESULTS Ten patients took 10 mg all through the study , while 22 patients took 20 mg after completing 4 weeks ' treatment with 10 mg . The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward ( LOCF ) in the former group and from 10.3 to 22.5 in the latter group , respectively . Importantly , there was a 5.0 point increase in erectile function domain score after up-titration in the latter group . Drug-related adverse events were observed in 22 % of patients including hot flushes ( 9 % ) and headache ( 6 % ) , but these were transient and mild in intensity . Serious adverse events and adverse events leading to discontinuation of the study drug were not reported . CONCLUSIONS Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI . Of interest , erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg Study design : Prospect i ve multicentre cohort study . Objectives : To determine mortality , causes and determinants of death of individuals with spinal cord injury ( SCI ) within five years after first inpatient rehabilitation . Setting : The Netherl and s. Methods : Patients were included on admission to first clinical rehabilitation after traumatic or nontraumatic SCI . Inclusion criteria : age between 18 and 65 , American Spinal Injury Association impairment scale A – D and expected long-term wheelchair dependency . Information about survival , cause of death , relevant comorbidity and psychosocial circumstances was obtained from the rehabilitation physician or general practitioner . Determinants of death were retrieved from a prospect ively collected data base . Deceased persons and survivors were compared using χ2-test and t-test . Cox regression analysis was performed to describe independent predictors of death . The Kaplan – Meier method was used to calculate survival curves for independent predictors . Excess mortality was described by a st and ardized mortality ratio ( SMR ) . Results : Mean duration of follow up was 6.2 years . A total of 27 persons ( 12.2 % ) died during this period ( SMR 5.3 ) . Main causes of death were cardiovascular disease ( 37.0 % ) , pulmonary disease ( 29.6 % ) and neoplasm ( 14.8 % ) . Older age at injury , nontraumatic SCI , family history of cardiovascular disease , less social support and a history of other medical conditions on admission were related to death . Older age at injury , nontraumatic SCI and a history of other medical conditions were independent predictors of death . Conclusion : Twelve per cent of persons with SCI who had survived the acute hospital phase died during follow up ( SMR 5.3 ) . The main causes of death were cardiovascular and pulmonary disease AIMS Risk of treatment-related problems in spinal cord injury ( SCI ) m and ates assessment of complication rates of different bladder management methods ( BMMs ) . The current study evaluated aging-related complications of various BMMs over a 6-year period in a population with spinal cord injury for at least 20 years . MATERIAL S AND METHODS Clinical parameters were compared using a linear mixed effects model , controlling for various confounding variables , to establish complication trends with aging and their association with BMM . Results for people whose BMM was changed during the study were evaluated separately as well as in combination with the whole population . RESULTS One hundred and ninety six people ( mean age 57.4 and years post injury ( YPI ) 33 ) were evaluated on three occasions . Both age and YPI were significantly associated with rising complication rates regardless of BMM . The BMMs assessed differed in terms of complication rates . In comparison with balanced reflex voiding , straining was significantly better for renal structural abnormality . Intermittent catheterization was associated with significantly worse renal function , possibly for demographic reasons . Overall , 28.8 % changed BMM during the study period , particularly , those using straining or balanced reflex voiding . The probability of change increased with age and YPI . Reasons for change of BMM were varied and there was no specific association between reason for change and BMM . CONCLUSIONS Aging and duration of injury substantially influence urological complication rates , and BMM options differ in respect of prevalence and incidence of complications . At a late stage post injury there remains a high probability of change in BMM . The findings indicate the importance of long-term planning from the time of injury to minimize late complications BACKGROUND Neurogenic detrusor overactivity ( NDO ) frequently results in urinary incontinence ( UI ) which impairs quality of life ( QOL ) and puts the upper urinary tract at risk . OBJECTIVE To assess the effects of onabotulinumtoxinA ( BOTOX ( ® ) , Allergan , Inc. ) on UI , urodynamic variables , and QOL in incontinent patients with NDO . DESIGN , SETTING , AND PARTICIPANTS This multicentre , r and omised , double-blind , placebo-controlled study enrolled patients with multiple sclerosis ( MS ; n=154 ) or spinal cord injury ( SCI ; n=121 ) with UI due to NDO ( ≥14 UI episodes per week ) . INTERVENTION Patients received 30 intradetrusor injections of onabotulinumtoxinA 200 U ( n=92 ) , 300 U ( n=91 ) , or placebo ( n=92 ) , avoiding the trigone . MEASUREMENTS Primary end point was change from baseline in UI episodes per week ( week 6 ) . Secondary end points included urodynamics ( maximum cystometric capacity [ MCC ] , maximum detrusor pressure during first involuntary detrusor contraction [ P(detmaxIDC ) ] ) , and Incontinence Quality of Life ( I-QOL ) total score . Adverse events ( AEs ) were assessed . RESULTS AND LIMITATIONS At baseline , mean UI episodes per week ( 33.5 ) were similar across groups . At week 6 , onabotulinumtoxinA 200 U and 300 U significantly reduced UI episodes per week ( -21.8 and -19.4 , respectively ) compared with placebo ( -13.2 ; p<0.01 ) ; onabotulinumtoxinA benefit was observed by the first posttreatment study visit at week 2 . Improvements in MCC , P(detmaxIDC ) , and I-QOL at week 6 were significantly greater with both onabotulinumtoxinA doses than with placebo ( p<0.001 ) . Benefits were observed in both the MS and SCI population s. The median time to patient request for retreatment was the same for both onabotulinumtoxinA doses ( 42.1 wk ) and greater than placebo ( 13.1 wk ; p<0.001 ) . Most frequent AEs were localised urologic events ( urinary tract infections and urinary retention , which were dose related in patients not using clean intermittent catheterisation [ CIC ] at baseline ) . Significant increases in postvoid residual were observed in patients not using CIC prior to treatment , and 12 % , 30 % , and 42 % of patients in the placebo , 200-U , and 300-U groups , respectively , initiated CIC posttreatment . CONCLUSIONS OnabotulinumtoxinA significantly reduced UI and improved urodynamics and QOL in MS and SCI patients with NDO . Both doses were well tolerated with no clinical ly relevant differences in efficacy or duration of effect between the two doses ( http://www . clinical trials.gov ; NCT00461292 ) PURPOSE We assessed the efficacy , safety and effects on quality of life of onabotulinumtoxinA in patients with neurogenic detrusor overactivity . MATERIAL S AND METHODS In this 52-week , international , multicenter , double-blind , r and omized , placebo controlled trial 416 patients with neurogenic detrusor overactivity and urinary incontinence ( 14 or more episodes per week ) result ing from multiple sclerosis ( 227 ) and spinal cord injury ( 189 ) were treated with intradetrusor injections of onabotulinumtoxinA ( 200 or 300 U ) or placebo . The primary end point was the change from baseline in the mean number of urinary incontinence episodes per week at week 6 . Maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life total score were secondary end points . Adverse events were monitored . RESULTS OnabotulinumtoxinA at a dose of 200 U in 135 patients and 300 U in 132 decreased mean urinary incontinence at week 6 by 21 and 23 episodes per week , respectively , vs 9 episodes per week in 149 on placebo ( each dose p<0.001 ) . Also , maximum cystometric capacity , maximum detrusor pressure during the first involuntary detrusor contraction and Incontinence Quality of Life score were significantly improved over values in the placebo group ( each dose p<0.001 ) . Median time to patient re-treatment request was greater for onabotulinumtoxinA 200 and 300 U than for placebo ( 256 and 254 days , respectively , vs 92 ) . The most common adverse events were urinary tract infection and urinary retention . Of patients who did not catheterize at baseline 10 % on placebo , 35 % on 200 U and 42 % on 300 U initiated catheterization due to urinary retention . CONCLUSIONS OnabotulinumtoxinA significantly improved neurogenic detrusor overactivity symptoms vs placebo . Clean intermittent catheterization initiation due to urinary retention appeared to increase in a dose dependent fashion . No clinical ly relevant benefit in efficacy or duration was identified for the 300 U dose over the 200 U dose OBJECTIVES To evaluate the efficacy and complications of ileovesicostomy in patients with neurogenic bladder dysfunction . METHODS Fifteen consecutive neurologically impaired patients ( 8 from multiple sclerosis , 4 from spinal cord injury , 3 from other causes ) with complications of previous bladder management underwent ileovesicostomy . There were 10 women and 5 men . All patients were either poor c and i date s for or refused continent urinary diversion or bladder augmentation cystoplasty . RESULTS At a mean follow-up of 23.2 months , 14 of 15 patients had low-pressure urine drainage through their ileovesicostomy . Four women with documented preoperative detrusor hyperreflexia had postoperative intermittent mild urge incontinence per native urethra . They did not require any further treatment , except for oral anticholinergic drugs ( oxybutynin and tolterodine ) . Because of persistent severe urge incontinence , 1 woman required conversion of her ileovesicostomy to an ileal conduit with concurrent cystectomy . The ileovesicostomy of another myelodysplastic man who had four failed artificial urinary sphincters in the past was also converted to an ileal conduit because of persistent urethroperineal fistula despite perineal urethral closure . Renal function was preserved in all patients . Long-term complications were stomal stenosis in 2 patients , bladder and kidney stone formation in 5 , and symptomatic urinary tract infections in 3 . CONCLUSIONS Ileovesicostomy can be safely performed in neurologically impaired women and men . Severe preoperative detrusor hyperreflexia with urge incontinence appears to be a risk factor for persistent urge incontinence postoperatively in women . Continued routine urologic surveillance for infection and stones is m and atory . Ileovesicostomy is a versatile procedure for neurologically impaired patients , because it can be converted to a conventional ileal conduit if necessary . In addition , in cases of neural recovery , the ileal " chimney " can be excised and the patient 's original lower urinary tract would be preserved To evaluate the efficacy , safety and patients ' preference of different treatment modalities of ED in men with SCI . Sixty SCI men with ED were included in the study . They were divided into three groups . Group A received sildenafil , group B received intracorporal injection ( ICI ) and were then shifted to sildenafil and group C used vacuum constriction devices ( VCD ) and were then shifted to sildenafil . Erection was evaluated before and after each treatment . Ninety percent of patients reported improvement of erection after sildenafil and ICI treatment according to IIEF-EF and only 70 % of patients reported improvement in erection with VCD . However , 14 patients reported that they preferred sildenafil due to the easier route of administration . In men with SCI , sildenafil is the most effective treatment and is widely accepted . ICI , VCD therapy in SCI patients should be used according to patient 's preference and choice To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction ( ED ) secondary to upper motor neuron ( UMN ) and lower motor neuron ( LMN ) spinal cord injury ( SCI ) . After taking consents 105 patients suffering from ED were enrolled in this prospect i ve study . Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed ( UMN and LMN ) spinal cord injuries . The patients took 50 - 100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse . Based on a IIEF question naire , success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries . In patients with UMN disease , sildenafil was effective in 82 % of patients and its efficacy was statistically higher than placebo ( 82 vs. 25 % , p < 0.05 ) . Twenty-eight per cent of patients with non-UMN disease had a favourable response to sildenafil that was not statistically different from placebo . Sildenafil seems more effective in the treatment of neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury . Actually , its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms In this study , we investigated whether elimination of CD4+/CD25 + Tregs using the recombinant IL-2 diphtheria toxin conjugate DAB(389)IL-2 ( also known as denileukin diftitox and ONTAK ) is capable of enhancing the immunostimulatory efficacy of tumor RNA-transfected DC vaccines . We show that DAB(389)IL-2 is capable of selectively eliminating CD25-expressing Tregs from the P BMC s of cancer patients without inducing toxicity on other cellular subsets with intermediate or low expression of CD25 . DAB(389)IL-2-mediated Treg depletion result ed in enhanced stimulation of proliferative and cytotoxic T cell responses in vitro but only when DAB(389)IL-2 was omitted during T cell priming . DAB(389)IL-2 significantly reduced the number of Tregs present in the peripheral blood of metastatic renal cell carcinoma ( RCC ) patients and abrogated Treg-mediated immunosuppressive activity in vivo . Moreover , DAB(389)IL-2-mediated elimination of Tregs followed by vaccination with RNA-transfected DCs significantly improved the stimulation of tumor-specific T cell responses in RCC patients when compared with vaccination alone . Our findings may have implication s in the design of immune-based strategies that may incorporate the Treg depletion strategy to achieve potent antitumor immunity with therapeutic impact PURPOSE We evaluated the safety and efficacy of sildenafil citrate for treating erectile dysfunction in patients with multiple sclerosis . MATERIAL S AND METHODS A total of 203 patients with multiple sclerosis ( age range 18 to 50 years old ) with erectile dysfunction were r and omly assigned to receive 50 to 100 mg sildenafil ( 102 patients in group 1 ) or a similar regimen of placebo ( 101 patients in group 2 ) 45 minutes to 2 hours before sexual stimulation . Patients were asked to use at least 24 doses/attempts at home . Primary outcome measures consisted of responses to questions 3 and 4 from the International Index of Erectile Function question naires well as responses to Sexual Encounter Profile diary questions 2 and 3 . We also assessed the number of attempts at sexual intercourse , the number of attempts that were successful and adverse drug effects . RESULTS Improved erections ( positive response to the Global Assessment Question naire ) were reported by 32.8 % of patients receiving sildenafil and 17.6 % of those receiving placebo ( p = 0.04 ) . For Sexual Encounter Profile question 2 ( successful penetration ) the increase from baseline in mean per patient percentage of yes responses was 29.4 % after sildenafil vs 18.8 % after placebo ( p = 0.04 ) . The proportion of successful sexual attempts ranged from 12 % to 26 % for sildenafil and from 9 % to 21 % for placebo , respectively ( p = 0.044 ) . Of patients taking sildenafil and placebo 24 ( 23.5 % ) and 9 ( 8.9 % ) experienced 81 and 31 adverse events , respectively ( p = 0.01 ) . CONCLUSIONS Compared with placebo , sildenafil has little effect on multiple sclerosis emergent erectile dysfunction and , therefore , can not be recommended for the routine treatment of erectile dysfunction in patients with multiple sclerosis . This finding implies that there must be other mechanisms that are not affected by sildenafil or are resistant to the effects of sildenafil Herein we combine 2 studies : a 25-year prospect i ve followup on 270 spinal cord injury patients and a more than 20-year ( average 24.2 years ) evaluation of 175 paraplegics . The mortality rate was 49 per cent after 25 years , with renal disease as the major cause of death ( 43 per cent ) . Vascular deaths were just as prevalent during the last 5 years of spinal cord life . There are probably several reasons why some patients have long-term survival ( more than 20 years ) , including patient motivation ( better followup ) , less vascular problems , less chronic decubitus and a higher percentage of lower motor neuron lesions . Patients with lower motor neuron lesions had the best bladder status associated with less upper tract deterioration OBJECTIVES To analyze the influence of bladder management on patient well-being by correlating the objective urodynamic results of bladder treatment with the perceived quality of life in patients with spinal cord lesions . METHODS In a prospect i ve study , 41 consecutive patients with neurogenic lower urinary tract dysfunction due to a spinal cord lesion who were performing intermittent self-catheterization underwent urodynamic examination and answered the German version of the Qualiveen ( Coloplast A/S , Humlebaek , Denmark ) question naire . The urodynamic results were classified as either treatment success or failure . The results of the Qualiveen question naire were correlated with these results . RESULTS The Qualiveen scales concerning fears and feelings were significantly worse in patients with suboptimal bladder function compared with those patients with treatment success . CONCLUSIONS The results of our study have demonstrated that a treatment regimen leading to favorable urodynamic data and continence correlates with better quality of life Hyposexuality is commonly associated with low bioavailable testosterone ( BAT ) and relative estradiol elevation in men with epilepsy . This prospect i ve , r and omized , double-blind trial compared the effects of depotestosterone+the aromatase inhibitor anastrozole ( T-A ) versus depotestosterone+placebo ( T-P ) on sexual function , hormone levels , mood , and seizure frequency in men with epilepsy . Forty men with focal epilepsy , hyposexuality , and hypogonadism were r and omized 1:1 to two groups ( T-A or T-P ) for a 3-month treatment trial of depotestosterone+either anastrozole or matching placebo . Outcomes included both efficacy and safety measures . Normalization of sexual function ( S-score ) occurred with greater frequency in the T-A ( 72.2 % ) than in the T-P ( 47.4 % ) group , but the difference was not statistically significant . T-A result ed in significantly lower estradiol levels and S-scores correlated inversely with estradiol levels at baseline and during treatment . Beck Depression Inventory II ( BDI-II ) scores improved significantly in both groups and changes in S-score correlated inversely with changes in BDI-II score . Changes in seizure frequency correlated with changes in BDI-II score . Seizure frequency decreased with both treatments and showed significant correlations with estradiol levels . Triglyceride levels increased with T-P and decreased with T-A. The difference in triglyceride changes between the two treatments was significant and correlated with changes in estradiol levels . Significant correlations between estradiol levels and S-scores , as well as seizure outcomes and triglyceride levels , suggest further study regarding a potential role for anastrozole in the treatment of men with epilepsy who have hyposexuality and hypogonadism |
2,428 | 22,131,562 | There is a paucity of evidence to support aerobic physical activity as a successful st and alone treatment for decreasing adiposity .
Despite the heterogeneity of the methods there is some evidence to support that school-aged children and youth benefit from aerobic physical activity to decrease adiposity and to limit weight gain | CONTEXT The role of aerobic physical activity as a st and alone treatment in decreasing adiposity in school-aged children and youth has not been well established .
OBJECTIVE To systematic ally search and assess the quality of the literature on the efficacy of aerobic physical activity to decrease adiposity in school-aged children and youth . | PURPOSE To determine the effect of increasing the aerobic component of the school 's physical activity program and improving the knowledge about weight control and blood pressure on the blood pressure and body fat of early adolescents . METHODS The subjects were 1140 youth aged 11 to 14 years ( 630 females , 510 males ; 64 % white , 24.4 % African-American , and 11.6 % " other " ) , who were r and omly assigned by school into four treatment groups : exercise only , education only , exercise and education combined , and control group . Heights , weights , and skinfold thicknesses were measured , and body mass index ( BMI ) was computed kg/m(2 ) . Blood pressure was obtained in duplicate using a r and om-zero mercury sphygmomanometer . Maximal oxygen uptake was predicted from a submaximal cycle ergometer test . Data were analyzed using analysis of covariance statistics , adjusting for gender , ethnicity , age , socioeconomic status , and initial baseline characteristics . RESULTS Systolic and diastolic blood pressures increased more in the control group than in the intervention groups ( p = .001 ) . The BMI did not change significantly ( p = .709 ) , but the sum of skinfolds increased less in subjects in the exercise intervention groups than the education only or control groups ( p = .0001 ) . The small increase in (p)VO(2)max of the combined exercise and education group was significantly greater than the education only group ( p = .0001 ) . CONCLUSION An exercise program for youth can have a positive effect on blood pressure independent of body weight loss BACKGROUND Little is known about how the intensity of exercise influences cardiovascular fitness and body composition , especially in obese adolescents . OBJECTIVE Our goal was to determine the effects of physical training intensity on the cardiovascular fitness , percentage of body fat ( % BF ) , and visceral adipose tissue ( VAT ) of obese adolescents . DESIGN Obese 13 - 16-y-olds ( n = 80 ) were assigned to 1 ) biweekly lifestyle education ( LSE ) , 2 ) LSE + moderate-intensity physical training , or 3 ) LSE + high-intensity physical training . The intervention lasted 8 mo . Physical training was offered 5 d/wk , and the target energy expenditure for all subjects in physical training groups was 1047 kJ ( 250 kcal)/session . Cardiovascular fitness was measured with a multistage treadmill test , % BF with dual-energy X-ray absorptiometry , and VAT with magnetic resonance imaging . RESULTS The increase in cardiovascular fitness in the high-intensity physical training group , but not in the moderate-intensity group , was significantly greater than that in the LSE alone group ( P = 0.009 ) ; no other comparisons of the 3 groups were significant . Compared with the LSE alone group , a group composed of subjects in both physical training groups combined who attended training sessions > or=2 d/wk showed favorable changes in cardiovascular fitness ( P < 0.001 ) , % BF ( P = 0.001 ) , and VAT ( P = 0.029 ) . We found no evidence that the high-intensity physical training was more effective than the moderate-intensity physical training in enhancing body composition . CONCLUSIONS The cardiovascular fitness of obese adolescents was significantly improved by physical training , especially high-intensity physical training . The physical training also reduced both visceral and total-body adiposity , but there was no clear effect of the intensity of physical training OBJECTIVES The aim of this study was to determine the effects of physical activity on systemic blood pressure ( BP ) and early markers of atherosclerosis in pre-pubertal obese children . BACKGROUND Hypertension and endothelial dysfunction are premature complications of obesity . METHODS We performed a 3-month r and omized controlled trial with a modified crossover design : 44 pre-pubertal obese children ( age 8.9 + or - 1.5 years ) were r and omly assigned ( 1:1 ) to an exercise ( n = 22 ) or a control group ( n = 22 ) . We recruited 22 lean children ( age 8.5 + or - 1.5 years ) for baseline comparison . The exercise group trained 60 min 3 times/week during 3 months , whereas control subjects remained relatively inactive . Then , both groups trained twice/week during 3 months . We assessed changes at 3 and 6 months in office and 24-h BP , arterial intima-media thickness ( IMT ) and stiffness , endothelial function ( flow-mediated dilation ) , body mass index ( BMI ) , body fat , cardiorespiratory fitness ( maximal oxygen consumption [ VO(2)max ] ) , physical activity , and biological markers . RESULTS Obese children had higher BP , arterial stiffness , body weight , BMI , abdominal fat , insulin resistance indexes , and C-reactive protein levels , and lower flow-mediated dilation , VO(2)max , physical activity , and high-density lipoprotein cholesterol levels than lean subjects . At 3 months , we observed significant changes in 24-h systolic BP ( exercise -6.9 + or - 13.5 mm Hg vs. control 3.8 + or - 7.9 mm Hg , -0.8 + or - 1.5 st and ard deviation score [ SDS ] vs. 0.4 + or - 0.8 SDS ) , diastolic BP ( -0.5 + or - 1.0 SDS vs. 0 + or - 1.4 SDS ) , hypertension rate ( -12 % vs. -1 % ) , office BP , BMI z-score , abdominal fat , and VO(2)max . At 6 months , change differences in arterial stiffness and IMT were significant . CONCLUSIONS A regular physical activity program reduces BP , arterial stiffness , and abdominal fat ; increases cardiorespiratory fitness ; and delays arterial wall remodeling in pre-pubertal obese children . ( Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children : A R and omized Controlled Trial ; NCT00801645 ) The aim of the present study was to examine the effect of exercise training on adipokines , inflammatory markers , and oxidative stress in overweight children . Nineteen overweight children were r and omly assigned to an aerobic exercise training or sedentary control group for 8 weeks . Measurements included peak oxygen uptake ( V o(2)max ) , body weight and composition , adipokines ( C-reactive protein , interleukin 6 , tumor necrosis factor alpha , adiponectin , leptin , and resistin ) , and oxidative stress ( 8-isoprostane ) . There were no differences between groups for change in body weight or composition over the 8 weeks . Exercise training improved V o(2)max ( exercise group , 1.64 + /- 0.13 to 1.85 + /- 0.17L/min vs control group , 1.83 + /- 0.12 to 1.60 + /- 0.13 L/min , P < .05 ) but did not change any of the measured adipokines or the marker of systemic oxidative stress , 8-isoprostane . These data suggest that in the absence of weight loss , exercise training alone does not improve the adipokine profile or levels of oxidative stress in overweight children OBJECTIVE To provide a review of the literature and rate the quality of published studies regarding chiropractic care , including spinal manipulation , for asthmatic patients . METHODS A multimodal search strategy was conducted , including multiple data base search es , along with reference and journal h and - search ing . Studies were limited to those published in English and in peer- review ed journals or conference proceedings between January 1980 and March 2009 . All study design s were considered except personal narratives or review s. Retrieved articles that met the inclusion criteria were rated for quality by using the Downs and Black checklist . A brief summary was also written for each retrieved study . RESULTS Eight articles met the inclusion criteria of this review in the form of one case series , one case study , one survey , two r and omized controlled trials ( RCTs ) , one r and omized patient and observer blinded cross-over trial , one single blind cross study design , and one self-reported impairment question naire . Their quality scores ranged from 5 to 22 out of 27 . CONCLUSION Results of the eight retrieved studies indicated that chiropractic care showed improvements in subjective measures and , to a lesser degree objective measures , none of which were statistically significant . It is evident that some asthmatic patients may benefit from this treatment approach ; however , at this time , the evidence suggests chiropractic care should be used as an adjunct , not a replacement , to traditional medical therapy OBJECTIVE To assess the impact of a 2-year recreational physical activity program in 1044 fourth- and fifth- grade primary schoolchildren from the Province of Cuenca , Spain . STUDY DESIGN Cluster-r and omized controlled trial with 10 intervention and 10 control schools . The program consisted of 3 90-minute sessions of physical activity per week , during 28 weeks every year . Changes in endpoints between baseline ( September 2004 ) and the end of follow-up ( June 2006 ) were compared between the control and intervention group by using mixed regression models , with adjustment for the baseline endpoint value , age , and the school . RESULTS Compared with control subjects , intervention girls reduced the frequency of overweight ( odds ratio , 0.55 ; 95 % CI , 0.39 - 0.78 ; P<.001 ) . However , intervention was associated with an increase in the percentage of body fat in boys ( 0.97 % ; 95 % CI , 0.14 - 1.81 ; P=.02 ) . Girls in the intervention group had lower total cholesterol level ( -6.86 mg/dL ; 95 % CI , -9.70 - -4.01 ; P<.001 ) and apolipoprotein B level ( -3.61 mg/dL ; 95 % CI , -6.27 - -0.95 ; P=.008 ) than control subjects . Results were similar in boys . CONCLUSION In 2 years , the physical activity program lowered the frequency of overweight in girls and reduced total cholesterol and apolipoprotein B in both girls and boys 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 : To determine the effect of exercise training ( ET ) on components of the insulin resistance syndrome ( IRS ) in obese children . DESIGN : R and omized , modified cross-over study , with subjects assigned to one of two conditions : ( 1 ) 4 months of ET followed by 4 months of no-ET ; or ( 2 ) 4 months of no-ET followed by 4 months of ET . Measurements were made at three time points : 0 , 4 and 8 months . SUBJECTS : 79 obese , but otherwise healthy children ( age : 7–11 y , percent fat ( % fat ) 27–61 % ) . MEASUREMENTS : Plasma lipid and lipoprotein concentrations , plasma insulin and glucose concentrations ; % fat ; submaximal heart rate ( HR ) as an index of fitness . EXERCISE TRAINING : ET was offered 5 d/week 40 min/d . For the 73 children who completed 4 months of ET , the mean attendance was 80 % ( that is , 4 d/week ) and the average HR during ET was 157 bpm . RESULTS : Significant ( P<0.05 ) group x time interactions were found for plasma triglyceride ( TG ) and insulin concentrations and % fat . The average change for both groups , from just before ET to just after the 4 month ET was −0.24 mmolċl−1 for TG , −25.4 pmolċl−1 for insulin and −1.6 units for % fat . When Group 1 ceased ET , over the following 4 month period the average change for insulin was + 26.6 pmolċl−1 and for % fat + 1.3 units . CONCLUSION : Some components ( plasma TG , insulin , % fat ) of the IRS are improved as a result of 4 months of ET in obese children . However , the benefits of ET are lost when obese children become less active PURPOSE Children with high levels of total body fat mass ( TFM ) and visceral adipose tissue ( VAT ) have elevated levels of certain risk factors for coronary artery disease and non-insulin-dependent diabetes mellitus . We tested the hypothesis that controlled physical training , without dietary intervention , would have a favorable impact on VAT and percent body fat ( % BF ) in obese children . METHODS A volunteer sample of 74 obese children , 7 - 11 yr of age , accepted r and om assignment to physical training or control groups . Before and after 4 months of intervention , measurements were obtained for VAT , TFM , % BF , daily physical activity , and cardiovascular fitness . The intervention involved 4 months of controlled physical training 5 d x wk(-1 ) , 40 min per session , at a mean heart rate ( HR ) of 157 beats x min(-1 ) . The estimated energy expenditure ( EE ) per training session was 925+/-201 kJ. RESULTS Compared with the control group , the physical training group declined significantly in % BF ( delta = -2.2 % ) ( P < 0.01 ) , TFM ( delta = -3.1 % ) ( P < 0.01 ) , and subcutaneous abdominal adipose tissue ( delta = - 16.1 % ) ( P < 0.05 ) , and increased significantly in fat-free mass ( delta = + 6.1 % ) ( P < 0.05 ) and moderate-to-very hard physical activity ( delta = + 14.1 % ) ( P < 0.05 ) . The increase in VAT was significantly less in the physical training group ( delta = + 0.5 % ) as compared with that in the control group ( delta = + 8.1 % ) ( P < 0.05 ) . CONCLUSIONS This study showed that during physical training obese children : 1 ) were capable of participating in a substantial amount of high intensity physical training over a 4-month period : 2 ) accumulated significantly less VAT as compared with nonexercising controls ; and 3 ) experienced other beneficial changes in total and regional body composition Sixteen postmenarcheal Type 1 diabetic adolescent girls were r and omized into training ( involving aerobic and strength exercises ) and nontraining groups . Body composition ( skinfold thickness ) , aerobic fitness ( PWC170 ) , plasma lipids , serum apolipoproteins , lipoprotein(a ) , leptin , and adiponectin were assessed before and after the 6-month period . After the 6-month period , fat mass and leptin increased significantly in the nontraining group but not in the training group . Conversely , in the latter group , fat-free mass increased ( P < .01 ) . Moreover , PWC170 improved and apolipoproteinB : apolipoproteinA-1 ratio decreased with physical training ( P < .05 ) . Thus , physical training reduces cardiovascular risks and the increase of insulin resistance risk factors in diabetic adolescent girls OBJECTIVES The present study aim ed to assess the effect of a 6-month exercise program in obese children on flow-mediated vasodilation ( FMD ) carotid intima-media thickness ( IMT ) and cardiovascular risk factors ( RF ) . BACKGROUND Childhood obesity contributes to adult obesity and subsequent cardiovascular disease . Physical inactivity is a major RF for obesity , endothelial dysfunction , and elevated carotid IMT , culminating in early atherosclerotic disease . METHODS Sixty-seven obese subjects ( age 14.7 + /- 2.2 years ) were r and omly assigned to 6 months ' exercise or non-exercise protocol . We examined the influence of exercises ( 1 h , 3 times/week ) on FMD , IMT , and cardiovascular risk profile . RESULTS Compared with lean control subjects , obese children demonstrated at baseline significantly impaired FMD ( 4.09 + /- 1.76 % vs. 10.65 + /- 1.95 % , p < 0.001 ) , increased IMT ( 0.48 + /- 0.08 mm vs. 0.37 + /- 0.05 mm , p < 0.001 ) , and a number of obesity-related cardiovascular RF . Significant improvements were observed in the exercise group for IMT ( 0.44 + /- 0.08 mm , p = 0.012 , -6.3 % ) and FMD ( 7.71 + /- 2.53 % , p < 0.001 , + 127 % ) . This improvement correlated with reduced RF , such as body mass index st and ard deviation scores , body fat mass , waist/hip ratio , ambulatory systolic blood pressure , fasting insulin , triglycerides , low-density lipoprotein/high-density lipoprotein ratio , and low-degree inflammation ( C-reactive protein , fibrinogen ) . CONCLUSIONS The present study documented increased IMT , impaired endothelial function , and various elevated cardiovascular RF in young obese subjects . Regular exercise over 6 months restores endothelial function and improves carotid IMT associated with an improved cardiovascular risk profile in obese children The purpose of this study was to apply the lactate threshold concept to develop a more evidence -informed exercise program for obese children . 60 obese children ( 26 girls and 34 boys , age : 9 - 10 years , BMI : 25.4 + /- 2.2kg/m(2 ) ) were recruited and half of them were r and omly selected to be trained for eight weeks with a controlled exercise intensity at lactate threshold . The trained children achieved significant improvements on their body composition and functional capacity compared with the control group . The findings suggested that the training program with intensity at lactate threshold is effective and safe for 9 - 10 year old children with obesity |
2,429 | 21,888,531 | The only possible exception to this is “ fruit only ” intervention studies where assessment of vitamin C alone may suffice | Observational evidence consistently shows that consumption of a diet rich in fruit and vegetables may offer protection against diseases such as cardiovascular disease and cancer .
Assessment of dietary intake is complex and prone to many sources of error .
More objective biomarkers of fruit and vegetable intake are therefore of interest .
The aim of this review is to examine the usefulness of the main biomarkers of fruit and vegetable intake to act as objective indicators of compliance in dietary intervention studies . | Background —Moderate red wine consumption is inversely associated with coronary ischemia , and both red wine and purple grape juice ( PGJ ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events . Acute cardiac events are also associated with decreased platelet-derived nitric oxide ( NO ) release . In this study , the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined . Methods and Results —Incubation of platelets with dilute PGJ led to inhibition of aggregation , enhanced release of platelet-derived NO , and decreased superoxide production . To confirm the in vivo relevance of these findings , 20 healthy subjects consumed 7 mL · kg−1 · d−1 of PGJ for 14 days . Platelet aggregation was inhibited after PGJ supplementation , platelet-derived NO production increased from 3.5±1.2 to 6.0±1.5 pmol/108 platelets , and superoxide release decreased from 29.5±5.0 to 19.2±3.1 arbitrary units ( P < 0.007 and P < 0.05 , respectively ) . & agr;-Tocopherol levels increased significantly after PGJ consumption ( from 15.6±0.7 to 17.6±0.9 & mgr;mol/L;P < 0.009 ) , and the plasma protein – independent antioxidant activity increased by 50.0 % ( P < 0.05 ) . Last , incubation of platelets with select flavonoid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation , platelet aggregation , and NO release . Conclusions —Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation , increase platelet-derived NO release , and decrease superoxide production . These findings may be a result of antioxidant-sparing and /or direct effects of select flavonoids found in PGJ . The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products , independent of alcohol consumption , in cardiovascular disease Summary . Background : Bioavailability of β-carotene is highly variable and depends on the source , the formulation and other nutritional factors . Objective : It was the aim of the study to compare β-carotene plasma response to b-carotene dosing with two commercially available drinks , containing β-carotene from carrot juice or as water dispersible β-carotene powder . Design In a r and omized , parallel group study design , 4 volunteers per group received daily β-carotene doses of 6–7 or 18–22 mg of either drink over 6 weeks . Blood sample s for determination of carotenoid and vitamin A plasma concentrations were collected before supplementation and over the dosing period . Results : Apparent steady-state β-carotene concentrations were attained after 40 days of supplementation . Consumption of the beverage containing β-carotene as a water dispersible powder result ed in a higher response of β-carotene plasma concentrations with increments of 3.84 ± 0.60 μmol/L ( p < 0.05 , dose : 7.2 mg/d ) and 5.04 ± 0.72 μmol/L ( p < 0.05 , dose : 21.6 mg/d ) , respectively , in comparison to the carrot juice-based drink with increments of 0.42 ± 0.33 μmol/L ( dose : 6 mg/d ) and 1.71 ± 0.55 μmol/L ( dose : 18 mg/d ) , respectively . β-carotene was cleared from the plasma with an apparent half-life of 6–11 days . Plasma concentrations of α-carotene , β-cryptoxanthin , lutein , zeaxanthin , and lycopene remained almost unchanged , whereas retinol plasma concentrations increased slightly . By contrast , with the exception of elevated 13-cis-retinoic acid in one group ( 21.6 mg/d , water dispersible powder ) , the concentrations of all-trans-retinoic acid , and the oxo-derivatives or retinoic acid were not significantly affected by b-carotene supplementation . Conclusions : The results confirm that the relative bioavailability of β-carotene depends largely on the source of b-carotene and demonstrate the superior bioavailability of β-carotene powder in comparison to that in carrot juice Background : There is a need for objective and universally applicable biomarkers for the intake of foods believed to affect human health . Objective : The purpose of this feeding study was to test whether plasma concentrations of carotenoids could be used to distinguish recommended consumption of mixed fruits and vegetables ( five a day ) from the current national intake of fruits and vegetables ( two a day ) . Design : A strict crossover design was chosen to correct for observed interindividual variations in carotenoid response . A total of 40 healthy subjects were included in the study . After 1 week run-in period with no fruits and vegetables in the diet , one group was given two portions ( 300 g ) of fruits and vegetables daily , while another group was given five portions ( 750 g ) for 14 days . Following a 2 week wash-out period and 1 week run-in , the regimens were switched between the groups . Fruits and vegetables were combined to match a typical Norwegian diet . Results : Enhanced intake from two to five portions of mixed fruits and vegetables increased plasma concentrations of α-carotene ( P=0.033 ) and lutein ( P=0.051 ) in a crossover analysis . Analysis of data in the parallel part of the study revealed differences between the high and low intake for plasma concentrations of α-carotene ( P=0.013 ) and β-carotene ( P=0.016 ) . A trend was also evident for plasma concentrations of lycopene ( P=0.057 ) and lutein ( P=0.076 ) in the parallel analysis . No effect of high vs low intake of fruits and vegetables was observed for plasma concentrations of β-cryptoxanthin , zeaxanthin , cholesterol and triacylglycerols . Conclusion : The study indicates that plasma concentration of α-carotene , β-carotene and lutein may be used to assess changes of fruit and vegetable intake corresponding to an increase from the present national intake in Norway to the recommended amount of five portions of fruits and vegetables daily . Sponsorship : Norwegian Research Council , National Nutrition Council , Throne Holst Foundation for Nutrition Research and Freia Chokoladefabriks Medisinske Fond In several epidemiological studies , high intakes of fruits and vegetables have been associated with a lower incidence of cancer . Theoretically , intake of antioxidants by consumption of fruits and vegetables should protect against reactive oxygen species and decrease the formation of oxidative DNA damage . We set up a parallel 24-day dietary placebo-controlled intervention study in which 43 subjects were r and omized into three groups receiving an antioxidant-free basal diet and 600 g of fruits and vegetables , or a supplement containing the corresponding amounts of vitamins and minerals , or placebo . Blood and urine sample s were collected before , once a week , and 4 weeks after the intervention period . The level of str and breaks , endonuclease III sites , formamidopyrimidine sites , and sensitivity to hydrogen peroxide was assessed in mononuclear blood cells by the comet assay . Excretion of 7-hydro-8-oxo-2'-deoxyguanine was measured in urine . The expressions of oxoguanine glycosylase 1 and excision repair cross complementing 1 DNA repair genes , determined by real-time reverse transcription-PCR of mRNAs , were investigated in leukocytes . Consumption of fruits and vegetables or vitamins and minerals had no effect on oxidative DNA damage measured in mononuclear cell DNA or urine . Hydrogen peroxide sensitivity , detected by the comet assay , did not differ between the groups . Expression of excision repair cross complementing 1 and oxoguanine glycosylase 1 in leukocytes was not related to the diet consumed . Our results show that after 24 days of complete depletion of fruits and vegetables , or daily ingestion of 600 g of fruit and vegetables , or the corresponding amount of vitamins and minerals , the level of oxidative DNA damage was unchanged . This suggests that the inherent antioxidant defense mechanisms are sufficient to protect circulating mononuclear blood cells from reactive oxygen species Background — Observational evidence has consistently linked increased fruit and vegetable consumption with reduced cardiovascular morbidity ; however , there is little direct trial evidence to support the concept that fruit and vegetable consumption improves vascular function . This study assessed the dose-dependent effects of a fruit and vegetable intervention on arterial health in subjects with hypertension . Methods and Results — After a 4-week run-in period during which fruit and vegetable intake was limited to 1 portion per day , participants were r and omized to consume either 1 , 3 , or 6 portions daily for the next 8 weeks . Endothelium-dependent and -independent arterial vasodilator responses were assessed by venous occlusion plethysmography in the brachial circulation before and after intervention . Compliance was monitored with serial contemporaneous 4-day food records and by measuring concentrations of circulating dietary biomarkers . A total of 117 volunteers completed the 12-week study . Participants in the 1- , 3- , and 6-portions/d groups reported consuming on average 1.1 , 3.2 , and 5.6 portions of fruit and vegetables , respectively , and serum concentrations of lutein and & bgr;-cryptoxanthin increased across the groups in a dose-dependent manner . For each 1-portion increase in reported fruit and vegetable consumption , there was a 6.2 % improvement in forearm blood flow responses to intra-arterial administration of the endothelium-dependent vasodilator acetylcholine ( P=0.03 ) . There was no association between increased fruit and vegetable consumption and vasodilator responses to sodium nitroprusside , an endothelium-independent vasodilator . Conclusions — The present study illustrates that among hypertensive volunteers , increased fruit and vegetable consumption produces significant improvements in an established marker of endothelial function and cardiovascular prognosis BACKGROUND Lutein is a hydroxy-carotenoid constituting the macular pigment of the human retina . Increasing lutein intake from foods could increase the density of this pigment and decrease the risk of developing macular degeneration . Yellow carrots are a novel food source that could increase lutein consumption . OBJECTIVE We evaluated and compared lutein uptake and clearance in humans from genetically selected lutein-containing yellow carrots fed chronically and from a lutein supplement . DESIGN Four women and 5 men aged 23 - 28 y participated in this r and omized , blinded , 3 x 3 crossover intervention . Treatments consisted of yellow carrots ( YC treatment , 1.7 mg lutein/d ) , white carrots as a negative control ( WC treatment , 0 mg lutein/d ) , and a lutein supplement in oil as a positive control ( LS treatment , 1.7 mg lutein/d ) . Each treatment lasted 7 d and was followed by a 7-d washout period . RESULTS Mean ( + /- SD ) peak changes in serum lutein concentration from baseline were 0.31 + /- 0.08 , 0.19 + /- 0.08 , and -0.04 + /- 0.04 micromol/L for the LS , YC , and WC treatments , respectively . The areas under the curve for 0 - 14 d ( AUC(0 - 14d ) ) differed significantly ( P < 0.0001 ) between treatments . Lutein from the YC treatment was 65 % as bioavailable as that from the LS treatment . The AUC(0 - 14d ) for beta-carotene ( -0.01 + /- 0.28 micromol.d/L ) also showed that the YC treatment maintained peak serum beta-carotene concentrations at 0.35 + /- 0.30 micromol/L , whereas the LS treatment did not ( AUC(0 - 14d ) = -0.71 + /- 0.59 micromol.d/L ) . CONCLUSION Lutein from this novel food source significantly increases serum lutein concentrations and does not result in the decrease in beta-carotene concentrations that accompanies administration of lutein supplements To determine the effects of vitamin C on cardiovascular risk factors , we studied dietary vitamin C enrichment in 36 healthy male students consuming a diet high in saturated fatty acids . After a 1-mo run-in period during which the subjects consumed approximately 50 mg ascorbic acid/d ( low-C diet ) , half of the subjects were r and omly assigned to receive 500 mg ascorbic acid/d for an additional 2 mo ( high-C diet ) . Plasma ascorbic acid increased from 13.5 micromol/L with the low-C diet to 51.7 micromol/L with the high-C diet . Plasma cholesterol increased slightly with the high-C diet , but not above baseline concentrations . This increase was offset by an increase in the lag period of in vitro LDL oxidation , which correlated with plasma ascorbic acid concentrations ( r = 0.735 , P = 0.0012 ) . Lipoprotein vitamin E concentrations were unchanged with the two diets . There were no effects on concentrations of fibrinogen or factor VII . The fact that ascorbic acid reduced the in vitro susceptibility of lipoproteins to oxidation provides presumptive evidence for an interaction between aqueous and lipophilic antioxidants ( vitamins C and E ) in maintaining the integrity of LDL particles The relative bioavailability of ascorbic acid from several sources was compared in 68 male non-smokers . Subjects underwent two 8-wk ascorbic acid depletion-repletion cycles . In repletion , subjects were r and omized to receive 108 mg/d ascorbic acid as tablets with or without iron , as orange segments or juice , or as raw or cooked broccoli with a crossover within each major treatment group ( e.g. , cooked to raw broccoli ) for the second repletion . Relative ascorbic acid bioavailability was estimated based on the slope obtained from linear regression of plasma ascorbic acid on time during each repletion . In the first repletion , slopes for all groups were similar except for the group consuming raw broccoli ( 20 % lower response , P < 0.01 ) . Second repletion responses were attenuated , but were similar to the first repletion . Ascorbic acid ingested as cooked broccoli , orange juice or fruit , or in synthetic form seems to be equally bioavailable . The lower relative bioavailability of ascorbic acid from raw broccoli is unlikely to be of practical importance in mixed diets BACKGROUND The amount of dietary fat required for optimal bioavailability of carotenoids in plant matrices is not clearly defined . OBJECTIVE The objective was to quantify the appearance of carotenoids in plasma chylomicrons after subjects ingested fresh vegetable salads with fat-free , reduced-fat , or full-fat salad dressings . DESIGN The subjects ( n = 7 ) each consumed 3 salads consisting of equivalent amounts of spinach , romaine lettuce , cherry tomatoes , and carrots with salad dressings containing 0 , 6 , or 28 g canola oil . The salads were consumed in r and om order separated by washout periods of > or = 2 wk . Blood sample s were collected hourly from 0 to 12 h. Chylomicrons were isolated by ultracentrifugation , and carotenoid absorption was analyzed by HPLC with coulometric array detection . RESULTS After ingestion of the salads with fat-free salad dressing , the appearance of alpha-carotene , beta-carotene , and lycopene in chylomicrons was negligible . After ingestion of the salads with reduced-fat salad dressing , the appearance of the carotenoids in plasma chylomicrons increased relative to that after ingestion of the salads with fat-free salad dressing ( P < 0.04 ) . Similarly , the appearance of the carotenoids in plasma chylomicrons was higher after the ingestion of salads with full-fat than with reduced-fat salad dressing ( P < 0.02 ) . CONCLUSIONS High-sensitivity HPLC with coulometric array detection enabled us to quantify the intestinal absorption of carotenoids ingested from a single vegetable salad . Essentially no absorption of carotenoids was observed when salads with fat-free salad dressing were consumed . A substantially greater absorption of carotenoids was observed when salads were consumed with full-fat than with reduced-fat salad dressing BACKGROUND Berries are a particularly rich source of polyphenols . They also contain other bioactive substances , such as vitamin C. Previous studies indicated that the consumption of polyphenol-rich foods ( eg , cocoa , tea , and red wine ) may induce beneficial changes in pathways related to cardiovascular health . Whether the consumption of berries has similar effects is unknown . OBJECTIVE We aim ed to investigate the effects of berry consumption on hemostatic function , serum lipids , and blood pressure ( BP ) . DESIGN Middle-aged unmedicated subjects ( n = 72 ) with cardiovascular risk factors consumed moderate amounts of berry or control products for 8 wk in a single-blind , r and omized , placebo-controlled intervention trial . RESULTS Berry consumption inhibited platelet function as measured with a platelet function analyzer ( using collagen and ADP as platelet activator ) [ changes : 11 % and -1.4 % in the berry and control groups , respectively ; P = 0.018 , analysis of covariance ( ANCOVA ) ] . Plasma biomarkers of platelet activation , coagulation , and fibrinolysis did not change during the intervention . Serum HDL-cholesterol concentrations increased significantly more ( P = 0.006 , ANCOVA ) in the berry than in the control group ( 5.2 % and 0.6 % , respectively ) , but total cholesterol and triacylglycerol remained unchanged . Systolic BP decreased significantly ( P = 0.050 , ANCOVA ) ; the decrease mostly occurred in subjects with high baseline BP ( 7.3 mm Hg in highest tertile ; P = 0.024 , ANCOVA ) . Polyphenol and vitamin C concentrations in plasma increased , whereas other nutritional biomarkers ( ie , folate , tocopherols , sodium , and potassium ) were unaffected . CONCLUSION The consumption of moderate amounts of berries result ed in favorable changes in platelet function , HDL cholesterol , and BP . The results indicate that regular consumption of berries may play a role in the prevention of cardiovascular disease Population s at risk of vitamin A deficiency usually rely on dietary provitamin A carotenoids to meet vitamin A needs , yet bioavailability of these compounds is influenced by several factors as follows : location in the plant source , the presence of other influencing dietary components , and type and extent of processing . The purpose of this study was to examine the plasma beta-carotene response to raw vs. processed carrots and spinach . Subjects were eight healthy females aged 23 - 36 y who consumed approximately 9.3 mg beta-carotene daily from either raw or thermally processed and pureed vegetables in two 4-wk treatment periods in a crossover study . Plasma concentrations of total , all-trans- , and cis-beta-carotene and alpha-carotene were measured at base line and the end of each treatment period by using HPLC assays . Total and all-trans ( but not cis ) plasma beta-carotene concentrations were significantly greater than base-line concentrations in the processed feeding period ( P < 0 . 04 ) and tended to be greater in the raw feeding period ( P = 0.08 ) . Daily consumption of processed carrots and spinach over a 4-wk period produced an increase in plasma beta-carotene concentration that averaged three times that associated with consumption of the same amount of beta-carotene from these vegetables in the raw form ( P = 0.09 ) . Increased cis isomers provided in the processed vegetables did not result in significantly greater plasma cis-beta-carotene isomer concentrations . These results suggest that isomerization of beta-carotene by heat treatment does not negate the enhanced beta-carotene uptake associated with consuming commercially processed vegetables compared with raw vegetables BACKGROUND Cruciferous vegetable ( CV ) consumption is associated with a reduced risk of several cancers in epidemiologic studies . OBJECTIVE The aim of this study was to determine the effects of watercress ( a CV ) supplementation on biomarkers related to cancer risk in healthy adults . DESIGN A single-blind , r and omized , crossover study was conducted in 30 men and 30 women ( 30 smokers and 30 nonsmokers ) with a mean age of 33 y ( range : 19 - 55 y ) . The subjects were fed 85 g raw watercress daily for 8 wk in addition to their habitual diet . The effect of supplementation was measured on a range of endpoints , including DNA damage in lymphocytes ( with the comet assay ) , activity of detoxifying enzymes ( glutathione peroxidase and superoxide dismutase ) in erythrocytes , plasma antioxidants ( retinol , ascorbic acid , alpha-tocopherol , lutein , and beta-carotene ) , plasma total antioxidant status with the use of the ferric reducing ability of plasma assay , and plasma lipid profile . RESULTS Watercress supplementation ( active compared with control phase ) was associated with reductions in basal DNA damage ( by 17 % ; P = 0.03 ) , in basal plus oxidative purine DNA damage ( by 23.9 % ; P = 0.002 ) , and in basal DNA damage in response to ex vivo hydrogen peroxide challenge ( by 9.4 % ; P = 0.07 ) . Beneficial changes seen after watercress intervention were greater and more significant in smokers than in nonsmokers . Plasma lutein and beta-carotene increased significantly by 100 % and 33 % ( P < 0.001 ) , respectively , after watercress supplementation . CONCLUSION The results support the theory that consumption of watercress can be linked to a reduced risk of cancer via decreased damage to DNA and possible modulation of antioxidant status by increasing carotenoid concentrations BACKGROUND The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial design ed to determine the effects of a high-fiber ( 4.30 g/MJ ) , high-fruit- and -vegetable ( 0.84 servings/MJ ) , low-fat ( 20 % of energy from fat ) diet on the recurrence of adenomatous polyps in the large bowel . OBJECTIVE Our goal was to determine whether the PPT intervention plan could effect change in 3 dietary goals and to examine the intervention 's effect on the intake of other food groups and nutrients . DESIGN Participants with large-bowel adenomatous polyps diagnosed in the past 6 mo were r and omly assigned to either the intervention ( n = 1037 ) or the control ( n = 1042 ) group and remained in the trial for 4 y. Three dietary assessment instruments were used to measure dietary change : food-frequency question naires ( in 100 % of the sample ) , 4-d food records ( in a 20 % r and om cohort ) , and 24-h dietary recalls ( in a 10 % r and om sample ) . RESULTS Intervention participants made and sustained significant changes in all PPT goals as measured by the dietary assessment instruments ; the control participants ' intakes remained essentially the same throughout the trial . The absolute differences between the intervention and control groups over the 4-y period were 9.7 % of energy from fat ( 95 % CI : 9.0 % , 10.3 % ) , 1.65 g dietary fiber/MJ ( 95 % CI : 1.53 , 1.74 ) , and 0.27 servings of fruit and vegetables/MJ ( 95 % CI : 0.25 , 0.29 ) . Intervention participants also reported significant changes in the intake of other nutrients and food groups . The intervention group also had significantly higher serum carotenoid concentrations and lower body weights than did the control group . CONCLUSION Motivated , free-living individuals , given appropriate support , can make and sustain major dietary changes over a 4-y period Observational epidemiologic studies have shown that a high consumption of fruits and vegetables is associated with a decreased risk of chronic diseases . Little is known about the bioavailability of constituents from vegetables and fruits and the effect of these constituents on markers for disease risk . Currently , the recommendation is to increase intake of a mix of fruits and vegetables ( " five a day " ) . We investigated the effect of this recommendation on plasma carotenoids , vitamins and homocysteine concentrations in a 4-wk dietary controlled , parallel intervention study . Male and female volunteers ( n = 47 ) were allocated r and omly to either a daily 500-g fruit and vegetable ( " high " ) diet or a 100-g fruit and vegetable ( " low " ) diet . Analyzed total carotenoid , vitamin C and folate concentrations of the daily high diet were 13.3 mg , 173 mg and 228.1 microg , respectively . The daily low diet contained 2.9 mg carotenoids , 65 mg vitamin C and 131.1 microg folate . Differences in final plasma levels between the high and low group were as follows : lutein , 46 % [ 95 % confidence interval ( CI ) 28 - 64 ] ; beta-cryptoxanthin , 128 % ( 98 - 159 ) ; lycopene , 22 % ( 8 - 37 ) ; alpha-carotene , 121 % ( 94 - 149 ) ; beta-carotene , 45 % ( 28 - 62 ) ; and vitamin C , 64 % ( 51 - 77 ) ( P < 0.05 ) . The high group had an 11 % ( -18 to -4 ) lower final plasma homocysteine and a 15 % ( 0.8 - 30 ) higher plasma folate concentration compared with the low group ( P < 0.05 ) . This is the first trial to show that a mix of fruits and vegetables , with a moderate folate content , decreases plasma homocysteine concentrations in humans BACKGROUND Recent evidence suggests that the vitamin A equivalency of beta-carotene from plant sources is lower than previously estimated . OBJECTIVE We assessed the effect of 60 d of daily supplementation with 750 microg retinol equivalents ( RE ) of either cooked , puréed sweet potatoes ; cooked , puréed Indian spinach ( Basella alba ) ; or synthetic sources of vitamin A or beta-carotene on total-body vitamin A stores in Bangladeshi men . DESIGN Total-body vitamin A stores in Bangladeshi men ( n = 14/group ) were estimated by using the deuterated-retinol-dilution technique before and after 60 d of supplementation with either 0 microg RE/d ( white vegetables ) or 750 microg RE/d as sweet potatoes , Indian spinach , retinyl palmitate , or beta-carotene ( RE = 1 microg retinol or 6 microg beta-carotene ) in addition to a low-vitamin A diet providing approximately 200 microg RE/d . Mean changes in vitamin A stores in the vegetable and beta-carotene groups were compared with the mean change in the retinyl palmitate group to estimate the relative equivalency of these vitamin A sources . RESULTS Overall geometric mean ( + /-SD ) initial vitamin A stores were 0.108 + /- 0.067 mmol . Relative to the low-vitamin A control group , the estimated mean changes in vitamin A stores were 0.029 mmol for sweet potato ( P = 0.21 ) , 0.041 mmol for Indian spinach ( P = 0.033 ) , 0.065 mmol for retinyl palmitate ( P < 0.001 ) , and 0.062 mmol for beta-carotene ( P < 0.002 ) . Vitamin A equivalency factors ( beta-carotene : retinol , wt : wt ) were estimated as approximately 13:1 for sweet potato , approximately 10:1 for Indian spinach , and approximately 6:1 for synthetic beta-carotene . CONCLUSION Daily consumption of cooked , puréed green leafy vegetables or sweet potatoes has a positive effect on vitamin A stores in population s at risk of vitamin A deficiency This study was aim ed at determining whether an increase of 5 portions of fruits and vegetables in the form of soups and beverages has a beneficial effect on markers of oxidative stress and cardiovascular disease risk factors . The study was a single blind , r and omized , controlled , crossover dietary intervention study . After a 2-wk run-in period with fish oil supplementation , which continued throughout the dietary intervention to increase oxidative stress , the volunteers consumed carotenoid-rich or control vegetable soups and beverages for 4 wk . After a 10-wk wash-out period , the volunteers repeated the above protocol , consuming the other intervention foods . Both test and control interventions significantly increased the % energy from carbohydrates and decreased dietary protein and vitamin B-12 intakes . Compared with the control treatment , consumption of the carotenoid-rich soups and beverages increased dietary carotenoids , vitamin C , alpha-tocopherol , potassium , and folate , and the plasma concentrations of alpha-carotene ( 362 % ) , beta-carotene ( 250 % ) and lycopene ( 31 % ) ( P < 0.01 ) and decreased the plasma homocysteine concentration by 8.8 % ( P < 0.01 ) . The reduction in plasma homocysteine correlated weakly with the increase in dietary folate during the test intervention ( r = -0.35 , P = 0.04 ) . The plasma antioxidant status and markers of oxidative stress were not affected by treatment . Consumption of fruit and vegetable soups and beverages makes a useful contribution to meeting dietary recommendations for fruit and vegetable consumption To gain better insight into the potential health effects of fruits and vegetables , reliable biomarkers of intake are needed . The main purpose of this study was to investigate the ability of flavonoid excretion in both 24-h and morning urine sample s to reflect a low intake and moderate changes in fruit and vegetable consumption . Furthermore , the urinary excretions of 4-pyridoxic acid ( 4-PA ) and potassium were investigated as other potential biomarkers of fruit and vegetable intake . The study was design ed as a 5-d r and omized , controlled crossover study . On d 1 - 3 , the men ( n = 12 ) consumed a self-restricted flavonoid-free diet . On d 4 , they were provided a strictly controlled diet containing no fruits or vegetables ( basic diet ) . On d 5 , they consumed the basic diet supplemented with 300 or 600 g of fruits and vegetables . The total excretion of flavonoids in 24-h urine sample s increased linearly with increasing fruit and vegetable intakes ( r(s ) = 0.86 , P < 1 x 10(-6 ) ) . The total excretion of flavonoids in morning urine also increased , but the association was weaker ( r(s ) = 0.59 , P < 0.0001 ) . Urinary 4-PA in 24-h and morning urine sample s increased significantly only with the 600-g increase in fruit and vegetable intake , whereas the excretion of potassium in urine did not reflect the changes in fruit and vegetable intake . We conclude that the total excretion of flavonoids in 24-h urine may be used as a new biomarker for fruit and vegetable intake BACKGROUND Cactus pear ( Opuntia ficus-indica ) fruit contains vitamin C and characteristic betalain pigments , the radical-scavenging properties and antioxidant activities of which have been shown in vitro . OBJECTIVE We investigated the effects of short-term supplementation with cactus pear fruit compared with vitamin C alone on total-body oxidative status in healthy humans . DESIGN In a r and omized , crossover , double-treatment study , 18 healthy volunteers received either 250 g fresh fruit pulp or 75 mg vitamin C twice daily for 2 wk , with a 6-wk washout period between the treatments . Before ( baseline ) and after each treatment , 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) and malondialdehyde in plasma , the ratio of reduced to oxidized glutathione ( GSH : GSSG ) in erythrocytes , and lipid hydroperoxides in LDL were measured as biomarkers of oxidative stress ; plasma Trolox-equivalent antioxidant activity ( TEAC ) and vitamins A , E , and C were evaluated as indexes of antioxidant status . RESULTS Both treatments caused comparable increases compared with baseline in plasma concentrations of vitamin E and vitamin C ( P < 0.05 ) ; vitamin A and TEAC did not change significantly . After supplementation with cactus pear fruit , 8-epi-PGF(2)alpha and malondialdehyde decreased by approximately 30 % and 75 % , respectively ; GSH : GSSG shifted toward a higher value ( P < 0.05 ) ; and LDL hydroperoxides were reduced by almost one-half . Supplementation with vitamin C did not significantly affect any marker of oxidative stress . CONCLUSIONS Consumption of cactus pear fruit positively affects the body 's redox balance , decreases oxidative damage to lipids , and improves antioxidant status in healthy humans . Supplementation with vitamin C at a comparable dosage enhances overall antioxidant defense but does not significantly affect body oxidative stress . Components of cactus pear fruit other than antioxidant vitamins may play a role in the observed effects We investigated predictors of change in plasma carotenoids from baseline to 3 y and examined plasma carotenoid concentrations at 1 and 3 y in response to a high vegetable diet . Participants were 56 women diagnosed with breast cancer and enrolled in a r and omized feasibility study for a trial examining the effect of a diet high in vegetables and fruits on the risk of breast cancer recurrence . Independent t test analysis revealed that the intervention group had significantly higher vegetable and fruit servings and fiber at 12 mo and significantly higher vegetable servings at 36 mo compared with the control group ( P < 0.05 ) . Energy intake from fat was significantly lower in the intervention group at 12 and 36 mo . The intervention group had significantly higher consumption of beta-carotene , alpha-carotene , lutein and beta-cryptoxanthin at 12 mo ( P < 0.05 ) . beta-Carotene , alpha-carotene and lutein intakes also were significantly higher at 36 mo ( P < 0.05 ) . At 36 mo , the intervention group had significantly higher plasma concentrations of alpha-carotene and beta-carotene compared with the control group . Repeated- measures ANOVA revealed that the intervention group had significantly increased ( P < 0.05 with Bonferroni correction ) plasma beta-carotene , alpha-carotene , lutein and lycopene concentrations at 12 and 36 mo compared with baseline . Baseline carotenoid concentrations were significantly inversely predictive ( P < 0.05 ) of plasma carotenoid change . In addition , change in body mass index ( BMI ) and plasma cholesterol concentrations were predictive of plasma carotenoid change from baseline to 3 y. Results of this study demonstrate that change in plasma carotenoid concentrations is associated with change in BMI , change in plasma cholesterol and baseline carotenoid concentrations . Plasma carotenoid response can be an indicator of long-term high vegetable intake for women at risk of breast cancer recurrence The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids , proteins and DNA and on ( functional ) markers of oxidative stress were evaluated . A r and omized , free living , open placebo-controlled cross-over trial of 3 wk , with a 2-wk washout period between treatments , was performed in a group of 22 male smokers with a relatively low vegetable and fruit intake using a vegetable burger and fruit drink . The vegetable burger and fruit drink increased serum levels of vitamin C , alpha-carotene , beta-carotene , beta-cryptoxanthin and zeaxanthin and plasma total antioxidant capacity . However , no effects were demonstrated on any marker of oxidative damage to lipids ( malondialdehyde F(2)-isoprostane ) proteins ( carbonyls ) and DNA ( Comet assay ) and ( functional ) markers of oxidative stress ( reduced/oxidized glutathione ratio , glutathione-S-transferase alpha , glutathione-S-transferase pi and nuclear transcription factor-kappaB ) . Apparently , these increased levels of antioxidants in serum were not sufficiently high to show beneficial changes with the selected biomarkers . Alternatively , oxidative stress in male smokers with a relatively low fruit and vegetable intake might have been still too low to demonstrate a beneficial effect of antioxidants To evaluate the bioavailability of beta-carotene from plant foods , the serum beta-carotene response to a single ingestion of various beta-carotene sources was determined in 10 healthy men . Tested beta-carotene sources included stir-fried shredded carrot , stir-fried water convolvulus leaves , deep-fried sweet potato ball , purified beta-carotene in a capsule ( beadlets ) and beadlets with beta-carotene free oriental radish ( beadlets + radish ) . The maximal change in serum beta-carotene concentration occurred at 24 or 32 h post ingestion . This response to beadlets was significantly higher than that to the other four tested beta-carotene sources ( P < 0.05 ) . The maximal serum response to beadlets + radish was also significantly higher than that to the three food beta-carotene sources ( P < 0.05 ) . The maximal serum response to sweet potato was significantly higher than that to water convolvulus leaves ( P < 0 . 05 ) . The bioavailability relative to beta-carotene beadlets was calculated by dividing the maximal change in serum concentration to each test meal of each subject by his own serum maximal change in response to beadlets . Accordingly , the bioavailability was 65 % for beadlets + radish , 33 % for carrots , 26 % for water convolvulus leaves and 37 % for sweet potatoes . Concurrent ingestion of oriental radish reduced the bioavailability of beadlets to two-thirds of its original value , which partially accounted for the difference between the bioavailability of beadlets and natural foods . The relative bioavailability of beta-carotene from stir-fried and deep-fried vegetables was about one-third to one-fourth that of the purified beta-carotene beadlets . These bioavailabilities are higher than previously reported values Flavonols are antioxidants that may reduce the risk of heart disease . Two major flavonols in the diet are quercetin and kaempferol , and their main sources in The Netherl and s are tea and onions . We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans could be used as biomarkers of intake . We provided 15 subjects with strong black tea ( 1600 mL/d ) or fried onions ( 129 g/d ) for 3 d each in r and om order separated by a 4-d washout period . The tea provided 49 mg quercetin and 27 mg kaempferol daily and the onions provided 13 mg quercetin and no kaempferol . Flavonols from both foods were clearly absorbed . However , the excretion of unmodified quercetin was 0.5 % of intake after tea and 1.1 % after onions . Thus , the absorption of quercetin from tea was half of that from onions . The onion treatment was repeated 7 - 14 d later to estimate within-subject CVs as a measure of reproducibility when the same treatment is given twice . CVs for quercetin were 30 % in plasma and 42 % in urine . The magnitude of these variations relative to actual variations of approximately 60 % between free-living subjects indicates that concentrations of quercetin in plasma and urine are applicable as biomarkers of its intake . We conclude that flavonols in plasma and urine reflect short-term flavonol intake and that they could be used as biomarkers to distinguish between high and low flavonol consumption in epidemiologic studies BACKGROUND Fruit and vegetables contain both nutritive and nonnutritive factors that might contribute to redox ( antioxidant and prooxidant ) actions . OBJECTIVE We investigated the relative influence of nutritive and nonnutritive factors in fruit and vegetables on oxidative damage and enzymatic defense . DESIGN A 25-d intervention study with complete control of dietary intake was performed in 43 healthy male and female nonsmokers who were r and omly assigned to 1 of 3 groups . In addition to a basic diet devoid of fruit and vegetables , the fruit and vegetables ( Fruveg ) group received 600 g fruit and vegetables/d ; the placebo group received a placebo pill , and the supplement group received a vitamin pill design ed to contain vitamins and minerals corresponding to those in 600 g fruit and vegetables . Biomarkers of oxidative damage to protein and lipids and of antioxidant nutrients and defense enzymes were determined before and during intervention . RESULTS Plasma lipid oxidation lag times increased during intervention in the Fruveg and supplement groups , and the increase was significantly higher in the former . Plasma protein carbonyl formation at lysine residues also increased in both of these groups . Glutathione peroxidase activity increased in the Fruveg group only . Other markers of oxidative damage , oxidative capacity , or antioxidant defense were largely unaffected by the intervention . CONCLUSIONS Fruit and vegetables increase erythrocyte glutathione peroxidase activity and resistance of plasma lipoproteins to oxidation more efficiently than do the vitamins and minerals that fruit and vegetables are known to contain . Plasma protein carbonyl formation at lysine residues increases because of the vitamins and minerals in fruit and vegetables Oxidative stress is thought to be a factor in the progression of chronic diseases , and even the aging process itself . We examined the effect of two moderate vitamin , mineral and phytochemical supplements and a dietary intervention on markers of oxidative stress and antioxidant status in older humans . Subjects ( n = 60 , 65 - 85 y old ) were enrolled in a 5-wk , double-blind , placebo-controlled study . The subjects were r and omly assigned to a group with one of four interventions : antioxidant supplement capsule , antioxidant supplement tablet , high carotenoid diet or placebo . Postintervention serum levels of some of the supplemented carotenoids and alpha-tocopherol were higher in all treated groups compared with the placebo group and with preintervention levels within groups . Markers of oxidative stress or antioxidant capacity were not significantly different from preintervention levels , although the diet and supplement capsule groups had lower levels of some of those markers than the placebo group postintervention . The results suggest that both moderate antioxidant supplementation and a diet high in carotenoids elevate serum carotenoids and antioxidant levels in an older adult population , although with different specific effects Watermelon is a rich natural source of lycopene , a carotenoid of great interest because of its antioxidant capacity and potential health benefits . Assessment of bioavailability of lycopene from foods has been limited to tomato products , in which heat processing promotes lycopene bioavailability . We examined the bioavailability of lycopene from fresh-frozen watermelon juice in a 19-wk crossover study . Healthy , nonsmoking adults ( 36 - 69 y ) completed three 3-wk treatment periods , each with a controlled , weight-maintenance diet . Treatment periods were preceded by " washout " periods of 2 - 4 wk during which lycopene-rich foods were restricted . All 23 subjects consumed the W-20 ( 20.1 mg/d lycopene , 2.5 mg/d beta-carotene from watermelon juice ) and C-0 treatments ( controlled diet , no juice ) . As a third treatment , subjects consumed either the W-40 ( 40.2 mg/d lycopene , 5.0 mg/d beta-carotene from watermelon juice , n = 12 ) or T-20 treatment ( 18.4 mg/d lycopene , 0.6 mg/d beta-carotene from tomato juice , n = 10 ) . After 3 wk of treatment , plasma lycopene concentrations for the W-20 , W-40 , T-20 and C-0 treatments were ( least squares means + /- SEM ) 1078 + /- 106 , 1183 + /- 139 , 960 + /- 117 and 272 + /- 27 nmol/L , respectively . Plasma concentrations of beta-carotene were significantly greater after W-20 ( 574 + /- 49 nmol/L ) and W-40 ( 694 + /- 73 nmol/L ) treatments than after the C-0 treatment ( 313 + /- 27 nmol/L ) . Plasma lycopene concentrations did not differ at wk 3 after W-20 , W-40 and T-20 treatments , indicating that lycopene was bioavailable from both fresh-frozen watermelon juice and canned tomato juice , and that a dose-response effect was not apparent in plasma when the watermelon dose was doubled BACKGROUND Whether different intakes of vegetables and fruit modulate immunologic markers is currently not known . OBJECTIVE We investigated the effects of low , medium , and high intakes of vegetables and fruit on markers of immune functions , including nonspecific markers of inflammation . DESIGN In a r and omized controlled trial , nonsmoking men consumed a diet that included < or = 2 servings/d of vegetables and fruit for 4 wk . The subjects were then r and omly assigned to 1 of 3 groups to consume 2 servings/d , 5 servings/d , or 8 servings/d of carotenoid-rich vegetables and fruit for another 4-wk period . Plasma concentrations of vitamins C and E and carotenoids were measured . The assessment of immunologic and inflammatory markers included the number and activity of natural killer cells , secretion of cytokines , lymphocyte proliferation , and plasma C-reactive protein concentrations . RESULTS The high intake ( 8 servings/d ) of vegetables and fruit significantly increased total carotenoid concentrations in plasma compared with the low intake ( 2 servings/d ; week 4 compared with week 8) , whereas concentrations of vitamins C and E did not differ between week 4 and week 8 . Immunologic markers were not significantly modulated . In contrast , C-reactive protein was significantly reduced at week 8 in the subjects who consumed 8 servings/d of vegetables and fruit compared with those who consumed 2 servings/d . CONCLUSIONS In healthy , well-nourished , nonsmoking men , 4 wk of low or high intakes of carotenoid-rich vegetables and fruit did not affect markers of immune function . However , a high intake of vegetables and fruit may reduce inflammatory processes , as indicated by the reduction of plasma C-reactive protein Plasma carotenoid responses were determined in 36 healthy men and women before and after being fed controlled diets with a moderate amount of fat ( 26 % of total energy ) and a high carotenoid content ( approximately 16 mg/d ) for two 15-d periods . In addition , broccoli ( 205 g/d ) was provided either during the first or the second 15-d residency period in a crossover design . Plasma was digested with lipase and cholesterol esterase , and carotenoids were extracted and measured by using HPLC . Three oxygenated carotenoids ( lutein , zeaxanthin , and cryptoxanthin ) , three hydro-carbon carotenoids ( alpha-carotene , all-trans-beta-carotene , and 13-cis-beta-carotene ) , and four geometric isomers of lycopene ( 15-cis- , 13-cis- , 9-cis- , and all-trans-lycopene ) were separated by using a C30 carotenoid column . A small unidentified peak coeluted with st and ard 9-cis-beta-carotene and was identified as zeta-carotene ( lambda(max ) = 400 nm ) . The concentrations of plasma lutein , cryptoxanthin , alpha-carotene , 13-cis-beta-carotene , all-trans-beta-carotene , and cis- and trans-lycopenes were all significantly increased ( P < 0.05 ) on days 6 - 16 by the high-fruit and -vegetable diets . The provision of additional broccoli for 5 d to the basic high-carotenoid diet result ed in a further significant increase in the serum concentration of lutein compared with the feeding of the basic high-carotenoid diet alone . Most of the measurable carotenoids of human plasma can be increased by moderate alterations in diet within a short time , although the magnitude of the plasma response may be related to the baseline carotenoid concentrations BACKGROUND More information is needed on the efficacy of carotenoids from plant foods in improving vitamin A status . OBJECTIVE We aim ed to quantify the efficacy of provitamin A-rich vegetables and fruit in improving vitamin A status . DESIGN Breastfeeding women in 9 rural communes in Vietnam were r and omly allocated to 1 of 4 groups : the vegetable group ( n = 73 ) , which ingested 5.6 mg beta-carotene/d from green leafy vegetables ; the fruit group ( n = 69 ) , which ingested 4.8 mg beta-carotene/d from orange or yellow fruit ; the retinol-rich group ( n = 70 ) , which ingested 610 microg retinol/d from animal foods and 0.6 mg beta-carotene/d ; and the control group ( n = 68 ) , which ingested 0.4 mg beta-carotene/d . Meals of groups 1 , 2 , and 4 contained < 30 microg retinol/d . Lunch and dinner were provided 6 d/wk for 10 wk . RESULTS Mean ( 95 % CI ) changes in serum retinol concentrations of the vegetable , fruit , retinol-rich , and control groups were 0.09 ( 0.03 , 0.16 ) , 0.13 ( 0.07 , 0.19 ) , 0.25 ( 0.17 , 0.33 ) , and 0.00 ( -0.06 , 0.06 ) micromol/L , respectively . Mean ( 95 % CI ) changes in breast-milk retinol concentrations were 0.15 ( 0.04 , 0.27 ) , 0.15 ( 0.02 , 0.28 ) , 0.48 ( 0.32 , 0.64 ) , and -0.06 ( -0.21 , 0.09 ) micromol/L , respectively . According to these findings , the equivalent of 1 microg retinol would be 12 microg beta-carotene ( 95 % CI : 8 , 22 microg ) for fruit and 28 microg beta-carotene ( 17 , 84 microg ) for green leafy vegetables . Thus , apparent mean vitamin A activity of carotenoids in fruit and in leafy vegetables was 50 % ( 95 % CI : 27 % , 75 % ) and 21 % ( 7 % , 35 % ) , respectively , of that assumed . CONCLUSION The bioavailability of carotenoids from vegetables and fruit is less than previously assumed BACKGROUND Health benefits associated with diets rich in vegetables and fruit ( VF ) are often attributed to the antioxidant activity of their constituent phytochemicals . However , in vivo evidence that VF actually reduce markers of oxidative stress is limited . OBJECTIVE An 8-wk dietary intervention was conducted to test the hypothesis that increased VF consumption decreases oxidative stress . Urinary excretion of 8-isoprostane F2alpha ( 8-iso-PGF2alpha ) was used as an index of whole-body lipid peroxidation . DESIGN The diets evaluated had comparable amounts of all macronutrients but varied in their content of VF . After a 2-wk low-VF ( 3.0 servings/d ) run-in diet , 246 women were r and omly assigned to receive either 3.6 ( low ) or 9.2 ( high ) servings VF/d . The low-VF group was switched to the high-VF diet during the final 2 wk of the study . Blood and first-void urine specimens were obtained at baseline and at 2-wk intervals thereafter . RESULTS The run-in diet reduced 8-iso-PGF2alpha concentrations by 33 % ( P < 0.0001 ) . The excretion of 8-iso-PGF2alpha with the low-VF diet remained the same as that with the run-in diet , whereas urinary concentrations of 8-iso-PGF2alpha were further reduced ( P < 0.01 ) by the high-VF diet , either fed throughout the study or when the diet was switched from low to high VF ( P = 0.05 ) . The greatest reductions in 8-iso-PGF2alpha were observed in subjects in the highest quartile of baseline concentrations of 8-iso-PGF2alpha . CONCLUSIONS A significant reduction in the excretion of 8-iso-PGF2alpha was induced by the run-in diet and the high-VF diet . The degree of reduction was related to the subject 's baseline urinary concentration of 8-iso-PGF2alpha Because of their antioxidant properties , carotenoids may have beneficial effects in preventing cancer and cardiovascular disease . However , in humans consuming carotenoid-rich vegetables , data concerning the antioxidant effects of carotenoids are rather scarce . A human intervention trial was conducted , therefore , to determine whether a moderately increased consumption of carotenoid-rich vegetables would influence the antioxidant status in 23 healthy men . This short-term feeding study lasted 8 wk during which the men consumed a low carotenoid diet . A 2-wk low carotenoid period was followed by daily consumption of 330 mL tomato juice , then by 330 mL carrot juice and then by 10 g of spinach powder , each for 2 wk . Antioxidant status [ water-soluble antioxidants in serum , ferric reducing ability of plasma ( FRAP ) and antioxidant enzyme activities ] and lipid peroxidation ( plasma malondialdehyde and ex vivo oxidation of LDL ) were determined . In a subgroup of 10 men , lipoprotein carotenoids were measured . The consumption of carotenoid-rich vegetables significantly increased selected carotenoids in lipoproteins but had only minor effects on their relative distribution pattern . Tomato juice consumption reduced plasma thiobarbituric acid reactive substances ( TBARS ) by 12 % ( P : < 0.05 ) and lipoprotein oxidizability in terms of an increased lag time ( 18 % , P : < 0.05 ) . Carrot juice and spinach powder had no effect on lipid peroxidation . Water-soluble antioxidants , FRAP , glutathione peroxidase and reductase activities did not change during any study period . In evaluating the low carotenoid diet , we conclude that the additional consumption of carotenoid-rich vegetable products enhanced lipoprotein carotenoid concentrations , but only tomato juice reduced LDL oxidation in healthy men Fruits and vegetables have been thought to be beneficial in cardiovascular disease . The beneficial effects of fruits and vegetables may be explained by the antioxidants and other components contained therein . These nutrients may function individually or in concert to protect lipoproteins and vascular cells from oxidation , or by other mechanisms such as reducing plasma lipid levels ( LDL cholesterol , triglycerides ) , and platelet aggregation response . Kiwi fruit which contains high amounts of vitamin C , vitamin E and polyphenols may be beneficial in cardiovascular disease ; however very little is known about its cardioprotective effects . Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease . To this end , we evaluated whether consuming kiwi fruit modulated platelet activity and plasma lipids in human volunteers in a r and omized cross-over study . We report that consuming two or three kiwi fruit per day for 28 days reduced platelet aggregation response to collagen and ADP by 18 % compared with the controls ( P<0.05 ) . In addition , consumption of kiwi fruit lowered blood triglycerides levels by 15 % compared with control ( P<0.05 ) , whereas no such effects were observed in the case of cholesterol levels . All these data indicate that consuming kiwi fruit may be beneficial in cardiovascular disease Objective : To evaluate the effect of fruit and vegetables consumption on markers of risk for cardiovascular disease . Design : R and omised , diet controlled , parallel study .Subjects : Forty-eight apparently healthy ( 40–60 y ) volunteers with a low usual consumption of fruit and vegetables . Forty-seven of them completed the study . Interventions : During 4 weeks 24 volunteers consumed a st and ardised meal , consisting of 500 g/day fruit and vegetables and 200 ml/day fruit juice ( ‘ high ’ group ) and 23 volunteers consumed 100 g/day fruit and vegetables ( ‘ low ’ group ) with an energy and fat controlled diet . Results : Final total cholesterol was 0.2 ( 95 % CI−0.5–0.03 ) mmol/l lower in the high group than in the low group ( P>0.05 ) . Final fibrinogen and systolic blood pressure were 0.1 ( −0.1–0.4 ) g/l and 2.8 ( −2.6–8.1 ) mmHg higher in the high group than in the low group ( P>0.05 ) , respectively . Also , other final serum lipid concentrations , diastolic blood pressure and other haemostatic factors did not differ between both groups . Conclusions : This was a small r and omised well-controlled dietary intervention trial of short duration with a considerable contrast in fruit and vegetable consumption . No effects on serum lipids , blood pressure and haemostatic variables were observed . Sponsorship : Product Board for Horticulture , The Greenery , Ministry of Agriculture , The Netherl and s . European Journal of Clinical Nutrition ( 2001 ) 55 , The leading cause of death in patients who have had curatively treated early-stage head and neck cancer is a second primary cancer of the upper aerodigestive tract ( lung , esophagus , larynx , pharynx , and oral cavity cancers ) . Low fruit and vegetable intake has been associated with increased risk of primary head and neck cancer and the available data suggest that increasing intake following diagnosis may reduce the risk of a second primary cancer . The goal of this study was to develop and test an easily administered intervention to increase fruit and vegetable intake in these patients following diagnosis and treatment . The 6-month intervention was based on the Stage of Change model . Seventy-five early-stage head and neck cancer patients were r and omized to either the intervention group or to the “ blinded ” control group , with diet change data available on 65 patients . Fruit and vegetable intake , assessed using a food frequency question naire , and plasma carotenoid concentrations were measured at baseline and at the end of the study period . The change in self-reported intake of fruit and vegetables ( servings per day ) over the study period was significantly greater ( P = 0.009 ) in the intervention group ( n = 35 ; + 2.1 ) compared with the control group ( n = 30 ; + 0.5 ) . Total plasma carotenoids , a biomarker of fruit and vegetable intake , increased by 70 nmol/L in the intervention group as compared with a reduction of 42 nmol/L in the control group , a relative difference of 12 % ( nonsignificant ) . An intervention that can be delivered in a physician 's office result ed in a significant increase in intake of fruit and vegetables in early-stage head and neck cancer patients . ( Cancer Epidemiol Biomarkers Prev 2005;14(12):2848 - 54 A recent meta- analysis of prospect i ve cohort studies suggests that high dietary intakes of flavonols are associated with a significantly lower risk of coronary heart disease mortality.1 The major dietary sources of flavonols such as quercetin , kaempferol , and isorhamnetin are tomatoes , onions , kale , broccoli , celery , apples , and cherries , while catechins are concentrated in tea and red wine.2,3 No clinical trials have examined the effect of interventions to increase habitual fruit and vegetable intake on plasma flavonol concentrations in free living population s. As the principal dietary sources of flavonols are restricted to a few specific food types , it is uncertain whether general dietary advice to increase fruit and vegetable consumption will increase plasma flavonol concentrations . We conducted a r and omised controlled trial to investigate the effect over six months of an intervention to increase fruit and vegetable intake in a free living population and investigated what impact this intervention had on plasma concentrations of flavonols.4 The methods are outlined in more detail elsewhere.4 In brief , we undertook a r and omised six month parallel group controlled trial using a brief negotiation model to encourage increased consumption of fruit and vegetables to at least five portions per BACKGROUND Epidemiological studies suggest a cardioprotective role for carotenoid-rich foods . Smokers have a high risk of cardiovascular disease and low dietary intake and plasma concentrations of carotenoids . The aim of this study was to determine the carotenoid response of smokers and nonsmokers to increased intake of 300 - 400 g of vegetables and its effect on LDL oxidation . METHODS After a depletion period of 8 days , 34 healthy females ( 18 nonsmokers , 16 smokers ) were supplemented with beta-carotene- and lutein-rich ( green ) and lycopene-rich ( red ) vegetable foods , each for 7 days . RESULTS Baseline concentrations ( mean + /- SD ) of plasma beta-carotene ( 0.203+/-0.28 micromol/L vs. 0.412+/-0.34 micromol/L ; P < 0.005 ) and lutein ( 0.180 + /-0.10 vs. 0.242+/-0.11 micromol/L ; P<0.05 ) but not lycopene ( 0.296+/-0.10 vs. 0.319+/-0.33 micromol/L ) were significantly lower in smokers compared with nonsmokers . After supplementation , the change ( supplementation minus depletion ) in plasma beta-carotene ( 0.152+/- 0.43 vs. 0.363+/-0.29 micromol/L in smokers vs. nonsmokers ; P = 0.002 ) and LDL lutein ( 0.015+/-0.03 vs. 0.029+/-0.03 micromol/mmol cholesterol ; P = 0.01 ) was significantly lower in smokers than nonsmokers . Green-vegetable supplementation had no effect on the resistance of LDL to oxidation ( lag-phase ) in either group . After red-vegetable supplementation , plasma and LDL lycopene concentrations were increased in both groups , but only nonsmokers showed a significant increase in the lag-phase ( 44.9+/-9.5 min at baseline , 41.4+/-6.5 min after depletion , and 49.0+/-8.9 min after supplementation ; P<0.01 ) compared with depletion . CONCLUSIONS In this short-term intervention study , a dietary intake of > 40 mg/day of lycopene by a group of nonsmoking individuals significantly reduced the susceptibility of LDL to oxidation , whereas an equivalent increase in lycopene by a group of smokers showed no such effect BACKGROUND Due to the r and om and systematic measurement errors associated with current dietary assessment instruments , there is a need to develop more objective methods of measuring the intake of foods of importance to human health . OBJECTIVE The purpose of this study was to test whether urinary excretion of flavonoids could be used to identify subjects who are meeting Norwegian recommendations for fruit and vegetable intake ( 5 servings per day ) from individuals who are consuming the national average amount of fruits and vegetables ( 2 servings per day ) . DESIGN Twenty-four-hour urine sample s were collected in a strict crossover controlled feeding study . Forty healthy subjects ( 19 - 34 years ) were included in the study . After a 1-week run-in period , one group was given a controlled diet that included 2 servings ( 300 g ) of fruits and vegetables daily for 14 days , while the other group was given a diet containing 5 servings ( 750 g ) per day . Following a 2-week washout and a 1 week run-in period , the regimens were switched between the groups . RESULTS An increased intake of mixed fruits and vegetables from 2 to 5 servings per day significantly enhanced urinary excretion of eriodictyol , naringenin , hesperetin , quercetin , kaempferol , isorhamnetin , and tamarixetin . The citrus flavonoids naringenin and hesperetin showed a steep dose-response relationship to dietary intake of fruits and vegetables , whereas the association to eriodictyol , quercetin , kaempferol , isorhamnetin , and tamarixetin was more moderate . CONCLUSION The present study indicates that urinary excretion of dietary flavonoids may be used to assess changes of mixed fruit and vegetable intake corresponding to an increase from the present national intake in Norway to the recommended amount of 5 servings of fruits and vegetables daily OBJECTIVE To examine the effectiveness of two methods of increasing fruit and fruit juice intake in pregnancy : midwives ' advice and vouchers exchangeable for juice . DESIGN Pregnant women were r and omly allocated to three groups : a control group , who received usual care ; an advice group , given advice and leaflets promoting fruit and fruit juice consumption ; and a voucher group , given vouchers exchangeable for fruit juice from a milk delivery firm . Dietary question naires were administered at ~16 , 20 and 32 weeks of pregnancy . Serum beta-carotene was measured at 16 and 32 weeks . SETTING An antenatal clinic in a deprived area . SUBJECTS Pregnant women aged 17 years and over . RESULTS The study comprised 190 women . Frequency of fruit consumption declined during pregnancy in all groups , but that of fruit juice increased substantially in the voucher group . Serum beta-carotene concentration increased in the voucher group , from 106.2 to 141.8 micromol l(-1 ) in women with measurements on both occasions ( P = 0.003 ) , decreased from 120.0 to 99.8 micromol l(-1 ) in the control group ( P = 0.005 ) , and was unchanged in the advice group . CONCLUSIONS Pregnant women drink more fruit juice if they receive vouchers exchangeable for juice supplied by the milk delivery service . Midwives ' advice to eat more fruit has no great effect . Providing vouchers for fruit juice is a simple method of increasing its intake in a deprived population and may be useful for other sections of the community Food composition tables were studied from nine European countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) : Denmark , France , Germany , Greece , Great Britain , Italy , The Netherl and s , Spain and Sweden . They were compared from the point view of availability , definition , analytical methods , and mode of expression of the nutrients of interest for EPIC , and it was seen that most of the nutrients in the tables are analysed and expressed in a compatible way . For some nutrients , however , common methods and definitions ( folate , dietary fibre ) , or modes of expression ( energy , protein , carbohydrates , carotenes , vitamin A and E ) have not yet been agreed upon , so values are not comparable . For vitamin C a wide range of values are found due to the high natural variation in foods . For compiled tables , an additional problem is the use of several sources which may mean that the nutritional values are not comparable within the same table ; and these values can not be converted if the source is not stated . In addition , some tables were compiled using food composition values produced over 20 years ago with out date d analytical methods . In view of the inconsistent values for some nutrients and due to the large amount of foods reported within EPIC , it was concluded that st and ardised food composition tables have to be developed for the nine European countries involved in EPIC in order to provide comparable nutrient intake data Objective : The aim in this study was to assess the association between individual plasma carotenoid levels ( α-carotene , β-carotene , lycopene , β-cryptoxanthin , lutein , zeaxanthin ) and fruit and vegetable intakes recorded by a calibrated food question naire ( FQ ) and 24-h dietary recall records ( 24HDR ) in nine different European countries with diverse population s and widely varying intakes of plant foods . Design : A stratified r and om sub sample of 3089 men and women from nine countries participating in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , who had provided blood sample s and dietary and other lifestyle information between 1992 and 2000 , were included . Results : β-Cryptoxanthin was most strongly correlated with total fruits ( FQ r=0.52 , 24HDR r=0.39 ) , lycopene with tomato and tomato products ( FQ r=0.38 , 24HDR r=0.25 ) , and α-carotene with intake of root vegetables ( r=0.39 ) and of total carrots ( r=0.38 ) for FQ only . Based on diet measured by FQ and adjusting for possible confounding by body mass index ( BMI ) , age , gender , smoking status , alcohol intake , and energy intake , the strongest predictors of individual plasma carotenoid levels were fruits ( R partial 2=17.2 % ) for β-cryptoxanthin , total carrots ( R partial 2=13.4 % ) and root vegetables ( R partial 2=13.3 % ) for α-carotene , and tomato products ( R partial 2=13.8 % ) for lycopene . For 24HDR , the highest R partial 2 was for fruits in relation to β-cryptoxanthin ( 7.9 % ) . Conclusions : Intakes of specific fruits and vegetables as measured by food question naires are good predictors of certain individual plasma carotenoid levels in our multicentre European study . At individual subject levels , FQ measurements of fruits , root vegetables and carrots , and tomato products are , respectively , good predictors of β-cryptoxanthin , α-carotene , and lycopene in plasma Estimation of dietary intake of polyphenols is difficult , due to limited availability of food composition data and bias inherent to dietary assessment methods . The aim of the present study was to evaluate the associations between the intake of polyphenol-rich foods and the urinary excretion of several phenolic compounds and therefore explore whether these phenolic compounds could be used as a biomarker of intake . Fifty-three participants of the SU.VI.MAX study ( a r and omised primary -prevention trial evaluating the effect of daily antioxidant supplementation on chronic diseases ) collected a 24 h urine and a spot urine sample and filled a dietary record during a 2 d period . Thirteen polyphenols and metabolites , chlorogenic acid , caffeic acid , m-coumaric acid , gallic acid , 4-O-methylgallic acid , quercetin , isorhamnetin , kaempferol , hesperetin , naringenin , phloretin , enterolactone and enterodiol , were measured using HPLC-electrospray ionisation-MS-MS . In spot sample s apple consumption was positively correlated to phloretin , grapefruit consumption to naringenin , orange to hesperetin , citrus fruit consumption to both naringenin and hesperetin , with r coefficients ranging from 0.31 to 0.57 ( P < 0.05 ) . The combination of fruits and /or fruit juices was positively correlated to gallic acid and 4-O-methylgallic acid , isorhamnetin , kaempferol , hesperetin , naringenin and phloretin ( r 0.24 - 0.44 , P < 0.05 ) . Coffee consumption was positively correlated to caffeic and chlorogenic acids ( r 0.29 and 0.63 , P < 0.05 respectively ) . Black tea and wine consumption were positively correlated with gallic and 4-O-methylgallic acids ( r 0.37 - 0.54 , P < 0.001 ) . The present results suggest that several polyphenols measured in a spot urine sample can be used as biomarkers of polyphenol-rich food intake BACKGROUND High dietary intakes of fruit and vegetables are associated with reduced risks of cancer and cardiovascular disease . Short-term intensive dietary interventions in selected population s increase fruit and vegetable intake , raise plasma antioxidant concentrations , and lower blood pressure , but long-term effects of interventions in the general population are not certain . We assessed the effect of an intervention to increase fruit and vegetable consumption on plasma concentrations of antioxidant vitamins , daily fruit and vegetable intake , and blood pressure . METHODS We undertook a 6-month , r and omised , controlled trial of a brief negotiation method to encourage an increase in consumption of fruit and vegetables to at least five daily portions . We included 690 healthy participants aged 25 - 64 years recruited from a primary -care health centre . FINDINGS Plasma concentrations of alpha-carotene , beta-carotene , lutein , beta-cryptoxanthin , and ascorbic acid increased by more in the intervention group than in controls ( significance of between-group differences ranged from p=0.032 to 0.0002 ) . Groups did not differ for changes in lycopene , retinol , alpha-tocopherol , gamma-tocopherol , or total cholesterol concentrations . Self-reported fruit and vegetable intake increased by a mean 1.4 ( SD 1.7 ) portions in the intervention group and by 0.1 ( 1.3 ) portion in the control group ( between-group difference=1.4 , 95 % CI 1.2 - 1.6 ; p<0.0001 ) . Systolic blood pressure fell more in the intervention group than in controls ( difference=4.0 mm Hg , 2.0 - 6.0 ; p<0.0001 ) , as did diastolic blood pressure ( 1.5 mm Hg , 0.2 - 2.7 ; p=0.02 ) . INTERPRETATION The effects of the intervention on fruit and vegetable consumption , plasma antioxidants , and blood pressure would be expected to reduce cardiovascular disease in the general population In several studies , many nutrients in fruits and vegetables , such as dietary fiber , potassium , and antioxidants , have been associated with reduced risk for cardiovascular disease ( 1 - 5 ) . However , as review ed elsewhere ( 6 ) , most prospect i ve studies that have specifically examined intake of fruits and vegetables in relation to risk for cardiovascular disease have been small , and their results have been inconsistent . Dietary assessment s were often crude and available only at baseline , and few studies have examined the effects of specific types of vegetables or fruits . In a recent report ( 7 ) , we evaluated the association between fruit and vegetable intake and risk for ischemic stroke . We found that persons in the highest quintile of fruit and vegetable intake had a relative risk of 0.69 ( 95 % CI , 0.52 to 0.92 ) compared with the lowest quintile of intake ; moreover , a 1-serving/d increase in fruit or vegetable intake was associated with a 6 % lower risk for ischemic stroke , after controlling for st and ard cardiovascular risk factors . In the current study , we sought to evaluate the association between intake of overall and specific fruits and vegetables and incidence of coronary heart disease . Methods Study Sample The sample s for this analysis consisted of participants in the Nurses ' Health Study ( 8) and Health Professionals ' Follow-Up Study ( 1 ) . The two studies have similar design s ; in both , participants complete mailed question naires about medical history , health behaviors , and occurrence of cardiovascular and other outcomes every 2 years . The Nurses ' Health Study began in 1976 , when 121 700 female registered nurses 30 to 55 years of age were recruited ; diet was first assessed in 1980 . Health Professionals ' Follow-up Study participants were recruited in 1986 and comprise 51 529 male health professionals , including dentists , veterinarians , pharmacists , optometrists , osteopaths , and podiatrists , 40 to 75 years of age . Sample for Analysis We excluded participants with incomplete dietary assessment s or with previously diagnosed cancer , diabetes or cardiovascular disease that was reported before the first dietary assessment . We followed 84 251 eligible women during 14 years of follow-up and 42 148 eligible men during 8 years follow-up for incidence of coronary heart disease . The rate of follow-up for nonfatal events was 97 % of the total potential person-years of follow-up in both cohorts . Assessment of Coronary Heart Disease End Points Our primary end point was nonfatal myocardial infa rct ion or fatal coronary disease occurring after return of the 1980 question naire but before 1 June 1994 in women and after return of the 1986 question naire but before 1 January 1994 in men . We sought to review medical records for all such reports . Records were review ed by physicians who were blinded to the participants ' risk factor status . Myocardial infa rct ion was confirmed by using World Health Organization criteria : symptoms plus either diagnostic electrocardiographic changes or elevated levels of cardiac enzymes ( 9 ) . Infa rct ions that required hospital admission and for which confirmatory information was obtained by interview or letter , but for which no medical records were available , were design ated as probable . We included all confirmed and probable cases in our analyses because results were the same after probable cases were excluded . Deaths were identified by using state vital records and the National Death Index or were reported by next of kin and the U.S. postal system . Follow-up for deaths was more than 98 % complete [ 10 ] . Death certificates along with medical records were used to ascertain cause of death . Fatal coronary disease was categorized as definite if 1 ) it was confirmed by hospital record or autopsy or 2 ) coronary disease was listed as the cause of death on the certificate , this was the underlying and most plausible cause , and evidence of previous coronary disease was available . We did not rely on the statement of the cause of death on the death certificate alone as providing sufficient confirmation of death due to coronary heart disease . If no medical records were available , we categorized persons in whom coronary heart disease was the underlying cause on the death certificate as presumed coronary heart disease . Analyses limited to confirmed cases yielded results very similar to those obtained when all cases were included , although with less precision . Persons who experienced sudden death within 1 hour of onset of symptoms and had no plausible cause other than coronary disease were categorized as coronary heart disease cases . Fatal cases of coronary heart disease constituted 30 % of all cases of coronary heart disease among women and 33 % among men . Dietary Assessment Diet was assessed in the Nurses ' Health Study in 1980 , 1984 , 1986 , and 1990 . A 61-item semi-quantitative food-frequency question naire that included 6 fruit items , 11 vegetable items , and 3 potato items was used in 1980 . In 1984 , the question naire was exp and ed to 126 items that covered 15 fruit items and 28 vegetable items plus potatoes ; similar question naires were repeated in 1986 and 1990 . In the Health Professionals ' Follow-up Study , diet was assessed in 1986 and 1990 by using food-frequency question naires very similar to those in the 1984 Nurses ' Health Study question naire . We excluded women who left 10 or more of the 61 items blank or who had implausible scores for total food intake ( < 500 or > 3500 kcal/d ) . Men who left 70 or more of the 131 dietary questions blank or who reported daily caloric intake outside the plausible range of 800 to 4200 calories were also excluded . For each food item , a st and ard serving size was specified . Natural portion sizesfor example , one banana or a small glass of tomato juicewere used whenever possible ; otherwise a weight or volume of that item commonly consumed by the U.S. population at one meal was used . On dietary question naires , participants reported their average intake of the specified portion size ( serving ) for each food over the past year . For each food item on the question naire , nine responses were possible , ranging from never or less than once per month to six or more times per day . Detailed descriptions of the reproducibility and validity of the food frequency question naire for men and women have been published elsewhere ( 11 - 13 ) . Frequencies and portions for the individual food items were converted to average daily intake of each fruit and vegetable item for each participant . The average daily intakes of individual food items were combined to compute total fruit and vegetable intake and intakes of composite fruit and vegetable groups . Definitions of the composite groups ( all fruits , all vegetables , citrus fruit , citrus fruit juice , cruciferous vegetables , green leafy vegetables , vitamin Crich fruits and vegetables , legumes , and potatoes ) were modified for our previous study ( 7 ) by using a report by Steinmetz and colleagues ( 14 ) . Vitamin Crich fruits and vegetables were defined as those containing more than 30 mg of vitamin C per serving . We did not include potatoes , tofu and soybeans , dried beans , and lentils as vegetables ; in addition , condiments such as chili sauce and garlic that had very small portion sizes were not counted in total vegetables . When aggregating items to compute the composite items , we assumed that individual foods for which values were missing implied no intake ( 15 ) . Statistical Analysis We found 1063 incident cases of coronary heart disease among men and 1127 among women . Person-time for each participant was calculated from the date of return of the 1980 question naire in the Nurses ' Health Study or the 1986 question naire in the Health Professionals ' Follow-up Study to the first coronary heart disease event , death , or the cutoff date ( 1 June 1994 for women and 31 January 1994 for men ) , whichever occurred first . We excluded participants who reported cardiovascular disease or cancer or diabetes before completion of the baseline dietary question naires . Each participant contributed only one end point , and the cohort at risk for each 2-year follow-up period included only those who remained free of reported coronary heart disease at the beginning of each follow-up period . The study hypotheses were defined before data were collected . The analyses were performed separately in each cohort because of differences in sex and the question naires administered to the two cohorts . This approach was selected to achieve better control of confounding . We used pooled logistic regression with 2-year follow-up increments ( 16 ) to estimate relative risks ( incidence rate ratios ) and 95 % CIs within each cohort . Analyses were adjusted for age ( 5-year categories ) , smoking ( never , former , or current [ 1 to 14 cigarettes/d , 15 to 24 cigarettes/d , or 25 cigarettes/d ] ) , alcohol consumption ( five categories in women and seven categories in men ) , family history of myocardial infa rct ion ( before 65 years of age in women and before 60 years of age in men ) , body mass index ( quintiles ) ; use of multivitamin supplements , use of vitamin E , use of aspirin , physical activity ( two categories in women and quintiles in men ) , reported hypertension and hypercholesterolemia , total daily caloric intake ( 17 ) , and time period ( each 2-year follow-up period ) . Among women , we also controlled for postmenopausal hormone use . We up date d information on diet and risk factors for coronary heart disease over time to better represent long-term patterns ( 8 , 18 ) . In the Nurses ' Health Study , we used data from the 1980 , 1984 , 1986 , and 1990 question naires , and in the Health Professionals ' Follow-up Study , we used data from the 1986 and 1990 question naires . For each 2-year follow-up period in which events were reported , we computed intake for each composite item as a cumulative average of intake from all available food-frequency question naires up to the start of the follow-up period . For participants who experienced angina , coronary artery bypass graft surgery or BACKGROUND It is known that obesity , sodium intake , and alcohol consumption factors influence blood pressure . In this clinical trial , Dietary Approaches to Stop Hypertension , we assessed the effects of dietary patterns on blood pressure . METHODS We enrolled 459 adults with systolic blood pressures of less than 160 mm Hg and diastolic blood pressures of 80 to 95 mm Hg . For three weeks , the subjects were fed a control diet that was low in fruits , vegetables , and dairy products , with a fat content typical of the average diet in the United States . They were then r and omly assigned to receive for eight weeks the control diet , a diet rich in fruits and vegetables , or a " combination " diet rich in fruits , vegetables , and low-fat dairy products and with reduced saturated and total fat . Sodium intake and body weight were maintained at constant levels . RESULTS At base line , the mean ( + /-SD ) systolic and diastolic blood pressures were 131.3+/-10.8 mm Hg and 84.7+/-4.7 mm Hg , respectively . The combination diet reduced systolic and diastolic blood pressure by 5.5 and 3.0 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; the fruits- and -vegetables diet reduced systolic blood pressure by 2.8 mm Hg more ( P<0.001 ) and diastolic blood pressure by 1.1 mm Hg more than the control diet ( P=0.07 ) . Among the 133 subjects with hypertension ( systolic pressure , > or = 140 mm Hg ; diastolic pressure , > or = 90 mm Hg ; or both ) , the combination diet reduced systolic and diastolic blood pressure by 11.4 and 5.5 mm Hg more , respectively , than the control diet ( P<0.001 for each ) ; among the 326 subjects without hypertension , the corresponding reductions were 3.5 mm Hg ( P<0.001 ) and 2.1 mm Hg ( P=0.003 ) . CONCLUSIONS A diet rich in fruits , vegetables , and low-fat dairy foods and with reduced saturated and total fat can substantially lower blood pressure . This diet offers an additional nutritional approach to preventing and treating hypertension Background : β-Carotene has been shown to enhance immune functions in humans . Whether vegetables rich in carotenoids , such as β-carotene or lycopene , modulate immune functions in healthy humans is presently not known . The objective of this study was to investigate the effects of a low-carotenoid diet supplemented with either tomato ( providing high amounts of lycopene ) or carrot juice ( providing high amounts of α- and β-carotene ) on immune functions in healthy men . Method : In a blinded , r and omized , cross-over study , male subjects on a low-carotenoid diet consumed 330 ml/day of either tomato juice ( 37.0 mg/day lycopene ) or carrot juice ( 27.1 mg/day β-carotene and 13.1 mg/day α-carotene ) for 2 weeks with a 2-week depletion period after juice intervention . Immune status was assessed by measuring lytic activity of natural killer ( NK ) cells , secretion of cytokines ( IL-2 , IL-4 , TNFα ) , and proliferation by activated peripheral blood mononuclear cells . Results : Juice consumption result ed in relatively fast responses in plasma carotenoid concentrations ( p < 0.0002 ) which were not accompanied by concomitant changes in immune functions . For IL-2 , NK cell cytotoxicity , and lymphocyte proliferation , maximum responses were observed during depletion periods . The highest production rate was measured only for TNFα at the end of the first intervention period . Juice intervention did not modulate the secretion of IL-4 . Conclusions : Increased plasma carotenoid concentrations after vegetable juice consumption are accompanied by a time-delayed modulation of immune functions in healthy men consuming a low-carotenoid diet A human intervention study was conducted to determine the effect of the consumption of carotenoid-rich vegetables on the immune system . Subjects , ( twenty-three men ) , who were non-smokers , were not restricted in their daily diet , except that they had to abstain from fruit and vegetables high in carotenoids throughout the whole study period . The study was divided into four periods , each lasting 2 weeks : weeks 1 - 2 : low-carotenoid period ; throughout weeks 3 - 8 : daily consumption of 330 ml tomato juice ( 40 mg lycopene/d , 1.5 mg beta-carotene/d ) ( weeks 3 - 4 ) , 330 ml carrot juice ( 21.6 mg beta-carotene/d , 15.7 mg alpha-carotene/d , 0.5 mg lutein/d ) ( weeks 5 - 6 ) , 10 g dried spinach powder ( 11.3 mg lutein/d , 3.1 mg beta-carotene/d ) ( weeks 7 - 8 ) . Blood was collected weekly from subjects after a 12 h fast . T-lymphocyte functions were assessed by measuring proliferation and secretion of immunoreactive cytokines . The consumption of a low-carotenoid diet result ed in a significantly reduced proliferation of peripheral blood mononuclear cells ( P BMC ) cultured with concanavalin A. After 2 weeks of tomato juice consumption and until the end of the intervention period lymphocyte proliferation was not significantly changed compared with proliferation at the end of the depletion period . Secretion of cytokines by T-helper-1-like lymphocytes ( interleukin (IL)-2 ) and by T-helper-2-like lymphocytes ( IL-4 ) was influenced by the dietary intervention . IL-2 and IL-4 secretion values were significantly suppressed after the low-carotenoid diet ( P < 0.001 and P < 0.05 respectively compared with baseline ) . Tomato juice consumption significantly enhanced IL-2 ( P < 0.001 ) and IL-4 secretion ( P < 0.05 ) compared with the end of depletion period . After carrot juice and spinach powder consumption the cytokine secretion capacity of P BMC was not significantly different from that at the end of the depletion period . In conclusion , the results of the present study indicate that a low-carotenoid diet reduces T-lymphocyte functions and addition of tomato juice restores these functions . This modulation could not be explained by changes in the plasma carotenoid concentrations . The active constituents in tomato juice as well as the biological significance of this immunomodulation remain to be determined Objective : To directly examine the contribution of vitamin C to the antioxidant potential of fruits and vegetables , the antioxidant effect of orange juice consumption ( 8 and 16 fl . oz . ) was compared to the antioxidant effect of supplemental vitamin C ( dosage equivalent to that supplied by 8 fl . oz . of orange juice ) . Methods : Subjects ( n = 11 ; 28.6 ± 2.1 years ) received each treatment in a 3 × 3 r and omized crossover design , and each two-week treatment was preceded by a two-week washout . During the entire trial , subjects restricted fruit and vegetable consumption to ≤3 servings per day except the vitamin C-rich foods ( items containing > 20 mg/serving ) , which were restricted to ≤3 servings per week . A fasting blood sample was collected at the end of each washout and each treatment period . Results : Following washouts , plasma vitamin C and lipid peroxidation ( plasma TBARS ) were similar by treatment group and averaged 25.4 ± 3.6 μmol/L and 3.82 ± 0.10 nmol/mL respectively . Plasma vitamin C concentrations were similar following each treatment period , 37.9 ± 8.1 , 45.8 ± 9.4 , and 38.3 ± 12.4 μmol/L for the 8 and 16 fl . oz . orange juice treatments and the supplement treatment , respectively . All intervention treatments reduced plasma TBARS as compared to pretreatment values : −47 % ( p = 0.013 ) , −40 % ( p = 0.083 ) , and −46 % ( p = 0.015 ) for the 8 and 16 fl . oz . orange juice treatments and supplement treatment respectively . Conclusions : These data indicate that the regular consumption of 8 fl . oz . orange juice or supplemental vitamin C ( ∼70 mg/day ) effectively reduced a marker of lipid peroxidation in plasma Polyphenolic compounds exert a variety of physiological effects in vitro including antioxidative , immunomodulatory and antigenotoxic effects . In a r and omized crossover study in healthy men on a low-polyphenol diet , we determined the effects of 2 polyphenol-rich juices ( 330 ml/d ) supplemented for 2 weeks on bioavailability of polyphenols , markers of antioxidative and immune status , and reduction of DNA damage . Juices provided 236 mg ( A ) and 226 mg ( B ) polyphenols with cyanidin glycosides ( A ) and epigallocatechin gallate ( B ) as major polyphenolic ingredients . There was no accumulation of plasma polyphenols after two weeks of juice supplementation . In contrast , plasma malondialdehyde decreased with time during juice interventions . Moreover , juice consumption also increased lymphocyte proliferative responsiveness , with no difference between the two juices . Interleukin-2 secretion by activated lymphocytes and the lytic activity of natural killer cells were significantly increased by both juices . Juice intervention had no effect on single DNA str and breaks , but significantly reduced oxidative DNA damage in lymphocytes . A time-delay was observed between the intake of fruit juice and the reduction of oxidative DNA damage and the increase in interleukin-2 secretion . We conclude that consumption of either juice enhanced antioxidant status , reduced oxidative DNA damage and stimulated immune cell functions . However , fruit juice consumption for 2 weeks did not result in elevated plasma polyphenols in subjects after overnight fasting . Further studies should focus on the time-delay between juice intake and changes in measured physiological functions , as well as on active polyphenolic metabolites mediating the observed effects The aim of the present study was to examine the effect of consumption of a high-fruit and vegetable diet , or a spray-dried extract of selected fruits and vegetables of high antioxidant content , on indices of antioxidant status of individuals consuming a background diet with minimal antioxidant intake . Plasma antioxidant concentrations were determined in twenty-five men following a 2-week depletion period during which they consumed self-selected low-antioxidant diets ( less than three servings of fruit and vegetables with no tea , coffee , red wine or fruit juice ) . Following this period the volunteers consumed either a self-selected diet containing five to seven servings of fruit and vegetables/d , or 30 g of a spray-dried supplement design ed to provide the equivalent antioxidant activity of five to seven servings of fruit and vegetables for 2 weeks in a crossover trial . Following consumption of a high-antioxidant diet for 2 weeks , plasma concentrations of ascorbic acid , alpha- and beta-carotene and lutein+zeaxanthin were all significantly increased ( P < 0.05 ) over the depletion period . However , concentrations of lycopene , retinol and tocopherol were not affected . Consumption of the supplement also raised the concentrations of these same antioxidants in plasma . Despite the increases in the concentrations of measured antioxidant nutrients , the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid-equivalent antioxidant capacity of plasma , as estimated by inhibition of metmyoglobin activity , was not significantly affected by any of the dietary treatments Objective : To assess the effect of an increased consumption of vegetables and fruit on body weight , risk factors for cardiovascular disease ( CVD ) and antioxidant defense in obese patients with sleep-related breathing disorders ( SRBD ) . Design : R and omized , controlled trial of an intervention to increase the intake of vegetables to 400 g/day and fruit to 300 g/day . Dietary intake was calculated from a food frequency question naire . Antioxidant status was assessed with the ferric-reducing/antioxidant power ( FRAP ) assay . Plasma carotenoids were biomarkers for the intake of vegetables and fruit . Setting : A hospital clinic preventing risk factors for CVD.Subjects : Subjects were 103 men and 35 women with a body mass index of 36.7±5.8 kg/m2 of which 57 ( 86 % ) in the control and 68 ( 94 % ) in the intervention group completed the study .Intervention : Group-based behavioral program during 3 months . Results : The mean between group differences in body weight was −2.0 % ( 95 % CI −3.6 , −0.5 ) , P<0.0001 . The mean between group difference in systolic and diastolic blood pressure ( BP ) was −7.1 mm Hg ( 95 % CI : −11.6 , −2.6 ) , P=0.0022 and −3.9 mm Hg ( 95 % CI : −7.0 , −0.9 ) , P=0.0120 , respectively . The mean change in daily intake of vegetables and fruit was 12 g ( 95 % CI : −33 , 57 ) and −4 g ( 95 % CI : −79 , 71 ) versus 245 g ( 95 % CI : 194 , 296 ) and 248 g ( 95 % CI : 176 , 320 ) in the control and intervention groups , respectively . This was reflected in higher concentrations of α-carotene and β-carotene . No change in FRAP was seen . In a multiple regression analysis the change in intake of vegetables was a significant contributor ( Radj2=0.073 ( 95 % CI : 0.019 , 0.214 ) ) to the change in weight . Conclusion : Targeted dietary advice to increase the intake of vegetables and fruit among subjects with SRBD contributed to weight reduction and reduced systolic and diastolic BP , but had no effect on antioxidant defense measured with FRAP.Sponsorship : None Objectives : To determine the fasting plasma concentrations of quercetin , hesperetin and naringenin in human subjects consuming their habitual diets , and diets either high or low in fruit and vegetables . To investigate whether plasma concentrations of flavanones can serve as biomarkers of their intake . Design : This was a cross-over , strictly controlled dietary intervention consisting of a 2 week baseline period , and two 5 week dietary periods with a 3 week wash-out period in between . The low-vegetable diet contained few fruit and vegetables and no citrus fruit . The high-vegetable diet provided various fruits and vegetables daily including on average one glass of orange juice , one-half orange and one-half m and arin . Subjects : Thirty-seven healthy females . Results : The high-vegetable diet provided 132 mg of hesperetin and 29 mg of naringenin . The low-vegetable diet contained no flavanones . The mean plasma hesperetin concentration increased from 12.2 nmol/l after the low-vegetable diet to 325 nmol/l after the high-vegetable diet . The respective increase for naringenin was from < 73.5 nmol/l for all subjects to a mean value of 112.9 nmol/l . The mean plasma quercetin concentration was 52 nmol/l after the baseline period , during which habitual diets were consumed , and it did not change significantly during the intervention . Interindividual variation in the plasma levels of hesperetin and naringenin was marked and , after the baseline and wash-out periods , and the low-vegetable diet , a majority of the sample s had plasma flavanone levels below the limit of detection . After the high-vegetable diet , hesperetin and naringenin were detectable in 54 and 22 % of all sample s. Quercetin was detectable in nearly all sample s after all study periods . Conclusion : Hesperetin , naringenin and quercetin are bioavailable from the diet , but the plasma concentrations of hesperetin and naringenin are poor biomarkers of intake Background : Cohort studies suggest that higher circulating carotenoid concentrations through food sources may reduce breast cancer events . Other intervention studies have not achieved the level of change in circulating carotenoids required to properly test this hypothesis . Methods : In a r and omized trial of 2,922 breast cancer survivors , we examined blood and self-reported diet at baseline and 1 year . Intensive telephone counseling encouraged a plant-based diet in the intervention group . Diet was measured via 24-hour recalls , and a panel of plasma carotenoid concentrations was assessed at both time points . Results : The study intervention was associated with a 51 % increase in total carotenoid concentration , from 2.272 ± 1.294 to 3.440 ± 2.320 μmol/L , achieved mainly by marked increases in targeted carotenoids : α-carotene , β-carotene , and lutein . For each of these targeted carotenoids , the proportion of the intervention sample remaining below the cutpoint for the lowest baseline quartile decreased by one third to one half . After 1 year of study , half of the intervention group was in the highest baseline quartile . No change in distribution was observed in comparison group . Intervention participants achieved this change by both dietary pattern and vegetable juice consumption . Participants who chose to change dietary pattern without consuming significant quantities of vegetable juice achieved 75 % of the level of change observed in other intervention participants . Conclusions : Innovative telephone counseling intervention and dietary targets in the Women 's Healthy Eating and Living study were associated with the level of change in circulating carotenoid concentration necessary to test the diet and breast cancer hypothesis suggested by cohort studies . ( Cancer Epidemiol Biomarkers Prev 2006;15(10):1886–92 High vegetable and fruit ( V&F ) consumption has been associated with a lower risk of several cancers . However , little is known about the ability of individuals to increase their intakes markedly . In this 1-year r and omized , controlled diet intervention study of men and women with a recent history of adenomas , the intervention group ( n = 100 ) was asked to increase V&F intake to at least eight servings per day ; the control group ( n = 101 ) continued eating their usual diet . End-point measures included V&F intake assessed by 3-day diet records , plasma carotenoids , serum lipids , urinary sodium and potassium , and body weight . The intervention group increased their daily V&F intake an average of 5.5 servings over 1 year ; the control group had an average decrease of 0.5 servings per day ( P < 0.001 ) . Plasma total carotenoids , alpha-carotene , beta-carotene , beta-cryptoxanthin , and lutein/zeaxanthin were each statistically significantly elevated over baseline ( 11 - 54 % ) in the intervention group compared with the control group over the duration of follow-up ( P < 0.001 ) . Urinary potassium excretion was elevated 14 % over baseline in the intervention group compared with no change in the control group ( P < 0.001 ) . Modest decreases in the intervention but not the control group were observed for total and low-density lipoprotein cholesterol . Plasma lycopene , triglycerides , high-density lipoprotein cholesterol , body weight , and urinary sodium were not affected by the intervention . V&F intake was significantly increased in this motivated population at higher risk of colon cancer and maintained for at least 12 months , as assessed using diet records and an ensemble of biomarkers Epidemiologic evidence supports the concept that diet influences risk for breast cancer and suggests that prognosis after the diagnosis of breast cancer may also be related to modifiable nutritional factors . The purpose of this study was to investigate the feasibility of a r and omized trial of a high-vegetable , reduced-fat , and increased-fiber diet intervention to reduce risk for recurrence among breast cancer survivors . This major change in dietary pattern was promoted through intensive telephone counseling . Participants were 93 women who had been diagnosed with breast cancer ( stages I , II , and IIIA ) within the previous four years and who had completed their initial treatment . We assessed adherence to the study diet using repeated 24-hour dietary recalls at 6 and 12 months and measurement of circulating carotenoid concentrations . Six months after r and omization , the intervention group had significantly increased their mean intake of vegetables ( + 4.6 servings/day ) , fruit ( + 0.7 servings/day ) , and fiber ( + 6.4 g/1,000 kcal ) and significantly reduced their intake of dietary fat ( -9.9 % of energy ) compared with the control group . Circulating concentrations of carotenoids also increased in the intervention group . These changes persisted at the 12-month visit . Results of this study demonstrate that telephone counseling can be a useful approach in diet intervention and that breast cancer survivors can adopt and maintain a high-vegetable , reduced-fat dietary pattern Objective : To determine whether consumption of five portions of fruit and vegetables per day reduces the enhancement of oxidative stress induced by consumption of fish oil . Subjects : A total of 18 free-living healthy smoking volunteers , aged 18–63 y , were recruited by posters and e-mail in The University of Reading , and by leaflets in local shops . Design : A prospect i ve study . Setting : Hugh Sinclair Unit of Human Nutrition , School of Food Biosciences , The University of Reading , Whiteknights PO Box 226 , Reading RG6 6AP , UK . Interventions : All subjects consumed a daily supplement of 4 × 1 g fish oil capsules for 9 weeks . After 3 weeks , they consumed an additional five portions of fruits and vegetables per day , and then they returned to their normal diet for the last 3 weeks of the study . Fasting blood sample s were taken at the ends of weeks 0 , 3 , 6 and 9 . Results : The plasma concentrations of ascorbic acid , lutein , β-cryptoxanthin , α-carotene and β-carotene all significantly increased when fruit and vegetable intake was enhanced ( P<0.05 ) . Plasma concentrations of α-tocopherol , retinol and uric acid did not change significantly during the period of increased fruit and vegetable consumption . Plasma oxidative stability , assessed by the oxygen radical absorbance capacity ( ORAC ) assay , also increased from weeks 3–6 ( P<0.001 ) but not in association with increases in measured antioxidants . Lag phase before oxidation of low-density lipoprotein ( LDL ) significantly decreased in the first 3 weeks of the study , reflecting the incorporation of EPA and DHA into LDL ( P<0.0001 ) . Subsequent enhanced fruit and vegetable consumption significantly reduced the susceptibility of LDL to oxidation ( P<0.005 ) . Conclusion : Fish oil reduced the oxidative stability of plasma and LDL , but the effects were partially offset by the increased consumption of fruit and vegetables . Sponsorship : This study was supported by funding from the Ministry of Agriculture , Fisheries and Food , and from Boots plc High vegetable intake has been associated with a decreased risk for various human cancers in epidemiological studies . Carotenoids are plant compounds that may both possess chemopreventive activity and be useful biomarkers of vegetable and fruit intake . Nineteen men and women were r and omized into a controlled cross-over feeding study to measure the effect of vegetable intake on plasma carotenoid concentrations . Participants consumed each of 4 experimental diets for 9 days . The control diet consisted of commonly consumed foods and was essentially carotenoid free . High vegetable diets ( carotenoid , cruciferous , and soy ) consisted of the control diet plus carrots and spinach ( carotenoid ) , broccoli and cauliflower ( cruciferous ) , and tofu and FriChik ( soy ) . Plasma carotenoid concentrations were highest on the carotenoid and cruciferous diets . When compared to the control , mean plasma alpha-carotene , beta-carotene , and lutein concentrations were 5.2 , 3.3 and 2.2 times higher on the carotenoid diet , respectively ( P < 0.001 ) . Mean plasma lutein concentrations were 2.1 times higher on the cruciferous versus the control diet ( P < 0.001 ) . There were no differences between diets in plasma beta-cryptoxanthin and lycopene concentrations . These data indicate that plasma alpha-carotene , beta-carotene , and lutein may be useful biomarkers of carotenoid-rich food intake and that lutein may act as an intake biomarker of commonly consumed vegetables in the Cruciferae family . These findings should prove useful in undertaking dietary intervention trials because they suggest the feasibility of monitoring intake of some plant foods and of distinguishing among plant food groups OBJECTIVE Our objective was to evaluate the effect of daily supplementation with foods high in vitamin C and beta carotene on plasma vitamin levels and oxidation of low-density lipoprotein ( LDL ) in cigarette smokers . SUBJECTS Fifteen normolipidemic male cigarette smokers who did not usually take vitamin supplements were recruited into the study . INTERVENTIONS Throughout the study , subjects consumed a diet rich in polyunsaturated fatty acids , which provided 36 % of energy as fat : 18 % from meat , dairy products , vegetable oils , and fat spreads and 18 % from walnuts ( 68 g/day ) . Subjects consumed a vitamin-free drink daily for 3 weeks ; then for 3 weeks they consumed daily supplements of orange juice ( 145 mg vitamin C ) and carrot juice ( 16 mg beta carotene ) . RESULTS Vitamin-rich food supplements raised plasma levels of ascorbic acid ( 1.6-fold ; P < .01 ) and beta carotene ( 2.6-fold ; P < .01 ) . Malondialdehyde , one end product of oxidation , was lower in copper-oxidized LDL after vitamin supplementation ( mean + /- st and ard error = 65.7 + /- 2.0 and 57.5 + /- 2.9 mumol/g LDL protein before and after supplementation , respectively ; P < .01 ) . Rate of LDL oxidation and lag time before the onset of LDL oxidation were not affected by antioxidant supplementation . CONCLUSIONS In habitual cigarette smokers , antioxidant vitamins , which can be feasibly provided from food , partly protected LDL from oxidation despite a diet rich in polyunsaturated fatty acids BACKGROUND Dietary intervention is one of the important fields in cancer and cardiovascular disease prevention . The Hiraka Dietary Intervention Study is a community-based r and omized cross-over trial design ed to develop an effective dietary modification tool and system in an area with high mortality of stomach cancer and stroke . METHODS The subjects were 550 healthy volunteers and were r and omized into two groups with tailored dietary education to decrease sodium intake and to increase vitamin C and carotene intakes either in the first year ( intervention group ) or in the second year ( control group ) . Dietary changes were assessed using a vali date d self-administered diet history question naire , fasting blood sample s , and 48-hour urine sample s , which were obtained before and after the one year period . RESULTS During the first year , changes differed significantly between the intervention and control group for both dietary sodium intake ( -384 and + 255 mg/day , intervention and control respectively , p < 0.001 ) and urinary sodium excretion ( -1003 and -84 mg/day , p < 0.001 ) . Although favorable net changes were also observed in dietary carotene ( + 418 and + 220 mug/day , p < 0.05 ) and vitamin C ( + 13 and + 2 mg/day , p < 0.05 ) , the serum level differences were modest ( + 13 and -25 mg/L , p = 0.09 for carotene , + 0.1 and -0.5 mg/L , p = 0.07 for ascorbic acid ) . CONCLUSION The present dietary intervention strategy effectively decreased sodium and increased carotene and vitamin C intakes , although the former was more distinct The Women 's Healthy Eating and Living ( WHEL ) Study is a multisite r and omized controlled trial of the effectiveness of a high-vegetable , low-fat diet , aim ed at markedly raising circulating carotenoid concentrations from food sources , in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer ( within 4 years of diagnosis ) . The study r and omly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006 . Two thirds of these women were under 55 years of age at r and omization . This research study has a coordinating center and seven clinical sites . R and omization was stratified by age , stage of tumor and clinical site . A comprehensive intervention program that includes intensive telephone counseling , cooking classes and print material s helps shift the dietary pattern of women in the intervention . Through an innovative telephone counseling program , dietary counselors encourage women in the intervention group to meet the following daily behavioral targets : five vegetable servings , 16 ounces of vegetable juice , three fruit servings , 30 g of fiber and 15 - 20 % energy from fat . Adherence assessment s occur at baseline , 6 , 12 , 24 or 36 , 48 and 72 months . These assessment s can include dietary intake ( repeated 24-hour dietary recalls and food frequency question naire ) , circulating carotenoid concentrations , physical measures and question naires about health symptoms , quality of life , personal habits and lifestyle patterns . Outcome assessment s are completed by telephone interview every 6 months with medical record verification . We will assess evidence of effectiveness by the length of the breast cancer event-free interval , as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years Racial differences in potassium ( K ) intake and urinary K excretion may contribute to the higher BP observed in black compared with white individuals . Although black individuals typically consume less dietary K than white individuals , the lower urinary K excretion observed in black individuals may reflect more than differences in intake . In this study , data from the Dietary Approaches to Stop Hypertension ( DASH ) trial ( 413 white and black participants ) were used to evaluate urinary K excretion in black and white individuals with similar K intake . At screening , mean urinary K excretion was higher in white than black individuals ( mean Delta = 645 mg/d for white minus black individuals , adjusted for age , gender , and weight ; P < 0.001 ) . After a 3-wk run-in period during which all participants received a low-K control diet , a significant racial difference remained ( mean Delta = 201 mg/d , adjusted for age , gender , and caloric intake ; P < 0.001 ) . Participants were then r and omly assigned to continue the control diet or switch to a high-K diet ( either a high fruit/vegetable diet or the DASH diet ) for 8 wk . At the end of intervention , the mean difference in urinary K in white compared with black individuals after adjustment for age , gender , and caloric intake was -6 mg/d ( P = 0.95 ) in the control group , 163 mg/d in the fruits/vegetables group ( P = 0.39 ) , and 903 mg/d in the DASH group ( P < 0.001 ) . Racial differences in urinary K excretion seem to reflect more than intake differences ; further studies are needed to underst and their potential impact on clinical outcomes Summary . Background : High intake of vegetables and fruits is associated with decreased risk of coronary heart disease . Part of these cardioprotective effects may be mediated via the antithrombotic effects of compounds found in vegetables and fruits , such as flavonoids . Aim of the study : To study the effects of high and low intake of vegetables , berries and apple on platelet function and inflammatory markers . Methods : The study was a r and omised , controlled parallel human dietary intervention with healthy female and male volunteers ( n = 77 , 19–52 y ) . Nineteen healthy volunteers served as controls . The volunteers consumed one of four strictly controlled isocaloric 6-week diets containing either 810 or 196 g/10 MJ of vegetables , berries and apple and rich either in linoleic acid ( 11 % of energy , en% ) or oleic acid ( 12 en% ) . Blood and three 24-hour urine sample s were collected at the beginning and at the end of the study period for analyses of various markers of platelet function and inflammation . Results : No differences between the treatment groups were seen in platelet count or volume , markers of platelet activation ( ex vivo aggregation to ADP and thrombin receptor activating peptide , protein kinase C activity , urinary 2,3-dinor-thromboxane B2 excretion , plasma P-selectin ) , plasma intercellular adhesion molecule-1 , sensitive C-reactive protein , or antiphospholipid antibodies . Conclusions : The results indicate that in healthy volunteers 6-week diets differing markedly in the amounts of vegetables , berries and apple do not differ in their effects on platelets or inflammation Potassium , which is abundant in vegetables , is inversely related to blood pressure . Although the situation has changed somewhat in recent years , the Okinawan diet has generally included a large amount of vegetables , and until recently Okinawans had the lowest rates of mortality due to stroke and coronary heart disease in Japan . Based on the hypothesis that these low mortality rates are partly attributable to increased potassium intake result ing from the high vegetable consumption , this study examined whether increasing the consumption of typical yellow-green Okinawan vegetables increases potassium intake . The purpose of this investigation was to determine whether increased consumption of these vegetables should be one of the dietary modifications recommended in public health promotion programs for Okinawans . The study employed 56 healthy , normotensive , free-living Japanese women aged 18–38 years living in Okinawa . They were r and omized to a dietary intervention group ( n=27 ) or a control group ( n=29 ) . Members of the dietary intervention group received an average weight of 371.4 g/day of a combination of the following vegetables twice weekly through an express home parcel deliver service for a period of 14 days : Goya ( Momordica charantia ) , green papaya ( Carica papaya ) , H and ama ( Gynura bicolor ) , Karashina ( Brassica juncea ) , Njana ( Crepidiastrum lanceolatium ) , Fuchiba ( Artemisia vulgaris ) and Fudanso ( Beta vulgaris ) ; and they consumed an average of 144.9 g/day , result ing in a 20.5 % increase in their urinary potassium excretion over the baseline ( p=0.045 ) . The members of the control group were asked to avoid these vegetables , and the change in potassium excretion in this group was not significant ( p=0.595 ) . Urinary sodium and magnesium excretions , systolic and diastolic blood pressures , folic acid , triglycerides and serum high density lipoprotein cholesterol , low density lipoprotein cholesterol and total cholesterols changed non-significantly in both groups . Also , post-intervention urinary potassium excretion correlated positively with vegetable consumption in both the dietary intervention ( p<0.0001 ) and control ( p=0.008 ) groups and with Okinawan vegetable intake in the dietary intervention group ( p=0.0004 ) Epidemiological studies suggest that a high vegetable diet may reduce risk for breast cancer and may also improve prognosis after the diagnosis of breast cancer . Circulating carotenoids may serve as a biomarker of vegetable and fruit intake , although several factors affect their bioavailability from food sources and may influence concentrations . One purpose of this study was to identify factors predictive of serum carotenoid , retinol , and alpha-tocopherol concentrations in 79 postsurgically resected breast cancer patients at enrollment and at 12 months in a feasibility study of a high vegetable , low fat diet intervention to reduce risk for cancer recurrence . Another purpose was to identify variables associated with change in these serum concentrations 12 months after r and omization into control and intervention groups . The diet intervention ( versus control ) group had significantly greater increases in carotenoid intakes ( P < 0.03 ) and significantly greater increases in serum concentrations of lutein , alpha- and beta-carotene , lycopene , and retinol ( P < 0.04 ) . Stepwise multiple regression revealed the level of dietary intake to be predictive of most serum carotenoid concentrations at baseline and 12 months , with additional associations between selected micronutrient concentrations and serum cholesterol , body mass index , age , percentage of energy intake from fat , and alcohol intake also observed at these time points . Intervention group change in serum carotenoid concentrations was inversely associated with baseline level , age , and change in serum cholesterol concentration and positively associated with change in carotenoid and alcohol intake . Circulating carotenoid concentrations are responsive to a high vegetable diet intervention , which also included reduced dietary fat and increased fiber intakes , to reduce risk for breast cancer recurrence The authors examined the feasibility of using plasma carotenoids and ascorbic acid as markers of compliance for dietary intervention trials aim ed at increasing the quantity and variety of the fruit and vegetable intake of free-living individuals . Nineteen former cancer patients who had been successfully treated for a stage I or II squamous cell carcinoma of the mouth , pharynx , larynx , or lung were recruited . Subjects served as their own controls . However , in order to detect any seasonal trends , 4 individuals among the 19 were r and omized to a nonintervention group . Subjects in the intervention group were counseled by dietitians with the goal of increasing their intake of fruits and vegetables to eight servings/day ( 1 serving each of dark green vegetables , yellow-orange vegetables , tomato products , and other vegetables ; 3 servings of vitamin C-rich fruits ; and 1 serving of other fruits ) . Subjects in the nonintervention group were advised to follow their usual diet . Three-day measured food records kept at base line and after 3 months of intervention , as well as unannounced 24-h dietary recalls , documented an increase in mean fruit and vegetable intake from 4.2 to 9.5 servings daily in the intervention group . A concomitant increase of 29 % was observed in total plasma carotenoids ( P = 0.02 ) , with increases of 25 % for plasma lycopene ( P = 0.06 ) , 31 % for plasma lutein ( P = 0.002 ) , 39 % for plasma beta-carotene ( P = 0.01 ) , and 57 % for plasma alpha-carotene ( P = 0.01 ) . Mean plasma levels of ascorbic acid increased by 27 % ( P < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To increase fruit , vegetable , and calcium-rich food consumption in community-dwelling , functionally impaired elderly . DESIGN Six-month , home-based nutrition intervention study . SUBJECTS Seventy men and women older than age 69 years were r and omized to either a nutrition education intervention ( n = 38 ) or a control group that received an exercise intervention ( n = 32 ) . INTERVENTION Nutrition education was design ed to increase fruit , vegetable , and calcium-rich food consumption . MAIN OUTCOME MEASURES Food intake was assessed by a food frequency question naire . Fasting blood measures of nutrients and carotenoids were performed . Statistical Analysis Two-group r and omized controlled trial with pre-test and post-test design and intention-to-treat analysis . Analysis of covariance to was used to assess differences between the two groups . Baseline and change partial correlation coefficients were performed between intake and blood nutrient levels . Paired t tests were conducted to test within-group changes . RESULTS Compared with the exercise group , subjects in nutrition group increased their self-reported intake of fruits by 1.1 + /- 0.2 ( mean + /- SEM ) servings per day ( 2.8 to 3.9 , P = .01 ) , vegetables 1.1 + /- 0.2 servings per day ( 2.3 to 3.4 , P = .001 ) , and milk/dairy 0.9 + /- 0.2 servings per day ( 3.0 to 3.9 , P = .001 ) . There was an increase in the dietary intake of alpha-carotene and beta-carotene in the nutrition group and this correlated with the increase in blood concentrations of alpha-carotene and beta-carotene ( P < or = .02 ; r = 0.33 and r = 0.33 , respectively ) . CONCLUSION The results of this study suggest that it is possible to improve the dietary intake of community dwelling elders to include more fruits , vegetables , and calcium-rich foods . Recommendations for increasing consumption of fruits , vegetables , and calcium-rich foods should be specific and individualized to meet the dietary pattern and lifestyle of the individual . Compliance should be encouraged with record keeping as well as through continuous monitoring and positive reinforcement BACKGROUND Oxidation of LDL ( oxLDL ) is thought to have an important role in early stages of atherogenesis . Antibody to oxLDL ( Ab-oxLDL ) has been proposed as a biomarker which might be directly associated with oxidative stress . Yet studies design ed to test this hypothesis are lacking . We tested the hypothesis that consumption of a healthy diet rich in fruits and vegetables and reduced in saturated fat , total fat , and cholesterol will concomitantly reduce oxidative stress and Ab-oxLDL . METHODS One hundred and three healthy individuals were r and omly assigned to consume a typical American ( control ) diet or the DASH diet rich in fruits , vegetables and low-fat dairy products and reduced in fat ( 27 % ) , saturated fat ( 7 % ) , and cholesterol ( 150 mg/day ) for 3 months . Outcomes were urinary isoprostanes ( in vivo marker of oxidative stress ) , oxygen radical absorbing capacity ( ORAC , an in vitro assay measuring antioxidant activity in serum ) , and Ab-oxLDL measured at baseline , 1 - 3 months of feeding . RESULTS Compared to the control diet , consumption of the DASH diet significantly lowered urinary isoprostane ( -226 pg/ml , 95 % CI : -420 to -32 , P=0.023 ) . Compared with the control group , change in ORAC was higher in the DASH group , 143 trolox units/ml ( 95 % CI : -23 to 308 , P=0.091 ) . In comparison with the control diet , increased titers of Ab-oxLDL ( 37 mU/ml [ 95 % CI : 16 - 57 , P=0.006 ] ) were seen after consumption of the DASH diet . Higher titers of Ab-oxLDL occurred at month 2 ( 56 mU/ml , 95 % CI : 20 - 90 , P=0.004 ) and month 3 ( 41 mU/ml , 95 % CI : -6 to 88 , P=0.082 ) , after initially small increases at month 1 ( 20 mU/ml , 95 % CI : -10 to 51 , P=0.176 ) . End-of- study increases in AB-oxLDL were highly correlated with increased ORAC ( Spearman 's rho=0.46 , P<0.0001 ) , but not with changes in specific carotenoids , tocopherols or with change in LDL cholesterol ( each : P>0.10 ) . CONCLUSION Consumption of a healthy diet replete in antioxidants reduced oxidative stress ( urinary isoprostanes ) yet increased Ab-oxLDL . This indirect association of Ab-oxLDL with urinary isoprostanes hinders use of Ab-oxLDL as a marker of oxidative damage Objective : Fruit and vegetable intake is inversely associated with cancer risk in many epidemiological studies . Accurate assessment of consumption of these foods is difficult , and biomarkers of intake would overcome several drawbacks of currently used dietary assessment methods . Therefore , we investigated the relation between plasma carotenoids and usual vegetable and fruit intake . Design : Plasma carotenoid concentrations were measured and vegetable , fruit and juice consumption was assessed by a food frequency question naire ( FFQ ) in a r and om sample of 591 Dutch men and women aged 20–59 y from the MORGEN-project , one of the contributions to the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)- study . Results : In this sample of the general Dutch population , in both genders , relative to the other carotenoids , plasma β-cryptoxanthin was the best indicator for fruit intake , and for the sum of vegetable , fruit and juice intake , while lutein concentrations best reflected intake of vegetables , although quartiles of intake were not consistently separated . Since levels of lycopene were not associated with any of the main food groups examined , associations with total carotenoids improved when excluding lycopene , and monotonously increasing plasma levels were seen for intakes of vegetables , of fruits , and of the sum of vegetables , fruits and juices . Several vegetable types and orange/grapefruit juice were associated with plasma levels of one of the carotenoids . Conclusion : Plasma carotenoids were only crude indicators of vegetable and fruit intake as assessed by a FFQ ; β-cryptoxanthin for fruit intake and lutein for vegetable intake . None of the plasma carotenoids could distinguish all four quartiles of vegetables , fruit and /or juice intake BACKGROUND The Mediterranean dietary pattern is thought to reduce the risk of cancer in addition to being cardioprotective . However , no trial has been conducted so far to prove this belief . METHODS We compared overall survival and newly diagnosed cancer rate among 605 patients with coronary heart disease r and omized in the Lyon Diet Heart Study and following either a cardioprotective Mediterranean-type diet or a control diet close to the step 1 American Heart Association prudent diet . RESULTS During a follow-up of 4 years , there were a total of 38 deaths ( 24 in controls vs 14 in the experimental group ) , including 25 cardiac deaths ( 19 vs 6 ) and 7 cancer deaths ( 4 vs 3 ) , and 24 cancers ( 17 vs 7 ) . Exclusion of early cancer diagnoses ( within the first 24 months after entry into the trial ) left a total of 14 cancers ( 12 vs 2 ) . After adjustment for age , sex , smoking , leukocyte count , cholesterol level , and aspirin use , the reduction of risk in experimental subjects compared with control subjects was 56 % ( P=.03 ) for total deaths , 61 % ( P=.05 ) for cancers , and 56 % ( P=.01 ) for the combination of deaths and cancers . The intakes of fruits , vegetables , and cereals were significantly higher in experimental subjects , providing larger amounts of fiber and vitamin C ( P<.05 ) . The intakes of cholesterol and saturated and polyunsaturated fats were lower and those of oleic acid and omega-3 fatty acids were higher ( P<.001 ) in experimental subjects . Plasma levels of vitamins C and E ( P<.05 ) and omega-3 fatty acids ( P<.001 ) , measured 2 months after r and omization , were higher and those of omega-6 fatty acids were lower ( P<.001 ) in experimental subjects . CONCLUSIONS This r and omized trial suggests that patients following a cardioprotective Mediterranean diet have a prolonged survival and may also be protected against cancer . Further studies are warranted to confirm the data and to explore the role of the different lipids and fatty acids in this protection For obese individuals seeking to optimize health and well-being , healthy dietary strategies are important . Vegetables and fruits contribute to a healthy diet , and increased consumption may cause weight reduction by displacing foods high in energy and fat . The objective of this study was to determine if advising high vegetable ( 8 servings ) and moderate fruit ( 2–3 servings ) consumption would result in weight reduction in obese individuals . We compared this to advising a more traditional strategy of reducing daily energy intake by 500 kcal ( 2.1 MJ)/d and limiting energy from fat to ≤25 % . A r and omized study design was used . Subjects ( age 21–50 y , n = 30/group ) received food ( 2 meals + 1 snack/d , 5 d/wk ) and education ( 2 group lessons/wk plus individual consultations as requested ) for the first 3 mo . Weight and body composition were measured at baseline and after 3 , 12 , and 18 mo . Fasting serum lipid panel , insulin , glucose , hematocrit , and C-reactive protein were measured at baseline , 3 , and 12 mo . Both groups lost weight after 3 mo ( P = 0.0087 for high vegetable diet and P < 0.0001 for energy reduction diet ) , and the energy and fat reduction diet result ed in lower weight over time ( P < 0.0001 , treatment effect ) . Total cholesterol and cholesterol : HDL decreased after 3 mo in both groups ( P ≤ 0.0061 ) . Both strategies produced initial weight loss at 3 mo , but only the group following the caloric and fat reduction advice maintained weight loss at the 12- and 18-mo follow-up assessment s. Nonetheless , the group following the high vegetable advice did not regain weight above baseline . In conclusion , traditional messages to reduce calories and fat are important , and increasing vegetable intake can assist individuals to maintain weight OBJECTIVE To determine whether a fat- and energy-reduced diet rich in antioxidant vitamins C and E , beta carotene , and soluble dietary fiber reduces free-radical stress and cardiac enzyme level and increases plasma ascorbic acid level 1 week after acute myocardial infa rct ion . DESIGN R and omized , single blind , controlled study . SETTING Primary - and secondary -care research center for patients with myocardial infa rct ion . SUBJECTS All subjects with suspected acute myocardial infa rct ion ( n = 505 ) were considered for entry to the study . Subjects with definite or possible acute myocardial infa rct ion and unstable angina ( according to World Health Organization criteria ) were assigned to either an intervention diet ( n = 204 ) or a control diet ( n = 202 ) within 48 hours of symptoms of infa rct ion . INTERVENTIONS Intervention and control groups were advised to consume a fat-reduced , oil-substituted diet . The intervention group was also advised to eat more fruits , vegetable soup , pulses , and crushed almonds and walnuts mixed with skim milk . MAIN OUTCOME MEASURES Reduction in plasma lipid peroxide and lactate dehydrogenase cardiac enzyme levels , increase in plasma ascorbic acid level , and compliance with diet , especially with vitamin C intake as determined by chemical analysis . STATISTICAL ANALYSIS A two- sample t test using one-way analysis of variance for comparison of data . RESULTS Plasma lipid peroxide level decreased significantly in the intervention group compared with the control group ( 0.59 pmol/L in the intervention group and 0.10 pmol/L in the control group ; 95 % confidence interval of difference = 0.19 to 0.83 ) . Lactate dehydrogenase level increased less in the intervention group than in the control group ( 427.7 vs 561.2 U/L ; confidence interval of difference = 82.9 to 184.7 ) . Plasma ascorbic acid level increased more in the intervention group than in the control group ( 23.38 vs 7.95 mumol/L ; confidence interval of difference = 12.85 to 26.13 ) . APPLICATIONS/ CONCLUSIONS Consumption of an antioxidant-rich diet may reduce the plasma levels of lipid peroxide and cardiac enzyme and increase the plasma level of ascorbic acid . Antioxidant-rich foods may reduce myocardial necrosis and reperfusion injury induced by oxygen free radicals To find out if the cancer protective effects of Brussels sprouts seen in epidemiological studies are due to protection against DNA-damage , an intervention trial was conducted in which the impact of vegetable consumption on DNA-stability was monitored in lymphocytes with the comet assay . After consumption of the sprouts ( 300 g/p/d , n = 8) , a reduction of DNA-migration ( 97 % ) induced by the heterocyclic aromatic amine 2-amino-1-methyl-6-phenyl-imidazo-[4,5-b]pyridine ( PhIP ) was observed whereas no effect was seen with 3-amino-1-methyl-5H-pyrido[4,3-b]-indole ( Trp-P-2 ) . This effect protection may be due to inhibition of sulfotransferase 1A1 , which plays a key role in the activation of PhIP . In addition , a decrease of the endogenous formation of oxidized bases was observed and DNA-damage caused by hydrogen peroxide was significantly ( 39 % ) lower after the intervention . These effects could not be explained by induction of antioxidant enzymes glutathione peroxidase and superoxide dismutase , but in vitro experiments indicate that sprouts contain compounds , which act as direct scavengers of reactive oxygen species . Serum vitamin C levels were increased by 37 % after sprout consumption but no correlations were seen between prevention of DNA-damage and individual alterations of the vitamin levels . Our study shows for the first time that sprout consumption leads to inhibition of sulfotransferases in humans and to protection against PhIP and oxidative DNA-damage OBJECTIVES To evaluate the feasibility of implementing a diet-based intervention in men with prostate cancer . METHODS Seventy-four men aged 50 to 80 years with biopsy-proven adenocarcinoma of the prostate were r and omized to receive either telephone-based dietary counseling or st and ardized , written nutritional information . Telephone dietary counseling targets included increased intakes of vegetables ( particularly cruciferous vegetables and tomato products ) , whole grains , and beans/legumes . Dietary intakes and plasma carotenoid levels were assessed at baseline and at 6 months ' follow-up . RESULTS In the intervention arm , mean daily intakes of total vegetables , crucifers , tomato products , and beans/legumes increased by 76 % , 143 % , 292 % , and 95 % , respectively , whereas fat intake decreased by 12 % ( P = 0.02 ) . In the control arm , there were no significant changes in mean intakes of total vegetables , tomato products , crucifers , beans/legumes , or fat . Similarly , in the intervention arm , mean plasma levels of alpha-carotene , beta-carotene , lutein , lycopene , and total carotenoids increased by 33 % , 36 % , 19 % , 30 % , and 26 % , respectively ( P < 0.05 ) . In the control arm , there were no significant changes in plasma levels of alpha- or beta-carotene , lutein , lycopene , or total carotenoids . CONCLUSIONS Telephone-based dietary counseling increases vegetable intake , decreases fat intake , and significantly increases plasma levels of potentially anticarcinogenic carotenoids in men with prostate cancer . These data support the feasibility of implementing clinical trials of dietary intervention in men with prostate cancer BACKGROUND AND AIM The health-promoting effects of fruit- and vegetable-based diets are known to be associated with their antioxidative components . We found in our preliminary in vitro laboratory tests that extracts of many common Finnish edible berries are potent scavengers of peroxyl radicals and inhibitors of lipid peroxidation . We therefore design ed the current study to evaluate both the long-term ( 8 weeks ) and short-term ( 5 hours ) effects of increased intake of three berries on antioxidant potential and lipid peroxidation . METHODS AND RESULTS Healthy 60-year-old men were r and omized to berry , supplement and control groups ( 20 men in each group ) . The berry group ate , in addition to their normal diet , a 100 g portion of deep-frozen berries ( bilberries , lingonberries , or black currants ) daily for 8 weeks . The other groups ingested daily 100 mg of alpha-tocopherol and 500 mg of ascorbic acid ( supplement group ) or 500 mg of calcium gluconate ( control group ) . In the short-term experiment 6 men ate 80 g of each of the three berries in one go . Serum ascorbate concentrations increased significantly in both the berry and the supplement group . Serum alpha-tocopherol levels and the antioxidant potential ( TRAP ) in low density lipoprotein ( LDL ) increased in the supplement group only . In the berry group , slightly lowered LDL diene conjugation ( p = 0.074 ) and slightly increased total serum TRAP ( p = 0.084 ) values were observed . No changes were found in these measures in the supplement or the control group . In the short-term experiment , LDL TRAP showed a small increase ( about 10 % , p = 0.039 ) during five hours after the intake of 240 g berries . CONCLUSIONS The effects of consumption of berries on antioxidant potential and diene conjugation in LDL particles in vivo appear to be small Abstract Objectives : To determine the extent to which plasma antioxidant concentrations in people with habitual low intake of fruit and vegetables respond to increased intakes of these foods . To examine whether advice to increase fruit and vegetables will result in reduction of concentrations of total and low density lipoprotein cholesterol . Design : R and omised controlled trial in which intervention and control groups were followed up for eight weeks . The intervention group was asked to consume eight servings of fruit and vegetables a day . Setting : Dunedin , New Zeal and . Subjects : Eighty seven subjects with normal lipid concentrations who ate three or fewer servings of fruit and vegetables daily . Main outcome measures : Plasma concentrations of vitamin C , retinol , α and ß carotene , α tocopherol , lipids , and lipoproteins . Dietary intake assessed with diet records over four days . Results : The mean plasma vitamin C , α carotene , and ß carotene concentrations increased in parallel with increased dietary intake of fruit and vegetables in the intervention group . Concentrations of retinol , α tocopherol , lipids , and lipoproteins remained unchanged despite some increase in dietary vitamin E and a small reduction in saturated fat intake . Conclusions : Following a recommendation to increase fruit and vegetable consumption produces change in plasma concentrations of vitamin C , α carotene , and ß carotene likely to reduce incidence of cancer . More specific dietary advice to modify fat intake may be necessary to reduce the risk of cardiovascular disease mediated by lipoprotein and vitamin E. Key messages Increasing intake of fruit and vegetables raises plasma concentrations of vitamin C and α and ß carotene These changes in plasma concentrations of antioxidants are probably associated with reduced risk of cancer A simple recommendation to increase fruit and vegetable intake has little effect on plasma concentrations of α tocopherol , lipids , and lipoproteins More specific dietary advice to modify fat intake may be necessary to reduce risk of cardiovascular disease associated with lipoproteins and vitamin Objectives : Higher plasma micronutrient levels have been associated with decreased cancer risks . The objective of this study was to determine the relative effects of reduced fat and /or increased fruit-vegetable ( FV ) intakes on plasma micronutrient levels . Methods : Healthy , premenopausal women with a family history of breast cancer ( n = 122 ) were r and omized across four diet arms for one year in a 2 × 2 factorial design study : control , low-fat , high fruit-vegetable and combination low-fat/high FV diets . Levels of plasma micronutrients were measured in plasma at 0 , 3 , 6 and 12 months . Results : The high FV intervention , regardless of fat intake , significantly increased α-carotene , β-carotene and vitamin C levels in plasma . Only the combination high FV , low-fat intervention significantly increased plasma β-cryptoxanthin and zeaxanthin levels over time . Although α-tocopherol was not affected , a potential concern is that the low-fat intervention result ed in significantly decreased both γ-tocopherol dietary intakes and plasma levels , regardless of whether or not FV intakes were concomitantly increased . Conclusions : Unlike α-tocopherol , γ-tocopherol plasma levels were decreased by a low fat diet , perhaps because γ-tocopherol is not generally added to foods nor widely used in vitamin E supplements . The decreased dietary intakes and plasma levels of γ-tocopherol with a low-fat diet may have implication s for health risks since the biological functions of the different tocopherol isomers have been reported to be distinct It is well established that vegetables and fruit ( VF ) contain antioxidant phytochemicals . Consequently , it is expected that individuals who consume diets with a high content of VF should be better protected against oxidative cellular damage than individuals who do not , but not all data support this assumption . The objective of this study was to identify possible explanations for this conundrum . The effects of two diets that differed in VF content on markers of oxidative damage were studied . Sixty-four women participated in a 14-day dietary intervention . Subjects consumed on average either 3.6 or 12.1 servings of VF per day . The primary end points assessed were 8-hydroxy-2-deoxyguanosine ( 8-oxo-dG ) in peripheral lymphocyte DNA and 8-isoprostagl and in F-2alpha ( 8-iso-PGF2alpha ) excreted in urine . Subjects consuming the high versus low VF diet had lower concentrations of 8-oxo-dG ( p < 0.01 ) and of 8-iso-PGF2alpha ( p < 0.01 ) . However , the reduction in oxidative end points by high VF was not uniform . Rather , an antioxidant effect was observed primarily in individuals whose oxidative end points at baseline were above the median for the study population . Using change in plasma carotenoids ( end point minus baseline measurements ) as an index of phytochemical intake , the reduction in oxidative markers was inversely proportional to change in plasma carotenoids ; this effect was stronger for lipid peroxidation ( p < 0.01 ) than DNA oxidation ( p < 0.05 ) . These findings imply that increasing exogenous antioxidant exposure may primarily benefit individuals with elevated levels of oxidative stress . Null findings do not necessarily indicate that an antioxidant compound lacks in vivo activity Oxidative cell damage is involved in the pathogenesis of atherosclerosis , cancer , diabetes and other diseases . Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols , might reduce oxidative cell damage . Therefore , an intervention study was performed with a red mixed berry juice [ trolox equivalent antioxidative capacity ( TEAC ) : 19.1 mmol/L trolox ] and a corresponding polyphenol‐depleted juice ( polyphenols largely removed , TEAC 2.4 mmol/L trolox ) , serving as control . After a 3‐week run‐in period , 18 male prob and s daily consumed 700 mL juice , and 9 consumed control juice , in a 4‐week intervention , followed by a 3‐week wash‐out . Sample s were collected weekly to analyze DNA damage ( comet assay ) , lipid peroxidation ( plasma malondialdehyde : HPLC/fluorescence ; urinary isoprostanes : GC‐MS ) , blood glutathione ( photometrically ) , DNA‐binding activity of nuclear factor‐κB ( ELISA ) and plasma carotenoid/α‐tocopherol levels ( HPLC‐DAD ) . During intervention with the fruit juice , a decrease of oxidative DNA damage ( p<5 × 10–4 ) and an increase of reduced glutathione ( p<5 × 10–4 ) and of glutathione status ( p<0.05 ) were observed , which returned to the run‐in levels in the subsequent wash‐out phase . The other biomarkers were not significantly modulated by the juice supplement . Intervention with the control juice did not result in reduction of oxidative damage . In conclusion , the fruit juice clearly reduces oxidative cell damage in healthy prob and Berry extracts possess antioxidant activity in cell free systems , whereas cell culture and animal experimental systems have produced mixed outcomes . Our aim was to investigate the effects of blackcurrant juice and specifically blackcurrant anthocyanins on the steady state level of oxidative DNA damage in mononuclear blood cells ( MNBC ) of humans , determined as str and breaks ( SB ) as well as endonuclease III ( Endo III ) and formamidopyrimidine DNA glycosylase ( Fpg ) sensitive sites by the comet assay . Fifty-seven healthy humans completed a 3-week controlled parallel intervention study with three groups r and omized to supplementation with blackcurrant juice , anthocyanin drink , or a control drink . The daily doses ranged from 475 to 1000ml/d according to body weight ( mean anthocyanin intakes in blackcurrant juice and anthocyanin drink groups were 397 and 365g/d , respectively ) and they were ingested during three daily meals while all volunteers were on the same strictly controlled low-flavonoid diet . Fasting venous blood sample s were obtained at baseline and after 3-week of supplementation . The baseline level of oxidative DNA damage was low ( e.g. less than 200 Fpg lesions per diploid cell ) . Fpg sensitive sites increased during the intervention within the blackcurrant juice group , whereas there were no differences between treatments in any of the DNA damage markers . In conclusion , this study shows that even large amounts of dietary antioxidants did not decrease the already low steady state levels of oxidative DNA damage in healthy adequately nourished humans The effects of different intake levels of vegetables and fruit ( VF ) on some cancer-relevant biomarkers such as DNA damage and oxidative stress were investigated . In a r and omized controlled trial , 64 nonsmoking male subjects were asked to consume a diet with 2 servings of VF/day for 4 wk . Then subjects were r and omly assigned to 1 of 3 groups with either a low ( 2 servings/day ) , medium ( 5 servings/day ) , or high ( 8 servings/day ) intake level of VF for another 4 wk . At the end of study , the plasma lutein , zeaxanthin , α -carotene , and β-carotene but not cryptoxanthin and lycopene concentrations were significantly higher in subjects consuming 8 servings/day than in those receiving 2 servings/day . Different levels of VF consumption and plasma carotenoid concentrations did not result in differences in the levels of endogenous DNA str and breaks , oxidative DNA damage , antigenotoxic capacity of lymphocytes , plasma markers for lipid peroxidation ( malondialdehyde , 8-iso-prostagl and in-F2α ) and antioxidant capacity [ trolox-equivalent antioxidant capacity assay ] . Thus , although consumption of 8 servings vs 2 servings/day of VF for 4 wk significantly increased the carotenoid level in plasma , there were no differences in DNA damage , lipid peroxidation , and antioxidant capacity markers among healthy , well-nourished , nonsmoking men |
2,430 | 30,289,768 | Conclusions : Based on the synthesized findings , three main factors that affect first time fathers ’ mental health and wellbeing during their transition to fatherhood were identified : the formation of the fatherhood identity , competing challenges of the new fatherhood role and negative feelings and fears relating to it .
The role restrictions and changes in lifestyle often result ed in feelings of stress , for which fathers used denial or escape activities , such as smoking , working longer hours or listening to music , as coping techniques .
Fathers wanted more guidance and support around the preparation for fatherhood , and partner relationship changes .
Better preparation for fatherhood , and support for couple relationships during the transition to parenthood could facilitate better experiences for new fathers , and contribute to better adjustments and mental wellbeing in new fathers | Objective : The aim of this systematic review was to identify and synthesize the best available evidence on first time fathers ’ experiences and needs in relation to their mental health and wellbeing during their transition to fatherhood .
Introduction : Men 's mental health and wellbeing during their transition to fatherhood is an important public health issue that is currently under- research ed from a qualitative perspective and poorly understood .
The phenomena of interest were their experiences and needs in relation to mental health and wellbeing during their transition to fatherhood , from commencement of pregnancy until one year after birth . | BACKGROUND A father who does not know how to assist the mother in relieving labor pains may experience a sense of powerlessness and anxiety . The objective of this study was to evaluate how an education program for expectant fathers who attended their partners ' labor and birth affected their anxiety . METHODS In a r and omized controlled trial , 87 expectant fathers who attended their pregnant partners through labor and birth at a hospital in central Taiwan were allocated by block r and omization to an experimental ( n = 45 ) and a control ( n = 42 ) group . The men completed their basic personal information , a childbirth expectations question naire , and a Trait Anxiety Inventory when they were recruited . Two hours after birth of their child , all the expectant fathers completed a State of Anxiety Inventory . RESULTS Our results showed no statistically significant differences between the experimental and control groups of fathers in trait anxiety and their prenatal childbirth expectations . After analysis of covariance ( ANCOVA ) was applied to correct for education level , sources of childbirth information , attendance at Lamaze childbirth classes , and childbirth expectations at baseline , the effect of the childbirth program was significant for the postnatal level of anxiety ( F = 3.38 , p = 0.001 ) . CONCLUSIONS The study findings justify the clinical implementation of a birth education program based on the self-efficacy theory as an effective means of reducing anxiety among expectant fathers This cross-sectional study aims to determine the prevalence and determinants of depressive symptoms in first-time expectant fathers during their partner ’s third trimester of pregnancy . As part of a prospect i ve study examining depressive symptoms in men over the first postnatal year , 622 men ( mean age = 34.3 years , ±5.0 years ) completed st and ardized online self-report question naires measuring depressed mood , physical activity , sleep quality , social support , marital adjustment , life events , financial stress , and demographics during their partner ’s third trimester of pregnancy . The Edinburgh Depression Scale was used to assess depressed mood . Partners also completed the Edinburgh Depression Scale in the third trimester . The results revealed that 13.3 % of expectant fathers exhibited elevated levels of depressive symptoms during their partner ’s third trimester of pregnancy . Significant independent factors associated with antenatal depressive symptoms in men were poorer sleep quality , family history of psychological difficulties , lower perceived social support , poorer marital satisfaction , more stressful life events in the preceding 6 months , greater number of financial stressors , and elevated maternal antenatal depressive symptoms . These findings highlight the importance of including fathers in the screening and early prevention efforts targeting depression during the transition to parenthood , which to date have largely focused only on women . Strategies to promote better sleep , manage stress , and mobilize social support may be important areas to address in interventions tailored to new fathers at risk for depression during the transition to parenthood OBJECTIVE to describe first-time-expectant fathers ' experiences of pregnancy . DESIGN an inductive method using narrative interview form and qualitative content text analysis . The text of the transcripts was coded and categorised . SETTING S AND PARTICIPANTS seven first-time-expectant fathers living in a multicultural industrial town in southern Sweden were interviewed individually when their partner was in the 38th to 39th week of pregnancy . MEASUREMENTS AND FINDINGS all the fathers-to-be experienced some psychological , social and /or physical change during the pregnancy . The main category , was ' time of transition ' . Eight categories were found under this . They were : ' feelings of unreality , ' insufficiency and inadequacy ' , ' exclusion ' , ' reality ' , ' social changes ' , ' physical changes ' , ' responsibility , and development ' . KEY CONCLUSION the fathers'-to-be special needs for support and encouragement during pregnancy may be as important as those of the mothers'-to-be . The caregiver needs to be as aware of and sensitive to these needs . However , before any interventions can be recommended more research is needed OBJECTIVE To examine the effects of early maternal and paternal depression on child expressive language at age 24 months and the role that parent-to-child reading may play in this pathway . PARTICIPANTS AND METHODS The 9-month and 24-month waves from a national prospect i ve study of children and their families , the Early Childhood Longitudinal Study - Birth Cohort ( ECLS-B ) , provided data on 4,109 two-parent families . Depressive symptoms were measured with a short form of the Center for Epidemiologic Studies Depression Scale ( CES-D ) . Parents reported on positive parent-infant interactions , child expressive vocabulary , and demographic and health information at child age 9 and 24 months . Linear regression was used to estimate associations between depression , parenting , and child vocabulary . Structural equation modeling was used to test the hypothesis that parent reading behavior mediates the parent depression to child vocabulary pathway . These models were adjusted for demographic indicators . RESULTS As previously reported from this national sample , 14 % of mothers and 10 % of fathers exhibited elevated levels of depressive symptoms at 9 months . For both mothers and fathers , depression at 9 months was negatively associated with contemporaneous parent-to-child reading . Only for fathers , however , was earlier depression associated with later reading to child and related child expressive vocabulary development . A model describing this pathway demonstrated a significant indirect pathway from depression to vocabulary via parent reading to child . CONCLUSIONS Depression is a significant problem among both mothers and fathers of young children , but has a more marked impact on the father 's reading to his child and , subsequently , the child 's language development Prenatally depressed women ( N=47 ) were r and omly assigned to a group that received massage twice weekly from their partners from 20 weeks gestation until the end of pregnancy or a control group . Self-reported leg pain , back pain , depression , anxiety and anger decreased more for the massaged pregnant women than for the control group women . In addition , the partners who massaged the pregnant women versus the control group partners reported less depressed mood , anxiety and anger across the course of the massage therapy period . Finally , scores on a relationship question naire improved more for both the women and the partners in the massage group . These data suggest that not only mood states but also relationships improve mutually when depressed pregnant women are massaged by their partners BACKGROUND The aim of this study was to explore the prospect i ve relationship between depressive symptoms and anxiety across pregnancy and the early postpartum . METHODS Participants ( N=207 ) completed the State-Trait Anxiety Inventory Trait subscale , Beck Depression Inventory , and social support and sleep quality measures at two time points during pregnancy and once in the early postpartum period . RESULTS After accounting for the relative stability of anxiety and depression over time , depressive symptoms earlier in pregnancy predicted higher levels of anxiety in late pregnancy and anxiety in late pregnancy predicted higher depressive symptomatology in the early postpartum . A bi-directional model of depression and anxiety in pregnancy was supported . LIMITATIONS Data were based on self-reports and participating women were predominantly tertiary educated with high family incomes . CONCLUSION Our findings suggest that depressive symptoms precede the development of higher levels of anxiety and that anxiety , even at non- clinical levels , can predict higher depressive symptoms . Clinicians are advised to screen for anxiety and depression concurrently during pregnancy OBJECTIVE To identify determinants of the initiation and duration of breastfeeding amongst Australian women . METHODS A prospect i ve cohort study of 556 women in Perth , Western Australia and 503 women from the Darling Downs area , Queensl and , Australia . RESULTS Breastfeeding at discharge was most strongly associated with perceived paternal support of breastfeeding with an adjusted odds ratio of 9.13 ( 95 % CI 4.83 - 17.26 ) , using multivariate logistic regression analysis . Duration of breastfeeding was most strongly associated with the length of time a mother intended to breastfeed with an adjusted relative risk of 4.18 ( 95 % CI 2.81 - 6.22 ) for > or = 4 months relative to < 4 months . CONCLUSIONS Interventions which aim to increase the length of time a woman intends to breastfeed , and which highlight the role of the father in successful breastfeeding , are recommended to help achieve recommended targets for breastfeeding initiation and duration BACKGROUND Although anxiety disorders are documented in the literature for new mothers ( but less so for fathers ) , rates of postpartum caseness tend to include only those with depression when diagnostic interviews or self-report measures vali date d on such interviews are used . This methodology therefore underestimates the true percentage of women and men who experience significant psychological difficulties postpartum . This has implication s for assessment , treatment and screening for postnatal mood disorders . METHOD Two studies were conducted on a total of 408 women and 356 men expecting their first child . They were recruited antenatally , and interviewed at 6 weeks postpartum using the Diagnostic Interview Schedule . DSM-IV criteria were applied to determine the presence since birth of depression ( major or minor ) , panic disorder , acute adjustment disorder with anxiety ( meeting the criteria for generalised anxiety disorder except for the duration criterion ) , and phobia . RESULTS The inclusion of diagnostic assessment for panic disorder and acute adjustment disorder with anxiety increased the rates of caseness by between 57 and 100 % for mothers , and 31 - 130 % for fathers , over the rates for major or minor depression . Inclusion of assessment for phobia further increased the rates of disorder in both sample s. Couple concordance rates were between 6.6 and 11.1 % , with no significant difference between rates for depressive or depressive and anxious caseness . For women , a previous history of an anxiety disorder appears to be a greater risk factor for a postnatal mood disorder ( i.e. depression or anxiety ) than a history of a depressive disorder . CONCLUSIONS These results clearly show the need to assess for both depression and anxiety in new and expectant parents , and we believe the term ' postnatal mood disorder ' ( PMD ) , rather than postnatal depression , more accurately reflects significant adjustment difficulties in new parents OBJECTIVE To examine incidence , trends , and correlates of parental depression in primary care from 0 to 12 years of child age . DESIGN Prospect i ve cohort study . SETTING Primary care records from more than 350 general practice s in The Health Improvement Network data base from 1993 to 2007 . PARTICIPANTS A total of 86 957 mother , father , and child triads identified in The Health Improvement Network data base by linking mothers and babies and then identifying an adult household man . Depressed parents were identified using Read code entries for depression and antidepressant prescriptions . MAIN EXPOSURES Child age , parental age at the birth , and area deprivation quintile . MAIN OUTCOME MEASURES Incidence rates for maternal and paternal episodes of depression . RESULTS Overall incidences of depression from the birth of the child up to age 12 years were 7.53 per 100 person-years for mothers and 2.69 per 100 person-years for fathers . Depression was highest in the first year post partum ( 13.93 and 3.56 per 100 person-years among mothers and fathers , respectively ) . By 12 years of child age , 39 % of mothers and 21 % of fathers had experienced an episode of depression . A history of depression , lower parental age at the birth of the child , and higher social deprivation were associated with a higher incidence of parental depression . CONCLUSIONS Parents are at highest risk for depression in the first year after the birth of their child . Parents with a history of depression , younger parents , and those from deprived areas are particularly vulnerable to depression . There is a need for appropriate recognition and management of parental depression in primary care |
2,431 | 28,421,600 | Effects on asthma control favoured the intervention but findings were not statistically significant .
Results from two studies with high levels of baseline smoking showed some promise for self-efficacy to stop smoking , but overall nicotine dependence and smoking-related knowledge were not significantly better in the intervention group .
Investigators did not report adverse events .
Although weak evidence suggests that lay-led and peer support interventions could lead to a small improvement in asthma-related quality of life for adolescents , benefits for asthma control , exacerbations and medication adherence remain unproven .
Current evidence is insufficient to reveal whether routine use of lay-led or peer support programmes is beneficial for adolescents receiving asthma care . | BACKGROUND Adolescents with asthma are at high risk of poor adherence with treatment .
This may be compounded by activities that worsen asthma , in particular smoking .
Additional support above and beyond routine care has the potential to encourage good self-management .
We wanted to find out whether sessions led by their peers or by lay leaders help to reduce these risks and improve asthma outcomes among adolescents .
OBJECTIVES To assess the safety and efficacy of lay-led and peer support interventions for adolescents with asthma . | Background Regular review and support for asthma self-management is promoted in guidelines . A r and omised controlled trial suggested that unscheduled health care usage was similar when patients were offered self management support by a lay-trainer or practice nurses . Methods Following the RCT , a costing study was undertaken using the trial data to account for the cost of delivery of the service under both strategies and the result ing impact on unscheduled healthcare ( measure of effectiveness ) in this trial . Results One year data ( n = 418 ) showed that 29 % ( 61/205 ) of the nurse group required unscheduled healthcare ( 177 events ) compared with 30.5 % ( 65/213 ) for lay-trainers ( 178 events).The training costs for the lay-trainers were greater than nurses ( £ 36 versus £ 18 respectively per patient , p<0.001 ) , however , the consultation cost for lay-trainers were lower than nurses ( £ 6 per patient versus £ 24 , p<0.001 ) . If the cost of unscheduled healthcare are accounted for then the costs of nurses is £ 161 , and £ 135 for lay-trainers ( mean difference £ 25 , [ 95 % CI = −£97 , £ 149 , p = 0.681 ] ) . The total costs ( delivery and unscheduled healthcare ) were £ 202 per patient for nurses versus £ 178 for lay-trainers , ( mean difference £ 24 , [ 95%CI = −£100 , £ 147 , p = 0.707 ] ) . Conclusions There were no significant differences in the cost of training and healthcare delivery between nurse and lay trainers , and no significant difference in the cost of unscheduled health care use OBJECTIVE To assess the outcomes of an education intervention for childhood asthma conducted by Australian Indigenous health care workers ( IHCWs ) . DESIGN AND SETTING R and omised controlled trial in a primary health care setting on Thursday Isl and and Horn Isl and , and in Bamaga , Torres Strait region of northern Australia , April 2005 to March 2007 . PARTICIPANTS 88 children , aged 1 - 17 years , with asthma diagnosed by a respiratory physician ( intervention group , 35 ; control group , 53 ; 98 % Indigenous children ) . INTERVENTIONS Children were r and omly allocated to : ( i ) three additional asthma education sessions with a trained IHCW , or ( ii ) no additional asthma education . Both groups were re-assessed at 12 months . MAIN OUTCOME MEASURES Primary endpoint : number of unscheduled visits to hospital or a doctor caused by asthma exacerbation . SECONDARY OUTCOMES measures of quality of life ( QoL ) and functional severity index ; asthma knowledge and underst and ing of asthma action plans ( AAPs ) ; and school days missed because of wheezing . RESULTS The groups were comparable at baseline ( except for asthma severity , which was adjusted for in the analysis ) . There were no significant differences in the primary outcome ( number of unscheduled medical visits for asthma ) . School children in the intervention group missed fewer school days because of wheezing ( 100 % < 7 days v 21 % of those in the control group missed 7 - 14 days ) . Significantly more carers in the intervention group could answer questions about asthma medication , knew where their AAP was kept ( 84 % v 56 % ) , and were able to describe the plan ( 67 % v 40 % ) . In both the intervention and control groups ( before- and -after comparison ) , there was a significantly reduced frequency of asthma exacerbations , as well as an improved QoL score and functional severity index , with no significant differences between the groups . CONCLUSIONS A community-based asthma education program conducted by trained IHCWs improves some important asthma outcomes in Indigenous children with asthma . TRIAL REGISTRATION Australian Clinical Trials Registry ACTRN012605000718640 OBJECTIVE To determine whether a parent-youth teamwork intervention improved medication adherence and related outcomes among youth with asthma . METHODS We used a r and omized clinical trial with 48 youth ( aged 9 - 15 years ) assigned to 1 of 3 groups : Teamwork Intervention ( TI ) , Asthma Education ( AE ) , or St and ard Care ( SC ) . Treatment occurred across 2 months , with a 3-month follow-up assessment . Adherence to inhaled corticosteroids was assessed via the MDILog-II . Parent-adolescent conflict , asthma functional severity , and spirometry assessment s were obtained pre-treatment , post-treatment , and on follow-up . Mixed linear model analysis was used to evaluate group and time effects for outcome measures . RESULTS TI group had significantly higher adherence and lower functional severity scores than AE or SC conditions , and lower parent-reported conflict and a trend for higher spirometry values compared with the SC group . CONCLUSIONS Results suggest support for the efficacy of TI for improving medication adherence as youth acquire more responsibility for their asthma management BACKGROUND Poor adherence to inhaled corticosteroids ( ICS ) is a critical risk factor contributing to asthma morbidity among low-income minority adolescents . OBJECTIVE This trial tested whether peer support group meetings and peer asthma messages delivered via mp3 players improved adherence to ICS . METHODS Low-income African American and /or Hispanic adolescents , ages 11 - 16 years old , with persistent asthma , and poor ( ≤ 48 % ) adherence to prescription ICS during the 3-week run-in were r and omized to intervention or attention control groups ( ATG ) for the 10-week treatment . During treatment , the intervention arm subjects participated in weekly coping peer group support sessions and received mp3 peer-recorded asthma messages that promoted adherence . The ATG participated in weekly meetings with a research assistant and received an equivalent number of mp3 physician-recorded asthma messages . Adherence was measured by using self-report and the Doser CT , an electronic dose counter . The primary outcome was the difference in adherence at 10 weeks between the 2 arms . RESULTS Thirty-four subjects were r and omized to each arm . At 10 weeks , no statistical difference in objective ly measured adherence could be detected between the 2 arms when adjusting for baseline adherence ( P = .929 ) . Adherence declined in both groups over the course of the active treatment period . In both study arms , self-reported adherence by participants was significantly higher than their objective ly measured adherence at week 10 ( P < .0001 ) . CONCLUSION Improving medication adherence in longitudinal studies is challenging . Peer support and mp3-delivered peer asthma messages may not be of sufficient dose to improve outcomes One hundred subjects with arthritis were r and omized into lay-taught , or professional-taught 12-h arthritis self-management courses , or a control group . Outcomes , knowledge , exercise , relaxation , disability , pain , and number of physician visits were measured aat baseline and 4 months . Professional-taught groups demonstrated greater knowledge gain while lay-taught groups had greater changes in relaxation ( p less than .01 ) and a tendency toward less disability . Although it is impossible to draw definitive conclusions , this study suggests that lay leaders can teach arthritis self-management courses with results similar to those achieved by professionals Background Estimates of asthma incidence and its possible determinants in adolescent population s have rarely been obtained using prospect i ve design s. We sought to identify socio-demographic and other patterns in the incidence of asthma among Canadian adolescents and to examine possible behavioural and environmental determinants of asthma incidence using longitudinal analyses . Methods We used data from the National Population Health Survey ( NPHS ) , a nationally representative longitudinal survey of Canadians . All persons aged 12–18 years without asthma at baseline were followed up to a maximum of 12 years . The outcome was a reported diagnosis of asthma during the follow-up period . Analyses were weighted to the population and bootstrapping procedures were used to estimate variances . Results Participants ( n = 956 ) represented 2,038,890 adolescents of whom 293,450 ( 14.4 % ) developed asthma over the 21,274,890 person-years of follow-up . Overall , the incidence of asthma was 10.2 per 1000 person-years . In adjusted Cox regression analysis , being female ( HR = 2.13 , 95 % CI = 1.26 - 3.62 , p = 0.005 ) and being exposed to passive smoking ( HR = 2.06 , 95 % CI = 1.27 - 3.34 , p = 0.003 ) were associated with the development of asthma while no statistically significant associations were identified for rural residence , being overweight , and other health behaviours . There was also an apparent cohort effect among girls where girls who were older at baseline reported being diagnosed with asthma more over the follow-up than their younger counterparts . This was not observed among males . Conclusions Asthma prevention initiatives for adolescents should target girls and focus on smoking exposures . The role that differential diagnostic patterns play in these observations should be investigated to more accurately assess the incidence of asthma OBJECTIVE : Because asthma disproportionately affects minorities , we evaluated the effects of parent mentors ( PMs ) on asthma outcomes in minority children . METHODS : This r and omized , controlled trial allocated minority asthmatic children to the PM intervention or traditional asthma care . Intervention families were assigned PMs ( experienced parents of asthmatic children who received specialized training ) . PMs met monthly with children and families at community sites , phoned parents monthly , and made home visits . Ten asthma outcomes and costs were monitored for 1 year . Outcomes were examined by using both intention-to-treat analyses and stratified analyses for high participants ( attending ≥25 % of community meetings and completing ≥50 % of PM phone interactions ) . RESULTS : Patients were r and omly assigned to PMs ( n = 112 ) or the control group ( n = 108 ) . In intention-to-treat analyses , intervention but not control children experienced significantly reduced rapid-breathing episodes , asthma exacerbations , and emergency department ( ED ) visits . High participants ( but not controls or low participants ) experienced significantly reduced wheezing , asthma exacerbations , and ED visits and improved parental efficacy in knowing when breathing problems are controllable at home . Mean reductions in missed parental work days were greater for high participants than controls . The average monthly cost per patient for the PM program was $ 60.42 , and net savings of $ 46.16 for high participants . CONCLUSIONS : For asthmatic minority children , PMs can reduce wheezing , asthma exacerbations , ED visits , and missed parental work days while improving parental self-efficacy . These outcomes are achieved at a reasonable cost and with net cost savings for high participants . PMs may be a promising , cost-effective means for reducing childhood asthma disparities OBJECTIVES We examined whether a home-based educational and environmental intervention delivered by lay health educators would improve asthma symptom control in inner-city children with asthma . METHODS Children 2 to 16 years of age with diagnosed asthma and at least 1 asthma-related hospitalization or 2 emergency visits in the prior year were r and omly assigned into 2 groups ( immediate and delayed intervention ) in a crossover study . Each group participated in the active phase ( intervention ) and the inactive phase . Outcomes included asthma symptoms , albuterol use , emergency department visits , hospitalizations , and trigger reduction . RESULTS A total of 264 primarily Black ( 94 % ) children were enrolled . The mean number of emergency visits decreased by 30 % and inpatient visits decreased by 53 % ( P < .001 ) after the intervention . Reductions were seen in pests , presence of carpets in bedrooms , and dust . Nighttime wheezing was significantly reduced after the intervention in both groups ( P < .001 ) . CONCLUSIONS Lay health educators effectively reduced asthma triggers and increased caregiver asthma knowledge , which result ed in reduced emergency department visits , hospitalizations , and asthma symptoms . The relationships formed between the caregivers and the lay health educators appeared to positively impact asthma outcomes in this disadvantaged population Abstract Objective : To determine the effect of a peer led programme for asthma education on quality of life and related morbidity in adolescents with asthma . Design : Cluster r and omised controlled trial . Setting : Six high schools in rural Australia . Participants : 272 students with recent wheeze , recruited from a cohort of 1515 students from two school years ( mean age 12.5 and 15.5 years ) ; 251 ( 92.3 % ) completed the study . Intervention : A structured education programme for peers comprising three steps ( the “ Triple A Program ” ) . Main outcome measures : Quality of life , school absenteeism , asthma attacks , and lung function . Results : When adjusted for year and sex , mean total quality of life scores showed significant improvement in the intervention than control group . Clinical ly important improvement in quality of life ( > 0.5 units ) occurred in 25 % of students with asthma in the intervention group compared with 12 % in the control group ( P=0.01 ) . The number needed to treat was 8 ( 95 % confidence interval 4.5 to 35.7 ) . The effect of the intervention was greatest in students in year 10 and in females . Significant improvements occurred in the activities domain ( 41 % v 28 % ) and in the emotions domain ( 39 % v 19 % ) in males in the intervention group . School absenteeism significantly decreased in the intervention group only . Asthma attacks at school increased in the control group only . Conclusion : The triple A programme leads to a clinical ly relevant improvement in quality of life and related morbidity in students with asthma . Wider dissemination of this programme in schools could play an important part in reducing the burden of asthma in Objectives : To determine whether well trained lay people could deliver asthma self-management education with comparable outcomes to that achieved by primary care based practice nurses . Design : R and omised equivalence trial . Setting : 39 general practice s in West London and North West Engl and . Participants : 567 patients with asthma who were on regular maintenance therapy . 15 lay educators were recruited and trained to deliver asthma self-management education . Intervention : An initial consultation of up to 45 min offered either by a lay educator or a practice based primary care nurse , followed by a second shorter face to face consultation and telephone follow-up for 1 year . Main outcome measures : Unscheduled need for healthcare . Secondary outcome measures : Patient satisfaction and need for courses of oral steroids . Results : 567 patients were r and omised to care by a nurse ( n = 287 ) or a lay educator ( n = 280 ) and 146 and 171 , respectively , attended the first face to face educational session . During the first two consultations , management changes were made in 35/146 patients seen by a practice nurse ( 24.0 % ) and in 56/171 patients ( 32.7 % ) seen by a lay educator . For 418/567 patients ( 73.7 % ) , we have 1 year data on use of unscheduled healthcare . Under an intention to treat approach , 61/205 patients ( 29.8 % ) in the nurse led group required unscheduled care compared with 65/213 ( 30.5 % ) in the lay led group ( 90 % CI for difference −8.1 % to 6.6 % ; 95 % CI for difference −9.5 % to 8.0 % ) . The 90 % CI contained the predetermined equivalence region ( −5 % to + 5 % ) giving an inconclusive result regarding the equivalence of the two approaches . Despite the fact that all patients had been prescribed regular maintenance therapy , 122/418 patients ( 29.2 % ) required courses of steroid tablets during the course of 1 year . Patient satisfaction following the initial face to face consultation was similar in both groups . Conclusions : It is possible to recruit and train lay educators to deliver a discrete area of respiratory care , with comparable outcomes to those seen by nurses . Trial registration number : Objectives : To determine the impact of a peer-led education program , developed in Australia , on health-related outcomes in high school students with asthma in Jordan . Methods : In this cluster-r and omized controlled trial , 4 high schools in Irbid , Jordan , were r and omly assigned to receive the Adolescent Asthma Action program or st and ard practice . Bilingual health workers trained 24 peer leaders from Year 11 to deliver asthma education to younger peers from Year 10 ( n = 92 ) , who in turn presented brief asthma skits to students in Years 8 and 9 ( n = 148 ) and to other members of the school community in the intervention schools . Students with asthma ( N = 261 ) in Years 8 , 9 , and 10 completed baseline surveys in December 2006 and 3 months after the intervention . Results : Students from the intervention group reported clinical ly significant improvements in health-related quality of life ( mean difference : 1.35 [ 95 % confidence interval : 1.04–1.76 ] ) , self-efficacy to resist smoking ( mean difference : 4.63 [ 95 % confidence interval : 2.93–6.35 ] ) , and knowledge of asthma self- management ( mean difference : 1.62 [ 95 % confidence interval : 1.15–2.19 ] ) compared with the control group . Conclusions : This trial demonstrated that the Adolescent Asthma Action program can be readily adapted to suit different cultures and context s. Adolescents in Jordan were successful in teaching their peers about asthma self-management and motivating them to avoid smoking . The findings revealed that peer education can be a useful strategy for health promotion programs in Jordanian schools when students are given the opportunity and training BACKGROUND The purpose of the present analysis is to examine changes in rural children 's asthma self-management after they received lay health educator (LHE)-delivered classes . METHODS Elementary schools were r and omly assigned to the treatment or attention-control condition and their participating students received either asthma education or general health promotion education , respectively . The triethnic sample was composed of 183 children ( 46 % Hispanic , 29.5 % non-Hispanic white , 22 % African American , and 2.6 % other categories ) who had a mean age of 8.78 years ( SD = 1.24 ) . The time frame from baseline to postintervention was 12 weeks . RESULTS Repeated measures analysis of variance found main effects in changes in scores for children 's asthma knowledge , asthma self-management , self-efficacy for managing asthma symptoms , and metered dose inhaler ( MDI ) technique and significant group interaction effects for the treatment intervention on the measures of children 's asthma knowledge , asthma self-management , and MDI technique . CONCLUSIONS The delivery of an asthma health education intervention by trained LHEs to school-aged children was an effective means for improving children 's knowledge and skills in asthma self-management CONTEXT Increasing urban asthma prevalence and severity is found among minority , underserved population s. Improving asthma self-management includes home management of complex medical protocol s as well as environmental trigger removal . OBJECTIVE To study the effectiveness of a low-cost approach to improve control of asthma symptoms in an urban population through lay educators who promote a generalized approach to asthma trigger avoidance in the bedrooms of children with asthma . DESIGN AND PATIENTS Prospect i ve , r and omized controlled trial with two arms : historical controls and matched controls for each subject . SUBJECTS Two-hundred-eighty-one patients living in an urban environment , r and omized to receive home visits only ( n = 128 ) or home visits with environmental remediation ( n = 153 ) . One-hundred-fifteen controls matched according to age , gender and ethnicity did not receive any intervention . INTERVENTIONS In-home education visits covered asthma physiology , asthma trigger avoidance and asthma management . Environmental remediation was conducted together with the caregiver . OUTCOMES Primary outcomes include length of hospital stay , number of emergency visits and number of sick visits . Secondary outcomes are symptom frequency , medication management and trigger reduction . RESULTS Both intervention groups experienced reduction of hospitalizations , emergency room visits , sick visits and asthma symptoms . Both groups showed outcomes significantly superior to the matched control group . Intervention effectively reduced the presence of rodents and carpet in home and increased the use of mattress and pillow covers . CONCLUSIONS This study shows that low-cost in-home education and environmental remediation improve outcomes for children with asthma . Lay educators can deliver effective asthma-specific education that results in improved asthma control BACKGROUND Children with chronic illnesses have a heightened risk for mental health problems . OBJECTIVES To develop , implement , and evaluate child outcomes of a 15-month , community-based , family-support intervention design ed to reduce risk for poor adjustment and mental health problems in children with 1 of 4 chronic illnesses ( diabetes mellitus , sickle cell anemia , cystic fibrosis , or moderate to severe asthma ) and their mothers . DESIGN R and omized , controlled clinical trial design with multiple measures of mental health based on both child and parent reports taken 1 year apart . SETTING Community-based intervention linked to subspecialty and general pediatric clinics and practice s in Baltimore , Md. PARTICIPANTS One hundred thirty-six mothers and children aged 7 to 11 years with diabetes mellitus , sickle cell anemia , cystic fibrosis , or moderate to severe asthma . INTERVENTION The program , provided by " experienced mothers " and child life specialists , included telephone contacts , face-to-face visits , and special family events . MAIN OUTCOME MEASURES Outcomes were measured using the following instruments : the Personal Adjustment and Role Skills Scale III , the Children 's Depression Inventory , the Revised Children 's Manifest Anxiety Scale , and the Self-Perception Profile for Children . RESULTS The experimental group 's mean adjustment score increased over the intervention period while the control group 's mean adjustment score decreased . Analysis of variance demonstrated that the intervention had a significant main effect on postintervention adjustment controlling for baseline scores ( P = .01 ) . Using a cutoff score indicating maladjustment , the percentage of experimental group children in the maladjustment range fell from 19 % at baseline to 10 % after the intervention ; the percentage of control group children in the maladjustment range rose from 15 % at baseline to 21 % after the intervention . The effect of the intervention was more pronounced for children who had low physical self-esteem than for those who had moderate to high physical self-esteem at the beginning of the program . CONCLUSIONS Our results demonstrate modest positive effects of a family support intervention in promoting the adjustment of children with selective chronic health conditions . Including child life specialists in a community-based intervention may be especially salient for children with chronic illnesses who have low physical self-esteem . The intervention had a similar outcome for all diagnostic groups , suggesting that it could be effective for children with any chronic illness and implemented in a variety of pediatric setting 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 This pilot study used a pretest and posttest design to examine the effect of a school-based intervention , Coping Skills Training , among teens with asthma ( N = 39 ) aged 14 to 18 years r and omly assigned to treatment and control groups from three midwestern high schools . Variables included asthma self-efficacy , social support , asthma-related quality of life , peak expiratory flow rate , asthma diary symptoms , and rescue medication usage . The treatment group scored significantly higher on self-efficacy ( p < .001 ) , activity-related quality of life ( p = .05 ) , and social support ( p < .001 ) compared with the control group after using ANCOVA to adjust for baseline scores . Significant improvements were also noted from pre- to posttest in the treatment group for self-efficacy ( p < .001 ) and quality of life ( p = .02 ) . This study indicates that Coping Skills Training is an important intervention for further study with teens with asthma PURPOSE To examine the impact of a peer-led asthma education program on asthma knowledge , attitudes , and quality of life among adolescents . METHODS A controlled trial was conducted in two girls ' high schools situated in an area of high unemployment and low socioeconomic status , and with a large non-English-speaking community . One school received the intervention and the second school acted as a comparison school . The Triple A ( Adolescent Asthma Action ) program was implemented in the intervention school and involved Year 11 student peer leaders instructing Year 10 students about asthma . The Year 10 students then developed asthma-related health messages into student asthma performances which were presented to the main student body . Outcomes were evaluated by question naire . RESULTS The Triple A program led to a significant improvement in asthma knowledge in both students with asthma and their peers . This effect occurred not only in students conducting the asthma performances ( Year 10 ) , but also in students in the audience ( Year 7 ) . Students held favorable attitudes toward asthma , with high degrees of tolerance and moderate internal locus of control . Asthma-related quality of life was not altered by the intervention . CONCLUSION Peer-led asthma education was well received in the high school setting and led to important improvements in asthma knowledge among students with asthma and their peers OBJECTIVE To evaluate the effectiveness of a peer-led asthma self-management program for adolescents . DESIGN R and omized controlled trial comparing a peer-led asthma program ( intervention group ) and a conventional adult-led asthma program ( control group ) . Each program was implemented at a full-day camp . SETTING A city and adjacent suburbs in upstate New York . PARTICIPANTS A total of 112 adolescents aged 13 to 17 years with persistent asthma . INTERVENTION A peer-led asthma self-management program implemented at a day camp . MAIN OUTCOME MEASURES The Child Attitude Toward Illness Scale and the Paediatric Asthma Quality of Life Question naire were administered at baseline and immediately and 3 , 6 , and 9 months after the intervention . Spirometry was conducted twice : before and 9 months after the intervention . RESULTS The intervention group reported more positive attitudes at 6 months ( mean difference , 4.11 ; 95 % confidence interval [ CI ] , 0.65 - 7.56 ) and higher quality of life at 6 months ( difference , 11.38 ; 95 % CI , 0.96 - 21.79 ) and 9 months ( difference , 12.97 ; 95 % CI , 3.46 - 22.48 ) than the control group . The intervention was found to be more beneficial to adolescents of male gender or low family income , as shown by greater improvement in positive attitudes toward asthma and quality of life than their counterparts . CONCLUSION An asthma self-management program led by peer leaders is a developmentally appropriate approach that can be effective in assisting adolescents with asthma in improving their attitudes and quality of life , particularly for males and those of low socioeconomic status . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01161225 Background : Pediatric summer camps are emerging as a means to increase social support and improve children 's attitudes about their chronic illness . Because of the high rate of camp attendance , it may be feasible to implement interventions within that setting ; however , it has yet to be determined what components of camp are beneficial . Objective : The objective of this pilot study was to determine the efficacy of a problem-solving intervention targeting disease management in improving psychosocial functioning of children with persistent asthma , over and above the benefits of participation in a pediatric summer camp . Methods : Fifty campers were r and omly assigned to receive camp plus a nightly problem-solving intervention activity or camp as usual . Changes in self-reported asthma knowledge and problem-solving skills and self- and parent-reported child self- and social competence health-related quality of life were assessed thrice : before camp , on the last day of camp , and 3-months post-camp . Results : There were no significant differences between the problem-solving intervention group and the camp as usual group in change across psychosocial variables from before camp to last day of camp or before camp to 3-months post-camp . Increases in asthma knowledge and problem-solving were found 3-months post-camp when groups were combined . Conclusions : Although support was found for improvements in disease knowledge and problem-solving skills after camp participation , there were no identified benefits to the problem-solving intervention . Children with asthma who participated in camp were functioning at a high level in terms of knowledge , problem-solving , and social and self-competence , suggesting that interventions may be more effective if targeted to patients with identified problems with disease management Abstract Objective : Puerto Rican children suffer disproportionately from asthma . Project CURA tested the efficacy of a community health worker ( CHW ) intervention to improve use of inhaled corticosteroids ( ICS ) and reduce home asthma triggers in Puerto Rican youth in Chicago . Methods : This study employed a behavioral r and omized controlled trial design with a community-based participatory research approach . Medications and technique were visually assessed ; adherence was determined using dose counters . Home triggers were assessed via self-report , visual inspection and salivary cotinine . All participants received education on core asthma topics and self-management skills . Participants in the CHW arm were offered home education by the CHW in four visits over four months . The attention control arm received four newsletters covering the same topics . Results : While most of the participants had uncontrolled persistent asthma , < 50 % had ICS at baseline . In the CHW arms , 67 % of participants received the full four-visit intervention . In the Elementary school cohort ( n = 51 ) , the CHW arm had lower odds of having an ICS ( OR = 0.2 ; p = 0.02 ) at 12-months ; no differences were seen in other outcomes between arms at any time point . The only significant treatment arm difference in the high school cohort ( n = 50 ) was in inhaler technique where the CHW arm performed 18.0 % more steps correct at five months ( p < 0.01 ) and 14.2 % more steps correct at 12 months ( p < 0.01 ) . Conclusions : While this CHW intervention did not increase the number of participants with ICS or reduce home asthma triggers , important lessons were learned including challenges to CHW intervention fidelity and the need for CHWs to partner with clinical providers Objectives .To assess the 1- and 2-year health status , health care utilization and self-efficacy outcomes for the Chronic Disease Self-Management Program ( CDSMP ) . The major hypothesis is that during the 2-year period CDSMP participants will experience improvements or less deterioration than expected in health status and reductions in health care utilization . Design .Longitudinal design as follow-up to a r and omized trial . Setting .Community . Participants .Eight hundred thirty-one participants 40 years and older with heart disease , lung disease , stroke , or arthritis participated in the CDSMP . At 1- and 2-year intervals respectively 82 % and 76 % of eligible participants completed data . Main Outcome Measures . Health status ( self-rated health , disability , social/role activities limitations , energy/fatigue , and health distress ) , health care utilization ( ER/outpatient visits , times hospitalized , and days in hospital ) , and perceived self-efficacy were measured . Main Results . Compared with baseline for each of the 2 years , ER/outpatient visits and health distress were reduced ( P < 0.05 ) . Self-efficacy improved ( P < 0.05 ) . The rate of increase is that which is expected in 1 year . There were no other significant changes . Conclusions .A low-cost program for promoting health self-management can improve elements of health status while reducing health care costs in population s with diverse chronic diseases The purpose of this study was to test the feasibility and short-term outcomes of Asthma : It 's a Family Affair ! , a school-based intervention for adolescents with asthma and their caregivers . Twenty-four ethnic minority families with a middle school student with asthma were r and omized to immediate intervention or no-treatment control . Intervention students received six group sessions on prevention and management of asthma . Caregivers received five group sessions teaching child-rearing skills to support the youth 's autonomy and asthma self-management . All students attended all sessions ; caregivers attended an average of three . Two months post-intervention , relative to controls , intervention caregivers reported better problem-solving with children . Intervention students were more responsible for carrying medication , took more prevention steps , and woke fewer nights from asthma . The intervention result ed in positive short-term changes in family relations , asthma management by students , and health status OBJECTIVE 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 . Frequent use of health-care services associated with pediatric asthma places substantial economic burden on families and society . The purpose of this study is to examine the cost-saving effects of a peer-led program through reduction in health-care utilization in comparison to an adult-led program . Methods . R and omly assigned adolescents ( 13–17 years ) participated in either peer-led ( n = 59 ) or adult-led ( n = 53 ) asthma self-management program . Health-care utilization data were collected at baseline and at 3- , 6- , and 9-months post-intervention . Negative binomial regression models were conducted to examine the effects of the peer-led program on health-care utilization . Net cost savings were estimated based on the differences in program costs and health-care utilization costs between groups . Results . Significant group differences were found in acute office visits and school clinic visits after controlling for race and socioeconomic status . The incidence rate of acute office visits was 80–82 % less for the peer-led group during follow-ups . The peer-led group was four to five times more likely to use school clinics due to asthma than the adult-led group during follow-ups . The non research cost of peer-led program per participant was lower than the adult-led program , $ 64 versus $ 99 , respectively . The net cost saving from the reduction in acute office visits and the lower program costs of the peer-led program was estimated $ 51.8 per person for a 3-month period . Conclusions . An asthma self-management program using peer leaders can potentially yield health-care cost savings through the reduction in acute office visits in comparison to a traditional program led by health-care professionals |
2,432 | 31,814,788 | Although the small number of trials and potential for treatment bias in the review , treatment with RUX was associated with improved QoL and PRO in PV patients intolerant or resistant to hydroxyurea | Polycythemia vera ( PV ) is a rare myeloproliferative neoplasm ( MPN ) associated with significant impairment in quality of life ( QoL ) due to disease-related symptoms and complications .
Assessment of disease burden constitutes st and ard monitoring of symptoms and response .
Conventional treatments for MPN , such as hydroxyurea , phlebotomy , or interferon , have not shown a significant impact in QoL or patient-reported outcomes ( PRO ) .
Ruxolitinib ( RUX ) is a JAK2 inhibitor approved for patients intolerant or resistant to hydroxyurea ( HA ) . | BACKGROUND Ruxolitinib , a selective inhibitor of Janus kinase ( JAK ) 1 and 2 , has clinical ly significant activity in myelofibrosis . METHODS In this double-blind trial , we r and omly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib ( 155 patients ) or placebo ( 154 patients ) . The primary end point was the proportion of patients with a reduction in spleen volume of 35 % or more at 24 weeks , assessed by means of magnetic resonance imaging . Secondary end points included the durability of response , changes in symptom burden ( assessed by the total symptom score ) , and overall survival . RESULTS The primary end point was reached in 41.9 % of patients in the ruxolitinib group as compared with 0.7 % in the placebo group ( P<0.001 ) . A reduction in spleen volume was maintained in patients who received ruxolitinib ; 67.0 % of the patients with a response had the response for 48 weeks or more . There was an improvement of 50 % or more in the total symptom score at 24 weeks in 45.9 % of patients who received ruxolitinib as compared with 5.3 % of patients who received placebo ( P<0.001 ) . Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group ( hazard ratio , 0.50 ; 95 % confidence interval , 0.25 to 0.98 ; P=0.04 ) . The rate of discontinuation of the study drug because of adverse events was 11.0 % in the ruxolitinib group and 10.6 % in the placebo group . Among patients who received ruxolitinib , anemia and thrombocytopenia were the most common adverse events , but they rarely led to discontinuation of the drug ( in one patient for each event ) . Two patients had transformation to acute myeloid leukemia ; both were in the ruxolitinib group . CONCLUSIONS Ruxolitinib , as compared with placebo , provided significant clinical benefits in patients with myelofibrosis by reducing spleen size , ameliorating debilitating myelofibrosis-related symptoms , and improving overall survival . These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period . ( Funded by Incyte ; COMFORT-I Clinical Trials.gov number , NCT00952289 . ) The r and omized , double‐blind , double‐dummy , phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide ( also termed hydroxyurea ) but reported PV‐related symptoms . Patients were r and omized 1:1 to ruxolitinib 10 mg BID ( n = 54 ) or hydroxycarbamide ( prer and omization dose/schedule ; n = 56 ) ; crossover to ruxolitinib was permitted after Week 16 . The primary endpoint , ≥50 % improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster ( TSS‐C ; sum of tiredness , itching , muscle aches , night sweats , and sweats while awake ) at Week 16 , was achieved by 43·4 % vs. 29·6 % of ruxolitinib‐ and hydroxycarbamide‐treated patients , respectively ( odds ratio , 1·82 ; 95 % confidence interval , 0·82–4·04 ; P = 0·139 ) . The primary endpoint was achieved by 34 % of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16 . In a post hoc analysis , the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores ( ratio ≤ 2 ) receiving ruxolitinib than hydroxycarbamide ( 47·4 % vs. 25·0 % ; P = 0·0346 ) . Ruxolitinib treatment after unblinding was associated with continued symptom score improvements . Adverse events were primarily grade s 1/2 with no unexpected safety signals . Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide , although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life . We sought to vali date a broadly applicable 18-item instrument ( Myeloproliferative Neoplasm Symptom Assessment Form [ MPN-SAF ] , coadministered with the Brief Fatigue Inventory ) to assess symptoms of myelofibrosis , essential thrombocythemia , and polycythemia vera among prospect i ve cohorts in the United States , Sweden , and Italy . A total of 402 MPN-SAF surveys were administered ( English [ 25 % ] , Italian [ 46 % ] , and Swedish [ 28 % ] ) in 161 patients with essential thrombocythemia , 145 patients with polycythemia vera , and 96 patients with myelofibrosis . Responses among the 3 administered language s showed great consistency after controlling for MPN subtype . Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Question naire-C30 . Enrolling physicians ' blinded opinion of patient symptoms ( 6 symptoms assessed ) were highly correlated with corresponding patients ' responses . Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated ( r > 0.5 , P < .001 ) and highly reproducible ( intraclass correlation coefficient > 0.7 ) . The MPN-SAF is a comprehensive and reliable instrument that is available in multiple language s to evaluate symptoms associated with all types of MPNs in clinical trials globally PURPOSE Myeloproliferative neoplasm ( MPN ) symptoms are troublesome to patients , and alleviation of this burden represents a paramount treatment objective in the development of MPN-directed therapies . We aim ed to assess the utility of an abbreviated symptom score for the most pertinent and representative MPN symptoms for subsequent serial use in assessing response to therapy . PATIENTS AND METHODS The Myeloproliferative Neoplasm Symptom Assessment Form total symptom score ( MPN-SAF TSS ) was calculated as the mean score for 10 items from two previously vali date d scoring systems . Questions focus on fatigue , concentration , early satiety , inactivity , night sweats , itching , bone pain , abdominal discomfort , weight loss , and fevers . RESULTS MPN-SAF TSS was calculable for 1,408 of 1,433 patients with MPNs who had a mean score of 21.2 ( st and ard deviation [ SD ] , 16.3 ) . MPN-SAF TSS results significantly differed among MPN disease subtypes ( P<.001 ) , with a mean of 18.7 ( SD , 15.3 ) , 21.8 ( SD , 16.3 ) , and 25.3 ( SD , 17.2 ) for patients with essential thrombocythemia , polycythemia vera , and myelofibrosis , respectively . The MPN-SAF TSS strongly correlated with overall quality of life ( QOL ; r=0.59 ; P<.001 ) and European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) functional scales ( all P<.001 and absolute r≥0.50 except social functioning r=0.48 ) . No significant trends were present when comparing therapy subgroups . The MPN-SAF TSS had excellent internal consistency ( Cronbach 's α=.83 ) . Factor analysis identified a single underlying construct , indicating that the MPN-SAF TSS is an appropriate , unified scoring method . CONCLUSION The MPN-SAF TSS is a concise , valid , and accurate assessment of MPN symptom burden with demonstrated clinical utility in the largest prospect i ve MPN symptom study to date . This new prospect i ve scoring method may be used to assess MPN symptom burden in both clinical practice and trial setting BACKGROUND Myelofibrosis is a Philadelphia chromosome – negative myeloproliferative neoplasm associated with cytopenias , splenomegaly , poor quality of life , and shortened survival . About half of patients with myelofibrosis carry a gain-of-function mutation in the Janus kinase 2 gene ( JAK2 V617F ) that contributes to the pathophysiology of the disease . INCB018424 is a potent and selective Janus kinase 1 ( JAK1 ) and JAK2 inhibitor . METHODS We conducted a phase 1−2 trial of INCB018424 in patients with JAK2 V617F−positive or JAK2 V617F−negative primary myelofibrosis , post – essential thrombocythemia myelofibrosis , or post – polycythemia vera myelofibrosis . RESULTS A total of 153 patients received INCB018424 for a median duration of more than 14.7 months . The initial dose-escalation phase established 25 mg twice daily or 100 mg once daily as maximum tolerated doses , on the basis of reversible thrombocytopenia . A dose-dependent suppression of phosphorylated signal transducer and activator of transcription 3 ( STAT3 ) , a marker of JAK signaling , was demonstrated in patients with wild-type JAK2 and in patients with the JAK2 V617F mutation . We studied additional doses and established that a 15-mg twice-daily starting dose , followed by individualized dose titration , was the most effective and safest dosing regimen . At this dose , 17 of 33 patients ( 52 % ) had a rapid objective response ( ≥50 % reduction of splenomegaly ) lasting for 12 months or more , and this therapy was associated with grade 3 or grade 4 adverse events ( mainly myelosuppression ) in less than 10 % of patients . Patients with debilitating symptoms , including weight loss , fatigue , night sweats , and pruritus , had rapid improvement . Clinical benefits were associated with a marked diminution of levels of circulating inflammatory cytokines that are commonly elevated in myelofibrosis . CONCLUSIONS INCB018424 was associated with marked and durable clinical benefits in patients with myelofibrosis for whom no approved therapies existed . ( Funded by Incyte ; Clinical Trials.gov number , NCT00509899 . BACKGROUND Ruxolitinib , a Janus kinase ( JAK ) 1 and 2 inhibitor , was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study . We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus st and ard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea . METHODS We r and omly assigned phlebotomy-dependent patients with splenomegaly , in a 1:1 ratio , to receive ruxolitinib ( 110 patients ) or st and ard therapy ( 112 patients ) . The primary end point was both hematocrit control through week 32 and at least a 35 % reduction in spleen volume at week 32 , as assessed by means of imaging . RESULTS The primary end point was achieved in 21 % of the patients in the ruxolitinib group versus 1 % of those in the st and ard-therapy group ( P<0.001 ) . Hematocrit control was achieved in 60 % of patients receiving ruxolitinib and 20 % of those receiving st and ard therapy ; 38 % and 1 % of patients in the two groups , respectively , had at least a 35 % reduction in spleen volume . A complete hematologic remission was achieved in 24 % of patients in the ruxolitinib group and 9 % of those in the st and ard-therapy group ( P=0.003 ) ; 49 % versus 5 % had at least a 50 % reduction in the total symptom score at week 32 . In the ruxolitinib group , grade 3 or 4 anemia occurred in 2 % of patients , and grade 3 or 4 thrombocytopenia occurred in 5 % ; the corresponding percentages in the st and ard-therapy group were 0 % and 4 % . Herpes zoster infection was reported in 6 % of patients in the ruxolitinib group and 0 % of those in the st and ard-therapy group ( grade 1 or 2 in all cases ) . Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving st and ard therapy . CONCLUSIONS In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea , ruxolitinib was superior to st and ard therapy in controlling the hematocrit , reducing the spleen volume , and improving symptoms associated with polycythemia vera . ( Funded by Incyte and others ; RESPONSE Clinical Trials.gov number , NCT01243944 . ) BACKGROUND Treatment options for myelofibrosis are limited . We evaluated the efficacy and safety of ruxolitinib , a potent and selective Janus kinase ( JAK ) 1 and 2 inhibitor , as compared with the best available therapy , in patients with myelofibrosis . METHODS We assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis , post-polycythemia vera myelofibrosis , or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy . The primary end point and key secondary end point of the study were the percentage of patients with at least a 35 % reduction in spleen volume at week 48 and at week 24 , respectively , as assessed with the use of magnetic resonance imaging or computed tomography . RESULTS A total of 28 % of the patients in the ruxolitinib group had at least a 35 % reduction in spleen volume at week 48 , as compared with 0 % in the group receiving the best available therapy ( P<0.001 ) ; the corresponding percentages at week 24 were 32 % and 0 % ( P<0.001 ) . At 48 weeks , the mean palpable spleen length had decreased by 56 % with ruxolitinib but had increased by 4 % with the best available therapy . The median duration of response with ruxolitinib was not reached , with 80 % of patients still having a response at a median follow-up of 12 months . Patients in the ruxolitinib group had an improvement in overall quality -of-life measures and a reduction in symptoms associated with myelofibrosis . The most common hematologic abnormalities of grade 3 or higher in either group were thrombocytopenia and anemia , which were managed with a dose reduction , interruption of treatment , or transfusion . One patient in each group discontinued treatment owing to thrombocytopenia , and none discontinued owing to anemia . Nonhematologic adverse events were rare and mostly grade 1 or 2 . Two cases of acute myeloid leukemia were reported with the best available therapy . CONCLUSIONS Continuous ruxolitinib therapy , as compared with the best available therapy , was associated with marked and durable reductions in splenomegaly and disease-related symptoms , improvements in role functioning and quality of life , and modest toxic effects . An influence on overall survival has not yet been shown . ( Funded by Novartis Pharmaceuticals ; Clinical Trials.gov number , NCT00934544 . ) Polycythemia vera (PV)‐related symptoms may not be adequately controlled with conventional therapy . This current analysis of the RESPONSE trial evaluated the effects of ruxolitinib compared with st and ard therapy on quality of life ( QoL ) and symptoms in patients with PV who were hydroxyurea resistant/intolerant Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in patients with primary and secondary myelofibrosis . This phase 2 , open-label , r and omized study evaluated the efficacy and safety of oral once-daily momelotinib ( 100 mg and 200 mg ) for the treatment of polycythemia vera ( PV ) and essential thrombocythemia ( ET ) . The primary endpoint for PV was overall response rate ( ORR ) , defined as the proportion of patients with hematocrit < 45 % , white blood cell count < 10 × 109/L , platelet count ≤400 × 109/L , and resolution of palpable splenomegaly , each lasting ≥4 weeks . The definition of ORR for ET excluded the hematocrit component . A total of 39 patients ( 28 PV , 11 ET ) were enrolled , with 28 patients receiving ≥12 weeks of treatment . The study was terminated due to limited efficacy . Two patients ( ORR 5.1 % ) met the primary efficacy endpoint ( both PV 200 mg ) . Predose plasma levels of momelotinib were stable over time . A total of 31 ( 79.5 % ) patients experienced momelotinib-related adverse events ( AEs ) , the most frequent being headache ( 23.1 % ) , dizziness ( 18.0 % ) , somnolence ( 15.4 % ) , nausea ( 15.4 % ) , and fatigue ( 15.4 % ) . Three patients experienced serious AEs ( 7.7 % ) , with 1 considered related to momelotinib ( dyspnea ) . Peripheral neuropathy occurred in 7 ( 17.9 % ) patients ( 4 PV , 3 ET ) Quality of life ( QoL ) in patients with myelofibrosis ( MF ) is severely compromised by severe constitutional symptoms ( i.e. fatigue , night sweats , fever , weight loss ) , pruritus , and symptoms from frequently massive hepatosplenomegaly . Given that no current instrument of patient reported outcomes ( PRO ) exists that covers the unique spectrum of symptomatology seen in MF patients , we sought to develop a new PRO instrument for MF patients for use in therapeutic clinical trials . Utilizing data from an international Internet-based survey of 458 patients with MF we created a 20-item instrument ( MFSAF : Myelofibrosis Symptom Assessment Form ) which measures the symptoms reported by > 10 % of MF patients and includes a measure of QoL. We subsequently vali date d the MFSAF in a prospect i ve trial of MF patients involving patient and provider feedback , as well as comparison to other vali date d instruments used in cancer patients . The MFSAF results were highly correlated with other instruments , judged comprehensive and underst and able by patients , and should be considered for evaluation of MF symptoms in therapeutic trials BACKGROUND In the pivotal RESPONSE study , ruxolitinib , a Janus kinase (JAK)1 and JAK2 inhibitor , was superior to best available therapy at controlling haematocrit and improving splenomegaly and symptoms in patients with polycythaemia vera with splenomegaly who were inadequately controlled with hydroxyurea . In this study , we assessed the efficacy and safety of ruxolitinib in controlling disease in patients with polycythaemia vera without splenomegaly who need second-line therapy . METHODS RESPONSE-2 is a r and omised , open-label , phase 3b study assessing ruxolitinib versus best available therapy in patients with polycythaemia vera done in 48 hospitals or clinics across 12 countries in Asia , Australia , Europe , and North America . Eligible patients ( aged ≥18 years ) with polycythaemia vera , no palpable splenomegaly , and hydroxyurea resistance or intolerance were stratified by their hydroxyurea therapy status ( resistance vs intolerance ) and r and omly assigned ( 1:1 ) by an interactive response technology provider using a vali date d system to receive either oral ruxolitinib 10 mg twice daily or investigator-selected best available therapy ( hydroxyurea [ at the maximum tolerated dose ] , interferon or pegylated interferon , pipobroman , anagrelide , approved immunomodulators , or no cytoreductive treatment ) . Investigators and patients were not masked to treatment assignment ; however , the study sponsor was masked to treatment assignment until data base lock . The primary endpoint was the proportion of patients achieving haematocrit control at week 28 . Analyses were done according to an intention-to-treat principle , including data from all patients r and omly assigned to treatment . This study is registered with Clinical Trials.gov ( NCT02038036 ) and is ongoing but not recruiting patients . FINDINGS Between March 25 , 2014 , and Feb 11 , 2015 , of 173 patients assessed for eligibility , 74 patients were r and omly assigned to receive ruxolitinib and 75 to receive best available therapy . At r and omisation , best available therapy included hydroxyurea ( 37 [ 49 % ] of 75 in the best available therapy group ) , interferon or pegylated interferon ( ten [ 13 % ] of 75 ) , pipobroman ( five [ 7 % ] of 75 ) , lenalidomide ( one [ 1 % ] of 75 ) , no treatment ( 21 [ 28 % ] of 75 ) , and other ( one [ 1 % ] of 75 ) . Haematocrit control was achieved in 46 ( 62 % ) of 74 ruxolitinib-treated patients versus 14 ( 19 % ) of 75 patients who received best available therapy ( odds ratio 7·28 [ 95 % CI 3·43 - 15·45 ] ; p<0·0001 ) . The most frequent haematological adverse events of any grade were anaemia ( ten [ 14 % ] of 74 in the ruxolitinib group vs two [ 3 % ] of 75 in the best available therapy group ) and thrombocytopenia ( two [ 3 % ] vs six [ 8 % ] ) . No cases of grade 3 - 4 anaemia or thrombocytopenia occurred with ruxolitinib ; one patient ( 1 % ) reported grade 3 - 4 anaemia and three patients ( 4 % ) reported grade 3 - 4 thrombocytopenia in the group receiving best available therapy . Frequent grade 3 - 4 non-haematological adverse events were hypertension ( five [ 7 % ] of 74 vs three [ 4 % ] of 75 ) and pruritus ( 0 of 74 vs two [ 3 % ] of 75 ) . Serious adverse events occurring in more than 2 % of patients in either group , irrespective of cause , included thrombocytopenia ( none in the ruxolitinib group vs two [ 3 % ] of 75 in the best available therapy group ) and angina pectoris ( two [ 3 % ] of 74 in the ruxolitinib group vs none in the best available therapy group ) . Two deaths occurred , both in the best available therapy group . INTERPRETATION RESPONSE-2 met its primary endpoint . The findings of this study indicate that ruxolitinib could be considered a st and ard of care for second-line therapy in this post-hydroxyurea patient population . FUNDING Novartis Studies have shown that the clinical impact of Janus kinase 2 ( JAK2 ) inhibitors in primary myelofibrosis patients is due to the regulation of cytokine levels , suggesting that cytokine profiles might play a critical role in myeloproliferative neoplasms ( MPNs ) physiopathology . In this study , we compared the plasma cytokine profiles of polycythemia vera ( PV ) patients and essential thrombocythemia ( ET ) patients as a function of their JAK2 V617F status and the presence of thrombohemorrhagic complications . Using a multiplex cytokine assay , cytokine measurements were taken of the plasma of 17 PV patients and 21 ET patients . Twenty-two of these patients ( 10 PV and 12 ET ) experienced at least one thrombohemorrhagic manifestation before diagnosis . We showed that cytokine levels were significantly increased in PV and ET patients compared with normal values and that several positive correlations existed between the cytokine concentrations and the biological parameters in each MPN . The comparison between the cytokine profiles of ET and PV patients showed a statistically significant increase of interleukin (IL)-4 , IL-8 , granulocyte macrophage-colony stimulating factor , interferon -γ , monocyte chemotactic protein -1 , platelet derived growth factor-BB , and vascular endothelial growth factor in the ET group . Only tumor necrosis factor-α and platelet derived growth factor-BB were specifically impacted by the JAK2 V617F status of the PV and ET patients , respectively , suggesting that there are both JAK2 V617F-driven and JAK2 V617F-independent inflammatory responses in MPNs . We also showed that the subgroup of PV patients with vascular complications displayed significantly different concentrations of IL-12(p70 ) and granulocyte macrophage-colony stimulating factor compared with patients without vascular complications . Altogether , these data suggest that cytokine measurement might be useful for the clinical and therapeutic stratification of PV and ET patients IMPORTANCE Myelofibrosis ( MF ) is a BCR-ABL-negative myeloproliferative neoplasm characterized by anemia , splenomegaly , debilitating constitutional symptoms , and shortened survival . Fedratinib , a JAK2-selective inhibitor , previously demonstrated clinical ly beneficial activity in patients with MF in early-phase trials . OBJECTIVE To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary ( post-polycythemia vera or post-essential thrombocythemia ) MF . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients ( ≥18 years of age ) with intermediate-2 or high-risk primary MF , post-polycythemia vera MF , or post-essential thrombocythemia MF were r and omly assigned between December 2011 and September 2012 to once-daily oral fedratinib , at a dose of 400 mg or 500 mg , or placebo , for at least 6 consecutive 4-week cycles . MAIN OUTCOMES AND MEASURES The primary end point was spleen response ( ≥35 % reduction in spleen volume from baseline as determined by magnetic resonance imaging or computed tomography ) at week 24 and confirmed 4 weeks later . The main secondary end point was symptom response ( ≥50 % reduction in total symptom score , assessed using the modified Myelofibrosis Symptom Assessment Form ) . RESULTS The primary end point was achieved by 35 of 96 ( 36 % [ 95 % CI , 27%-46 % ] ) and 39 of 97 ( 40 % [ 95 % CI , 30%-50 % ] ) patients in the fedratinib 400-mg and 500-mg groups , vs 1 of 96 ( 1 % [ 95 % CI , 0%-3 % ] ) in the placebo group ( P < .001 ) . Symptom response rates at week 24 were 33 of 91 ( 36 % [ 95 % CI , 26%-46 % ] ) , 31 of 91 ( 34 % [ 95 % CI , 24%-44 % ] ) , and 6 of 85 ( 7 % [ 95 % CI , 2%-13 % ] ) in the fedratinib 400-mg , 500-mg , and placebo groups , respectively ( P < .001 ) . Common adverse events with fedratinib treatment were anemia , gastrointestinal symptoms , and increased levels of liver transaminases , serum creatinine , and pancreatic enzymes . Encephalopathy was reported in 4 women who received fedratinib 500 mg/d . A diagnosis of Wernicke encephalopathy was supported by magnetic resonance imaging in 3 cases and suspected clinical ly in 1 case . CONCLUSIONS AND RELEVANCE Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF . These benefits were accompanied by toxic effects in some patients , the most important being encephalopathy of unknown mechanism . Clinical development of fedratinib was subsequently discontinued . TRIAL REGISTRATION clinical trials.gov identifier : NCT01437787 PURPOSE To assess the effects of ruxolitinib on symptom burden and quality of life ( QoL ) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form ( MFSAF ) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis . PATIENTS AND METHODS COMFORT-I ( Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment-I ) is a double-blind , placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis . Exploratory analyses were conducted on the following patient-reported outcomes ( PROs ) assessment s : modified MFSAF v2.0 ( individual symptoms and Total Symptom Score [ TSS ] ) , European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ( EORTC QLQ-C30 ) , Patient Reported Outcomes Measurement Information System ( PROMIS ) Fatigue Scale , and Patient Global Impression of Change ( PGIC ) . RESULTS Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms , although patients receiving placebo experienced worsening ( P < .001 ) . The majority ( 91 % ) of ruxolitinib-treated patients design ated as ≥ 50 % TSS responders ( ≥ 50 % TSS improvement ) self-reported their condition as either " Much improved " or " Very much improved " on the PGIC . These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo , who experienced worsening on these measures ( P ≤ .0135 ) . Ruxolitinib-treated patients with a lesser degree of symptom improvement ( < 50 % TSS responders ) also achieved improvements over placebo on these measures . The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS , PGIC , PROMIS Fatigue Scale , and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35 % reduction in spleen volume experienced the greatest improvements in these PROs . CONCLUSION Ruxolitinib-treated patients achieved clinical ly meaningful improvements in myelofibrosis-related symptoms and QoL , but patients receiving placebo reported worsening of symptoms and other PROs Micro‐ Abstract Data from REVEAL ( Prospect i ve Observational Study of Patients With Polycythemia Vera in US Clinical Practice s ; n = 2309 ) , the first study of its kind , confirm that many patients experience quality of life and work productivity impairments that might negatively affect their lives . In the future , longitudinal data from REVEAL will be important for evaluating how such burdens change over time . Background Patients with polycythemia vera ( PV ) often experience symptoms that adversely affect their quality of life ( QoL ) . The ongoing , prospect i ve , observational REVEAL ( Prospect i ve Observational Study of Patients With Polycythemia Vera in US Clinical Practice s ) study was design ed to collect contemporary data regarding burden of disease , clinical management , patient‐reported outcomes ( PROs ) , and health care re source utilization from adult patients with PV in the United States . Patients and Methods Data on PROs were collected at enrollment using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score ( MPN‐SAF TSS ; range , 0‐100 ) ; the European Organization for Research and Treatment of Cancer – Core Quality of Life Question naire , version 3.0 ( EORTC QLQ‐C30 ; range , 0‐100 ) ; and the Work Productivity and Activity Impairment Question naire – Specific Health Problem ( WPAI‐SHP ; range , 0%‐100 % ) . Results Among 2309 patients , mean ( SD ) disease duration was 5.8 ( 6.1 ) years and Charlson Comorbidity Index was 3.4 ( 0.8 ) ; 54.0 % ( 1247/2309 ) were male . Mean ( SD ) MPN‐SAF TSS was 18.8 ( 15.5 ) . The most common symptoms were fatigue ( 80.1 % [ 1844/2302 ] ) , early satiety ( 60.9 % [ 1402/2302 ] ) , and inactivity ( 57.6 % [ 1324/2302 ] ) . The most common severe symptoms were fatigue ( 16.8 % [ 387/2302 ] ) , itching ( 13.4 % [ 308/2302 ] ) , and inactivity ( 11.8 % [ 271/2302 ] ) . The mean ( SD ) EORTC QLQ‐C30 global health status/QoL score was 73.1 ( 23.2 ) : mean functional subscale scores ranged from 80.5 ( 23.9 ) for cognitive functioning to 85.7 ( 24.6 ) for social functioning . The mean WPAI‐SHP activity impairment score was 19.7 % ( n = 2300 ) . Employed patients had mean WPAI‐SHP scores for absenteeism , presenteeism , and overall work impairment of 3.2 % ( n = 810 ) , 12.1 % ( n = 807 ) , and 13.4 % ( n = 802 ) , respectively . Conclusion These data confirm that many patients with PV experience symptoms , QoL impairments , and work productivity impairments that negatively affect their lives . Longitudinal data from REVEAL will be important for evaluating how PROs change over time in these patients |
2,433 | 28,734,045 | Light therapy can relieve BD , improve sleep quality , and alleviate symptoms of depression for cognitively impaired persons | OBJECTIVES To explore the effects of light therapy on behavioral disturbances ( BDs ) , sleep quality , and depression . | This study examined the effects of bright light exposure on three measures of depression and four measures of agitation in persons with dementia residing in long-term care . Using a r and omized controlled design , participants were r and omly assigned to receive either bright light ( n = 30 ) or low intensity light ( n = 30 ) for eight weeks . Bright light exposure was associated with significant improvement in depression and agitation , while participants receiving low intensity light displayed higher levels of depression and agitation or no significant change . Findings support the use of bright light exposure to reduce depression and agitation in this population BACKGROUND Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer 's disease ( AD ) . Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes . In most institutional environments , light levels are very low and may not be sufficient to enable the circadian clock to entrain to the 24-hour day . The purpose of this r and omized , placebo-controlled , clinical trial was to test the effectiveness of morning bright light therapy in reducing rest-activity ( circadian ) disruption in institutionalized patients with severe AD . METHOD Subjects ( n = 46 , mean age 84 years ) meeting the NINCDS-ADRDA ( National Institute of Neurological and Communicative Disorders and Stroke -- the Alzheimer 's Disease and Related Disorders Association ) AD diagnostic criteria were recruited from two large , skilled nursing facilities in San Francisco , California . The experimental group received one hour ( 09:30 - 10:30 ) of bright light exposure ( > or = 2500 lux in gaze direction ) Monday through Friday for 10 weeks . The control group received usual indoor light ( 150 - 200 lux ) . Nighttime sleep efficiency , sleep time , wake time and number of awakenings and daytime wake time were assessed using actigraphy . Circadian rhythm parameters were also determined from the actigraphic data using cosinor analysis and nonparametric techniques . Repeated measures analysis of variance ( ANOVA ) was used to test the primary study hypotheses . RESULTS AND CONCLUSION Although significant improvements were found in subjects with aberrant timing of their rest-activity rhythm , morning bright light exposure did not induce an overall improvement in measures of sleep or the rest-activity in all treated as compared to control subjects . The results indicate that only subjects with the most impaired rest-activity rhythm respond significantly and positively to a brief ( one hour ) light intervention We investigated whether low intensity dawn-dusk simulation ( DDS ) , a ' naturalistic ' form of light therapy design ed to embed sleep in its accustomed phase , could improve the disturbed circadian rest-activity cycle , nocturnal sleep and and /or cognitive functions in dementia . A protocol of 3 weeks each of baseline , treatment and follow-up was completed by 13 patients ( 85yr old+/-5yr , MMSE 14+/-5 ; n=9 DDS versus n=4 ' placebo ' dim red light ) who wore an activity/lux monitor throughout . There were no significant changes in clinical or cognitive status , nor modification of circadian stability or amplitude characteristics of the rest-activity cycle . However , two aspects of sleep responded to DDS but not to dim red light . The main sleep episode was 1:14h earlier during treatment ( p=0.03 ) compared with before and after DDS . With respect to actimetry-determined sleep variables , the DDS group tended to have shortened ' sleep latency ' , longer ' sleep duration ' , more nocturnal immobility and less nocturnal activity than the dim red group ( p<0.1 ) . In parallel , nighttime light exposure tended to be reduced ( p=0.07 ) . These promising findings -after only 3 weeks of light treatment in elderly patients with advanced dementia-suggest that the circadian timing system remains functionally responsive even to low intensity DDS light . Increasing zeitgeber strength is an important strategy for improving sleep quality and timing in dementia , and DDS light therapy may provide one of the appropriate means to do so OBJECTIVE Preliminary data suggest that morning bright light might improve symptoms of agitation , a serious problem in patients with dementia . The authors exp and on an earlier pilot study by evaluating the effect of bright light therapy on agitated behavior in a large sample of patients with severe dementia . METHODS Ninety-two patients were r and omly assigned to morning bright light , morning dim red light , or evening bright light . Agitation was rated by research staff who observed the patients every 15 minutes throughout the treatment period and by caregivers at one time-point before and one time-point after treatment . RESULTS Morning bright light delayed the acrophase of the agitation rhythm by over 1.5 hours . Bright light was associated with improved caregivers ' ratings but had little effect on observational ratings of agitation . CONCLUSION Although the result that light shifted the peak of the agitated behavior might be generalizable to patients with milder forms of AD , the fact that agitation was not ameliorated might not be . Because the suprachiasmatic nucleus ( SCN ) of patients with severe AD is likely to be more degenerated , and the circadian activity rhythms deteriorate as the disease progresses , it is still possible that patients with more intact SCNs , that is , patients with mild or moderate AD , might benefit from light treatment even more than those with severe AD OBJECTIVES To test the effects of walking , light exposure , and a combination intervention ( walking , light , and sleep education ) on the sleep of persons with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial with blinded assessors . SETTING Independent community living . PARTICIPANTS One hundred thirty-two people with AD and their in-home caregivers . INTERVENTIONS Participants were r and omly assigned to one of three active treatments ( walking , light , combination treatment ) or contact control and received three or six in-home visits . MEASUREMENTS Primary outcomes were participant total wake time based on wrist actigraphy and caregiver ratings of participant sleep quality on the Sleep Disorders Inventory ( SDI ) . Secondary sleep outcomes included additional actigraphic measurements of sleep percentage , number of awakenings , and total sleep time . RESULTS Participants in walking ( P=.05 ) , light ( P=.04 ) , and combination treatment ( P=.01 ) had significantly greater improvements in total wake time at posttest ( effect size 0.51 - 0.63 ) than controls but no significant improvement on the SDI . Moderate effect size improvements in actigraphic sleep percentage were also observed in active treatment participants . There were no significant differences between the active treatment groups and no group differences for any sleep outcomes at 6 months . Participants with better adherence ( 4 d/wk ) to walking and light exposure recommendations had significantly less total wake time ( P=.006 ) and better sleep efficiency ( P=.005 ) at posttest than those with poorer adherence . CONCLUSION Walking , light exposure , and their combination are potentially effective treatments for improving sleep in community-dwelling persons with AD , but consistent adherence to treatment recommendations is required Sleep disorders are problematic for persons with dementia and their family caregivers . This r and omized controlled trial with crossover evaluated the effects of an innovative blue-white light therapy on 17 pairs of home-dwelling persons with dementia and their caregivers . Subjects with dementia received blue-white light and control ( ‘ red-yellow ’ light ) for six weeks separated by a four-week washout . Neither actigraphic nor most self-reported sleep measures significantly differed for subjects with dementia . For caregivers , both sleep and role strain improved . No evidence of retinal light toxicity was observed . Six weeks of modest doses of blue-white light appear to improve sleep in caregivers but not in persons with dementia . Greater or prolonged circadian stimulation may be needed to determine if light is an effective treatment for persons with dementia Neuropsychiatric behaviors are common in people with Alzheimer 's disease ( AD ) and make both professional and lay caregiving difficult . Light therapy has been somewhat successful in ameliorating disruptive behaviors . This r and omized trial tested the effects of morning or afternoon bright light exposure compared with usual indoor light on the presence , frequency , severity , and occupational disruptiveness of neuropsychiatric behaviors in nursing home residents with AD . Light was administered for 1 hr daily ( Monday-Friday ) for 10 weeks . The Neuropsychiatric Inventory — Nursing Home was used to assess behavior at baseline and end of the intervention . Analyses revealed statistically significant differences between groups on agitation/aggression , depression/dysphoria , aberrant motor behavior , and appetite/eating disorders . The magnitude of change was small and may not represent clinical ly significant findings . Agitation/aggression and nighttime behaviors commonly occurred and were highly correlated with occupational disruptiveness . Interventions that decrease the presence and /or severity of neuropsychiatric behaviors have the potential to significantly decrease caregiver burden BACKGROUND Agitation is common in people with dementia , is distressing to patients and stressful to their carers . Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate . Alternatives to drug treatment for agitation should be sought . The study aim ed to assess the effects of bright light therapy on agitation and sleep in people with dementia . METHODS A single center r and omized controlled trial of bright light therapy versus st and ard light was carried out . The study was completed prior to the m and atory registration of r and omized controls on the clinical trials registry data base and , owing to delays in writing up , retrospective registration was not completed . RESULTS There was limited evidence of reduction in agitation in people on active treatment , sleep was improved and a suggestion of greater efficacy in the winter months . CONCLUSIONS Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated OBJECTIVES To determine whether fragmented sleep in nursing home patients would improve with increased exposure to bright light . DESIGN R and omized controlled trial . SETTING Two San Diego-area nursing homes . PARTICIPANTS Seventy-seven ( 58 women , 19 men ) nursing home residents participated . Mean age + /- st and ard deviation was 85.7 + /- 7.3 ( range 60 - 100 ) and mean Mini-Mental State Examination was 12.8 + /- 8.8 ( range 0 - 30 ) . INTERVENTIONS Participants were assigned to one of four treatments : evening bright light , morning bright light , daytime sleep restriction , or evening dim red light . MEASUREMENTS Improvement in nighttime sleep quality , daytime alertness , and circadian activity rhythm parameters . RESULTS There were no improvements in nighttime sleep or daytime alertness in any of the treatment groups . Morning bright light delayed the peak of the activity rhythm ( acrophase ) and increased the mean activity level ( mesor ) . In addition , subjects in the morning bright light group had improved activity rhythmicity during the 10 days of treatment . CONCLUSION Increasing exposure to morning bright light delayed the acrophase of the activity rhythm and made the circadian rhythm more robust . These changes have the potential to be clinical ly beneficial because it may be easier to provide nursing care to patients whose circadian activity patterns are more socially acceptable Sleep in the nursing home environment is extremely fragmented , possibly in part as a result of decreased light exposure . This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer 's disease . Results showed that both morning and evening bright light result ed in more consoli date d sleep at night , as measured with wrist actigraphy . Evening light also increased the quality of the circadian activity rhythm , as measured by a 5-parameter extended cosine model ( amplitude , acrophase , nadir , slope of the curve , and relative width of the peak and trough ) . Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia . It would behoove nursing homes to consider increasing ambient light in multi purpose rooms where patients often spend much of their days BACKGROUND Dementia is a progressive neurological disorder that causes a high degree of dependency . This dependency has been defined as an increased need for assistance due to deterioration in cognition and physical functioning , and changes in behavior . Highly dependent people with dementia are more likely to be institutionalized . OBJECTIVES To investigate the association between specific categories of physical dependency and the presence of neuropsychiatric symptoms in people with dementia admitted to a long-term care institution . DESIGN A prospect i ve observational cohort study . SETTING S Home care and long-term care institutions in eight European countries . PARTICIPANTS People with dementia living at home but at risk of institutionalization and recently institutionalized people with dementia . METHOD Baseline and 3-month follow-up interviews were performed between November , 2010 and April , 2012 . The sample consisted of 116 recently institutionalized dementia sufferers and 949 people with dementia still living at home . Physical dependency was measured using the Katz Activity of Daily Living index , and neuropsychiatric symptoms were assessed through The Neuropsychiatric Inventory . Specific categories of dependency were analyzed by performing a logistic regression analysis . This followed examination of baseline characteristics to define the degree of physical dependency , as factors associated with institutionalization , and evaluation of the same characteristics at 3-month follow-up to detect changes in the degree of physical dependency and neuropsychiatric symptoms associated with recent admission to a long-term care institution . RESULTS Toileting , dressing and continence dependency was higher in institutionalized people than in those receiving home-care . Delusion , hallucination , agitation , anxiety , apathy , motor-disturbances , night-time behavior and eating disorders were also worse in the institutionalized . Logistic regression analysis showed that independent factors significantly associated with being recently institutionalized were toileting ( odds ratio=2.3 ; 95 % confidence interval=1.43 - 3.71 ) and motor disturbances ( odds ratio=1.81 ; 95 % confidence interval=1.15 - 2.87 ) . CONCLUSIONS This study supports the association between type and degree of physical dependency in people with dementia and long-term institutionalization . Institutionalization is associated with physical dependency and the presence of neuropsychiatric symptoms BACKGROUND Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer 's disease ( AD ) . Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes . In most institutional environments , light levels are very low and may not be sufficient to entrain the circadian clock to the 24-hour day . METHOD The purpose of this r and omized clinical trial was to test the effectiveness of timed bright light therapy in reducing rest-activity ( circadian ) disruption in institutionalized patients with AD . The experimental groups received either morning ( 9.30 - 10.30 am ) or afternoon ( 3.30 - 4.30 pm ) bright light exposure ( > or = 2500 lux in gaze direction ) Monday through Friday for 10 weeks . The control group received usual indoor light ( 150 - 200 lux ) . Nighttime sleep , daytime wake , and rest-activity parameters were determined by actigraphy . Repeated measures analysis of variance was employed to test the primary study hypotheses . RESULTS Seventy institutionalized subjects with AD ( mean age 84 ) completed the study . No significant differences in actigraphy-based measures of nighttime sleep or daytime wake were found between groups . Subjects in either experimental light condition evidence d a significantly ( p < 0.01 ) more stable rest-activity rhythm acrophase over the 10-week treatment period compared to the control subjects whose rhythm phase delayed by over two hours . CONCLUSIONS One hour of bright light , administered to subjects with AD either in the morning or afternoon , did not improve nighttime sleep or daytime wake compared to a control group of similar subjects . However , exposure to one-hour of bright light in either the morning or afternoon may provide sufficient additional input to the circadian pacemaker to facilitate entrainment to the 24-hour day |
2,434 | 5,338,265 | Studies in the United States,9 Canada,10 and the Netherl and s11 showed variations that correlated more with hospital or individual preferences than with patient severity . | Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection .
It is the most common lower respiratory infection in this age group .
It is characterized by acute inflammation , edema , and necrosis of epithelial cells lining small airways , increased mucus production , and bronchospasm .
The American Academy of Pediatrics convened a committee composed of primary care physicians and specialists in the fields of pulmonology , infectious disease , emergency medicine , epidemiology , and medical informatics .
This guideline addresses the diagnosis of bronchiolitis as well as various therapeutic interventions including bronchodilators , corticosteroids , antiviral and antibacterial agents , hydration , chest physiotherapy , and oxygen .
Bronchiolitis is a disorder most commonly caused in infants by viral lower respiratory tract infection ( LRTI ) .
It is the most common lower respiratory infection in this age group .
It is characterized by acute inflammation , edema and necrosis of epithelial cells lining small airways , increased mucus production , and bronchospasm .
Signs and symptoms are typically rhinitis , tachypnea , wheezing , cough , crackles , use of accessory muscles , and /or nasal flaring.1 Many viruses cause the same constellation of symptoms and signs .
The most common etiology is the respiratory syncytial virus ( RSV ) , with the highest incidence of RSV infection occurring between December and March.2 Ninety percent of children are infected with RSV in the first 2 years of life,3 and up to 40 % of them will have lower respiratory infection.4,5 Infection with RSV does not grant permanent or longterm immunity .
Reinfections are common and may be experienced throughout life.6 Other viruses identified as causing bronchiolitis are human metapneumovirus , influenza , adenovirus , and parainfluenza .
RSV infection leads to more than 90 000 hospitalizations annually .
Mortality result ing from RSV has decreased from 4500 deaths annually in 1985 in the United States2,6 to an estimated 510 RSV-associated deaths in 19976 and 390 in 1999.7 The cost of hospitalization for bronchiolitis in children less than 1 year old is estimated to be more than $ 700 million per year.8 Several studies have shown a wide variation in how bronchiolitis is diagnosed and treated .
In addition , length of hospitalization in some countries averages twice that of others.12 This variable pattern suggests a lack of consensus among clinicians as to best practice s. In addition to morbidity and mortality during the acute illness , infants hospitalized with bronchiolitis are more likely to have respiratory problems as older children , especially recurrent wheezing , compared with those who did not have severe disease.13–15 Severe disease is characterized by persistently increased respiratory effort , apnea , or the need for intravenous hydration , supplemental oxygen , or mechanical ventilation .
It is unclear whether severe viral illness early in life predisposes children to develop recurrent wheezing or if infants who experience severe bronchiolitis have an underlying predisposition to recurrent wheezing . | A DOUBLE-BLIND study on the effect of betamethasone sodium phosphate in the treatment of 297 infants and children with acute bronchiolitis was conducted at five hospitals from December 1963 to June 1965 . For this study , the investigators design ed a common protocol and st and ard case report forms for use at the five collaborating centers . The information obtained permitted an evaluation of the effects of the corticosteroid in bronchiolitis and provided further insight into the natural history of the disease . The study was not design ed to explore the causes of bronchiolitis or the effect of supportive treatment . In recent years , corticosteroids have been used in the treatment of bronchiolitis on the hypothesis that their anti-inflammatory action would reduce bronchiolar inflammation and swelling . These drugs have been regarded as ineffective by some investigators and lifesaving by others . In 1964 , Sussman et al1reported no change in the clinical course of 49 arthritis , particularly with actively inflamed large joints , and ankylosing spondylitis . The fact that indomethacin is a rapidly effective , non-steroidal , anti-inflammatory agent , like phenylbutazone , makes it a useful alternative to predni-steroid therapy . As with many other drugs used in the treatment of chronic rheumatic disorders , indomethacin causes undesired effects which are particularly apt to occur in the early stages of treatment . Fortunately most of these are trivial and clear rapidly after withdrawal of the drug . In view of the occurrence of severe neurological disturbance in seven of our cases we feel that it would be unwise to ignore and dangerous to suppress the headache and associated symptoms so commonly encountered . If these can not be avoided by gradual induction or by subsequent reduction of dosage , they must be taken as an indication for stopping the drug . It would seem reasonable to insist that indomethacin should only be given with caution to any patient with a history of depressive illness . Active or recent peptic ulceration should be regarded as an absolute contraindication , and therapy should not be resumed in any patient who exhibits a rash during treatment A double blind trial of prednisolone treatment was carried out on 95 children with clinical evidence of epidemic bronchiolitis . The trial showed that there was no difference between the prednisoIone and the placebo group in the duration of symptoms and signs |
2,435 | 26,329,399 | We have very little confidence that massage is an effective treatment for LBP .
Acute , sub-acute and chronic LBP had improvements in pain outcomes with massage only in the short-term follow-up .
Functional improvement was observed in participants with sub-acute and chronic LBP when compared with inactive controls , but only for the short-term follow-up .
There were only minor adverse effects with massage | BACKGROUND Low-back pain ( LBP ) is one of the most common and costly musculoskeletal problems in modern society .
It is experienced by 70 % to 80 % of adults at some time in their lives .
Massage therapy has the potential to minimize pain and speed return to normal function .
OBJECTIVES To assess the effects of massage therapy for people with non-specific LBP . | Background Chronic back pain is a major public health problem and the primary reason patients seek massage treatment . Despite the growing use of massage for chronic low back pain , there have been few studies of its effectiveness . This trial will be the first evaluation of the effectiveness of relaxation massage for chronic back pain and the first large trial of a focused structural form of massage for this condition . Methods and Design A total of 399 participants ( 133 in each of three arms ) between the ages of 20 and 65 years of age who have low back pain lasting at least 3 months will be recruited from an integrated health care delivery system . They will be r and omized to one of two types of massage ( " focused structural massage " or " relaxation massage " ) , or continued usual medical care . Ten massage treatments will be provided over 10 weeks . The primary outcomes , st and ard measures of dysfunction and bothersomeness of low back pain , will be assessed at baseline and after 10 , 26 , and 52 weeks by telephone interviewers masked to treatment assignment . General health status , satisfaction with back care , days of back-related disability , perceived stress , and use and costs of healthcare services for back pain will also be measured . Outcomes across assigned treatment groups will be compared using generalized estimating equations , accounting for participant correlation and adjusted for baseline value , age , and sex . For both primary outcome measures , this trial will have at least 85 % power to detect the presence of a minimal clinical ly significant difference among the three treatment groups and 91 % power for pairwise comparisons . Secondary analyses will compare the proportions of participants in each group that improve by a clinical ly meaningful amount . Conclusion Results of this trial will help clarify the value of two types of massage therapy for chronic low back pain . Trial registration Clinical Trials.gov NCT 00371384 Objective : This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability . Methods : A single blind , r and omized , controlled trial was employed . Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning . In addition , patients received manual therapy or sham manual therapy . Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily . Results : Seventy-two out of 100 patients completed the study . Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction ( P = 0.04 and P = 0.05 , respectively ) , indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received . When controlling for pretreatment scores , patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain . No change in perceived disability was observed , with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment . Discussion : Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain . Despite changes in pain , perceived function did not improve . It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability . Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population Non-specific low back pain ( NLBP ) is an increasing health problem for athletes . This r and omized controlled trial was design ed to investigate the effects of Chinese massage combined with herbal ointment for NLBP . 110 athletes with NLBP were r and omly assigned to experimental group with Chinese massage combined with herbal ointment or control group with simple massage therapy . The primary outcome was pain by Chinese Short Form McGill Pain Question naire ( C-SFMPQ ) . The secondary outcome was local muscle stiffness by Myotonometer . After 4 weeks , the experimental group experienced significant improvements in C-SFMPQ and in local muscle stiffness compared with control group ( between-group difference in mean change from baseline , −1.24 points , P = 0.005 in sensory scores ; −3.14 points , P < 0.001 in affective scores ; −4.39 points , P < 0.001 in total scores ; −0.64 points , P = 0.002 in VAS ; −1.04 points , P = 0.005 in local muscle stiffness during relaxation state ) . The difference remained at one month followup , but it was only significant in affective scores ( −2.83 points , P < 0.001 ) at three months followup . No adverse events were observed . These findings suggest that Chinese massage combined with herbal ointment may be a beneficial complementary and alternative therapy for athletes with NLBP Objective To determine the effectiveness of lessons in the Alex and er technique , massage therapy , and advice from a doctor to take exercise ( exercise prescription ) along with nurse delivered behavioural counselling for patients with chronic or recurrent back pain . Design Factorial r and omised trial . Setting 64 general practice s in Engl and . Participants 579 patients with chronic or recurrent low back pain ; 144 were r and omised to normal care , 147 to massage , 144 to six Alex and er technique lessons , and 144 to 24 Alex and er technique lessons ; half of each of these groups were r and omised to exercise prescription . Interventions Normal care ( control ) , six sessions of massage , six or 24 lessons on the Alex and er technique , and prescription for exercise from a doctor with nurse delivered behavioural counselling . Main outcome measures Rol and Morris disability score ( number of activities impaired by pain ) and number of days in pain . Results Exercise and lessons in the Alex and er technique , but not massage , remained effective at one year ( compared with control Rol and disability score 8.1 : massage −0.58 , 95 % confidence interval −1.94 to 0.77 , six lessons −1.40 , −2.77 to −0.03 , 24 lessons −3.4 , −4.76 to −2.03 , and exercise −1.29 , −2.25 to −0.34 ) . Exercise after six lessons achieved 72 % of the effect of 24 lessons alone ( Rol and disability score −2.98 and −4.14 , respectively ) . Number of days with back pain in the past four weeks was lower after lessons ( compared with control median 21 days : 24 lessons −18 , six lessons −10 , massage −7 ) and quality of life improved significantly . No significant harms were reported . Conclusions One to one lessons in the Alex and er technique from registered teachers have long term benefits for patients with chronic back pain . Six lessons followed by exercise prescription were nearly as effective as 24 lessons . Trial registration National Research Register N0028108728 . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . Three treatments for non-specific lumbar pain -- balneotherapy , underwater traction bath , and underwater massage -- were assessed in a r and omised prospect i ve controlled trial in 158 out patients . Each group was treated for four weeks and patients were review ed at the end of this period and at 12 months after entry to the trial . The prescription of analgesics and the pain score were significantly reduced in all three treated groups , but there was no difference between the three groups . No significant change occurred in spinal motion and the straight leg raising test . After one year only the analgesic consumption was significantly lower than in the control group Objective An economic evaluation of therapeutic massage , exercise , and lessons in the Alex and er technique for treating persistent back pain . Design Cost consequences study and cost effectiveness analysis at 12 month follow-up of a factorial r and omised controlled trial . Participants 579 patients with chronic or recurrent low back pain recruited from primary care . Interventions Normal care ( control ) , massage , and six or 24 lessons in the Alex and er technique . Half of each group were r and omised to a prescription for exercise from a doctor plus behavioural counselling from a nurse . Main outcome measures Costs to the NHS and to participants . Comparison of costs with Rol and -Morris disability score ( number of activities impaired by pain ) , days in pain , and quality adjusted life years ( QALYs ) . Comparison of NHS costs with QALY gain , using incremental cost effectiveness ratios and cost effectiveness acceptability curves . Results Intervention costs ranged from £ 30 for exercise prescription to £ 596 for 24 lessons in Alex and er technique plus exercise . Cost of health services ranged from £ 50 for 24 lessons in Alex and er technique to £ 124 for exercise . Incremental cost effectiveness analysis of single therapies showed that exercise offered best value ( £ 61 per point on disability score , £ 9 per additional pain-free day , £ 2847 per QALY gain ) . For two-stage therapy , six lessons in Alex and er technique combined with exercise was the best value ( additional £ 64 per point on disability score , £ 43 per additional pain-free day , £ 5332 per QALY gain ) . Conclusions An exercise prescription and six lessons in Alex and er technique alone were both more than 85 % likely to be cost effective at values above £ 20 000 per QALY , but the Alex and er technique performed better than exercise on the full range of outcomes . A combination of six lessons in Alex and er technique lessons followed by exercise was the most effective and cost effective option . How does the Alex and er Technique work ? What are the authors findings about the clinical and cost effectiveness of the treatment ? Watch this video to find out ( 12 mins ) . Background and Purpose — The Safe Implementation of Thrombolysis in Stroke-MOnitoring STudy ( SITS-MOST ) unadjusted results demonstrated that intravenous alteplase is well tolerated and that the effects were comparable with those seen in r and omized , controlled trials ( RCTs ) when used in routine clinical practice within 3 hours of ischemic stroke onset . We aim ed to identify outcome predictors and adjust the outcomes of the SITS-MOST to the baseline characteristics of RCTs . Methods — The study population was SITS-MOST ( n=6483 ) and pooled RCTs ( n=464 ) patients treated with intravenous alteplase within 3 hours of stroke onset . Multivariable , backward stepwise regression analyses ( until P≤0.10 ) were performed to identify the outcome predictors for SITS-MOST . Variables appearing either in the final multivariable model or differing ( P<0.10 ) between SITS-MOST and RCTs were included in the prediction model for the adjustment of outcomes . Main outcome measures were symptomatic intracerebral hemorrhage , defined as National Institutes of Health Stroke Scale deterioration ≥1 within 7 days with any hemorrhage ( RCT definition ) , mortality , and independency as defined by modified Rankin Score of 0 to 2 at 3 months . Results — The adjusted proportion of symptomatic intracerebral hemorrhage for SITS-MOST was 8.5 % ( 95 % CI , 7.9 to 9.0 ) versus 8.6 % ( 6.3 to 11.6 ) for pooled RCTs ; mortality was 15.5 % ( 14.7 to 16.2 ) versus 17.3 % ( 14.1 to 21.1 ) ; and independency was 50.4 % ( 49.6 to 51.2 ) versus 50.1 % ( 44.5 to 54.7 ) , respectively . In the multivariable analysis , older age , high blood glucose , high National Institutes of Health Stroke Scale score , and current infa rct ion on imaging scans were related to poor outcome in all parameters . Systolic blood pressure , atrial fibrillation , and weight were additional predictors of symptomatic intracerebral hemorrhage . Current smokers had a lower rate of symptomatic intracerebral hemorrhage . Disability before current stroke ( modified Rankin Score 2 to 5 ) , diastolic blood pressure , antiplatelet other than aspirin , congestive heart failure , patients treated in new centers , and male sex were related to high mortality at 3 months . Conclusions — The adjusted outcomes from SITS-MOST were almost identical to those in relevant RCTs and reinforce the conclusion drawn previously in the unadjusted analysis . We identified several important outcome predictors to better identify patients suitable for thrombolysis OBJECTIVE --To compare the effectiveness of manipulative therapy , physiotherapy , treatment by the general practitioner , and placebo therapy in patients with persistent non-specific back and neck complaints . DESIGN --R and omised clinical trial . SETTING -- Primary health care in the Netherl and s. PATIENTS --256 patients with non-specific back and neck complaints of at least six weeks ' duration who had not received physiotherapy or manipulative therapy in the past two years . INTERVENTIONS --At the discretion of the manipulative therapists , physiotherapists , and general practitioners . Physiotherapy consisted of exercises , massage , and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manipulative therapy consisted of manipulation and mobilisation of the spine . Treatment by general practitioners consisted of drugs ( for example , analgesics ) , advice about posture , home exercises , and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 minutes ) and detuned ultrasound ( 10 minutes ) . MAIN OUTCOME MEASURES --Changes in severity of the main complaint and limitation of physical functioning measured on 10 point scales by a blinded research assistant and global perceived effect measured on a 6 point scale by the patients . RESULTS --Many patients in the general practitioner and placebo groups received other treatment during follow up . Improvement in the main complaint was larger with manipulative therapy ( 4.5 ) than with physiotherapy ( 3.8 ) after 12 months ' follow up ( difference 0.9 ; 95 % confidence interval 0.1 to 1.7 ) . Manipulative therapy also gave larger improvements in physical functioning ( difference 0.6 ; -0.1 to 1.3 ) . The global perceived effect after six and 12 months ' follow up was similar for both treatments . CONCLUSIONS --Manipulative therapy and physiotherapy are better than general practitioner and placebo treatment . Furthermore , manipulative therapy is slightly better than physiotherapy after 12 months BACKGROUND The effectiveness of massage therapy for low-back pain has not been documented . This r and omized controlled trial compared comprehensive massage therapy ( soft-tissue manipulation , remedial exercise and posture education ) , 2 components of massage therapy and placebo in the treatment of subacute ( between 1 week and 8 months ) low-back pain . METHODS Subjects with subacute low-back pain were r and omly assigned to 1 of 4 groups : comprehensive massage therapy ( n = 25 ) , soft-tissue manipulation only ( n = 25 ) , remedial exercise with posture education only ( n = 22 ) or a placebo of sham laser therapy ( n = 26 ) . Each subject received 6 treatments within approximately 1 month . Outcome measures obtained at baseline , after treatment and at 1-month follow-up consisted of the Rol and Disability Question naire ( RDQ ) , the McGill Pain Question naire ( PPI and PRI ) , the State Anxiety Index and the Modified Schober test ( lumbar range of motion ) . RESULTS Of the 107 subjects who passed screening , 98 ( 92 % ) completed post-treatment tests and 91 ( 85 % ) completed follow-up tests . Statistically significant differences were noted after treatment and at follow-up . The comprehensive massage therapy group had improved function ( mean RDQ score 1.54 v. 2.86 - 6.5 , p < 0.001 ) , less intense pain ( mean PPI score 0.42 v. 1.18 - 1.75 , p < 0.001 ) and a decrease in the quality of pain ( mean PRI score 2.29 v. 4.55 - 7.71 , p = 0.006 ) compared with the other 3 groups . Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function . At 1-month follow-up 63 % of subjects in the comprehensive massage therapy group reported no pain as compared with 27 % of the soft-tissue manipulation group , 14 % of the remedial exercise group and 0 % of the sham laser therapy group . INTERPRETATION Patients with subacute low-back pain were shown to benefit from massage therapy , as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists OBJECTIVES To assess the effect of acupoint stimulation with electrodes combined with acupressure using an aromatic essential oil ( lavender ) as an add-on-treatment on pain relief and enhancing the physical functional activities among adults with sub-acute or chronic non-specific low back pain . DESIGN R and omised controlled trial . SETTING The community centre , Old-Aged Home and Women Workers Association , Hong Kong . INTERVENTION 8-session relaxation acupoint stimulation followed by acupressure with lavender oil over a 3-week period . The control group received usual care only . OUTCOME MEASURES Changes from baseline to the end of treatment were assessed in pain intensity ( by Visual Analogue Scale ) and duration ; lateral fingertip-to-ground distance in centimetres ; walking time and interference on daily activities . RESULTS The baseline VAS scores for the intervention and control groups were 6.38 ( S.E.M. = 0.22 ) and 5.70 ( S.E.M. = 0.37 ) out of 10 , respectively ( P=0.24 ) . One week after the end of treatment , the intervention group had 39 % greater reduction in VAS pain intensity than the control group ( P=0.0001 ) , improved walking time ( P=0.05 ) and greater lateral spine flexion range ( P=0.01 ) . CONCLUSIONS Our results show that 8-sessions of acupoint stimulation followed by acupressure with aromatic lavender oil were an effective method for short-term LBP relief . No adverse effects were reported . To complement mainstream medical treatment for sub-acute LBP , the combined therapy of acupoint stimulation followed by acupressure with aromatic lavender oil may be one of the choices as an add-on therapy for short-term reduction of LBP Study Design . Clinical practice guideline . Objective . To develop evidence -based recommendations on use of interventional diagnostic tests and therapies , surgeries , and interdisciplinary rehabilitation for low back pain of any duration , with or without leg pain . Summary of Background Data . Management of patients with persistent and disabling low back pain remains a clinical challenge . A number of interventional diagnostic tests and therapies and surgery are available and their use is increasing , but in some cases their utility remains uncertain or controversial . Interdisciplinary rehabilitation has also been proposed as a potentially effective noninvasive intervention for persistent and disabling low back pain . Methods . A multidisciplinary panel was convened by the American Pain Society . Its recommendations were based on a systematic review that focused on evidence from r and omized controlled trials . Recommendations were grade d using methods adapted from the US Preventive Services Task Force and the Grading of Recommendations , Assessment , Development , and Evaluation Working Group . Results . Investigators review ed 3348 abstract s. A total of 161 r and omized trials were deemed relevant to the recommendations in this guideline . The panel developed a total of 8 recommendations . Conclusion . Recommendations on use of interventional diagnostic tests and therapies , surgery , and interdisciplinary rehabilitation are presented . Due to important trade-offs between potential benefits , harms , costs , and burdens of alternative therapies , shared decision-making is an important component of a number of the recommendations Stopping r and omized trials early because of an apparent benefit is a growing phenomenon . A recent systematic review found that the number of r and omized trials stopped early for benefit has more than doubled since 1990 ( 1 ) . To protect and promote the interests of trial participants , investigators may feel ethically obligated to stop a trial early because of the unexpected harm or apparent benefit of a study treatment . If a study treatment 's benefit far outweighs its adverse effects , is it not unethical to continue enrolling patients in a trial in which , as is typically the case , patients have a 50 % chance of receiving a placebo or an inferior treatment ? In this article , we argue that stopping a r and omized trial early for apparent benefit is often unethical and can be justified only under restricted circumstances . If the scientific community were to accept our arguments , then the approach that investigators , institutional review boards , and data monitoring committees take to the practice of stopping trials early for apparent benefit would substantially change . Ethical Considerations Emanuel and colleagues ( 2 ) describe a framework of 7 requirements for determining whether clinical research is ethical . We use this framework to identify and assess the ethical issues raised by stopping trials early because of apparent benefit ( Table ) . Table . Ethical Violations Result ing from Stopping a Trial Early for Apparent Benefit Scientific Validity The purpose of a trial of alternative interventions is to generate an estimate of treatment effect that closely approximates the true effect and is not misleading . This requires application of scientific procedures that yield valid and reliable data and thus minimize both systematic and r and om error . A systematic review of r and omized trials stopped early for apparent benefit ( 1 ) found that many of the trials yielded implausibly large treatment effects ; the median relative risk was 0.53 . Apparent large treatment effects occurred much more frequently when trials accrued only a small number of events . The odds of a treatment effect larger than the overall median relative risk of 0.53 was 28 times greater ( 95 % CI , 11 to 73 ) among trials in which fewer than the median of 66 events accrued than among trials in which more events accrued . These results , which are consistent with predictions from statistical theory ( 3 ) , suggest that stopping trials early for apparent benefit will systematic ally overestimate treatment effects . The scientific validity of trials that are stopped early is further compromised when trials yield inconclusive data about outcomes that did not influence trial truncation but are nonetheless important to patients , such as disease-free survival , symptom control , quality of life , and adverse effects of treatment . For example , a trial of vitamin E supplementation in premature newborns that was stopped early because of an apparent reduction in intracranial hemorrhage ( 4 ) failed to detect the increase in sepsis associated with vitamin E supplementation that subsequent trials identified ( 5 ) . Social or Scientific Value and Favorable RiskBenefit Ratio It is underst and able that investigators focus their ethical obligations on research participants . Such focus , however , risks neglecting obligations to society . The tendency of truncated trials to overestimate the effect of a treatment on the end point that result ed in trial truncation and to yield insufficient data about other important outcomes endangers the wider community to whom the results will be applied ( 6 ) . On review ing the results of a truncated trial , astute clinicians might appropriately conclude that the benefits of the intervention remain uncertain . However , less skeptical clinicians might assume that the results are true and inappropriately expose patients to the intervention and its unknown harms . Consider the results of a trial in which the investigators continued to enroll patients even though prespecified criteria for early stopping were met . Two interim analyses of a r and omized trial of 5 versus 4 courses of chemotherapy in patients with acute myeloid leukemia ( 7 ) found apparent large benefits to the 5-course regimen ( relative odds reduction of 53 % [ CI , 23 % to 71 % ; P= 0.003 ] in the first analysis and 45 % [ CI , 20 % to 62 % ; P= 0.0002 ] in the second analysis ) . Finding these results too good to be true , the data monitoring committee recommended continuing the trial , which ultimately showed a trend in favor of the 4-course regimen . Had the investigators terminated the trial in accordance with their stopping rule , subsequent patients with leukemia may have experienced the toxicity of an additional course of chemotherapy without benefit . Harm result ing from the misleading findings of truncated trials can be compounded if the findings influence the recommendations of clinical practice guideline panels . Investigators conducting a trial that involved patients undergoing vascular surgery ( 8) stopped the trial early when 2 of 53 patients r and omly assigned to receive the -blocker bisoprolol and 18 of 59 control patients had major cardiovascular events ( relative risk reduction , 90 % [ CI , 59 % to 98 % ] ) . These results contributed to recommendations by the American Heart Association and the American College of Cardiology favoring administration of -blockers to patients with cardiac risk factors who were undergoing noncardiac surgery ( 9 ) . However , these results contradict those of 2 much larger subsequently published trials , neither of which suggested that -blockers reduce cardiac risk in patients undergoing noncardiac surgery ( 10 , 11 ) . Further social detriment may occur when clinicians compromise the ability of others to conduct more definitive studies by placing undue confidence in the results of a truncated trial . Investigators ( including 2 contributors to this article ) who obtained funding for a trial of -blockers in noncardiac surgery with an enrollment target of 10000 patients ( 12 ) faced challenges in persuading clinicians that the question remained unanswered . Participant Consent and Respect for Participants Key prerequisites for informed consent include the participant 's decision-making capacity and voluntariness and whether he or she had received adequate information to decide that participation in the research was in alignment with his or her values and goals . However , informed consent is not a single event , but it is an ongoing collaboration between participants and investigators . When important changes occur during a trial , investigators should inform participants of the changes . One justification for stopping a trial early for benefit is to inform study participants of the preliminary results and offer them the superior treatment . According to this argument , uncertainty about the relative merits of alternative interventions ( equipoise ) has been lost and informed clinicians and patients will overwhelmingly choose the superior treatment ( 13 ) . However , as we have pointed out , the astute clinician or patient may remain skeptical about a treatment 's apparent benefits if the findings come from a truncated trial . Unfortunately , many clinicians and even more patients probably will not have the knowledge and underst and ing to appropriately interpret the results . Disclosing interim results to study participants may therefore prove misleading . Furthermore , if investigators were to continue a trial after informing patients of the interim results , patients would be unblinded and may cross over or leave the trial . These behaviors create problems in interpreting trial results by further weakening inferences about the efficacy and safety of the intervention and compromising the ethical requirement of scientific validity . Finally , stopping a trial early does not guarantee that current and potential trial participants will receive the apparently beneficial treatment ( assuming that one believes they should ) . Studies of dissemination of new treatments reveal that long delays , such as those between reports of r and omized trials and recommendations of experts in review articles and textbooks , are common ( 14 ) . Continuing a 2-group trial gives participants at least a 50 % chance of receiving the experimental treatment , whereas if the trial is stopped early , the probability that participants will receive the treatment due to rapid dissemination is likely to be considerably less than 50 % . Independent Review Trials may have stopping rules that allow early termination because of genuine ( although misguided ) ethical concerns . However , investigators , trial sponsors , journals , and patients may all have additional motives for stopping trials early for apparent benefit . For example , truncated trials that report a large treatment effect tend to be published in the most prestigious medical journals ( 1 ) , which enhances the careers of the investigators and increases the likelihood that they will receive grants . Funding agencies have an interest in stopping trials early to minimize research costs . Pharmaceutical and for-profit sources that financially support trials are interested not only in controlling costs but also in the publicity and market share that result from reporting a trial stopped early for apparent benefit . Medical journals are interested in these trials because of publicity and citations , which result in increased journal impact factor , prestige , and advertising revenue . And patients and their advocates are motivated to stop a trial early when the experimental intervention is promising in order to hasten delivery of the intervention to clinical practice . All of these motives may affect investigators ' decisions and encourage an inappropriately early stop to a trial . These considerations m and ate that institutional review boards and data monitoring committees underst and the principles outlined in this article and insist on appropriate st and ards for stopping a trial early for apparent benefit to maintain the ethical integrity of clinical trials . Delayed onset muscle soreness is a common problem that can interfere with rehabilitation as well as activities of daily living . The purpose of this study was to test the impact of therapeutic massage , upper body ergometry , or microcurrent electrical stimulation on muscle soreness and force deficits evident following a high-intensity eccentric exercise bout . Forty untrained , volunteer female subjects were r and omly assigned to one of three treatment groups or to a control group . Exercise consisted of high-intensity eccentric contractions of the elbow flexors . Resistance was reduced as subjects fatigued , until they reached exhaustion . Soreness rating was determined using a visual analog scale . Force deficits were determined by measures of maximal voluntary isometric contraction at 90 degrees of elbow flexion and peak torque for elbow flexion at 60 degrees/sec on a Cybex II isokinetic dynamometer . Maximal voluntary isometric contraction and peak torque were determined at the 0 hour ( before exercise ) and again at 24 and 48 hours postexercise . Treatments were applied immediately following exercise and again at 24 hours after exercise . The control group subjects rested following their exercise bout . Statistical analysis showed significant increases in soreness rating and significant decreases in force generated when the 0 hour was compared with 24- and 48-hour measures . Further analysis indicated no statistically significant differences between massage , microcurrent electrical stimulation , upper body ergometry , and control groups The purpose of this study was to investigate the immediate effects of traditional Thai massage ( TTM ) on stress-related parameters including heart rate variability ( HRV ) , anxiety , muscle tension , pain intensity , pressure pain threshold , and body flexibility in patients with back pain associated with myofascial trigger points . Thirty-six patients were r and omly allocated to receive a 30-min session of either TTM or control ( rest on bed ) for one session . Results indicated that TTM was associated with significant increases in HRV ( increased total power frequency ( TPF ) and high frequency ( HF ) ) , pressure pain threshold ( PPT ) and body flexibility ( p<0.05 ) and significant decreases in self-reported pain intensity , anxiety and muscle tension ( p<0.001 ) . For all outcomes , similar changes were not observed in the control group . The adjusted post-test mean values for TPF , HF , PPT and body flexibility were significantly higher in the TTM group when compared with the control group ( p<0.01 ) and the values for pain intensity , anxiety and muscle tension were significantly lower . We conclude that TTM can increase HRV and improve stress-related parameters in this patient population We conducted a pilot study to evaluate a practical exercise program for elderly people with chronic musculo-skeletal pain . Thirty-three subjects ( mean age , 73 years ; 69 % back pain ; 24 % knee pain ; 9 % hip pain ) were r and omly assigned to one of three groups . Group 1 received a 6-week supervised program of walking . Group 2 received a pain education program that included instruction and demonstration of use of heat , cold , massage , relaxation and distraction . Group 3 received usual care . Outcomes including pain , self-reported health and functional status , and performance-based measures of functional status were evaluated at baseline , at two weeks and at eight weeks ( end of study ) . Attendance was 100 % for the education sessions and 93 % for walking sessions . No injuries were sustained . Both intervention groups demonstrated significant improvements in pain ( p<0.05 ) and performance-based measures of functional status ( p<0.05 ) , while the control group had no changes . These data suggest that patient education and fitness walking can improve overall pain management and related functional limitations among elderly people with chronic musculo-skeletal pain The objective of this r and omized comparative study was to provide preliminary data of comparative effectiveness of Thai traditional massage ( TTM ) and Chinese acupuncture for the treatment of myofascial back pain in young military personnel . Eighteen Thai military personnel , aged ranging from 20 - 40 years were r and omly divided into TTM and acupuncture groups . Each group received 5 sessions of massage or acupuncture during a 10-day period . The Thai version McGill Pain Question naire , 100-mm , visual analog scale ( VAS ) and summation of pain threshold in each trigger point measured by pressure algometer were assessed at day 0 , 3 , 8 and 10 . At the end of treatment protocol s , McGill scores decreased significantly in TTM and acupuncture groups ( p = 0.024 and 0.002 , respectively ) . VAS also decreased significantly ( p = 0.029 and 0.003 , respectively ) . However , the pain pressure threshold increased significantly in the acupuncture group but not in the TTM group ( p = 0.006 and 0.08 , respectively ) . When outcomes were compared between the two groups , no significant difference was found in the VAS ( p = 0.115 ) and pain pressure threshold ( p = 0.116 ) , whereas the acupuncture group showed significantly lower McGill scores than the TTM group ( p = 0.039 ) . In conclusion , five sessions of Thai traditional massage and Chinese acupuncture were effective for the treatment of myofascial back pain in young Thai military personnel . Significant effects in both groups begin after the first session . Acupuncture is more effective than Thai traditional massage when affective aspect is also evaluated A report of a r and omized , controlled trial ( RCT ) should convey to the reader , in a transparent manner , why the study was undertaken and how it was conducted and analyzed . For example , a lack of adequately reported r and omization has been associated with bias in estimating the effectiveness of interventions ( 1 , 2 ) . To assess the strengths and limitations of an RCT , readers need and deserve to know the quality of its methods . Despite several decades of educational efforts , RCTs still are not being reported adequately ( 3 - 6 ) . For example , a review of 122 recently published RCTs that evaluated the effectiveness of selective serotonin-reuptake inhibitors as first-line management strategy for depression found that only 1 ( 0.8 % ) paper described r and omization adequately ( 5 ) . Inadequate reporting makes the interpretation of RCT results difficult if not impossible . Moreover , inadequate reporting borders on unethical practice when biased results receive false credibility . History of CONSORT In the mid-1990s , two independent initiatives to improve the quality of reports of RCTs led to the publication of the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement ( 7 ) , which was developed by an international group of clinical trialists , statisticians , epidemiologists , and biomedical editors . CONSORT has been supported by a growing number of medical and health care journals ( 8 - 11 ) and editorial groups , including the International Committee of Medical Journal Editors ( ICMJE , also known as the Vancouver Group ) ( 12 ) , the Council of Science Editors ( CSE ) , and the World Association of Medical Editors ( WAME ) . CONSORT is also published in Dutch , English , French , German , Japanese , and Spanish . It can be accessed on the Internet , along with other information about the CONSORT group ( 13 ) . The CONSORT statement comprises a checklist and flow diagram for reporting an RCT . For convenience , the checklist and diagram together are called simply CONSORT . They are primarily intended for use in writing , review ing , or evaluating reports of simple two-group , parallel RCTs . Preliminary data indicate that the use of CONSORT does indeed help to improve the quality of reports of RCTs ( 14 , 15 ) . In an evaluation ( 14 ) of 71 RCTs published in three journals in 1994 , allocation concealment was not clearly reported in 43 ( 61 % ) of the RCTs . Four years later , after these three journals required that authors reporting an RCT use CONSORT , the proportion of papers in which allocation concealment was not clearly reported had dropped to 39 % ( 30 of 77 ; mean difference , 22 % [ 95 % CI of the difference , 38 % to 6 % ] ) . The usefulness of CONSORT is enhanced by continuous monitoring of the biomedical literature ; this monitoring allows CONSORT to be modified depending on the merits of maintaining or dropping current items and including new items . For example , when Meinert ( 16 ) observed that the flow diagram did not provide important information about the number of participants who entered each phase of an RCT ( enrollment , treatment allocation , follow-up , and data analysis ) , the diagram could be modified to accommo date the information . The checklist is similarly flexible . This iterative process makes the CONSORT statement a continually evolving instrument . While participants in the CONSORT group and their degree of involvement vary over time , members meet regularly to review the need to refine CONSORT . At the 1999 meeting , the participants decided to revise the original statement . This report reflects changes determined by consensus of the CONSORT group , partly in response to emerging evidence on the importance of various elements of RCTs . Revision of the CONSORT Statement Thirteen members of the CONSORT group met in May 1999 with the primary objective of revising the original CONSORT checklist and flow diagram , as needed . The group discussed the merits of including each item in the light of current evidence . As in developing the original CONSORT statement , our intention was to keep only those items deemed fundamental to reporting st and ards for an RCT . Some items not considered essential may well be highly desirable and should still be included in an RCT report even though they are not included in CONSORT . Such items include approval of an institutional ethical review board , sources of funding for the trial , and a trial registry number ( as , for example , the International St and ard R and omized Controlled Trial Number [ IS RCT N ] used to register an RCT at its inception [ 17 ] ) . Shortly after the meeting , a revised version of the checklist was circulated to the group for additional comments and feedback . Revisions to the flow diagram were similarly made . All these changes were discussed when CONSORT participants met in May 2000 , and the revised statement was finalized shortly afterward . The revised CONSORT statement includes a 22-item checklist ( Table ) and a flow diagram ( Figure ) . Its primary aim is to help authors improve the quality of reports of simple two-group , parallel RCTs . However , the basic philosophy underlying the development of the statement can be applied to any design . In this regard , additional statements for other design s will be forthcoming from the group ( 13 ) . CONSORT can also be used by peer review ers and editors to identify reports with inadequate description of trials and those with potentially biased results ( 1 , 2 ) . Table . Checklist of Items To Include When Reporting a R and omized Trial Figure . Flow diagram of the progress through the phases of a r and omized trial ( enrollment , intervention allocation , follow-up , and data analysis ) . During the 1999 meeting , the group also discussed the benefits of developing an explanatory document to enhance the use and dissemination of CONSORT . The document is patterned on reporting of statistical aspects of clinical research ( 18 ) , which was developed to help facilitate the recommendations of the ICMJE 's Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals . Three members of the CONSORT group , with assistance from members on some checklist items , drafted an explanation and elaboration document . That document ( 19 ) was circulated to the group for additions and revisions and was last revised after review at the latest CONSORT group meeting . Changes to CONSORT 1 . In the revised checklist , a new column for Paper Section and Topic integrates information from the Subheading column that was contained in the original statement . 2 . The Was It Reported ? column has been integrated into a Reported on Page Number column , as requested by some journals . 3 . Each item of the checklist is now numbered , and the syntax and order have been revised to improve the flow of information . 4 . Title and Abstract are now combined in the first item . 5 . While the content of the revised checklist is similar to that of the original one , some items that previously were combined are now separate . For example , authors had been asked to describe primary and secondary outcome ( s ) measure(s ) and the minimum important difference(s ) , and indicate how the target sample size was projected . In the new version , issues pertaining to outcomes ( item 6 ) and sample size ( item 7 ) are separate , enabling authors to be more explicit about each . Moreover , some items request additional information . For example , for outcomes ( item 6 ) authors are asked to report any methods used to enhance the quality of measurements , such as multiple observations . 6 . The item asking for the unit of r and omization ( for example , cluster ) has been dropped because specific checklists have been developed for reporting cluster RCTs ( 20 ) and other design types ( 13 ) since publication of the original checklist . 7 . Whenever possible , new evidence is incorporated into the revised checklist . For example , authors are asked to be explicit about whether the analysis reported is by intention to treat ( item 16 ) . This request is based in part on the observations ( 21 ) that authors do not adequately describe and apply intention-to-treat analysis and that reports not providing this information are less likely to provide other relevant information , such as losses to follow-up ( 22 ) . 8 . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow-up , and analysis ) . The revised diagram explicitly includes the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers lets the reader know whether the authors have performed an intention-to-treat analysis ( 21 - 23 ) . Because some of the information may not always be known and to accommo date other information , the structure of the flow diagram may need to be modified for a particular trial . Inclusion of the participant flow diagram in the report is strongly recommended but may be unnecessary for simple trials , such as those without any participant withdrawals or dropouts . Discussion Specifically developed to guide authors about how to improve the quality of reporting of simple two-group , parallel RCTs , CONSORT encourages transparency with reporting of the methods and results so that reports of RCTs can be interpreted both readily and accurately . However , CONSORT does not address other facets of reporting that also require attention , such as scientific content and readability of RCT reports . Some authors , in their enthusiasm to use CONSORT , have modified the checklist ( 24 ) . We recommend against such modifications because they may be based on a different process than the one used by the CONSORT group . The use of CONSORT seems to reduce ( if not eliminate ) inadequate reporting of RCTs ( 14 , 15 ) . Potentially , the use of CONSORT should positively influence the manner in which RCTs are conducted . Granting agencies have noted this potential relationship and , in at least in one case ( 25 ) , have encouraged grantees to consider in their application how they have dealt with the CONSORT items . The evidence -based approach used to develop CONSORT has also been used Objectives : To analyse the effectiveness of a combined procedure of massage and electrotherapy with interferential current in individuals with chronic non-specific low back pain of mechanical aetiology . Design : A single blinded r and omized controlled trial . Setting : Clinical setting . Participants : Sixty-two individuals with chronic non-specific low back pain were r and omly assigned to an experimental or control group . For 10 weeks the experimental group underwent treatment comprising 20 sessions ( twice a week ) of massage with interferential current in the lumbar and dorsal – lumbar area , and the control group received superficial lower back massage ( effleurage , superficial pressure and skin rolling ) . Main outcome variables : Oswestry Disability Index , pain visual analogue scale , Tampa Scale for Kinesiophobia , Rol and Morris Disability Question naire , McQuade Test , Side Bridge Test , quality of life scores and the range of trunk anteflexion motion , which were all assessed before the treatment and immediately after the last treatment session . Results : The 2 × 2 mixed model ANOVA with repeated measurements showed statistically significant group * time interactions for the visual analogue scale ( F = 12.839 ; P = 0.001 ) , Oswestry Disability Index ( F = 5.850 ; P = 0.019 ) , Rol and Morris Disability Question naire ( F = 8.237 ; P = 0.006 ) and quality of life ( physical function ( F = 16.792 ; P = 0.001 ) , physical role ( F = 14.839 ; P = 0.001 ) and body pain ( F = 11.247 ; P = 0.001 ) ) . Conclusions : In individuals with chronic non-specific low back pain , interferential current electro-massage achieved a significantly greater improvement in disability , pain and quality of life in comparison to superficial massage after 20 treatment sessions Evaluating the effectiveness of nursing interventions in decreasing pain is a top priority for clinical research . Unfortunately , most of the research on cancer pain relief has been limited to treatment studies involving the administration of analgesics . Research is needed to determine which nonanalgesic methods of pain control are effective and under what conditions . Consequently , an experimental study was design ed to test the effectiveness of massage as an intervention for cancer pain . Twenty-eight patients were r and omly assigned to a massage or control group . The patients in the massage group were given a 10 minute massage to the back ; the patients in the control group were visited for 10 minutes . For males , there was a significant decrease in pain level immediately after the massage . For females , there was not a significant decrease in pain level immediately after the massage . There were no significant differences between pain 1 hour and 2 hours after the massage in comparison with the initial pain for males or females . Massage was shown to be an effective short-term nursing intervention for pain in males in this sample Objective To introduce a newly design ed massage instrument , the H and Grip T-bar ( HT-bar ) and use it to relieve chronic non-specific low back pain ( nLBP ) through deep cross-friction massage ( roptrotherapy ) . Method 22 subjects ( 9 males and 13 females , aged 51.6±6.7 ) with chronic nLBP were allocated r and omly to a Roptrotherapy group ( n=12 ) and a Transcutaneous Electrical Nerve Stimulation ( TENS ) group ( n=10 ) . The Roptrotherapy group received deep cross-friction massage with the HT-bar , which was made of metal and had a cylinder for increasing weight and grooves for an easy grip . It was applied across the middle and lower back for 20 minutes a day , 3 days a week for 2 weeks . The TENS group received TENS for 20 minutes a day , 5 days a week for 2 weeks . The outcome was measured on the pain numeric rating scale ( PNRS ) , by the Oswestry disability index ( ODI ) , and by the Rol and & Morris Disability Question naire ( RMDQ ) at pre-treatment , at immediate post-treatment and 2 weeks later . The application of the HT-bar was assessed by a question naire to 19 therapists . Results At post-treatment , immediately and 2 weeks later , both groups showed significant improvement in PNRS , ODI and RMDQ . During the two weeks after post-treatment , however , the Roptrotherapy group improved in PNRS , ODI and RMDQ , but the TENS group did not . Over 80 % of the therapists responded that the HT-bar was useful and comfortable . Conclusion This study suggests that deep cross-friction massage can be a beneficial therapeutic technique and that the HT-bar can be a useful instrument in deep cross-friction massage for chronic nLBP patients Abstract Objective To evaluate the effectiveness of acupressure in terms of disability , pain scores , and functional status . Design R and omised controlled trial . Setting Orthopaedic clinic in Kaohsiung , Taiwan . Participants 129 patients with chronic low back pain . Intervention Acupressure or physical therapy for one month . Main outcome measures Self administered Chinese versions of st and ard outcome measures for low back pain ( primary outcome : Rol and and Morris disability question naire ) at baseline , after treatment , and at six month follow-up . Results The mean total Rol and and Morris disability question naire score after treatment was significantly lower in the acupressure group than in the physical therapy group regardless of the difference in absolute score ( - 3.8 , 95 % confidence interval - 5.7 to - 1.9 ) or mean change from the baseline ( - 4.64 , - 6.39 to - 2.89 ) . Acupressure conferred an 89 % ( 95 % confidence interval 61 % to 97 % ) reduction in significant disability compared with physical therapy . The improvement in disability score in the acupressure group compared with the physical group remained at six month follow-up . Statistically significant differences also occurred between the two groups for all six domains of the core outcome , pain visual scale , and modified Oswestry disability question naire after treatment and at six month follow-up . Conclusions Acupressure was effective in reducing low back pain in terms of disability , pain scores , and functional status . The benefit was sustained for six months & NA ; It has recently been shown that ice massage of the web between the thumb and index finger produces significantly greater relief of dental pain than a placebo control procedure . These results indicate that ice massage may be comparable to transcutaneous electrical stimulation ( TES ) and acupuncture , and may be mediated by similar neural mechanisms . The purpose of this study was to examine the relative effectiveness of ice massage and TES for the relief of low‐back pain . Patients suffering chronic low‐back pain were treated with both ice massage and TES . The order of treatments was balanced , and changes in the intensity of pain were measured with the McGill Pain Question naire ( MPQ ) . The results show that both methods are equally effective : based on the Pain Rating Index of the MPQ , 67–69 % of patients obtained pain relief greater than 33 % with each method . The results indicate that ice massage is an effective therapeutic tool , and appears to be more effective than TES for some patients . It may also serve as an additional sensory‐modulation method to alternate with TES to overcome adaptation effects . Evidence that cold signals are transmitted to the spinal cord exclusively by A‐delta fibers and not by C fibers suggests that ice massage provides a potential method for differentiating among the multiple feedback systems that mediate analgesia produced by different forms of intense sensory input Abstract . When measuring treatment effect in chronic low back pain with multi-item outcome instruments , it is necessary , both for clinical decision-making and research purpose s , to underst and the clinical importance of the outcome scores . The aims of the present study were three-fold . Firstly , it aim ed to estimate the minimal clinical ly important difference of three multi-item outcome instruments ( the Oswestry Disability Index , the General Function Score and the Zung Depression Scale ) and of the visual analogue scale ( VAS ) of back pain . Secondly , it aim ed to estimate the error of measurement of these instruments ; and its third aim was to describe the clinical meaning of score change . The study population consisted of 289 patients treated surgically or non-surgically in a r and omised controlled trial . The minimal clinical ly important difference was estimated with patient global assessment as the external criterion . It was compared with the st and ard error of measurement of the instruments . The individual items of the instruments were compared for score changes related to improvement and deterioration . The st and ard error of measurement of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale was 4 , 6 and 3 units , respectively . The 95 % tolerance interval was 10 , 16 and 8 units , respectively . The minimal clinical ly important difference was 10 , 12 and 8–9 units , respectively , thus not significantly exceeding the tolerance interval . The minimal clinical ly important difference of VAS back pain was 18–19 units , well exceeding the 95 % tolerance interval , which was 15 units . Improvement after treatment for chronic low back pain tends to occur to a greater extent in sleep disturbance , ability to do usual things and psychological irritability , but to a lesser extent in the ability to sit , st and and lift . We conclude that the VAS of back pain is responsive enough to detect the minimal clinical ly important difference , whereas the smallest acceptable score changes of the Oswestry Disability Index , the General Function Score and the Zung Depression Scale may require an increase to exceed the 95 % tolerance interval when used for clinical decision making and for power calculation . Despite improvement after treatment , the ability to sit , st and and lift , remain notable problems BACKGROUND Although acupressure has been reported to be effective in managing various types of pain , its efficacy in relieving pain associated with low back pain ( LBP ) remains unclear . The aim of this study is to compare the efficacy of acupressure with that of physical therapy in reducing low back pain . METHODS A r and omized controlled clinical trial in an orthopedic referral hospital in Taiwan was conducted between December 20 , 2000 , and March 2 , 2001 . A total of 146 participants with chronic low back pain were r and omly assigned to the acupressure group ( 69 ) or the physical therapy group ( 77 ) , each with a different treatment technique . Self-appraised pain scores were obtained before treatment as baseline and after treatment as outcomes using the Chinese version of Short-Form Pain Question naire ( SF-PQ ) . RESULTS There were no significant differences in baseline characteristics among patients r and omized into the two groups . The mean of posttreatment pain score after a 4-week treatment ( 2.28 , SD = 2.62 ) in the acupressure group was significantly lower than that in the physical therapy group ( 5.05 , SD = 5.11 ) ( P = 0.0002 ) . At the 6-month follow-up assessment , the mean of pain score in the acupressure group ( 1.08 , SD = 1.43 ) was still significantly lower than that in the physical therapy group ( 3.15 , SD = 3.62 ) ( P = 0.0004 ) . CONCLUSIONS Our results suggest that acupressure is another effective alternative medicine in reducing low back pain , although the st and ard operating procedures involved with acupressure treatment should be carefully assessed in the future BACKGROUND Although classic massage is used widely in Germany and elsewhere for treating chronic pain conditions , there are no r and omized controlled trials ( RCT ) . DESIGN Pragmatic RCT of classic massage compared to st and ard medical care ( SMC ) in chronic pain conditions of back , neck , shoulders , head and limbs . OUTCOME MEASURE Pain rating ( nine-point Likert-scale ; predefined main outcome criterion ) at pretreatment , post-treatment , and 3 month follow-up , as well as pain adjective list , depression , anxiety , mood , and body concept . RESULTS Because of political and organizational problems , only 29 patients were r and omized , 19 to receive massage , 10 to SMC . Pain improved significantly in both groups , but only in the massage group was it still significantly improved at follow-up . Depression and anxiety were improved significantly by both treatments , yet only in the massage group maintained at follow-up . CONCLUSION Despite its limitation result ing from problems with numbers and r and omization this study shows that massage can be at least as effective as SMC in chronic pain syndromes . Relative changes are equal , but tend to last longer and to generalize more into psychologic domains . Because this is a pilot study , the results need replication , but our experiences might be useful for other research ers An experimental design was used to measure the effects of back massage on anxiety levels of elderly residents in a long-term care institution . Twenty-one residents , 17 females and four males , participated in the study . Subjects were r and omly assigned to three groups which received ' back massage with normal conversation ' , ' conversation only ' and ' no intervention ' respectively . The dependent variable , anxiety , was measured prior to back massage , immediately following , and 10 minutes later , on four consecutive evenings . The Spielberger Self-Evaluation Question naire ( STAI ) , electromyographic recordings , systolic blood pressure , diastolic blood pressure ( DBP ) and heart rate were used as measures of anxiety . Analysis of variance was used to examine differences in group mean scores over the pre-test to post-test , post-test to delayed time interval , and pre-test to delayed time intervals , Scheffé comparisons being made where indicated . With the exception of mean DBP which showed no change from pre-test to post-test and HR which increased from post-test to delayed time interval , there was a statistically insignificant decrease in mean scores on all variables in the back massage group from pre-test to post-test and from post-test to delayed time interval . There was a statistically significant difference in the mean anxiety ( STAI ) score between the back massage group and the no intervention group . The difference between the back massage group and the conversation only group approached statistical significance . ( ABSTRACT TRUNCATED AT 250 WORDS One year after head trauma , 23 patients with post-traumatic headache entered a prospect i ve clinical controlled trial to find out if specific manual therapy on the neck could reduce the headache . The study was completed by 19 patients ( 83 % ) . Ten patients were treated twice with manual therapy and nine patients were treated twice with cold packs on the neck . The pain index was calculated blindly . Two weeks after the last treatment the mean pain index was significantly reduced to 43 % in the group treated with manual therapy compared with the pretreatment level . At follow-up five weeks later , the pain index was still lower in this group compared with the group treated with cold packs , but this difference was not statistically significant . The pain index for all 19 patients was significantly correlated to the use of analgesics as well as to the frequency of associated symptoms ( number of days per week with dizziness , visual disturbances and ear symptoms ) . It is concluded that the type of manual therapy used in this study seems to have a specific effect in reducing post-traumatic headache . The result supports the hypothesis of a cervical mechanism causing post-traumatic headache and suggests that post-traumatic dizziness , visual disturbances and ear symptoms could be part of a cervical syndrome Patients with acute or chronic low back pain were treated in a double-blind study that compared transcutaneous electrical nerve stimulation at intense levels and gentle , mechanically administered massage . Transcutaneous electrical nerve stimulation produced significantly greater pain relief , based on two measures of the McGill Pain Question naire , and significant improvement in straight leg raising . There were no significant differences between the two groups in backflexion scores . Pain-relief scores and range-of-motion scores were significantly correlated . The results indicate that pain-relief scores provide valuable information and can easily be obtained from patients for whom pain is a major symptom Gua Sha is a traditional East Asian healing technique where the body surface is " press-stroked " with a smooth-edged instrument to raise therapeutic petechiae that last 2 - 5 days . The technique is traditionally used in the treatment of both acute and chronic neck and back pain . This study aim ed to measure the effects of Gua Sha therapy on the pain ratings and pressure pain thresholds of patients with chronic neck pain ( CNP ) and chronic low back pain ( CLBP ) . A total of 40 patients with either CNP or CLBP ( mean age 49.23 ± 10.96 years ) were r and omized to either a treatment group ( TG ) or a waiting list control group ( WLC ) . At baseline assessment ( T1 ) , all patients rated their pain on a 10 cm visual analog scale ( VAS ) . Patients ' pressure pain thresholds ( PPT ) at a site of maximal pain ( pain-maximum ) and an adjacent ( pain-adjacent ) site were also established . The treatment group then received a single Gua Sha treatment . Post-intervention measurements were taken for both groups at T2 , seven days after baseline assessment ( T1 ) , using the same VAS and PPT measurements in precisely the same locations as at T1 . Final analysis were conducted with 21 patients with CNP and 18 patients with CLBP . The study groups were equally distributed with regard to r and omization . Patients in both the CNP and the CLBP treatment groups reported pain reduction ( p < 0.05 ) and improved health status from their one Gua Sha treatment , as compared to the waiting list group . Pain sensitivity improved in the TG in CNP , but not in CLBP patients , possibly due to higher pressure sensitivity in the neck area . No adverse events were reported . These results suggest that Gua Sha may be an effective treatment for patients with chronic neck and low back pain . Further study of Gua Sha is warranted OBJECTIVES To investigate the effects of Swedish massage with aromatic ginger oil ( SMGO ) on chronic low back pain and disability in older adults compared with traditional Thai massage ( TTM ) . DESIGN R and omized controlled trial . SETTING Massage clinic in Ratchaburi province , Thail and . PARTICIPANTS 164 patients were screened ; 140 were eligible , and r and omized to either SMGO ( n=70 ) or TTM ( n=70 ) . INTERVENTION Trained staff provided participants with a 30-min SMGO or TTM twice a week for five weeks . MEASUREMENT The Visual Analogue Scale ( VAS ) assessed immediate effect ( after each massage ) and the short form McGill Pain Question naire ( MPQ ) assessed effectiveness of massage in short-term ( six weeks ) and long-term ( 15 weeks ) . Disability improvement was measured by the Owestry Disability Question naire ( ODQ ) at baseline , short- and long-term . RESULTS Both SMGO and TTM led to significant improvements in pain intensity ( p<0.05 ) and disability ( p<0.05 ) across the period of assessment s , indicating immediate , short- and long-term effectiveness . SMGO was more effective than TTM in reducing pain ( p=0.04 ) and improving disability at short- and long-term assessment s ( p=0.04 ) . CONCLUSIONS These findings suggest that the integration of either SMGO or TTM therapy as additional options to provide holistic care to older people with chronic low back pain could be considered by health professionals . Further research into the use of ginger as an adjunct to massage therapy , particularly TTM , is recommended BACKGROUND Because the value of popular forms of alternative care for chronic back pain remains uncertain , we compared the effectiveness of acupuncture , therapeutic massage , and self-care education for persistent back pain . METHODS We r and omized 262 patients aged 20 to 70 years who had persistent back pain to receive Traditional Chinese Medical acupuncture ( n = 94 ) , therapeutic massage ( n = 78 ) , or self-care educational material s ( n = 90 ) . Up to 10 massage or acupuncture visits were permitted over 10 weeks . Symptoms ( 0 - 10 scale ) and dysfunction ( 0 - 23 scale ) were assessed by telephone interviewers masked to treatment group . Follow-up was available for 95 % of patients after 4 , 10 , and 52 weeks , and none withdrew for adverse effects . RESULTS Treatment groups were compared after adjustment for prer and omization covariates using an intent-to-treat analysis . At 10 weeks , massage was superior to self-care on the symptom scale ( 3.41 vs 4.71 , respectively ; P = .01 ) and the disability scale ( 5.88 vs 8.92 , respectively ; P<.001 ) . Massage was also superior to acupuncture on the disability scale ( 5.89 vs 8.25 , respectively ; P = .01 ) . After 1 year , massage was not better than self-care but was better than acupuncture ( symptom scale : 3.08 vs 4.74 , respectively ; P = .002 ; dysfunction scale : 6.29 vs 8.21 , respectively ; P = .05 ) . The massage group used the least medications ( P<.05 ) and had the lowest costs of subsequent care . CONCLUSIONS Therapeutic massage was effective for persistent low back pain , apparently providing long-lasting benefits . Traditional Chinese Medical acupuncture was relatively ineffective . Massage might be an effective alternative to conventional medical care for persistent back pain STUDY DESIGN A r and omized trial design ed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting . OBJECTIVE To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage . SUMMARY OF BACKGROUND DATA Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany . No reports of previous r and omized trials for the outcome from interferential therapy were found . METHODS Consenting patients were r and omly assigned into one of two groups . A pretreatment interview was performed by the patient using a computer-based question naire . It also incorporated the Oswestry Disability Index and a pain visual analog scale . Management consisted of six sessions over a 2- to 3-week period . Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment . RESULTS A total of 152 patients were recruited . The two treatment groups had similar demographic and clinical baseline characteristics . The mean Oswestry Disability Index before treatment was 30 for both groups ( n = 147 ) . After treatment , this had dropped to 25 , and , at 3 months , were 21 ( interferential therapy ) and 22 ( motorized lumbar traction and massage ) . The mean pain visual analog scale score before treatment was 50 ( interferential therapy ) and 51 ( motorized lumbar traction and massage ) . This had dropped , respectively , to 46 and 44 after treatment and to 42 and 39 at 3 months . CONCLUSIONS This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage . There was no difference in the improvement between the two groups at the end of treatment . Although there is evidence from several trials that traction alone is ineffective in the management of low back pain , this study could not exclude some effect from the concomitant massage OBJECTIVE To observe the therapeutic effect of lumbar tender point deep tissue massage plus lumbar traction on chronic non-specific low back pain using change in pressure pain threshold , muscle hardness and pain intensity as indices . METHODS We r and omly divided 64 patients into a treatment group ( 32 cases ) and a control group ( 32 cases ) . Two drop-outs occurred in each group . Patients in the treatment group received tender point deep tissue massage plus lumbar traction and patients in the control group received lumbar traction , alone . We used a tissue hardness meter/algometer and visual analog scale ( VAS ) to assess the pressure pain threshold , muscle hardness and pain intensity . RESULTS Following treatment , we obtained the following results in the treatment and control groups , respectively : the pressure pain threshold difference was 1.5 + /- 0.8 and 1.1 + /- 0.7 ; the muscle hardness difference was 4.2 + /- 1.6 and 3.5 + /- 1.3 ; and the VAS score difference was 1.9 + /- 0.9 and 1.4 + /- 0.8 . Compared to the control group , the treatment group had higher pressure pain threshold ( t = 2.09 , P < 0.05 ) , and lower muscle hardness ( t = 2.05 , P < 0.05 ) and pain intensity ( t = 2.46 , P < 0.05 ) . CONCLUSION Lumbar tender point deep tissue massage combined with lumbar traction produced better improvement in pressure pain threshold , muscle hardness and pain intensity in patients with chronic non-specific low back pain than with lumbar traction alone A r and omized clinical trial of rotational manipulation was conducted on 95 patients with low back pain selected for ( 1 ) the absence of any contraindications for vertebral manipulation , ( 2 ) the absence of any psychosocial problems that might affect the outcome of treatment , ( 3 ) the absence of any previous experience with manipulative therapy , and ( 4 ) the presence of palpatory cues indicating that manipulation might be successful . Patients were r and omly assigned to one of two groups : an experimental group receiving manipulation therapy and a control group receiving soft-tissue massage . Comparison of the two groups indicated that ( 1 ) patients who received manipulative treatment were much more likely to report immediate relief after the first treatment , and ( 2 ) at discharge , there was no significant difference between the two groups because both showed substantial improvement Forty patients with acute mechanical low-back pain were treated in a double-blind manner with either Rado-Salil ® or placebo for 14 days . Statistically significant improvements in spontaneous pain , muscular contracture and in both the patient 's and physician 's opinions occurred by day 3 . These improvements persisted at day 14 and , in addition , there were statistically significant improvements in the finger – floor distance and the degree of lumbar extension . Treatment with Rado-Salil ® also allowed significant reduction in the use of oral analgesics . Only a few localized transient side-effects , requiring no specific treatment , were observed INTRODUCTION This study compared the effectiveness of two different kind of massage : therapeutic and deep tissue on chronic low back pain . METHODS The research was made on 26 patient aged from 60 to 75 years who were separated into 2 groups : I [ n=13 ] and II [ n=13 ] . Group I had therapeutic massage [ TM ] which uses effleurage , petrissage , tapping and friction . Group II had deep tissue massage [ DTM ] which uses oblique pressure , a combination of lengthening and cross-fiber strokes , anchor and stretch , freeing muscle from entrapment . TM and DTM lasted for 10 days , each 30 min and were made by qualify massage therapist . Both groups did not have other treatment . Outcome measures obtained at baseline and after treatment consisted of Modified Oswestry Low Back Pain Disability Index [ ODI ] , Quebec Back Pain Disability Scale[QBPD ] and Visual Analog Scale [ VAS ] . RESULTS There was not statistically significant differences between groups according to age and BMI . Statistically significant differences were noted after TM in every test [ ODI p=0.010 ; QBPD p<0.001 ; VAS p<0.001 ] and after DTM in every test [ ODI p<0.001 ; QBPD p<0.001 ; VAS p<0.001 ] . DTM was statistically significant better therapy than TM in ODI [ p=0.038 ] and VAS [ p=0.015 ] . Further research is needed to verify the results BACKGROUND CONTEXT There have been no full-scale trials of the optimal number of visits for the care of any condition with spinal manipulation . PURPOSE To identify the dose-response relationship between visits to a chiropractor for spinal manipulation and chronic low back pain ( cLBP ) outcomes and to determine the efficacy of manipulation by comparison with a light massage control . STUDY DESIGN / SETTING Practice -based r and omized controlled trial . PATIENT SAMPLE Four hundred participants with cLBP . OUTCOME MEASURES The primary cLBP outcomes were the 100-point modified Von Korff pain intensity and functional disability scales evaluated at the 12- and 24-week primary end points . Secondary outcomes included days with pain and functional disability , pain unpleasantness , global perceived improvement , medication use , and general health status . METHODS One hundred participants with cLBP were r and omized to each of four dose levels of care : 0 , 6 , 12 , or 18 sessions of spinal manipulation from a chiropractor . Participants were treated three times per week for 6 weeks . At sessions when manipulation was not assigned , they received a focused light massage control . Covariate-adjusted linear dose effects and comparisons with the no-manipulation control group were evaluated at 6 , 12 , 18 , 24 , 39 , and 52 weeks . RESULTS For the primary outcomes , mean pain and disability improvement in the manipulation groups were 20 points by 12 weeks and sustainable to 52 weeks . Linear dose-response effects were small , reaching about two points per six manipulation sessions at 12 and 52 weeks for both variables ( p<.025 ) . At 12 weeks , the greatest differences from the no-manipulation control were found for 12 sessions ( 8.6 pain and 7.6 disability points , p<.025 ) ; at 24 weeks , differences were negligible ; and at 52 weeks , the greatest group differences were seen for 18 visits ( 5.9 pain and 8.8 disability points , p<.025 ) . CONCLUSIONS The number of spinal manipulation visits had modest effects on cLBP outcomes above those of 18 h and s-on visits to a chiropractor . Overall , 12 visits yielded the most favorable results but was not well distinguished from other dose levels OBJECTIVE To study the efficacy of manual therapy and physiotherapy in subgroups of patients with persistent back and neck complaints . The second objective was to determine the correlation between three important outcome measures used in this trial . DESIGN R and omized clinical trial ( subgroup analysis ) . SETTING Primary health care in the Netherl and s. PATIENTS Two hundred fifty-six patients with nonspecific back and neck complaints of at least 6 wk duration who had not received physiotherapy or manual therapy in the past 2 yr . INTERVENTIONS At the discretion of the manual therapists , physiotherapists and general practitioners . Physiotherapy consisted of exercises , massage and physical therapy ( heat , electrotherapy , ultrasound , shortwave diathermy ) . Manual therapy consisted of manipulation and mobilization of the spine . Treatment by the general practitioner consisted of drugs ( e.g. , analgesics ) , advice about posture , home exercises and (bed)rest . Placebo treatment consisted of detuned shortwave diathermy ( 10 min ) and detuned ultrasound ( 10 min ) . MAIN OUTCOME MEASURES Changes in severity of the main complaint and limitation of physical functioning measured on 10-point scales by a blinded research assistant and global perceived effect measured on a 6-point scale by the patients . RESULTS Improvement in the main complaint was larger with manual therapy ( 4.3 ) than with physiotherapy ( 2.5 ) for patients with chronic conditions ( duration complaint of 1 yr or longer ) . Also , improvement in the main complaint was larger with manual therapy ( 5.5 ) than with physiotherapy ( 4.0 ) for patients younger than 40 yr ( both were measured after 12-mo follow-up ) . Labeling of patients by the treating manual therapists as " suitable " or " not suitable " for treatment with manual therapy did not predict differences in outcomes . Generally , there was a moderate to strong correlation between the three outcome measures , although a considerable number of patients gave a relatively low score for perceived benefit , while the research assistant gave a high improvement score for the main complaint and physical functioning . CONCLUSIONS The subgroup analysis suggests better results of manual therapy compared to physiotherapy in chronic patients ( duration of present complaints of 1 yr or longer ) and in patients younger than 40 yr old ) . Differences for other subgroups were less clear . The explorative findings of these subgroup analyses have to be investigated in future research BACKGROUND Few studies have evaluated the effectiveness of massage for chronic low back pain . OBJECTIVE To compare the effectiveness of 2 types of massage and usual care for chronic back pain . DESIGN Parallel-group r and omized , controlled trial . R and omization was computer-generated , with central ized allocation concealment . Participants were blinded to massage type but not to assignment to massage versus usual care . Massage therapists were unblinded . The study personnel who assessed outcomes were blinded to treatment assignment . ( Clinical Trials.gov registration number : NCT00371384 ) SETTING An integrated health care delivery system in the Seattle area . PATIENTS 401 persons 20 to 65 years of age with nonspecific chronic low back pain . INTERVENTION Structural massage ( n = 132 ) , relaxation massage ( n = 136 ) , or usual care ( n = 133 ) . MEASUREMENTS Rol and Disability Question naire ( RDQ ) and symptom bothersomeness scores at 10 weeks ( primary outcome ) and at 26 and 52 weeks ( secondary outcomes ) . Mean group differences of at least 2 points on the RDQ and at least 1.5 points on the symptom bothersomeness scale were considered clinical ly meaningful . RESULTS The massage groups had similar functional outcomes at 10 weeks . The adjusted mean RDQ score was 2.9 points ( 95 % CI , 1.8 to 4.0 points ) lower in the relaxation group and 2.5 points ( CI , 1.4 to 3.5 points ) lower in the structural massage group than in the usual care group , and adjusted mean symptom bothersomeness scores were 1.7 points ( CI , 1.2 to 2.2 points ) lower with relaxation massage and 1.4 points ( CI , 0.8 to 1.9 points ) lower with structural massage . The beneficial effects of relaxation massage on function ( but not on symptom reduction ) persisted at 52 weeks but were small . LIMITATION Participants were not blinded to treatment . CONCLUSION Massage therapy may be effective for treatment of chronic back pain , with benefits lasting at least 6 months . No clinical ly meaningful difference between relaxation and structural massage was observed in terms of relieving disability or symptoms . PRIMARY FUNDING SOURCE National Center for Complementary and Alternative Medicine The use of complementary and alternative medicine ( CAM ) for the management of chronic low back pain ( CLBP ) continues to rise . However , questions regarding the efficacy of many CAM therapies for CLBP remain unresolved . The present study investigated the effectiveness of reflexology for CLBP . A pragmatic r and omised controlled trial was conducted . N=243 patients were r and omised to one of three groups : reflexology , relaxation , or non-intervention ( usual care ) . All completed a question naire booklet before and after the treatment phase , and at six months follow up . This measured their general health status , pain , functioning , coping strategies and mood . After adjusting for pre-treatment scores repeated measures ANCOVA found no significant differences between the groups pre and post treatment on the primary outcome measures of pain and functioning . There was a main effect of pain reduction , irrespective of group . Trends in the data illustrated the pain reduction was greatest in the reflexology group . Thus , the current study does not indicate that adding reflexology to usual GP care for the management of CLBP is any more effective than usual GP care alone The purpose of this study was to compare the magnitude and duration of motoneuron inhibition occurring as a sequel to spinal manipulation or paraspinal and limb massage . The physiologic mechanisms involved in spinal manipulative therapy and massage therapy are largely unknown . One possible hypothesis is based upon the theory that these two distinct and different modalities may attenuate the activity of alpha motoneurons . Both modalities have been reported to produce short-term inhibition of motoneurons . Asymptomatic volunteers were r and omly assigned to either a spinal manipulation , massage , or control group . Baseline tibial nerve H-reflex amplitudes were obtained prior to the application of either lumboscaral spinal manipulation or paralumbar and limb massage . Post-interventional H-reflex recordings were recorded immediately following the application of either modality . Spinal manipulation significantly ( p < 0.05 ) attenuated alpha motoneuronal activity immediately post-therapy , as measured by the amplitude of the tibial nerve H-reflex . Massage subjects exhibited no significant reduction in motoneuronal activity immediately following administration . Spinal manipulation produced a transient attenuation of alpha motoneuronal excitability . Paraspinal and limb massage did not inhibit the motoneuron pool as measured immediately post-therapy . These findings support the supposition that spinal manipulation procedures lead to short-term inhibitory effects on motoneuron excitability to a greater magnitude than massage Although r and omized controlled trials ( RCT ) are the gold st and ard for establishing causation in clinical research , their aggregated results can be misleading when applied to individual patients . A treatment may be beneficial in some patients , but its harms may outweigh benefits in others . While conventional one‐variable‐at‐a‐time subgroup analyses have well‐known limitations , multivariable risk‐based analyses can help uncover clinical ly significant heterogeneity in treatment effects that may be otherwise obscured . Trials in kidney transplantation have yielded the finding that a reduction in acute rejection does not translate into a similar benefit in prolonging graft survival and improving graft function . This paradox might be explained by the variation in risk for acute rejection among included kidney transplant recipients varying the likelihood of benefit or harm from intense immunosuppressive regimens . Analyses that stratify patients by their immunological risk may resolve these otherwise puzzling results . Reliable risk models should be developed to investigate benefits and harms in rationally design ed risk‐based subgroups of patients in existing RCT data sets . These risk strata would need to be vali date d in future prospect i ve clinical trials examining long‐term effects on patient and graft survival . This approach may allow better individualized treatment choices for kidney transplant recipients OBJECTIVE To observe the difference in the efficacy on lumbar intervertebral disc protrusion ( LIDP ) between Santong tuina therapy and conventional tuina therapy . METHODS Multi- central , r and om and controlled clinical trial was carried out . One hundred and twenty cases of LIDP were r and omized into an observation group and a control group , 60 cases in each one . In observation group , Santong tuina therapy was used . In control group , conventional tuina therapy was adopted . The clinical efficacy was observed in two groups , and lumbar vertebral function was scaled before and after treatment in two groups . RESULTS The total effective rate was 95.0 % ( 57/60 ) in observation group and was 96.7 % ( 58/60 ) in control group , without significant statistical difference in comparison ( P > 0.05 ) . The cured and markedly effective rate was 81.7 % ( 49/60 ) in observation group and was 63.3 % ( 38/60 ) in control group , indicating significant statistical difference in comparison ( P < 0.05 ) . The self-comparison of lumbar vertebral function before and after treatment presented statistical significance in either observation group ( 12.25 + /- 3.15 , 25.56 + /- 5.27 ) or control group ( 13.32 + /- 3.26 , 20.46 + /- 4.25 , both P < 0.05 ) ; additionally , there was significant difference in the comparison between groups after treatment ( P < 0.05 ) . The therapy adopted in observation group improved lumbar vertebral function much significantly . CONCLUSION In the treatment of LIDP , Santong tuina therapy achieves much better clinical efficacy as compared with conventional tuina therapy Study Design : A r and omized between-groups design evaluated massage therapy versus relaxation for chronic low back pain . Objectives : Treatment effects were evaluated for reducing pain , depression , anxiety and stress hormones , and sleeplessness and for improving trunk range of motion associated with chronic low back pain . Summary of Background Data : Twenty-four adults ( M age = 39.6 years ) with low back pain of nociceptive origin with a duration of at least 6 months participated in the study . The groups did not differ on age , socioeconomic status , ethnicity or gender . Methods : Twenty-four adults ( 12 women ) with lower back pain were r and omly assigned to a massage therapy or a progressive muscle relaxation group . Sessions were 30 minutes long twice a week for five weeks . on the first and last day of the 5-week study participants completed question naires , provided a urine sample and were assessed for range of motion . Results : By the end of the study , the massage therapy group , as compared to the relaxation group , reported experiencing less pain , depression , anxiety and improved sleep . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher . Conclusions : Massage therapy is effective in reducing pain , stress hormones and symptoms associated with chronic low back pain . Precis : Adults ( M age = 39.6 years ) with low back pain with a duration of at least 6 months received two 30-min massage or relaxation therapy sessions per week for 5 weeks . Participants receiving massage therapy reported experiencing less pain , depression , anxiety and their sleep had improved . They also showed improved trunk and pain flexion performance , and their serotonin and dopamine levels were higher & NA ; The effect of intensive dynamic back extensor exercises for patients with chronic low back pain was investigated in a controlled clinical trial in which chronic low back pain patients underwent a 3‐month intensive training program with a total of 30 sessions . The 105 patients were divided into 3 groups : a treatment group , an alternative group which underwent 1/5 of the treatment group 's exercise program per session , and an alternative group in which treatment consisted of thermotherapy , massage and mild exercise . Regardless of whether the treatment outcome is assessed qualitatively or quantitatively , a statistically significant , favorable difference was found between the results for the treatment group and for the alternative groups at conclusion and at the 3‐month follow‐up . It appeared from the quantitative assessment that patients in the treatment group who completed the training program at least once a week for the entire 1‐year follow‐up period were the only patients with a significantly better back status after 1 year compared to the time of inclusion . Irrespective of sex , age , duration and degree of severity of back trouble , or of pre‐existing sciatica or pathological findings upon X‐ray of the spine , patients obtained a favorable result from the training program . The therapy was found to be without risk , but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the spine were excluded from the study The effect of intensive dynamic back extensor exercises for patients with chronic low back was investigated in a controlled clinical trial where the patients underwent a three months intensive training program a total 30 sessions . The 105 patients were divided into three groups : a treatment group , an alternative group which underwent 1/5 of the treatment group 's exercise program per session , and an alternative group in which the treatment consisted of thermotherapy , massage and mild exercise . Regardless of whether the outcome of treatment is assessed qualitatively or quantitatively , a statistically significant , favourable difference was found between the results for the treatment group and those for the alternative groups . The therapy was found to be without risk , but patients with clinical signs of current lumbar nerve root compression or radiological signs of spondylolysis or halisteresis of the column were excluded from the study . The authors recommend the introduction of this form of treatment as a general offer in the primary and secondary health sector . Back exercises can advantageously be conducted in a group ; thus , the re sources required for this treatment do not differ significantly from those required for many of the other forms of treatment generally employed , which often require individual attention Study Design A r and omized prospect i ve trial of manipulation , massage , corset and transcutaneous muscle stimulation ( TMS ) was conducted in patients with subacute low back pain . Objectives The authors determined the relative efficacy of chiropractic treatment to massage , corset , and TMS . Summary of Background Data Although all of these treatments are used for subacute low back pain treatment , there have been few comparative trials using objective outcome criteria . Patients were enrolled for a period of 3 weeks . They were evaluated once a week by question naires , visual analog scale , range of motion , maximum voluntary extension effort , straight leg raising and Biering-Sorensen fatigue test . The dropout rate was highest in the muscle stimulation and corset groups and lowest in the manipulation group . Rates of full compliance did not differ significantly across treatments . A measure of patient confidence was greatest in the manipulation group . Results After 3 weeks , the manipulation group scored the greatest improvements in flexion and pain while the massage group had the best extension effort and fatigue time , and the muscle stimulation group the best extension . Conclusion None of the changes in physical outcome measures ( range of motion , fatigue , strength or pain ) were significantly different between any of the groups STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up OBJECTIVE The aim of this study was to investigate the comparison of massage therapy and routine physical therapy on patients with sub acute and chronic nonspecific low back pain . METHODS AND MATERIAL S Thirty volunteer female subjects with a sub acute or chronic nonspecific low back pain were r and omly enrolled in two groups , massage therapy and routine physical therapy . After massage application , the hamstring and paravertebral muscles stretching and also stabilizing exercises were prescribed . In the routine physical therapy group , TENS , US and vibrator were used besides exercises . Pain intensity according to Numerical Rating Scale , functional disability level in accordance to Oswestry Disability Index , and modified Schober test , for measurement of flexion range of motion , before and after ten sessions of treatment were used to evaluate the effectiveness of the treatment . RESULTS Pain intensity , Oswestry Disability Index and flexion range of motion had shown significant differences before and after intervention in both groups ( p<0.001 ) . The statistical analysis revealed that the massage therapy had significantly improved the pain intensity and Oswestry Disability Index compared to routine physical therapy ( p=0.015 , p=0.013 respectively ) , but the range of motion changes were not significant between two groups ( p=1.00 ) . CONCLUSION It can be concluded that both massage therapy and routine physical therapy are useful for sub acute and chronic nonspecific low back pain treatment especially if accompanied with exercise . However , massage is more effective than other electrotherapy modalities , and it can be used alone or with electrotherapy for the treatment of patients with low back pain The authors carried out a single-blind , r and omized controlled clinical trial of rotational manipulation for low-back pain of recent onset in 81 adults . Control treatments were minimal massage and low-level electrostimulation . Initial status and outcome were measured on scales quantifying symptoms , activities of dally life , mobility , tenderness to palpation , aggravation of pain by coughing or sneezing , limitation of motion on testing , and forward flexion . Both treated and control patients improved rapidly in the 2 - 3-week observation period . On retest there was no statistically significant difference between the improvement scores of the treated or control groups on any of the scales OBJECTIVE To explore an exercise method for the prevention and treatment of the patients with shoulder and back fasciitis . METHODS From 2006.8 to 2008.3 , 120 patients with shoulder and back fasciitis were r and omly divided into control group ( n = 60 , including 21 females and 39 males , the average age was ( 47.0 + /- 12.0 ) years , and the average course of disease was ( 14.1 + /- 12.0 ) months ) and treatment group ( n = 60,including 19 females and 41 males , the average age was ( 43.7 + /- 9.9 ) years , and the average course of disease was ( 16.4 + /- 13.4 ) months ) . The patients in the control group received massage therapy and the ones in the treatment group were treated with massage therapy and horizontal bar exercise . After 3 weeks treatment , the curative effects of the patients in two groups were observed . All the patients were followed up for 6 to 26 months , the recurrence were observed . RESULTS After 3 weeks treatment , the scores of pain , sense of heaviness , strip sign , tenderness , shoulder and back function of the patients in two groups had significant differences compared with those before treatment ( all P < 0.01 ) . After treatment , the scores of pain , sense of heaviness , strip sign , tenderness , shoulder and back function of the patients in the treatment group were lower than those in the control group ( P < 0.05 ) . After 6 to 26 months following-up , the rate of recurrence in the treatment group was lower than that in the control group ( P < 0.01 ) . CONCLUSION Horizontal bar exercise is a simple , no expense and effective method in the prevention and treatment of shoulder and back fasciitis , which can improve the effect of the treatment and reduce the rate of recurrence There has been a recent increase in research evaluating treatment-based subgroups of non-specific low back pain . The aim of these sub-classification schemes is to identify subgroups of patients who will respond preferentially to one treatment as opposed to another . Our article provides accessible guidance on to how to interpret this research and determine its implication s for clinical practice . We propose that studies evaluating treatment-based subgroups can be interpreted in the context of a three-stage process : ( 1 ) hypothesis generation-proposal of clinical features to define subgroups ; ( 2 ) hypothesis testing-a r and omised controlled trial ( RCT ) to test that subgroup membership modifies the effect of a treatment ; and ( 3 ) replication-another RCT to confirm the results of stage 2 and ensure that findings hold beyond the specific original conditions . At this point , the bulk of research evidence in defining subgroups of patients with low back pain is in the hypothesis generation stage ; no classification system is supported by sufficient evidence to recommend implementation into clinical practice OBJECTIVE The current study was design ed as a pilot study for a r and omised controlled trial to investigate the effectiveness of reflexology in the management of low back pain ( LBP ) . MATERIAL S AND METHODS Participants suffering non-specific LBP were recruited and r and omised into either a reflexology or a sham group . Patients and outcome assessor were blinded to group allocation . Each patient received either a 40 min reflexology treatment or sham treatment ( according to group allocation ) once per week for six consecutive weeks . The primary outcome measure was pain ( visual analogue scale ) , secondary outcome measures were the McGill pain question naire , Rol and -Morris disability question naire , and SF-36 health survey . Outcome measures were performed at baseline , week 6 , week 12 and week 18 . RESULTS VAS scores for pain reduced in the treatment group by a median value of 2.5 cm , with minimal change in the sham group ( 0.2 cm ) . Secondary outcome measures produced an improvement in both groups ( McGill pain question naire : 18 points in the reflexology group and 11.5 points in the sham group ) . Results indicate that reflexology may have a positive effect on LBP . CONCLUSION Reflexology appears to offer promise as a treatment in the management of LBP ; however , an adequately powered trial is required before any more definitive pronouncements are possible OBJECTIVE To observe and compare the clinical effect of Dingweiban and Xieban manipulation , and to compare the change of the deviation of spinous processes between two methods . METHODS One hundred and twenty-two cases were divided into two groups . Sixty-two cases were treated with Dingweiban manipulation method and 60 cases by Xieban manipulation . The changes of Fairbank scores , the clinical effects and the difference of the deviation of the spinous processes ( L3 , L4 , L5 ) from the lumbar posterior-anterior X-ray were compared . RESULTS The scores before and after treatment and 3 months after treatment were compared . There were significant differences between two groups ( P < 0.05 ) by nonparametric test . The result of Dingweiban manipulation group : 53 cases cured , 5 cases better , 3 cases effective and 1 case no effect . The result of clinical Xieban manipulation group : 43 cases cured , 6 cases better , 7 cases effective and 4 cases no effect . The clinical effects had significant differences after treatment and 3 months after treatment ( P < 0.05 , P < 0.0l ) by nonparametric test . After the first treating , there was clear difference of the deviations ' distance of the L4 spinous process compared with the Xieban manipulation group ( P < 0.05 ) . After the last treating , there were clear differences of the deviation distance of the L4 and L5 spinous processes compared with the Xieban manipulation group ( P < 0.05 , P < 0.01 ) . CONCLUSION Dingweiban manipulation is better than Xieban manipulation in effects and has influence on the deviation of spinous processes , especially for the L5 spinous process Study Design . A sub analysis of data derived from a r and omized clinical trial was performed . Objective . To evaluate the association of a patient ’s expectation for benefit from a specific treatment with improved functional outcome . Summary of Background Data . Psychosocial factors , ambiguous diagnoses , and lack of a clearly superior treatment have complicated the management of patients with chronic low back pain . The authors hypothesized that patient expectation for benefit from a specific treatment is associated with improved functional outcomes when that treatment is administered . Methods . In a r and omized trial , 135 patients with chronic low back pain who received acupuncture or massage were studied . Before r and omization , study participants were asked to describe their expectations regarding the helpfulness of each treatment on a scale of 0 to 10 . The primary outcome was level of function at 10 weeks as measured by the modified Rol and Disability scale . Results . After adjustment for baseline characteristics , improved function was observed for 86 % of the participants with higher expectations for the treatment they received , as compared with 68 % of those with lower expectations ( P = 0.01 ) . Furthermore , patients who expected greater benefit from massage than from acupuncture were more likely to experience better outcomes with massage than with acupuncture , and vice versa ( P = 0.03 ) . Conclusions . The results of this study suggest that patient expectations may influence clinical outcome independently of the treatment itself . In contrast , general optimism about treatment , divorced from a specific treatment , is not strongly associated with outcome . These results may have important implication s for clinical trial design and recruitment , and may help to explain the apparent success of some conventional and alternative therapies in trials that do not control for patient expectations . The findings also may be important for therapy choices made in the clinical setting The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods 105 patients who had chronic low back pain without clinical signs of lumbar nerve root compression or radiological evidence of spondylolysis or osteomalacia were r and omised to three treatments : 30 sessions of intensive dynamic back extensor exercises over three months ; a similar programme at one-fifth the exercise intensity ; or one month of thermotherapy , massage , and mild exercises . The results consistently favoured intensive exercise , which had no adverse effects . Since these exercises can be conducted in groups , the intensive programme is no more costly than conventional strategies that require individual attention BACKGROUND CONTEXT Systematic review s of r and omized controlled trials suggest that spinal manipulative therapy ( SMT ) is efficacious for care of cervicogenic headache ( CGH ) . The effect of SMT dose on outcomes has not been studied . PURPOSE To compare the efficacy of two doses of SMT and two doses of light massage ( LM ) for CGH . PATIENT SAMPLE Eighty patients with chronic CGH . MAIN OUTCOME MEASURES Modified Von Korff pain and disability scales for CGH and neck pain ( minimum clinical ly important difference=10 on 100-point scale ) , number of headaches in the last 4 weeks , and medication use . Data were collected every 4 weeks for 24 weeks . The primary outcome was the CGH pain scale . METHODS Participants were r and omized to either 8 or 16 treatment sessions with either SMT or a minimal LM control . Patients were treated once or twice per week for 8 weeks . Adjusted mean differences ( AMD ) between groups were computed using generalized estimating equations for the longitudinal outcomes over all follow-up time points ( profile ) and using regression modeling for individual time points with baseline characteristics as covariates and with imputed missing data . RESULTS For the CGH pain scale , comparisons of 8 and 16 treatment sessions yielded small dose effects : |AMD|</=5.6 . There was an advantage for SMT over the control : AMD=-8.1 ( 95 % confidence interval=-13.3 to -2.8 ) for the profile , -10.3 ( -18.5 to -2.1 ) at 12 weeks , and -9.8 ( -18.7 to -1.0 ) at 24 weeks . For the higher dose patients , the advantage was greater : AMD=-11.9 ( -19.3 to -4.6 ) for the profile , -14.2 ( -25.8 to -2.6 ) at 12 weeks , and -14.4 ( -26.9 to -2.0 ) at 24 weeks . Patients receiving SMT were also more likely to achieve a 50 % improvement in pain scale : adjusted odds ratio=3.6 ( 1.6 to 8.1 ) for the profile , 3.1 ( 0.9 to 9.8 ) at 12 weeks , and 3.1 ( 0.9 to 10.3 ) at 24 weeks . Secondary outcomes showed similar trends favoring SMT . For SMT patients , the mean number of CGH was reduced by half . CONCLUSIONS Clinical ly important differences between SMT and a control intervention were observed favoring SMT . Dose effects tended to be small OBJECTIVE To investigate whether Myofascial release ( MFR ) when used as an adjunct to specific back exercises ( SBE ) reduces pain and disability in chronic low back pain ( CLBP ) in comparison with a control group receiving a sham Myofascial release ( SMFR ) and specific back exercises ( SBE ) among nursing professionals . DESIGN R and omized , controlled , single blinded trial . SETTING Nonprofit research foundation clinic in Kerala , India . PARTICIPANTS Nursing professionals ( N = 80 ) with chronic low back pain ( CLBP ) . INTERVENTIONS MFR group or control group . The techniques were administered by physiotherapists certified in MFR and consisted of 24 sessions per client over 8 weeks . MAIN OUTCOME MEASURE The McGill Pain Question naire ( MPQ ) was used to assess subjective pain experience and Quebec Back Pain Disability Scale ( QBPDS ) was used to assess the disability associated with CLBP . The primary outcome measure was the difference in MPQ and QBPDS scores between week 1 ( pretest score ) , week 8 ( posttest score ) , and follow-up at week 12 after r and omization . RESULTS The simple main effects analysis showed that the MFR group performed better than the control group in weeks 8 and 12 ( P < 0.005 ) . The patients in the MFR group reported a 53.3 % reduction in their pain and 29.7 % reduction in functional disability as shown in the MPQ and QBPDS scores in week 8 , whereas patients in the control group reported a 26.1 % and 9.8 % reduction in their MPQ and QBPDS scores in week 8 , which persisted as a 43.6 % reduction of pain and 22.7 % reduction of functional disability in the follow-up at week 12 in the MFR group compared to the baseline . The proportion of responders , defined as participants who had at least a 50 % reduction in pain between weeks 1 and 8 , was 73 % in the MFR group and 0 % in the control group , which was 0 % for functional disability in the MFR and control group . CONCLUSIONS This study provides evidence that MFR when used as an adjunct to SBE is more effective than a control intervention for CLBP in nursing professionals |
2,436 | 25,973,415 | OUTCOME / CONCLUSION Most of the studies showed favorable effects of Mediterranean diet on glycemic control and CVD , although a certain degree of controversy remains regarding some issues , such as obesity . | BACKGROUND Over the past few years , there has been a worldwide significant increase in the incidence of type II diabetes mellitus with both increase in morbidity and mortality .
Controlling diabetes through life style modifications , including diet and exercise has always been the cornerstone in diabetes management .
Increasing evidence suggests that the Mediterranean diet could be of benefit in diseases associated with chronic inflammation , including metabolic syndrome , diabetes , obesity as well as atherosclerosis , cancer , pulmonary diseases , and cognition disorders As a matter of fact , a number of studies addressed the relationship between Mediterranean diet and diabetes control .
The result of these studies was conflicting .
Some were able to elicit a protective role , while others showed no added benefit .
As a result ; we decided to conduct a systematic review to have a better underst and ing of the relationship between adherence to Mediterranean diet and diabetes control .
METHODS A systematic review was conducted on the effect of Mediterranean diet in diabetes control and cardiovascular risk modification as well as the possible mechanism through which this diet might exhibit its beneficial role . | BACKGROUND The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus ( DM2 ) is unclear . Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates . AIM The effects of a low carbohydrate Mediterranean ( LCM ) , a traditional Mediterranean ( TM ) , and the 2003 American Diabetic Association ( ADA ) diet were compared , on health parameters during a 12-month period . METHODS In this 12-month trial , 259 overweight diabetic patients ( mean age 55 years , mean body mass index 31.4 kg/m(2 ) ) were r and omly assigned to one of the three diets . The primary end-points were reduction of fasting plasma glucose , HbA1c and triglyceride ( TG ) levels . RESULTS 194 patients out of 259 ( 74.9 % ) completed follow-up . After 12 months , the mean weight loss for all patients was 8.3 kg : 7.7 kg for ADA , 7.4 kg for TM and 10.1 kg for LCM diets . The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet ( -2.0 and -1.6 % , respectively , p < 0.022 ) . HDL cholesterol increased ( 0.1 mmol/l + /- 0.02 ) only on the LCM ( p < 0.002 ) . The reduction in serum TG was greater in the LCM ( -1.3 mmol/l ) and TM ( -1.5 mmol/l ) than in the ADA ( -0.7 mmol/l ) , p = 0.001 . CONCLUSIONS An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups . Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control OBJECTIVE To test the effects of two Mediterranean diet ( MedDiet ) interventions versus a low-fat diet on incidence of diabetes . RESEARCH DESIGN AND METHODS This was a three-arm r and omized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center ( PREDIMED-Reus , northeastern Spain ) of the Prevención con Dieta Mediterránea [ PREDIMED ] study , a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk . Participants were r and omly assigned to education on a low-fat diet ( control group ) or to one of two MedDiets , supplemented with either free virgin olive oil ( 1 liter/week ) or nuts ( 30 g/day ) . Diets were ad libitum , and no advice on physical activity was given . The main outcome was diabetes incidence diagnosed by the 2009 American Diabetes Association criteria . RESULTS After a median follow-up of 4.0 years , diabetes incidence was 10.1 % ( 95 % CI 5.1–15.1 ) , 11.0 % ( 5.9–16.1 ) , and 17.9 % ( 11.4–24.4 ) in the MedDiet with olive oil group , the MedDiet with nuts group , and the control group , respectively . Multivariable adjusted hazard ratios of diabetes were 0.49 ( 0.25–0.97 ) and 0.48 ( 0.24–0.96 ) in the MedDiet supplemented with olive oil and nuts groups , respectively , compared with the control group . When the two MedDiet groups were pooled and compared with the control group , diabetes incidence was reduced by 52 % ( 27–86 ) . In all study arms , increased adherence to the MedDiet was inversely associated with diabetes incidence . Diabetes risk reduction occurred in the absence of significant changes in body weight or physical activity . CONCLUSIONS MedDiets without calorie restriction seem to be effective in the prevention of diabetes in subjects at high cardiovascular risk BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS Boston University Patricia Cortes Harvard University Claudia Goldin Swarthmore College Jennifer BACKGROUND Nuts appear to have cardiovascular benefits but their effect in diabetic patients is unclear . OBJECTIVE The objective was to assess effects of almond-enriched diets on insulin sensitivity and lipids in patients with normoglycemia or type 2 diabetes . DESIGN Study 1 assessed the effect of almonds on insulin sensitivity in 20 free-living healthy volunteers who received 100 g almonds/d for 4 wk . Study 2 was a r and omized crossover study that compared 4 diets in 30 volunteers with type 2 diabetes : 1 ) high-fat , high-almond ( HFA ; 37 % total fat , 10 % from almonds ) ; 2 ) low-fat , high-almond ( LFA ; 25 % total fat , 10 % from almonds ) ; 3 ) high-fat control ( HFC ; 37 % total fat , 10 % from olive or canola oil ) ; and 4 ) low-fat control ( LFC ; 25 % total fat , 10 % from olive or canola oil ) . After each 4-wk diet , serum lipids and oral glucose tolerance were measured . RESULTS In study 1 , almond consumption did not change insulin sensitivity significantly , although body weight increased and total and LDL cholesterol decreased by 21 % and 29 % , respectively ( P < 0.05 ) . In study 2 , total cholesterol was lowest with the HFA diet ( 4.46 + /- 0.14 , 4.52 + /- 0.14 , 4.63 + /- 0.14 , and 4.63 + /- 0.14 mmol/L with the HFA , HFC , LFA , and LFC diets , respectively ; P = 0.0004 for fat level ) . HDL cholesterol was significantly lower with the almond diets ( P = 0.002 ) ; however , no significant effect of fat source on LDL : HDL was observed . Glycemia was unaffected . CONCLUSIONS Almond-enriched diets do not alter insulin sensitivity in healthy adults or glycemia in patients with diabetes . Almonds had beneficial effects on serum lipids in healthy adults and produced changes similar to high monounsaturated fat oils in diabetic patients BACKGROUND Although the typical diet of the Mediterranean region has received much recognition over the past several years for its association with substantial health benefits , it remains unknown whether its favorable effects are mediated through changes in adiponectin concentrations . OBJECTIVE The objective was to determine whether adherence to a Mediterranean-type diet is associated with higher plasma adiponectin concentrations . DESIGN This study was a prospect i ve and cross-sectional evaluation of plasma adiponectin concentrations and dietary data from 987 diabetic women from the Nurses ' Health Study who had no history of cardiovascular disease at the time blood was drawn in 1990 . RESULTS Women who scored highest on a 9-point scale that measures adherence to a Mediterranean-type dietary pattern tended to be older , were less likely to be current smokers , had lower body mass indexes and waist circumferences , and had higher total energy intakes , physical activities , and plasma adiponectin concentrations than did women with the lowest scores . Median plasma adiponectin concentrations were 23 % higher in women who most closely followed a Mediterranean-type diet than in low adherers after adjustment for age and energy intake ( P < 0.01 ) . Body composition , lifestyle , and medical history explained some , but not all , of the observed association between diet and adiponectin concentrations because high adherers tended to have greater adiponectin concentrations than did moderate or low adherers , even after adjustment for these variables . CONCLUSIONS Our data suggest that , of the several components of the Mediterranean dietary pattern score , alcohol , nuts , and whole grains show the strongest association with adiponectin concentrations . Close adherence to a Mediterranean-type diet is associated with higher adiponectin concentrations BACKGROUND Adherence to the Mediterranean diet ( Med-Diet ) is associated with a reduced risk of cardiovascular disease ( CVD ) . However , the molecular mechanisms involved are not fully understood . OBJECTIVE The objective was to compare the effects of 2 Med-Diets with those of a low-fat diet on immune cell activation and soluble inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . DESIGN In a controlled study , we r and omly assigned 112 older subjects with diabetes or > or =3 CVD risk factors to 3 dietary intervention groups : Med-Diet with supplemental virgin olive oil ( VOO ) , Med-Diet with supplemental nuts , and low-fat diet . Changes from baseline in cellular and serum inflammatory biomarkers were assessed at 3 mo . RESULTS One hundred six participants ( 43 % women ; average age : 68 y ) completed the study . At 3 mo , monocyte expression of CD49d , an adhesion molecule crucial for leukocyte homing , and of CD40 , a proinflammatory lig and , decreased ( P < 0.05 ) after both Med-Diets but not after the low-fat diet . Serum interleukin-6 and soluble intercellular adhesion molecule-1 , inflammatory mediators crucial in firm adhesion of leukocytes to endothelial surfaces , decreased ( P < 0.05 ) in both Med-Diet groups . Soluble vascular cellular adhesion molecule-1 and C-reactive protein decreased only after the Med-Diet with VOO ( P < 0.05 ) , whereas interleukin-6 , soluble vascular cellular adhesion molecule-1 , and soluble intercellular adhesion molecule-1 increased ( P < 0.05 ) after the low-fat diet . CONCLUSIONS Med-Diets supplemented with VOO or nuts down-regulate cellular and circulating inflammatory biomarkers related to atherogenesis in subjects at high risk of CVD . The results support the recommendation of the Med-Diet as a useful tool against CVD 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 OBJECTIVE Few multiple lifestyle behavior change programs have been design ed to reduce the risk of coronary heart disease in postmenopausal women with type 2 diabetes . This study tested the effectiveness of the Mediterranean Lifestyle Program ( MLP ) , a comprehensive lifestyle self-management program ( Mediterranean low-saturated fat diet , stress management training , exercise , group support , and smoking cessation ) , in reducing cardiovascular risk factors in postmenopausal women with type 2 diabetes . RESEARCH DESIGN AND METHODS Postmenopausal women with type 2 diabetes ( n = 279 ) were r and omized to either usual care ( control ) or treatment ( MLP ) conditions . MLP participants took part in an initial 3-day retreat , followed by 6 months of weekly meetings , to learn and practice program components . Biological end points were changes in HbA(1c ) , lipid profiles , BMI , blood pressure , plasma fatty acids , and flexibility . Impact on quality of life was assessed . RESULTS Multivariate ANCOVAs revealed significantly greater improvements in the MLP condition compared with the usual care group on HbA(1c ) , BMI , plasma fatty acids , and quality of life at the 6-month follow-up . Patterns favoring intervention were seen in lipids , blood pressure , and flexibility but did not reach statistical significance . CONCLUSIONS These results demonstrate that postmenopausal women with type 2 diabetes can make comprehensive lifestyle changes that may lead to clinical ly significant improvements in glycemic control , some coronary heart disease risk factors , and quality of life OBJECTIVE Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes . Adiponectin , an adipocyte-derived plasma protein , has been found to be negatively associated with adiposity and positively associated with insulin sensitivity . Moderate alcohol consumption may increase adiponectin , which in turn causes a decrease of tumor necrosis factor (TNF)-alpha . A decreased TNF-alpha level may consequently increase insulin sensitivity . RESEARCH DESIGN AND METHODS To test this hypothesis , we performed a r and omized crossover partially diet-controlled study . A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky ( 40 g ethanol ) or tap water with dinner during two successive periods of 17 days . RESULTS Moderate alcohol consumption increased plasma adiponectin level ( 11 % ; P = 0.0002 ) but did not affect plasma TNF-alpha level . An increase in insulin sensitivity index was observed in an insulin-resistant subgroup ( 21 % ; P = 0.11 ) , which positively correlated with the relative alcohol-induced increase in plasma adiponectin level ( r = 0.73 , P = 0.02 ) . CONCLUSIONS The experimental results are in agreement with observational data . Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men , an effect that may be mediated through alcohol-induced increases in adiponectin Abstract Aim The aim of the study was to compare the effect of different dietary interventions on alanine aminotransferase ( ALT ) in obese patients with diabetes . Methods A post hoc analysis of an open label , parallel design , quasi-r and omised ( allocation by alternation ) , controlled trial , conducted in Israel . Obese patients with diabetes ( n = 259 ) , treated in the community , were central ly allocated to one of three diets : ( 1 ) the 2003 recommended American Diabetes Association diet ( ADA ) : 50–55 % carbohydrate , 30 % fat and 20 % protein , n = 85 ; ( 2 ) a low glycaemic index ( LGI ) diet : 50–55 % LGI carbohydrate , 30 % fat , 15–20 % protein , n = 89 ; or ( 3 ) a modified Mediterranean diet ( MMD ) : 35 % LGI carbohydrate , 45 % fat that was high in monounsaturated fat , 15–20 % protein , n = 85 . ALT was measured at 6 and 12 months . Results ALT levels decreased in all arms ; however , the MMD was associated with the lowest ALT levels at month 6 ( n = 201 : ADA n = 64 , LGI n = 73 , MMD n = 64 ) and month 12 of follow-up ( n = 179 ) . At 12 months mean ALT levels were 19.8 ± 1.4 U/l in the ADA diet arm ( n = 54 ) , 18.0 ± 1.5 U/l in the LGI diet arm ( n = 64 ) and 14.4 ± 1.7 in the MMD arm ( n = 61 , p < 0.001 ) . Evidence for an effect of diet on ALT levels persisted when controlling for post-r and omisation changes in waist to hip ratio , BMI , homeostasis model assessment ( HOMA ) or triacylglycerol . Conclusions A Mediterranean diet may have a beneficial effect on liver steatosis in obese patients with diabetes . Results of trials assessing the effect of dietary composition on clinical outcomes should be awaited before a decisive conclusion can be reached . In addition to clinical outcomes , such studies should address the issue of primary prevention of steatosis in high-risk and healthy individuals . Trial registration : Clinical Trials.gov NCT00520182 Funding : This study was supported by a grant from Tnuva Research Institute , Rehovot , Israel Background / Objectives : Although benefits have been attributed to the Mediterranean diet , its effect on glycaemic control has not been totally eluci date d. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects . Subjects/ Methods : A multicentric parallel trial was conducted on 191 participants ( 77 men and 114 women ) of the PREDIMED study in order to compare three dietary interventions : two Mediterranean diets supplemented with virgin olive oil ( n=67 ; body mass index ( BMI ) = 29.4±2.9 ) or mixed nuts ( n=74 ; BMI = 30.1±3.1 ) and a low-fat diet ( n=50 ; BMI = 29.8±2.8 ) . There were no drop-outs . Changes in body weight and waist circumference were determined . Insulin resistance was measured by HOMA-IR index , adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up . Results : Increased values of adiponectin/leptin ratio ( P=0.043 , P=0.001 and P<0.001 for low-fat , olive oil and nut diets , respectively ) and adiponectin/HOMA-IR ratio ( P=0.061 , P=0.027 and P=0.069 for low-fat , olive oil and nut diets , respectively ) and decreased values of waist circumference ( P=0.003 , P=0.001 and P=0.001 for low-fat , olive oil and nut diets , respectively ) were observed in the three groups . In both Mediterranean diet groups , but not in the low-fat diet group , this was associated with a significant reduction in body weight ( P=0.347 , P=0.003 and P=0.021 for low-fat , olive oil and nut diets , respectively ) . Conclusions : Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet BACKGROUND The rapid emergence of coronary artery disease ( CAD ) in south Asian people is not explained by conventional risk factors . In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid , we assessed the benefits of this diet for patients at high risk of CAD . METHODS We did a r and omised , single-blind trial in 1000 patients with angina pectoris , myocardial infa rct ion , or surrogate risk factors for CAD . 499 patients were allocated to a diet rich in whole grains , fruits , vegetables , walnuts , and almonds . 501 controls consumed a local diet similar to the step I National Cholesterol Education Program ( NCEP ) prudent diet . FINDINGS The intervention group consumed more fruits , vegetables , legumes , walnuts , and almonds than did controls ( 573 g [ SD 127 ] vs 231 g [ 19 ] per day p<0.001 ) . The intervention group had an increased intake of whole grains and mustard or soy bean oil . The mean intake of alpha-linolenic acid was two-fold greater in the intervention group ( 1.8 g [ SD 0.4 ] vs 0.8 g [ 0.2 ] per day , p<0.001 ) . Total cardiac end points were significantly fewer in the intervention group than the controls ( 39 vs 76 events , p<0.001 ) . Sudden cardiac deaths were also reduced ( 6 vs 16 , p=0.015 ) , as were non-fatal myocardial infa rct ions ( 21 vs 43 , p<0.001 ) . We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups , but especially in the intervention diet group . In the treatment group , patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group . INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet AIMS Individuals with Type 2 diabetes are at high risk for coronary heart disease , and may benefit from aggressive lifestyle modification . We evaluated the prevalence of Type 2 diabetes , in a Greek adult population , in relation to physical activity and dietary habits . METHODS From May 2001 to December 2002 , we r and omly enrolled 1514 men and 1528 women , with no evidence of cardiovascular or any other chronic disease . The sampling was stratified by the age and gender distribution of the general population in the greater area of Athens ( census 2001 ) . Diabetes was defined according to the established American Diabetes Association criteria . Dietary habits were assessed through a vali date d food frequency question naire and a diet score was developed , in which higher values suggest greater adherence to the Mediterranean diet . Weekly energy expenditure was assessed by considering frequency , duration and intensity of sports-related physical activity during a usual week . RESULTS After age adjustment for the Greek adult population ( 2001 census ) , the projected prevalence of Type 2 diabetes was 7.6 % in men and 5.9 % in women . A significant proportion of diabetic subjects ( 24 % of men and 30 % of women ) were unaware of their condition . Moreover , a 10-unit increase in the diet score was associated with 21 % lower odds of diabetes ( P < 0.05 ) , while individuals taking light physical activity were at 35 % lower odds ratio of diabetes compared with sedentary individuals ( P < 0.05 ) . CONCLUSIONS Diabetes mellitus is common in our population , with approximately 1 in 5 individuals with Type 2 diabetes being unaware of their condition . The lifestyle approach described here may contribute significantly to the reduction in the prevalence of diabetes , at a population level The " Spanish Ketogenic Mediterranean Diet " ( SKMD ) has been shown to be an effective and safe way to cure patients suffering from metabolic syndrome ( MS ) . Keeping in mind that nonalcoholic fatty liver disease ( NAFLD ) is closely associated with MS , the purpose of this study was to evaluate the potential therapeutic properties under free living conditions of the SKMD in patients with MS ( following the International Diabetes Federation [ IDF ] consensus guidelines ) and NAFLD ( suspected by using a cutoff value of alanine aminotransferase [ ALT ] levels of > 40 U/L and confirmed by abdominal ultrasonography ) over a 12-week period . A prospect i ve study was carried out in 14 obese men meeting the inclusion criteria and whose body mass index ( BMI ) and age were 36.58±0.54 kg/m² and 41.18±2.28 years , respectively . Statistical differences between the parameters studied before and after administration of the SKMD ( week 0 and 12 ) were analyzed by paired Student 's t test ( continuous variables ) and the χ² test ( discontinuous variables ) . P<.05 was considered statistically significant . There was an extremely significant ( P<.001 ) improvement in body weight ( from 109.79 kg to 95.86 kg ) , low-density lipoprotein-cholesterol ( from 123.43 mg/dL to 100.35 mg/dL ) , ALT ( from 71.92 U/L to 37.07 U/L ) , aspartate aminotransferase ( from 47.71 U/L to 29.57 U/L ) , steatosis degree ( complete fatty liver regression was observed in 21.4 % of the patients , and an overall reduction was found in 92.86 % of the patients ) , and all the parameters studied associated with the MS : BMI ( from 36.99 kg/m² to 32.42 kg/m² ) , waist circumference ( from 114.01 cm to 98.59 cm ) , fasting plasma glucose ( from 118.57 mg/dL to 90.14 mg/dL ) , triacylglycerols ( from 232.64 mg/dL to 111.21 mg/dL ) , high-density lipoprotein-cholesterol ( HDLc ) ( from 42.81 mg/dL to 58.71 mg/dL ) , systolic blood pressure ( from 142.86 mm Hg to 125.36 mm Hg ) , and diastolic blood pressure ( from 89.64 mm Hg to 77.86 mm Hg ) . After the diet all the subjects were free of MS according to the IDF definition , and 100 % of them had normal triacylglycerols and HDLc levels , in spite of the fact that 100 % of them still had a BMI of > 30 kg/m² . We conclude that the SKMD could be an effective and safe way to treat patients suffering from MS and the associated NAFLD Objective : We investigated the association between adherence to Mediterranean diet and fasting indices of glucose homoeostasis , in a Greek adult population . Methods : During 2001–2002 we r and omly enrolled 1514 men and 1528 women ( 18–89 years old ) without history of CVD , from the Attica area . Diabetes mellitus ( type 2 ) and impaired fasting glucose ( IFG ) were defined according to the established ADA criteria . Insulin resistance was evaluated by HOMA-IR . Dietary habits were assessed through a vali date d food frequency question naire and a diet score ( range 0–55 ) was developed ( higher values means greater adherence to the Mediterranean diet ) . Results : The overall prevalence of diabetes type 2 was 7.9 % in men and 6.0 % in women ( P = 0.05 ) . Mean diet score was 26.3 ± 6.8 in normoglycemic , 25.7 ± 6.4 in IFG and 22.2 ± 5.8 in diabetic subjects ( p < 0.001 ) . In normoglycemic subjects who were in the upper tertile of the diet score we observed 7 % lower glucose ( p < 0.05 ) , 5 % lower insulin ( p < 0.05 ) and 15 % lower HOMA-IR ( p < 0.01 ) levels compared to subjects in the lower tertile of the diet score . Additionally , in diabetic/IFG participants who where in the upper tertile of the diet score we observed 15 % lower glucose ( p < 0.05 ) , 15 % lower insulin ( p < 0.05 ) and 27 % lower HOMA-IR ( p < 0.01 ) levels compared to those in the lower tertile . However , multiple regression analysis , adjusted for age , sex , BMI , waist-to-hip ratio , physical activity , smoking status , and presence of hypertension and hypercholesterolemia , confirmed the previous associations in normoglycemic , but not in diabetic/IFG people . Conclusion : An inverse association was observed between adherence to Mediterranean diet and indices of glucose homeostasis , only in normoglycemic people BACKGROUND AND AIMS To investigate the impact of a diet modeled on the traditional Cretan Mediterranean diet on metabolic control and vascular risk in type 2 diabetes . METHODS AND RESULTS Twenty-seven subjects ( 47 - 77 yrs ) with type 2 diabetes were r and omly assigned to consume either the intervention diet ad libitum or their usual diet for 12 weeks and then cross over to the alternate diet . Most of the meals and staple foods for the intervention diet were provided . Lipids , glycemic variables , blood pressure , homocysteine , C-reactive protein , plasma carotenoids and body composition ( anthropometry and dual energy X-ray absorptiometry ) were assessed at baseline , and at the end of both diet periods . Dietary adherence was monitored using plasma carotenoid and fatty acid ( FA ) analysis , complemented by diet diaries . Compared with usual diet , on the ad libitum Mediterranean intervention diet glycosylated haemoglobin fell from 7.1 % ( 95 % CI : 6.5 - 7.7 ) to 6.8 % ( 95 % CI : 6.3 - 7.3 ) ( p=0.012 ) and diet quality improved significantly [ plant : animal ( g/day ) food ratio increased from 1.3 ( 95 % CI : 1.1 - 1.5 ) to 5.4 ( 95 % CI : 4.3 - 6.6 ) ( p<0.001 ) ] , plasma lycopene and lutein/zeaxanthin increased ( 36 % and 25 % , respectively ) , plasma saturated and trans FAs decreased , and monounsaturated FAs increased . CONCLUSION A traditional moderate-fat Mediterranean diet improves glycemic control and diet quality in men and women with well-controlled type 2 diabetes , without adverse effects on weight |
2,437 | 29,308,828 | We found insufficient evidence to determine whether administration of propofol would improve the quality and quantity of sleep in adults in the ICU . | BACKGROUND People in the intensive care unit ( ICU ) experience sleep deprivation caused by environmental disruption , such as high noise levels and 24-hour lighting , as well as increased patient care activities and invasive monitoring as part of their care .
Sleep deprivation affects physical and psychological health , and people perceive the quality of their sleep to be poor whilst in the ICU .
Propofol is an anaesthetic agent which can be used in the ICU to maintain patient sedation and some studies suggest it may be a suitable agent to replicate normal sleep .
OBJECTIVES To assess whether the quantity and quality of sleep may be improved by administration of propofol to adults in the ICU and to assess whether propofol given for sleep promotion improves both physical and psychological patient outcomes . | Introduction Many intensive care patients experience sleep disruption potentially related tonoise , light and treatment interventions . The purpose of this study was tocharacterise , in terms of quantity and quality , the sleep of intensive care patients , taking into account the impact of environmental factors . Methods This observational study was conducted in the adult ICU of a tertiary referralhospital in Australia , enrolling 57 patients . Polysomnography ( PSG ) was performedover a 24-hour period to assess the quantity ( total sleep time : hh : mm ) and quality ( percentage per stage , duration of sleep episode ) of patients ' sleep while in ICU.Rechtschaffen and Kales criteria were used to categorise sleep . Interrater checkswere performed . Sound pressure and illuminance levels and care events weresimultaneously recorded . Patients reported on their sleep quality in ICU using theRichards Campbell Sleep Question naire and the Sleep in Intensive Care Question naire . Data were summarised using frequencies and proportions or measures of central tendency and dispersion as appropriate and Cohen 's Kappa statistic wasused for interrater reliability of the sleep data analysis . Results Patients ' median total sleep time was 05:00 ( IQR : 02:52 to 07:14 ) . The majority ofsleep was stage 1 and 2 ( medians : 19 and 73 % ) with scant slow wave and REM sleep . The median duration of sleep without waking was 00:03 . Sound levels were high(mean Leq 53.95 dB(A ) during the day and 50.20 dB(A ) at night ) and illuminancelevels were appropriate at night ( median < 2 lux ) but low during the day(median : 74.20 lux ) . There was a median 1.7 care events/h . Patients ' meanself-reported sleep quality was poor . Interrater reliability of sleep staging washighest for slow wave sleep and lowest for stage 1 sleep . Conclusions The quantity and quality of sleep in intensive care patients are poor and may berelated to noise , critical illness itself and treatment events that disturb sleep . The study highlights the challenge of quantifying sleep in the critical care setting and the need for alternative methods of measuring sleep . The results suggest that a sound reduction program is required and other interventions toimprove clinical practice s to promote sleep in intensive care patients .Trial registration Australian New Zeal and clinical trial registry(http://www.anzctr.org.au/ ) : ACTRN12610000688088 Objective To assess and compare the impact of overnight sedation with midazolam or propofol on anxiety and depression levels , as well as sleep quality , in non-intubated patients in intensive care . Design Open , comparative , prospect i ve , r and omised study . Setting Surgical intensive care unit ( ICU ) in a university hospital . Patients 40 conscious patients expected to stay in the ICU for at least 5 days who were admitted following trauma or elective orthopaedic , thopaedic , thoracic or abdominal surgery . Measurements and results Evaluation of a self- assessment scale ( Hospital Anxiety and Depression Scale , HAD ) on the day following the 1st , 3rd and 5th night of sedation with either midazolam or propofol . Heart rate , pulse oximetry and blood gases were monitored . Eight patients were excluded from the analysis . The level of anxiety was severe ( HAD>10 ) in 31 % of the patients receiving midazolam and in 26 % ( p=0.1 ) receiving propofol after the first night of sedation , with no significant improvement over the next few days . The levels of depression remained high ( > 10 ) in 54 % of patients receiving midazolam , and in 16 % of the patients receiving propofol ( p=0.15 ) . Sleep quality tended to improve during the study in the two groups . Conclusions These data show that half of the patients in the ICU experienced high levels of anxiety and depression during the first 5 postoperative or post-trauma days in the ICU . The beneficial effects of sedation on sleep quality were comparable for midazolam and propofol , regardless of a lack of improvement in anxiety and depression . However , an improved quality of sleep could help to re-establish a physiological night and day rhythm Objective : To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium , coma , and delayed liberation from mechanical ventilation . Design : Single-center , prospect i ve cohort study nested within the Awakening and Breathing Controlled r and omized trial . Setting : Saint Thomas Hospital in Nashville , TN , from 2004 to 2006 . Patients : Adult patients receiving mechanical ventilation for > 12 hrs with continuous recording of hourly sedation dosing . Interventions : We measured hourly doses of benzodiazepine and propofol exposure during the daytime ( 7 AM to 11 PM ) and nighttime ( 11 PM to 7 AM ) for 5 days . We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose . We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium , coma , and delayed liberation from mechanical ventilation . Measurements and Main Results : Among 140 patients , the median Acute Physiology and Chronic Health Evaluation II score was 27 ( interquartile range 22–33 ) . Among those receiving the sedatives , benzodiazepine and propofol doses were increased at night on 40 % and 41 % of patient-days , respectively . Of 485 patient-days , delirium was present on 160 ( 33 % ) and coma on 206 ( 42 % ) . In adjusted models , greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation , and subsequent delirium ( p < .02 for all ) . Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial ( p < .01 ) and delirium ( p = .05 ) . Daytime propofol dose was marginally associated with subsequent delirium ( p = .06 ) . Conclusions : Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night , a practice associated with failed spontaneous breathing trials , coma , and delirium . Over the first 5 days in our study , patients spent 75 % of their time in coma or delirium , outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit Objective To assess survival , morbidity ( physical and psychological ) , quality of life ( QOL ) , and employment status of intensive care survivors up to 12 months after discharge from the intensive care unit ( ICU ) . Design Prospect i ve study . Setting University hospital adult ICU . Patients Between August 1 , 1995 , and July 31 , 1996 , 370 patients were admitted . Of these patients , 29 % died in the ICU . Three months after discharge from the ICU , 227 patients were alive , and 143 agreed to participate . Cumulative mortality was calculated using the original complete cohort . Measurements and Main Results Demographic data , severity of acute illness ( Acute Physiology and Chronic Health Evaluation [ APACHE ] II ) , admitting specialty , primary diagnosis , and length of stay were recorded . Physical and ICU-related psychological morbidity ( Hospital Anxiety and Depression scale score ) were recorded . Health-related QOL was assessed using the Short-Form 36 . All the question naires were completed in the clinic at 3 months . Assessment of physical morbidity and employment status at 6 and 12 months were conducted by telephone . The cumulative mortality was 39 % at 3 months , 41 % at 6 months , and 43 % at 12 months . Deaths after 3 months occurred in the group who refused follow-up . The median age for the follow-up group was 51 yrs ; the gender split was 68 women and 75 men ; the mean admission APACHE II score was 18.79 ( sd 6.15 ) ; and the median length of ICU stay was 3.8 days . At 3 months , ∼80 % of all patients interviewed were satisfied with their QOL . Older men ( > 65 yrs ) and younger women ( < 65 yrs ) demonstrated significantly better health with respect to some subdomains of the Short-Form 36 compared with their counterparts . The prevalence of psychological distress ( Hospital Anxiety and Depression scale score , ≥8 ) was low : 11.9 % had heightened anxiety , and 9.8 % were depressed . There were high levels of fatigue , poor concentration , and sleep disturbance ; the latter was more marked in women ( p = .022 ) . Improvement in all three symptoms occurred during the next 9 months . Significantly more women reported loss of hair ( p < .0001 ) . Men were slower to return to employment ; 75 % of women had returned by 6 months compared with only 65 % of men at 1 yr . Conclusion Assessment of outcome after ICU stay must include QOL measurements . Three months after discharge , there is a low incidence of ICU-related psychological or psychiatric illness and the majority of patients are satisfied . Differences in the incidence and nature of morbidity exist between the genders STUDY OBJECTIVES The effect of opioid medications on sleep architecture has been demonstrated in patients with comorbid pain or opioid addiction . This study examined whether commonly used opioid medications have an adverse effect on sleep architecture in healthy adults . METHODS Forty-two healthy subjects were examined with polysomnography after a bedtime dose of placebo , sustained-release morphine sulfate ( 15 mg ) , or methadone ( 5 mg ) on each of 3 different nights in a double-blind multiple crossover study in a sleep laboratory in the General Clinical Research Center at an academic medical center . RESULTS Both opioid drugs significantly reduced deep sleep and increased stage 2 sleep ( both p < .01 ) ; neither had an effect on sleep efficiency , wake after sleep onset , or total sleep time . CONCLUSIONS Single doses of oral opioid medications can significantly affect sleep architecture in healthy adults , and observed reductions in slow-wave sleep following opioid administration may have important implication s for the pathogenesis of opioid-use related fatigue Objective : The assessment of propofol to produce diurnal sedation in critically ill patients Design : Prospect i ve clinical study Setting : Intensive Care Unit , University Hospital Patients and participants : Thirty consecutive patients admitted to the Intensive Care Unit older than 18 years who were expected to be se date d for more than 50 h Interventions : The patients were r and omised into two groups . All received sedation with a constant background infusion of morphine and a variable infusion rate of propofol , which was altered hourly to maintain the intended sedation score . The first group received constant light sedation ( CLS ) over 50 h aim ing for a Ramsay score of 2–3 . The second group received CLS between 0600 h and 2200 h and additional night sedation ( ANS ) with propofol between 2200 h and 0600 h , aim ing for a sedation score of 4–5 . Measurements and results : Patients were studied for 50 h from 1800 h on the first day of admission . Recordings of heart rate , blood pressure , sedation scores and propofol and morphine infusion rates were made hourly . An APACHE II score was recorded for each patient . Sedation scores were analysed by blind visual assessment and cosinor analysis , which is used in chronobiology to examine the correlation of data with a cosine curve . Patients in the ANS group had significantly better rhythmicity of sedation levels using cosinor analysis ( r = 26 % v 8 % ) p < 0.01 . There was no difference between the CLS and ANS groups with respect to age , sex or APACHE II scores . Nine out of 15 patients in the ANS group achieved diurnal sedation . Three patients in the CLS group showed diurnal rhythmicity of sedation , which can be attributed to natural sleep , and had a median APACHE II score of 12 . Five patients in the CLS group and three in the ANS group showed a deep constant sedation pattern . They had high APACHE II scores ( median 21.5 ) and an obtunded conscious level on admission due to severe sepsis . Conclusion : Propofol can safely provide diurnal sedation in the critically ill when titrated against the Ramsay score . Sedation levels can not be manipulated in some severely ill patients CONTEXT In the intensive care unit ( ICU ) , delirium is a common yet underdiagnosed form of organ dysfunction , and its contribution to patient outcomes is unclear . OBJECTIVE To determine if delirium is an independent predictor of clinical outcomes , including 6-month mortality and length of stay among ICU patients receiving mechanical ventilation . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study enrolling 275 consecutive mechanically ventilated patients admitted to adult medical and coronary ICUs of a US university-based medical center between February 2000 and May 2001 . Patients were followed up for development of delirium over 2158 ICU days using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale . MAIN OUTCOME MEASURES Primary outcomes included 6-month mortality , overall hospital length of stay , and length of stay in the post-ICU period . Secondary outcomes were ventilator-free days and cognitive impairment at hospital discharge . RESULTS Of 275 patients , 51 ( 18.5 % ) had persistent coma and died in the hospital . Among the remaining 224 patients , 183 ( 81.7 % ) developed delirium at some point during the ICU stay . Baseline demographics including age , comorbidity scores , dementia scores , activities of daily living , severity of illness , and admission diagnoses were similar between those with and without delirium ( P>.05 for all ) . Patients who developed delirium had higher 6-month mortality rates ( 34 % vs 15 % , P = .03 ) and spent 10 days longer in the hospital than those who never developed delirium ( P<.001 ) . After adjusting for covariates ( including age , severity of illness , comorbid conditions , coma , and use of sedatives or analgesic medications ) , delirium was independently associated with higher 6-month mortality ( adjusted hazard ratio [ HR ] , 3.2 ; 95 % confidence interval [ CI ] , 1.4 - 7.7 ; P = .008 ) , and longer hospital stay ( adjusted HR , 2.0 ; 95 % CI , 1.4 - 3.0 ; P<.001 ) . Delirium in the ICU was also independently associated with a longer post-ICU stay ( adjusted HR , 1.6 ; 95 % CI , 1.2 - 2.3 ; P = .009 ) , fewer median days alive and without mechanical ventilation ( 19 [ interquartile range , 4 - 23 ] vs 24 [ 19 - 26 ] ; adjusted P = .03 ) , and a higher incidence of cognitive impairment at hospital discharge ( adjusted HR , 9.1 ; 95 % CI , 2.3 - 35.3 ; P = .002 ) . CONCLUSION Delirium was an independent predictor of higher 6-month mortality and longer hospital stay even after adjusting for relevant covariates including coma , sedatives , and analgesics in patients receiving mechanical ventilation The Bispectral Index ( BIS ) is a system used to measure sedation levels . Some investigators recently analyzed changes in the BIS during natural sleep in adults and found that the BIS diminished considerably as sleep became deeper . No such studies have been undertaken to investigate changes in the BIS in sleeping children . The aim of this work was to assess the trend of the BIS in the various stages of sleep in a group of children , performing a descriptive analysis on a limited number of cases . We evaluated 15 children with negative clinical findings and a normal electroencephalogram ( EEG ) as part of their follow-up for prior episodes of epilepsy , recording the BIS and EEG in a waking state , in the various stages of sleep and on reawaking . For each stage , the mean value , the st and ard deviation , and the range of BIS values were calculated . The results showed that the BIS decreased progressively as sleep became deeper . The correlation between the stage of sleep and the BIS was significant . On reawaking , a slow increase was apparent in the BIS STUDY OBJECTIVES The electrophysiological correlates of anesthetic sedation remain poorly understood . We used high-density electroencephalography ( hd-EEG ) and source modeling to investigate the cortical processes underlying propofol anesthesia and compare them to sleep . DESIGN 256-channel EEG recordings in humans during propofol anesthesia . SETTING Hospital operating room . PATIENTS OR PARTICIPANTS 8 healthy subjects ( 4 males ) . INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Initially , propofol induced increases in EEG power from 12 - 25 Hz . Loss of consciousness ( LOC ) was accompanied by the appearance of EEG slow waves that resembled the slow waves of NREM sleep . We compared slow waves in propofol to slow waves recorded during natural sleep and found that both population s of waves share similar cortical origins and preferentially propagate along the mesial components of the default network . However , propofol slow waves were spatially blurred compared to sleep slow waves and failed to effectively entrain spindle activity . Propofol also caused an increase in gamma ( 25 - 40 Hz ) power that persisted throughout LOC . Source modeling analysis showed that this increase in gamma power originated from the anterior and posterior cingulate cortices . During LOC , we found increased gamma functional connectivity between these regions compared to the wakefulness . CONCLUSIONS Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity STUDY OBJECTIVES To objective ly measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population . DESIGN Prospect i ve cohort analysis . SETTING University teaching hospital medical-surgical ICU . PATIENTS Twenty critically ill ( APACHE II [ acute physiology and chronic health evaluation II ] acute physiology score [ APS ] , 10 + /- 5 ) , mechanically ventilated adults ( male 12 , female 8 , age 62 + /- 15 years ) with mild to moderate acute lung injury ( lung injury score , 1.8 + /- 0.9 ) 10 + /- 7 days after admission to the ICU . MEASUREMENTS AND RESULTS Patients were divided into three groups based on 24-h polysomnography ( PSG ) findings . No patient demonstrated normal sleep . In the " disrupted sleep " group ( n = 8) , electrophysiologic sleep was identified and was distributed throughout the day ( 6:00 AM to 10:00 PM ; 4.0 + /- 2.9 h ) and night ( 10:00 PM to 6:00 AM ; 3.0 + /- 1.9 h ) with equivalent proportions of non-rapid eye movement ( NREM ) and rapid eye movement ( REM ) sleep . Nocturnal sleep efficiency was severely reduced ( 38 + /- 24 % ) with an increased proportion of stage 1 NREM sleep ( 40 + /- 28 % total sleep time [ TST ] ) and a reduced proportion of REM sleep ( 10 + /- 14 % TST ) . Severe sleep fragmentation was reflected by a high frequency of arousals ( 20 + /- 17/h ) and awakenings ( 22 + /- 25/h ) . Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients . These were classified either as " atypical sleep " ( n = 5 ) , characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep , or " coma " ( n = 7 ) , characterized by > 50 % delta or theta EEG activity with ( n = 5 ) and without ( n = 2 ) evidence of EEG activation either spontaneously or in response to deep painful stimuli . The combined atypical sleep and coma groups had a higher APS ( 13 + /- 4 vs 6 + /- 4 ) and higher doses of sedative medications than the disrupted sleep group . CONCLUSION Sleep , as it is conventionally measured , was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted . We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population Purpose To access the effect of propofol administration on sleep quality in critically ill patients ventilated on assisted modes . Methods This was a r and omized crossover physiological study conducted in an adult ICU at a tertiary hospital . Two nights ’ polysomnography was performed in mechanically ventilated critically ill patients with and without propofol infusion , while respiratory variables were continuously recorded . Arterial blood gasses were measured in the beginning and at the end of the study . The rate of propofol infusion was adjusted to maintain a sedation level of 3 on the Ramsay scale . Sleep architecture was analyzed manually using predetermined criteria . Patient – ventilator asynchrony was evaluated breath by breath using the flow – time and airway pressure – time waveforms . Results Twelve patients were studied . Respiratory variables , patient – ventilator asynchrony , and arterial blood gasses did not differ between experimental conditions . With or without propofol all patients demonstrated abnormal sleep architecture , expressed by lack of sequential progression through sleep stages and their abnormal distribution . Sleep efficiency , sleep fragmentation , and sleep stage distribution ( 1 , 2 , and slow wave ) did not differ with or without propofol . Compared to without propofol , both the number of patients exhibiting REM sleep ( p = 0.02 ) and the percentage of REM sleep ( p = 0.04 ) decreased significantly with propofol . Conclusions In critically ill patients ventilated on assisted modes , propofol administration to achieve the recommended level of sedation suppresses the REM sleep stage and further worsens the poor sleep quality of these patients Disturbed sleep and sleep deprivation is common in patients in critical care setting s. Noise and inappropriate use of light/dark cycles are two of the causes of sleep interruptions . The purpose of the study was to evaluate eye masks and earplugs to help control patients ' exposure to noise and light within the critical care environment . An intervention study using a two group post-test quasi-experimental design of high dependency patients within a cardiothoracic critical care unit was undertaken by a group of critical care nurses . Sleep assessment rating scales and open-ended questions were used to obtain patients ' reported experiences of their sleep . Patients self-selected into either an intervention or non-intervention group . Sixty-four patients consented to take part in the study , 34 patients tried the interventions earplugs and eye masks and many found they improved sleep . However , noise was still a factor preventing sleep for both groups of patients . Mixed reports were found with the interventions from very comfortable to very uncomfortable . At a cost of 2.50 pounds sterling/patient , earplugs and eye masks were a relatively cheap intervention with notable improvements for some critically ill patients . Further research is required with a larger sample size , plus an examination of both earplugs and eye masks separately . Offering patient 's earplugs and eye masks to improve sleep should be considered as a matter of routine nursing practice , this should include time to show patients how to use and try them out for comfort OBJECTIVE To se date the mechanically ventilation patients in intensive care unit ( ICU ) with stimulative circadian rhythm , and evaluate whether the protocol has advantages in recovering natural circadian rhythm , duration of mechanical ventilation , and length of ICU stay after weaning of sedation . METHODS A prospect i ve r and om control trial was conducted . One hundred and twenty ventilated patients in ICU were r and omly assigned to four groups : circadian rhythm ( CR ) , daily interruption ( DI ) , continuous sedation ( CS ) or dem and sedation ( DS ) group , each n = 30 . Given more complications , DS group was deleted after recruiting 10 cases and 90 patients were admitted ultimately . Patients ' age , gender , body weight , acute physiology and chronic health evaluation II ( APACHE II ) scores , sedatives dosages , daily arousal time , duration of mechanical ventilation , length of ICU stay , complications ( ventilator-associated pneumonia , barotrauma with intrathoracic drain tube ) and untoward reactions ( accidental extubation , reintubation , tracheotomy , death ) were recorded , the biochemical indicators were determined , as well as number of nurses on duty at 10:00 and 22:00 . RESULTS The patients ' sex ratio , age , body weight , APACHEII scores , duration of mechanical ventilation , length of ICU stay showed no difference among CR , DI and CS groups . The total sedatives dosages ( mg : 5466.7 ± 620.4 ) and average sedatives dosages [ mg × h(-1 ) ×kg(-1 ) : 2.19 ± 0.61 ] in CS group were significantly higher than those in CR group ( 4344.5 ± 816.0 , 1.00 ± 0.51 ) and DI group ( 4154.3 ± 649.4 , 1.23 ± 0.62 , all P < 0.01 ) , and there was no difference between CR group and DI group . Daily arousal time in the CR group ( hours : 4.40 ± 1.30 ) was significantly lengthened compared with that in DI group ( 0.59 ± 0.26 ) and CS group ( 0.15 ± 0.02 , both P < 0.05 ) . The complications showed no differences in each group , but incidences of the untoward reactions in DI group ( 2 cases ) were significantly increased compared with that in CR group ( 1 case ) and CS group ( 0 case , P = 0.0477 ) . After weaning of sedation , patients with normal circadian rhythm were significantly more in CR group than that in CS group ( 19 vs. 9 , P = 0.0339 ) . Among CR group , DI group and CS group , there were significant differences in the numbers of nurses on duty in the daytime ( 1.65 , 1.41 , 1.14 , all P < 0.01 ) , but there was no difference in the night . The biochemistry index showed no difference in each group . CONCLUSIONS It demonstrated that sedation with stimulative circadian rhythm be helpful to create circadian rhythm after weaning of sedation . While complications and untoward reactions did not increase , as well as duration of mechanical ventilation and length of ICU stay . Therefore , the clinical applicability of this sedative strategy was highlighted Background / objectives Delirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit ( ICU ) population . It was first described more than half a century ago , where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay , reduced quality of life and increased mortality . However , in most cases , there is still lack of proof for causal relationship . Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form . Furthermore , in the general ICU population , it has been shown that the duration of delirium is associated with worse long-term cognitive function . Due to the multifactorial origin of delirium , we have several but no incontestable treatment options . Nonetheless , delirium bears a high burden for patient , family members and the medical care team . The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients . We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan . Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general . This could further contribute to higher patient safety . The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU . We hypothesise that dexmedetomidine , compared with propofol administered at night , shortens both the duration and severity of delirium . Methods / design The Basel ProDex Study is an investigator-initiated , one-institutional , two-centre r and omised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium . The primary outcome measure is delirium duration in hours . Secondary outcomes include delirium-free days at day 28 , death at day 28 , delirium severity , amount of ventilator days , amount of rescue sedation with haloperidol , length of ICU and hospital stay , and pharmaceutical economic analysis of the treatments . Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours . The trial will be externally monitored according to good clinical practice ( GCP ) requirements . There are no interim analyses planned for this trial . Ethics and dissemination This study will be conducted in compliance with the protocol , the current version of the Declaration of Helsinki , the International Conference on Harmonization- Good Clinical Practice ( ICH-GCP ) or Europäische Norm International Organization for St and ardization ( ISO EN 14155 ; as far as applicable ) as well as all national legal and regulatory requirements . Only the study team will have access to trial specific data . Anonymisation will be achieved by a unique patient identification code . Trial data will be archived for a minimum of 10 years after study termination . We plan to publish the data in a major peer- review ed clinical journal . Trials registration Clinical Trials.gov Identifier : NCT02807467 Protocol version Clinical Study Protocol Version 2 , Context : Sleep deprivation is a common problem on intensive care units ( ICUs ) influencing not only cognition , but also cellular functions . An appropriate sleep-wake cycle should therefore be maintained to improve patients ’ outcome . Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-se date d. Aims : The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam . Setting s and Design : Monocentric , r and omized , double-blinded trial . Material s and Methods : A total of 66 ICU patients were enrolled in the study ( flunitrazepam n = 32 , propofol n = 34 ) . Propofol was injected continuously ( 2 mg/kg/h ) , flunitrazepam as a bolus dose ( 0.015 mg/kg ) . Differences between groups were evaluated using a st and ardized sleep diary and the bispectral index ( BIS ) . Statistical Analysis Used : Group comparisons were performed by Mann-Whitney U-Test . P < 0.05 was considered to be statistically significant . Results : Sleep quality and the frequency of awakenings were significantly better in the propofol group ( Pg ) . In the same group lower BIS values were recorded ( median BIS propofol 74.05 , flunitrazepam 78.7 [ P = 0.016 ] ) . BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam . Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration . Conclusions : Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-se date d was superior to flunitrazepam regarding sleep quality and sleep structure Background : Patients admitted to the intensive care unit ( ICU ) after surgery often develop sleep disturbances . The authors tested the hypothesis that low-dose dexmedetomidine infusion could improve sleep architecture in nonmechanically ventilated elderly patients in the ICU after surgery . Methods : This was a pilot , r and omized controlled trial . Seventy-six patients age 65 yr or older who were admitted to the ICU after noncardiac surgery and did not require mechanical ventilation were r and omized to receive dexmedetomidine ( continuous infusion at a rate of 0.1 & mgr;g kg−1 h−1 ; n = 38 ) or placebo ( n = 38 ) for 15 h , i.e. , from 5:00 PM on the day of surgery until 8:00 AM on the first day after surgery . Polysomnogram was monitored during the period of study -drug infusion . The primary endpoint was the percentage of stage 2 non – rapid eye movement ( stage N2 ) sleep . Results : Complete polysomnogram recordings were obtained in 61 patients ( 30 in the placebo group and 31 in the dexmedetomidine group ) . Dexmedetomidine infusion increased the percentage of stage N2 sleep from median 15.8 % ( interquartile range , 1.3 to 62.8 ) with placebo to 43.5 % ( 16.6 to 80.2 ) with dexmedetomidine ( difference , 14.7 % ; 95 % CI , 0.0 to 31.9 ; P = 0.048 ) ; it also prolonged the total sleep time , decreased the percentage of stage N1 sleep , increased the sleep efficiency , and improved the subjective sleep quality . Dexmedetomidine increased the incidence of hypotension without significant intervention . Conclusions : In nonmechanically ventilated elderly patients who were admitted to the ICU after noncardiac surgery , the prophylactic low-dose dexmedetomidine infusion may improve overall sleep quality |
2,438 | 28,219,420 | Findings from this review suggest that documentation of cord-care practice s is not consistent throughout low- and middle-income countries , yet existing literature depicts a firm tradition of umbilical cord care in every culture . | Background Neonatal sepsis is the third leading cause of deaths for infants in their first month of life .
The newly cut umbilical cord can be a pathway for bacteria that can cause newborn sepsis and death .
Optimal umbilical cord care practice s for newborns and during the first week of life , especially in setting s with poor hygiene , has the potential to avoid these preventable neonatal deaths .
The purpose of this review of cord care practice s is to assist in the development of behavior-change strategies to support introduction of novel cord-care regimens , particularly 7.1 % chlorhexidine digluconate for umbilical cord care . | Background Every year four million babies die in the first month of life and a quarter of these take place in India . A package of essential newborn care practice s exists , which has a proven impact on reducing mortality , and can be implemented in low re source setting s. However , childbirth and the neonatal period are culturally important times , during which there is strong adherence to traditional practice s. Successful implementation of the package therefore requires in-depth knowledge of the local context and tailored behaviour change communication . Methods This study was carried out in rural Karnataka , India . It uses quantitative data from a prospect i ve survey following mothers through their experience of pregnancy and the postnatal period ; and qualitative data from in depth interviews and focus group discussion s conducted with mothers , gr and mothers and birth attendants . It explores local newborn care practice s and beliefs , analyses their harmful or beneficial characteristics and eluci date s areas of potential resistance to behaviour change and implementation of the essential newborn care package . Results Findings show that many potentially harmful newborn care practice s are being carried out in the study area , such as unhygienic cord cutting , delayed breastfeeding and early bathing . Some are more amenable to change than others , depending on the strength of the underlying beliefs , and acceptability of alternative care . However , movement away from traditional practice s is already taking place , particularly amongst the more educated and better off , and there is a clear opportunity to broaden , direct and accelerate this process . Conclusion Community education should be a focus of the National Rural Health Mission ( NRHM ) and Integrated Management of Neonatal and Childhood Illness ( IMNCI ) program being implemented in Karnataka . The added capacity of the new Accredited Social Health Activists ( ASHAs ) could enable more women to be reached . With careful tailoring of behaviour change messages to the local context , government outreach workers can become effective brokers of positive change and significant improvements in home newborn care and neonatal mortality are possible BACKGROUND In low-income countries , including the east African region , a third of neonatal deaths are due to infections . A substantial proportion of these have been attributed to sepsis , which can result from umbilical cord infections . Evidence from Asia suggests that chlorhexidine application to the neonatal umbilical cord reduces mortality , but no data from Africa are available . We aim ed to assess the effect of umbilical cord cleansing with 4 % chlorhexidine solution on neonatal mortality and omphalitis in rural setting s of sub-Saharan Africa . METHODS We did a community-based r and omised controlled trial on Pemba Isl and , Zanzibar , Tanzania . All eligible babies ( aged 1 h to 48 h , without congenital malformations ) from hospital-based and community-based deliveries on Pemba Isl and were enrolled . Participants were r and omly assigned to either 4 % free chlorhexidine for cord care or to dry cord care using a computer-generated r and om sequence . For babies allocated to the chlorhexidine group , mothers or caretakers were advised to apply the solution to the cord every day until 3 days after the cord had dropped off . Cord stumps were examined for redness , pus , swelling , and foul odour on day 0 , 1 , 4 , 10 , and 28 . The primary outcome for this study was mortality until day 28 on an intention-to-treat basis . The trial is registered with Clinical Trials.gov , number NCT01528852 . FINDINGS Between May 19 , 2011 , and Aug 31 , 2014 , 36 911 newborn babies were enrolled into the chlorhexidine ( n=18 015 ) and dry cord care study ( n=18 896 ) groups . 17 468 ( 96·9 % ) of 18 015 neonates in the chlorhexidine group were available for complete follow-up ( 28 days ) compared with 18 384 ( 97·3 % ) of 18 896 neonates in the dry cord care group . Mortality rate in the chlorhexidine group ( 10·5 deaths per 1000 livebirths ) was not significantly lower than that in the dry cord care group ( 11·7 per 1000 livebirths ; relative risk 0·90 , 0·74 - 1·09 ; p=0·27 ) . INTERPRETATION Our findings do not support the use of chlorhexidine for reduction of neonatal mortality in this east African setting , which might not justify a change in the WHO policy . To inform global policy , a detailed meta- analysis and pooled analysis needs to be undertaken using data from both African and Asian setting s. FUNDING Bill & Melinda Gates Foundation BACKGROUND Chlorhexidine umbilical cord washes reduce neonatal mortality in south Asian population s with high neonatal mortality rates and predominantly home-based deliveries . No data exist for sub-Saharan African population s with lower neonatal mortality rates or mostly facility-based deliveries . We compared the effect of chlorhexidine with dry cord care on neonatal mortality rates in Zambia . METHODS We undertook a cluster-r and omised controlled trial in Southern Province , Zambia , with 90 health facility-based clusters . We enrolled women who were in their second or third trimester of pregnancy , aged at least 15 years , and who would remain in the catchment area for follow-up of 28 days post-partum . Newborn babies received clean dry cord care ( control ) or topical application of 10 mL of a 4 % chlorhexidine solution once per day until 3 days after cord drop ( intervention ) , according to cluster assignment . We used stratified , restricted r and omisation to divide clusters into urban or two rural groups ( located < 40 km or ≥40 km to referral facility ) , and r and omly assigned clusters ( 1:1 ) to use intervention ( n=45 ) or control treatment ( n=45 ) . Sites , participants , and field monitors were aware of their study assignment . The primary outcomes were all-cause neonatal mortality within 28 days post-partum and all-cause neonatal mortality within 28 days post-partum among babies who survived the first 24 h of life . Analysis was by intention to treat . Neonatal mortality rate was compared with generalised estimating equations . This study is registered at Clinical Trials.gov ( NCT01241318 ) . FINDINGS From Feb 15 , 2011 , to Jan 30 , 2013 , we screened 42 356 pregnant women and enrolled 39 679 women ( mean 436·2 per cluster [ SD 65·3 ] ) , who had 37 856 livebirths and 723 stillbirths ; 63·8 % of deliveries were facility-based . Of livebirths , 18 450 ( 99·7 % ) newborn babies in the chlorhexidine group and 19 308 ( 99·8 % ) newborn babies in the dry cord care group were followed up to day 28 or death . 16 660 ( 90·0 % ) infants in the chlorhexidine group had chlorhexidine applied within 24 h of birth . We found no significant difference in neonatal mortality rate between the chlorhexidine group ( 15·2 deaths per 1000 livebirths ) and the dry cord care group ( 13·6 deaths per 1000 livebirths ; risk ratio [ RR ] 1·12 , 95 % CI 0·88 - 1·44 ) . Eliminating day 0 deaths yielded similar findings ( RR 1·12 , 95 % CI 0·86 - 1·47 ) . INTERPRETATION Despite substantial reductions previously reported in south Asia , chlorhexidine cord applications did not significantly reduce neonatal mortality rates in Zambia . Chlorhexidine cord applications do not seem to provide clear benefits for newborn babies in setting s with predominantly facility-based deliveries and lower ( < 30 deaths per 1000 livebirths ) neonatal mortality rates . FUNDING Bill & Melinda Gates Foundation The potential for traditional birth attendants ( TBAs ) to improve neonatal health outcomes has largely been overlooked during the current debate regarding the role of TBAs in improving maternal health . R and omly-selected TBAs ( n=93 ) were interviewed to gain a more thorough underst and ing of their knowledge , attitudes , and practice s regarding maternal and newborn care . Practice s , such as using a clean cord-cutting instrument ( 89 % ) and h and -washing before delivery ( 74 % ) , were common . Other beneficial practice s , such as thermal care , were low . Trained TBAs were more likely to wash h and s with soap before delivery , use a clean delivery-kit , and advise feeding colostrum . Although mustard oil massage was a universal practice , 52 % of the TBAs indicated their willingness to consider alternative oils . Low-cost , evidence -based interventions for improving neonatal outcomes might be implemented by TBAs in this setting where most births take place in the home and neonatal mortality risk is high . Continuing efforts to define the role of TBAs may benefit from an emphasis on their potential as active promoters of essential newborn care Newborn cord care practice s may directly contribute to infections , which account for a large proportion of the four million annual global neonatal deaths . This formative research study assessed current umbilical and skin care knowledge and practice s for neonates in Sylhet District , Bangladesh , in preparation for a cluster-r and omized trial of the impact of topical chlorhexidine cord cleansing on neonatal mortality and omphalitis . Unstructured interviews ( n=60 ) , structured observations ( n=20 ) , rating and ranking exercises ( n=40 ) and household surveys ( n=400 ) were conducted to elicit specific behaviors regarding newborn cord and skin care practice s. These included h and -washing , skin and cord care at the time of birth , persons engaged in cord care , cord cutting practice s , topical applications to the cord at the time of birth , wrapping/dressing of the cord stump and use of skin-to-skin care . Overall 90 % of deliveries occurred at home . The umbilical cord was almost always ( 98 % ) cut after delivery of the placenta , and cut by mothers in more than half the cases ( 57 % ) . Substances were commonly ( 52 % ) applied to the stump after cord cutting ; turmeric was the most common application ( 83 % ) . Umbilical stump care revolved around bathing , skin massage with mustard oil and heat massage on the umbilical stump . Overall 40 % of newborns were bathed on the day of birth . Mothers were the principal provider for skin and cord care during the neonatal period and 9 % of them reported umbilical infections in their infants . Unhygienic cord care practice s are prevalent in the study area . Efforts to promote h and -washing , cord cutting with clean instruments and avoiding unclean home applications to the cord may reduce exposure and improve neonatal outcomes . Such efforts should broadly target a range of caregivers , including mothers and other female household members BACKGROUND Omphalitis contributes to neonatal morbidity and mortality in developing countries . Umbilical cord cleansing with antiseptics might reduce infection and mortality risk , but has not been rigorously investigated . METHODS In our community-based , cluster-r and omised trial , 413 communities in Sarlahi , Nepal , were r and omly assigned to one of three cord-care regimens . 4934 infants were assigned to 4.0 % chlorhexidine , 5107 to cleansing with soap and water , and 5082 to dry cord care . In intervention clusters , the newborn cord was cleansed in the home on days 1 - 4 , 6 , 8 , and 10 . In all clusters , the cord was examined for signs of infection ( pus , redness , or swelling ) on these visits and in follow-up visits on days 12 , 14 , 21 , and 28 . Incidence of omphalitis was defined under three sign-based algorithms , with increasing severity . Infant vital status was recorded for 28 completed days . The primary outcomes were incidence of neonatal omphalitis and neonatal mortality . Analysis was by intention-to-treat . This trial is registered with , number NCT00109616 . FINDINGS Frequency of omphalitis by all three definitions was reduced significantly in the chlorhexidine group . Severe omphalitis in chlorhexidine clusters was reduced by 75 % ( incidence rate ratio 0.25 , 95 % CI 0.12 - 0.53 ; 13 infections/4839 neonatal periods ) compared with dry cord-care clusters ( 52/4930 ) . Neonatal mortality was 24 % lower in the chlorhexidine group ( relative risk 0.76 [ 95 % CI 0.55 - 1.04 ] ) than in the dry cord care group . In infants enrolled within the first 24 h , mortality was significantly reduced by 34 % in the chlorhexidine group ( 0.66 [ 0.46 - 0.95 ] ) . Soap and water did not reduce infection or mortality risk . INTERPRETATION Recommendations for dry cord care should be reconsidered on the basis of these findings that early antisepsis with chlorhexidine of the umbilical cord reduces local cord infections and overall neonatal mortality BACKGROUND In rural India , most births take place in the home , where high-risk care practice s are common . We developed an intervention of behaviour change management , with a focus on prevention of hypothermia , aim ed at modifying practice s and reducing neonatal mortality . METHODS We did a cluster-r and omised controlled efficacy trial in Shivgarh , a rural area in Uttar Pradesh . 39 village administrative units ( population 104,123 ) were allocated to one of three groups : a control group , which received the usual services of governmental and non-governmental organisations in the area ; an intervention group , which received a preventive package of interventions for essential newborn care ( birth preparedness , clean delivery and cord care , thermal care [ including skin-to-skin care ] , breastfeeding promotion , and danger sign recognition ) ; or another intervention group , which received the package of essential newborn care plus use of a liquid crystal hypothermia indicator ( ThermoSpot ) . In the intervention clusters , community health workers delivered the packages via collective meetings and two antenatal and two postnatal household visitations . Outcome measures included changes in newborn-care practice s and neonatal mortality rate compared with the control group . Analysis was by intention to treat . This study is registered as International St and ard R and omised Control Trial , number NCT00198653 . FINDINGS Improvements in birth preparedness , hygienic delivery , thermal care ( including skin-to-skin care ) , umbilical cord care , skin care , and breastfeeding were seen in intervention arms . There was little change in care-seeking . Compared with controls , neonatal mortality rate was reduced by 54 % in the essential newborn-care intervention ( rate ratio 0.46 [ 95 % CI 0.35 - 0.60 ] , p<0.0001 ) and by 52 % in the essential newborn care plus ThermoSpot arm ( 0.48 [ 95 % CI 0.35 - 0.66 ] , p<0.0001 ) . INTERPRETATION A socioculturally context ualised , community-based intervention , targeted at high-risk newborn-care practice s , can lead to substantial behavioural modification and reduction in neonatal mortality . This approach can be applied to behaviour change along the continuum of care , harmonise vertical interventions , and build community capacity for sustained development . FUNDING USAID and Save the Children-US through a grant from the Bill & Melinda Gates Foundation Introduction The World Health Organisation recommends home visits conducted by Community Health Workers ( in Ug and a known as Village Health Teams — VHTs ) in order to improve maternal and newborn health . This study measured the effect of home visits combined with mobile phone consultations on maternal and newborn care practice s. Method In a community intervention trial design 16 health centres in Masindi and Kiry and ongo districts , Ug and a were r and omly and equally allocated to one of two arms : control and intervention arms . Eight control health centres received the usual maternal and newborn educational messages offered by professional health workers and eight intervention health centres that received an intervention package for maternal care and essential newborn care practice s. In the intervention arm VHTs made two prenatal and one postnatal home visit to households . VHTs were provided with mobile phones to enable them make regular telephone consultations with health workers at the health centre serving the catchment area . The primary outcome was health facility delivery . Other outcomes included antenatal attendances , birth preparedness , cord and thermal care and breastfeeding practice s. Analysis was by intention-to-treat . Results A total of 1385 pregnant women were analysed : 758 and 627 in the control and intervention arms respectively . Significant post-intervention differences were : delivery place [ adjusted Odds Ratio aOR : 17.94(95%CI : 6.26–51.37 ) ; p<0.001 ] , cord care [ aOR : 3.05(95%CI : 1.81–5.12 ) ; p<0.001 ] thermal care [ aOR : 7.58(95%CI : 2.52–22.82 ) ; p<0.001 ] , and timely care-seeking for newborn illness [ aOR : 4.93(95%CI : 1.59–15.31 ) ; p = 0.006 ] . Conclusion VHTs can have an effect in promoting proper cord and thermal care for the newborn and improve timely care-seeking for health facility delivery and newborn illness , because they could answer questions and refer patients correctly . However , VHTs should be supported by professional health workers through the use of mobile phones . Trial Registration Clinical Trials.gov Background Global policy regarding optimal umbilical cord care to prevent neonatal illness is an active discussion among research ers and policy makers . In preparation for a large cluster-r and omized control trial to measure the impact of 4 % chlorhexidine as an umbilical wash versus dry cord care on neonatal mortality in Southern Province , Zambia , we performed a qualitative study to determine local perceptions of cord health and illness and the cultural belief system that shapes umbilical cord care knowledge , attitudes , and practice s. Methods and Findings This study consisted of 36 focus group discussion s with breastfeeding mothers , gr and mothers , and traditional birth attendants , and 42 in-depth interviews with key community informants . Semi-structured field guides were used to lead discussion s and interviews at urban and rural sites . A wide variation in knowledge , beliefs , and practice s surrounding cord care was discovered . For home deliveries , cords were cut with non-sterile razor blades or local grass . Cord applications included drying agents ( e.g. , charcoal , baby powder , dust ) , lubricating agents ( e.g. , Vaseline , cooking oil , used motor oil ) and agents intended for medicinal/protective purpose s ( e.g. , breast milk , cow dung , chicken feces ) . Concerns regarding the length of time until cord detachment were universally expressed . Blood clots in the umbilical cord , bulongo-longo , were perceived to foreshadow neonatal illness . Management of bulongo-longo or infected umbilical cords included multiple traditional remedies and treatment at government health centers . Conclusion Umbilical cord care practice s and beliefs were diverse . Dry cord care , as recommended by the World Health Organization at the time of the study , is not widely practice d in Southern Province , Zambia . A cultural health systems model that depicts all stakeholders is proposed as an approach for policy makers and program implementers to work synergistically with existing cultural beliefs and practice s in order to maximize effectiveness of evidence -based interventions BACKGROUND Up to half of neonatal deaths in high mortality setting s are due to infections , many of which can originate through the freshly cut umbilical cord stump . We aim ed to assess the effectiveness of two cord-cleansing regimens with the promotion of dry cord care in the prevention of neonatal mortality . DESIGN We did a community-based , parallel cluster-r and omised trial in Sylhet , Bangladesh . We divided the study area into 133 clusters , which were r and omly assigned to one of the two chlorhexidine cleansing regimens ( single cleansing as soon as possible after birth ; daily cleansing for 7 days after birth ) or promotion of dry cord care . R and omisation was done by use of a computer-generated sequence , stratified by cluster-specific participation in a previous trial . All livebirths were eligible ; those visited within 7 days by a local female village health worker trained to deliver the cord care intervention were enrolled . We did not mask study workers and participants to the study interventions . Our primary outcome was neonatal mortality ( within 28 days of birth ) per 1000 livebirths , which we analysed on an intention-to-treat basis . This trial is registered with Clinical Trials.gov , number NCT00434408 . RESULTS Between June , 2007 , and September , 2009 , we enrolled 29 760 newborn babies ( 10 329 , 9423 , and 10 008 in the multiple-cleansing , single-cleansing , and dry cord care groups , respectively ) . Neonatal mortality was lower in the single-cleansing group ( 22·5 per 1000 livebirths ) than it was in the dry cord care group ( 28·3 per 1000 livebirths ; relative risk [ RR ] 0·80 [ 95 % CI ] 0·65 - 0·98 ) . Neonatal mortality in the multiple-cleansing group ( 26·6 per 1000 livebirths ) was not statistically significantly lower than it was in the dry cord care group ( RR 0·94 [ 0·78 - 1·14 ] ) . Compared with the dry cord care group , we recorded a statistically significant reduction in the occurrence of severe cord infection ( redness with pus ) in the multiple-cleansing group ( risk per 1000 livebirths=4·2 vs risk per 1000 livebirths=1·2 ; RR 0·35 [ 0·15 - 0·81 ] ) but not in the single-cleansing group ( risk per 1000 livebirths=3·3 ; RR 0·77 [ 0·40 - 1·48 ] ) . INTERPRETATION Chlorhexidine cleansing of a neonate 's umbilical cord can save lives , but further studies are needed to establish the best frequency with which to deliver the intervention . FUNDING United States Agency for International Development and Save the Children 's Saving Newborn Lives program , through a grant from the Bill & Melinda Gates Foundation This study examined the effect of a job aids-focused intervention on quality of facility-based postnatal counseling , and whether increased communication improved in-hospital newborn care and maternal knowledge of home practice s and danger signs requiring urgent care . Ensuring mothers and newborns receive essential postnatal services , including health counseling , is integral to their survival . Yet , quality of clinic-based postnatal services is often low , and evidence on effective improvement strategies is scarce . Using a pre – post r and omized design , data were drawn from direct observations and interviews with 411 mother – newborn pairs . Multi-level regression models with difference-in-differences analyses estimated the intervention ’s relative effect , adjusting for changes in the comparison arm . The mean percent of recommended messages provided to recently-delivered women significantly improved in the intervention arm as compared to the control ( difference-in-differences [ ∆i − ∆c ] + 30.9 , 95 % confidence interval ( CI ) 19.3 , 42.5 ) , and the proportion of newborns thermally protected within the first hour ( ∆i − ∆c + 33.7 , 95 % CI 19.0 , 48.4 ) and delayed for bathing ( ∆i − ∆c + 23.9 , 95 % CI 9.4 , 38.4 ) significantly increased . No significant changes were observed in early breastfeeding ( ∆i − ∆c + 6.8 , 95 % CI −2.8 , 16.4 ) which was nearly universal . Omitting traditional umbilical cord substances rose slightly , but was insignificant ( ∆i − ∆c + 8.5 , 95 % CI −2.8 , 19.9 ) . The proportion of mothers with correct knowledge of maternal ( ∆i − ∆c + 27.8 , 95 % CI 11.0 , 44.6 ) and newborn ( ∆i − ∆c + 40.3 , 95 % CI 22.2 , 58.4 ) danger signs grew substantially , as did awareness of several home-care practice s ( ∆i − ∆c + 26.0 , 95 % CI 7.7 , 44.3 ) . Counseling job aids can improve the quality of postnatal services . However , achieving reduction goals in maternal and neonatal mortality will likely require more comprehensive approaches to link enhanced facility services with community-based initiatives BACKGROUND Umbilical cord infection ( omphalitis ) is a risk factor for neonatal sepsis and mortality in low-re source setting s where home deliveries are common . We aim ed to assess the effect of umbilical-cord cleansing with 4 % chlorhexidine ( CHX ) solution , with or without h and washing with antiseptic soap , on the incidence of omphalitis and neonatal mortality . METHODS We did a two-by-two factorial , cluster-r and omised trial in Dadu , a rural area of Sindh province , Pakistan . Clusters were defined as the population covered by a functional traditional birth attendant ( TBA ) , and were r and omly allocated to one of four groups ( groups A to D ) with a computer-generated r and om number sequence . Implementation and data collection teams were masked to allocation . Liveborn infants delivered by participating TBAs who received birth kits were eligible for enrolment in the study . One intervention comprised birth kits containing 4 % CHX solution for application to the cord at birth by TBAs and once daily by family members for up to 14 days along with soap and educational messages promoting h and washing . One intervention was CHX solution only and another was h and washing only . St and ard dry cord care was promoted in the control group . The primary outcomes were incidence of neonatal omphalitis and neonatal mortality . The trial is registered with Clinical Trials.gov , number NCT00682006 . FINDINGS 187 clusters were r and omly allocated to one of the four study groups . Of 9741 newborn babies delivered by participating TBAs , factorial analysis indicated a reduction in risk of omphalitis with CHX application ( risk ratio [RR]=0·58 , 95 % CI 0·41 - 0·82 ; p=0·002 ) but no evidence of an effect of h and washing ( RR=0·83 , 0·61 - 1·13 ; p=0·24 ) . We recorded strong evidence of a reduction in neonatal mortality in neonates who received CHX cleansing ( RR=0·62 , 95 % CI 0·45 - 0·85 ; p=0·003 ) but no evidence of an effect of h and washing promotion on neonatal mortality ( RR=1·08 , 0·79 - 1·48 ; p=0·62 ) . We recorded no serious adverse events . INTERPRETATION Application of 4 % CHX to the umbilical cord was effective in reducing the risk of omphalitis and neonatal mortality in rural Pakistan . Provision of CHX in birth kits might be a useful strategy for the prevention of neonatal mortality in high-mortality setting s. FUNDING The United States Agency for International Development |
2,439 | 28,775,845 | This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity .
The impact on measures of lung function or asthma control was however less clear .
We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT .
SLIT had a favorable safety profile when compared to SCIT , particularly in relation to the risk of systemic reactions .
Conclusions AIT has the potential to achieve reductions in symptom and medication scores , but there is no clear or consistent evidence that measures of lung function can be improved . | Background There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy ( AIT ) for the treatment of allergic asthma .
Objectives To undertake a systematic overview of the effectiveness , cost-effectiveness and safety of AIT for the treatment of allergic asthma . | RATIONALE Heterogeneity in asthma expression is multidimensional , including variability in clinical , physiologic , and pathologic parameters . Classification requires consideration of these disparate domains in a unified model . OBJECTIVES To explore the application of a multivariate mathematical technique , k-means cluster analysis , for identifying distinct phenotypic groups . METHODS We performed k-means cluster analysis in three independent asthma population s. Clusters of a population managed in primary care ( n = 184 ) with predominantly mild to moderate disease , were compared with a refractory asthma population managed in secondary care ( n = 187 ) . We then compared differences in asthma outcomes ( exacerbation frequency and change in corticosteroid dose at 12 mo ) between clusters in a third population of 68 subjects with predominantly refractory asthma , clustered at entry into a r and omized trial comparing a strategy of minimizing eosinophilic inflammation ( inflammation-guided strategy ) with st and ard care . MEASUREMENTS AND MAIN RESULTS Two clusters ( early-onset atopic and obese , noneosinophilic ) were common to both asthma population s. Two clusters characterized by marked discordance between symptom expression and eosinophilic airway inflammation ( early-onset symptom predominant and late-onset inflammation predominant ) were specific to refractory asthma . Inflammation-guided management was superior for both discordant subgroups leading to a reduction in exacerbation frequency in the inflammation-predominant cluster ( 3.53 [ SD , 1.18 ] vs. 0.38 [ SD , 0.13 ] exacerbation/patient/yr , P = 0.002 ) and a dose reduction of inhaled corticosteroid in the symptom-predominant cluster ( mean difference , 1,829 mug beclomethasone equivalent/d [ 95 % confidence interval , 307 - 3,349 mug ] ; P = 0.02 ) . CONCLUSIONS Cluster analysis offers a novel multidimensional approach for identifying asthma phenotypes that exhibit differences in clinical response to treatment algorithms Abstract Background The occurrence of allergic multimorbidity ( coexistence of asthma , allergic rhinitis and eczema ) has not been evaluated longitudinally from early childhood up to adulthood in a population ‐based study sample . We aim ed to determine the prevalence of allergic multimorbidity up to age 20 stratified by parental allergies and sex/gender using extensive prospect i ve follow‐up data from two decades of a birth cohort study . Methods In 1990 , we recruited 1314 healthy newborns from 6 maternity wards across Germany for the population ‐based MAS birth cohort study . The sample was purpose ly risk‐enriched by increasing the proportion of children at high allergy risk ( i.e. at least 2 allergic family members among parents and siblings ) from 19 % in the source population to 38 % in the final sample . The remaining 62 % of all MAS children had a low or no allergy risk . Symptoms , medication and doctor 's diagnoses of allergic diseases have been assessed using st and ardized question naires including vali date d ISAAC questions in 19 follow‐up assessment s up to age 20 . Allergic multimorbidity at each time point was defined as the coexistence of at least 2 of the following diseases in one participant : asthma , allergic rhinitis and eczema . Results Response at age 20 was 72 % ( n = 942 ) of all recruited participants . At age 20 , 18.5 % ( 95 % CI , 15.0–22.5 % ) of all participants with allergic parents had 2 or 3 concurrent allergies as compared to only 6.3 % ( 95 % CI , 4.3–9.0 % ) of those with non‐allergic parents . At this age , allergic multimorbidity was similar in women and men ( 12.7 % ( 95 % CI , 9.7–16.2 % ) vs. 11.6 % ( 95 % CI , 8.9–14.8 % ) ) , whereas single allergic diseases were slightly more common in women than men ( 24.2 % ( 95 % CI , 20.2–28.5 % ) vs. 20.1 % ( 95 % CI , 16.6–24.0 % ) ) . Asthma occurred more frequently with coexisting allergic rhinitis and /or eczema than as a single entity from pre‐puberty to adulthood . Conclusion Having parents with allergies is not only a strong predictor to develop any allergy , but it strongly increases the risk of developing allergic multimorbidity . In males and females alike , coexisting allergies were increasingly common throughout adolescence up to adulthood . Particularly asthma occurred in both sexes more frequently with coexisting allergies than as a single entity BACKGROUND Although several studies support the efficacy of specific immunotherapy in allergic asthma , its benefit compared with that of st and ardized pharmacologic intervention remains unknown . OBJECTIVE A double-blind , placebo-controlled trial in 72 patients with mild-to-moderate asthma and allergy to house dust mite ( HDM ; Dermatophagoides species ) was conducted to assess the effects of specific immunotherapy added to guideline -adjusted pharmacologic treatment and allergen avoidance . METHODS After 1 observational year of pharmacologic treatment and st and ard measures of HDM avoidance , 2 groups of asthmatic subjects were r and omly assigned to receive specific immunotherapy consisting of subcutaneous injections of either a mixture of Dermatophagoides pteronyssinus and Dermatophagoides farinae vaccine ( n=41 ) or placebo ( n=31 ) for 3 years . Medications were adjusted every 3 months according to the Global Initiative for Asthma guidelines . RESULTS The adjustment of treatment was associated with a reduction in asthma symptom scores in all subjects . The addition of specific immunotherapy was associated with a decrease in the number of subjects requiring rescue bronchodilators , an increase in morning and evening peak expiratory flow , and a reduced skin sensitivity to HDM extracts . The addition of specific immunotherapy had no significant effects on the cumulative dose of inhaled corticosteroids , asthma symptoms , lung volumes , or bronchial responsiveness to methacholine . CONCLUSION These results suggest that specific immunotherapy added to pharmacologic treatment and HDM avoidance provides marginal but statistically significant clinical benefits , possibly by reducing the allergic response of asthmatic patients sensitized to HDM BACKGROUND Allergen specific immunotherapy and allergen reduction are the only therapies in perennial allergic diseases to reduce symptoms in the long term . Specific immunotherapy has the potential to reduce symptoms and the need for medication significantly and furthermore to prevent progression into more severe disease e. g. asthma . METHODS The clinical value of specific immunotherapy has been studied for the last 30 years . We undertook an analysis of clinical trials of subcutaneous specific immunotherapy with Der p or Der f in adults to assess the efficacy of this controversial form of allergy treatment . RESULTS A computerized bibliographic search revealed 13 r and omised double-blind , placebo-controlled trials of specific immunotherapy with Der p/Der f for rhinitis and /or asthma in adults since 1970 . The results extracted included patients symptoms , medication requirements , lung function , specific challenge-tests as titrated nasal , conjunctival or bronchial challenge test and side effects . For studies with continuous outcomes as symptom score and medication score the effect size was obtained by the difference in the scores between the active therapy and the placebo groups . For studies with categorical outcomes as increase or decrease in challenge-tests the results were expressed as odds ratios for improvement against no change and 95 % confidence intervals were calculated . DISCUSSION Focused on the studies after 1980 there was a significant improvement on symptom score and medication score in the actively treated group compared to the placebo group , while the lung function was not significantly altered . Allergen provocation tests reflect the sensitivity of the shock organ . As the documentation of the clinical effects measured by challenge tests shows a highly significant improvement in the actively treated group , we recommend allergen provocation tests as a useful and sensitive parameter during specific immunotherapy . The risk of life-threatening side effects is low , although severe anaphylactic reactions may be induced . Specific immunotherapy using a st and ardized house-dust mite extract is effective and safe in adults when administered under optimal conditions To evaluate the tolerability and efficacy of specific immunotherapy with mite extracts , we performed a double‐blind , placebo‐controlled immunotherapy study in 30 patients with proven allergy to mite allergens . The specific immunotherapy with st and ardized extracts of Dermatophagoides pteronyssinus and D. farinae by a clustered rush protocol was well tolerated . After 1 year of treatment , the actively treated group showed a significant improvement compared to their starting value as well as to the placebo‐treated patients with regard to skin prick test , conjunctival provocation test , and subjective rhinitis score . The subjective asthma score and bronchial hyperreactivity , measured by the methacholine provocation test , was improved in comparison to the starting value , but not to the placebo group , after 12 months . However , a further , open comparison of the placebo‐ and verum‐treated groups at 18 months revealed a significant reduction . The drug intake was not increased in the verum‐treated group . Exposure to mite levels was constant throughout this time period , as revealed by antigen measurement . We conclude that specific immunotherapy in perennial , mite‐allergen‐induced asthma may reduce not only immediate , IgE‐mediated symptoms but , after a rather long time period of 12–18 months , also the inflammatory component of bronchial asthma , thus leading to a reduction of unspecific hyperreactivity The efficacy of immunotherapy in cat-induced asthma was studied by use of a purified fraction of cat-pelt extract and a double-blind protocol . Nine active-treatment subjects who received a mean cumulative dose of cat allergen , 1 of 10.9 units , and eight placebo-treatment subjects completed the study . Active treatment result ed in significant reductions in bronchial sensitivity ( p less than 0.05 ) and prick test titer ( p less than 0.01 ) . In addition , active treatment result ed in a significant delay in the onset of ocular ( p less than 0.05 ) and pulmonary ( p less than 0.02 ) symptoms on exposure to living cats . Significant increases in IgG antibody to cat allergen 1 ( p less than 0.001 ) and cat albumin ( p less than 0.01 ) also occurred with active treatment . There was no significant change in bronchial reactivity to methacholine or in the sensitivity of circulating basophils . These results confirm the validity of immunotherapy in allergic asthma where there is careful patient selection and well defined treatment preparations T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings . We studied the role of IL-10 in the induction of clinical , cellular , and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis . Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen ( Phleum pratense , Phl P ) immunotherapy . We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy , but only during the pollen season . IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA+ cells . These changes were not observed in placebo-treated subjects or in healthy controls . Fifteen and 35 % of IL-10 mRNA signals were colocalized to CD3 + T cells and CD68 + macrophages , respectively , whereas only 1–2 % of total CD3 + cells and 4 % of macrophages expressed IL-10 . Following immunotherapy , peripheral T cells cultured in the presence of grass pollen extract also produced IL-10 . Immunotherapy result ed in blunting of seasonal increases in serum allergen Phl p 5-specific IgE , 60- to 80-fold increases in Phl p 5-specific IgG , and 100-fold increases in Phl p 5-specific IgG4 . Post-immunotherapy serum exhibited inhibitory activity , which coeluted with IgG4 , and blocked IgE-facilitated binding of allergen-IgE complexes to B cells . Both the increases in IgG and the IgG “ blocking ” activity correlated with the patients ’ overall assessment of improvement . Thus , grass pollen immunotherapy may induce allergen-specific , IL-10-dependent “ protective ” IgG4 responses BACKGROUND Both specific immunotherapy ( SIT ) and nasal steroid ( NS ) have been shown to effectively reduce symptoms of allergic rhinitis . Although a number of investigators have convincingly shown anti-inflammatory effects of both treatments in separate studies , few comparative studies have been performed . OBJECTIVE The purpose of this study was to compare the effects of preseason SIT with a st and ardized allergen extract and NS in seasonal allergic disease ( rhinoconjunctivitis and asthma ) . METHODS We examined 41 patients allergic to birch pollen , 21 with rhinoconjunctivitis and 20 with both rhinoconjunctivitis and asthma ; they were treated in a r and omized , double-blinded comparative study with birch SIT and NS ( budesonide 400 microg daily ) . Bronchial hyperresponsiveness was measured before and during the season . Changes in eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity ( ECA ) in peripheral blood were investigated . RESULTS Symptoms of rhinoconjunctivitis increased significantly less in the NS-treated patients than in the SIT-treated patients during the final 2 weeks of the season ( P = .03 and P = .04 , respectively ) . Seasonal peak expiratory flow values decreased significantly only in the NS-treated patients ( P = .01 ) . In the NS-treated patients , bronchial hyperresponsiveness increased significantly during the season ( P = .0001 ) ; however , SIT treatment prevented seasonal PC(20 ) increase in the asthmatic patients . Measurement of blood eosinophils , eosinophil cationic protein , and eosinophil chemotactic activity demonstrated significant seasonal increase only in the NS-treated asthmatic patients . CONCLUSION Treatment with NS was more effective than short-course preseason SIT in reducing symptoms of rhinoconjunctivitis ; however , the 2 therapies were equivalent in terms of the need for rescue medication . SIT prevented seasonal increase in bronchial hyperresponsiveness , eosinophil number , eosinophil cationic protein , and eosinophil chemotactic activity only in asthmatic patients . The mechanisms underlying bronchial hyperresponsiveness developing during allergen exposure in rhinitis might be different from those operating in asthma Thirty‐one adult patients with asthma caused by house‐dust mites ( HDM ) were included in this placebo‐controlled , double‐blind study to evaluate the efficacy and safety of specific immunotherapy ( SIT ) with biologically st and ardized extracts of HDM . The specific diagnosis was confirmed by skin prick tests , specific IgE , and bronchial provocation tests with HDM allergens . The patients were r and omized to receive active treatment with extracts of either Dermatophagoides pteronyssinus ( Dpt ) or D. farinae ( Dfa ) ( Alutard ® SQ , ALK , Denmark ) or placebo injections . Twenty‐three patients completed the study . After 1 year of treatment , we found a clinical ly important and significant reduction in both asthma medicine consumption ( inhaled steroids 38 % and p2–agonists 46 % ) and symptom score ( 57 % ) in the actively treated group , but not the placebo group . These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group . Additionally , there was a significant difference in the patients ' scores for effect in favor of the actively treated group . Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group . Spirometric lung‐function measurements showed a significant increase in forced expiratory volume in 1 s ( FEV1 ) from 85 % before to 89 % of predicted values after treatment for the actively treated group . Peak‐flow measurements at home showed no significant changes during the study . It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM |
2,440 | 24,651,044 | The common toxicities included fatigue , diarrhea , nausea , h and foot skin reaction ( HFSR ) , hematological events , hepatotoxicity , alopecia , hepatotoxicity , hypertension and rash/desquamation .
AEs are generally manageable with dose reductions .
Combination therapy may bring benefits for unresectable HCC patients in terms of TTP but not OS . | BACKGROUND AND AIM A large number of studies have tried to combine sorafenib with TACE for patients with unresectable hepatocellular carcinoma ( HCC ) and the results were controversial .
We conducted this systematic review and meta- analysis to evaluate the safety and efficacy of combination therapy of sorafenib and TACE in the management of unresectable HCC . | PURPOSE To evaluate safety and efficacy of combined transarterial chemoembolization ( TACE ) with doxorubicin-eluting beads ( DEB ) and sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS A prospect i ve single-center phase II study was undertaken involving patients with unresectable HCC . The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE . Safety and response were assessed . Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients : mean age , 63 years ; Child 's A , 89 % ; Barcelona Clinic Liver Cancer stage C , 64 % ; Eastern Cooperative Oncology Group performance status of 0 and 1 , 46 % and 54 % , respectively ; and mean index tumor size , 7.7 cm ( st and ard deviation , ± 4.2 cm ) . Patients underwent 128 cycles of therapy ( sorafenib plus DEB-TACE , 60 cycles ; sorafenib alone , 68 cycles ) . Median number of cycles per patient was two ( range , one to five cycles ) ; median number of days treated with sorafenib was 71 ( range , 4 to 620 days ) . The most common toxicities during cycle one were fatigue ( 94 % ) , anorexia ( 67 % ) , alterations in liver enzymes ( 64 % ) , and dermatologic adverse effects ( 48 % ) . Although most patients experienced at least one grade 3 to 4 toxicity , most toxicities were minor ( grade 1 to 2 , 83 % v grade 3 to 4 , 17 % ) . Toxicity during cycle two was decreased . Over the course of the study , there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions . Sorafenib plus DEB-TACE was associated with a disease control rate of 95 % ( Response Evaluation Criteria in Solid Tumors Group)/100 % ( European Association for the Study of the Liver [ EASL ] ) , with an objective response of 58 % ( EASL ) . CONCLUSION The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe , with most toxicities related to sorafenib . Toxicity is manageable with dose adjustment of sorafenib . Preliminary efficacy data are promising BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses Background Disease progression of hepatocellular cancer ( HCC ) in patients eligible for liver transplantation ( LTx ) occurs in up to 50 % of patients , result ing in withdrawal from the LTx waiting list . Transarterial chemoembolization ( TACE ) is used as bridging therapy with highly variable response rates . The oral multikinase inhibitor sorafenib significantly increases overall survival and time-to-progression in patients with advanced hepatocellular cancer . Design The HeiLivCa study is a double-blinded , controlled , prospect i ve , r and omized multi-centre phase III trial . Patients in study arm A will be treated with transarterial chemoembolization plus sorafenib 400 mg bid . Patients in study arm B will be treated with transarterial chemoembolization plus placebo . A total of 208 patients with histologically confirmed hepatocellular carcinoma or HCC diagnosed according to EASL criteria will be enrolled . An interim patients ' analysis will be performed after 60 events . Evaluation of time-to-progression as primary endpoint ( TTP ) will be performed at 120 events . Secondary endpoints are number of patients reaching LTx , disease control rates , OS , progression free survival , quality of live , toxicity and safety . Discussion As TACE is the most widely used primary treatment of HCC before LTx and sorafenib is the only proven effective systemic treatment for advanced HCC there is a strong rational to combine both treatment modalities . This study is design ed to reveal potential superiority of the combined TACE plus sorafenib treatment over TACE alone and explore a new neo-adjuvant treatment concept in HCC before LTx LBA154^ Background : The global SPACE trial was conducted to evaluate the efficacy and safety of S in combination with TACE with DEBDOX in patients ( pts ) with intermediate-stage HCC ( BCLC B ) . METHODS Pts were eligible if they had asymptomatic , unresectable , multinodular tumors without vascular invasion ( VI ) or extrahepatic spread ( EHS ) ; Child-Pugh A liver functional status ; and ECOG PS 0 . Pts were r and omized to receive S 400 mg bid or matching P continuously ( 1 cycle = 4 wks ) until progression . All pts received TACE with DEBDOX ( 150 mg doxorubicin ; Biocompatibles UK Ltd ) 3 - 7d after first dose of study drug , and then on d1 ( ±4d ) of months 3 , 7 , and 13 , and q6 months thereafter . The primary endpoint was time to radiologic progression ( TTP ) by independent review ( predefined alpha = 0.15 ) . Secondary endpoints were overall survival ( OS ) , time to VI/EHS , time to untreatable progression ( TTUP ) , and safety . RESULTS Of 452 pts screened , 307 were r and omized to S ( n=154 ) or P ( n=153 ) . The HR for TTP was 0.797 ( 95 % CI , 0.588 , 1.080 ; p=0.072 ) . Median TTP ( 50th percentile ) was 169d/166d in the S and P groups , respectively ; TTP at the 25th and 75th percentiles ( preplanned ) was 112/88d and 285/224d in the S and P groups , respectively . There were no unexpected safety findings . Median treatment duration in the S and P groups was 4.8 and 6.3 months , respectively , and median daily dose of study drug was 566 mg and 791 mg , respectively . CONCLUSIONS The study met its primary endpoint of improving TTP when S was added to a regimen of TACE with DEBDOX , compared with TACE with DEBDOX alone . The combination was well tolerated ; no new safety findings that would preclude use of the combination were observed . The encouraging efficacy signal requires confirmation with data from ongoing phase III trials evaluating the combination of S plus TACE . [ Table : see text ] Abstract Objectives To investigate the safety of transarterial chemoembolisation ( TACE ) in combination with sorafenib in patients with hepatocellular carcinoma ( HCC ) . Methods Patients with Child – Pugh A/B liver function , ECOG performance status 0–2 and HCC treatable with TACE received continuous sorafenib 800 mg/day , and TACE with doxorubicin ( 75 , 50 and 25 mg/m2 according to serum bilirubin : < 1.5 , 1.5–3 , and > 3 mg/dL ) and lipiodol 2 weeks after sorafenib initiation and repeated every 4 weeks . Results Fifteen patients were included ( Child – Pugh A/B , n = 12/3 ; Barcelona Clinic Liver Cancer-A/B/C , n = 1/9/5 ; ECOG 0/2 , n = 14/1 ) . Median time on sorafenib was 5.2 months ( 2.6–7.4 months ) ; median number of TACE sessions was 3 . Common adverse events were abdominal pain ( n = 14 ) , weight loss ( n = 13 ) , alopecia ( n = 12 ) , fatigue ( n = 12 ) and hyperbilirubinaemia ( n = 11 ) . There were 32 serious adverse events ( grade ≥3 ) ; 9/10-unscheduled hospital admissions and 4/5 deaths were considered TACE-related . The study was stopped prematurely because of safety concerns . At 6 months , 2 and 5 patients had complete or partial responses ; 1 had stable disease . Median overall survival was 10.6 months ( 95 % CI : 5.2–16 months ) . Conclusion These findings do not support use of an intensive , high-dose doxorubicin-based TACE regimen in combination with sorafenib in this study population .Key Points• Transarterial chemoembolisation ( TACE ) is widely used in patients with hepatocellular carcinoma ( HCC ) • Various antiangiogenic and other agents have been used to augment this treatment • We tested lipiodol-TACE with bilirubin-adjusted doxorubicin dosing in combination with sorafenib • This trial was stopped prematurely because of safety reasons • Our safety results do not support the combination of sorafenib with this TACE BACKGROUND & AIMS Transarterial chemoembolization ( TACE ) is an important palliative treatment for unresectable hepatocellular carcinoma ( HCC ) , but TACE-induced ischemic injury can upregulate angiogenic factors and is associated with poor prognosis . The aim of this study was to evaluate the safety and efficacy of concurrent conventional TACE and sorafenib in patients with unresectable HCC . METHODS The primary objectives of this prospect i ve , single-arm , phase II study were to evaluate safety and time to progression ( TTP ) . Sorafenib was given 3 days after TACE and was administered for up to 24 weeks . Repeated TACE was performed on dem and . Tumor response was assessed every 8 weeks . RESULTS Fifty patients were treated and followed from July 2009 to May 2011 . All patients were in Barcelona Clinic Liver Cancer ( BCLC ) stage B ( 82 % ) or C ( 18 % ) . The median time of follow-up was 14.9 months and a median of 1 TACE session was given ( range , 1 - 4 ) . The median dose intensity of sorafenib was 68.7 % ( range , 37.3 - 100 ) of 800 mg daily . The most common reasons for dose reduction were h and -foot syndrome and thrombocytopenia . Thirty patients completed the study and 17 patients discontinued sorafenib due to disease progression . The overall median TTP was 7.1 months ( 95 % confidence interval ( CI ) , 4.8 - 7.5 months ) : 7.3 months in BCLC stage B ; 5.0 months in BCLC stage C. The 6-month progression-free survival rate was 52 % ( 95 % CI , 37.3 - 66.1 ) . CONCLUSIONS Concurrent treatment of unresectable HCC with conventional TACE and sorafenib demonstrates a manageable safety profile and a possibility of promising efficacy This prospect i ve non‐r and omized controlled trial aim ed to compare the efficacy of sorafenib in combination with transarterial chemoembolization ( TACE ) vs TACE alone for the treatment of patients with unresectable intermediate or advanced hepatocellular carcinoma Transarterial chemoembolization ( TACE ) represents a first-line noncurative therapy for hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospect i ve Phase II , open label , trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC . Patients with histologically or clinical ly diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later . TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol ( 5 - 20 ml ) and doxorubicin ( 30 - 60 mg ) followed by embolization with absorbable particles ( gel foam ) . TACE/sorafenib cycles were repeated every 6 - 8 weeks . Primary objectives were to evaluate the safety and tolerability , in addition to the efficacy of TACE combined with sorafenib for HCC . A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib . Gastrointestinal AEs were reported by 62.6 % of patients while 57.8 % reported skin AEs although most were mild to moderate . The mean number of cycles undertaken was 2.1 and 63.3 % of patients achieved either partial response or stable disease . Clinical ly , the disease control rate was 91.2 % while the overall response rate was calculated as 52.4 % . Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects BACKGROUND AND AIM It is unknown whether sorafenib can be combined with transarterial chemoembolization ( TACE ) in patients with hepatocellular carcinoma . This study assesses the safety and tolerability of a continuous regimen of sorafenib combined with TACE . METHODS This was an open-label phase I study testing a continuous administration of sorafenib ( dose escalation from 200 mg twice daily [ bid ] to 400 mg bid ) starting 7 days prior to TACE with doxorubicin ( 50 mg ) . RESULTS Twenty-one patients were screened and 14 received sorafenib combined with TACE . Because there were no dose-limiting toxicities in the first three patients who received sorafenib at a dose of 200 mg bid , subsequent patients received 400 mg bid . Twenty-seven procedures were performed ( median , two per patient ) and two local therapy-related severe adverse events occurred . The median duration of sorafenib therapy was 246 days ( range , 14 - 547 days ) . Sorafenib-related adverse events of grade ≥3 were h and -foot skin reaction ( n = 3 ) , weight loss ( n = 2 ) , diarrhea ( n = 1 ) , abdominal pain ( n = 1 ) , and thrombocytopenia ( n = 3 ) . After treatment with sorafenib and TACE , there was a significant decrease in the concentration of plasma vascular endothelial growth factor ( VEGF ) from 93 ng/l to 67 ng/l . CONCLUSIONS Continuous administration of sorafenib at a dose of 400 mg bid combined with TACE was tolerable . The adverse event profile of this regimen was comparable with that of sorafenib monotherapy with the exception of thrombocytopenia , which may be more frequent . There were no increases in the circulating VEGF levels after TACE with this combined regimen . ( Swiss Association for the Study of the Liver study number 25 ; Clinical Trials.gov trial identifier , NCT00478374 ) BACKGROUND Recurrence of hepatocellular carcinoma ( HCC ) is a major problem after surgical or ablative treatments . The aim of this prospect i ve , single-center , placebo-controlled , r and omized , double-blind clinical study was to evaluate the effectiveness of transarterial chemoembolization ( TACE ) combined with sorafenib as a sequential treatment regimen in delaying time to progression ( TTP ) of intermediate-stage HCC in patients with chronic hepatitis C virus ( HCV ) infection . MATERIAL AND METHODS Between October , 2007 and January , 2011 , 80 HCV-infected patients with Barcelona Clinic Liver Cancer stage B HCC underwent the TACE procedure . All had Child-Pugh class A disease . They were r and omized 1:1 to receive sorafenib at a dose of 400 mg twice daily or placebo . Endpoints were the TTP and the rates of adverse events and toxicity . RESULTS Sixty-two of 80 patients ( 77 % ) , 31 in the sorafenib group and 31 in the control group , completed the study . The median TTP was 9.2 months in the sorafenib group and 4.9 months in the placebo group ( hazard ratio , 2.5 ; 95 % confidence interval , 1.66 - 7.56 ; p < .001 ) . Metachronous , multicentric HCC progression occurred less frequently in sorafenib-treated patients ( p < .05 ) . Adverse reactions to sorafenib caused withdrawal from the study of 9 ( 22 % ) patients . CONCLUSION A conventional TACE procedure followed by sorafenib treatment result ed in a significantly longer TTP in patients with intermediate-stage HCV-related HCC , with no unexpected side effects |
2,441 | 24,423,035 | The 50 g oral glucose challenge test with a glucose threshold of 130 mg/dL versus 140 mg/dL improves sensitivity and reduces specificity .
Method ologically strong studies showed a continuous positive relationship between increasing glucose levels and the incidence of primary cesarean section and macrosomia .
There was more childhood obesity for Carpenter and Coustan GDM versus patient groups with no GDM .
Moderate evidence found less shoulder dystocia with treatment for GDM .
Low evidence showed no difference for neonatal hypoglycemia between treated and untreated GDM .
Moderate evidence showed benefits of treatment for reduction of macrosomia ( > 4,000 g ) .
While evidence supports a positive association with increasing plasma glucose on a 75 g or 100 g oral glucose tolerance test and macrosomia and primary cesarean section , clear thresholds for increased risk were not found .
The 50 g oral glucose challenge test has high NPV but variable PPV .
Treatment of GDM results in less preeclampsia and macrosomia .
Current evidence does not show that treatment of GDM has an effect on neonatal hypoglycemia or future poor metabolic outcomes .
There is little evidence of short-term harm from treating GDM other than an increased dem and for services . | BACKGROUND There is uncertainty as to the optimal approach for screening and diagnosis of gestational diabetes mellitus ( GDM ) .
Based on systematic review s published in 2003 and 2008 , the U.S. Preventive Services Task Force concluded that there was insufficient evidence upon which to make a recommendation regarding routine screening of all pregnant women .
OBJECTIVES ( 1 ) Identify properties of screening tests for GDM , ( 2 ) evaluate benefits and harms of screening for GDM , ( 3 ) assess the effects of different screening and diagnostic thresholds on outcomes for mothers and their offspring , and ( 4 ) determine the benefits and harms of treatment for a diagnosis of GDM . | AIMS To describe the prevalence of impaired glucose tolerance and obesity in offspring of mothers whose pregnancies were complicated by gestational diabetes mellitus ( GDM ) in a low-risk population and to investigate the effect on these outcomes of minimal intervention compared with tight control for management of GDM . METHODS Eighty-nine children ( mean age 9.1 years , 93 % Caucasian ) were recruited through a follow-up study of women previously involved in a r and omized controlled trial of minimal intervention ( control group ) vs. tight glycaemic control ( treatment group ) for GDM . Fasting blood glucose ( FBG ) and 2-h glucose tolerance tests ( 2hGTT ) were performed on offspring and body mass index ( BMI ) calculated . Glucose tolerance and BMI of treatment groups were compared using non-inferiority tests ( non-inferiority margin -15 % ) . RESULTS Of those offspring , 6.9 % ( 5/72 ) had abnormal glucose metabolism [ four children had impaired glucose tolerance ( IGT ) and one had Type 2 diabetes mellitus ( DM ) ( all Caucasian ) ] . Of the four children with IGT , three were male , three had normal BMI , and three had a family history of Type 2 diabetes . Of the 71 offspring who underwent 2hGTT , 25/25 ( 100 % ) of the control offspring and 46/46 ( 100 % ) of the treatment offspring had normal FBG ( FBG < 5.7 mmol/l ) . Twenty-five of 25 ( 100 % ) of control and 42/46 ( 91.3 % ) of the treatment offspring had normal glucose tolerance ( 2hGTT < 7.8 mmol/l ) ( % difference 8.7 , 95 % CI -5.6 , 20.3 ) . BMI < 85th percentile was found in 25/33 ( 75.8 % ) of the treatment group and 44/52 ( 84.6 % ) of the control group ( difference in percentage -8.9 , 95 % CI -27.2 , 7.8 ) . CONCLUSIONS School-age children of mothers with GDM are at risk of IGT and overweight , even if from a low-risk ethnic population . FBG was not adequate for screening this population . Minimal intervention for glycaemic control in GDM pregnancies appears to be as effective as tight control for preventing IGT in childhood but not for preventing obesity In this study , we assessed maternal-fetal outcomes in untreated patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes mellitus ( GDM ) , examined the relationship between birth weight and mode of delivery among women with untreated borderline GDM , treated overt GDM , and normoglycemia , and established more efficient screening strategies for detection of GDM . This was a prospect i ve analytic cohort study in which nondiabetic women aged > or = 24 years were eligible for enrollment . A 50-g glucose challenge test ( GCT ) and a 100-g oral glucose tolerance test ( OGTT ) were administered at 26 and 28 weeks gestational age , respectively . Risk factors for unfavorable maternal-fetal outcomes were recorded . Time since the last meal prior to the screening test was recorded , as well . Caregivers and patients were blinded to glucose values except when test results met the National Diabetes Data Group criteria for GDM . Maternal and fetal outcomes , including the mode of the delivery , were recorded in the postpartum period . Of 4,274 patients screened , 3,836 ( 90 % ) continued to the diagnostic oral glucose tolerance test . GDM was seen in 145 women . Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean section , preeclampsia , macrosomia , and need for phototherapy , as well as an increased length of maternal and neonatal hospital stay . Multivariate analysis showed that increasing carbohydrate intolerance remained an independent predictor for various unfavorable outcomes , but the strength of the associations was diminished . Compared with normoglycemic control subjects , the untreated borderline GDM group had increased rates of macrosomia ( 28.7 vs. 13.7 % , P < 0.001 ) and cesarean delivery ( 29.6 vs. 20.2 % , P = 0.03 ) . Usual care of known GDM patients normalized birth weights , but the cesarean delivery rate was about 33 % , whether macrosomia was present or absent . An increased risk of cesarean delivery among treated patients compared with normoglycemic control subjects persisted after adjustment for multiple maternal risk factors . As for the screening tests , time since the last meal had a marked effect on mean plasma glucose . Receiver operating characteristic curve analysis allowed the selection of the most efficient cut points for the GCT based on the time since the last meal . These cut points were 8.2 , 7.9 , and 8.3 mmol/l ( 1 mmol/l = 18.015 mg/dl ) for elapsed postpr and ial time of < 2 , 2 - 3 , and > 3 h , respectively . With this change from the current threshold of 7.8 mmol/l , the number of patients with a positive screening test dropped from 18.5 to 13.7 % . There was an increase in positive predictive value from 14.4 to 18.7 % . The overall rate of patient misclassification fell from 18.0 to 13.1 % . In conclusion , increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a grade d increase in adverse maternal and fetal outcomes . Infant macrosomia is an important factor in high cesarean delivery rates for women with untreated borderline GDM . Although detection and treatment of GDM normalizes birth weights , rates of cesarean delivery remain inexplicably high . Recognition of GDM may lead to a lower threshold for surgical delivery . The efficiency of screening for GDM can be enhanced by adjusting the current GCT threshold of 7.8 mmol/l to new values related to time since the last meal before screening . Further analyses are underway to eluci date whether maternal risk factors can be used to achieve additional efficiency gains in screening Background In conjunction with the growing prevalence of obesity and the older age of pregnant women gestational diabetes ( GDM ) is a major health problem . The aim of the study was to evaluate if a lifestyle intervention since early pregnancy is feasible in improving the glucose tolerance of women at a high-risk for GDM in Finl and . Methods A 75-g oral glucose tolerance test ( OGTT ) was performed in early pregnancy ( n = 102 ) . Women at high risk for GDM ( n = 54 ) were r and omized at weeks 8 - 12 from Apr 2005 to May 2006 to a lifestyle intervention group ( n = 27 ) or to a close follow-up group ( n = 27 ) . An OGTT was performed again at weeks 26 - 28 for the lifestyle intervention and close follow-up groups . Results The values of the OGTT during the second trimester did not differ between the lifestyle intervention and close follow-up groups . In the lifestyle intervention group three women had GDM in the second trimester and respectively one woman in the close follow up group . Insulin therapy was not required in both groups . The intervention result ed in somewhat lower weight gain 11.4 ± 6.0 kg vs. 13.9 ± 5.1 kg , p = 0.062 , adjusted by the prepregnancy weight . Conclusions Early intervention with an OGTT and simple lifestyle advice is feasible . A more intensive lifestyle intervention did not offer additional benefits with respect to glucose tolerance , although it tended to ameliorate the weight gain . Trial Registration Clinical Trials.gov : Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 Emerging evidence suggests that fetal environmental exposures impact on future development of obesity . The objectives of this study were to assess the relationships between ( i ) maternal insulin sensitivity and glucose tolerance status in pregnancy and ( ii ) early infant weight gain and adiposity in the first year of life . In this prospect i ve cohort study , 301 women underwent oral glucose tolerance testing for assessment of glucose tolerance status and insulin sensitivity ( IS(OGTT ) ) in pregnancy . Their infants underwent anthropometric assessment at 12 months of age , including determination of weight gain in the first year of life and sum of skinfold thickness ( SFT ) , a measure of infant adiposity . Infant weight gain and sum of SFT at 12 months did not differ according to maternal glucose tolerance status . On univariate analyses , weight gain from 0 to 12 months and sum of SFT were negatively associated with maternal IS(OGTT ) during pregnancy . On multiple linear regression analysis , negative independent predictors of weight gain from 0 to 12 months were maternal IS(OGTT ) during pregnancy ( t = -2.73 ; P = 0.007 ) , infant female gender ( t = -3.16 ; P = 0.002 ) , and parental education ( t = -1.98 ; P = 0.05 ) , whereas white ethnicity was a positive independent predictor ( t = 2.68 ; P = 0.008 ) . Maternal IS(OGTT ) ( t = -2.7 ; P = 0.008 ) and parental education ( t = -2.58 ; P = 0.01 ) were independent negative predictors of sum of SFT at 12 months . Independent of maternal glucose tolerance status , maternal insulin resistance during pregnancy is associated with increased infant weight gain and adiposity over the first year of life . Further longitudinal study to evaluate obesity in this group of children will increase our underst and ing of the contribution of the intrauterine environment to their long-term health Aims /hypothesisNew diagnostic criteria for gestational diabetes mellitus ( GDM ) have recently been published . We wished to evaluate what impact these new criteria would have on GDM prevalence and outcomes in a predominantly European population . Methods The Atlantic Diabetes In Pregnancy ( DIP ) programme performed screening for GDM in 5,500 women with an oral glucose tolerance test at 24–28 weeks . GDM was defined according to the new International Association of Diabetes and Pregnancy Study Groups ( IADPSG ) criteria and compared with previous WHO criteria ; maternal and neonatal adverse outcomes were prospect ively recorded . Results Of the participants , 12.4 % and 9.4 % were diagnosed with GDM using IADPSG and WHO criteria , respectively . IADPSG GDM pregnancies were associated with a statistically significant increased incidence of adverse maternal outcomes ( gestational hypertension , polyhydramnios and Caesarean section ) and neonatal outcomes ( prematurity , large for gestational age , neonatal unit admission , neonatal hypoglycaemia and respiratory distress ) . The odds ratio for the development of these adverse outcomes remained significant after adjustment for maternal age , body mass index and non-European ethnicity . Those women who were classified as having normal glucose tolerance by WHO criteria but as having GDM by IADPSG criteria also had significant adverse pregnancy outcomes . Conclusions /interpretationGDM prevalence is higher when using newer IADPSG , compared with WHO , criteria , and these women and their offspring experience significant adverse pregnancy outcomes . Higher rates of GDM pose a challenge to healthcare systems , but improved screening provides an opportunity to attempt to reduce the associated morbidity for mother and child OBJECTIVE Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes . STUDY DESIGN We conducted a prospect i ve analytic cohort study in which nondiabetic women aged > or = 24 years , receiving prenatal care in three Toronto teaching hospitals , were eligible for enrollment . A glucose challenge test and an oral glucose tolerance test were administered at 26 and 28 weeks ' gestation , respectively ; risk factors for unfavorable maternal-fetal outcomes were recorded . Caregivers and patients were blinded to glucose values except when test results met the current criteria for gestational diabetes . RESULTS Of 4274 patients screened , 3836 ( 90 % ) continued to the diagnostic oral glucose tolerance test . The study cohort was formed by the 3637 ( 95 % ) patients without gestational diabetes , carrying singleton fetuses . Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean sections , preeclampsia , macrosomia , and need for phototherapy , as well as an increased length of maternal and neonatal hospital stay . Multivariate analysis showed that increasing carbohydrate intolerance is an independent predictor for various unfavorable outcomes . CONCLUSION Increasing maternal carbohydrate intolerance in pregnant women without gestational diabetes is associated with a grade d increase in adverse maternal-fetal outcomes Gestational diabetes mellitus ( GDM ) is one of the most common medical disorders found in pregnancy . Rates can range from 2 to > 10 % , and sometimes much higher , depending on the population being tested and the diagnostic criteria being used ( 1 ) . The prevalence of GDM ultimately reflects the background rate of type 2 diabetes . There has also been an increase in the rate of GDM over the last generation , possibly related to community lifestyle factors as well as better case ascertainment ( 2,3 ) . # # # Significance of GDM GDM is associated with a trilogy of risks . Significant pregnancy complications including increased perinatal morbidity and possibly mortality can occur ( 4,5 ) . A diagnosis of GDM also identifies a mother at high risk for the future development of type 2 diabetes ( 1 ) . The effects of maternal hyperglycemia ( of any kind ) are associated with the development of metabolic problems including type 2 diabetes in the offspring ( 6 ) . It is , perhaps , for this effect of intrauterine programming that the disorder is most worthy of detection . It has now been demonstrated that the treatment of GDM improves pregnancy outcomes . In the Australian Carbohydrate Intolerance Study in Pregnant Women ( ACHOIS ) , the incidence of serious perinatal complications ( a composite of death , shoulder dystocia , nerve palsy , and fracture ) was 4 % among women r and omized to routine care compared with 1 % among the intervention group ( 5 ) . The number of GDM cases that needed to be treated to prevent one serious perinatal complication was 34 . This indicates that excess serious perinatal complications will occur in 3 % of cases of untreated or unrecognized GDM . This is a most compelling immediate argument for the screening of GDM given that the failure to identify a woman with GDM denies her the opportunity to have treatment for potentially preventable serious fetal complications . # # # Why conduct selective screening for GDM ? Therefore , if we accept that GDM is OBJECTIVE To determine if pregnancies with an abnormal glucose challenge test ( GCT ) but a normal ( GTT ) are at increased risk for fetal macrosomia or an adverse pregnancy outcome . STUDY DESIGN This prospect i ve observational study matched women with an abnormal glucose challenge test and a normal GTT with the next patient with a normal GCT . RESULTS Over 12 months , 107 women with abnormal GCT were matched with 107 women with normal GCT . Women with an abnormal GCT were older ( 27.3 vs. 24.7 , p = 0.001 ) and less likely to be African-American ( OR = 2.2 , 95 % CI 1.06 - 4.49 ) but no more likely to have an adverse pregnancy outcome . ROC curves could not differentiate between macrosomic vs non-macrosomic newborns using GCT values . CONCLUSION Women with an abnormal GCT but a normal GTT are more likely to be older , less likely to be African-American , but no more likely to have an adverse pregnancy outcome or a macrosomic fetus CONTEXT Raised maternal body mass index ( BMI ) in association with hyperglycemia is associated with adverse pregnancy outcome . The contribution of raised BMI as an independent risk factor for adverse pregnancy outcome is of growing concern and increasing prevalence . OBJECTIVE The aim of this study was to investigate the effects of raised maternal BMI on pregnancy outcome in glucose-tolerant women using the International Association of Diabetes and Pregnancy Study Groups criteria . PARTICIPANTS AND SETTING We studied a cohort of glucose-tolerant , pregnant women ( n = 3656 ) who were attending antenatal obstetric clinics and were recruited to a universal screening program for gestational diabetes under the ATLANTIC-DIP partnership . DESIGN We conducted a prospect i ve observational study of pregnancy outcome . Maternal outcomes include glucose , delivery mode , pregnancy-induced hypertension , preeclampsia , antepartum hemorrhage , and postpartum hemorrhage . Fetal outcomes included birthweight , congenital malformation , fetal death , neonatal jaundice , hypoglycemia , and respiratory distress . RESULTS Increasing maternal BMI was associated with adverse pregnancy outcomes : higher cesarean section rates , preeclampsia , pregnancy-induced hypertension , increased birth weight , and congenital malformation . The association of glucose with adverse pregnancy outcome was weak and did not interact with raised BMI . A BMI threshold of 28 kg/m(2 ) was associated with a significant rise in adverse pregnancy outcome . CONCLUSIONS Raised maternal BMI , within the overweight range , is associated with adverse pregnancy outcomes . These adverse effects of BMI occur independently of maternal glucose . It is apparent that pregnancy unmasks an underlying unhealthy metabolic milieu in obese and overweight women Background Mild gestational diabetes is a common complication of pregnancy , affecting up to 9 % of pregnant women . Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries , such as shoulder dystocia , bone fractures and nerve palsies . This study aim ed to compare the plasma glucose concentrations and serum insulin , leptin and adiponectin in cord blood of babies of women ( a ) without gestational diabetes mellitus ( GDM ) , ( b ) with mild GDM under routine care , or ( c ) mild GDM with treatment . Methods 95 women with mild GDM on oral glucose tolerance testing ( OGTT ) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and r and omised to either Treatment ( n = 46 ) or Routine Care ( n = 49 ) and Control women with a normal OGTT ( n = 133 ) were included in the study . Women with mild GDM ( treatment or routine care group ) and OGTT normal women received routine pregnancy care . In addition , women with treated mild GDM received dietary advice , blood glucose monitoring and insulin if necessary . The primary outcome measures were cord blood concentrations of glucose , insulin , adiponectin and leptin . Results Cord plasma glucose was higher in women receiving routine care compared with control , but was normalized by treatment for mild GDM ( p = 0.01 ) . Cord serum insulin and insulin to glucose ratio were similar between the three groups . Leptin concentration in cord serum was lower in GDM treated women compared with routine care ( p = 0.02 ) and not different to control ( p = 0.11 ) . Adiponectin was lower in both mild GDM groups compared with control ( Treatment p = 0.02 and Routine Care p = 0.07 ) , while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment ( p = 0.08 ) and control ( p = 0.05 ) . Conclusion Treatment of women with mild GDM using diet , blood glucose monitoring and insulin if necessary , influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy OBJECTIVE To determine the frequency of screening for gestational diabetes mellitus ( GDM ) among a population receiving regular prenatal care and to assess the extent to which National Diabetes Data Group ( NDDG ) criteria for the diagnosis of GDM are used by practicing obstetricians . RESEARCH DESIGN AND METHODS We studied participants in the Nurses ' Health Study II , a large prospect i ve cohort study of 116,678 nurses aged 25–42 years in 1989 . A total of 422 women who reported a first diagnosis of GDM between 1989 and 1991 were sent supplementary question naires regarding diagnosis and treatment , and medical records were requested for a subset of 120 to vali date self-reported GDM and assess criteria used for diagnosis . A sample of 100 women who reported a pregnancy not complicated by GDM were sent question naires addressing GDM screening and prenatal care . RESULTS Among a sample of 93 women who reported a pregnancy not complicated by GDM and responded to the supplementary question naire , 16 ( 17 % ) reported no glucose loading test ; 69 % of unscreened women had one or more risk factors for GDM . Among a sample of 114 women who self-reported GDM in a singleton pregnancy and whose medical records were available for review , a physician diagnosis of GDM was confirmed in 107 ( 94 % ) . Records and supplementary question naires indicated that oral glucose tolerance tests ( OGTTs ) were performed in 96 ( 86 % ) of these women . Of women with a physician diagnosis of GDM whose OGTT results were available , 25 % failed to meet NDDG criteria for this diagnosis , although all had evidence of abnormal glucose homeostasis . CONCLUSIONS Screening for GDM is not universal , even among a group of health professionals in whom screening prevalence is likely to be higher than in the general population . Diagnostic criteria for GDM among obstetricians in practice remain nonst and ard despite NDDG recommendations . Better underst and ing of the implication s of differing degrees of glucose intolerance and of varying GDM screening and management strategies is required to make policy recommendations for appropriate and cost-effective care CONTEXT AND OBJECTIVE Lack of consensus about which screening tests to use for gestational diabetes mellitus ( GDM ) and difficulties in performing the gold-st and ard diagnostic test , the 100-g glucose tolerance test ( 100-g GTT ) , justify comparison with alternatives . The aim was to compare this with two other screening tests : combined fasting glucose with risk factors ( FG + RF ) and 50-g GTT . DESIGN AND SETTING Prospect i ve longitudinal cohort study in the Hospital School of Universidade Federal de Mato Grosso do Sul . METHODS The three tests were performed independently on 341 pregnant women . Sensitivity ( S ) , specificity ( Sp ) , positive ( PPV ) and negative ( NPV ) predictive values , positive ( PLR ) and negative ( NLR ) likelihood ratios , and false-positive ( FP ) and false-negative ( FR ) rates obtained with FG + RF and 50-g GTT were compared with values from 100-g GTT . The average one-hour post-intake glucose levels ( 1hPG ) with 50-g and 100-g were compared . Students t test was used in the statistical analysis . RESULTS FG + RF led more pregnant women ( 53.9 % ) to diagnostic confirmation than did 50-g GTT ( 14.4 % ) . The tests were equivalent for S ( 86.4 and 76.9 % ) , PPV ( 98.7 and 98.9 % ) , NLR ( 0.3 and 0.27 ) and FR ( 15.4 and 23.1 % ) . Average 1hPG values were similar : 50-g GTT = 106.8 mg/dl and 100-g GTT = 107.5 mg/dl . CONCLUSION Diagnostic efficiency with simplicity , practicality and low cost make FG + RF more appropriate for screening for GDM . The equivalence of 1hPG allows a new , cheaper and less uncomfortable protocol to be proposed for screening and diagnosing GDM The relationship between optimal levels of glycemic control and perinatal outcome was assessed in a prospect i ve study of 334 gestational diabetic women and 334 subjects matched for control of obesity , race , and parity . All women with gestational diabetes mellitus were instructed in the use of a memory-based reflectance meter . They were treated with the same metabolic goal according to a predetermined protocol . Three groups were identified on the basis of mean blood glucose level throughout pregnancy ( low , less than or equal to 86 mg/dl ; mid , 87 to 104 mg/dl ; and high , greater than or equal to 105 mg/dl ) . The low group had a significantly higher incidence of small-for-gestational-age infants ( 20 % ) . In contrast , the incidence of large-for-gestational-age infants was 21-fold higher in the mean blood glucose category than in the low mean blood glucose category ( 24 % vs. 1.4 % , p less than 0.0001 ) . An overall incidence of 11 % small-for-gestational-age and 12 % large-for-gestational-age infants was calculated for the control group . A significantly higher incidence of small-for-gestational-age infants ( 20 % vs. 11 % , p less than 0.001 ) was found between the control and the low category . In the high mean blood glucose category an approximate twofold increase was found in the incidence of large-for-gestational-age infants when compared with the control group ( p less than 0.03 ) . No significant difference was found between the control and mean blood glucose categories ( 87 to 104 mg/dl ) . Our data suggest that a relationship exists between level of glycemic control and neonatal weight . This information is helpful in targeting the level of glycemic control while optimizing pregnancy outcome in gestational diabetes comparable to the general population The significance of gestational diabetes ( GDM ) has long been a subject of debate and controversy . Whilst observational studies and retrospective medical record review s have demonstrated that gestational diabetes is associated with adverse perinatal outcomes , there has been a paucity of level 1 evidence to demonstrate that intensive treatment of gestational diabetes improves these outcomes . The few r and omised studies examining the treatment of gestational diabetes were small and lacked the power to demonstrate any impact of treatment on serious perinatal morbidity or mortality . In the absence of solid evidence , strong opinions have prevailed , and a range of different guidelines have been put forth by various organisations regarding the screening , diagnosis and management of gestational diabetes . Neither the Royal College of Obstetricians and Gynaecologists nor the Royal Australian and New Zeal and College of Obstetricians and Gynaecologists currently recommends routine screening for gestational diabetes . In Australia , the majority of hospitals offering obstetric services screen for gestational diabetes , but practice s differ in screening and diagnostic criteria , as well as in glucose targets for treatment . The recent publication of the l and mark Australian Carbohydrate Intolerance Study in Pregnant Women ( ACHOIS ) has changed the l and scape and provides convincing evidence to support the treatment of gestational diabetes . This study was commenced in 1993 and it is a tribute to the persistence and enthusiasm of the investigators that it has now reached completion . The study r and omised 1000 women with gestational diabetes ( gestational glucose intolerance by the then World Health Organization ( WHO ) criteria , that is , fasting glucose level < 7.8 mmol/L and 2 h glucose 7.8−11.0 mmol/L on a 75 g oral glucose tolerance test ( OGTT ) ) to receive intervention or routine care . Women in the routine care group and their attending obstetricians were not aware that they had gestational diabetes , and continued with st and ard antenatal care . Women in the intervention group were managed by the obstetric team with physician , diabetes education and dietetic support . The initial intervention comprised dietary advice and home blood glucose monitoring . Insulin therapy was commenced if treatment targets were not met . The treatment targets in the intervention group were : fasting glucose 3.5– 5.5 mmol/L ; prepr and ial glucose < 5.5 mmol/L and 2 h postpr and ial glucose < 7.0 mmol/L based on home capillary glucose testing , in accordance with the recommendations of the Australasian Diabetes in Pregnancy Society . In the intervention group , there was a significant reduction in the rate of serious perinatal complications ( 1 vs 4 % , adjusted P = 0.01 ) . This was a composite primary outcome comprising death , shoulder dystocia , bone fracture and nerve palsy . The reduction in perinatal death approached statistical significance ( 0 cases vs 5 cases , adjusted P = 0.07 ) . Treatment was associated with a reduction in large for gestational age babies , but not at the expense of increased numbers of small for gestational age infants . There was a significant increase in the admissions to the neonatal nursery in the treatment group , but no differences in the incidence of jaundice requiring phototherapy , hypoglycaemia , respiratory distress or neonatal convulsions between the two groups . Contrary to earlier concerns , women treated for gestational diabetes had an improved sense of well-being and lower depression scores when measured by the SF-36 and Edinburgh Postnatal Depression Scale . What are the implication s of the findings of ACHOIS ? First , ACHOIS confirms that gestational diabetes is associated with serious adverse perinatal consequences and that treatment of the type and intensity given within the study improves outcomes . The diagnosis of gestational diabetes should therefore m and ate intervention with dietary advice and home blood glucose monitoring , with insulin added if treatment targets are not met . The failure to treat gestational diabetes with the previously mentioned measures could be considered suboptimal practice . Treatment may be best managed by a multidisciplinary team comprising the obstetrician , physician Background . The clinical significance of gestational diabetes diagnosed in the third trimester is unclear . A prospect i ve observational study was performed on a cohort of women without pre‐existing gestational diabetes or other medical disorders to examine the effect of gestational diabetes on pregnancy complications and infant outcome OBJECTIVE To determine how glucose control in women with GDM treated with metformin and /or insulin influenced pregnancy outcomes . RESEARCH DESIGN AND METHODS Women r and omly assigned to metformin or insulin treatment in the Metformin in Gestational Diabetes ( MiG ) trial had baseline glucose tolerance test ( OGTT ) results and A1C documented , together with all capillary glucose measurements during treatment . In the 724 women who had glucose data for analysis , tertiles of baseline glucose values and A1C and of mean capillary glucose values during treatment were calculated . The relationships between maternal factors , glucose values , and outcomes ( including a composite of neonatal complications , preeclampsia , and large-for-gestational-age [ LGA ] and small-for-gestational-age infants ) were examined with bivariable and multivariate models . RESULTS Baseline OGTT did not predict outcomes , but A1C predicted LGA infants ( P = 0.003 ) . During treatment , fasting capillary glucose predicted neonatal complications ( P < 0.001 ) and postpr and ial glucose predicted preeclampsia ( P = 0.016 ) and LGA infants ( P = 0.001 ) . Obesity did not influence outcomes , and there was no interaction between glycemic control , r and omized treatment , or maternal BMI in predicting outcomes . The lowest risk of complications was seen when fasting capillary glucose was < 4.9 mmol/l ( mean ± SD 4.6 ± 0.3 mmol/l ) compared with 4.9–5.3 mmol/l or higher and when 2-h postpr and ial glucose was 5.9–6.4 mmol/l ( 6.2 ± 0.2 mmol/l ) or lower . CONCLUSIONS Glucose control in women with gestational diabetes mellitus treated with metformin and /or insulin is strongly related to outcomes . Obesity is not related to outcomes in this group . Targets for fasting and postpr and ial capillary glucose may need to be lower than currently recommended BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life OBJECTIVE The International Association of Diabetes and Pregnancy Study Groups ( IADPSG ) has proposed new criteria for the diagnosis of gestational diabetes mellitus ( GDM ) . The aim of this study was to compare the prevalence of GDM when IADPSG criteria were used with the prevalence when the current Australasian Diabetes in Pregnancy Society ( ADIPS ) criteria were used . DESIGN , SETTING AND PARTICIPANTS This was a prospect i ve study over a 6-month period , examining the results of all glucose tolerance tests ( GTTs ) conducted for the diagnosis of GDM in Wollongong , a city using the public and private sectors . MAIN OUTCOME MEASURES The prevalence of GDM using the existing ( ADIPS ) and the proposed ( IADPSG ) criteria . RESULTS There were 1275 evaluable GTTs ( 571 public and 704 private ) . Using the current ADIPS diagnostic criteria , the prevalence of GDM was 8.6 % ( public ) , 10.5 % ( private ) and 9.6 % ( overall ) . Using the proposed IADPSG criteria , the prevalence of GDM was 9.1 % ( public ) , 16.2 % ( private ) and 13.0 % ( overall ) . CONCLUSIONS The proposed IADPSG criteria would increase the prevalence of GDM from 9.6 % to 13.0 % ( P < 0.001 ) . In our study in the Wollongong area , which has a population with a predominantly white background , this increase came mainly from older women attending a private pathology provider . Data from both the public and private sectors need to be included in any discussion on the change in prevalence of GDM Objective . To evaluate the feasibility of a telemedicine system based on Internet and a short message service in pregnancy and its influence on delivery and neonatal outcomes of women with gestational diabetes mellitus ( GDM ) . Methods . 100 women diagnosed of GDM were r and omized into two parallel groups , a control group based on traditional face-to-face outpatient clinic visits and an intervention group , which was provided with a Telemedicine system for the transmission of capillary glucose data and short text messages with weekly professional feedback . 97 women completed the study ( 48/49 , resp . ) . Main Outcomes Measured . The percentage of women achieving HbA1c values < 5.8 % , normal vaginal delivery and having a large for-gestational-age newborn were evaluated . Results . Despite a significant reduction in outpatient clinic visits in the experimental group , particularly in insulin-treated women ( 2.4 versus 4.6 hours per insulin-treated woman resp . ; P < .001 ) , no significant differences were found between the experimental and traditional groups regarding HbA1c levels ( all women had HbA1c < 5.8 % during pregnancy ) , normal vaginal delivery ( 40.8 % versus 54.2 % , resp . ; P > .05 ) and large-for-gestational-age newborns ( 6.1 % versus 8.3 % , resp . ; P > .05 ) . Conclusions . The system significantly reduces the need for outpatient clinic visits and achieves similar pregnancy , delivery , and newborn outcomes OBJECTIVE To develop a model for the prediction of gestational diabetes mellitus ( GDM ) from maternal characteristics and biochemical markers at 11 to 13 weeks ' gestation . METHODS A prospect i ve screening study on early prediction of pregnancy complications ( n = 11 , 464 ) , including 297 ( 2.6 % ) cases of GDM was used to create the predictive model of GDM based on maternal characteristics . Maternal serum concentrations of adiponectin , follistatin-like-3 ( FSTL3 ) and sex hormone-binding globulin ( SHBG ) were measured in a case-control study of 80 women who developed GDM and 300 controls . RESULTS In the screening study , maternal age , body mass index , racial origin , previous history of GDM and macrosomic neonate were significant independent predictors of future GDM . In the GDM group , compared to controls , the median multiple of the normal median adiponectin ( 0.66 ; IQR : 0.5 - 0.9 vs 1.02 ; IQR : 0.7 - 1.29 ) and SHBG ( 0.81 ; IQR : 0.6 - 1.04 vs 1.02 ; IQR : 0.8 - 1.2 ) was lower ( p < 0.05 ) , but FSTL3 was not significantly different . In screening for GDM by maternal characteristics , the detection rate was 61.6 % at a false-positive rate of 20 % and the detection increased to 74.1 % by the addition of adiponectin and SHBG . CONCLUSION First-trimester screening for GDM can be provided by a combination of maternal characteristics and biomarkers OBJECTIVE —The purpose of this study was to test the hypothesis that any degree of abnormal glucose homeostasis detected on antepartum screening for gestational diabetes mellitus ( GDM ) should be associated with an increased risk of postpartum pre-diabetes or diabetes . RESEARCH DESIGN AND METHODS —In this prospect i ve cohort study , 487 women underwent 1 ) antepartum GDM screening by a glucose challenge test ( GCT ) and a diagnostic oral glucose tolerance test ( OGTT ) and 2 ) postpartum metabolic characterization by OGTT at 3 months after delivery . Four baseline glucose tolerance groups were defined on the basis of the antepartum GCT/OGTT : 1 ) GDM ( n = 137 ) ; 2 ) gestational impaired glucose tolerance ( GIGT ) ( n = 91 ) ; 3 ) abnormal GCT with normal glucose tolerance on an OGTT ( abnormal GCT NGT ) ( n = 166 ) ; and 4 ) normal GCT with NGT on an OGTT ( normal GCT NGT ) ( n = 93 ) . RESULTS —The prevalence of postpartum glucose intolerance ( pre-diabetes or diabetes ) increased across the groups from normal GCT NGT ( 3.2 % ) to abnormal GCT NGT ( 10.2 % ) to GIGT ( 16.5 % ) to GDM ( 32.8 % ) ( Ptrend < 0.0001 ) . On logistic regression analysis , all three categories of abnormal glucose homeostasis in pregnancy independently predicted postpartum glucose intolerance : abnormal GCT NGT odds ratio ( OR ) 3.6 ( 95 % CI 1.01–12.9 ) ; GIGT OR 5.7 ( 1.6–21.1 ) ; and GDM OR 14.3 ( 4.2–49.1 ) . Furthermore , both in pregnancy and at 3 months postpartum , insulin sensitivity ( ISOGTT ) and pancreatic β-cell function ( insulinogenic index/homeostasis model assessment of insulin resistance ) progressively decreased across the groups from normal GCT NGT to abnormal GCT NGT to GIGT to GDM ( all Ptrend < 0.0001 ) . CONCLUSIONS —Any degree of abnormal glucose homeostasis in pregnancy independently predicts an increased risk of glucose intolerance postpartum OBJECTIVE To examine anxiety levels of women diagnosed with gestational diabetes mellitus ( GDM ) and to compare these with glucose-tolerant ( GT ) women at similar stages of pregnancy . RESEARCH DESIGN AND METHODS Prospect i ve longitudinal study conducted on 50 women with GDM and 50 GT women . All women completed the Mental Health Inventory ( MHI-5 ) forms and the Speilberger State-Trait Anxiety Inventory ( STAI ) at the beginning of the third trimester , antepartum , and 6 weeks postpartum . Specific questions were also assessed using a Likert scale . RESULTS Women with GDM , compared with GT women , had a higher level of anxiety ( state rather than trait ) at the time of the first assessment . However , before delivery and in the postpartum period , there were no significant differences in anxiety scores between the two groups . Women in both groups were positive about being tested for GDM and wished to be tested during future pregnancies . CONCLUSIONS There were no sustained increased levels of anxiety for women diagnosed with GDM . Concerns expressed about causing sustained maternal anxiety by testing for GDM could not be substantiated OBJECTIVES To assess the maternal and fetal complications of pregnancy in mothers with gestational diabetes mellitus ( GDM ) compared with non-diabetic patients who delivered in the hospital during the study period . METHODS The outcome of pregnancy in 220 Saudi patients with GDM identified from the delivery register/hospital data base and matched for age , parity and body mass index with 220 non-diabetic controls were studied retrospectively from their case files . Patients with multiple pregnancies and abnormal presentation of the fetus were excluded from the study . RESULTS The GDM patients were treated with either diet alone or with additional insulin in some patients who required better control of their blood sugar levels . Patients with GDM had a significantly higher incidence of pre-eclampsia ( p<0.0001 ) ; preterm delivery ( p=0.0226 ) ; induction of labor ( p<0.0001 ) ; cesarean section ( p=0.0019 ) ; higher mean birth weight ( p<0.0001 ) of babies ; large for gestational age infants ( p=0.0011 ) ; macrosomia ( p=0.0186 ) ; and admission to the neonatal intensive care unit ( p=0.0003 ) , compared with the control group . However , the rates of Apgar score < 7 at 5 minutes , respiratory distress syndrome , neonatal hypoglycemia , hyperbilirubinemia and the need for phototherapy were similar in both groups of patients . Congenital anomalies and perinatal mortality rates were not significantly different in the two groups . CONCLUSION GDM is recognized to be associated with increased rates of adverse maternal and neonatal outcomes , which are supported by the findings of this study . Even the mild form of GDM seems to have significant consequences for women and their offspring and is recommended to be aggressively treated . Evidence suggests that early diagnosis and strict control of blood sugar levels throughout the pregnancy can significantly reduce maternal and fetal complications . A multicenter , r and omized controlled trial , based on universally accepted criteria for GDM screening test , st and ardized diagnostic OGTT and management of all patients with GDM versus the st and ard obstetric management of the control is warranted OBJECTIVE Gestational diabetes mellitus ( GDM ) may cause obesity in the offspring . The objective was to assess the effect of treatment for mild GDM on the BMI of 4- to 5-year-old children . RESEARCH DESIGN AND METHODS Participants were 199 mothers who participated in a r and omized controlled trial of the treatment of mild GDM during pregnancy and their children . Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance program in the state of South Australia . The main outcome measure was age- and sex-specific BMI Z score based on st and ards of the International Obesity Task Force . RESULTS At birth , prevalence of macrosomia ( birth weight ≥4,000 g ) was 5.3 % among the 94 children whose mothers were in the intervention group , and 21.9 % among the 105 children in the routine care control group . At 4- to 5-years-old , mean ( SD ) BMI Z score was 0.49 ( 1.20 ) in intervention children and 0.41 ( 1.40 ) among controls . The difference between treatment groups was 0.08 ( 95 % CI −0.29 to 0.44 ) , an estimate minimally changed by adjustment for maternal race , parity , age , and socio-economic index ( 0.08 [ −0.29 to 0.45 ] ) . Evaluating BMI ≥85th percentile rather than continuous BMI Z score gave similarly null results . CONCLUSIONS Although treatment of GDM substantially reduced macrosomia at birth , it did not result in a change in BMI at age 4- to 5-years-old We examined the pregnancy outcome of 112 women classified as minor degrees of glucose intolerance ( MDGI ) in pregnancy in a screening program based on Carpenter and Coustan 's criteria . The MDGI group comprised 49 women with abnormal oral glucose challenge test ( OGCT ) followed by normal OGTT ( group A ) , and 63 with " borderline " OGTT ( 1 abnormal value , group B ) . No treatment was offered to 88 MDGI women , while 26 received dietary advice and metabolic monitoring . A control group was constituted from 112 age- and BMI -matched negative screenees . Similar rates of cesarean sections and macrosomia , but higher rate of large for gestational age ( LGA ) babies ( 25.9 % vs 14.3 % ) were found in MDGI , without difference between groups A and B. When comparing treated and untreated MDGI , lower LGA incidence ( 11.5 % vs 30.2 % ) and no macrosomia were found in the former . In conclusion , untreated MDGI may present excessive fetal growth , which can be normalized by dietary treatment and metabolic monitoring OBJECTIVE To assess blood glucose control and neonatal outcomes when women with gestational diabetes mellitus ( GDM ) were treated with metformin or glyburide . METHODS When an appropriate diet was insufficient to control their blood glucose levels , women with GDM were r and omized to a glyburide or a metformin treatment group . If the maximum dose was reached , the assessed drug was replaced by insulin . The primary outcome measures analyzed were maternal glucose levels during pregnancy , birth weight , and neonatal glucose levels . RESULTS The only significant difference in outcome between the 2 treatment drugs was that maternal weight gain during pregnancy was less in the metformin ( n=40 ) than in the glyburide group ( n=32 ) ( 10.3 kg vs 7.6 kg ; P=0.02 ) . No differences were found in treatment failure , mean level of fasting or postpr and ial plasma glucose , rate of participants with glycated hemoglobin , birth weight , rate of large-for-gestational-age newborns , or newborns with hypoglycemia . CONCLUSION The treatment of GDM with metformin or glyburide was found to be equivalent for both women and newborns AIMS The effects of glargine insulin therapy in pregnancies are not well established . We compared maternal and neonatal outcomes of women with pregestational and gestational diabetes treated with glargine or NPH insulin . METHODS A prospect i ve cohort study was conducted analyzing outcomes from 56 women with pregestational and 82 with gestational diabetes treated with either insulin regimen . RESULTS Comparisons were performed among 138 women : 56 with pregestational and 82 with gestational diabetes . In relation to maternal complications , worsening of retinopathy and nephropathy , preeclampsia , micro and macroalbuminuria , and all kinds of hypoglycemia were found higher in women with pregestational diabetes NPH-treated vs. glargine-treated . In women with gestational diabetes NPH-treated , it was observed increased incidence of prepregnancy and new-onset pregnancy hypertension , micro and macroalbuminuria , as well as mild and frequent hypoglycemia , compared to glargine-treated . Among the neonatal outcomes , 1-min Apgar score < 7 , necessity of intensive care unit and fetal death in pregestational , while jaundice and congenital malformations in gestational diabetes , respectively , were more frequently observed in infants born to NPH-treated , compared to glargine-treated . CONCLUSIONS Glargine use during pregnancy from preconception through delivery , showed to be safe since it is associated with decreased maternal and neonatal adverse outcomes compared with NPH insulin-treated patients Objective . To determine the prevalence of diabetes and impaired glucose tolerance after gestational diabetes mellitus in relation to different categories of glucose tolerance during pregnancy . Design . Prospect i ve study . Setting . Four delivery departments and three hospitals in southern Sweden took part in recruitment and follow‐up . Population . Women undergoing a 75 g oral glucose tolerance test during pregnancy delivering in 2003–2005 . Methods . At first follow‐up , one to two years after delivery , 29 % of eligible women with abnormal glucose tolerance during pregnancy had an oral glucose tolerance test – 160 with gestational diabetes and 309 with gestational impaired glucose tolerance – in addition to 167 control women . Cut‐off levels defining gestational diabetes and impaired glucose tolerance were two‐hour capillary blood glucose levels of 9.0 and 7.8mmol/l or plasma glucose 10.0 and 8.6mmol/l , respectively . Main outcome measures . Frequency of abnormal test results at follow‐up . Results : Diabetes was diagnosed in 11 % and impaired glucose tolerance in 24 % of women with gestational diabetes vs. 4 and 23 % in those with gestational impaired glucose tolerance , respectively . Combining women with abnormal test results during pregnancy revealed diabetes or impaired glucose tolerance in 29 % as compared to 10 % among controls ; the odds ratio ( 95 % confidence interval ) for having abnormal test results was 3.3 ( 1.8–5.9 ) in a multivariate logistic regression analysis . Conclusions : Lowering the cut‐off level for gestational diabetes to include the category of impaired glucose tolerance would identify a high percentage of women with diabetes and impaired glucose tolerance postpartum , who constitute target groups for intervention and /or diabetes prevention Aims /hypothesisWe evaluated diabetes-related pregnancy outcomes in a cohort of Spanish women in relation to their glucose tolerance status , prepregnancy BMI and other predictive variables . Methods The present paper is part of a prospect i ve study to evaluate the impact of American Diabetes Association ( 2000 ) criteria in the Spanish population . A total of 9,270 pregnant women were studied and categorised as follows according to prepregnancy BMI quartiles and glucose tolerance status : ( 1 ) negative screenees ; ( 2 ) false-positive screenees ; ( 3 ) gestational diabetes mellitus ( GDM ) according to American Diabetes Association criteria only ; and ( 4 ) GDM according to National Diabetes Data Group criteria ( NDDG ) . We evaluated fetal macrosomia , Caesarean section and seven secondary outcomes as diabetes-related pregnancy outcomes . The population -attributable and population -prevented fractions of predictor variables were calculated after binary logistic regression analysis with multiple predictors . Results Both prepregnancy BMI and abnormal glucose tolerance categories were independent predictors of pregnancy outcomes . The upper quartile of BMI accounted for 23 % of macrosomia , 9.4 % of Caesarean section , 50 % of pregnancy-induced hypertension and 17.6 % of large-for-gestational-age newborns . In contrast , NDDG GDM accounted for 3.8 % of macrosomia , 9.1 % of pregnancy-induced hypertension and 3.4 % of preterm births . Conclusions /interpretationIn terms of population impact , prepregnancy maternal BMI exhibits a much stronger influence than abnormal blood glucose tolerance on macrosomia , Caesarean section , pregnancy-induced hypertension and large-for-gestational-age newborns Objective . To evaluate the accuracy of diagnosing gestational diabetes mellitus ( GDM ) by a 2‐h blood glucose value ≥9.0 mmol/l in the 75 g oral glucose tolerance test ( OGTT ) . The maternal and neonatal outcome in women with a 2‐h blood glucose value just below this limit , 8.0–8.9 mmol/l , is analyzed . The outcome is compared to a r and omly selected control group OBJECTIVE We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender . STUDY DESIGN This is a secondary analysis of a masked r and omized controlled trial of treatment for mild gestational diabetes mellitus . The results included preeclampsia or gestational hypertension , birthweight , neonatal fat mass , and composite adverse outcomes for both neonate ( preterm birth , small for gestational age , or neonatal intensive care unit admission ) and mother ( labor induction , cesarean delivery , preeclampsia , or gestational hypertension ) . After stratification according to fetal gender , the interaction of gender with treatment status was estimated for these outcomes . RESULTS Of the 469 pregnancies with male fetuses , 244 pregnancies were assigned r and omly to treatment , and 225 pregnancies were assigned r and omly to routine care . Of the 463 pregnancies with female fetuses , 233 pregnancies were assigned r and omly to treatment , and 230 pregnancies were assigned r and omly to routine care . The interaction of gender with treatment status was significant for fat mass ( P = .04 ) and birthweight percentile ( P = .02 ) . Among women who were assigned to the treatment group , male offspring were significantly more likely to have both a lower birthweight percentile ( 50.7 ± 29.2 vs 62.5 ± 30.2 percentile ; P < .0001 ) and less neonatal fat mass ( 487 ± 229.6 g vs 416.6 ± 172.8 g ; P = .0005 , ) whereas these differences were not significant among female offspring . There was no interaction between fetal gender and treatment group with regard to other outcomes . CONCLUSION The magnitude of the reduction of a newborn 's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates OBJECTIVE The objective of the study was to compare premixed insulin aspart 30 ( BIAsp 30 ) vs premixed human insulin 30 ( BHI 30 ) on efficacy , safety , fetal and perinatal outcomes in pregnancies associated with gestational diabetes mellitus [ GDM ] . This was the first r and omized study to use pre mixed insulin analogue [ BIAsp ] in GDM . METHODS The study population consisted of 76 GDM women assigned to BIAsp 30 ( group A ) and an equal number to BHI 30 ( group B ) . RESULTS There was no statistically significant difference between the age , BMI , gestational weeks and glycemic level at entry between the group A and group B women ( p > 0.05 ) . There was no statistical difference between the two groups in glycemic control or insulin dose ( p > 0.05 ) before confinement . The frequency of birth weight of new born above 90 percentile was 6.8 % in Group 1 and 9.2 % in Group 2 . The proportion of macrosomia was higher in Group 2 when compared to Group 1 , however the difference was not statistically significant ( P = 0.819 ) . CONCLUSION BIAsp was safe during pregnancy and pregnant women found it convenient due to meal time dosing . Fetal outcome using BIAsp was also comparable with BHI 30 OBJECTIVE The objective of this study was to compare 2-hour postpr and ial glucose measurements with the st and ard 1-hour , 50 gm glucola screen as a predictor of gestational diabetes . STUDY DESIGN In this prospect i ve study , 448 patients were screened for gestational diabetes mellitus after 20 weeks ' gestation . Each patient was instructed to ingest a meal containing at least 100 gm of carbohydrate , and 2 hours later a plasma glucose level was obtained . Shortly after , each patient was given 50 gm glucola followed by a 1-hour glucose measurement . If either screen showed a result of 140 mg/dl or more , a formal 3-hour glucose tolerance test was done . Data were analyzed with use of the receiver operating characteristic curve . RESULTS Of the 448 patients screened , 39 ( 8.7 % ) had a screening result of 140 mg/dl or greater and 16 ( 3.6 % ) of these had gestational diabetes mellitus . The receiver operating characteristic curve showed that the 1-hour glucose screen was more predictive of gestational diabetes than the postmeal assessment . The area under the receiver operating characteristic curve ( plus or minus the SEM ) for the 1-hour glucose test was 0.746 + /- 0.086 ( p < 0.005 ) whereas the 2-hour postpr and ial test produced an area of 0.524 + /- 0.097 ( p = NS ) . The range of optimal 1-hour glucola discriminatory values was 182 to 190 mg/dl . Thus the critical cutoff value of the 1-hour glucola test that minimizes false-positive results and maximizes true-positive screening for gestational diabetes is 182 mg/dl or greater . CONCLUSIONS The 1-hour glucola test is a reliable screening test for gestational diabetes mellitus whereas the 2-hour post-pr and ial test is not Objective . To investigate relationship between glycemic control in first half of pregnancy by measuring mid-pregnancy HbA1c and neonatal birth weight and amniotic fluid volume . Methods . We prospect ively enrolled 220 pregnant women who received oral glucose tolerance test ( OGTT ) after positive gestational diabetes mellitus screening . We included 102 women with normal OGTT results into final analysis . We measured birth weight and amniotic fluid index ( AFI ) at 32–34 weeks . Results . Mean birth weight was 3313 ± 426 g , and 15.7 % of neonates were classified as large-for-gestational age ( LGA ) . Mean Hb1Ac was 4.96 ± 0.28 % . Median AFI was 145 mm , and polyhydramnios rate was 2.9 % . Birth weight was positively correlated with HbA1c level ( r = 0.373 , p < 0.001 ) and pre-pregnancy body mass index ( BMI ; r = 0.351 , p < 0.001 ) . Linear regression analysis showed that HbA1c and pre-pregnancy BMI were positive independent determinants of neonatal birth weight , and HbA1c was positive independent determinant of AFI . Receiver operating characeristics curve identified HbA1c level of 4.99 as optimal threshold for prediction of LGA with 93.8 % sensitivity , 61.6 % specificity and positive likelihood ratio ( + LR ) of 2.45 and pre-pregnancy BMI value of 25.2 as optimal threshold for prediction of LGA with 81.3 % sensitivity , 57 % specificity and + LR of 1.9 . Conclusion . In non-diabetic pregnant women with abnormal screening test , mid-pregnancy HbA1c level and pre-pregnacy BMI may predict neonatal birth weight . AFI in 32–34 weeks of gestation is related with mid-pregnacy HbA1c level OBJECTIVES To vali date a diagnostic test for gestational diabetes which predicts the risk of macrosomia . METHODS A prospect i ve study was carried out among 354 women at risk for gestational diabetes to compare two glucose tests diagnosing pregnancies at risk of macrosomia . The " practical " test consisted in glucose measurement in the fasting state and two hours after an usual breakfast and the " reference " test was the test proposed in France ( O'Sullivan test with or without a 100 g oral glucose tolerance test ) . Both tests were made between the 24(th ) and 28(th ) week of gestation . Women at high risk for macrosomia were treated . The first assessment criterion was macrosomia ( babies large for gestational age ) . Because of the presence of women treated for gestational diabetes in our sample , the sensitivity and specificity of the tests in diagnosing pregnancies at risk of macrosomia were calculated using either the incidence of macrosomia observed in our population , or the incidence of macrosomia observed theoretically in the absence of treatment ( 22 % in literature ) . RESULTS Macrosomia was diagnosed in 49 neonates ( 14 % ) . The " practical " test was significantly more sensitive than the reference test ( respectively 46.9 % versus 16.3 % , p=0.0001 in the first case , and 54.3 % versus 20.1 % , p=0.0001 in the second case ) . The " reference " test was significantly more specific than the " practical " test ( respectively 80 % versus 68.2 % , p=0.0001 in the first case , and 80.6 % versus 70 % , p=0.0001 in the second case ) . CONCLUSION Our study shows that the simplified " practical " test is more sensitive than the " reference " test currently used in France in screening women at risk of macrosomia OBJECTIVE To examine the association between levels of hyperglycemia , determined by each prenatal oral glucose tolerance test ( OGTT ) value ( fasting , 1 and 2 h ) , and maternal and perinatal outcomes and to determine whether the risk for these outcomes differs for women whose value(s ) equaled or exceeded the thresholds for gestational diabetes mellitus ( GDM ) established by the International Association of Diabetes in Pregnancy Study Groups ( IADPSG ) . RESEARCH DESIGN AND METHODS This article discusses a retrospective study of 8,711 women , delivering at ≥20 weeks ' gestation , who had a prenatal 2-h 75-g OGTT without a prior 50-g challenge and were not treated with insulin , glyburide , diet , and /or exercise during pregnancy . Associations between adverse outcomes and elevated OGTT values are reported . RESULTS After excluding treated women , 19.4 % of the remaining women had IADPSG-defined GDM . Continuous fasting , 1- and 2-h OGTT measures , and GDM ( yes/no ) were significantly associated with most adverse outcomes . However , the magnitude and significance of risk for these outcomes differed by various combinations of abnormal glucose values . Women with normal fasting and elevated postload values were at higher risk for preterm delivery , gestational hypertension , and having an infant with hyperbilirubinema , whereas women with elevated fasting and normal postload values were at higher risk of having a large-for-gestational-age infant , compared with women without GDM . CONCLUSIONS Risks for different adverse outcomes vary depending on which single or combined IADPSG-defined OGTT thresholds are equaled or exceeded . Prospect i ve studies are needed to determine whether changing pre- and postpr and ial glucose targets during pregnancy will more uniformly reduce adverse outcomes OBJECTIVE To provide a guide family physicians can use to interpret current evidence on treating women with pregestational and gestational diabetes mellitus ( GDM ) and to develop a model for managing these patients . QUALITY OF EVIDENCE A MEDLINE search from January 1980 to December 2002 found r and omized controlled trials ( RCTs ) and descriptive studies that had conflicting results regarding screening recommendations . Studies of intensive insulin therapy were predominantly large RCTs ( level I evidence ) . Glycemic targets and guidelines for monitoring pregnant women are based primarily on consensus statements from large national societies . MAIN MESSAGE Most pregnant women should be screened for GDM . Good glycemic control during pregnancy reduces congenital anomalies and stillbirths . Women failing to meet glycemic targets should be referred to multidisciplinary teams and considered for insulin therapy . Intensive insulin therapy reduces the risk of macrosomia and might reduce cesarean section rates and other serious outcomes . CONCLUSION Despite controversy , family physicians can follow a plan for managing diabetic patients during pregnancy that is supported by the best available evidence OBJECTIVE Prior studies have suggested that macrosomia is the only morbid condition associated with gestational diabetes and that this association is the result of confounding by maternal obesity rather than a result of gestational diabetes itself . We sought to determine whether unrecognized gestational diabetes is an independent predictor of macrosomia and other perinatal morbid conditions after controlling for confounding variables . STUDY DESIGN A retrospective analysis of 472 consecutive cases of gestational diabetes diagnosed between 24 and 30 weeks ' gestation was undertaken including 16 prospect ively identified but clinical ly unrecognized cases , 297 cases treated with diet alone , and 76 treated with diet plus insulin . Unrecognized cases were matched to 64 nondiabetic controls for race , age , body mass index , parity , pregnancy weight gain , and gestational age at delivery . RESULTS In the unrecognized gestational diabetes group versus the nondiabetic control versus gestational diabetes diet groups rates of large for gestational age infants ( 44 % vs 5 % vs 9 % , p < 0.0005 ) , macrosomia ( 44 % vs 8 % vs 15 % , p < 0.01 ) , shoulder dystocia ( 19 % vs 3 % vs 3 % , p < 0.05 ) , and birth trauma ( 25 % vs 0 % vs 0.3 % , p < 0.001 ) were all significantly increased . These differences remained significant after controlling for maternal age , race , parity , body mass index , pregnancy weight gain , and gestational age at delivery . CONCLUSIONS This study suggests that unrecognized gestational diabetes increases risks of large for gestational age infants , macrosomia , shoulder dystocia , and birth trauma independent of maternal obesity and other confounding variables . Clinical recognition and dietary control of gestational diabetes are associated with a reduction in these perinatal morbid conditions OBJECTIVE Our aim was to study whether universal screening of all pregnant women by Oral Glucose Challenge Test ( OGCT ) would identify a higher number of women with Gestational Diabetes ( GDM ) than risk factor based screening . STUDY DESIGN A 50 g OGCT test was performed prospect ively in 532 unselected women at 26 - 28 weeks of gestation . The 1-h venous plasma glucose concentration of > 7.3 mmol/l was considered as a positive screening result . Patients with a positive OGCT underwent a 75 g 2-h OGTT , which was used as the actual diagnostic test for GDM . When two or all three of the glucose concentrations in OGTT ( measured at fasting state and 1 and 2 h after the 75 g glucose load ) were above the 97.5th percentile the patient was considered as having GDM . In addition , women with risk factors for GDM also underwent a 75 g OGTT regardless of the result of the OGCT . RESULTS A positive 50 g OGCT was obtained in 123 ( 23 % ) of the women . In 15 ( 12 % ) of these , a diagnosis of GDM was established by the subsequent OGTT . Out of the 409 remaining women with a normal OGCT , 148 ( 36 % ) had risk factors for GDM . An OGTT performed in these patients identified 4 additional women with a GDM . Seventy-nine percent of GDM was thus found with 50 g OGCT without regarding risk factors . Forty-seven percent of the women with GDM would have been missed in screening by risk factors only . CONCLUSIONS In our population 50 g OGCT appears to identify a higher number of GDM than risk factor based screening . Combined with risk factor screening a few more cases of GDM would be found OBJECTIVE The objective of the study was to evaluate the effect of a resistance exercise program with an elastic b and on insulin requirement and glycemic control in patients with gestational diabetes mellitus ( GDM ) . STUDY DESIGN Sixty-four patients with gestational diabetes mellitus were r and omly assigned into 2 groups : an exercise group ( EG ; n = 32 ) and a control group not su bmi tted to the exercise program ( CG ; n = 32 ) . RESULTS A significant reduction in the number of patients who required insulin was observed in the EG ( 7/32 ) compared with the CG group ( 18/32 ) ( P = .005 ) . The percentage of time spent within the proposed target glucose range ( of at least 80 % of weekly measurements below the limits preestablished for the disease ) was significantly higher in EG compared with the CG group ( EG = 0.63 ± 0.30 ; CG = 0.41 ± 0.31 ; P = .006 ) . CONCLUSION The resistance exercise program was effective in reducing the number of patients with GDM who required insulin and in improving capillary glycemic control in this population OBJECTIVES To test the validity of a 75-g , 2-h oral glucose tolerance test ( OGTT ) for diagnosing gestational diabetes mellitus ( GDM ) using the criteria and reference values suggested by the American Diabetes Association for the 100-g , 3-h OGTT . METHODS The results of a 75-g , 2-h OGTT were compared with those of a 100-g , 3-h OGTT in 42 pregnant women . The women 's mean+/-S.D. age and gestational age were 33.6+/-5.4 years and 28.2+/-4.2 weeks , respectively . Each subject was r and omly scheduled within 1 week for both the 75-g and 100-g OGTTs . RESULTS The mean plasma glucose concentrations at 1 , 2 , and 3 h during the 100-g OGTT were significantly higher than those during the 75-g OGTT . Using the Carpenter and Coustan criteria , the prevalence of GDM was 21.4 % when using the 100-g , 3-h OGTT , whereas it was found to be at only 7.1 % when using the 75-g , 2-h OGTT . CONCLUSIONS Plasma glucose responses during the 75-g OGTT were found to be lower than those during the 100-g OGTT . When using the same diagnostic criteria , the prevalence of GDM was also found lower using the 75-g glucose load . It would therefore not be appropriate to use the 75-g OGTT for diagnosing GDM using the criteria and reference values of the 100-g OGTT . To give a comparable prevalence of GDM , the threshold of abnormal plasma glucose levels of the 75-g OGTT would need to be lower than that of the 100-g OGTT INTRODUCTION Early diagnosis of gestational diabetes mellitus ( GDM ) is a prerequisite to reducing fetal and neonatal complications of GDM . OBJECTIVES ( a ) To ascertain the prevalence of GDM in a Sri Lankan pregnant population . Using the 75 g oral glucose tolerance test ( GTT ) and WHO criteria . ( b ) To establish the predictive value of a 50 g glucose challenge test ( GCT ) compared to the GTT ( c ) To compare the outcome of pregnancy in GDM with ' non-diabetic pregnancy ' ( NDP ) STUDY DESIGN : Prospect i ve study on a cohort of pregnant women attending antenatal clinics . SETTING Sri Jayawardenepura General Hospital ( SJGH ) RESULTS : Of the 721 patients , 131 ( 18 % ) had a positive GCT . 40 ( 5.5 % ) patients had GDM . If a one-hour GCT of 7.8 mmol/l was considered suspicious of GDM the sensitivity of the glucose challenge test was 63 % and the specificity 84 % . Statistically significant differences in the prevalence was found when the women were > 35 years [ Relative risk ( RR ) = 3.87 ( 95 % CI-2.06 to 7.27 ) ] or the body mass index > or = 25 . ( RR = 2.45 ( 95 CI-1.30 to 4.61 ) Presence or absence of high parity , family history of diabetes or recurrent abortions had no significant impact on the prevalence of GDM . Mean birth weight was higher ( p < 0.05 ) in GDM ( 3615 SD 103 ) than in NDP ( 2898 SD 143.6 ) . The likelihood of having a caesarean section was higher ( p < 0.01 , Relative risk ( RR ) 2.50 , 95 % CI 1.56 - 3.95 ) in GDM when compared to NDP . A higher incidence of hydramnios ( p < 0.01 RR 3.41 95 % CI 1.44 - 8.05 ) was recorded in GDM when compared to NDP . CONCLUSION The prevalence of GDM in the antenatal clinics at SJGH is 5.5 % . Traditional risk factors did not predict GDM . GDM is associated with a higher risk of caesarean section , hydramnios and macrosomia . Hence screening for GDM should be performed in all pregnant women at 24 to 28 weeks of pregnancy using a GCT OBJECTIVE This study was performed to prospect ively evaluate a screening model for gestational diabetes mellitus on the basis of clinical risk indicators . STUDY DESIGN In a prospect i ve multicenter study with 5235 consecutive pregnant women , diagnostic testing with a 2-hour 75-g oral glucose tolerance test was routinely performed in women with risk indicators and offered to women without risk indicators as part of the study . RESULTS Forty-four percent of the women underwent testing , 43 % declined participation , 6 % did not speak Danish , and 7 % could not be contacted . By extrapolation of the results from tested women to the whole group in question , a 2.4 % prevalence of gestational diabetes mellitus was calculated . Sensitivity and specificity of the model was 80.6 ( 73.7 - 87.6 ) and 64.8 ( 63.5 - 66.1 ) , respectively ( 95 % CIs ) . CONCLUSION Under ideal conditions , sensitivity of the model was comparable with universal screening by fasting glucose or a 1-hour 50-g glucose challenge test . Both screening and diagnostic testing could be avoided in two thirds of all pregnant women OBJECTIVE This study tested the hypothesis that a st and ardized dose of jelly beans could be used as an alternative sugar source to the 50-g glucose beverage to screen for gestational diabetes mellitus . STUDY DESIGN One hundred sixty pregnant women at 24 to 28 weeks ' gestation were recruited for a prospect i ve study to compare 2 sugar sources for serum glucose response , side effects , preference , and ability to detect gestational diabetes mellitus . Patients were r and omly assigned to consume 50-g glucose beverage or 28 jelly beans ( 50 g simple carbohydrate ) . Serum glucose values were determined 1 hour later . The test was later repeated with the other sugar source . Finally , a 100-g 3-hour oral glucose tolerance test was performed . Participants completed a question naire recording subjective outcome variables . American Diabetes Association criteria were used to interpret all test results . RESULTS Among 136 participants completing the study no significant differences were found between 1-hour serum glucose values ( 116.5 + /- 27 mg/dL with 50-g glucose beverage , 116.9 + /- 23.6 mg/dL with jelly beans ; P = .84 ) , frequency of discrepant results ( P = .47 ) , sensitivity , specificity , or predictive value . Jelly beans yielded fewer side effects ( 38 % with 50-g glucose beverage , 20 % with jelly beans ; P < .001 ) and were preferred by 76 % of participants ( P < .001 ) . Five cases ( 3.7 % incidence ) of gestational diabetes mellitus were diagnosed , 3 with 50-g glucose beverage alone , 1 with jelly beans alone , and 1 with both sugar sources . CONCLUSIONS Jelly beans may be used as an alternative to the 50-g glucose beverage as a sugar source for gestational diabetes mellitus screening . The 2 sources provoke similar serum glucose responses . Patients report fewer side effects after a jelly bean challenge than after a 50-g glucose beverage challenge AIM The objectives of this pilot study were to determine the feasibility and effect on glycaemic control of a low-glycaemic-index ( GI ) diet in women with gestational diabetes or impaired glucose tolerance of pregnancy . METHODS participants , recruited from the Diabetes-in-Pregnancy Clinic of an inner-city teaching hospital serving a predominantly non-Caucasian population , were r and omized to a low-GI ( n=23 ) or control ( n=24 ) diet and followed from 28 weeks gestation until delivery . Self-monitored-blood-glucose ( SMBG ) , maternal and infant weight were collected from medical charts . Dietary intakes were assessed using diet records and question naires . RESULTS diet GI on control ( 58 , 95 % CI : 56,60 ) was significantly higher than on low-GI ( 49 , 95 % CI : 47,51 ; p=0.001 ) . Glycaemic control improved on both diets , but more postpr and ial glucose values were within target on low-GI ( 58.4 % of n=1891 ) than control ( 48.7 % of n=1834 ; p<0.001 ) . SMBG post-breakfast was directly related to pre-pregnancy BMI in the control , but not the low-GI group ( BMI * diet interaction ; p=0.021 ) . Participants accepted the study foods and were willing to consume them post-intervention . CONCLUSIONS a low-GI diet was feasible and acceptable in this sample and facilitated control of postpr and ial glucose . A larger study is needed to determine the effect of a low-GI diet on maternal and infant outcomes CONTEXT Obesity and diabetes are increasing in the United States . OBJECTIVE To estimate the prevalence of obesity and diabetes among US adults in 2001 . DESIGN , SETTING , AND PARTICIPANTS R and om-digit telephone survey of 195 005 adults aged 18 years or older residing in all states participating in the Behavioral Risk Factor Surveillance System in 2001 . MAIN OUTCOME MEASURES Body mass index , based on self-reported weight and height and self-reported diabetes . RESULTS In 2001 the prevalence of obesity ( BMI > or = 30 ) was 20.9 % vs 19.8 % in 2000 , an increase of 5.6 % . The prevalence of diabetes increased to 7.9 % vs 7.3 % in 2000 , an increase of 8.2 % . The prevalence of BMI of 40 or higher in 2001 was 2.3 % . Overweight and obesity were significantly associated with diabetes , high blood pressure , high cholesterol , asthma , arthritis , and poor health status . Compared with adults with normal weight , adults with a BMI of 40 or higher had an odds ratio ( OR ) of 7.37 ( 95 % confidence interval [ CI ] , 6.39 - 8.50 ) for diagnosed diabetes , 6.38 ( 95 % CI , 5.67 - 7.17 ) for high blood pressure , 1.88 ( 95 % CI,1.67 - 2.13 ) for high cholesterol levels , 2.72 ( 95 % CI , 2.38 - 3.12 ) for asthma , 4.41 ( 95 % CI , 3.91 - 4.97 ) for arthritis , and 4.19 ( 95 % CI , 3.68 - 4.76 ) for fair or poor health . CONCLUSIONS Increases in obesity and diabetes among US adults continue in both sexes , all ages , all races , all educational levels , and all smoking levels . Obesity is strongly associated with several major health risk factors OBJECTIVE To evaluate tests used for screening and confirmation of gestational diabetes mellitus ( GDM ) in Sri Lanka . METHODS FIELD BASED Consecutive pregnant women in Homagama DDHS area ( n = 853 ) , were assessed for risk factors and subjected to r and om and postpr and ial urinary Benedict 's and Dipstick tests , fasting and 2 hour post 75 g glucose capillary blood glucose ( FBG and 2hBG ) which were vali date d against 75 g oral glucose tolerance test ( OGTT ) performed at 24 - 28 weeks ( WHO criteria ) . HOSPITAL BASED Retrospective analysis of consecutive high-risk women ( n = 999 ) and prospect i ve study of r and omly selected GDM women ( n = 66 ) to assess predictive value of the OGTT . RESULTS FIELD BASED Sensitivity and specificity respectively of r and om urine Benedict 's , 10 % , 99.2 % ; postpr and ial urine Benedict 's , 52.2 % , 94.5 % ; postpr and ial urine Dipstick , 68.7 % , 90 % ; capillary FBG threshold 4.1 mmol/l , 62.6 % , 73 % ; capillary 2hBG threshold 7.2 mmol/l , 98.5 % , 95.2 % ; risk factors , 93.1 % , 22.2 % . HOSPITAL BASED OGTT-11.6 % lag curves , 16.3 % abnormal , FPG accuracy at 4.7mmol/l ; predictive value of 2 hPG > or = 8.9 mmol/l for insulin treatment-sensitivity 97.2 % , specificity 71.4 % . CONCLUSIONS Current practice of r and om urine testing in community screening for gestational diabetes is unreliable , and glucose specific postpr and ial urine test improves sensitivity . FPG is unsuitable for screening , the 2 hour post 75 g blood glucose at a threshold of > 7.2 mmol/l is sensitive and specific . In laboratory confirmation using 75 g OGTT the fasting plasma glucose has low predictive value , 2 hour test performed alone is liable to false positives and 2 hour glucose > 8.9 mmol/l following a peak at 1 hour suggests the need for insulin treatment AIM This study aim ed to investigate the cut-off value of the glucose challenge test in an Iranian population . MATERIAL S AND METHODS A total of 1804 consecutive native Iranian women who underwent a glucose challenge test were prospect ively investigated . The test was performed between 24 and 28 weeks of gestation ; each subject received a 50-g oral glucose load regardless of her fasting or fed state ; the 1-h venous plasma glucose level was then determined . Women exceeding 130 mg/dl received the diagnostic 100-g , 3-h oral glucose tolerance test to determine whether or not they had gestational diabetes mellitus . RESULTS The prevalence of the glucose challenge test for the whole cohort was 7.2 % . The receiver-operator characteristic curve identified a glucose challenge test finding above 135 mg/dl as the cut-off value for detecting gestational diabetes mellitus , which showed a sensitivity and specificity of 95 % and 80 % , respectively . CONCLUSION Our results suggest that the cut-off value of a 50-g glucose challenge test is 135 mg/dl to identify pregnancies with gestational diabetes mellitus in an Iranian population OBJECTIVES To evaluate the applicability of the 50-g glucose challenge test as a screening test for gestational diabetes mellitus in relation to pregnancy outcomes . METHODS A prospect i ve study was conducted on 818 Saudi pregnant females who were r and omly recruited from the Antenatal Clinics at King Abdulaziz University Hospital and New Jeddah Clinic Hospital , Jeddah . All females underwent a 50-g glucose challenge test between 24 - 28 weeks gestation . A result for 50-g glucose challenge test was considered positive at > 7.2 mmol/L and the female was asked to undergo a 100-g oral glucose tolerance test . The diagnosis of gestational diabetes mellitus was carried out according to the National Diabetes Data Group criteria . RESULTS A total of 289 females exhibited plasma glucose level > 7.2 mmol/L following the 50-g glucose challenge test . Of the 289 females enrolled for the 100-g oral glucose tolerance test , 102 were diagnosed to have gestational diabetes mellitus ( positive oral glucose tolerance test ) and 187 were considered oral glucose tolerance test negative according to the National Diabetes Data Group diagnostic criteria . This gave a prevalence of gestational diabetes mellitus of 12.5 % . Gestational diabetes mellitus females were significantly older in age , heavier in weight , with higher gravidity , greater percentage of operative deliveries and still-births , and heavier fetal birth weight as compared with the non-gestational diabetes mellitus group ( P<0.05 in each case ) . The maximum sensitivity and specificity of the 50-g glucose challenge test were found to be at plasma glucose value of 7.8 mmol/L post the 50 g glucose load . The sensitivity and specificity of this value was 88 % and 84 % , with a positive predictive value of 82 % . To determine whether the values of plasma glucose after a 50-g glucose load were detecting abnormalities similar to those detected according to that of oral glucose tolerance test ; the values obtained one-hour post the 50-g glucose challenge test were compared with zero- , one- , 2- and 3-hour values and also the area under the curve in the 100-g oral glucose tolerance test . Plasma glucose post the 50-g glucose challenge test showed marked correlation with oral glucose tolerance test results . This was mostly occurring at the one- and 2-hour oral glucose tolerance test values and was stronger in the gestational diabetes mellitus group and in both the gestational diabetes mellitus plus negative oral glucose tolerance test combined , than in the negative oral glucose tolerance test group on its own . CONCLUSION It is concluded that plasma glucose level measured one-hour post a 50-g glucose challenge test at 24 - 28 weeks of gestation with a cut-off value of 7.8 mmol/L is a reliable screening test for gestational diabetes mellitus in the local population studied . This test offers the best combination of ease and economy of use and reproducibility in screening for gestational diabetes mellitus CONTEXT The increasing prevalence of obesity is a major public health concern , since obesity is associated with several chronic diseases . OBJECTIVE To monitor trends in state-specific data and to examine changes in the prevalence of obesity among adults . DESIGN Cross-sectional r and om-digit telephone survey ( Behavioral Risk Factor Surveillance System ) of noninstitutionalized adults aged 18 years or older conducted by the Centers for Disease Control and Prevention and state health departments from 1991 to 1998 . SETTING States that participated in the Behavioral Risk Factor Surveillance System . MAIN OUTCOME MEASURES Body mass index calculated from self-reported weight and height . RESULTS The prevalence of obesity ( defined as a body mass index > or = 30 kg/m2 ) increased from 12.0 % in 1991 to 17.9 % in 1998 . A steady increase was observed in all states ; in both sexes ; across age groups , races , educational levels ; and occurred regardless of smoking status . The greatest magnitude of increase was found in the following groups : 18- to 29-year-olds ( 7.1 % to 12.1 % ) , those with some college education ( 10.6 % to 17.8 % ) , and those of Hispanic ethnicity ( 11.6 % to 20.8 % ) . The magnitude of the increased prevalence varied by region ( ranging from 31.9 % for mid Atlantic to 67.2 % for South Atlantic , the area with the greatest increases ) and by state ( ranging from 11.3 % for Delaware to 101.8 % for Georgia , the state with the greatest increases ) . CONCLUSIONS Obesity continues to increase rapidly in the United States . To alter this trend , strategies and programs for weight maintenance as well as weight reduction must become a higher public health priority OBJECTIVE : We sought to describe the predictive value for gestational diabetes mellitus ( GDM ) using different glucose challenge test thresholds in Mexican-American women . METHODS : A prospect i ve population -based study of 6,857 gravid women , who were tested with a 50-g glucose challenge test at 24–28 weeks of gestation , was performed . A screening value of 130 mg/dL or greater was followed by a 3-hour , 100-g oral glucose tolerance test . Gestational diabetes mellitus was diagnosed by 2 or more abnormal values using the Carpenter and Coustan criteria . For purpose of analysis , GDM diagnosis was categorized with glucose challenge test values in 10-mg/dL increments . A comparison between Carpenter-Coustan and the National Diabetic Data Group criteria for GDM diagnosis was performed for each glucose challenge test threshold category . Sensitivity and specificity for GDM diagnosis were further calculated for different glucose challenge test thresholds ( 130 , 135 , and 140 mg/dL ) . RESULTS : Overall , GDM was diagnosed in 469 of 6,857 ( 6.8 % ) women , and one abnormal oral glucose tolerance test value was tested in 351 of 6,857 women ( 5.1 % ) . Normal glucose challenge test results ( threshold less than 130 mg/dL ) were obtained in 4,316 of 6,857 women . An elevated glucose challenge test value increases the risk of GDM , but even in high glucose challenge test thresholds ( more than 180 mg/dL ) , the predictive value for GDM was only 50 % . The sensitivity and specificity for GDM diagnosis using 3 different glucose challenge test thresholds were as follows : threshold 130 mg/dL or more : 97 % and 63 % ; threshold 135 mg/dL or more : 91 % and 73 % ; and threshold 140 mg/dL or more : 85 % and 78 % , respectively . CONCLUSION : Data suggests that an elevated glucose challenge test level can not be used as a single diagnostic tool for GDM even in high test thresholds . A threshold of 130 mg/dL may be recommended as a screening threshold for GDM in Mexican-American women . LEVEL OF EVIDENCE : We evaluated variations in glucose measurements and the reproducibility of glucose tolerance classification in a high-risk screening setting in general practice . Screening for diabetes was performed in persons aged 40 - 69 years . Based on capillary fasting ( FBG ) and 2-h blood glucose ( 2 hBG ) individuals with impaired fasting glycaemia ( IFG ) , impaired glucose tolerance ( IGT ) and diabetes had a second test done after 14 days . Intra-individual coefficients of variation ( CV ) were estimated in each glucose tolerance class using the approximation CV(2)(x)=var(ln(x ) ) . Bl and -Altman plots with limits of agreement were made . In the total population , the CV(intra ) was 7.9 % and 13.8 % for FBG and 2 hBG , respectively . Limits of agreement ranged from -1.15 to 1.67 mmol/l for FBG and from - 2.62 to 3.27 mmol/l for 2 hBG . One individual with IFG and 22.5 % with IGT had diabetes at the second test , 76.1 % with diabetes had this diagnosis confirmed , and about 30 % with IFG and IGT had normal glucose tolerance at the second test . The expected values of repeated capillary blood glucose measurements were about+/-1 and + /-3 mmol/l for FBG and 2 hBG , respectively . Yet , 70 % of high-risk prediabetic individuals were persistently classified with abnormal glucose regulation ; diabetes was confirmed in 76 % of the cases Infant macrosomia is a serious medical concern . Pregnant women who do not meet the specific diagnosis for gestational diabetes may still have glucose-mediated macrosomia . In Santa Barbara County all pregnant women are screened for gestational diabetes at 24 - 28 weeks with a 50-g , 1-hr glucose challenge test ( GCT ) . All patients who fail this test are placed on a st and ard euglycemic diet ( 40 % carbohydrate , 20 % protein , 40 % fat ) and perform home glucose monitoring of fasting and postpr and ial glucose levels . The objective of this study was to examine the effectiveness of this treatment program in decreasing infant macrosomia , maternal and infant morbidity , maternal complications , and operative delivery . We studied 103 women who had a positive GCT , but a negative 100-g , 3-hr oral glucose tolerance test ( OGTT ) . The women were r and omly assigned to either experimental or control groups with experimental women receiving dietary counseling and home glucose monitoring instruction ( HBGM ) . HBGM diaries were review ed weekly by clinic nurses . All women had hemoglobin A1c ( HbA1c ) tests at 28 and 32 weeks . Maternal and fetal charts were review ed to determine delivery type and complications , indications for cesarean section ( C-section ) , and infant gestational age , gender , Apgar scores , birth weight , morbidities , and congenital anomalies . Of the 103 women , 5 women required insulin treatment , 1 woman had an abortion , and 14 women were indeterminate regarding compliance or were control women who received diet counseling and HBGM . The results are based on 83 women--48 control and 35 experimental . There were no significant differences between the groups for age , parity , or weight at 28 - 30 weeks or 37 weeks to delivery , or HbA1c at 28 weeks . HbA1c was significantly higher in control women at 32 weeks . Birth weight expressed in grams or as a percentile specific for gender , ethnicity , and gestational age was significantly higher in control infants . Birth weight was significantly correlated with maternal intake weight , weight at 28 - 30 weeks , and weight at delivery and with HbA1c at 32 weeks ' gestation . There were no significant differences between groups for maternal complications . Groups were significantly different for mode of delivery with experimental women having more induced vaginal deliveries but fewer repeat C-sections than control women . Groups were not different for primary C-sections . Women who fail the GCT , but not the OGTT and thus do not receive the diagnosis of GDM are still at risk for delivering a macrosomic infant and operative delivery . Our program of treatment for all women who fail the GCT improves outcome by reducing infant birth weight and the number of cesarean sections AIM Currently , there is no international consensus for gestational diabetes mellitus ( GDM ) diagnosis . This is a report of our experience of GDM screening according to the 1996 French guidelines . METHODS For 5 years , all pregnant women followed at our hospital ( n=11,545 ) were prospect ively screened for GDM between weeks 24 and 28 of pregnancy with a two-step strategy : the O'Sullivan test ( OS ) with a threshold at 130 mg/dL , followed by a 100-g OGTT if positive . GDM was diagnosed according to Carpenter and Coustan criteria . RESULTS Prevalence of GDM was 4.26 % [ 344/1451 of patients with an OS of 130 - 199 mg/dL ( 12.1 % ) ; and 148 patients with an OS greater than 200 mg/dL ] . The false-positive rate for the OS was 76.8 % . Compared with 140 mg/dL , a threshold of 130 mg/dL caused 401 additional negative OGTTs in 90 % of cases . In 80.7 % GDM patients , fasting glucose was less than 95 mg/dL. The time lag between OS and OGTT was 3 weeks ( 1 - 84 days ) . Risk factors associated with GDM were maternal age , preconception overweight and obesity , parity , personal history of GDM or macrosomia , and familial history of obesity ( P<0.05 ) , but not diabetes . Also , 20 % of GDM patients had no risk factors , whereas they were present in 75 % of patients without GDM . CONCLUSION In our population , a two-step screening strategy for GDM was neither relevant nor efficient . It could be simplified with a single-step definitive screening strategy using a 75-g OGTT , as used in the HAPO study , and as recommended by the IADPSG and the recent French Expert Consensus . At present , there are still no evidence -based arguments to help in deciding between selective or universal screening for GDM Objective To test the hypothesis that glucose abnormality , as shown by glucose tolerance test ( GTT ) periodicity , is not affected by different glucose loads , allowing for the identification of gestational diabetes mellitus ( GDM ) under varying glucose challenges . Methods Eighty subjects were tested by multiple GTTs 1 week apart . Each woman served as her own control , undergoing a st and ard 3-hour , 100-g GTT ; then , half of the subject group r and omly underwent a 50-g and the other half a 75-g , 2-hour GTT . Subjects were classified using National Diabetes Data Group thresholds for the 100-g GTT . Those with two or more abnormal values were classified as gestational diabetic ( GDM group ) ; the rest of the women were considered to be nondiabetic . The projected time for the GTT to revert to fasting value , GTT periodicity , was then deter-mined for each glucose load in the GDM and nondiabetic groups . Results All glucose values for the nondiabetic group were significantly lower at 1 and 2 hours than those for the GDM group , regardless of the glucose load ( P < .04 ) . There was a statistically significant difference within the GDM and non-diabetic groups between glucose values of the 100- and 50-g GTTs at 1 hour ( P < .02 ) and between all loads at 2 hours ( P < .04 ) . The GTT periodicity for the 3-hour , 100-g test was significantly longer for patients with GDM , as shown previously ( 5.6 ± 1.9 versus 3.2 ± 1.7 hours , P < .0001 ) . In addition , similar values were found for nondiabetic and GDM subjects for the 75-g ( 5.1 ± 2 versus 3.6 ± 1.8 hours , P < .04 ) , but not the 50-g load ( 2.2 ± .6 versus 1.34 ± .8 hours , P < .01 ) . Conclusion Glucose tolerance test periodicity will identify subjects with GDM regardless of GTT load because the physiologic disturbance of glucose level measured by this time period remains comparably longer than in normal subjects . We speculate that the relatively shorter cycle of the 50-g load may reflect an insufficient challenge to pancreatic function AIMS To clarify risk factors predictive of glucose intolerance in later pregnancy . METHODS We prospect ively studied 509 pregnant women who visited the obstetrics clinic in Tokyo prior to week 13 of gestation , between September 2008 and January 2010 . Biochemical parameters were measured in fasting plasma sample s collected at week 8.0 ± 2.0 of gestation . A 50 g glucose challenge test ( GCT ) was performed between weeks 26 and 29 : plasma glucose levels ≥ 7.8 mmol/l 1h after ingestion indicated a positive GCT . Logistic regression was performed , adjusting for relevant covariates . RESULTS We identified 114 patients with positive GCTs , including 8 with gestational diabetes mellitus ( GDM ) . After correcting for baseline body mass index , only the homeostasis model assessment of insulin resistance value remained a significant predictor of GCT positivity ( OR 2.07 ; 1.21 - 3.55 ) . We identified threshold values of fasting plasma glucose ( FPG ) ≥ 3.66 mmol/l and fasting plasma insulin ( FPI ) ≥ 36.69 pmol/l as indicative of a higher risk of positive GCT ( OR 2.38 ; 1.49 - 3.80 ) . CONCLUSIONS First trimester FPI levels improve the predictive ability of FPG level on subsequent GCT positivity OBJECTIVE : To estimate the association between fasting and 2-hour postpr and ial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes . METHODS : In this secondary analysis of a multicenter r and omized treatment trial of mild gestational diabetes , the median fasting and 2-hour postpr and ial glucose levels were analyzed in 2-week intervals and change over time ( slope ) was calculated for women with gestational diabetes ( abnormal oral glucose tolerance test ) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed . Regression analyses were performed to estimate the relationship between median fasting and postpr and ial glucose and neonatal fat mass , cord blood C-peptide , birth weight , large-for-gestational-age neonates , macrosomia ( greater than 4,000 g ) , and neonatal hypoglycemia . RESULTS : Among 460 women with gestational diabetes , median fasting ( P<.001 ) , postpr and ial breakfast ( P<.001 ) , and postpr and ial lunch ( P<.001 ) glucose values declined over the treatment period , whereas postpr and ial dinner values remained stable ( P=.83 ) . Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass ( 1.35 ; 95 % CI 1.09–1.66 ; P=.006 ) and elevated C-peptide ( 1.29 ; CI 1.09–1.52 ; P=.003 ) . Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates ( 1.27 ; CI 1.05–1.53 ; P=.01 ) , macrosomia ( 1.32 ; CI 1.04–1.65 ; P = .02 ) , and elevated C-peptide ( 1.19 ; CI 1.03–1.38 ; P=.02 ) . CONCLUSION : In women treated for mild gestational diabetes , higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia , large-for-gestational age , and elevated C-peptide . LEVEL OF EVIDENCE : This study compared the results of a 75-g , 3-hour oral glucose tolerance test with those of a traditional 100-g oral glucose tolerance test . Thirty-two pregnant women participated in the study . Each patient served as her own control , undergoing both a 100- and a 75-g oral glucose tolerance test within 1 week . Despite a strong positive correlation between the results of the two tests , the 1- , 2- , and 3-hour glucose values of the 100-g glucose load were significantly higher than the comparable values of the 75-g oral glucose tolerance test . Sixteen of 32 women were diagnosed as having gestational diabetes mellitus using the National Diabetes Data Group criteria and the 100-g oral glucose tolerance test , whereas only 6 of these 16 women would have been identified with the 75-g oral glucose tolerance test . If data from one test are to be compared with the other , new thresholds of glucose abnormality need to be developed Please cite this paper as : Meltzer S , Snyder J , Penrod J , Nudi M , Morin L. Gestational diabetes mellitus screening and diagnosis : a prospect i ve r and omised controlled trial comparing costs of one‐step and two‐step methods . BJOG 2010;117:407–415 OBJECTIVE The purpose of this study was to compare the perinatal outcomes of women after diagnosis of gestational diabetes by the current American College of Obstetricians and Gynecologists-National Diabetes Data Group recommendations with outcomes after diagnosis by the American Diabetes Association criteria . STUDY DESIGN We identified records of 242 women who had had the st and ard 3-hour oral glucose tolerance test between 1995 and 1999 at the Regional Medical center in Memphis . Patients were categorized into 1 of 3 groups as follows : euglycemic control subjects ( n = 69 ) , subjects with gestational diabetes diagnosed by the National Diabetes Data Group criteria ( n = 130 ) , and subjects with gestational diabetes diagnosed by the American Diabetes Association criteria ( n = 43 ) . Maternal and infant charts were review ed . Primary outcomes included frequency of cesarean delivery , preeclampsia , and macrosomia . In univariate analysis the chi2 test was used to compare group differences , and in multivariate analysis we used stepwise logistic regression and controlled for confounding factors . RESULTS No differences existed among the 3 groups regarding maternal race , body mass index , history of preeclampsia , or family history of diabetes . The frequency of overall cesarean delivery , of cesarean delivery for macrosomia or arrest disorder , of preeclampsia , and of macrosomia did not differ significantly among the 3 groups . Neonatal hypoglycemia was more frequent in the groups with a diagnosis by the American Diabetes Association criteria ( 23.3 % ) and by the National Diabetes Data Group criteria ( 16.2 % ) than in the control subjects ( 7.2 % ) , reaching near significance ( P = .057 ) . In the multivariate analysis , cesarean delivery for macrosomia or an arrest disorder correlated negatively with parity and positively with body mass index . Preeclampsia was associated with African American race and body mass index ; macrosomia correlated with a history of macrosomia and familial diabetes . Neonatal hypoglycemia was more common in the American Diabetes Association group ( odds ratio , 2.45 ; 95 % confidence interval , 1.004 - 5.97 ) and in the insulin-requiring National Diabetes Data Group category ( odds ratio , 3.71 ; 95 % confidence interval , 1.20 - 11.44 ) . CONCLUSION The benefits of defining an additional high-risk population of women with gestational diabetes by the American Diabetes Association criteria are unclear . Further large-scale prospect i ve clinical trials are required AIM To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes . METHODS The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009 . Subjects were r and omly assigned to receive either myoinositol supplementation ( 4 g daily ) plus folic acid ( 400 μg daily)-the study group-or folic acid only ( 400 μg daily)-the control group . Both groups received the same diet prescription . Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment . RESULTS There were 69 evaluable patients , 24 in the study group and 45 in the control group . Fasting glucose and insulin , and consequently homeostasis model assessment of insulin resistance , decreased in both groups ( 50 % in the study group vs. 29 % in the control group ) , but the decline in the study group was significantly greater than that in the control group ( P = 0.0001 ) . Adiponectin increased in the myoinositol group while it decreased in the control group ( P = 0.009 ) . CONCLUSION Myoinositol improves insulin resistance in patients with gestational diabetes Objective . To examine pregnancy outcomes in relation to different categories of glucose tolerance during pregnancy . Design . Prospect i ve observational cohort study . Setting . Patient recruitment and data collection were performed in four delivery departments in southern Sweden . Population . Women delivering during 2003–2005 ; 306 with gestational diabetes mellitus , 744 with gestational impaired glucose tolerance and 329 r and omly selected controls . Methods . All women were offered a 75 g oral glucose tolerance test during pregnancy . On the basis of their capillary 2‐hour plasma glucose concentrations , three groups were identified : gestational diabetes mellitus ( > 10.0 mmol/l ) , gestational impaired glucose tolerance ( 8.6–9.9 mmol/l ) and controls ( < 8.6 mmol/l ) . Data for the groups were compared using a population ‐based data base . Main outcome measures . Maternal and fetal outcomes . Results . For the gestational diabetes mellitus group , adjusted odds ratios ( 95 % confidence intervals ) for hypertensive disorders during pregnancy and induction of labor and emergency cesarean section were 2.7 ( 1.3–5.8 ) , 3.1 ( 1.8–5.2 ) and 2.5 ( 1.5–4.4 ) , respectively ; and for Apgar score < 7 at 5 minutes , need for neonatal intensive care > 1 day and large‐for‐gestational age infant were 9.6 ( 1.2–78.0 ) , 5.2 ( 2.8–9.6 ) and 2.5 ( 1.3–5.1 ) , respectively . The increases in odds ratios for the gestational impaired glucose tolerance group were less pronounced but still significant for hypertension during pregnancy , induction of labor , large‐for‐gestational age infant and use of neonatal intensive care > 1 day , with odds ratios ( 95 % confidence interval ) 2.0 ( 1.0–4.1 ) , 1.8 ( 1.1–3.0 ) , 2.1 ( 1.1–3.9 ) and 2.1 ( 1.1–3.8 ) , respectively . Conclusions . These data indicate that even limited degrees of maternal hyperglycemia may affect the outcome of pregnancy |
2,442 | 30,640,272 | Psychometric characteristics of the selected apps were robust , but heterogeneity of the studies did not enable comparisons between apps to identify the most valid one . | Mobile health apps are growing constantly in number and popularity .
Some mobile apps are used for clinical assessment , and consequently need to be verified and vali date d appropriately , along with the mobile platform , to ensure their safe and effective operation .
We review the current literature on available smartphone goniometric apps vali date d for joint angle measurement and their main psychometric characteristics . | In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old . Such investigations are often analysed inappropriately , notably by using correlation coefficients . The use of correlation is misleading . An alternative approach , based on graphical techniques and simple calculations , is described , together with the relation between this analysis and the assessment of repeatability Background There are easily accessible tools on smartphones ( APP ) for measuring elbow range of motion ( ROM ) . The purpose of this study is to evaluate the validity of a particular APP in determining elbow ROM in comparison with the commonly used goniometer ( GON ) , surgeon estimation of range ( EST ) and measurement on X-ray ( XR ) . Methods The study included 20 patients ( 40 elbows ) . Flexion , extension , pronation and supination were measured using three different methods : EST , GON and APP . Radiographic measurements were taken using the average humeral diaphysis axis and dorsal midthird of ulna in flexion and extension . Results The accuracy of the three different methods has been compared to GON using statistical analysis ( ANOVA and paired sample s test ) . There was no statistically significant difference for XR flexion measurement ( mean of 2.8 ° ± 1.5 ° ) . The APP overestimated flexion ( mean of 6.4 ° ± 1.0 ° ) , and EST underestimated it ( mean of − 7.9 ° ± 1.1 ° ) . For extension , the mean difference was 2.8 ° ± 0.7 ° for EST and − 26.8 ° ± 3.1 ° for XR . The APP method did not significantly differ from GON . Supination accuracy was greater with EST ( 2.7 ° ± 1.7 ° ) than with APP ( 5.9 ° ± 1.9 ° ) . There was no difference for pronation measurement with both EST and APP . Conclusions This study is the first comparing four measurement techniques of elbow ROM . Our results showed that EST was only accurate for forearm rotation . The XR scored the best for flexion but is less reliable for extension . Surprisingly , compared to GON , APP did not correlate as we expected for flexion and supination , but the other methods were also inaccurate . We found APP to be very useful to measure complete arc of motion ( difference between maximal flexion and maximal extension).Level of Evidence III , Retrospective review of a prospect i ve cohort of elbow fracture patients : Diagnostic Study Objectives The aim of our study was to develop a smartphone-aided end vertebra selection method and to investigate its effectiveness in Cobb angle measurement . Methods Twenty-nine adolescent idiopathic scoliosis patients ' pre-operative posteroanterior scoliosis radiographs were used for end vertebra selection and Cobb angle measurement by st and ard method and smartphone-aided method . Measurements were performed by 7 examiners . The intraclass correlation coefficient was used to analyze selection and measurement reliability . Summary statistics of variance calculations were used to provide 95 % prediction limits for the error in Cobb angle measurements . A paired 2-tailed t test was used to analyze end vertebra selection differences . Results Mean absolute Cobb angle difference was 3.6 ° for the manual method and 1.9 ° for the smartphone-aided method . Both intraobserver and interobserver reliability were found excellent in manual and smartphone set for Cobb angle measurement . Both intraobserver and interobserver reliability were found excellent in manual and smartphone set for end vertebra selection . But reliability values of manual set were lower than smartphone . Two observers selected significantly different end vertebra in their repeated selection s for manual method . Conclusion Smartphone-aided method for end vertebra selection and Cobb angle measurement showed excellent reliability . We can expect a reduction in measurement error rates with the widespread use of this method in clinical practice . Level of evidence Level III , Diagnostic The use of smartphones in clinical practice is steadily increasing with the availability of low cost/freely available " apps " that could be used to assess human gait . The primary aim of this manuscript is to test the concurrent validity of kinematic measures recorded by a smartphone application in comparison to a 3D motion capture system in the sagittal plane . The secondary aim was to develop a protocol for clinicians on the set up of the smartphone camera for video movement analysis . The sagittal plane knee angle was measured during heel strike and toe off events using the smart phone app and a 3D motion-capture system in 32 healthy subjects . Three trials were performed at near ( 2-m ) and far ( 4-m ) smartphone camera distances . The order of the distances was r and omized . Regression analysis was performed to estimate the height of the camera based on either the subject 's height or leg length . Absolute measurement errors were least during toe off ( 3.12 ± 5.44 degrees ) compared to heel strike ( 5.81 ± 5.26 degrees ) . There were significant ( p < 0.05 ) but moderate agreements between the application and 3D motion capture measures of knee angles . There were also no significant ( p > 0.05 ) differences between the absolute measurement errors between the two camera positions . The measurement errors averaged between 3 - 5 degrees during toe off and heel strike events of the gait cycle . The use of smartphone apps can be a useful tool in the clinic for performing gait or human movement analysis . Further studies are needed to establish the accuracy in measuring movements of the upper extremity and trunk OBJECTIVES The weight bearing lunge test is increasing being used by health care clinicians who treat lower limb and foot pathology . This measure is commonly established accurately and reliably with the use of expensive equipment . This study aims to compare the digital inclinometer with a free app , TiltMeter on an Apple iPhone . DESIGN This was an intra-rater and inter-rater reliability study . Two raters ( novice and experienced ) conducted the measurements in both a bent knee and straight leg position to determine the intra-rater and inter-rater reliability . Concurrent validity was also established . METHODS Allied health practitioners were recruited as participants from the workplace . A preconditioning stretch was conducted and the ankle range of motion was established with the weight bearing lunge test position with firstly the leg straight and secondly with the knee bent . The measurement device and each participant were r and omised during measurement . RESULTS The intra-rater reliability and inter-rater reliability for the devices and in both positions were all over ICC 0.8 except for one intra-rater measure ( Digital inclinometer , novice , ICC 0.65 ) . The inter-rater reliability between the digital inclinometer and the tilmeter was near perfect , ICC 0.96 ( CI : 0.898 - 0.983 ) ; Concurrent validity ICC between the two devices was 0.83 ( CI : -0.740 to 0.445 ) . CONCLUSIONS The use of the Tiltmeter app on the iPhone is a reliable and inexpensive tool to measure the available ankle range of motion . Health practitioners should use caution in applying these findings to other smart phone equipment if surface areas are not comparable BACKGROUND An accurate and reliable measurement of shoulder range of motion ( ROM ) is important in the evaluation of the shoulder . A smartphone digital clinometer application is a potentially simpler method for measuring shoulder ROM . The goal of this study was to establish the reliability and validity of shoulder ROM measurements among varying health care providers using a smartphone clinometer application in healthy and symptomatic adults . METHODS An attending surgeon , fellow , resident , physician assistant , and student served as examiners . Bilateral shoulders of 24 healthy subjects were included . Fifteen postoperative patients served as the symptomatic cohort . Examiners measured ROM of each shoulder , first using visual estimation and then using a goniometer and smartphone clinometer in a r and omized fashion . RESULTS The interobserver reliability among examiners showed significant correlation , with average intraclass correlation coefficient [ ICC(2,1 ) ] values of 0.61 ( estimation ) , 0.69 ( goniometer ) , and 0.80 ( smartphone ) . All 5 examiners had substantial agreement with the gold st and ard in healthy subjects , with average ICC(2,1 ) values ranging from 0.62 to 0.79 . The interobserver reliability in symptomatic patients showed significant correlation , with average ICC(2,1 ) values of 0.72 ( estimation ) , 0.79 ( goniometer ) , and 0.89 ( smartphone ) . Examiners had excellent agreement with the gold st and ard in symptomatic patients , with an average ICC(2,1 ) value of 0.98 . CONCLUSION The smartphone clinometer has excellent agreement with a goniometer-based gold st and ard for measurement of shoulder ROM in both healthy and symptomatic subjects . There is good correlation among different skill levels of providers for measurements obtained using the smartphone . A smartphone-based clinometer is a good re source for shoulder ROM measurement in both healthy subjects and symptomatic patients This study aim ed to improve clinical examination techniques by determining the reliability of different methods to evaluate forearm movements . Two methods using the iPhone ™ 5 and its gyroscope application ( alone [ I5 ] or attached to a selfie stick [ ISS ] ) were compared with two conventional measurement devices ( a plastic goniometer with a h and -held pencil [ HHP ] and a bubble goniometer [ BG ] ) to evaluate the active range of movement ( AROM ) of the wrist during pronation and supination . Two independent groups of subjects took part in this prospect i ve single-center diagnostic study : 20 healthy subjects and 20 patients . The four evaluation methods had high intra-observer consistency after three measurements ( intra-class correlation coefficient [ ICC ] [ 3 , 1 ] of 0.916 for the HHP ; 0.944 for ISS ; 0.925 for BG ; 0.933 for I5 ) and excellent inter-observer reliability ( ICC [ 2 , k ] of 0.926 for HHP ; 0.934 for ISS ; 0.899 for BG ; 0.894 for I5 ) , with an agreement of plus or minus 2 ° . When these devices are used with rigorous methodology , they are reliable for the goniometric evaluation of AROM of wrist pronation and supination ABSTRACT Purpose /hypothesis : The purpose of this study was to determine the reliability and validity of two smartphone applications : ( 1 ) GetMyROM – inclinometery-based and ( 2 ) DrGoniometry – photo-based in the measurement of active shoulder external rotation ( ER ) as compared to st and ard goniometry ( SG ) . Participants : Ninety-four Texas Woman 's University Doctor of Physical Therapy students from the School of Physical Therapy – Houston campus , were recruited to participate in this study . Material s/ methods : Two iPhone applications were compared to SG using both novice and experienced raters . Active shoulder ER range of motion was measured over two time periods in r and om order by blinded novice and experienced raters . Results : Intra-rater reliability using novice raters for the two applications ranged from an intraclass correlation coefficient ( ICC ) of 0.79 to 0.81 with SG at 0.82 . Inter-rater reliability ( novice/expert ) for the two applications ranged from an ICC of 0.92 to 0.94 with SG at 0.91 . Concurrent validity ( when compared to SG ) ranged from 0.93 to 0.94 . There were no significant differences between the novice and experienced raters . Conclusion : Both applications were found to be reliable and comparable to SG . A photo-based application potentially offers a superior method of measurement as visualizing the l and marks may be simplified in this format and it provides a record of measurement . Clinical relevance : Further study using patient population s may find the two studied applications are useful as an adjunct for clinical practice |
2,443 | 31,214,620 | Conversely , we also drew a statically significant conclusion that older patients failed to acquire benefit from ICIs when subdivided with a further cut-off of 75 yr | Objectives Despite the fact that it is widely acknowledged that immune checkpoint inhibitors ( ICIs ) rely on the presence of immune response to take their antitumor effect , little is known whether there is an influence exerted on the efficacy of ICIs based on patients ' age .
We performed a systematic review and meta- analysis to explore the efficacy of ICIs between younger and older patients . | BACKGROUND Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab ( an anti-PD-1 antibody ) plus ipilimumab ( an anti-CTLA-4 antibody ) compared with ipilimumab alone . We report 2-year overall survival data from a r and omised controlled trial assessing this treatment in previously untreated advanced melanoma . METHODS In this multicentre , double-blind , r and omised , controlled , phase 2 trial ( CheckMate 069 ) we recruited patients from 19 specialist cancer centres in two countries ( France and the USA ) . Eligible patients were aged 18 years or older with previously untreated , unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients were r and omly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo , every 3 weeks for four doses . Subsequently , patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity , whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase . R and omisation was done via an interactive voice response system with a permuted block schedule ( block size of six ) and stratification by BRAF mutation status . The study funder , patients , investigators , and study site staff were masked to treatment assignment . The primary endpoint , which has been reported previously , was the proportion of patients with BRAFV600 wild-type melanoma achieving an investigator-assessed objective response . Overall survival was an exploratory endpoint and is reported in this Article . Efficacy analyses were done on the intention-to-treat population , whereas safety was assessed in all treated patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01927419 , and is ongoing but no longer enrolling patients . FINDINGS Between Sept 16 , 2013 , and Feb 6 , 2014 , we screened 179 patients and enrolled 142 , r and omly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone . In each treatment group , one patient no longer met the study criteria following r and omisation and thus did not receive study drug . At a median follow-up of 24·5 months ( IQR 9·1 - 25·7 ) , 2-year overall survival was 63·8 % ( 95 % CI 53·3 - 72·6 ) for those assigned to nivolumab plus ipilimumab and 53·6 % ( 95 % CI 38·1 - 66·8 ) for those assigned to ipilimumab alone ; median overall survival had not been reached in either group ( hazard ratio 0·74 , 95 % CI 0·43 - 1·26 ; p=0·26 ) . Treatment-related grade 3 - 4 adverse events were reported in 51 ( 54 % ) of 94 patients who received nivolumab plus ipilimumab compared with nine ( 20 % ) of 46 patients who received ipilimumab alone . The most common treatment-related grade 3 - 4 adverse events were colitis ( 12 [ 13 % ] of 94 patients ) and increased alanine aminotransferase ( ten [ 11 % ] ) in the combination group and diarrhoea ( five [ 11 % ] of 46 patients ) and hypophysitis ( two [ 4 % ] ) in the ipilimumab alone group . Serious grade 3 - 4 treatment-related adverse events were reported in 34 ( 36 % ) of 94 patients who received nivolumab plus ipilimumab ( including colitis in ten [ 11 % ] of 94 patients , and diarrhoea in five [ 5 % ] ) compared with four ( 9 % ) of 46 patients who received ipilimumab alone ( including diarrhoea in two [ 4 % ] of 46 patients , colitis in one [ 2 % ] , and hypophysitis in one [ 2 % ] ) . No new types of treatment-related adverse events or treatment-related deaths occurred in this up date d analysis . INTERPRETATION Although follow-up of the patients in this study is ongoing , the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma . The results suggest encouraging survival outcomes with immunotherapy in this population of patients . FUNDING Bristol-Myers Squibb Purpose Patients with squamous non-small-cell lung cancer ( NSCLC ) have poor prognosis and limited treatment options . This r and omized , double-blind , phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC . Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were r and omly assigned ( 1:1 ) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles , with ipilimumab or placebo from cycles 3 to 6 and then , after induction treatment , ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better . The primary end point was overall survival ( OS ) in patients receiving at least one dose of blinded study therapy . Results Of 956 r and omly assigned patients , 749 received at least one dose of blinded study therapy ( chemotherapy plus ipilimumab , n = 388 ; chemotherapy plus placebo , n = 361 ) . Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo ( hazard ratio , 0.91 ; 95 % CI , 0.77 to 1.07 ; P = .25 ) . Median progression-free survival was 5.6 months for both groups ( hazard ratio , 0.87 ; 95 % CI , 0.75 to 1.01 ) . Rates of grade 3 or 4 treatment-related adverse events ( TRAEs ) , any- grade serious TRAEs , and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab ( 51 % , 33 % , and 28 % , respectively ) than with chemotherapy plus placebo ( 35 % , 10 % , and 7 % , respectively ) . Seven treatment-related deaths occurred with chemotherapy plus ipilimumab , and one occurred with chemotherapy plus placebo . Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC . The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies . Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population 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 . ) BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) Purpose : While immune checkpoint inhibitors are disrupting the management of patients with cancer , anecdotal occurrences of rapid progression ( i.e. , hyperprogressive disease or HPD ) under these agents have been described , suggesting potentially deleterious effects of these drugs . The prevalence , the natural history , and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown . Experimental Design : Medical records from all patients ( N = 218 ) prospect ively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed . The tumor growth rate ( TGR ) prior ( “ REFERENCE ” ; REF ) and upon ( “ EXPERIMENTAL ” ; EXP ) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth . Associations between TGR , clinicopathologic characteristics , and overall survival ( OS ) were computed . Results : HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods . Of 131 evaluable patients , 12 patients ( 9 % ) were considered as having HPD . HPD was not associated with higher tumor burden at baseline , nor with any specific tumor type . At progression , patients with HPD had a lower rate of new lesions than patients with disease progression without HPD ( P < 0.05 ) . HPD is associated with a higher age ( P < 0.05 ) and a worse outcome ( overall survival ) . Interestingly , REF TGR ( before treatment ) was inversely correlated with response to anti-PD-1/PD-L1 ( P < 0.05 ) therapy . Conclusions : A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1 . This observation raises some concerns about treating elderly patients ( > 65 years old ) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon . Clin Cancer Res ; 23(8 ) ; 1920–8 . © 2016 AACR . See related commentary by Sharon , p. Introduction : The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second‐ or third‐line treatment in patients with advanced NSCLC in the primary ( n = 850 ) and secondary ( n = 1225 ) efficacy population s of the r and omized phase III OAK study ( respectively referred to as the intention‐to‐treat [ ITT ] 850 [ ITT850 ] and ITT1225 ) at an up date d data cutoff were assessed . Methods : Patients received atezolizumab , 1200 mg , or docetaxel , 75 mg/m2 , intravenously every 3 weeks until loss of clinical benefit or disease progression , respectively . The primary end point was overall survival ( OS ) in the ITT population and programmed death‐lig and 1–expressing subgroup . A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab . Results : Atezolizumab demonstrated an OS benefit versus docetaxel in the up date d ITT850 ( hazard ratio [ HR ] = 0.75 , 95 % confidence interval : 0.64–0.89 , p = 0.0006 ) and the ITT1225 ( HR = 0.80 , 95 % confidence interval : 0.70–0.92 , p = 0.0012 ) after minimum follow‐up times of 26 and 21 months , respectively . Improved survival with atezolizumab was observed across programmed death‐lig and 1 and histological subgroups . In the immunotherapy sensitivity analysis , the relative OS benefit with atezolizumab was slightly greater in the ITT850 ( HR = 0.69 ) and ITT1225 ( HR = 0.74 ) than the conventional OS estimate . Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment‐related adverse events ( 14.9 % ) than did patients receiving docetaxel ( 42.4 % ) ; no grade 5 adverse events related to atezolizumab were observed . Conclusions : The results of the up date d ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel . Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow‐up Purpose Patients with extensive-stage disease small-cell lung cancer ( SCLC ) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum . This r and omized , double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC . Patients and Methods Patients were r and omly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum ( cisplatin or carboplatin ) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule ( chemotherapy in cycles one to four ; ipilimumab or placebo beginning in cycle three up to cycle six ) , followed by ipilimumab or placebo maintenance every 12 weeks . Primary end point was overall survival ( OS ) among patients receiving at least one dose of blinded study therapy . Results Of 1,132 patients r and omly assigned , 954 received at least one dose of study therapy ( chemotherapy plus ipilimumab , n = 478 ; chemotherapy plus placebo , n = 476 ) . Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo ( hazard ratio , 0.94 ; 95 % CI , 0.81 to 1.09 ; P = .3775 ) . Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo ( hazard ratio , 0.85 ; 95 % CI , 0.75 to 0.97 ) . Rates and severity of treatment-related adverse events were similar between arms , except for diarrhea , rash , and colitis , which were more frequent with chemotherapy plus ipilimumab . Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab ( 18 % v 2 % with chemotherapy plus placebo ) . Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo . Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC . No new or unexpected adverse events were observed with chemotherapy plus ipilimumab . Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC & NA ; Respiratory syncytial virus ( RSV ) is the leading cause of lower respiratory tract infections in young children and is further associated with increased healthcare utilization and cost of care in the first years of life . Severe RSV disease during infancy has also been linked to the later development of allergic asthma , yet there remains no licensed RSV vaccine or effective treatment . Pre‐ clinical and clinical studies have shown that disease severity and development of allergic asthma are associated with differences in cytokine production . As a result , stimulation of the innate host immune response with immune potentiators is gaining attention for their prospect i ve application in population s with limited immune responses to antigenic stimuli or against pathogens for which vaccines do not exist . Specifically , macrophage‐activating cytokines such as interferon gamma ( IFN&ggr ; ) and granulocyte colony‐stimulating factor ( GM‐CSF ) are commercially available immune potentiators used to prevent infections in patients with chronic granulomatous disease and febrile neutropenia , respectively . Moreover , an increasing number of reports describe the protective function of IFN&ggr ; and GM‐CSF as vaccine adjuvants . Although a positive correlation between cytokine production and age has previously been reported , little is known about age‐dependent cytokine metabolism or immune activating responses in infant compared to adult lungs . Here we use a non‐compartmental pharmacokinetic model in naïve and RSV‐infected infant and adult BALB/c mice to determine the effect of age on IFN&ggr ; and GM‐CSF elimination and innate cell activation following intranasal delivery . HighlightsAdult mice clear pulmonary cytokines faster than infant mice . IFN&ggr ; , but not GM‐CSF , enhances RSV clearance from the infant murine airway . Intranasal IFN&ggr ; and GM‐CSF achieve higher levels in adult vs infant airways . Low levels of IFN&ggr ; and GM‐CSF are detected in the blood after intranasal delivery . Cytokine blood levels are delayed in infant vs. adult mice after pulmonary delivery BACKGROUND Antibodies targeting the immune checkpoint molecules PD-1 or PD-L1 have demonstrated clinical efficacy in patients with metastatic non-small-cell lung cancer ( NSCLC ) . In this trial we investigated the efficacy and safety of avelumab , an anti-PD-L1 antibody , in patients with NSCLC who had already received platinum-based therapy . METHODS JAVELIN Lung 200 was a multicentre , open-label , r and omised , phase 3 trial at 173 hospitals and cancer treatment centres in 31 countries . Eligible patients were aged 18 years or older and had stage IIIB or IV or recurrent NSCLC and disease progression after treatment with a platinum-containing doublet , an Eastern Cooperative Oncology Group performance status score of 0 or 1 , an estimated life expectancy of more than 12 weeks , and adequate haematological , renal , and hepatic function . Participants were r and omly assigned ( 1:1 ) , via an interactive voice-response system with a stratified permuted block method with variable block length , to receive either avelumab 10 mg/kg every 2 weeks or docetaxel 75 mg/m2 every 3 weeks . R and omisation was stratified by PD-L1 expression ( ≥1 % vs < 1 % of tumour cells ) , which was measured with the 73 - 10 assay , and histology ( squamous vs non-squamous ) . The primary endpoint was overall survival , analysed when roughly 337 events ( deaths ) had occurred in the PD-L1-positive population . Efficacy was analysed in all PD-L1-positive patients ( ie , PD-L1 expression in ≥1 % of tumour cells ) r and omly assigned to study treatment ( the primary analysis population ) and then in all r and omly assigned patients through a hierarchical testing procedure . Safety was analysed in all patients who received at least one dose of study treatment . This trial is registered with Clinical Trials.gov , number NCT02395172 . Enrolment is complete , but the trial is ongoing . FINDINGS Between March 24 , 2015 , and Jan 23 , 2017 , 792 patients were enrolled and r and omly assigned to receive avelumab ( n=396 ) or docetaxel ( n=396 ) . 264 participants in the avelumab group and 265 in the docetaxel group had PD-L1-positive tumours . In patients with PD-L1-positive tumours , median overall survival did not differ significantly between the avelumab and docetaxel groups ( 11·4 months [ 95 % CI 9·4 - 13·9 ] vs 10·3 months [ 8·5 - 13·0 ] ; hazard ratio 0·90 [ 96 % CI 0·72 - 1·12 ] ; one-sided p=0·16 ) . Treatment-related adverse events occurred in 251 ( 64 % ) of 393 avelumab-treated patients and 313 ( 86 % ) of 365 docetaxel-treated patients , including grade 3 - 5 events in 39 ( 10 % ) and 180 ( 49 % ) patients , respectively . The most common grade 3 - 5 treatment-related adverse events were infusion-related reaction ( six patients [ 2 % ] ) and increased lipase ( four [ 1 % ] ) in the avelumab group and neutropenia ( 51 [ 14 % ] ) , febrile neutropenia ( 37 [ 10 % ] ) , and decreased neutrophil counts ( 36 [ 10 % ] ) in the docetaxel group . Serious treatment-related adverse events occurred in 34 ( 9 % ) patients in the avelumab group and 75 ( 21 % ) in the docetaxel group . Treatment-related deaths occurred in four ( 1 % ) participants in the avelumab group , two due to interstitial lung disease , one due to acute kidney injury , and one due to a combination of autoimmune myocarditis , acute cardiac failure , and respiratory failure . Treatment-related deaths occurred in 14 ( 4 % ) patients in the docetaxel group , three due to pneumonia , and one each due to febrile neutropenia , septic shock , febrile neutropenia with septic shock , acute respiratory failure , cardiovascular insufficiency , renal impairment , leucopenia with mucosal inflammation and pyrexia , infection , neutropenic infection , dehydration , and unknown causes . INTERPRETATION Compared with docetaxel , avelumab did not improve overall survival in patients with platinum-treated PD-L1-positive NSCLC , but had a favourable safety profile . FUNDING Merck and Pfizer Background St and ard first‐line therapy for metastatic , squamous non – small‐cell lung cancer ( NSCLC ) is platinum‐based chemotherapy or pembrolizumab ( for patients with programmed death lig and 1 [ PD‐L1 ] expression on ≥50 % of tumor cells ) . More recently , pembrolizumab plus chemotherapy was shown to significantly prolong overall survival among patients with nonsquamous NSCLC . Methods In this double‐blind , phase 3 trial , we r and omly assigned , in a 1:1 ratio , 559 patients with untreated metastatic , squamous NSCLC to receive 200 mg of pembrolizumab or saline placebo for up to 35 cycles ; all the patients also received carboplatin and either paclitaxel or nanoparticle albumin‐bound [nab]–paclitaxel for the first 4 cycles . Primary end points were overall survival and progression‐free survival . Results After a median follow‐up of 7.8 months , the median overall survival was 15.9 months ( 95 % confidence interval [ CI ] , 13.2 to not reached ) in the pembrolizumab‐combination group and 11.3 months ( 95 % CI , 9.5 to 14.8 ) in the placebo‐combination group ( hazard ratio for death , 0.64 ; 95 % CI , 0.49 to 0.85 ; P<0.001 ) . The overall survival benefit was consistent regardless of the level of PD‐L1 expression . The median progression‐free survival was 6.4 months ( 95 % CI , 6.2 to 8.3 ) in the pembrolizumab‐combination group and 4.8 months ( 95 % CI , 4.3 to 5.7 ) in the placebo‐combination group ( hazard ratio for disease progression or death , 0.56 ; 95 % CI , 0.45 to 0.70 ; P<0.001 ) . Adverse events of grade 3 or higher occurred in 69.8 % of the patients in the pembrolizumab‐combination group and in 68.2 % of the patients in the placebo‐combination group . Discontinuation of treatment because of adverse events was more frequent in the pembrolizumab‐combination group than in the placebo‐combination group ( 13.3 % vs. 6.4 % ) . Conclusions In patients with previously untreated metastatic , squamous NSCLC , the addition of pembrolizumab to chemotherapy with carboplatin plus paclitaxel or nab‐paclitaxel result ed in significantly longer overall survival and progression‐free survival than chemotherapy alone . ( Funded by Merck Sharp & Dohme ; KEYNOTE‐407 Clinical Trials.gov number , NCT02775435 . BACKGROUND An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression‐free survival , as compared with placebo , among patients with stage III , unresectable non – small‐cell lung cancer ( NSCLC ) who did not have disease progression after concurrent chemoradiotherapy . Here we report the results for the second primary end point of overall survival . METHODS We r and omly assigned patients , in a 2:1 ratio , to receive durvalumab intravenously , at a dose of 10 mg per kilogram of body weight , or matching placebo every 2 weeks for up to 12 months . R and omization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age , sex , and smoking history . The primary end points were progression‐free survival ( as assessed by blinded independent central review ) and overall survival . Secondary end points included the time to death or distant metastasis , the time to second progression , and safety . RESULTS Of the 713 patients who underwent r and omization , 709 received the assigned intervention ( 473 patients received durvalumab and 236 received placebo ) . As of March 22 , 2018 , the median follow‐up was 25.2 months . The 24‐month overall survival rate was 66.3 % ( 95 % confidence interval [ CI ] , 61.7 to 70.4 ) in the durvalumab group , as compared with 55.6 % ( 95 % CI , 48.9 to 61.8 ) in the placebo group ( two‐sided P=0.005 ) . Durvalumab significantly prolonged overall survival , as compared with placebo ( stratified hazard ratio for death , 0.68 ; 99.73 % CI , 0.47 to 0.997 ; P=0.0025 ) . Up date d analyses regarding progression‐free survival were similar to those previously reported , with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group ( stratified hazard ratio for disease progression or death , 0.51 ; 95 % CI , 0.41 to 0.63 ) . The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group ( stratified hazard ratio , 0.53 ; 95 % CI , 0.41 to 0.68 ) . A total of 30.5 % of the patients in the durvalumab group and 26.1 % of those in the placebo group had grade 3 or 4 adverse events of any cause ; 15.4 % and 9.8 % of the patients , respectively , discontinued the trial regimen because of adverse events . CONCLUSIONS Durvalumab therapy result ed in significantly longer overall survival than placebo . No new safety signals were identified . ( Funded by AstraZeneca ; PACIFIC Clinical Trials.gov number , NCT02125461 . BACKGROUND Enhancing tumor‐specific T‐cell immunity by inhibiting programmed death lig and 1 (PD‐L1)–programmed death 1 ( PD‐1 ) signaling has shown promise in the treatment of extensive‐stage small‐cell lung cancer . Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy . METHODS We conducted this double‐blind , placebo‐controlled , phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive‐stage small‐cell lung cancer who had not previously received treatment . Patients were r and omly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21‐day cycles ( induction phase ) , followed by a maintenance phase during which they received either atezolizumab or placebo ( according to the previous r and om assignment ) until they had unacceptable toxic effects , disease progression according to Response Evaluation Criteria in Solid Tumors , version 1.1 , or no additional clinical benefit . The two primary end points were investigator‐assessed progression‐free survival and overall survival in the intention‐to‐treat population . RESULTS A total of 201 patients were r and omly assigned to the atezolizumab group , and 202 patients to the placebo group . At a median follow‐up of 13.9 months , the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group ( hazard ratio for death , 0.70 ; 95 % confidence interval [ CI ] , 0.54 to 0.91 ; P=0.007 ) . The median progression‐free survival was 5.2 months and 4.3 months , respectively ( hazard ratio for disease progression or death , 0.77 ; 95 % CI , 0.62 to 0.96 ; P=0.02 ) . The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents , with no new findings observed . CONCLUSIONS The addition of atezolizumab to chemotherapy in the first‐line treatment of extensive‐stage small‐cell lung cancer result ed in significantly longer overall survival and progression‐free survival than chemotherapy alone . ( Funded by F. Hoffmann – La Roche/Genentech ; IMpower133 Clinical Trials.gov number , NCT02763579 . |
2,444 | 28,128,441 | There is low- quality evidence that a restrictive RBC transfusion policy has little or no effect on : mortality at 30 to 100 days , bleeding , or hospital stay . | BACKGROUND Many people diagnosed with haematological malignancies experience anaemia , and red blood cell ( RBC ) transfusion plays an essential supportive role in their management .
Different strategies have been developed for RBC transfusions .
A restrictive transfusion strategy seeks to maintain a lower haemoglobin level ( usually between 70 g/L to 90 g/L ) with a trigger for transfusion when the haemoglobin drops below 70 g/L ) , whereas a liberal transfusion strategy aims to maintain a higher haemoglobin ( usually between 100 g/L to 120 g/L , with a threshold for transfusion when haemoglobin drops below 100 g/L ) .
In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy .
However , it is not known whether it is safe in people with haematological malignancies .
OBJECTIVES To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy , or both , with or without a haematopoietic stem cell transplant ( HSCT ) . | A 2008 r and omized trial of critically ill , but stable , children reported the safety of transfusing red blood cells at a hemoglobin threshold of 7 g/dL. In 2009 , we adopted the same transfusion criteria in our hematopoietic stem cell transplantation patients . Regression modeling was used to compare data obtained during primary admission for hematopoietic stem cell transplantation in calendar years before and after our practice change . Sixty-six patients admitted in the preintervention year were compared with 75 postintervention . Pre- and post patients were similar in diagnoses and type of transplantations . Postintervention , median hemoglobin pretransfusion significantly decreased from 8.8 g/dL to 6.8 g/dL ( P < .0001 ) . In addition , transfused red blood cell units received by patients dropped from 4 ( interquartile range [ IQR ] 3 , 8) to 3 ( IQR , 2 , 5 ) , ( P = .002 ) , and number of transfusion days per patients decreased from 4 ( IQR , 2,5 ) to 3 ( IQR , 2 , 5 ) , ( P = .01 ) . There were no differences in length of stay , time to engraftment , or 100-day mortality . Median blood product charges per patient significantly decreased ( $ 3,624 [ IQR , $ 2,265 , $ 6,040 ] to $ 2,185 [ IQR , $ 1,812 , $ 3,997 ] , P = .004 ) . Our initial experience suggests that implementation of a conservative transfusion strategy in otherwise stable children undergoing hematopoietic stem cell transplantation appears safe and lowers transfusion exposures BACKGROUND Red blood cell ( RBC ) transfusion thresholds have yet to be examined in large r and omized trials in hematologic malignancies . This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy . STUDY DESIGN AND METHODS A r and omized ( 2:1 ) study was conducted of restrictive ( LOW ) hemoglobin ( Hb ) trigger ( 7 g/dL ) compared to higher ( HIGH ) Hb trigger ( 8 g/dL ) . The primary outcome was feasibility of conducting a larger trial . The four requirements for success required that more than 50 % of the eligible patients could be consented , more than 75 % of the patients r and omized to the LOW arm tolerated the transfusion trigger , fewer than 15 % of patients crossed over from the LOW arm to the HIGH arm , and no indication for the need to pause the study for safety concerns . Secondary outcomes included fatigue , bleeding , and RBCs and platelets transfused . RESULTS Ninety patients were consented and r and omly assigned to LOW to HIGH . The four criteria for the primary objective of feasibility were met . When the number of units transfused was compared , adjusting for baseline Hb , the LOW arm was transfused on average 8.0 ( 95 % confidence interval [ CI ] , 6.9 - 9.1 ) units/patient while the HIGH arm received 11.7 ( 95 % CI , 10.1 - 13.2 ) units ( p = 0.0003 ) . There was no significant difference in bleeding events or neutropenic fevers between study arms . CONCLUSION This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile . This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting Objective : To examine the impact of a restrictive vs. liberal transfusion strategy on arterial lactate and oxygen content differences in children with single-ventricle physiology post cavopulmonary connection . Children with single-ventricle physiology are routinely transfused postoperatively to increase systemic oxygen delivery , and transfusion thresholds in this population have not been studied . Design : Prospect i ve , r and omized , controlled , clinical trial . Setting : Pediatric cardiac intensive care unit in a teaching hospital . Patients : Infants and children ( n = 60 ) with variations of single-ventricle physiology presenting for cavopulmonary connection . Interventions : Subjects were r and omized to a restrictive ( hemoglobin of < 9.0 g/dL ) , or liberal ( hemoglobin of ≥13.0 g/dL ) transfusion strategy for 48 hrs post operation . Primary outcome measures were mean and peak arterial lactate . Secondary end points were arteriovenous ( C(a-v)o2 ) and arteriocerebral oxygen content ( C(a-c)o2 ) differences and clinical outcomes . Measurements and Main Results : A total of 30 children were in each group . There were no significant preoperative differences . Mean hemoglobin in the restrictive and liberal groups were 11 ± 1.3 g/dL and 13.9 ± 0.5 g/dL , respectively ( p < .01 ) . No differences in mean ( 1.4 ± 0.5 mmol/L [ Restrictive ] vs. 1.4 ± 0.4 mmol/L [ Liberal ] ) or peak ( 3.1 ± 1.5 mmol/L [ Restrictive ] vs. 3.2 ± 1.3 mmol/L [ Liberal ] ) lactate between groups were found . Mean number of red blood cell transfusions were 0.43 ± 0.6 and 2.1 ± 1.2 ( p < .01 ) , and donor exposure was 1.2 ± 0.7 and 2.4 ± 1.1 to ( p < .01 ) , for each group , respectively . No differences were found in C(a-v)o2 , C(a-c)o2 , or clinical outcome measures . Conclusion : Children with single-ventricle physiology do not benefit from a liberal transfusion strategy after cavopulmonary connection . A restrictive red blood cell transfusion strategy decreases the number of transfusions , donor exposures , and potential risks in these children . Larger studies with clinical outcome measures are needed to determine the transfusion threshold for children post cardiac repair or palliation for congenital heart disease BACKGROUND Whether a restrictive threshold for hemoglobin level in red-cell transfusions , as compared with a liberal threshold , reduces postoperative morbidity and health care costs after cardiac surgery is uncertain . METHODS We conducted a multicenter , parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom . Patients with a postoperative hemoglobin level of less than 9 g per deciliter were r and omly assigned to a restrictive transfusion threshold ( hemoglobin level < 7.5 g per deciliter ) or a liberal transfusion threshold ( hemoglobin level < 9 g per deciliter ) . The primary outcome was a serious infection ( sepsis or wound infection ) or an ischemic event ( permanent stroke [ confirmation on brain imaging and deficit in motor , sensory , or coordination functions ] , myocardial infa rct ion , infa rct ion of the gut , or acute kidney injury ) within 3 months after r and omization . Health care costs , excluding the index surgery , were estimated from the day of surgery to 3 months after surgery . RESULTS A total of 2007 patients underwent r and omization ; 4 participants withdrew , leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group . Transfusion rates after r and omization were 53.4 % and 92.2 % in the two groups , respectively . The primary outcome occurred in 35.1 % of the patients in the restrictive-threshold group and 33.0 % of the patients in the liberal-threshold group ( odds ratio , 1.11 ; 95 % confidence interval [ CI ] , 0.91 to 1.34 ; P=0.30 ) ; there was no indication of heterogeneity according to subgroup . There were more deaths in the restrictive-threshold group than in the liberal-threshold group ( 4.2 % vs. 2.6 % ; hazard ratio , 1.64 ; 95 % CI , 1.00 to 2.67 ; P=0.045 ) . Serious postoperative complications , excluding primary - outcome events , occurred in 35.7 % of participants in the restrictive-threshold group and 34.2 % of participants in the liberal-threshold group . Total costs did not differ significantly between the groups . CONCLUSIONS A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs . ( Funded by the National Institute for Health Research Health Technology Assessment program ; Current Controlled Trials number , IS RCT N70923932 . ) BACKGROUND The hemoglobin threshold at which postoperative red-cell transfusion is warranted is controversial . We conducted a r and omized trial to determine whether a higher threshold for blood transfusion would improve recovery in patients who had undergone surgery for hip fracture . METHODS We enrolled 2016 patients who were 50 years of age or older , who had either a history of or risk factors for cardiovascular disease , and whose hemoglobin level was below 10 g per deciliter after hip-fracture surgery . We r and omly assigned patients to a liberal transfusion strategy ( a hemoglobin threshold of 10 g per deciliter ) or a restrictive transfusion strategy ( symptoms of anemia or at physician discretion for a hemoglobin level of < 8 g per deciliter ) . The primary outcome was death or an inability to walk across a room without human assistance on 60-day follow-up . RESULTS A median of 2 units of red cells were transfused in the liberal- strategy group and none in the restrictive- strategy group . The rates of the primary outcome were 35.2 % in the liberal- strategy group and 34.7 % in the restrictive- strategy group ( odds ratio in the liberal- strategy group , 1.01 ; 95 % confidence interval [ CI ] , 0.84 to 1.22 ) , for an absolute risk difference of 0.5 percentage points ( 95 % CI , -3.7 to 4.7 ) . The rates of in-hospital acute coronary syndrome or death were 4.3 % and 5.2 % , respectively ( absolute risk difference , -0.9 % ; 99 % CI , -3.3 to 1.6 ) , and rates of death on 60-day follow-up were 7.6 % and 6.6 % , respectively ( absolute risk difference , 1.0 % ; 99 % CI , -1.9 to 4.0 ) . The rates of other complications were similar in the two groups . CONCLUSIONS A liberal transfusion strategy , as compared with a restrictive strategy , did not reduce rates of death or inability to walk independently on 60-day follow-up or reduce in-hospital morbidity in elderly patients at high cardiovascular risk . ( Funded by the National Heart , Lung , and Blood Institute ; FOCUS Clinical Trials.gov number , NCT00071032 . ) IMPORTANCE There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury . OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds ( 7 and 10 g/dL ) on neurological recovery after traumatic brain injury . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial of 200 patients ( erythropoietin , n = 102 ; placebo , n = 98 ) with closed head injury who were unable to follow comm and s and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012 . The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20 % and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications . Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks ( n = 74 ) and then the 24- and 48-hour doses were stopped for the remainder of the patients ( n = 126 ) . There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS Intravenous erythropoietin ( 500 IU/kg per dose ) or saline . Transfusion threshold maintained with packed red blood cells . MAIN OUTCOMES AND MEASURES Glasgow Outcome Scale score dichotomized as favorable ( good recovery and moderate disability ) or unfavorable ( severe disability , vegetative , or dead ) at 6 months postinjury . RESULTS There was no interaction between erythropoietin and hemoglobin transfusion threshold . Compared with placebo ( favorable outcome rate : 34/89 [ 38.2 % ; 95 % CI , 28.1 % to 49.1 % ] ) , both erythropoietin groups were futile ( first dosing regimen : 17/35 [ 48.6 % ; 95 % CI , 31.4 % to 66.0 % ] , P = .13 ; second dosing regimen : 17/57 [ 29.8 % ; 95 % CI , 18.4 % to 43.4 % ] , P < .001 ) . Favorable outcome rates were 37/87 ( 42.5 % ) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 ( 33.0 % ) for 10 g/dL ( 95 % CI for the difference , -0.06 to 0.25 , P = .28 ) . There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL ( 22/101 [ 21.8 % ] vs 8/99 [ 8.1 % ] for the threshold of 7 g/dL , odds ratio , 0.32 [ 95 % CI , 0.12 to 0.79 ] , P = .009 ) . CONCLUSIONS AND RELEVANCE In patients with closed head injury , neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL result ed in improved neurological outcome at 6 months . The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events . These findings do not support either approach in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313716 Background Transfusion with red blood cells ( RBC ) may be needed during hip revision surgery but the appropriate haemoglobin concentration ( Hb ) threshold for transfusion has not been well established . We hypothesized that a higher transfusion threshold would improve ambulation after hip revision surgery . Methods The trial was registered at Clinical trials.gov ( NCT00906295 ) . Sixty-six patients aged 18 years or older undergoing hip revision surgery were r and omized to receive RBC at a Hb threshold of either 7.3 g/dL ( restrictive group ) or 8.9 g/dL ( liberal group ) . Postoperative ambulation was assessed using Timed Up and Go-test ( TUG ) and ability to walk was also assessed daily by a physiotherapist blinded to the allocation . Results Fifty-three patients were able to perform the TUG and included in the analysis . The TUG could be completed in a median of 36 sec vs. 30 sec in the restrictive group and the liberal group , respectively ( P = 0.02 ) . The mean difference in TUG was 14.5 sec ( 95 % CI 2.8 - 26.2 sec ) . No difference was found in the day patients could perform TUG or walk 10 meters . The Hb at the day of testing was 10.2 g/dL in the restrictive group and 9.9 g/dL in the liberal group . Only 26 patients received RBC . Conclusions A Hb transfusion threshold of 8.9 g/dL was associated with a statistically significantly faster TUG after hip revision surgery compared to a threshold of 7.3 g/dL but the clinical importance is question able and the groups did not differ in Hb at the time of testing Background Packed red blood cell ( PRBC ) transfusion is required in hematology patients treated with chemotherapy for acute leukemia , autologous ( auto ) or allogeneic ( allo ) hematopoietic stem cell transplantation ( HSCT ) . In certain situations like septic shock , hip surgery , coronary disease or gastrointestinal hemorrhage , a restrictive transfusion strategy is associated with a reduction of infection and death . A transfusion strategy using a single PRBC unit has been retrospectively investigated and showed a safe reduction of PRBC consumption and costs . We therefore design ed a study to prospect ively demonstrate that the transfusion of a single PRBC unit is safe and not inferior to st and ard care . Methods The 1versus2 trial is a r and omized trial which will determine if a single-unit transfusion policy is not inferior to a double-unit transfusion policy . The primary endpoint is the incidence of severe complication ( grade ≥ 3 ) defined as stroke , transient ischemic attack , acute coronary syndrome , heart failure , elevated troponin level , intensive care unit transfer , death , new pulmonary infiltrates , and transfusion-related infections during hospital stays . The secondary endpoint is the number of PRBC units transfused per patient per hospital stay . Two hundred and thirty patients will be r and omized to receive a single unit or double unit every time the hemoglobin level is less than 8 g/dL. All patients admitted for induction remission chemotherapy , auto-HSCT or allo-HSCT in hematology intensive care units will be eligible for inclusion . Sample size calculation has determined that a patient population of 230 will be required to prove that the 1-unit PRBC strategy is non-inferior to the 2-unit PRBC strategy . Hemoglobin threshold for transfusion is below 8 g/dL. Estimated percentage of complication-free hospital stays is 93 % . In a non-inferiority hypothesis , the number of patients to include is 230 with a power of 90 % and an alpha risk of 5 % .Trial Registration 14–128 ; Clinical trials.gov NCT02461264 ( registered on 3 June 2015 Background Insight regarding transfusion practice s in Hematopoietic Stem cell Transplantation ( HSCT ) are lacking and the impact of red cell transfusion in this high risk group on outcomes following HSCT are not well appreciated . Red blood cell transfusion can be life-saving , however , liberal use of transfusion in critically ill patients failed to demonstrate significant clinical benefit . A large number of other observational studies have also demonstrated an association between red blood cell transfusions and increased morbidity such as infections and multi organ failure as well as increased mortality . The role of red cell transfusion on the clinical outcomes observed in patients undergoing HSCT remains poorly understood and a prospect i ve r and omized study of transfusion is required to gain insight and knowledge on best transfusion practice s in this high risk population . Methods This report describes the design and method ological issues of a r and omized pilot study evaluating red cell transfusion triggers in the setting of Hematopoietic Stem Cell Transplantation . This study has been funded by a peer review grant from the Canadian Blood Services and is registered on Clinical trials.gov NCT01237639 . Results In 3 Canadian centres , 100 patients undergoing Hematopoietic Stem Cell Transplantation will be r and omized to either a restrictive ( target hemoglobin of 70 - 90 g/L ) or liberal ( target hemoglobin of 90 - 110 g/L ) red cell transfusion strategy , based daily hemoglobin values up to 100 days post-transplant . The study will stratify participants by centre and type of transplant . The primary goal is to demonstrate study feasibility and we will collect clinical outcomes on 1 ) Transfusion Requirements , 2 ) Transplant Related Mortality , 3 ) Maximum grade of acute Graft versus Host Disease , 4 ) Veno-occlusive Disease , 5 ) Serious Infections , 6 ) Bearman Toxicity Score , 7 ) Bleeding , 8) Quality of Life , 9 ) Number of Hospitalizations and 10 ) Number of Intensive Care Unit ( ICU ) Admissions . Conclusion Upon completion , this pilot trial will provide preliminary insight into red cell transfusion practice and its influence in hematopoietic stem cell transplant outcomes . The results of this trial will inform the conduct of a larger study BACKGROUND Transfusion thresholds for acute upper gastrointestinal bleeding are controversial . So far , only three small , underpowered studies and one single-centre trial have been done . Findings from the single-centre trial showed reduced mortality with restrictive red blood cell ( RBC ) transfusion . We aim ed to assess whether a multicentre , cluster r and omised trial is a feasible method to substantiate or refute this finding . METHODS In this pragmatic , open-label , cluster r and omised feasibility trial , done in six university hospitals in the UK , we enrolled all patients aged 18 years or older with new presentations of acute upper gastrointestinal bleeding , irrespective of comorbidity , except for exsanguinating haemorrhage . We r and omly assigned hospitals ( 1:1 ) with a computer-generated r and omisation sequence ( r and om permuted block size of 6 , without stratification or matching ) to either a restrictive ( transfusion when haemoglobin concentration fell below 80 g/L ) or liberal ( transfusion when haemoglobin concentration fell below 100 g/L ) RBC transfusion policy . Neither patients nor investigators were masked to treatment allocation . Feasibility outcomes were recruitment rate , protocol adherence , haemoglobin concentration , RBC exposure , selection bias , and information to guide design and economic evaluation of the phase 3 trial . Main exploratory clinical outcomes were further bleeding and mortality at day 28 . We did analyses on all enrolled patients for whom an outcome was available . This trial is registered , IS RCT N85757829 and NCT02105532 . FINDINGS Between Sept 3 , 2012 , and March 1 , 2013 , we enrolled 936 patients across six hospitals ( 403 patients in three hospitals with a restrictive policy and 533 patients in three hospitals with a liberal policy ) . Recruitment rate was significantly higher for the liberal than for the restrictive policy ( 62 % vs 55 % ; p=0·04 ) . Despite some baseline imbalances , Rockall and Blatchford risk scores were identical between policies . Protocol adherence was 96 % ( SD 10 ) in the restrictive policy vs 83 % ( 25 ) in the liberal policy ( difference 14 % ; 95 % CI 7 - 21 ; p=0·005 ) . Mean last recorded haemoglobin concentration was 116 ( SD 24 ) g/L for patients on the restrictive policy and 118 ( 20 ) g/L for those on the liberal policy ( difference -2·0 [ 95 % CI -12·0 to 7·0 ] ; p=0·50 ) . Fewer patients received RBCs on the restrictive policy than on the liberal policy ( restrictive policy 133 [ 33 % ] vs liberal policy 247 [ 46 % ] ; difference -12 % [ 95 % CI -35 to 11 ] ; p=0·23 ) , with fewer RBC units transfused ( mean 1·2 [ SD 2·1 ] vs 1·9 [ 2·8 ] ; difference -0·7 [ -1·6 to 0·3 ] ; p=0·12 ) , although these differences were not significant . We noted no significant difference in clinical outcomes . INTERPRETATION A cluster r and omised design led to rapid recruitment , high protocol adherence , separation in degree of anaemia between groups , and non-significant reduction in RBC transfusion in the restrictive policy . A large cluster r and omised trial to assess the effectiveness of transfusion strategies for acute upper gastrointestinal bleeding is both feasible and essential before clinical practice guidelines change to recommend restrictive transfusion for all patients with acute upper gastrointestinal bleeding . FUNDING NHS Blood and Transplant Research and Development BACKGROUND The optimal hemoglobin threshold for erythrocyte transfusions in critically ill children is unknown . We hypothesized that a restrictive transfusion strategy of using packed red cells that were leukocyte-reduced before storage would be as safe as a liberal transfusion strategy , as judged by the outcome of multiple-organ dysfunction . METHODS In this noninferiority trial , we enrolled 637 stable , critically ill children who had hemoglobin concentrations below 9.5 g per deciliter within 7 days after admission to an intensive care unit . We r and omly assigned 320 patients to a hemoglobin threshold of 7 g per deciliter for red-cell transfusion ( restrictive- strategy group ) and 317 patients to a threshold of 9.5 g per deciliter ( liberal- strategy group ) . RESULTS Hemoglobin concentrations were maintained at a mean ( + /-SD ) level that was 2.1+/-0.2 g per deciliter lower in the restrictive- strategy group than in the liberal- strategy group ( lowest average levels , 8.7+/-0.4 and 10.8+/-0.5 g per deciliter , respectively ; P<0.001 ) . Patients in the restrictive- strategy group received 44 % fewer transfusions ; 174 patients ( 54 % ) in that group did not receive any transfusions , as compared with 7 patients ( 2 % ) in the liberal- strategy group ( P<0.001 ) . New or progressive multiple-organ dysfunction syndrome ( the primary outcome ) developed in 38 patients in the restrictive- strategy group , as compared with 39 in the liberal- strategy group ( 12 % in both groups ) ( absolute risk reduction with the restrictive strategy , 0.4 % ; 95 % confidence interval , -4.6 to 5.4 ) . There were 14 deaths in each group within 28 days after r and omization . No significant differences were found in other outcomes , including adverse events . CONCLUSIONS In stable , critically ill children a hemoglobin threshold of 7 g per deciliter for red-cell transfusion can decrease transfusion requirements without increasing adverse outcomes . ( Controlled-trials.com number , IS RCT N37246456 [ controlled-trials.com ] . ) BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients , we compared the rates of death from all causes at 30 days and the severity of organ dysfunction . METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and r and omly assigned 418 patients to a restrictive strategy of transfusion , in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter , and 420 patients to a liberal strategy , in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter . RESULTS Overall , 30-day mortality was similar in the two groups ( 18.7 percent vs. 23.3 percent , P= 0.11 ) . However , the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or = 20 ( 8.7 percent in the restrictive- strategy group and 16.1 percent in the liberal- strategy group ; P=0.03 ) -- and among patients who were less than 55 years of age ( 5.7 percent and 13.0 percent , respectively ; P=0.02 ) , but not among patients with clinical ly significant cardiac disease ( 20.5 percent and 22.9 percent , respectively ; P=0.69 ) . The mortality rate during hospitalization was significantly lower in the restrictive- strategy group ( 22.3 percent vs. 28.1 percent , P=0.05 ) . CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients , with the possible exception of patients with acute myocardial infa rct ion and unstable angina BACKGROUND AND OBJECTIVES Blood recipient and blood product utilisation data are needed for assessment of current transfusion practice in hospitals . Such data can help monitoring blood use , improving blood transfusion practice and estimating future blood use . MATERIAL S AND METHODS In this cross sectional study , the rate of blood consumption has been evaluated in three r and omly selected hospitals of Yazd , Iran in 2011 - 2012 . Data of blood recipients including patient identification number , age , sex , principal diagnoses , date of transfusion , type and number of transfused blood components and indication for transfusion were prospect ively collected . RESULTS The data set included information about 814 patients ( 53 % males ) who received 1110 RBCs , 410 plasma and 1484 platelet ( PLT ) units . Transfusion rate per 1000 population per year was 24 , 10 and 15 for red blood cells ( RBCs ) , plasma and PLT units , respectively . Age group 17 - 64 years had the highest consumption of blood components ( 55 % ) . Most of the RBCs and PLT units were transfused to patients with neoplasm ( 42 and 82 % , respectively ) . Cardiovascular surgery was the diagnosis category with most plasma usage ( 32 % ) . The category with highest haemoglobin level before transfusion was surgery ; Orthopaedic and ENT surgeries were at the top of ranking ( 11·96 ± 1·85 g dL(-1 ) ) . PLT count before transfusion was 11·160 ± 5·282 × 10(9 ) L(-1 ) in neoplasm category and 12·3637 ± 6·2267 × 10(10 ) L(-1 ) in neonatal disease . CONCLUSION Study results showed the first epidemiological data of blood recipients on a regional basis in Iran . It is suggested to study blood utilisation at the national level to assist in improving transfusion practice in hospitals Previous studies have shown that maintaining high hemoglobin levels in patients after chemotherapy reduced the length of neutropenia . Thus , we undertook a r and omized , controlled , clinical trial in children undergoing allogeneic bone marrow transplantation after receiving a myeloablative conditioning regimen to compare 2 hemoglobin thresholds as triggers for red blood cell transfusion : 120 g/L in the experimental arm and 70 g/L in the control arm . The Data and Safety Monitoring Board closed the study after enrollment of the sixth patient because 3 patients in the experimental arm contracted veno-occlusive disease , but none in the control arm did ( P = .05 ) . Ascites was present in all 3 patients , pleura effusion in 2 , and portal vein thrombosis in 2 . One patient experienced hepatic failure and required treatment with the molecular adsorbent recycling system . Another patient required hemodialysis for renal failure . No major imbalance between groups was seen with regard to risk factors for veno-occlusive disease . Therefore , maintaining the hemoglobin at higher levels should be avoided after hematopoietic stem cell transplantation Red-cell transfusions are required for symptomatic treatment of severe anaemia caused by intensive chemotherapy . Concerns about the transfusion-related complications , such as infections ( e.g. the very low risk of human immunodeficiency virus (HIV)/hepatitis C virus ( HCV ) transmission and the risk of postoperative infections ) , haemolytic transfusion reaction , immunological effects and the costs , prompt a reevaluation of the transfusion practice . Retrospective analysis of prospect ively collected data on 84 patients with acute myeloid leukaemia ( AML ) , who were treated with combination chemotherapy between June 1 , 1997 and December 7 , 2001 , was performed . The use of red-cell transfusions with a restrictive transfusion policy ( haemoglobin = 7.2 - 8.8 g dL(-1 ) , dependent on age and symptoms , n = 38 ) was compared with a more liberal transfusion trigger ( haemoglobin = 9.6 g dL(-1 ) , n = 46 ) . The number of units transfused was recorded . Signs and symptoms of anaemia , chemotherapy-related effects and complications were investigated for both transfusion policies . The more restrictive transfusion policy led to a significant decrease of 11 % of red blood cell ( RBC ) transfusions in patients with AML . No significant differences were found in the incidence of infections , number of platelet units transfused , bleeding complications , cardiac symptoms or response to chemotherapy . The more restrictive transfusion policy was feasible in this clinical setting , and it might be concluded that a restrictive transfusion policy is safe in supporting clinical patients treated with intensive chemotherapy for AML BACKGROUND The hemostatic effect of platelets has been well established , but the possible role of red cells in hemostasis has not yet been well studied . An evaluation of the hemostatic effect of packed red cell transfusion in patients with chronic anemia was the purpose of this study . STUDY DESIGN AND METHODS In a prospect i ve study , bleeding time ( BT ) , activated partial thromboplastin time ( APTT ) , and prothrombin time ( PT ) were measured before and after the transfusion of allogeneic packed red cells in 42 patients with chronic anemia . The results were compared and analyzed . RESULTS APTT and BT decreased significantly after transfusion , by a mean of 1.3 seconds ( p = 0.01 ) and 2.6 minutes ( p < 0.01 ) , respectively . PT did not change significantly after transfusion ( p = 0.65 ) . Factors studied ( patient 's age , sex , and renal function measurements ; pretransfusion and posttransfusion hemoglobin levels , platelet counts , and PTs ; change in platelet count [ delta platelet count ] and PT [ delta PT ] after transfusion ) did not independently affect the change in BT ( delta BT ) or in APTT ( delta APTT ) . The delta BT was not affected by the pretransfusion or posttransfusion levels of APTT or by the delta APTT . The delta APTT was not affected by the pretransfusion or posttransfusion levels of BT or by the delta BT . Diagnosis of malignant or benign diseases was found to affect delta APTT , but not delta BT . Patients with pretransfusion hemoglobin < or = 60 g per L had a 4.07 times greater chance of posttranfusion increase in BT than the patients with hemoglobin > 60 g per L ( p = 0.04 ) . CONCLUSION Red cell transfusion might decrease the APTT and BT in some anemic patients , though the actual cause of the decrease was not determined in the present study BACKGROUND Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients . Patients with acute coronary syndrome may benefit from higher hemoglobin levels . METHODS We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin < 10 g/dL. Patients in the liberal transfusion strategy received one or more units of blood to raise the hemoglobin level ≥10 g/dL. Patients in the restrictive transfusion strategy were permitted to receive blood for symptoms from anemia or for a hemoglobin < 8 g/dL. The predefined primary outcome was the composite of death , myocardial infa rct ion , or unscheduled revascularization 30 days post r and omization . RESULTS Baseline characteristics were similar between groups except age ( liberal , 67.3 ; restrictive , 74.3 ) . The mean number of units transfused was 1.6 in the liberal group and 0.6 in the restrictive group . The primary outcome occurred in 6 patients ( 10.9 % ) in the liberal group and 14 ( 25.5 % ) in the restrictive group ( risk difference = 15.0 % ; 95 % confidence interval of difference 0.7 % to 29.3 % ; P = .054 and adjusted for age P = .076 ) . Death at 30 days was less frequent in liberal group ( n = 1 , 1.8 % ) compared to restrictive group ( n = 7 , 13.0 % ; P = .032 ) . CONCLUSIONS The liberal transfusion strategy was associated with a trend for fewer major cardiac events and deaths than a more restrictive strategy . These results support the feasibility of and the need for a definitive trial Few studies have examined the association between perioperative blood transfusion and postoperative delirium ( POD ) in aged patients undergoing total hip replacement surgery . In this prospect i ve study , 186 patients older than 65 years undergoing elective unilateral total hip replacement surgery were enrolled . Of those , 94 patients were r and omly assigned to the restrictive strategy transfusion strategy group , in which red blood cells were transfused in order to maintain 10.0 g/dL > hemoglobin≧8.0 g/dL. Ninety-two patients were r and omly assigned to the liberal transfusion strategy group , in which red blood cells were transfused in order to maintain hemoglobin≧10.0 g/dL. POD was diagnosed by confusion assessment method . The baseline characteristics of patients , the length of hospital stay , the incidence of POD , myocardial infa rct ion , stroke , wound infection , pulmonary embolism , and the transfusion volume were recorded . No difference was observed in the baseline characteristics , the length of hospital stay , and the incidence of POD , myocardial infa rct ion , stroke , wound infection , and pulmonary embolism between the two groups ( P>0.05 ) . The proportion of patients transfused with red blood cell and frozen plasma was decreased in the restrictive transfusion group compared with the liberal transfusion group ( P<0.05 ) . In conclusion , restrictive transfusion does not influence the incidence of POD but reduces blood transfusion . Thus , restrictive transfusion may serve as an effective and safe strategy for aged patients following total hip replacement The ‘ optimal ’ hematocrit to which patients should be resuscitated after shock and trauma is controversial . To test the hypothesis that sufficient oxygen delivery can be provided at a lower hematocrit without impairing oxygen consumption or hemodynamic function , 25 patients were prospect ively Objective To investigate the safety and effects of a restrictive red blood cell ( RBC ) transfusion strategy in pediatric cardiac surgery patients . Design R and omized controlled trial . Setting Pediatric ICU in an academic tertiary care center , Leiden University Medical Center , Leiden , The Netherl and s. Patients One hundred seven patients with non-cyanotic congenital heart defects between 6 weeks and 6 years of age . One hundred three patients underwent corrective surgery on cardiopulmonary bypass . Interventions Prior to surgery patients were r and omly assigned to one of two groups with specific RBC transfusion thresholds : Hb 10.8 g/dl ( 6.8 mmol/l ) and Hb 8.0 g/dl ( 5.0 mmol/l ) . Measurements Length of stay in hospital ( primary outcome ) , length of stay in PICU , duration of ventilation ( secondary outcome ) , incidence of adverse events and complications related to r and omization ( intention to treat analysis ) . Results In the restrictive transfusion group , mean volume of transfused RBC was 186 ( ±70 ) ml per patient and in the liberal transfusion group 258 ( ±87 ) ml per patient , ( 95 % CI 40.6–104.6 ) , p < 0.001 . Length of hospital stay was shorter in patients with a restrictive RBC transfusion strategy : median 8 ( IQR 7–11 ) vs. 9 ( IQR 7–14 ) days , p = 0.047 . All other outcome measures and incidence of adverse effects were equal in both RBC transfusion groups . Cost of blood products for the liberal transfusion group was 438.35 ( ±203.39 ) vs. 316.27 ( ±189.96 ) euros ( 95 % CI 46.61–197.51 ) per patient in the restrictive transfusion group , p = 0.002 . Conclusions For patients with a non-cyanotic congenital heart defect undergoing elective cardiac surgery , a restrictive RBC transfusion policy ( threshold of Hb 8.0 g/dl ) during the entire perioperative period is safe , leads to a shorter hospital stay and is less expensive BACKGROUND Anemia may be an important factor contributing to an increased risk of bleeding , particularly in patients with thrombocytopenia . STUDY DESIGN AND METHODS A multicenter , single-blinded pilot r and omized controlled trial ( RCT ) was performed to evaluate the feasibility of conducting a larger RCT to determine the effect of the hemoglobin ( Hb ) concentration on bleeding risk . Patients with acute leukemia receiving induction chemotherapy or those undergoing stem cell transplantation were assigned to one of two treatment groups : st and ard transfusion strategy ( transfusion of 2 units of red blood cells [ RBCs ] when their Hb level was less than 80 g/L ) or an augmented transfusion strategy ( transfusion of 2 units of RBCs when their Hb level was less than 120 g/L ) . RESULTS Sixty patients were enrolled : 29 in the control group and 31 in the experimental group . The proportions of patients experiencing clinical ly significant bleeding and the time to first bleed were not significantly different between the control and experimental groups . The experimental group received more RBC transfusions ( transfusions/patient-day ) than the control group ( 0.233 vs. 0.151 ; relative risk , 1.56 ; 95 % confidence interval , 1.16 - 2.10 ; p = 0.003 ) . The proportion of patient-days with platelet ( PLT ) transfusions was not different between the experimental and control groups . The mean number of donor exposures ( PLT and RBC transfusions ) was not different between experimental and control groups . Bleeding symptoms were systematic ally documented . CONCLUSION This pilot study thus indicated that it would be feasible to enroll the required number of patients to enable the performance of a large RCT to investigate the effect of Hb on bleeding risk in thrombocytopenic patients |
2,445 | 29,393,280 | Conclusions : In conclusion , this meta- analysis shows that cetuximab- and panitumumab-based chemotherapy have different toxicity profiles in terms of the rate of severe adverse events | Background : Over the last few years only one large r and omized phase III study has tried to prospect ively assess the safety of cetuximab and panitumumab in a head-to-head comparison .
Despite the similar overall toxicity profile , cetuximab and panitumumab retain peculiar safety characteristics that deserve to be deeply investigated . | BACKGROUND Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer . The mechanism of this side-effect is unknown , and if all or a subset of patients are affected is also unclear . We aim ed to assess the incidence , characteristics , and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies , and to study the pathophysiology of this phenomenon . METHODS We measured prospect ively magnesium concentrations in a cohort of 98 patients with colorectal cancer treated with EGFR-targeting antibodies with or without combined chemotherapy . The primary outcome measure was the slope of the serum magnesium concentrations over time . In 35 patients , 24-h urinary magnesium excretion was measured . In a subset of patients ( n=5 ) , an intravenous magnesium load test was done . 16 patients who had chemotherapy alone acted as controls . A clinical protocol was written before initiation of the study , but because this was a non-interventional study , the protocol was not formally registered . FINDINGS 95 ( 97 % ) patients had decreasing serum magnesium concentrations during EGFR-targeting treatment compared with baseline measurements . The mean serum magnesium slope during EGFR-targeting treatment ( with or without combined chemotherapy ) was significantly lower compared with chemotherapy alone ( -0.00157 mmol/L/day , SD 0.00162 [ 95 % CI -0.00191 to -0.00123 ] vs 0.00014 mmol/L/day , SD -00076 [ -0.00026 to 0.00055 ] ; ( t test , p < 0.0001 ) . 24-h urine analysis and intravenous magnesium load tests showed a defect in renal magnesium reabsorption . INTERPRETATION EGFR-inhibiting antibodies compromised the renal magnesium retention capacity , leading to hypomagnesaemia in most patients . Future studies should address the effects of exposure and target affinity . Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis 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 BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) This r and omized phase II trial compared panitumumab plus fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) with bevacizumab plus FOLFIRI as second‐line chemotherapy for wild‐type ( WT ) KRAS exon 2 metastatic colorectal cancer ( mCRC ) and to explore the values of oncogenes in circulating tumor DNA ( ctDNA ) and serum proteins as predictive biomarkers . Patients with WT KRAS exon 2 mCRC refractory to first‐line chemotherapy containing oxaliplatin and bevacizumab were r and omly assigned to panitumumab plus FOLFIRI or bevacizumab plus FOLFIRI . Of 121 r and omly assigned patients , 117 were eligible . Median overall survival ( OS ) for panitumumab plus FOLFIRI and bevacizumab plus FOLFIRI were 16.2 and 13.4 months [ hazard ratio ( HR ) , 1.16 ; 95 % CI , 0.76–1.77 ] , respectively . Progression‐free survival ( PFS ) was also similar ( HR , 1.14 ; 95 % CI , 0.78–1.66 ) . KRAS , NRAS , and BRAF status using ctDNA was successfully examined in 109 patients , and mutations were identified in 19 patients ( 17.4 % ) . Panitumumab plus FOLFIRI showed favorable survival compared with bevacizumab plus FOLFIRI in WT patients and unfavorable survival in those with mutations ( P for interaction = 0.026 in OS and 0.054 in PFS ) . OS with bevacizumab plus FOLFIRI was better than panitumumab plus FOLFIRI in patients with high serum vascular endothelial growth factor‐A ( VEGF‐A ) levels and worse in those with low levels ( P for interaction = 0.016 ) . Second‐line FOLFIRI plus panitumumab and FOLFIRI plus bevacizumab showed a similar efficacy in patients with WT KRAS exon 2 mCRC . RAS and BRAF mutation in ctDNA could be a negative predictive marker for panitumumab BACKGROUND The OPUS study demonstrated that addition of cetuximab to 5-fluorouracil , folinic acid and oxaliplatin ( FOLFOX4 ) significantly improved objective response and progression-free survival ( PFS ) in the first-line treatment of patients with KRAS exon 2 wild-type metastatic colorectal cancer ( mCRC ) . In patients with KRAS exon 2 mutations , a detrimental effect was seen upon addition of cetuximab to FOLFOX4 . The current study reports outcomes in subgroups defined by extended RAS testing . PATIENTS AND METHODS Sample s from OPUS study KRAS exon 2 wild-type tumours were reanalysed for other RAS mutations in four additional KRAS codons ( exons 3 - 4 ) and six NRAS codons ( exons 2 - 4 ) using BEAMing . A cutoff of ⩾5 % mutant/wild-type sequences was selected to define RAS status ; we also report an analysis using a cutoff based on the technical lower limit for mutation identification ( 0.1 % ) . RESULTS Other RAS mutations were detected in 31/118 ( 26 % ) evaluable patients . In the extended analysis of RAS wild-type tumours ( n=87 ) , objective response was significantly improved by addition of cetuximab to FOLFOX4 ( 58 % versus 29 % ; odds ratio 3.33 [ 95 % confidence interval 1.36 - 8.17 ] ; P=0.0084 ) ; although limited by population size , there also appeared to be trends favouring the cetuximab arm in terms of PFS and overall survival in the RAS wild-type group compared with the RAS evaluable group . There was no evidence that patients with other RAS mutations benefited from cetuximab , but small numbers precluded precise estimations of treatment effects . In the combined population of patients with any RAS mutation ( KRAS exon 2 or other RAS ) , a clear detrimental effect was associated with addition of cetuximab to FOLFOX4 . CONCLUSION Patients with RAS-mutant mCRC , as defined by mutations in KRAS and NRAS exons 2 - 4 , derive no benefit and may be harmed by the addition of cetuximab to FOLFOX4 . Restricting cetuximab administration to patients with RAS wild-type tumours will further tailor therapy to maximise benefit Summary Background Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer , but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain . Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer . Methods In this open-label , r and omised trial , we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK . From December , 2006 until June , 2008 , molecularly unselected patients were recruited to a three-arm design including irinotecan ( control ) , irinotecan plus ciclosporin , and irinotecan plus panitumumab ( IrPan ) groups . From June 10 , 2008 , in response to new data , the trial was amended to a prospect ively stratified design , restricting panitumumab r and omisation to patients with KRAS wild-type tumours ; the results of the comparison between the irinotcan and IrPan groups are reported here . We used a computer-generated r and omisation sequence ( stratified by previous EGFR targeted therapy and then minimised by centre , WHO performance status , previous oxaliplatin , previous bevacizumab , previous dose modifications , and best previous response ) to r and omly allocate patients to either irinotecan or IrPan . Patients in both groups received 350 mg/m2 intravenous irinotecan every 3 weeks ( 300 mg/m2 if aged ≥70 years or a performance status of 2 ) ; patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks . The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy , analysed by intention to treat . Tumour DNA was pyrosequenced for KRASc.146 , BRAF , NRAS , and PIK3CA mutations , and predefined molecular subgroups were analysed for interaction with the effect of panitumumab . This study is registered , number IS RCT N93248876 . Results Between Dec 4 , 2006 , and Aug 31 , 2010 , 1198 patients were enrolled , of whom 460 were included in the primary population of patients with KRASc.12–13,61 wild-type tumours and no previous EGFR targeted therapy . 230 patients were r and omly allocated to irinotecan and 230 to IrPan . There was no difference in overall survival between groups ( HR 1·01 , 95 % CI 0·83–1·23 ; p=0·91 ) , but individuals in the IrPan group had longer progression-free survival ( 0·78 , 0·64–0·95 ; p=0·015 ) and a greater number of responses ( 79 [ 34 % ] patients vs 27 [ 12 % ] ; p<0·0001 ) than did individuals in the irinotecan group . Grade 3 or worse diarrhoea ( 64 [ 29 % ] of 219 patients vs 39 [ 18 % ] of 218 patients ) , skin toxicity ( 41 [ 19 % ] vs none ) , lethargy ( 45 [21]% vs 24 [ 11 % ] ) , infection ( 42 [ 19 % ] vs 22 [ 10 % ] ) and haematological toxicity ( 48 [ 22 % ] vs 27 [ 12 % ] ) were reported more commonly in the IrPan group than in the irinotecan group . We recorded five treatment-related deaths , two in the IrPan group and three in the irinotecan group . Interpretation Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours . Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents . Funding Cancer Research UK , Amgen PURPOSE The phase III CRYSTAL study demonstrated that addition of cetuximab to fluorouracil , leucovorin , and irinotecan ( FOLFIRI ) significantly improved overall survival , progression-free survival , and objective response in the first-line treatment of patients with KRAS codon 12/13 ( exon 2 ) wild-type metastatic colorectal cancer ( mCRC ) . Outcome was reassessed in subgroups defined by extended RAS mutation testing . PATIENTS AND METHODS Existing DNA sample s from KRAS exon 2 wild-type tumors from CRYSTAL study patients were reanalyzed for other RAS mutations in four additional KRAS codons ( exons 3 and 4 ) and six NRAS codons ( exons 2 , 3 , and 4 ) using beads , emulsion , amplification , and magnetics technology . No tissue microdissection was performed . A ≥ 5 % mutant allele cutoff was used to call mutations . RESULTS Mutation status was evaluable in 430 ( 64.6 % ) of 666 patients with KRAS exon 2 wild-type tumors . Other RAS mutations were detected in 63 ( 14.7 % ) of 430 patients . In those with RAS wild-type tumors , a significant benefit across all efficacy end points was associated with the addition of cetuximab to FOLFIRI . In patients with other RAS tumor mutations , no difference in efficacy outcomes between treatment groups was seen . The safety profile in RAS subgroups was similar and in line with expectations . CONCLUSION In the first-line treatment of mCRC , patients with RAS wild-type tumors derived a significant benefit from the addition of cetuximab to FOLFIRI ; patients with RAS tumor mutations did not . Molecular testing of tumors for all activating RAS mutations is essential before considering anti-epidermal growth factor receptor therapy , thereby allowing the further tailoring of cetuximab administration to maximize patient benefit Irinotecan is cytotoxic in patients with advanced colorectal cancer ( CRC ) . SN‐38 ( 10‐hydroxy‐7‐ethyl‐camptothecin ) is the active metabolite of irinotecan . Attachment of polyethylene glycol ( PEG ) polymer chains ( pegylation ) to SN‐38 ( EZN‐2208 ) increases the solubility , exposure , and half‐life of SN‐38 . Pre clinical studies demonstrated superior in vitro efficacy of EZN‐2208 when it was tested in irinotecan‐refractory human CRC cell lines |
2,446 | 32,180,431 | Conclusion : This study suggests that physical training can preserve and even significantly increase the bone mass of the hip and femoral neck during weight reduction .
Of note , various exercise modalities affected BMD at different sites .
Similar results were not found for lumbar spine and total body BMD | Background : A major therapeutic goal in weight management should be total body fat reduction whereas as preserving lean body mass and bone mass density .
It is uncertain if an exercise program reduces the adverse effects of calorie restriction-induced weight loss in adults .
Objective : The aim of the present study was to evaluate the differences in bone mass between adults who enrolled in a calorie restriction or an exercise-calorie restriction induced weight loss program . | BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults ; however , the appropriate treatment for obese older adults is controversial . METHODS In this 1-year , r and omized , controlled trial , we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese . Participants were r and omly assigned to a control group , a weight-management ( diet ) group , an exercise group , or a weight-management-plus-exercise ( diet-exercise ) group . The primary outcome was the change in score on the modified Physical Performance Test . Secondary outcomes included other measures of frailty , body composition , bone mineral density , specific physical functions , and quality of life . RESULTS A total of 93 participants ( 87 % ) completed the study . In the intention-to-treat analysis , the score on the Physical Performance Test , in which higher scores indicate better physical status , increased more in the diet-exercise group than in the diet group or the exercise group ( increases from baseline of 21 % vs. 12 % and 15 % , respectively ) ; the scores in all three of those groups increased more than the scores in the control group ( in which the score increased by 1 % ) ( P<0.001 for the between-group differences ) . Moreover , the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group ( increases of 17 % vs. 10 % and 8 % , respectively ; P<0.001 ) ; the score on the Functional Status Question naire , in which higher scores indicate better physical function , increased more in the diet-exercise group than in the diet group ( increase of 10 % vs. 4 % , P<0.001 ) . Body weight decreased by 10 % in the diet group and by 9 % in the diet-exercise group , but did not decrease in the exercise group or the control group ( P<0.001 ) . Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group ( reductions of 3 % and 1 % , respectively , in the diet-exercise group vs. reductions of 5 % and 3 % , respectively , in the diet group ; P<0.05 for both comparisons ) . Strength , balance , and gait improved consistently in the diet-exercise group ( P<0.05 for all comparisons ) . Adverse events included a small number of exercise-associated musculoskeletal injuries . CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00146107 . ) Bone loss accompanies a diet-induced weight loss and could be prevented with a combination of exercises . This study was conducted to examine the effects of additional resistance training during diet-induced weight loss on whole-body and selected regional bone mineral density ( BMD ) . The participants of a 14-week weight-loss study were 42 overweight premenopausal Japanese women who were r and omly placed in either a diet-only group ( D ; n = 21 ) or a diet plus resistance training group ( DR ; n = 21 ) . Whole-body BMD and body composition , lumbar spine BMD , and 1/3 radial BMD were measured by dual-energy X-ray absorptiometry before and after the intervention . Bone formation and resorption markers were also measured . Thirty-five participants ( 83 % ) completed the study . Individuals in groups D ( n = 17 ) and DR ( n = 18 ) lost 6.2 ± 3.5 kg and 8.6 ± 3.6 kg body weight , respectively . Reductions in percentage fat mass and fat mass in group DR were significantly greater than in group D ; lean mass decreased significantly in both groups . The effect of time on whole-body BMD was significant ( −0.3 % ) ; however , whole-body bone mineral content , lumbar spine BMD , and 1/3 radial BMD remained unchanged . There were no significant timeby-group interactions in the whole-body and regional BMD and bone markers . These results suggest that additional resistance training during weight loss has no effect on BMD in overweight premenopausal Japanese women . Further long-term studies with large numbers of subjects are needed Purpose This study aim ed to evaluate the hypothesis that exercise attenuates the reductions in lean mass , muscle strength , bone mineral density , and V˙O2max that accompany modest weight loss induced by calorie restriction ( CR ) . Methods Overweight , sedentary women and men ( n = 52 , 45–65 yr ) were r and omized to 6%–8 % weight loss by using CR , endurance exercise training ( EX ) , or both ( CREX ) . The CR and the CREX groups underwent counseling to reduce energy intake by 20 % and 10 % , respectively . The EX and the CREX groups exercised 7.4 ± 0.5 and 4.4 ± 0.5 h·wk−1 , respectively . Before and after 16.8 ± 1.1 wk of weight loss , lean mass and bone mineral density were measured with dual-energy x-ray absorptiometry , strength was measured with dynamometry , and aerobic capacity ( V˙O2max ) was measured with indirect calorimetry during maximal-intensity treadmill exercise . Results Weight loss was ~7 % in all groups . Decreases in whole-body ( ~2 % , P = 0.003 ) and lower extremity ( ~4 % , P < 0.0001 ) lean mass occurred in the CR group ( both P < 0.05 ) . Despite similar weight loss , these reductions were attenuated in the CREX group ( ~1 % , P = 0.44 and ~2 % , P = 0.05 , respectively ) and absent in the EX group . Absolute aerobic capacity decreased ~6 % in the CR group ( P = 0.04 ) , was unchanged in the CREX group ( P = 0.28 ) , and increased ~15 % in the EX group ( P < 0.0001 ) . No changes in muscle strength or bone were observed . Conclusions Modest weight loss ( ~7 % ) induced by 20 % CR in overweight women and men decreases lean mass and reduces absolute V˙O2max . Exercise protects against these effects . Although the CR-induced changes might be considered physiologically appropriate for a reduced body weight , exercise preserves and /or improves these parameters during weight loss , which likely improves physical function . These findings support the notion of using exercise as an important component of weight loss programs Background To examine the effect of exercise modality during weight loss on hip and spine bone mineral density ( BMD ) in overweight and obese , older adults . Methods This analysis compared data from two 5-month , r and omized controlled trials of caloric restriction ( CR ; inducing 5 - 10 % weight loss ) with either resistance training ( RT ) or aerobic training ( AT ) in overweight and obese , older adults . Participants in the RT + CR study underwent 3 days/week of 8 upper/lower body exercises ( 3 sets , 10 repetitions at 70 % 1 RM ) and participants in the AT+CR study underwent 4 days/week of treadmill walking ( 30 min at 65 - 70 % heart rate reserve ) . BMD at the total hip , femoral neck , and lumbar spine was assessed via dual-energy X-ray absorptiometry at baseline and 5 months . Results A total of 123 adults ( 69.4 ± 3.5 years , 67 % female , 81 % Caucasian ) participated in the RT+CR ( n = 60 ) and AT+CR ( n = 63 ) interventions . Average weight loss was 5.7 % ( 95 % CI : 4.6 - 6.7 % ) and 8.2 % ( 95 % CI : 7.2 - 9.3 % ) in RT+CR and AT+CR groups , respectively . After adjustment for age , gender , race , baseline BMI and BMD , and weight change , differential treatment effects were observed for total hip and femoral neck ( both p < .05 ) , but not lumbar spine . Total hip ( 1.83 [ -3.90 , 7.55 ] mg/cm2 ) and femoral neck ( 9.14 [ -0.70 , 18.98 ] mg/cm2 ) BMD was unchanged in RT+CR participants , and modestly decreased in AT+CR participants ( total hip : -7.01 [ -12.73 , -1.29 ] mg/cm2 ; femoral neck : -5.36 [ -14.92 , 4.20 ] mg/cm2 ) . Conclusions Results suggest performing resistance , rather than aerobic , training during CR may attenuate loss of hip and femoral neck BMD in overweight and obese older adults . Findings warrant replication from a long-term , adequately powered , RCT BACKGROUND Calorie restriction ( CR ) is promoted to increase longevity , yet this regimen could lead to bone loss and fracture and therefore affect quality of life . METHODS Forty-six individuals were r and omized to 4 groups for 6 months : ( 1 ) healthy diet ( control group ) ; ( 2 ) 25 % CR from baseline energy requirements ( CR group ) ; ( 3 ) 25 % energy deficit by a combination of CR and increased aerobic exercise ( CR + EX group ) ; and ( 4 ) low-calorie diet ( 890 kcal/d ; goal , 15 % weight loss ) followed by weight maintenance ( LCD group ) . Bone mineral density ( total body and hip by dual-energy x-ray absorptiometry ) and serum bone markers ( bone-specific alkaline phosphatase , osteocalcin , cross-linked C-telopeptide of type I collagen , and cross-linked N-telopeptide of type I collagen ) were measured at baseline and after 6 months . RESULTS Mean + /- SE body weight was reduced by -1.0 % + /- 1.1 % ( control ) , -10.4 % + /- 0.9 % ( CR ) , -10.0 % + /- 0.8 % ( CR + EX ) , and -13.9 % + /- 0.7 % ( LCD ) . Compared with the control group , none of the groups showed any change in bone mineral density for total body or hip . Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups , with the largest change observed in the LCD group ( CR , 23 % + /- 10 % ; CR + EX , 22 % + /- 9 % ; and LCD , 74 % + /- 16 % vs control , 4 % + /- 10 % ) . Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group . With regard to bone formation , bone alkaline phosphatase levels were decreased in the CR group ( -23 % + /- 10 % ) but were unchanged in the CR + EX , LCD , and control groups . CONCLUSIONS Moderate CR , with or without exercise , that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults . Longer studies with assessment s of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00099151 This study examines the effects of weight loss by caloric restriction ( WL ) and aerobic exercise plus weight loss ( AEx+WL ) on total and regional bone mineral density ( BMD ) in older women . Healthy , postmenopausal women [ age 63 + /- 1 ( SE ) yr ] not on hormone-replacement therapy underwent 6 mo of WL ( n = 15 ) consisting of dietary counseling one time per week with a caloric deficit ( 250 - 350 kcal/day ) or AEx+WL ( n = 15 ) consisting of treadmill exercise three times per week in addition to the weight loss . Maximal aerobic capacity increased only in the AEx+WL group ( P < 0 . 001 ) . Body weight , percent fat , and fat mass decreased similarly in both groups ( P < 0.005 ) , with no changes in fat-free mass . Total body BMD ( by dual-energy X-ray absorptiometry ) decreased in both groups ( P < 0.05 ) . Femoral neck , Ward 's triangle , and greater trochanter BMD decreased in the WL group ( P < /= 0.05 ) but were not significantly different after AEx+WL . L2-L4 BMD did not significantly change in either group . Thus WL and AEx+WL both result in losses of total body BMD ; however , AEx+WL appears to prevent the loss in regional BMD seen with WL alone in healthy , older women . This suggests that the addition of exercise to weight-loss programs may reduce the risk for bone loss Objective The aim of this study was to assess the impact of caloric restriction diet versus caloric restriction diet combined with aerobic exercises on bone mineral density ( BMD ) in obese premenopausal women . Subjects and methods Forty premenopausal obese women were classified r and omly into two groups equal in number . The first group ( group A ) received caloric restriction diet , while the second ( group B ) received caloric restriction diet combined with a program of aerobic exercises , over 3 months . The variables measured in this study included age , weight , height , body mass index , fat weight , lean mass , fat percent , basal metabolic rate , and BMD . Results The comparison between group A and group B showed significantly higher post-treatment lean mass , basal metabolic rate , and BMD in weight-bearing bones ( L2-L4 lumbar spine and total hip ) in group B compared to group A. In contrast to the BMD of the weight-bearing bones , the BMD of the radius showed significant decrease between the pre- and post-treatment results in groups A and B with no significant differences between the two groups . Conclusion A greater improvement in the BMD of weight-bearing bones was observed in obese premenopausal women undergoing caloric restriction combined with exercise than in those not undergoing exercise . Anaerobic exercises incorporated into weight loss programs help offset the adverse effects of dietary restriction on bone The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program ( RT+WLoss ) could maintain bone mineral density ( BMD ) and lean mass compared to moderate weight loss ( WLoss ) alone in older overweight adults with type 2 diabetes . We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program . This was a 12-month trial in which 36 sedentary , overweight adults aged 60 to 80 years with type 2 diabetes were r and omized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months ( phase 1 ) . Thereafter , all participants completed an additional 6-month home-based training without further dietary modification ( phase 2 ) . Total body and regional BMD and bone mineral content ( BMC ) , fat mass ( FM ) and lean mass ( LM ) were assessed by DXA every 6 months . Diet , muscle strength ( 1-RM ) and serum total testosterone , estradiol , SHBG , insulin and IGF-1 were measured every 3 months . No between group differences were detected for changes in any of the hormonal parameters at any measurement point . In phase 1 , after 6 months of gymnasium-based training , weight and FM decreased similarly in both groups ( P<0.01 ) , but LM tended to increase in the RT+WLoss ( n=16 ) relative to the WLoss ( n=13 ) group [ net difference ( 95 % CI ) , 1.8 % ( 0.2 , 3.5 ) , P<0.05 ] . Total body BMD and BMC remained unchanged in the RT+WLoss group , but decreased by 0.9 and 1.5 % , respectively , in the WLoss group ( interaction , P<0.05 ) . Similar , though non-significant , changes were detected at the femoral neck and lumbar spine ( L2-L4 ) . In phase 2 , after a further 6 months of home-based training , weight and FM increased significantly in both the RT+WLoss ( n=14 ) and WLoss ( n=12 ) group , but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months . These results indicate that in older , overweight adults with type 2 diabetes , dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES To examine the effect of diet and exercise-induced weight loss on bone mineral density in overweight postmenopausal women DESIGN A 1-year prospect i ve , r and omized clinical trial . SETTING Two university medical school research centers . PARTICIPANTS Sixty-seven overweight postmenopausal women , a subset of the women who participated in the Trial of Nonpharmacological Interventions in the Elderly ( TONE ) to control hypertension . The participants were assigned r and omly to one of four groups : usual care , weight loss only , sodium restriction only , or combined weight loss/sodium restriction . INTERVENTION All TONE participants in the treatment groups attended regular dietary intervention sessions to lose weight , reduce sodium intake , or both that they might refrain from using antihypertensive medications for a period of 15 to 36 months ( median = 29 months ) . MEASUREMENTS Bone mineral density ( BMD ) assessed by dual energy X-ray absorptiometry ( DXA ) , serum and urine markers of bone metabolism , and other demographic and clinical data were collected at baseline , 6 months , and 12 months . RESULTS Women assigned to the weight loss interventions lost 9.2 + /- 1.2 lbs ( mean + /- SE ) at 6 months and 7.7 + /- 2.0 lbs at 12 months compared with 1.8 + /- 1.0 lbs at 6 months and 1.9 + /- 1.6 lbs at 12 months for those assigned to no weight loss intervention ( P < .0001 ) . Weight loss was correlated with a decrease in total body BMD ( P = .004 ) and an increase in osteocalcin ( P = .004 ) after controlling for baseline bone measures , intervention assignment , and other baseline covariates . Regression analyses indicated that total body BMD decreased by 6.25 + /- 2.06 g/cm2 x 10 - 4 for each pound of weight loss . CONCLUSIONS Voluntary weight loss in overweight postmenopausal women is associated with modest decrease in total body BMD . Clinicians recommending weight loss for older postmenopausal women may need to include recommendations for reducing the risk of bone loss It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years . Here we report on results of the 3-year EFOPS exercise trial in osteopenic women . The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics . Forty-eight fully compliant women ( 55.1±3.3 years ) with no medication or illness affecting bone metabolism participated in the exercise group ( EG ) ; 30 women ( 55.5±3.0 years ) served as non-training controls ( CG ) . At baseline there were no significant between-group differences with respect to physical fitness , bone mineral density , pain and nutritional status . The training consisted of two group training and two home training sessions per week . The study participants of both groups were individually supplemented with calcium and vitamin D ( cholecalciferol ) . Bone mineral density ( BMD ) was measured by DXA at the lumbar spine , proximal femur and distal forearm and by QCT at the lumbar spine . Speed of sound and broadb and ultrasound attenuation were determined at the calcaneus by quantitative ultrasound ( QUS ) . Pain frequency and intensity at different skeletal sites were assessed via question naire . After 38 months , the following within-group changes were measured : DXA lumbar spine , EG : 0.8 % n.s . ; CG : −3.3 % P < 0.001 ; QCT trabecular ROI , EG : 1.1 % n.s ; CG : −7.7 % P < 0.001 ; QCT cortical ROI , EG : 5.3 % P < 0.001 ; CG : −2.6 % P < 0.001 ; DXA total hip : EG : −0.2 % n.s ; CG −1.9 % , P < 0.001 ; DXA distal forearm , EG : −2.8 % P < 0.001 ; CG : −3.8 % P < 0.001 ; BUA , EG : −0.3 % n.s ; CG −5.4 % P < 0.001 ; SOS , EG : 0.3 % n.s ; CG −1.0 % P < 0.001 . At year 3 between-group differences relative to the exercise group were : DXA lumbar spine : 4.1 % P < 0.001 ; QCT trabecular ROI : 8.8 % P < 0.001 ; QCT cortical ROI : 7.9 % P < 0.001 ; DXA total hip : 2.1 % , P < 0.001 ; DXA distal forearm : 1.0 % n.s . ; BUA : 5.8 % P < 0.05 ; SOS : 1.3 % P < 0.001 . Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group , while no between-group differences were detected in the main joints . In summary , over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine , hip and calcaneus , but not at the forearm Purpose . Evaluate the effects of weight loss on muscle mass and area , muscle fat infiltration , strength , and their association with physical function . Methods . Thirty-six overweight to moderately obese , sedentary older adults were r and omized into either a physical activity plus weight loss ( PA+WL ) or physical activity plus successful aging health education ( PA+SA ) program . Measurements included body composition by dual-energy X-ray absorptiometry , computerized tomography , knee extensor strength , and short physical performance battery ( SPPB ) . Results . At 6 months , PA+WL lost greater thigh fat and muscle area compared to PA+SA . PA+WL lost 12.4 % strength ; PA+SA lost 1.0 % . Muscle fat infiltration decreased significantly in PA+WL and PA+SA . Thigh fat area decreased 6-fold in comparison to lean area in PA+WL . Change in total SPPB score was strongly inversely correlated with change in fat but not with change in lean or strength . Conclusion . Weight loss result ed in additional improvements in function over exercise alone , primarily due to loss of body fat Cigarette smoking , alcohol consumption and low relative weight are often cited as risk factors for osteoporosis . In a prospect i ve cohort study of 96,508 middle-aged nurses 35 to 59 years of age we found that smoking was not a risk factor for hip and forearm fracture . Women who drank more than 15 grams of alcohol per day and whose relative weight was less than 21 kg/m2 were at increased risk of fractures , but these risk factors were not independent . Only the combination of alcohol intake and thinness substantially increased the likelihood of fracture . The low weight women consuming more than one drink per day comprised but 4 per cent of our population of middle-class women and sustained 6 per cent of the fractures Summary We examined the independent and combined effects of a multi-component exercise program and calcium – vitamin-D3-fortified milk on bone mineral density ( BMD ) in older men . Exercise result ed in a 1.8 % net gain in femoral neck BMD , but additional calcium – vitamin D3 did not enhance the response in this group of older well-nourished men . Introduction This 12-month r and omised controlled trial assessed whether calcium – vitamin-D3-fortified milk could enhance the effects of a multi-component exercise program on BMD in older men . Methods Men ( n = 180 ) aged 50–79 years were r and omised into : ( 1 ) exercise + fortified milk ; ( 2 ) exercise ; ( 3 ) fortified milk ; or ( 4 ) controls . Exercise consisted of high intensity progressive resistance training with weight-bearing impact exercise . Men assigned to fortified milk consumed 400 mL/day of low fat milk providing an additional 1,000 mg/day calcium and 800 IU/day vitamin D3 . Femoral neck ( FN ) , total hip , lumbar spine and trochanter BMD and body composition ( DXA ) , muscle strength 25-hydroxyvitamin D and parathyroid hormone ( PTH ) were assessed . Results There were no exercise-by-fortified milk interactions at any skeletal site . Exercise result ed in a 1.8 % net gain in FN BMD relative to no-exercise ( p < 0.001 ) ; lean mass ( 0.6 kg , p < 0.05 ) and muscle strength ( 20–52 % , p < 0.001 ) also increased in response to exercise . For lumbar spine BMD , there was a net 1.4–1.5 % increase in all treatment groups relative to controls ( all p < 0.01 ) . There were no main effects of fortified milk at any skeletal site . Conclusion A multi-component community-based exercise program was effective for increasing FN BMD in older men , but additional calcium – vitamin D3 did not enhance the osteogenic response OBJECTIVES To test the hypothesis that unintentional weight loss increases the rate of bone loss and risk of hip fracture more than intentional weight loss . DESIGN Prospect i ve cohort study . SETTING Four communities within the United States . PARTICIPANTS Six thous and seven hundred eighty-five elderly white women with measurement of weight change and assessment of intention to lose weight . MEASUREMENTS Weight change between baseline and fourth examinations ( average 5.7 years between examinations ) and assessment of intention to lose weight . Weight loss was defined as a decrease of 5 % or more from baseline weight , stable weight was defined as less than a 5 % change from baseline weight , and weight gain was defined as an increase of 5 % or more from baseline weight . Rate of change in bone mineral density at the hip between fourth and sixth examinations ( average 4.4 years between examinations ) was measured using dual-energy x-ray absorptiometry . Incident hip fractures occurring after the fourth examination until June 1 , 2001 ( average follow-up 6.6 years ) was confirmed using radiographic reports . RESULTS The adjusted average rate of decline in total hipbone density steadily increased from -0.52 % per year in women with weight gain to -0.68 % per year in women with stable weight to -0.92 % per year in women with weight loss ( P-value for trend < .001 ) . Higher rates of hip-bone loss were observed in women with weight loss irrespective of body mass index ( BMI ) or intention to lose weight . During follow-up of an average 6.6 years after the fourth examination , 400 ( 6 % ) of the cohort suffered a first hip fracture . Women with weight loss had 1.8 times the risk ( 95 % confidence interval (CI)=1.43 - 2.24 ) of subsequent hip fracture as those with stable or increasing weight . The association between weight loss and increased risk of hip fracture was consistent across categories of BMI and intention to lose weight . Even voluntary weight loss in overweight women with a BMI of 25.9 kg/m2 ( median ) or greater increased the risk of hip fracture ( multivariate hazard ratio=2.48 , 95 % CI=1.33 - 4.62 ) . CONCLUSION Older women who experience weight loss in later years have increased rates of hip-bone loss and a two-fold greater risk of subsequent hip fracture , irrespective of current weight or intention to lose weight . These findings indicate that even voluntary weight loss in overweight elderly women increases hip fracture risk Increased inflammation and weight loss are associated with a reduction in bone mineral density ( BMD ) . Aerobic exercise may minimize the loss of bone and weight loss may contribute to a decrease in cytokines . We tested the hypothesis that aerobic exercise in combination with a weight loss program would decrease circulating concentrations of inflammatory markers , thus mediating changes in BMD . This was a nonr and omized controlled trial . Eighty-six overweight and obese postmenopausal women ( 50–70 years of age ; BMI , 25–40 kg/m2 ) participated in a weight loss ( WL ; n = 40 ) or weight loss plus walking ( WL + AEX ; n = 46 ) program . Outcome measures included BMD and bone mineral content of the femoral neck and lumbar spine measured by dual energy X-ray absorptiometry , interleukin-6 , tumor necrosis factor-α , soluble receptors of IL-6 , and TNF-α ( sTNFR1 and sTNFR2 ; receptors in a subset of the population ) , VO2 max , fat mass , and lean mass . Weight decreased in the WL ( p < 0.001 ) and WL + AEX ( p < 0.001 ) groups . VO2 max increased ( p < 0.001 ) after WL + AEX . There was a 2 % increase in femoral neck BMD in the WL + AEX group ( p = 0.001 ) , which was significantly different from the WL group . The change in sTNFR1 was significantly associated with the change in femoral neck BMD ( p < 0.05 ) . The change in VO2 max was an independent predictor of the change in femoral neck BMD . Our findings suggest that the addition of aerobic exercise is recommended to decrease inflammation and increase BMD during weight loss in overweight postmenopausal women Weight regain is a problem among many bariatric surgery patients . Whether a high-volume exercise program ( HVEP ) , a strategy to limit weight regain , is feasible in these patients is unknown . The feasibility of an HVEP in obese post-bariatric-surgery patients was determined by r and omizing 33 Roux-en-Y gastric bypass ( RYGB ) and gastric b and ing ( GB ) surgery patients with a mean BMI of 41 ± 6 kg/m2 to an HVEP or control group for 12 weeks . The HVEP group was instructed to expend ≥ 2,000 kcal/week in moderate-intensity exercise . All patients were counseled to limit energy intake . Treatment effect was assessed by repeated measures analysis . During the last 4 weeks of the study , 53 % of the HVEP group expended ≥ 2,000 kcal/week and 82 % expended ≥ 1,500 kcal/week . Step count , reported time spent and energy expended during moderate physical activity , maximal oxygen consumption relative to weight , and incremental area under the postpr and ial blood glucose curve were significantly improved over 12 weeks in the HVEP group compared to controls ( group-by-week effect : P = 0.009 - 0.03 ) . Both groups reported significant improvement in some quality -of-life scales . Changes in weight , energy and macronutrient intake , resting energy expenditure ( REE ) , fasting lipids and glucose , and fasting and postpr and ial insulin concentrations were not different between the two groups . HVEP is feasible in about 50 % of the patients and enhances physical fitness and reduces postpr and ial blood glucose in bariatric surgery patients To test the hypothesis that weight loss in older men is associated with increased rates of hip bone loss regardless of adiposity and intention to lose weight , we measured body weight , body composition , hip bone mineral density ( BMD ) , and intention to lose weight in a cohort of 1342 older men enrolled in the Osteoporotic Fractures in Men ( MrOS ) study and followed them prospect ively for an average of 1.8 yr for changes in weight and BMD . The adjusted average rate of change in total hip BMD was 0.1%/yr in men with weight gain , -0.3%/yr in men with stable weight , and -1.4%/yr in men with weight loss ( test for trend , P < 0.001 ) . Higher rates of hip bone loss were observed in men with weight loss regardless of category of body mass index , body composition , or intention to lose weight . Even among obese ( body mass index , > or = 30 kg/m2 ) men trying to lose weight , those with documented voluntary weight reduction experienced an increase in hip bone loss ( average rate of change in total hip BMD , 0.5%/yr in those with weight gain , -0.1%/yr in those with stable weight , and -1.7%/yr in those with weight loss ; test for trend , P < 0.001 ) . Older men who experience weight loss have increased rates of hip bone loss , even among overweight and obese men undergoing voluntary weight reduction OBJECTIVE To determine the effects of dietary-induced weight loss ( D ) and weight loss plus exercise ( D + E ) compared to exercise alone ( E ) on bone mineral density ( BMD ) in older adults with knee osteoarthritis ( OA ) . DESIGN Data come from 284 older ( 66.0 ± 6.2 years ) , overweight/obese ( body mass index ( BMI ) 33.4 ± 3.7 kg/m2 ) , adults with knee OA enrolled in the Intensive Diet and Exercise for Arthritis ( IDEA ) study . Participants were r and omized to 18 months of walking and strength training ( E ; n = 95 ) , dietary-induced weight loss targeting 10 % of baseline weight ( D ; n = 88 ) or a combination of the two ( D + E ; n = 101 ) . Body weight and composition ( DXA ) , regional BMD , were obtained at baseline and 18 months . RESULTS E , D , and D + E groups lost 1.3 ± 4.5 kg , 9.1 ± 8.6 kg and 10.4 ± 8.0 kg , respectively ( P < 0.01 ) . Significant treatment effects were observed for BMD in both hip and femoral neck regions , with the D and D + E groups showing similar relative losses compared to E ( both P < 0.01 ) . Despite reduced BMD , fewer overall participants had T-scores indicative of osteoporosis after intervention ( 9 at 18 months vs 10 at baseline ) . Within the D and D + E groups , changes in hip and femoral neck , but not spine , BMD correlated positively with changes in body weight ( r = 0.21 and 0.54 respectively , both P ≤ 0.01 ) . CONCLUSIONS Weight loss via an intensive dietary intervention , with or without exercise , results in bone loss at the hip and femoral neck in overweight and obese , older adults with OA . Although the exercise intervention did not attenuate weight loss-associated reductions in BMD , classification of osteoporosis and osteopenia remained unchanged . CLINICAL TRIAL REGISTRATION NUMBER NCT00381290 Summary We evaluated whether age moderated the effect of impact + resistance exercise on hip BMD in older post-menopausal breast cancer survivors ( BCS ) . Exercise was more beneficial among younger than older women within our sample , suggesting that much older BCS may require different training programs to improve hip health . Purpose Previously , we reported that a program of resistance + impact training stopped bone loss at the spine in older , post-menopausal BCS but had no effect on bone mineral density ( BMD ) at the hip . Aging may blunt the responsiveness of the hip to mechanical loading , so we conducted a secondary data analysis to evaluate whether age moderated the effect of exercise on hip BMD . Methods We analyzed data from our r and omized , controlled trial in older ( ≥ 50 years of age at diagnosis ) , post-menopausal , post-adjuvant treatment BCS ( n = 106 ) comparing women assigned to impact + resistance exercise ( POWIR ) or to a control program of low-intensity stretching ( FLEX ) . We examined effect modification by age on BMD at three hip sites ( greater trochanter , femoral neck , and total hip ) using hierarchical linear modeling adjusting for time since diagnosis and use of adjuvant hormone therapy . Results Age moderated the effect of exercise on total hip BMD such that younger women in POWIR were more likely to see a positive net benefit than FLEX compared to older women where there was little difference between groups ( p = 0.02 ) . Conclusions The skeletal response to loading at the hip within post-menopausal BCS diminishes with age . Whether more vigorous exercise programs and /or longer training periods are required to favorably change hip health in older BCS will require future study and careful thought about the risks and benefits of tougher training programs Significant reductions in total-body bone mineral density ( BMD ) have been reported in obese women who consume very-low-calorie diets . A reduction in bone mass is highly correlated with an increased risk of osteoporosis . The present study investigated whether strength training would prevent such reductions in dieters . Twenty-one healthy obese women weighing ( mean + /- SD ) 91.1 + /- 9 kg and aged 38 + /- 9 years were r and omly assigned to receive either diet alone or diet plus resistance training . Both groups consumed a 925-kcal/d portion-controlled diet for the first 16 of 17 weeks and a 1,000 to 1,500-kcal/d balanced deficit diet thereafter . Bone mineral content ( BMC ) , BMD , fat-free mass ( FFM ) , and fat mass were measured with dual-energy x-ray absorptiometry ( DEXA ) before and after 24 weeks of dieting . No significant changes in total-body or lumbar spine BMC and BMD were observed in either condition at the end of treatment . However , both groups demonstrated a significant loss of both BMC and BMD in the femoral neck and greater trochanter . Diet plus resistance training was not associated with a significantly better outcome on either of these measures versus diet alone . The results suggest that increasing the energy content of very-low-calorie diets to 925 kcal/d may prevent the loss of total BMD , but not the loss from the femoral neck and greater trochanter . These findings raise a concern in light of the high frequency of dieting in American women Abstract Obesity in older adults is a growing public health problem , yet the appropriate treatment remains controversial partly due to evidence that weight loss reduces bone mass and may increase fracture risk . The purpose of this review is to summarize the research to date on the effects of diet-induced weight loss on bone health in obese ( body mass index 30 kg/m2 and above ) older ( aged 65 years or older ) adults . Observational studies have shown that weight loss in this population decreases total hip bone mineral density and increases the risk of frailty fractures ( composite of proximal femur , pelvis , and proximal humerus fractures ) . R and omized controlled trials have largely confirmed these earlier observations but have also shown that exercise , particularly progressive resistance training , can attenuate or even alleviate this bone loss . Further research incorporating outcomes concerning bone quality and mass are needed to identify the optimal exercise and nutritional regimens to counteract the bone loss Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss . Therefore , it is recommended that weight loss therapy should include an intervention such as exercise training ( ET ) to minimize bone loss . The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density ( BMD ) in obese older adults . One-hundred-seven older ( age > 65 years ) obese ( body mass index [ BMI ] ≥ 30 kg/m(2 ) ) adults were r and omly assigned to a control group , diet group , exercise group , and diet-exercise group for 1 year . Body weight decreased in the diet ( -9.6 % ) and diet-exercise ( -9.4 % ) groups , not in the exercise ( -1 % ) and control ( -0.2 % ) groups ( between-group p < 0.001 ) . However , despite comparable weight loss , bone loss at the total hip was relatively less in the diet-exercise group ( -1.1 % ) than in the diet group ( -2.6 % ) , whereas BMD increased in the exercise group ( 1.5 % ) ( between-group p < 0.001 ) . Serum C-terminal telopeptide ( CTX ) and osteocalcin concentrations increased in the diet group ( 31 % and 24 % , respectively ) , whereas they decreased in the exercise group ( -13 % and -15 % , respectively ) ( between-group p < 0.001 ) . In contrast , similar to the control group , serum CTX and osteocalcin concentrations did not change in the diet-exercise group . Serum procollagen propeptide concentrations decreased in the exercise group ( -15 % ) compared with the diet group ( 9 % ) ( p = 0.04 ) . Serum leptin and estradiol concentrations decreased in the diet ( -25 % and -15 % , respectively ) and diet-exercise ( -38 % and -13 % , respectively ) groups , not in the exercise and control groups ( between-group p = 0.001 ) . Multivariate analyses revealed that changes in lean body mass ( β = 0.33 ) , serum osteocalcin ( β = -0.24 ) , and one-repetition maximum ( 1-RM ) strength ( β = 0.23 ) were independent predictors of changes in hip BMD ( all p < 0.05 ) . In conclusion , the addition of ET to weight loss therapy among obese older adults prevents weight loss-induced increase in bone turnover and attenuates weight loss-induced reduction in hip BMD despite weight loss-induced decrease in bone-active hormones |
2,447 | 15,361,261 | The results may provide evidence for the usefulness of pharmacogenetic testing for individualised ACE inhibitor therapy | Background The Angiotensin Converting Enzyme ( ACE ) insertion/deletion ( I/D ) polymorphism has received much attention in pharmacogenetic research because observed variations in response to ACE inhibitors might be associated with this polymorphism .
Pharmacogenetic testing raises the hope to individualise ACE inhibitor therapy in order to optimise its effectiveness and to reduce adverse effects for genetically different subgroups .
However , the extent of its effect modification in patients treated with ACE inhibitors remains inconclusive .
Therefore our objective is to quantify the effect modification of the insertion/deletion polymorphism of the angiotensin converting enzyme gene on any surrogate and clinical ly relevant parameters in patients with cardiovascular diseases , diabetes , renal transplantation and /or renal failure .
Discussion This protocol describes a strategy to quantify the effect modification of the ACE polymorphism on ACE inhibitors in relevant clinical domains using meta-epidemiological research methods . | Diabetic nephropathy is one of the leading causes of end-stage renal disease . We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate ( GFR ) , and whether any effect was associated with the ACE genotype . In a prospect i ve double-blind r and omized study , normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril , an ACE inhibitor . Urine albumine/creatinine ratio ( ACR ) , mean blood pressure ( MBP ) and index of glomerular filtration rate ( GFR ) based on S-creatinine were determined . ACE genotype was determined by electrophoresis . ACR was higher in the placebo group than in the perindopril group after 4 months , and continued to increase during the study period . After 36 months of observation , ACR in the placebo group was 1.7+/-1.1 mg/mmol , and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group ( p<0.001 , Mann-Whitney test ) . During treatment , a significant increase in ACR in the placebo group ( p=0.007 ) , Wilcoxon matched paired test ) was observed . There were no differences between the groups regarding MBP or GFR . The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype ( II , ID , DD ) BACKGROUND In a previous study , men with a history of myocardial infa rct ion were found to have an increased prevalence of homozygosity for the deletional allele ( D ) of the angiotensin-converting-enzyme ( ACE ) gene . The D allele is associated with higher levels of ACE , which may predispose a person to ischemic heart disease . We investigated the association between the ACE genotype and the incidence of myocardial infa rct ion , as well as other manifestations of ischemic heart disease , in a large , prospect i ve cohort of U.S. male physicians . METHODS In the Physicians ' Health Study , ischemic heart disease as defined by angina , coronary revascularization , or myocardial infa rct ion developed in 1250 men by 1992 . They were matched with 2340 controls according to age and smoking history . Zygosity for the deletion-insertion ( D-I ) polymorphism of the ACE gene was determined by an assay based on the polymerase chain reaction . Data were analyzed for both matched pairs and unmatched sample s , with adjustment for the effects of known or suspected risk factors by conditional and nonconditional logistic regression , respectively . RESULTS The ACE genotype was not associated with the occurrence of either ischemic heart disease or myocardial infa rct ion . The adjusted relative risk associated with the D allele was 1.07 ( 95 percent confidence interval , 0.96 to 1.19 ; P = 0.24 ) for ischemic heart disease and 1.05 ( 95 percent confidence interval , 0.89 to 1.25 ; P = 0.56 ) for myocardial infa rct ion , if an additive mode of inheritance is assumed . Additional analyses assuming dominant and recessive effects of the D allele also failed to show any association , as did the examination of low-risk subgroups . CONCLUSIONS In a large , prospect ively followed population of U.S. male physicians , the presence of the D allele of the ACE gene conferred no appreciable increase in the risk of ischemic heart disease or myocardial infa rct ion The D/I ( deletion , D , insertion , I ) polymorphism of the angiotensin‐converting enzyme ( ACE ) gene has been extensively studied for its association with a number of cardiovascular and other disease states . However , its potential association with differential clinical efficacy of ACE inhibitors ( ACE‐I ) administered to patients who had suffered a myocardial infa rct ion ( MI ) , i.e. the prevention of left ventricular ( LV ) remodeling , has so far not been specifically studied . The aim of the study was to investigate whether the D/I polymorphism of the ACE gene is associated with the incidence of post‐MI LV remodeling in patients drawn from the ‘ Healing and Early Afterload Reducing Therapy ’ ( HEART ) Study . The ACE D/I polymorphism was characterized by the polymerase chain reaction ( PCR ) in 265 subjects from the ‘ Healing and Early Afterload Reducing Therapy ’ Study , a double‐blind , placebo‐controlled trial with the objective of determining whether early or delayed administration of the ACE‐I , ramipril , in patients with acute anterior wall MI would be optimal in reducing LV enlargement . Selected frequencies for the ACE D and I alleles were 0.59 and 0.41 ( placebo – high dose group ) , 0.56 and 0.44 ( low dose – low dose group ) , and , 0.60 and 0.40 ( high dose – high dose group ) , respectively . All observed genotype frequencies were in Hardy – Weinberg equilibrium . There was no evidence for an association between genotype and outcome regarding LV size or function , nor with the initial blood pressure response after ACE‐I administration ( adjusted for covariates ) . Our data provide no evidence for an association of the ACE D/I polymorphism with the risk of LV remodeling post‐MI in the presence of ACE‐I therapy , and therefore do not suggest that differential clinical efficacy of ACE‐inhibitors is related to this genetic marker BACKGROUND Cardiac complications are the main cause of death in renal transplantation ( RT ) , and left ventricular hypertrophy ( LVH ) may play an important role in these patients . The unfavorable genotype of the angiotensin-converting enzyme ( ACE ) gene has been associated with cardiovascular disease , including LVH . ACE inhibitors ( ACEIs ) reduce LVH , but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion ( I/D ) genotypes of the ACE gene . METHODS We prospect ively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 + /- 5.6 months . Patients r and omly received either lisinopril 10 mg/day ( group A , N = 29 ; 5 were excluded due to reversible acute renal failure ) or placebo ( group B , N = 28 ) for 12 months . Echocardiography ( M-mode , 2-B , and color flow Doppler ) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing . The ACE genotype ( I or D alleles ) was ascertained by polymerase chain reaction ( PCR ; group A , DD = 10 and ID/II = 14 ; group B , DD = 15 and ID/II = 13 ) . RESULTS All patients maintained a good renal function ( serum creatinine < 2.5 mg/dL ) during the follow-up and both groups received a similar proportion of antihypertensive drugs ( beta-blockers 83 vs. 79 % ; Ca antagonists 66 vs. 68 % ; alpha1-adrenoreceptor antagonists 50 vs. 67 % ) during the study . As expected , mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B ( -4 + /- 2.8 vs. 2.1 + /- 2.6 % , P = 0.07 , and -11.5 + /- 1.5 vs. -0.5 + /- 2.3 % , P < 0.01 , respectively ) . Group A patients showed a significantly higher decrement in LV mass index ( LVMI ) than group B at the end of follow-up , after adjusting for age , baseline LVMI , time after grafting and changes in systolic blood pressure , renal function , and hemoglobin levels ( group A , -9.5 + /- 3.5 % vs. group B , 3 + /- 3.2 % , P < 0.05 ) . As a result , 46 % of group A and only 7 % of group B patients showed a reduction of LVMI > /=15 % ( P < 0.01 ) . The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients ( placebo DD , 8.4 + /- 4.1 % vs. lisinopril DD , -7.2 + /- 5.3 , P < 0.05 ) , and a trend was observed in patients with other genotypes ( placebo ID/II , 2.8 + /- 5.4 % vs. lisinopril ID/II , -11.4 + /- 5 % , P = 0.33 ) . CONCLUSIONS Lisinopril decreases LVM in renal transplant patients with hypertension and LVH , and the ACE gene polymorphism may predict the beneficial effect of this therapy . This finding may be important in targeting prophylactic interventions in this population |
2,448 | 29,344,847 | There were no significant differences in pregnancy rate per cycle , clinical pregnancy rate and live birth rate between women who underwent surgery for endometrioma and those who did not .
Conclusion Current evidence suggests that women with endometriosis-related infertility have similar cycle outcomes to other patients going through ART . | Objective To assess the impact of surgical management of endometrioma on the outcome of assisted reproduction treatment ( ART ) . | OBJECTIVE Retrospective studies suggest that laparoscopic excision of endometriomas is associated with a reduced responsiveness to ovarian hyperstimulation . In this study , we prospect ively evaluated ovarian response to hyperstimulation in women selected for in vitro fertilization and intracytoplasmic sperm injection cycles who previously underwent laparoscopic enucleation of a monolateral endometrioma . STUDY DESIGN Operated and contralateral intact ovaries of the same patient were compared in terms of number of follicles , number of oocytes retrieved , fertilization rate , and rate of high- quality embryos . RESULTS Thirty-eight subjects were included . A reduced number of dominant follicles , oocytes , embryos , and high- quality embryos was observed in the operated gonad . The mean percentage of reduction was 60 % ( 95 % confidence interval 38 - 81 % ) , 53 % ( 95 % confidence interval 30 - 75 % ) , 55 % ( 95 % confidence interval 28 - 81 % ) , and 52 % ( 95 % confidence interval 17 - 87 % ) , respectively . Fertilization rate and rate of good- quality embryos were similar . CONCLUSION Laparoscopic excision of endometriomas is associated with a quantitative but not a qualitative damage to ovarian reserve OBJECTIVES Different gonadotropin-releasing-hormone agonist ( GnRH-a ) formulations with different potency and associated side effects , therefore , different compliance and persistence of therapy . This study was to evaluate the difference of hormonal profile and side effects due to hypoestrogenic status after treatment of leuprorelin and triptorelin in Chinese women with ovarian endometrioma after conservative surgical treatment . STUDY DESIGN A total of 302 women underwent laparoscopic excision of ovarian endometriomas with rASRM III and IV were enrolled in the study .Subjects were r and omized into two groups with use of a r and om table . Twenty two patients dropped out during the study . Thus 142 patients had three doses of i.m . leuprorelin ( group A ) and 138 patients had three doses of i.m . triptorelin(group B ) at 4 weeks intervals after surgical treatment . Menopausal symptoms were evalutaed using a question naire and serum sex hormonal levels were also measured during the follow-up . RESULTS At week 4 after the treatment , most of the patients in leuprorelin group have no obvious side effects . After 9 weeks , bone pain , hot flashes and sweating , and irregular bleeding were the main side effects and showed no difference between the groups . Anxiety , depression , vaginal dryness , headache , and acne rates were all significantly higher in triptorelin group than in leuprorelin group . A significant difference in FSH ( p=0.003 ) , LH ( p=0.026 ) and E2 ( p=0.002 ) levels between the groups were observed after 21 days of the GnRHa treatment . The FSH ( p=0.021 ) and E2 ( p=0.033 ) levels remained higher in the leuprorelin group than the triptorelin group after six weeks of treatment , but the difference of LH(p=0.917 ) level was no longer discernible . CONCLUSION Leuprorelin in down-regulating the pituitary-ovarian function was more moderate , and the hormonal levels decrease progressively and gradually , therefore , with lower rate of menopausal symptoms . Leuprorelin acetate maybe better tolerated than triptorelin OBJECTIVE To investigate whether aspiration of ovarian endometriomas before controlled ovarian stimulation ( COH ) improves intracytoplasmic sperm injection ( ICSI ) outcomes . DESIGN Prospect i ve study . SETTING University hospital . PATIENT(S ) A prospect i ve analysis of 171 patients with ovarian endometriosis and tubal factor infertility were divided into four groups : aspiration of endometriomas at the beginning of COH in patients with ovarian endometriomas and no history of previous surgery ( n = 41 ) ( group 1 ) ; nonaspirated endometriomas ( n = 40 ) ( group 2 ) ; history of ovarian surgery for endometriomas in patients without ovarian endometriomas at the beginning of COH ( n = 44 ) ( group 3 ) ; and tubal factor infertility ( n = 46 ) ( control group 4 ) . INTERVENTION(S ) Aspiration of endometriomas . MAIN OUTCOME MEASURE(S ) Clinical parameters , characteristics of COH , and ICSI results were analyzed . RESULT ( S ) We observed higher levels of E(2 ) on the day of hCG injection after aspiration of endometriomas compared with nonaspirated endometriomas . When we compared all endometriomas and tubal factor ( control ) groups , we observed a lower number of total follicles ( > 17 mm ) and metaphase II ( MII ) oocytes in nonaspirated and resected endometrioma groups and a longer duration of COH in the nonaspirated endometrioma group compared with the tubal factor group . Implantation and clinical pregnancy rates were similar among all groups . CONCLUSION ( S ) In the current study , all patients with endometriomas had significantly lower numbers of MII oocytes compared with those in patients with tubal factor infertility . We propose that aspiration of endometriomas before COH neither reduces the amount of gonadotropins nor increases the number of follicles > 17 mm , the number of MII oocytes retrieved , the implantation rates , or the clinical pregnancy rates . Resection of small endometriomas ( 1 - 6 cm ) may not present any additional benefits to the IVF-ICSI cycle outcomes OBJECTIVE To assess the impact of prior unilateral or bilateral endometrioma cystectomy on controlled ovarian hyperstimulation ( COH ) and intracytoplasmic sperm injection ( ICSI ) outcome . DESIGN Retrospective case-control study . SETTING Department of Obstetrics and Gynecology , School of Medicine , Hacettepe University , Ankara , Turkey . PATIENT(S ) Fifty-seven consecutive infertile patients were enrolled who had previously undergone unilateral ( n = 34 ) or bilateral ( n = 23 ) laparoscopic cystectomy for endometriomas more than 3 cm in diameter and underwent ICSI . The control group consisted of 99 patients with tubal factor infertility . INTERVENTION(S ) Controlled ovarian hyperstimulation and ICSI . MAIN OUTCOME MEASURE(S ) Cycle cancellation rate , number of oocytes , fertilization rate , embryo quality , clinical pregnancy rate ( PR ) , and implantation rate . RESULT ( S ) The mean number of oocytes , metaphase II oocytes , and two-pronucleated oocytes were significantly lower in the bilateral cystectomy group compared to the unilateral cystectomy and control groups . However , all other parameters , including fertilization rate , the mean number of embryos transferred , the mean number of grade 1 embryos transferred , the clinical PR per embryo transfer , and implantation rate , were comparable among the three groups . Within the unilateral cystectomy group , the mean number of oocyte retrieved from the operated site was significantly less than in the contralateral nonoperated site . CONCLUSION ( S ) Laparoscopic endometrioma cystectomy does reduce the ovarian reserve . However , diminished ovarian reserve does not translate into impaired pregnancy outcome Background : Endometriosis is a common hormone-dependent gynecologic disease with a high recurrence . Laparotomy or laparoscopy is the st and ard surgery for the large endometrioma . Also , sclerotherapy is basically used to treat different diseases one of which is endometrioma . Objective : The study was design ed to assess the value of transvaginal ultrasound-guided ethanol sclerotherapy in patients with a recurrent endometrioma . Material s and Methods : In a r and omized clinical trial , an interventional group of 20 patients underwent transvaginal ethanol sclerotherapy for recurrent ovarian endometrioma . The patients were followed up first after one and two weeks and then after one , two , and three months . If the patients had no endometrioma , they were treated with in vitro fertilization ( IVF ) ( st and ard long protocol ) . A control group of 20 patients with endometrioma were enrolled for an IVF protocol . They had no treatment by ethanol sclerotherapy . IVF parameters , pregnancy rates , and implantation rates were compared in both groups . Results : The demographic data showed no difference between the two groups . The initial mean endometria size was 41.45±15.9 cm , the recurrence rate after 6 months was 4 ( 20 % ) , FSH before and after sclerotherapy was 6.97±2.25 IU/L and 6.78±1.88 IU/L ( p=0.343 ) . The clinical pregnancy rate was 6 ( 33.3 % ) vs. 3 ( 15 % ) , ( p=0.616 ) . The fertilization rate emerged 63.06 % in study group vs. 60.38 % , ( p=0.57 ) . The implantation rate turned out 12.9 % in study group vs. 7.5 % , ( p=0.52 ) . None of these results were significant . However , the data pointed to a better trend toward the ethanol sclerotherapy group . Conclusion : Ethanol sclerotherapy could be an effective strategy for the treatment of recurrent endometrioma especially before IVF Background : Our objective was to evaluate the effect of ovarian endometrioma on ovarian stimulation outcomes in in vitro fertilization cycles ( IVF ) . Material s and Methods : In this prospect i ve cohort study , we followed 103 patients who underwent intra-cytoplasmic sperm injection ( ICSI ) procedures over a 24-months period . The study group consisted of 47 infertile women with either unilateral or bilateral ovarian endometrial cysts of less than 3 cm . The control group consisting of 57 patients with mild male factor infertility was c and i date for ICSI treatment during the same time period as the study groups . Both groups were compared for number of oocytes retrieved , grade s of oocytes , as well as embryo quantity and quality . Results : Our results showed similar follicle numbers , good embryo grade s ( A or B ) and pregnancy rates in the compared groups . However , patients with endometrioma had higher gonadotropin consumption than the control group . The mean number of retrieved oocytes in patients with endometrioma was significantly lower than control group ( 6.6 ± 3.74 vs. 10.4 ± 5.25 ) ( p<0.001 ) . In addition , patients with endometrioma had significantly lower numbers of metaphase II ( MII ) oocytes ( 5 ± 3.21 ) than controls ( 8.2 ± 5.4 ) ( p<0.001 ) . In patients with unilateral endometrioma , there were no significant differences in main outcome measures between normal and involved ovaries in the patients with endometrioma . Conclusion : Patients with ovarian endometrioma had poor outcome . They showed poor ovarian response with lower total numbers of retrieved oocytes and lower MII oocytes during the stimulation phase ; however , it does not affect the total number of embryos transferred per patient , quality of embryos , and pregnancy rate per patient OBJECTIVE To evaluate the effects of laparoscopic cystectomy on ovarian reserve in patients with endometriomas . DESIGN Prospect i ve study . SETTING Private and university hospitals . PATIENT(S ) A total of 193 patients with endometriomas undergoing laparoscopic cyctectomy . INTERVENTION(S ) Serum levels of antimüllerian hormone ( AMH ) , FSH , and E₂ , as well as antral follicle count ( AFC ) were measured preoperatively and 1 week , 3 and 9 months postoperatively for AMH , and 3 months for other values . MAIN OUTCOME MEASURE(S ) Ovarian reserve based on the comparison of AMH alterations . The secondary end points are changes in FSH , E₂ , and AFC . RESULT ( S ) Serum AMH level decreased significantly from the baseline ( 3.86 ± 3.58 ng/mL ) to 1 week ( 1.66 ± 1.92 ng/mL ) , 3 months ( 2.06 ± 2.5 ng/mL ) , and 9 months ( 1.77 ± 1.76 ng/mL ) postoperatively . Those patients with bilateral endometriomas had significantly lower levels of AMH , 1 week , 3 and 9 months after operation . Also , patients older than 38 years had lower postoperative AMH levels . The FSH levels increased significantly from baseline to 3 months postoperatively . The AFC level increased significantly from baseline to 3 months after operation . CONCLUSION ( S ) The AMH level decreased and the FSH level increased after laparoscopic cystectomy for endometriomas , especially in older patients and those with bilateral cysts OBJECTIVE To determine the difference between two laparoscopic methods for the management of endometriomas with regard to recurrence of signs and symptoms and pregnancy rate . DESIGN Prospect i ve , r and omized clinical trial . SETTING Infertility and gynecologic endoscopy units of two medical university hospitals . PATIENT(S ) One hundred patients with endometriomas who had either infertility or pelvic pain . INTERVENTION(S ) Patients were r and omly divided into two groups ; one group underwent cystectomy ( group 1 ) , and fenestration and coagulation were performed for the other ( group 2 ) . MAIN OUTCOME MEASURE(S ) A comparison of recurrence of signs and symptoms of endometriomas and pregnancy rates in two groups . RESULT ( S ) Fifty-two patients were studied in group 1 and 48 in group 2 . The recurrence of symptoms , such as pelvic pain and dysmenorrhea , was 15.8 % in group 1 and 56.7 % in group 2 after 2 years . The rate of reoperation was 5.8 % in group 1 and 22.9 % in group 2 and these differences were statistically significant . The cumulative pregnancy rate was significantly higher in group 1 ( 59.4 % ) than in group 2 ( 23.3 % ) at 1-year follow-up . CONCLUSION ( S ) Laparoscopic cystectomy of endometriomas is a better choice than fenestration and coagulation because the former technique leads to a lower recurrence of signs and symptoms and a lower rate of reoperation and a higher cumulative pregnancy rate than the latter OBJECTIVE To assess the efficacy of two laparoscopic methods for the management of endometriomas with regard to pain relief , pregnancy rate , and disease recurrence . DESIGN Prospect i ve , r and omized clinical trial . SETTING Tertiary care hospital . PATIENT(S ) Sixty-four patients with advanced stages of endometriosis . INTERVENTION(S ) Patients were r and omly allocated at the time of laparoscopy to undergo either cystectomy of the endometrioma ( group 1 ) or drainage of the endometrioma and bipolar coagulation of the inner lining ( group 2 ) . MAIN OUTCOME MEASURE(S ) Pain relief and pregnancy rate . RESULT ( S ) Thirty-two patients were enrolled in each group . The 24-month cumulative recurrence rates of dysmenorrhea , deep dyspareunia , and nonmenstrual pelvic pain were lower in group 1 than in group 2 ( dysmenorrhea : 15.8 % versus 52.9 % ; deep dyspareunia : 20 % versus 75 % ; nonmenstrual pelvic pain : 10 % versus 52.9 % ) . The median interval between the operation and the recurrence of moderate to severe pelvic pain was longer in group 1 than in group 2 ( 19 months [ range , 13.5 - 24 months ] versus 9.5 months [ range , 3 - 20 months ] ) . The 24-month cumulative pregnancy rate was higher in group 1 than in group 2 ( 66.7 % versus 23.5 % ) . CONCLUSION ( S ) For the treatment of ovarian endometriomas , a better outcome with a similar rate of complications is achieved with laparoscopic cystectomy than with drainage and coagulation OBJECTIVE To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas . DESIGN Retrospective study with prospect i ve selection of participants and controls . SETTING Instituto de Ginecología y Fertilidad Buenos Aires , Argentina . PATIENT(S ) Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle ( group A ) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility ( group B ) . INTERVENTION(S ) Laparoscopic endometrioma cystectomy , IVF-ET cycle . MAIN OUTCOME MEASURE(S ) E(2 ) levels , number of gonadotropin ampoules , follicles , oocytes retrieved , number and quality of embryos transferred , and clinical pregnancy rate . RESULT ( S ) There were no differences in all the parameters studied ( E(2 ) levels , number of follicles , oocytes retrieved , number and quality of embryos transferred , and clinical pregnancy rate ) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation , which was significantly higher in group A than in group B. CONCLUSION ( S ) Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET OBJECTIVE To investigate the outcomes of intracytoplasmic sperm injection ( ICSI ) cycles after controlled ovarian hyperstimulation ( COH ) with GnRH antagonist or GnRH agonist ( GnRH-a ) in mild-to-moderate endometriosis and endometrioma . DESIGN Prospect i ve r and omize trial . SETTING A private IVF center . PATIENT(S ) A total of 246 ICSI cycles in 246 patients were divided into three groups : women with mild-to-moderate endometriosis ( n = 98 ) ; women who had ovarian surgery for endometrioma ( n = 81 ) ; women with endometrioma and no history of previous surgery ( n = 67 ) . INTERVENTION(S ) Patients in each group were r and omized to COH with either triptrolein or cetrorelix . MAIN OUTCOME MEASURE(S ) Clinical parameters , characteristics of COH , and ICSI results were analyzed . RESULT ( S ) Outcomes of COH with both GnRH antagonist and GnRH-a were similar in patients with mild-to-moderate endometriosis . Implantation rates were 15.9 % vs. 22.6 % and clinical pregnancy rates were 27.5 % vs. 39 % with GnRH antagonist and GnRH-a protocol s , respectively , in patients who had ovarian surgery for endometrioma . Implantation rates were 12.5 % vs. 14.8 % and clinical pregnancy rates were 20.5 % vs. 24.2 % with GnRH antagonist and GnRH-a protocol s , respectively , in patients with endometrioma and no history of ovarian surgery . CONCLUSION ( S ) Considering the implantation and clinical pregnancy rates , COH with both GnRH antagonist and GnRH-a protocol s may be equally effective in patients with mild-to-moderate endometriosis and endometrioma who did and did not undergo ovarian surgery The study was conducted to investigate the effect of conservative surgery of ovarian endometriomas before an ICSI cycle . Ninety-nine patients with endometriomas who were referred to an intracytoplasmic sperm injection ( ICSI ) cycle were enrolled in the study . The patients were prospect ively r and omized into two groups ; group I ( 49 patients ) underwent conservative ovarian surgery before the ICSI cycle and group II ( 50 patients ) underwent the ICSI cycle directly . The stimulation was started 3 months after the operation in group I and directly in group II . In the ovarian surgery group , stimulation was significantly longer ( 14.0 days in group I and 10.8 days in group II ; P = 0.001 ) , total recombinant FSH dose was significantly higher ( 4575 IU in group I and 3675 IU in group II ; P = 0.001 ) , and mean number of mature oocytes was significantly lower ( 7.8 in group I and 8.6 in group II ; P = 0.032 ) . There was no difference in terms of fertilization ( 86 % in group I and 88 % in group II ) , implantation ( 16.5 % in group I and 18.5 % in group II ) and pregnancy rates ( 34 % in group I and 38 % in group II ) . Ovarian surgery result ed in longer stimulation , higher FSH requirement and lower oocyte number , but fertilization , pregnancy and implantation rates did not differ between the groups |
2,449 | 25,265,259 | All currently used diagnostic strategies were cost-effective compared with no testing at current National Institute for Health and Care Excellence thresholds .
All the diagnostic pathways are a cost-effective use of NHS re sources .
The cost-effectiveness analyses suggest that CE CMR and revascularising everyone were the optimal strategies . | BACKGROUND Cardiac magnetic resonance imaging ( CMR ) is increasingly used to assess patients for myocardial viability prior to revascularisation .
This is important to ensure that only those likely to benefit are subjected to the risk of revascularisation .
OBJECTIVES To assess current evidence on the accuracy and cost-effectiveness of CMR to test patients prior to revascularisation in ischaemic cardiomyopathy ; to develop an economic model to assess cost-effectiveness for different imaging strategies ; and to identify areas for further primary research . | Background —Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation . It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium . Accordingly , the time courses of functional recovery in hibernating and stunned myocardium were compared . Methods and Results — Patients ( n=26 ) with ischemic cardiomyopathy undergoing surgical revascularization were studied ; regional perfusion ( resting 201Tl single-photon emission CT ) , glucose utilization ( 18F-2-deoxyglucose single-photon emission CT ) , and contractile function ( 2D echocardiography ) were assessed before revascularization . Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned , and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating . Contractile function was reevaluated 3 months ( early ) and 14 months ( late ) after revascularization . Of the 266 dysfunctional segments , 57 ( 22 % ) were stunned , 62 ( 23 % ) were hibernating , and 147 ( 55 % ) were scar tissue . In stunned myocardium , contractile function improved significantly at 3 months , without further improvement at 14 months ; 61 % of the stunned segments improved at 3 months , and 9 % improved at 14 months . In hibernating myocardium , contractile function improved at 3 months , with a further improvement at 14 months ; 31 % of the hibernating segments improved at 3 months , and 61 % showed ( additional ) recovery at 14 months . Conclusions —Stunned myocardium is likely to demonstrate early recovery of function , whereas hibernating myocardium may take a longer time to ( fully ) recover in function after revascularization Background —Low-dose dobutamine challenge ( DSMR ) by MRI was compared with delayed enhancement imaging with Gd-DTPA ( SCAR ) as a predictor of improvement of wall motion after revascularization ( RECOVERY ) . Methods and Results —In 29 patients with coronary artery disease ( 68±7 years of age , 2 women , 32±8 % ejection fraction ) , wall motion was evaluated semiquantitatively by MRI before and 3 months after revascularization . SCAR and DSMR were performed before revascularization . The transmural extent of scar was assessed semiquantitatively . Binary prediction of RECOVERY was performed by logistic regression in 288 segments with wall motion abnormalities at rest . Receiver operating characteristic – area under curve ( AUC ) statistics were used to compare different models . Low-dose DSMR ( AUC 0.838 ) was superior to SCAR ( AUC 0.728 ) in predicting RECOVERY . SCAR did not improve accuracy of prediction by DSMR . Subgroup analysis showed superiority of DSMR for 1 % to 74 % transmural extent of infa rct ion . Conclusions —Low-dose DSMR is superior to SCAR in predicting RECOVERY . This advantage is largest in segments with a delayed enhancement of 1 % to 74 % OBJECTIVES To assess the acceptability and feasibility of functional tests as a gateway to angiography for management of coronary artery disease ( CAD ) , the ability of diagnostic strategies to identify patients who should undergo revascularisation , patient outcomes in each diagnostic strategy , and the most cost-effective diagnostic strategy for patients with suspected or known CAD . DESIGN A rapid systematic review of economic evaluations of alternative diagnostic strategies for CAD was carried out . A pragmatic and generalisable r and omised controlled trial was undertaken to assess the use of the functional cardiac tests : angiography ( controls ) ; single photon emission computed tomography ( SPECT ) ; magnetic resonance imaging ( MRI ) ; stress echocardiography . SETTING The setting was Papworth Hospital NHS Foundation Trust , a tertiary cardiothoracic referral centre . PARTICIPANTS Patients with suspected or known CAD and an exercise test result that required non-urgent angiography . INTERVENTIONS Patients were r and omised to one of the four initial diagnostic tests . MAIN OUTCOME MEASURES Eighteen months post-r and omisation : exercise time ( modified Bruce protocol ) ; cost-effectiveness compared with angiography ( diagnosis , treatment and follow-up costs ) . The aim was to demonstrate equivalence in exercise time between those r and omised to functional tests and those r and omised to angiography [ defined as the confidence interval ( CI ) for mean difference from angiography within 1 minute ] . RESULTS The 898 patients were r and omised to angiography ( n = 222 ) , SPECT ( n = 224 ) , MRI ( n = 226 ) or stress echo ( n = 226 ) . Initial diagnostic tests were completed successfully with unequivocal results for 98 % of angiography , 94 % of SPECT ( p = 0.05 ) , 78 % of MRI ( p < 0.001 ) and 90 % of stress echocardiography patients ( p < 0.001 ) . Some 22 % of SPECT patients , 20 % of MRI patients and 25 % of stress echo patients were not subsequently referred for an angiogram . Positive functional tests were confirmed by positive angiography in 83 % of SPECT patients , 89 % of MRI patients and 84 % of stress echo patients . Negative functional tests were followed by positive angiograms in 31 % of SPECT patients , 52 % of MRI patients and 48 % of stress echo patients tested . The proportions that had coronary artery bypass graft surgery were 10 % ( angiography ) , 11 % ( MRI ) and 13 % ( SPECT and stress echo ) and percutaneous coronary intervention 25 % ( angiography ) , 18 % ( SPECT ) and 23 % ( MRI and stress echo ) . At 18 months , comparing SPECT and stress echo with angiography , a clinical ly significant difference in total exercise time can be ruled out . The MRI group had significantly shorter mean total exercise time of 35 seconds and the upper limit of the CI was 1.14 minutes less than in the angiography group , so a difference of at least 1 minute can not be ruled out . At 6 months post-treatment , SPECT and angiography had equivalent mean exercise time . Compared with angiography , the MRI and stress echo groups had significantly shorter mean total exercise time of 37 and 38 seconds , respectively , and the upper limit of both CIs was 1.16 minutes , so a difference of at least 1 minute can not be ruled out . The differences were mainly attributable to revascularised patients . There were significantly more non-fatal adverse events in the stress echo group , mostly admissions for chest pain , but no significant difference in the number of patients reporting events . Mean ( 95 % CI ) total additional costs over 18 months , compared with angiography , were 415 pounds ( -310 pounds to 1084 pounds ) for SPECT , 426 pounds ( -247 pounds to 1088 pounds ) for MRI and 821 pounds ( 10 pounds to 1715 pounds ) for stress echocardiography , with very little difference in quality -adjusted life-years ( QALYs ) amongst the groups ( less than 0.04 QALYs over 18 months ) . Cost-effectiveness was mainly influenced by test costs , clinicians ' willingness to trust negative functional tests and by a small number of patients who had a particularly difficult clinical course . CONCLUSIONS Between 20 and 25 % of patients can avoid invasive testing using functional testing as a gateway to angiography , without substantial effects on outcomes . The SPECT strategy was as useful as angiography in identifying patients who should undergo revascularisation and the additional cost was not significant , in fact it would be reduced further by restricting the rest test to patients who have a positive stress test . MRI had the largest number of test failures and , in this study , had the least practical use in screening patients with suspected CAD , although it had similar outcomes to stress echo and is still an evolving technology . Stress echo patients had a 10 % test failure rate , significantly shorter total exercise time and time to angina at 6 months post-treatment , and a greater number of adverse events , leading to significantly higher costs . Given the level of skill required for stress echo , it may be best to reserve this test for those who have a contraindication to SPECT and are unable or unwilling to have MRI . Further research , using blinded re assessment of functional test results and angiograms , is required to formally assess diagnostic accuracy . Longer-term cost-effectiveness analysis , and further studies of MRI and new generation computed tomography are also required Background Monitoring contrast medium wash-in kinetics in hyperemic myocardium by magnetic resonance ( MR ) allows for the detection of stenosed coronary arteries . In this prospect i ve study , the quality of a multislice MR approach with respect to the detection and sizing of compromised myocardium was determined and compared with positron emission tomography ( PET ) and quantitative coronary angiography . Methods and Results A total of 48 patients and 18 healthy subjects were studied by MR using a multislice hybrid echo-planar pulse sequence for monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine pentaacetic acid bismethylamide ( Omniscan ; 0.1 mmol/kg injected at 3 mL/s IV ) during hyperemia ( dipyridamole 0.56 mg/kg ) . Signal intensity upslope as a measure of myocardial perfusion was calculated in 32 sectors per heart from pixelwise parametric maps in the subendocardial layer and for full wall thickness . Before coronary angiography , coronary flow reserve ( hyperemia induced by dipyridamole 0.56 mg/kg ) was determined in corresponding sectors by 13N-ammonia PET . Receiver-operator characteristic analysis of subendocardial upslope data revealed a sensitivity and specificity of 91 % and 94 % , respectively , for the detection of coronary artery disease as defined by PET ( mean coronary flow reserve minus 2SD of controls ) and a sensitivity and specificity of 87 % and 85 % , respectively , in comparison with quantitative coronary angiography ( diameter stenosis ≥50 % ) . The number of pathological sectors per patient on PET and MR studies correlated linearly ( slope , 0.94;r = 0.76;P < 0.0001 ) . Conclusions The presented MR approach reliably identifies patients with coronary artery stenoses and provides information on the amount of compromised myocardium , even when perfusion abnormalities are confined to the subendocardial layer . This modality may qualify for its clinical application in the management of coronary artery disease Background — Although impairment in perfusion reserve is well recognized in hibernating myocardium , there is substantial controversy as to whether resting myocardial blood flow ( MBF ) is reduced in such circumstances . Quantitative first-pass cardiovascular magnetic resonance ( CMR ) perfusion imaging allows absolute quantification of MBF . We hypothesized that MBF assessed at rest by quantitative CMR perfusion imaging is reduced in hibernating myocardium . Methods and Results — Twenty-seven patients with 1 or 2-vessel coronary disease and at least 1 dysfunctional myocardial segment undergoing PCI were studied with preprocedure , early ( 24 hours ) , and late ( 9 months ) postprocedure CMR imaging . First-pass perfusion images at rest were acquired in 3 short-axis planes by use of a T1-weighted turboFLASH sequence . In each slice , MBF was determined for 8 myocardial segments in mL · min−1 · g−1 by deconvolution of signal intensity curves with an arterial input function measured in the left ventricular blood pool . Cine MRI for assessment of global and segmental function and delayed enhancement MRI for detection of viability were also obtained . All coronary lesions were 80 % to 95 % stenosis in severity . Over all segments , mean MBF normalized by rate-pressure product ( “ corrected MBF ” ) was 1.2±0.3 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 in segments without significant coronary stenosis and 0.7±0.2 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 in segments with coronary stenosis before PCI ( mixed model controlling for slice and segment z=−23.9 , P<0.001 ) . Early after the procedure , the MBF was 1.2±0.2 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 in revascularized segments and 1.3±0.2 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 in nondiseased segments ( z=−6.1 , P<0.001 ) . Late after PCI , the systolic wall thickening and end-diastolic wall thickness both increased significantly more ( both P<0.001 ) in the myocardial segments subtended by severe coronary stenosis ( 8±17 % to 40±19 % and 6.5±1.1 to 9.3±2 mm , respectively ) than in the myocardial segments supplied by nondiseased vessels . Mean MBF in dysfunctional segments with significantly improved contraction after revascularization was 0.8±0.2 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 before PCI and 1.2±0.2 mL · min−1 · g−1 · ( mm Hg · bpm/104)−1 after PCI ( z=2.0 , P=0.04 ) . Conclusions — CMR perfusion imaging detects impaired resting MBF in hibernating myocardial segments Background —This study was design ed to define myocardial viability and establish practical cut-off values for differentiating normal myocardial tissue from subendocardial and transmural scar tissue by using electromechanical mapping ( EMM ) . We vali date d our results by delayed-enhancement cardiac MRI ( DE-MRI ) . Methods and Results —We prospect ively studied 15 ambulatory patients with stable coronary disease who were c and i date s for cardiac catheterization . Within 48 hours of EMM , DE-MRI was performed . Using EMM software , we created a bull ’s eye precisely matched to that generated by DE-MRI . Segment by segment , we compared the MRI results to the corresponding unipolar voltage value for that same segment in the EMM bull ’s eye . Of 300 total segments , 275 were compared . The segments were divided into normal ( n=211 ) , subendocardial scar ( n=49 ) , and transmural scar ( n=15 ) . We found that subendocardial ( 6.8±2.9 mV ) and transmural ( 4.6±1.9 mV ) scar segments had significantly less unipolar voltage than normal ( 11.6±4.5 mV ) segments ( P < 0.05 for each comparison ) . When normal myocardium was compared with myocardium with subendocardial scar , the threshold for differentiating between the two areas was 7.9 mV ( sensitivity , 80 % ; specificity , 80 % ) . Comparison of normal tissue to transmural scar yielded a threshold of 6.9 mV ( sensitivity , 93 % ; specificity , 88 % ) . Conclusions —Our results demonstrate that normal myocardium can be accurately distinguished from myocardium with subendocardial or transmural infa rcts on the basis of unipolar voltage values obtained through EMM . This is the first study to vali date these results by using cardiac DE-MRI in humans BACKGROUND The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting ( CABG ) will provide a survival benefit . However , the efficacy of this approach is uncertain . METHODS In a sub study of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a r and omized trial of medical therapy with or without CABG , we used single-photon-emission computed tomography ( SPECT ) , dobutamine echocardiography , or both to assess myocardial viability on the basis of prespecified thresholds . RESULTS Among the 1212 patients enrolled in the r and omized trial , 601 underwent assessment of myocardial viability . Of these patients , we r and omly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone . A total of 178 of 487 patients with viable myocardium ( 37 % ) and 58 of 114 patients without viable myocardium ( 51 % ) died ( hazard ratio for death among patients with viable myocardium , 0.64 ; 95 % confidence interval [ CI ] , 0.48 to 0.86 ; P=0.003 ) . However , after adjustment for other baseline variables , this association with mortality was not significant ( P=0.21 ) . There was no significant interaction between viability status and treatment assignment with respect to mortality ( P=0.53 ) . CONCLUSIONS The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction , but this relationship was not significant after adjustment for other baseline variables . The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG , as compared with medical therapy alone . ( Funded by the National Heart , Lung , and Blood Institute ; STICH Clinical Trials.gov number , NCT00023595 . ) Abstract . Acceptance of technetium-99 m sestamibi as a tracer of myocardial viability is growing , particularly when nitrate-enhanced imaging is used . However , few data are available on the ability of 99mTc-sestamibi to predict the evolution of global left ventricular ejection fraction ( EF ) . The aim of this study was to examine the ability of resting and nitrate 99mTc-sestamibi single-photon emission tomography ( SPET ) to predict EF changes after revascularisation in patients who have chronic coronary artery disease with left ventricular dysfunction . Using baseline resting and nitrate 99mTc-sestamibi SPET , we studied 61 patients scheduled for revascularisation because of left ventricular dysfunction . EF was estimated using two-dimensional echocardiography before and after the intervention . A post-revascularisation improvement of ≥5 EF units was defined as significant . Using a 13-segment model , 99mTc-sestamibi activity was quantified and the nitrate-induced activity changes calculated . Three different criteria for detecting viability ( defined as post-revascularisation reversible dysfunction ) in asynergic segments were compared : ( 1 ) resting 99mTc-sestamibi activity ≥60 % ; ( 2 ) nitrate 99mTc-sestamibi activity ≥65 % ; and ( 3 ) nitrate-induced increase > + 10 % or nitrate-induced increase ≤+10 % and nitrate activity ≥65 % . EF increased significantly in 32 patients . The number of viable asynergic segments was significantly higher in these patients than in the remaining 29 subjects , and the difference was greater ( P<0.0002 ) using definition ( 3 ) than using either baseline ( P<0.002 ) or nitrate activity ( P<0.0005 ) . There was a significant relationship between EF changes and number of viable asynergic segments : Spearman R=0.38 , P<0.005 using baseline ; Spearman R=0.39 , P<0.002 using nitrate activity ; and Spearman R=0.55 , P<0.000005 using definition ( 3 ) . According to receiver operating characteristic ( ROC ) curve analysis , this last criterion achieved the best results ( 81 % sensitivity , 69 % specificity and 75 % accuracy ) , with an area under the ROC curve of 0.838 ; this area was significantly larger than when using either baseline ( 0.744 , P<0.02 ) or nitrate activity ( 0.747 , P<0.005 ) . 99mTc-sestamibi SPET appears able to predict the evolution of global left ventricular EF after revascularisation , thereby confirming the value of 99mTc-sestamibi as a tracer of myocardial viability . The combination of baseline resting and nitrate imaging seems to significantly improve the diagnostic accuracy of 99mTc-sestamibi SPET for this particular purpose Background —Despite the accepted utility of delayed-enhancement MRI in identifying irreversible myocardial injury , no study has yet assessed its role as a viability tool exclusively in the setting of coronary artery bypass surgery ( CABG ) , and no study has repeated delayed-enhancement MRI late after revascularization . In a clinical trial in which patients underwent CABG by either the off-pump or on-pump surgical technique , we hypothesized that ( 1 ) preoperative delayed-enhancement MRI would have high diagnostic accuracy in predicting viability and ( 2 ) the occurrence of perioperative myocardial necrosis would affect late regional wall motion recovery . Methods and Results —Fifty-two patients undergoing multivessel CABG were studied by preoperative and early ( day 6 ) and late ( 6 months ) postoperative cine MRI for global and regional functional assessment and delayed-enhancement MRI for assessment of irreversible myocardial injury . Preoperatively , 611 segments ( 21 % ) had abnormal regional function , whereas 421 segments ( 14 % ) showed evidence of hyperenhancement . At 6 months after revascularization , 57 % ( 343 of 611 ) of dysfunctional segments improved contraction by at least 1 grade . When all preoperative dysfunctional segments were analyzed , there was a strong correlation between the transmural extent of hyperenhancement and the recovery in regional function at 6 months ( P<0.001 ) . Of a total of 96 previously dysfunctional but nonenhancing or minimally hyperenhancing myocardial segments that did not improve regional function at 6 months , 35 ( 36 % ) demonstrated new perioperative hyperenhancement in the early postoperative MRI scan . Conclusions —Delayed-enhancement MRI is a powerful predictor of myocardial viability after surgery , suggesting an important role for this technique in clinical viability assessment Background —Recent studies indicate that MRI , after administration of gadolinium-diethylenetriamine pentaacetic acid , can identify nonviable areas in dysfunctional myocardium . We compared MRI hyperenhancement with PET as a gold st and ard for detection and quantification of myocardial scar tissue . Methods and Results —Thirty-one patients with ischemic heart failure ( ejection fraction , 28±9 % ) were imaged with PET and MRI . Scar was defined as regionally increased MRI signal intensity 20 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid and as concordantly reduced perfusion and glucose metabolism as defined by PET . Sensitivity and specificity of MRI in identifying patients and segments ( n=1023 ) with matched flow/metabolism defects was 0.96 of 1.0 and 0.86 of 0.94 , respectively . Eleven percent of segments defined as viable by PET showed some degree of MRI hyperenhancement . Defect severity score based on visual analysis was 44.3±9.1 for PET and 47.6±11.1 for MRI ( r = 0.91 , P < 0.0001 ) . Quantitatively assessed relative MRI infa rct mass correlated well with PET infa rct size ( r = 0.81 , P < 0.0001 ) . Furthermore , MRI hyperenhancement was a better predictor of scar tissue than end-diastolic and end-systolic wall thickness or thickening . Conclusions —In severe ischemic heart failure , MRI hyperenhancement as a marker of myocardial scar closely agrees with PET data . Although hyperenhancement correlated with areas of decreased flow and metabolism , it seems to identify scar tissue more frequently than PET , reflecting the higher spatial resolution . Additional functional studies after revascularization are required to define the significance of small isl and s of scar detected by MRI OBJECTIVES We sought to evaluate the usefulness of a comprehensive assessment of four cardiovascular magnetic resonance imaging (CMR)-derived myocardial viability indexes in the setting of myocardial stunning . BACKGROUND Cardiovascular magnetic resonance imaging allows the simultaneous assessment of several viability indexes . METHODS We studied 40 patients with a first ST-segment elevation myocardial infa rct ion ( MI ) and an open infa rct -related artery . At the first week , using CMR , wall motion ( WM ) , and four viability indexes were determined : wall thickness , WM improvement with low-dose dobutamine , perfusion , and transmural extent of necrosis . We created a comprehensive score based on the presence and the relative power of these viability indexes for predicting normal WM at the sixth month . RESULTS Of 153 dysfunctional segments at the first week , 59 ( 39 % ) exhibited normal WM at the sixth month . According to the odds ratio of viability indexes for predicting normal WM , we developed a five-level predictive score . The proportions of segments showing normal WM at sixth month were as follows ; Level 1 ( 0 indexes ) : 0 of 13 ( 0 % ) ; Level 2 ( normal thickness and /or perfusion ) : 14 of 82 ( 17 % ) ; Level 3 ( dobutamine response ) : 5 of 11 ( 45 % ) ; Level 4 ( non-transmural necrosis ) : 20 of 26 ( 77 % ) ; Level 5 ( non-transmural necrosis and dobutamine response ) : 20 of 21 ( 95 % ) , p < 0.0001 for the trend . These proportions were similar in a matched prospect i ve validation group comprising 16 patients ( 0 % , 18 % , 62 % , 77 % , and 90 % for levels 1 to 5 , respectively , p < 0.0001 for the trend ) . CONCLUSIONS A comprehensive analysis of the four more widely used CMR-derived viability indexes is useful for predicting late systolic function after myocardial infa rct ion Background : There are many factors which influence regional left ventricular wall thickening ( WT ) in ischemic heart disease ( IHD ) . We used magnetic resonance imaging ( MRI ) to explore , in patients with chronic ischemic heart disease ( CIHD ) , how regional WT is affected by both infa rct transmurality ( IT ) and the function of adjacent segments . We also compared these findings with a group of healthy volunteers ( controls ) Background —In some patients with heart failure , & bgr;-blockers can improve left ventricular ( LV ) function and reduce morbidity and mortality . We hypothesized that gadolinium-enhanced cardiovascular magnetic resonance imaging ( CMR ) can predict reversible myocardial dysfunction and remodeling in heart failure patients treated with & bgr;-blockers . Methods and Results —Forty-five patients with chronic heart failure underwent CMR . Contrast imaging using gadolinium was performed to obtain high-resolution spatial maps of myocardial scarring and viability . Cine imaging was performed to assess LV function and morphology and was repeated in 35 patients after 6 months of & bgr;-blockade . Gadolinium CMR demonstrated scarring in 30 of 45 patients ( 67 % ) . Scarring was found in 100 % of patients with ischemic cardiomyopathy ( 28 of 28 ) but in only 12 % with nonischemic cardiomyopathy ( 2 of 17 ) . In the 35 patients who were maintained on & bgr;-blockers and had a second study , there was an inverse relation between the extent of scarring at baseline and the likelihood of contractile improvement 6 months later ( P < 0.001 ) . For instance , contractility improved in 56 % ( 674 of 1207 ) of regions with no scarring but in only 3 % with > 75 % scarring ( 8 of 232 ) . Multivariate analysis showed that the amount of dysfunctional but viable myocardium by CMR was an independent predictor of the change in ejection fraction ( P = 0.01 ) , mean wall motion score ( P = 0.0007 ) , LV end-diastolic volume index ( P = 0.007 ) , and LV end-systolic volume index ( P ≤0.0001 ) . Conclusions —For heart failure patients treated with & bgr;-blockers , gadolinium-enhanced CMR predicts the response in LV function and remodeling OBJECTIVE Assessment of myocardial viability in akinetic areas is essential in surgery for ischemic heart disease , including coronary artery bypass grafting and left ventriculoplasty . The aim of this study is to evaluate the utility of quantitative indices of perfusion uptake , wall motion , and wall thickening of each region calculated by quantitative electrocardiogram-gated single photon emission computed tomography ( SPECT ) for prediction of functional recovery after coronary artery bypass grafting . METHODS Forty patients scheduled for coronary artery bypass grafting were prospect ively included . Electrocardiogram-gated SPECT was performed before and 1 week and 3 months after operation , and coronary angiography was performed before and after operation . The myocardium was divided into 9 segments and myocardial viability , assessed by improvement of the wall motion score using a cine mode display , and evaluated by radionuclide criteria ( perfusion uptake , wall motion , wall thickening ) . Twenty-four segments with moderate hypokinesis and 14 segments with akinesis with patent grafts were assessed . RESULTS All segments with moderate hypokinesis except 1 ( 96 % ) had improved wall motion scores postoperatively , whereas of 14 segments with akinesis only 7 segments ( 50 % ) had improved wall motion scores . The preoperative perfusion uptake in the improved segments was significantly higher than in the nonimproved segments ( 62.7 % + /- 15.6 % vs 46.4 % + /- 24.5 % , P = .01 ) . There was a significant difference in wall motion between the improved and nonimproved segments ( 3.8 + /- 2.2 mm vs 1.4 + /- 1.4 mm , P = .001 ) , and the preoperative wall thickening of the improved segments was significantly higher than in the nonimproved segments ( 27.2 % + /- 14.1 % vs 8.2 % + /- 10.3 % , P < .0001 ) . The optimal cutoff level of perfusion uptake was 50 % , with the highest accuracy of 72 % , and the optimal cutoff levels of wall thickening and wall motion were 10 % and 1.5 mm , with the highest accuracies of 76 % and 85 % , respectively . CONCLUSION The regional functional index calculated by electrocardiogram-gated SPECT indicated that wall thickening was well correlated with functional recovery compared with wall motion or perfusion uptake . This suggests that the wall thickening calculated by electrocardiogram-gated SPECT may be more useful to predict functional recovery than regional myocardial perfusion . Or , it could suggest that in addition to perfusion uptake , wall thickening could enhance the objective assessment of myocardial viability Background Reperfusion strategies salvage myocardium at risk in acute myocardial infa rct ion ( MI ) . This clinical study was performed to determine whether areas without evidence of delayed MRI contrast enhancement in MI correspond to viability by means of percent systolic wall thickening ( % SWT ) and enddiastolic wall thickness ( EDWT ) in chronic infa rct ion . Methods Twenty MRI studies were performed in ten patients within 6 days of MI and 3 months post-MI . On a segmental basis the percentage of viable myocardium as defined by contrast-enhanced MRI ( no delayed MRI contrast enhancement ) in acute MI was measured and was compared with % SWT and EDWT in chronic MI . Results Of the 1718 segments in acute infa rct ion in which the percentage of viable myocardium was measured 1333 were found to be completely viable by means of contrast-enhanced MRI ( no delayed MRI contrast enhancement ) . All of these segments revealed % SWT on day 90 post-MI , and 97 % of segments were viable by means of an EDWT of more than 5.5 mm . In 85 segments the proportion of viable myocardium was 50–99 % ( mean 56±8 % ) , with 92 % segments found to be viable by means of % SWT and 92 % by EDWT , and of 156 segments with viable myocardium between 1–49 % ( 36±8 % ) 79 % were found to be viable by means of % SWT and 82 % by EDWT . Corresponding proportions of 144 segments with transmural delayed MRI contrast enhancement in acute MI were 45 % and 17 % . Conclusions In acute reperfused MI viable myocardium as delineated by contrast-enhanced MRI is correlated with clinical parameters of viability . Delayed MRI contrast enhancement resolves nontransmural MI and may become a valuable clinical tool when planning revascularization procedures UNLABELLED The goal of this study was to vali date the accuracy of the Emory Cardiac Tool Box ( ECTB ) in assessing left ventricular end-diastolic or end-systolic volume ( EDV , ESV ) and ejection fraction ( LVEF ) from gated (99m)Tc-methoxyisobutylisonitrile ( (99m)Tc-MIBI ) SPECT using cardiac MRI ( cMRI ) as a reference . Furthermore , software-specific characteristics of ECTB were analyzed in comparison with 4D-MSPECT and Quantitative Gated SPECT ( QGS ) results ( all relative to cMRI ) . METHODS Seventy patients with suspected or known coronary artery disease were examined using gated (99m)Tc-MIBI SPECT ( 8 gates/cardiac cycle ) 60 min after tracer injection at rest . EDV , ESV , and LVEF were calculated from gated (99m)Tc-MIBI SPECT using ECTB , 4D-MSPECT , and QGS . Directly before or after gated SPECT , cMRI ( 20 gates/cardiac cycle ) was performed as a reference . EDV , ESV , and LVEF were calculated using Simpson 's rule . RESULTS Correlation between results of gated (99m)Tc-MIBI SPECT and cMRI was high for EDV ( R = 0.90 [ ECTB ] , R = 0.88 [ 4D-MSPECT ] , R = 0.92 [ QGS ] ) , ESV ( R = 0.94 [ ECTB ] , R = 0.96 [ 4D-MSPECT ] , R = 0.96 [ QGS ] ) , and LVEF ( R = 0.85 [ ECTB ] , R = 0.87 [ 4D-MSPECT ] , R = 0.89 [ QGS ] ) . EDV ( ECTB ) did not differ significantly from cMRI , whereas 4D-MSPECT and QGS underestimated EDV significantly compared with cMRI ( mean + /- SD : 131 + /- 43 mL [ ECTB ] , 127 + /- 42 mL [ 4D-MSPECT ] , 120 + /- 38 mL [ QGS ] , 137 + /- 36 mL [ cMRI ] ) . For ESV , only ECTB yielded values that were significantly lower than cMRI . For LVEF , ECTB and 4D-MSPECT values did not differ significantly from cMRI , whereas QGS values were significantly lower than cMRI ( mean + /- SD : 62.7 % + /- 13.7 % [ ECTB ] , 59.0 % + /- 12.7 % [ 4DM-SPECT ] , 53.2 % + /- 11.5 % [ QGS ] , 60.6 % + /- 13.9 % [ cMRI ] ) . CONCLUSION EDV , ESV , and LVEF as determined by ECTB , 4D-MSPECT , and QGS from gated (99m)Tc-MIBI SPECT agree over a wide range of clinical ly relevant values with cMRI . Nevertheless , any algorithm-inherent over- or underestimation of volumes and LVEF should be accounted for and an interchangeable use of different software packages should be avoided OBJECTIVES We sought to characterize the clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy . BACKGROUND Patients with ischemic cardiomyopathy may have a worse prognosis than patients with nonischemic cardiomyopathy . Few studies have assessed the effect of ischemic versus nonischemic etiology on outcomes . METHODS We analyzed prospect ively collected data on 3,787 patients with a left ventricular ejection fraction < or = 40 % who underwent coronary angiography . Patients were considered to have ischemic cardiomyopathy ( n = 3,112 ) if they had a history of myocardial infa rct ion , percutaneous transluminal coronary angioplasty , coronary artery bypass graft surgery or at least one major epicardial coronary artery with > or = 75 % stenosis ; all others were considered to have nonischemic cardiomyopathy ( n = 675 ) . RESULTS The median age , ejection fraction and proportion of patients with New York Heart Association functional class III or IV symptoms for the nonischemic and ischemic groups were 55 years versus 63 years , 27 % versus 32 % and 57 % versus 25 % , respectively . After adjustment for baseline clinical risk factors and presenting characteristics , ischemic etiology remained an important independent predictor of 5-year mortality ( p < 0.0001 ) . The extent of coronary artery disease was a better predictor of survival than ischemic or nonischemic etiology ( log likelihood chi-square 700 vs. 675 , respectively ) . CONCLUSIONS Ischemic etiology is a significant independent predictor of mortality in patients with cardiomyopathy . However , the extent of coronary artery disease contributes more prognostic information than the clinical diagnosis of ischemic or nonischemic cardiomyopathy . Further research is needed to refine the clinical definition of ischemic cardiomyopathy so that physicians can appropriately prescribe treatment and accurately predict outcome Previous studies have demonstrated that myocardial perfusion imaging using 99mTc-tetrofosmin at rest allows viability assessment similar to that obtained with 201Tl imaging and 18F-fluorodeoxyglucose positron emission tomography ( 18F-FDG PET ) . The simultaneous assessment of perfusion and regional function is now available by quantitative gated myocardial perfusion single-photon emission computed tomography ( SPECT ) . This study was design ed to evaluate the utility of quantitative values of wall motion and wall thickening , calculated by quantitative gated myocardial perfusion SPECT , for the prediction of functional recovery after coronary bypass grafting ( CABG ) . Fifty-six patients with coronary artery disease scheduled for CABG were included prospect ively . All patients underwent 99mTc-tetrofosmin gated SPECT imaging at rest preoperatively and 3 months after CABG . The myocardium was divided into nine segments and the average quantitative values of regional perfusion ( percentage uptake ) ( % ) , wall motion ( mm ) and wall thickening ( % ) were determined automatically using quantitative gated SPECT ( QGS ) software . The wall motion score was defined visually using a four-point scale ( 0 , normal ; 3 , akinesis ) , and segments with severe asynergy ( score of 2 or 3 ) with patent grafts were assessed . Of 77 segments with severe asynergy , 56 segments showed improved wall motion and 21 segments did not improve after CABG . The area under the receiver operating characteristic curve of wall thickening for the prediction of functional recovery was significantly higher ( 0.92 ) than that of the percentage uptake ( 0.77 , P<0.017 ) or wall motion ( 0.60 , P<0.0001 ) . When each analysis used the optimal threshold , the wall thickening analysis ( ⩾10 % ) had a sensitivity of 95 % and a specificity of 81 % . These values tended to be higher than those of the percentage uptake ( sensitivity , 86 % ; specificity , 67 % ) . The wall motion analysis ( ⩾1.5 mm ) had a significantly lower sensitivity of 75 % and specificity of 43 % than the wall thickening analysis ( P = 0.0038 and P = 0.011 , respectively ) . The results indicate that wall thickening , calculated by QGS software , may be more useful than regional perfusion or wall motion analysis for the prediction of functional recovery after CABG . The areas of asynergy with relatively preserved wall thickening may have the potential for improved function despite severely decreased perfusion BACKGROUND Regional abnormalities in myocardial systolic function can be detected with myocardial strain measurements derived from Doppler tissue echocardiography . We studied longitudinal strain measurements in patients with evidence of myocardial infa rct ion by cardiac magnetic resonance imaging to determine whether end-systolic strain could identify the severity of the infa rct ion . METHODS A total of 20 patients with chronic myocardial infa rct ions and 10 healthy volunteers underwent 2-dimensional echocardiography and cardiac magnetic resonance with delayed gadolinium ( Gd ) gadopentetate dimeglumine ( DTPA ) contrast hyperenhancement . Delayed Gd hyperenhancement was grade d using the following scale : 0 = none , 1 = less than 25 % , 2 = 26 % to 50 % , 3 = 51 % to 75 % , and 4 = greater than 75 % . RESULTS There was a progressive decrease in peak systolic strain in the infa rct segments as the transmural extent of infa rct ion increased . When compared with the peak systolic strain in remote segments without evidence of infa rct ion ( -19.7 + /- 0.9 ) , the strain was significantly lower in segments with greater than 25 % Gd hyperenhancement ( grade 2 , -14.8 + /- 1.1 , P = .001 ; grade 3 , -12.9 + /- 2.1 , P = .001 ; grade 4 , -9.1 + /- 2.0 , P < .001 ) . CONCLUSIONS In patients with chronic myocardial infa rct ions , strain measurements with echocardiography show a grade d response of decreasing regional strain in segments with increasing transmural extent of infa rct ion defined by Gd hyperenhancement Patients with ischemic heart disease and depressed left ventricular ( LV ) ejection fraction ( LVEF ) develop varying degrees of LV remodeling after cardiac surgical revascularization . Fifty-three patients with stable ischemic heart disease and impaired LV function ( LVEF 34.9 ± 4 % ) were prospect ively followed up for 24 months . Thirty-seven patients underwent coronary artery bypass grafting ( CABG ) , 16 patients were treated conservatively . Cardiac magnetic resonance imaging ( MRI ) and SPECT were performed at baseline and after 12 and 24 months of follow-up . The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up ( > 5%—responders ) . MRI with ≤5 segments with DE/wall thickness ratio ( DEWTR ) ≥50 % predicted LV reverse remodeling with a sensitivity of 86 % and a specificity of 75 % ( AUC 0.81 ) . An MRI finding of ≤2 segments with the DEWTR ≥75 % had a corresponding sensitivity of 71 % and specificity of 67 % ( AUC 0.75 ) while fixed perfusion defect on SPECT < 16.5 % of LV predicted reverse remodeling with a sensitivity of 64 % and a specificity of 69 % ( AUC 0.64 ) . A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75 % obtained by MRI , was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT . No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG Background Positron emission tomography ( PET ) with inhaled oxygen 15-labeled carbon monoxide ( CO ) is used as a marker of myocardial blood pool . Only a limited number of studies with small numbers of patients have reported on the assessment of left ventricular ( LV ) volumes by use of O-15-labeled CO . The aim of this study was to compare LV volumes and function as measured by routinely acquired blood pool images by use of gated O-15-labeled CO PET with the reference technique , cardiovascular magnetic resonance imaging ( MRI ) . Methods and Results Thirty-four subjects with a varying degree of LV function were studied . LV end-diastolic volume ( LVEDV ) , LV end-systolic volume ( LVESV ) , and LV ejection fraction ( LVEF ) were determined by both MRI and gated PET by use of O-15-labeled CO . Volumes were comparable with respect to LVEDV ( 196 ± 83 and 192 ± 91 mL , respectively ; P ± not significant ) . LVESV , however , was slightly overestimated by PET ( 119 ± 85 and 136 ± 94 mL , respectively ; P < .05 ) , result ing in a significant underestimation of LVEF ( 44 % ± 19 % and 35 % ± 18 % , respectively ; P < .05 ) . Observed correlations for LVEDV , LVESV , and LVEF were 0.90 , 0.96 , and 0.86 , respectively ( all P < .01 ) . Conclusions Gated O-15-labeled CO PET measurements of LVEDV , LVESV , and LVEF show good correlation with MRI over a wide range of LV volumes during routinely acquired blood pool images . LVEF , however , may be underestimated compared with MRI OBJECTIVES The rationale and design of the Surgical Treatment for Ischemic Heart Failure trial is described . Before the Surgical Treatment for Ischemic Heart Failure trial , less than 1000 patients with ischemic cardiomyopathy had been studied in r and omized comparisons of medical therapy versus coronary artery bypass grafting . Trial data reflect how these therapies were delivered more than 20 years ago and do not indicate the relative benefits of medical therapy versus coronary artery bypass grafting in contemporary practice . METHODS R and omization of consenting patients with heart failure , left ventricular ejection fraction of 0.35 or less , and coronary artery disease is based on whether patients are judged by attending physicians to be c and i date s only for coronary artery bypass grafting or can be treated with medical therapy without coronary artery bypass grafting . Patients eligible for surgical ventricular reconstruction because of significant anterior wall akinesis or dyskinesis but ineligible for medical therapy are r and omly assigned to coronary artery bypass grafting with or without surgical ventricular reconstruction . Patients eligible for medical therapy are r and omly assigned between medical therapy only and medical therapy with coronary artery bypass grafting . Patients eligible for all 3 are r and omly assigned evenly to medical therapy only , medical therapy and coronary artery bypass grafting , or medical therapy and coronary artery bypass grafting and surgical ventricular reconstruction . Major sub studies will examine quality of life , cost-effectiveness , changes in left ventricular volumes , effect of myocardial viability , selected biomarkers , and selected polymorphisms on treatment differences . RESULTS Enrollment is now complete in both STICH hypotheses . Follow-up will continue until sufficient end points are available to address both hypotheses with at least 90 % power . The primary outcome of hypothesis 2 is expected to be reported in 2009 . The primary outcome of hypothesis 1 is expected to be reported in 2011 . CONCLUSIONS The Surgical Treatment for Ischemic Heart Failure trial is a National Heart , Lung , and Blood Institute-funded multicenter international r and omized trial addressing 2 specific primary hypotheses : ( 1 ) coronary artery bypass grafting with intensive medical therapy improves long-term survival compared with survival with medical therapy alone , and ( 2 ) in patients with anterior left ventricular dysfunction , surgical ventricular reconstruction to a more normal left ventricular size plus coronary artery bypass grafting improves survival free of subsequent hospitalization for cardiac cause when compared with that with coronary artery bypass grafting alone OBJECTIVES This study evaluated the predictive value of myocardial deformation imaging for improvement in cardiac function after revascularization therapy in comparison with contrast-enhanced cardiac magnetic resonance imaging ( ceMRI ) . BACKGROUND Myocardial deformation imaging allows analysis of myocardial viability in ischemic left ventricular dysfunction . METHODS In 53 patients with ischemic left ventricular dysfunction , myocardial viability was assessed using pixel-tracking-derived myocardial deformation imaging and ceMRI to predict recovery of function at 9 + /- 2 months follow-up . For each left ventricular segment in a 16-segment model , peak systolic radial strain was determined from parasternal 2-dimensional echocardiographic views using an automatic frame-by-frame tracking system of natural acoustic echocardiographic markers ( EchoPAC , GE Ultrasound , Horton , Norway ) , and the relative extent of hyperenhancement using ceMRI . RESULTS Of 463 segments with abnormal baseline function , 227 showed regional recovery . Compared with segments showing functional improvement , those that failed to recover had lower peak radial strain ( 15.2 + /- 7.5 % vs. 22.6 + /- 6.3 % ; p < 0.001 ) and a greater extent of hyperenhancement ( 56 + /- 29 % vs. 14 + /- 17 % ; p < 0.001 ) . Using a cutoff of 17.2 % for peak systolic radial strain , functional recovery could be predicted with high accuracy ( sensitivity 70.2 % , specificity 85.1 % , area under the curve 0.859 , 95 % confidence interval 0.825 to 0.893 ) . The predictive value was similar to that of hyperenhancement by ceMRI ( sensitivity 71.6 % , specificity 92.1 % , area under the curve 0.874 , 95 % confidence interval 0.840 to 0.901 , at a cutoff of 43 % hyperenhancement ) . CONCLUSIONS Myocardial deformation imaging based on frame-to-frame tracking of acoustic markers in 2-dimensional echocardiographic images is a powerful novel modality to identify reversible myocardial dysfunction The REvascularization in Ischemic HEart Failure Trial ( REHEAT ) is a nonr and omized , case-controlled , prospect i ve study assessing the hypothesis that surgical and percutaneous revascularizations in patients with ischemic cardiomyopathy are associated with comparable improvement in left ventricular ejection fraction ( LVEF ) and functional status 12 months after myocardial revascularization . The study population consisted of 141 patients with LVEFs of < 40 % and angiographically confirmed coronary artery disease . The primary end point was improvement in LVEF 12 months after intervention . Secondary end points were in-hospital major adverse events , length of hospitalization , exercise tolerance of treadmill stress testing after 12 months , 1-year survival , 1-year event-free survival , angina , and heart failure severity after 12 months . The case-controlled study included 55 patients who underwent percutaneous coronary intervention ( PCI ) and 54 who underwent coronary artery bypass grafting ( CABG ) . The incidence of 30-day major adverse events was higher in the CABG group ( 40.7 % vs 9 % , p = 0.0003 ) , whereas duration of hospital stay was shorter in the PCI group ( 6.8 + /- 3.6 vs 9.2 + /- 2.1 days , p = 0.00001 ) . Increase in LVEF was comparable after PCI and CABG ( 6.0 + /- 7.2 % vs 4.4 + /- 9.0 % p = 0.12 ) . Long-term functional status based on treadmill stress testing was better after PCI ( Student 's t test , p = 0.0003 ) but , according to Canadian Cardiovascular Society and New York Heart Association classifications , was similar in the 2 treatment arms ( Wilcoxon test , p < 0.01 ) . Long-term survival was significantly better for patients after PCI ( Wilcoxon test , p < 0.01 ) ; however , major adverse event-free survival was better after CABG ( Cox-Mantel test , p = 0.0013 ) . In conclusion , PCI and CABG are associated with comparable improvements in LVEF in patients with ischemic cardiomyopathy . PCI offers a better 1-year survival rate than CABG , but the incidence of repeat revascularization is lower with CABG The aim of this study was to analyse the influence of rest technetium-99m-methoxy-isobutyl-isonitrile ( 99mTc-MIBI ) uptake , left ventricular ejection fraction ( EF ) and dysfunctional location in the prediction of myocardial viability . Rest 99mTc-MIBI single photon emission computed tomography ( SPECT ) was analysed in 82 patients ( 59±9 years , 70 men , 12 women ) with one or more segments showing severe hypokinesia , akinesia or dyskinesia who had undergone coronary revascularization . Before and within 3 - 6 months after the revascularization , gated blood pool scintigraphy was performed . In the post-revascularization control , contractile recovery was observed in 48.7 % ( 155/318 ) of the segments with severe hypokinesia , akinesia or dyskinesia . Significant increases in sensitivity ( 53 % , 72 % and 91 % , P<0.0001 ) and negative predictive value ( 62 % , 68 % and 79 % , P = 0.01 ) were observed with decreasing rest uptake 99mTc-MIBI levels of 50 % , 40 % and 30 % , respectively . The decrease in specificity was also significant ( 67 % , 53 % and 32 % , P<0.0001 ) . The negative predictive value was higher than the positive predictive value mainly in patients with EF⩽0.35 and with anterior dysfunction . In logistic regression analysis , uptake levels and EF were independent variables that influenced sensitivity and specificity . The negative predictive value was influenced by EF and the positive predictive value only by dysfunctional location . This study suggests that the negative predictive value of 99mTc-MIBI SPECT is higher than the positive predictive value , mainly in patients with EF⩽0.35 , and that the rest uptake level , EF and dysfunctional location are factors that must be considered when results of 99mTc-MIBI SPECT are analysed OBJECTIVES We conducted a r and omized trial to assess the effectiveness of F-18-fluorodeoxyglucose ( FDG ) positron emission tomography (PET)-assisted management in patients with severe ventricular dysfunction and suspected coronary disease . BACKGROUND Such patients may benefit from revascularization , but have significant perioperative morbidity and mortality . F-18-fluorodeoxyglucose PET can detect viable myocardium that might recover after revascularization . METHODS Included were patients with severe left ventricular ( LV ) dysfunction and suspected coronary disease being considered for revascularization , heart failure , or transplantation work-ups or in whom PET was considered potentially useful . Patients were stratified according to recent angiography or not , then r and omized to management assisted by FDG PET ( n = 218 ) or st and ard care ( n = 212 ) . The primary outcome was the composite of cardiac death , myocardial infa rct ion , or recurrent hospital stay for cardiac cause , within 1 year . RESULTS At 1 year , the cumulative proportion of patients who had experienced the composite event was 30 % ( PET arm ) versus 36 % ( st and ard arm ) ( relative risk 0.82 , 95 % confidence interval [ CI ] 0.59 to 1.14 ; p = 0.16 ) . The hazard ratio ( HR ) for the composite outcome , PET versus st and ard care , was 0.78 ( 95 % CI 0.58 to 1.1 ; p = 0.15 ) ; for patients that adhered to PET recommendations for revascularization , revascularization work-up , or neither , HR = 0.62 ( 95 % CI 0.42 to 0.93 ; p = 0.019 ) ; in those without recent angiography , for cardiac death , HR = 0.4 ( 95 % CI 0.17 to 0.96 ; p = 0.035 ) . CONCLUSIONS This study did not demonstrate a significant reduction in cardiac events in patients with LV dysfunction and suspected coronary disease for FDG PET-assisted management versus st and ard care . In those who adhered to PET recommendations and in patients without recent angiography , significant benefits were observed . The utility of FDG PET is best realized in this sub population and when adherence to recommendations can be achieved OBJECTIVE To prospect ively compare a selective short axis slice positioning method ( selective 3-of-5 ) used in combination with a single long-axis slice , to the conventional short axis multi-slice technique in the assessment of myocardial viability . MATERIAL S AND METHODS Thirty-one patients with recent or chronic ST segment elevation myocardial infa rct ( STEMI ) were recruited to undergo delayed enhancement ( DE ) cardiac magnetic resonance imaging ( CMR ) . All patients underwent both methods of DE imaging , with subsequent review of both sets of data by two experienced observers . Sensitivity and specificity , as well as intra and interobserver reproducibility for both techniques were assessed . RESULTS There was good agreement between the selective 3-of-5 and the conventional multi-slice method for the assessment of viability , with no significant difference in results for sensitivity or reproducibility between the techniques . CONCLUSION In patients with STEMI , a selective 3-of-5 short axis slice acquisition used in combination with a single vertical long-axis slice can be utilised to produce a st and ard American Heart Association ( AHA ) 17-segment model for the assessment of myocardial viability PURPOSE To prospect ively determine the accuracy of a combined magnetic resonance ( MR ) imaging approach ( stress first-pass perfusion imaging followed by delayed-enhancement imaging ) for depicting clinical ly significant coronary artery stenosis ( > or = 70 % stenosis ) in patients suspected of having or known to have coronary artery disease ( CAD ) , with coronary angiography serving as the reference st and ard . MATERIAL S AND METHODS The committee on human research approved the study protocol , and all participants gave written informed consent . This study was HIPAA compliant . Forty-seven patients ( 38 men and nine women ; mean age , 63 years + /- 5.3 [ st and ard deviation ] ) scheduled for coronary angiography were prospect ively enrolled : 33 were suspected of having CAD ( group A ) and 14 had experienced a previous myocardial infa rct ion and were suspected of having new lesions ( group B ) . The MR imaging protocol included cine function , gadolinium-enhanced stress and rest first-pass perfusion MR imaging , and delayed-enhancement MR imaging . Myocardial ischemia was defined as a segment with perfusion deficit at stress first-pass perfusion MR imaging and no hyperenhancement at delayed-enhancement imaging . Myocardial infa rct ion was defined as an area with hyperenhancement at delayed-enhancement imaging . RESULTS One patient was excluded from analysis because of poor- quality MR images . Coronary angiography depicted significant stenosis in 30 of 46 patients ( 65 % ) . In a per-vessel analysis ( n = 138 ) , stress first-pass perfusion MR imaging and delayed-enhancement imaging yielded sensitivity of 0.87 , specificity of 0.89 , and accuracy of 0.88 , when compared with coronary angiography . The diagnostic accuracy of stress first-pass perfusion MR imaging and delayed-enhancement imaging was slightly better than that of stress and rest first-pass perfusion MR imaging in the entire population ( 0.88 vs 0.85 ) , in group A ( 0.86 vs 0.82 ) , and in group B ( 0.93 vs 0.90 ) . CONCLUSION Stress first-pass perfusion MR imaging followed by delayed-enhancement imaging is an accurate method to depict significant coronary stenosis in patients suspected of having or known to have CAD The purpose of this work was to test the diagnostic value of dobutamine stress magnetic resonance imaging ( MRI ) for predicting recovery of regional myocardial contractility after revascularization . Cardiac wall motion abnormalities are due to either non-viable and /or scarred , or viable , but hibernating , myocardial tissue . Dobutamine stress leads to increased systolic wall thickening only in viable myocardium . Twenty-five patients with akinetic or dyskinetic myocardial regions were examined with a Cine FLASH-2D sequence at rest and during dobutamine stress ( 10 microg/kg/min ) . Patients were re-examined at rest 3 , and in case of persisting wall motion defects , 6 months after revascularization . Criterion of viability was increasing end-systolic wall thickening during stress and /or at follow-up . Akinetic regions related either to the LAD ( n = 19 ) or to the RCA ( n = 6 ) were judged viable if > or = 50 % of the affected segments improved . MR studies were completed in all subjects without arrhythmia or need for early terminations due to symptoms . Sensitivity , specificity , and positive predictive value for the prediction of myocardial viability were 61 % , 90 % , and 87 % for the segment-related analysis , and 76 % , 100 % , and 100 % for the patient-related analysis based on coronary artery distribution , respectively . Dobutamine stress MRI allows to predict global functional recovery of akinetic myocardial regions after revascularization with a high positive predictive value and high specificity Dobutamine echocardiography ( DE ) , magnetic resonance imaging ( MRI ) , and thallium redistribution ( TS ) are used to assess cardiac viability . However , these modalities sometimes yield contradictory results . Our aim was to establish the degrees of agreement among DE , MRI , and TS in identifying myocardial viability and to analyze the minimum critical mass of live ( viable ) cells required for each test to identify viability . A prospect i ve study was done in which DE , MRI , and TS were consecutively performed in 10 ischemic patients scheduled for heart transplantation . The explanted heart was analyzed to quantify the amount of live cells per segment . The pathologic data were compared with the test results to analyze the minimum mass of viable cells required by each technique to identify viability . Mean age was 58 + /- 8 years ( 8 men ) . The mean ejection fraction was 0.27 + /- 0.04 . Seven patients had severe cardiac failure ( New York Heart Association functional class IV ) and 6 patients had refractory angina . A total of 150 cardiac segments were analyzed . Among the 150 segments , 107 ( 71.3 % ) showed some degree of myocardial necrosis . Mean total area , mean fatty area , and mean necrotic area per segment were 2.53 + /- 0.7 , 0.13 + /- 0.2 , and 0.55+/-0.5 cm(2 ) , respectively . As expected , a higher amount of necrotic tissue was found in nonviable segments . From the 150 segments , DE identified 90 as viable and 60 as nonviable . These data were similar to that of MRI ( 98 viable and 52 nonviable ) . A higher proportion of viable segments was found by TS ( 117 viable vs 33 nonviable ) . The concordance between DE and TS was only moderate ( kappa 0.49 ) . The agreement between MRI and TS also showed moderate concordance ( kappa 0.56 ) . The highest agreement was found between DE and MRI ( kappa 0.73 ) . Thus , discrepancies in assessing viability by DE , MRI , and TS may be due to differences in the minimum critical mass of live myocytes required by each technique to diagnose viability . Thallium requires a lesser amount of live tissue than DE or MRI to detect viability ; also , its maximum diagnostic efficiency is obtained with lesser amounts of live tissue on each segment . These considerations should be taken into account when these diagnostic tests are used for the detection of viability before revascularization procedures BACKGROUND Traditionally , cardiac fluorodeoxyglucose ( FDG ) uptake is combined with regional perfusion for optimal evaluation of viability . Gated FDG-positron emission tomography ( PET ) may be an alternative technique for detection of viability because it permits combined assessment of glucose metabolism uptake and wall thickening ( WT ) . In this study the value of FDG uptake and WT ( analyzed from a st and -alone gated FDG-PET study ) for the prediction of recovery of regional and global left ventricular ( LV ) function in patients with coronary artery disease undergoing revascularization is studied . METHODS AND RESULTS Thirty-eight patients with chronic coronary artery disease and LV dysfunction were included . Patients underwent gated FDG-PET to assess viability . Magnetic resonance imaging was performed before and 6 months after revascularization to assess regional and global LV function and LV volumes . Of the 213 revascularized dysfunctional segments , 133 ( 62 % ) exhibited functional recovery on follow-up magnetic resonance imaging . Receiver operating characteristic curve analysis indicated that a cutoff level for FDG uptake of 50 % or greater yielded a sensitivity and specificity of 93 % and 85 % , respectively , on gated FDG-PET for prediction of improvement in regional function . Similarly , a cutoff level of 10 % or greater for WT was optimal with a sensitivity and specificity of 89 % and 78 % , respectively . Improvement in LV ejection fraction was best predicted by the number of viable segments . Reverse LV remodeling could be predicted with a sensitivity and specificity of 89 % and 65 % , respectively , by use of FDG uptake of 50 % or greater and 78 % and 70 % , respectively , by use of WT of 10 % or greater . CONCLUSION Accurate prediction of outcome after revascularization ( including improvement in regional and global LV function and reverse remodeling ) is possible with gated FDG-PET by use of a threshold of 50 % or greater for FDG uptake or a threshold of 10 % or greater for WT |
2,450 | 25,384,492 | Postsurgical patients , those with neurologic disorders , and those with medical devices had higher preventable hospitalization rates , as did those with public insurance and nonwhite race/ethnicity .
Passive smoke exposure , nonadherence to medications , and lack of follow-up after discharge were additional risks .
Hospitalizations for ambulatory care sensitive conditions were less common in more complex patients .
Patients receiving home visits , care coordination , chronic care-management , and continuity across setting s had fewer preventable hospitalizations .
Risk of bias was moderate due primarily to limited controlled experimental design s. Reductions in hospital use among CMC might be possible . | BACKGROUND AND OBJECTIVES Children with medical complexity ( CMC ) account for disproportionately high hospital use , and it is unknown if hospitalizations may be prevented .
Our objective was to summarize evidence from ( 1 ) studies characterizing potentially preventable hospitalizations in CMC and ( 2 ) interventions aim ing to reduce such hospitalizations . | OBJECTIVE To test the hypothesis that missing primary care follow-up plans in the discharge summary is associated with higher 30-day readmissions . STUDY DESIGN This retrospective cohort study included pediatric patients discharged from Mattel Children 's Hospital , University of California , Los Angeles between July 2008 and July 2010 . Exclusions included deaths , transfers , neonatal discharges , stays under 24 hours , and patients over 18 years of age . Bivariate and propensity weighted multivariate logistic regressions tested relationships between 30-day readmission and patient demographics , illness severity , and documentation of primary care provider ( PCP ) follow-up plans at discharge . RESULTS There were 7794 index discharges ( representing 5056 unique patients ) , with 1457 readmissions within 30 days ( 18.7 % ) . Average length of stay was 6.3 days . Being 15 - 18 years old , ( OR 1.42 [ 1.02 - 1.96 ] ) , having public insurance ( OR 1.48 [ 1.20 - 1.83 ] ) , or having higher All-Patient Refined Diagnosis-Related Group severity scores ( for severity = 4 vs 1 , OR 6.88 [ 4.99 - 9.49 ] ) was associated with increased odds of 30-day readmission . After adjusting for insurance status , Asian ( OR 1.46 [ 1.01 - 2.12 ] ) but not Black or Hispanic , race/ethnicity was associated with greater odds of readmission . Fifteen percent of 172 medical records from a r and omly selected month in 2010 documented PCP follow-up plans . After adjusting for demographics , length of stay and severity , documenting PCP follow-up plans was associated with significantly increased odds of 30-day readmission ( OR 4.52 [ 1.01 - 20.31 ] ) . CONCLUSION Readmission rates are complex quality measures , and documenting primary care follow-up may be associated with higher rather than lower 30-day readmissions . Additional studies are needed to underst and the inpatient-outpatient transition BACKGROUND Patients with complex care needs who require care across different health care setting s are vulnerable to experiencing serious quality problems . A care transitions intervention design ed to encourage patients and their caregivers to assert a more active role during care transitions may reduce rehospitalization rates . METHODS R and omized controlled trial . Between September 1 , 2002 , and August 31 , 2003 , patients were identified at the time of hospitalization and were r and omized to receive the intervention or usual care . The setting was a large integrated delivery system located in Colorado . Subjects ( N = 750 ) included community-dwelling adults 65 years or older admitted to the study hospital with 1 of 11 selected conditions . Intervention patients received ( 1 ) tools to promote cross-site communication , ( 2 ) encouragement to take a more active role in their care and to assert their preferences , and ( 3 ) continuity across setting s and guidance from a " transition coach . " Rates of rehospitalization were measured at 30 , 90 , and 180 days . RESULTS Intervention patients had lower rehospitalization rates at 30 days ( 8.3 vs 11.9 , P = .048 ) and at 90 days ( 16.7 vs 22.5 , P = .04 ) than control subjects . Intervention patients had lower rehospitalization rates for the same condition that precipitated the index hospitalization at 90 days ( 5.3 vs 9.8 , P = .04 ) and at 180 days ( 8.6 vs 13.9 , P = .046 ) than controls . The mean hospital costs were lower for intervention patients ( $ 2058 ) vs controls ( $ 2546 ) at 180 days ( log-transformed P = .049 ) . CONCLUSION Coaching chronically ill older patients and their caregivers to ensure that their needs are met during care transitions may reduce the rates of subsequent rehospitalization OBJECTIVE To determine whether parent-reported quality of primary care was associated with subsequent health care use for children with special health care needs . DESIGN Secondary analysis of prospect ively collected data . SETTING The 2004 - 2005 and 2005 - 2006 Medical Expenditure Panel Survey panels . PARTICIPANTS A total of 1591 children with special health care needs . MAIN EXPOSURES Composite measures for family centeredness of care , timeliness of care , and realized access derived from the Consumer Assessment of Healthcare Providers and Systems survey . MAIN OUTCOME MEASURES Rates of parent-reported emergency department visits ( nonurgent and urgent ) and hospitalizations . Only encounters occurring after completion of the Consumer Assessment of Healthcare Providers and Systems survey were assessed . Weighted multivariate Poisson regression analyses , yielding incident rate ratios , were used for analysis . RESULTS Of the parents of the 1591 children included , 68.3 % rated family centeredness , 51.5 % rated timeliness , and 80.4 % rated realized access as high quality . Low- quality family centeredness was associated with higher rates ( incident rate ratio , 2.24 ; 95 % confidence interval , 1.32 - 3.80 ) of nonurgent emergency department visits compared with corresponding rates associated with high- quality family centeredness . There were no associations between quality -of-care domains and rates of urgent emergency department visits . For privately insured children , low- quality family centeredness was associated with higher rates ( incident rate ratio , 3.87 ; 95 % confidence interval , 1.23 - 12.13 ) of hospitalizations compared with corresponding rates associated with high- quality family-centered care . For publicly insured children , no significant associations were found . CONCLUSIONS Parent-reported , low- quality family centeredness was associated with higher rates of subsequent nonurgent emergency department visits and hospitalizations among children with special health care needs . These findings highlight family-centered care as a critical area for primary care intervention to reduce potentially preventable health care use IMPORTANCE Socioeconomic and behavioral factors can negatively influence posthospital outcomes among patients of low socioeconomic status ( SES ) . Traditional hospital personnel often lack the time , skills , and community linkages required to address these factors . OBJECTIVE To determine whether a tailored community health worker ( CHW ) intervention would improve posthospital outcomes among low-SES patients . DESIGN , SETTING , AND PARTICIPANTS A 2-armed , single-blind , r and omized clinical trial was conducted between April 10 , 2011 , and October 30 , 2012 , at 2 urban , academically affiliated hospitals . Of 683 eligible general medical in patients ( ie , low-income , uninsured , or Medicaid ) that we screened , 237 individuals ( 34.7 % ) declined to participate . The remaining 446 patients ( 65.3 % ) were enrolled and r and omly assigned to study arms . Nearly equal percentages of control and intervention group patients completed the follow-up interview ( 86.6 % vs 86.9 % ) . INTERVENTIONS During hospital admission , CHWs worked with patients to create individualized action plans for achieving patients ' stated goals for recovery . The CHWs provided support tailored to patient goals for a minimum of 2 weeks . MAIN OUTCOMES AND MEASURES The prespecified primary outcome was completion of primary care follow-up within 14 days of discharge . Prespecified secondary outcomes were quality of discharge communication , self-rated health , satisfaction , patient activation , medication adherence , and 30-day readmission rates . RESULTS Using intention-to-treat analysis , we found that intervention patients were more likely to obtain timely posthospital primary care ( 60.0 % vs 47.9 % ; P = .02 ; adjusted odds ratio [ OR ] , 1.52 ; 95 % CI , 1.03 - 2.23 ) , to report high- quality discharge communication ( 91.3 % vs 78.7 % ; P = .002 ; adjusted OR , 2.94 ; 95 % CI , 1.5 - 5.8 ) , and to show greater improvements in mental health ( 6.7 vs 4.5 ; P = .02 ) and patient activation ( 3.4 vs 1.6 ; P = .05 ) . There were no significant differences between groups in physical health , satisfaction with medical care , or medication adherence . Similar proportions of patients in both arms experienced at least one 30-day readmission ; however , intervention patients were less likely to have multiple 30-day readmissions ( 2.3 % vs 5.5 % ; P = .08 ; adjusted OR , 0.40 ; 95 % CI , 0.14 - 1.06 ) . Among the subgroup of 63 readmitted patients , recurrent readmission was reduced from 40.0 % vs 15.2 % ( P = .03 ; adjusted OR , 0.27 ; 95 % CI , 0.08 - 0.89 ) . CONCLUSIONS AND RELEVANCE Patient-centered CHW intervention improves access to primary care and quality of discharge while controlling recurrent readmissions in a high-risk population . Health systems may leverage the CHW workforce to improve posthospital outcomes by addressing behavioral and socioeconomic drivers of disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01346462 ABSTRACT BACKGROUND Patient activation is linked to better health outcomes and lower rates of health service utilization . The role of patient activation in the rate of hospital readmission within 30 days of hospital discharge has not been examined . METHODS A secondary analysis using data from the Project RED-LIT r and omized controlled trial conducted at an urban safety net hospital . Data from 695 English-speaking general medical inpatient subjects were analyzed . We used an adapted , eight-item version of the vali date d Patient Activation Measure ( PAM ) . Total scores were categorized , according to st and ardized methods , as one of four PAM levels of activation : Level 1 ( lowest activation ) through Level 4 ( highest activation ) . The primary outcome measure was total 30-day post-discharge hospital utilization , defined as total emergency department ( ED ) visits plus hospital readmissions including observation stays . Poisson regression was used to control for confounding . RESULTS Of the 695 subjects , 67 ( 9.6 % ) were PAM Level 1 , 123 ( 17.7 % ) were Level 2 , 193 ( 27.8 % ) were Level 3 , and 312 ( 44.9 % ) were Level 4 . Compared with highly activated patients ( PAM Level 4 ) , a higher rate of 30-day post-discharge hospital utilization was observed for patients at lower levels of activation ( PAM Level 1 , incident rate ratio [ IRR ] 1.75 , 95 % CI,1.18 to 2.60 ) and ( PAM Level 2 , IRR 1.50 , 95 % CI 1.06 to 2.13 ) . The rate of returning to the hospital among patients at PAM Level 3 was not statistically different than patients with PAM Level 4 ( IRR 1.30 , 95 % CI , 0.94 to 1.80 ) . The rate ratio for PAM Level 1 was also higher compared with Level 4 for ED use alone ( 1.68(1.07 to 2.63 ) ) and for hospital readmissions alone ( 1.93 [ 1.22 to 3.06 ] ) . CONCLUSION Hospitalized adult medical patients in an urban academic safety net hospital with lower levels of Patient Activation had a higher rate of post-discharge 30-day hospital utilization OBJECTIVES To evaluate an integrated telehealth intervention ( Integrated Telehealth Education and Activation of Mood ( I-TEAM ) ) to improve chronic illness ( congestive heart failure , chronic obstructive pulmonary disease ) and comorbid depression in the home healthcare setting . DESIGN R and omized controlled trial . SETTING Hospital-affiliated home healthcare setting . PARTICIPANTS Medically frail older homebound individuals ( N = 102 ) . INTERVENTION The 3-month intervention consisted of integrated telehealth chronic illness and depression care , with a telehealth nurse conducting daily telemonitoring of symptoms , body weight , and medication use ; providing eight weekly sessions of problem-solving treatment for depression ; and providing for communication with participants ' primary care physicians , who also prescribed antidepressants . Control participants were allocated to usual care with in-home nursing plus psychoeducation ( UC+P ) . MEASUREMENTS The two groups were compared at baseline and 3 and 6 months after baseline on clinical measures ( depression , health , problem-solving ) and 12 months after baseline on health utilization ( readmission , episodes of care , and emergency department ( ED ) visits ) . RESULTS Depression scores were 50 % lower in the I-TEAM group than in the UC+P group at 3 and 6 months . Those who received the I-TEAM intervention significantly improved their problem-solving skills and self-efficacy in managing their medical condition . The I-TEAM group had significantly fewer ED visits ( P = .01 ) but did not have significantly fewer days in the hospital at 12 months after baseline . CONCLUSION Integrated telehealth care for older adults with chronic illness and comorbid depression can reduce symptoms and postdischarge ED use in home health setting 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 : To determine whether pediatric readmissions within 15 days of discharge were considered preventable . METHODS : Retrospective chart review of 200 r and omly selected readmissions ( 8 % of all readmissions ) occurring within 15 days of discharge from a freest and ing children ’s hospital between January 1 , 2007 , and December 31 , 2008 . The degree of preventability was assessed independently for each case by 4 pediatricians using a 5-point Likert scale and was correlated with chronic conditions and reason for index admission with 3 M ’s Clinical Risk Groups and All Patient-Refined Diagnostic-Related Groups , respectively . RESULTS : The rate of 15-day readmissions considered more likely preventable by the discharging hospital was 20.0 % ( 1.7 % of total admissions , 95 % confidence interval 14.8%–26.4 % ) . Review ers failed to reach initial consensus in 62.5 % of cases , although final consensus was achieved after the panel review ed cases together . Consensus ratings served as the st and ard for the remainder of the study . Readmissions in children with malignancies were considered less preventable than those in children with other chronic illnesses ( 5.8 % vs 25.8 % , P = .003 ) . Readmissions following surgical admissions were considered more likely preventable than those following medical admissions ( 38.9 % vs 15.9 % , P = .002 ) . Central venous catheter infections and ventricular shunt malfunctions accounted for 8.5 % of all readmissions review ed . CONCLUSIONS : Although initial consensus about which readmissions were more likely preventable was difficult to achieve , the overall rate of preventable pediatric 15-day readmissions was low . Pediatric readmissions are unlikely to serve as a highly productive focus for cost savings or quality measurement BACKGROUND Patients are routinely ill-prepared for the transition from hospital to home . Inadequate communication between Hospitalists and primary care providers can further compromise post-discharge care . Re design ing the discharge process may improve the continuity and the quality of patient care . OBJECTIVES To evaluate a low-cost intervention design ed to promptly reconnect patients to their “ medical home ” after hospital discharge . DESIGN R and omized controlled study . Intervention patients received a “ user-friendly ” Patient Discharge Form , and upon arrival at home , a telephone outreach from a nurse at their primary care site . PARTICIPANTS A culturally and linguistically diverse group of patients admitted to a small community teaching hospital . MEASUREMENTS Four undesirable outcomes were measured after hospital discharge : ( 1 ) no outpatient follow-up within 21 days ; ( 2 ) readmission within 31 days ; ( 3 ) emergency department visit within 31 days ; and ( 4 ) failure by the primary care provider to complete an outpatient workup recommended by the hospital doctors . Outcomes of the intervention group were compared to concurrent and historical controls . RESULTS Only 25.5 % of intervention patients had 1 or more undesirable outcomes compared to 55.1 % of the concurrent and 55.0 % of the historical controls . Notably , only 14.9 % of the intervention patients failed to follow-up within 21 days compared to 40.8 % of the concurrent and 35.0 % of the historical controls . Only 11.5 % of recommended outpatient workups in the intervention group were incomplete versus 31.3 % in the concurrent and 31.0 % in the historical controls . CONCLUSIONS A low-cost discharge – transfer intervention may improve the rates of outpatient follow-up and of completed workups after hospital discharge |
2,451 | 19,421,385 | Polyols like maltitol and sorbitol are by no means inert and are thus not valid controls for xylitol .
Xylitol has beneficial effects on the oral flora not shared by other polyols .
The evidence so far supports specific xylitol-effects on oral bacteria , but not on saliva .
Xylitol can not be metabolized by plaque bacteria , contrary to sorbitol and other 6-carbon polyols , and may thus favour mineralization .
Some authors have cl aim ed that the beneficial effects of xylitol are solely based on saliva stimulation and that all sugar-free gums are similar in this respect .
In fact , in conditions where caries occurrence is high , even sorbitol gum can prevent caries.8 A recent study elegantly shows caries prevention with xylitol without any saliva stimulation .
Though strict inclusion criteria prevent conclusions based on systematic review s of the literature , evidence -based treatment guidelines can still be given for the use of xylitol .
Xylitol is a useful adjunct to traditional methods for caries control and prevention . | Xylitol research has been conducted since the early 70 ’s ; at the beginning of 2009 there were almost 500 PubMed - indexed papers on “ xylitol and dental ” .
Xylitol research was initiated in Finl and , but nowadays the majority of papers are published by non-Finnish authors .
Xylitol studies have been criticized mainly by European research ers .
This criticism is reflected for example in the most recent textbook of cariology , Dental Caries – The Disease and its Clinical Management ( 2008 ) , used by students in all Nordic countries .
It shows a figure with reduction in caries occurrence in the Turku Sugar Studies as an example , not of the effect of total substitution of dietary sugars with xylitol , but rather “ indicating the importance of removal of sugar from the diet , rather than starch , in caries control “ .
Moreover , a frequently cited review in Caries Research in 2004 came to the conclusion that “ there is no evidence for a caries-therapeutic effect of xylitol”.1 Xylitol studies are easy to criticize especially by authors who have never been involved in field trials .
For example , to avoid exchange of test products between children of the same class r and omisation has to be done by schools or school classes .
This is rarely recognized by the critics of xylitol studies .
In addition , it is hard to find volunteers to comply with 2–3 years chewing of a hard and tasteless gum base , which is the control often suggested for chewing gum trials .
On the other h and , xylitol has been recommended for use in caries control and prevention by several dental associations .
The accumulated evidence suggests that 1 ) mutans streptococci are the target organisms of xylitol in vivo , 2 ) mutans streptococci are reduced and stay on a lower level even during long-term xylitol consumption as long as the consumption lasts , 3 ) xylitol consumption reduces the accumulation of plaque , 4 ) xylitol consumed by mothers reduces the mother-child transmission of mutans streptococci and consequently , caries occurrence in their children,6,7 and 5 ) xylitol consumption reduces the risk of caries in children.4 In clinical trials on xylitol mostly chewing gum with high xylitol concentrations has been used .
Studies with low daily doses of xylitol are known as a rule to fail to show any caries-preventive effects .
To obtain beneficial xylitol-effects on mutans streptococci , on plaque and caries occurrence xylitol must be consumed three times or more per day , with a daily dose of 5–6 grams.4,7 When using chewing gums or pastilles , saliva stimulation always occurs due to chewing or sucking .
In spite of the abundant literature still more studies are needed on the action of xylitol .
Biofilm models could be very useful in xylitol research .
Clinical trials often aim to improve treatment methods . | Previous in situ and in vitro studies have demonstrated that the chewing of sucrose-free gum after eating reduces the development of dental caries . To investigate the extrapolation of these findings to the clinical setting , we conducted a two-year study on 547 schoolchildren in Budapest , Hungary . Subjects in the " Gum " group were instructed to chew one stick of a commercially available sorbitol-sweetened chewing gum for 20 minutes after meals , three times daily . The " Control " group was not provided with chewing gum . After two years , the " Gum " group exhibited a 38.7 % reduction in incremental caries , excluding white spots , compared with the " Control " group . Including white spots , a corresponding 33.1 % reduction was indicated . These results clearly suggest that even in a moderate caries population practicing normal oral hygiene , including the use of fluoride dentifrices , an after-meal gum-chewing regimen can significantly reduce the rate of caries development Xylitol is effective as a non-cariogenic sugar substitute . Habitual xylitol consumption appears to select for mutans streptococci ( MS ) with impaired adhesion properties , i.e. , they shed easily to saliva from plaque . One hundred sixty-nine mother-child pairs participated in a two-year study exploring whether the mothers ' xylitol consumption could be used to prevent mother-child transmission of mutans streptococci . All mothers showed high salivary levels of mutans streptococci during pregnancy . The mothers in the xylitol group ( n = 106 ) were requested to chew xylitol-sweetened gum ( 65 % w/w ) at least 2 or 3 times a day , starting three months after delivery . In the two control groups , the mothers received either chlorhexidine ( n = 30 ) or fluoride ( n = 33 ) varnish treatments at 6 , 12 , and 18 months after delivery . The children did not chew gum or receive varnish treatments . MS were assessed from the mothers ' saliva at half-year intervals and from the children 's plaque at the one- and two-year examinations . The MS were cultured on Mitis salivarius agars containing bacitracin . The salivary MS levels of the mothers remained high and not significantly different among the three study groups throughout the study . At two years of age , 9.7 % of the children in the xylitol , 28.6 % in the chlorhexidine , and 48.5 % in the fluoride varnish group showed a detectable level of MS . In conclusion , therefore , habitual xylitol consumption by mothers was associated with a statistically significant reduction of the probability of mother-child transmission of MS assessed at two years of age . The effect was superior to that obtained with either chlorhexidine or fluoride varnish treatments performed as single applications at six-month intervals |
2,452 | 27,228,096 | Results tended to be similar for all categories of intervention , although there was no evidence that behavioural instruction reduced the outcome pain .
Narratively review ed evidence for the outcome behavioural recovery provided very low quality evidence that psychological preparation , in particular behavioural instruction , may have potential to improve behavioural recovery outcomes , but no clear conclusions could be reached .
The evidence suggested that psychological preparation may be beneficial for the outcomes postoperative pain , behavioural recovery , negative affect and length of stay , and is unlikely to be harmful .
However , at present , the strength of evidence is insufficient to reach firm conclusions on the role of psychological preparation for surgery . | BACKGROUND In a review and meta- analysis conducted in 1993 , psychological preparation was found to be beneficial for a range of outcome variables including pain , behavioural recovery , length of stay and negative affect .
Since this review , more detailed bibliographic search ing has become possible , additional studies testing psychological preparation for surgery have been completed and hospital procedures have changed .
The present review examines whether psychological preparation ( procedural information , sensory information , cognitive intervention , relaxation , hypnosis and emotion-focused intervention ) has impact on the outcomes of postoperative pain , behavioural recovery , length of stay and negative affect .
OBJECTIVES To review the effects of psychological preparation on postoperative outcomes in adults undergoing elective surgery under general anaesthetic . | This study evaluated whether preoperative preparations for cardiac surgery ( a ) reduced psychological distress and facilitated physical recovery , ( b ) reduced preoperative anxiety by making patients feel well-informed or by increasing their sense of control over recovery , and ( c ) reduced the incidence of sympathetically mediated , acute postoperative hypertension . Information-only and informationplus-coping preparations were compared with a contact-control preparation . Preoperatively ( 1 day after preparation ) , both experimental groups were significantly less anxious and fearful than the control group . The experimental groups did not differ from each other . Both experimental preparations increased patients ' belief in control over recovery . Consistent with Lazarus 's theory of stress , belief in control over recovery best predicted preoperative anxiety . Regression analyses indicated that information reduced anxiety by increasing feelings of control , Postoperatively , both experimental groups ( a ) reported less emotional distress , ( b ) were judged by nurses as making better physical and psychological recoveries , and ( c ) had a 32.5 % lower incidence of postoperative hypertension Abstract Each year , hundreds of thous and s of women undergo excisional breast biopsies for definitive diagnosis . Not only do these patients experience pain associated with the procedure , but they also endure distress associated with the threat of cancer . Hypnosis has been demonstrated as effective for controlling patients ' pain in other surgical setting s , but breast surgery patients have received little attention . To determine the impact of brief presurgical hypnosis on these patients ' postsurgery pain and distress and to explore possible mediating mechanisms of these effects , 20 excisional breast biopsy patients were r and omly assigned to a hypnosis or control group ( st and ard care ) . Hypnosis reduced postsurgery pain and distress . Initial evidence suggested that the effects of hypnosis were mediated by presurgery expectations Background Improving functional status preoperatively through exercise may improve postoperative outcome . Previous knowledge on preoperative exercise in knee osteoarthritis is insufficient . The aim of the study was to compare the difference in change between groups in lower extremity function from baseline to 3 months after Total Knee Replacement ( TKR ) following a neuromuscular exercise programme ( NEMEX-TJR ) plus a knee school educational package ( KS ) or KS alone . Methods 45 patients ( 55–83 years , 53 % male , waiting for TKR ) were r and omized to receive a minimum of 8 sessions of NEMEXTJR plus 3 sessions of KS or 3 sessions of KS alone . Function was assessed with the Chair St and Test ( CST , primary endpoint ) and the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) subscales focusing on daily living function ( ADL ) and pain ( secondary endpoints ) . Assessment s were performed immediately before and after the intervention , and at 6 weeks , 3 months and 12 months after surgery by a physiotherapist , blinded to group allocation . Results After intervention before surgery we observed a small improvement for primary and secondary endpoints in both groups , which did not differ significantly between groups : comparing the exercise to the control group the treatment effect for the CST was −1.5 seconds ( 95 % CI : −5.3 , 2.2 ) , for KOOS ADL and KOOS pain the treatment effect was 1.3 points ( −10.1 , 12.8 ) and −2.3 ( −12.4 , 7.9 ) respectively . At 3 months after surgery we observed a small improvement in the primary endpoint in the control group and a significant improvement in the secondary endpoints in both exercise and control groups , which did not differ significantly between groups : comparing the exercise group to the control group the treatment effect in the CST was 2.0 seconds ( −1.8 , 5.8 ) , for KOOS ADL and KOOS pain the treatment effect was −4.9 points ( −16.3 , 6.5 ) and −3.3 points ( −13.5 , 6.8 ) respectively . Conclusions A median ( IQR ) of 10 ( 8 , 14 ) exercise sessions before surgery showed an additional small but non-significant improvement in all functional assessment s compared to patient education alone . These benefits were not sustained after TKR . Our trial does n’t give a conclusive answer to whether additional preoperative exercise on postoperative functional outcomes is beneficial & NA ; Cardiovascular diseases cause more disability and economic loss in industrialized nations than any other group of diseases . In previous work [ Nurs Res 49 ( 2000a ) 1 ] , most coronary artery bypass graft patients ( CABG , N=225 ) reported unrelieved pain and received inadequate analgesics . This study proposed to evaluate a preadmission education intervention to reduce pain and related activity interference after CABG surgery . Patients ( N=406 ) were r and omly assigned to ( a ) st and ard care or ( b ) st and ard care+pain booklet group . Data were examined at the preadmission clinic and across days 1–5 after surgery . Outcomes were pain‐related interference ( BPI‐I ) , pain ( MPQ‐SF ) , analgesics ( chart ) , concerns about taking analgesics ( BQ‐SF ) , and satisfaction ( American Pain Society‐POQ ) . The impact of sex was explored related to primary and secondary outcomes . The intervention group did not have better overall pain management although they had some reduction in pain‐related interference in activities ( t(355)=2.54 , P<0.01 ) and fewer concerns about taking analgesics ( F(1,313)=2.7 , P<0.05 ) on day 5 . Despite moderate 24‐h pain intensity across 5 days , patients in both groups received inadequate analgesics ( i.e. 33 % prescribed dose ) . Women reported more pain and pain‐related interference in activities than men . The booklet was rated as helpful , particularly by women . In conclusion , the intervention did not result in a clinical ly significant improvement in pain management outcomes . In future , an intervention that considers sex‐specific needs and also involves educating the health professionals caring for these patients may influence these results UNLABELLED Hip osteoarthritis ( OA ) is a degenerative disease , and total hip arthroplasty ( THA ) is one of the surgical procedures of choice to improve the OA patient 's quality of life . Without a rehabilitation program , THA patients will develop functional limitations . A r and omized double-blind trial was performed between July 2009 and October 2011 to compare in a short follow-up time two groups of patients who underwent THA for OA . The THA protocol ( THAP ) group received verbal instructions and physiotherapy exercise demonstrations , and the THA physiotherapy care protocol ( THAPCP ) group received the same verbal instructions and demonstrations associated with daily exercise practice guided by a physiotherapist . The outcomes that were assessed preoperatively and 15 d postoperatively in 106 patients were muscle strength force , goniometry , Medical Outcomes Study 36-Item Short Form Health Survey , and Merle d'Aubigné and Postel score . Higher muscle strength force scores and degrees in range of motion were found in the THAPCP group . Higher improvements were also observed for the THAPCP group compared with the THAP group in the Merle d'Aubigné and Postel score . At the end of the follow-up period , the intervention in the THAPCP group improved functional capacity , quality of life , mobility , muscle strength , goniometry , and pain . It appears to be a safe tool for accelerating recovery in THA patients . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ; NCT01491048 In investigating the effects of a treatment or experience on a group of patients , it is usually necessary to observe a control group . The comparison between the two groups may be influenced by the characteristics of the subjects : for example , their sex , age , body weight , and original clinical state . In order to secure comparability for such relevant " extraneous " factors , the controls are frequently matched with the experimental subjects . An alternative is to select the controls at r and om from an appropriate population , and to rely on statistical analysis to make allowance for the effects of concomitant variables . Medical research workers often prefer to select matched instead of r and omly selected controls . The usual reasons seem to be that The current trial compared patient education before total hip arthroplasty with the usual verbal information . A r and omized , controlled 24-month prospect i ve single-center study was done . Patients scheduled for a first elective total hip arthroplasty for primary hip osteoarthritis were enrolled . All patients were given the usual information and an information leaflet and completed a self-evaluation question naire ( Spielberger State and Trait Anxiety Inventory ) . The patients were assigned r and omly to two groups : Group 1 attended a collective multidisciplinary information session 2 to 6 weeks before surgery and the control group did not attend . All patients completed another State Anxiety Inventory just before surgery and then 1 and 7 days after surgery . One hundred patients were r and omized . Forty-eight attended the collective information session . Patients receiving education were significantly less anxious just before surgery than patients in the control group , in linear regression after adjustment for gender , trait and state anxiety at baseline , depression score , and health assessment question naire score . They experienced less pain before surgery and were able to st and sooner . However , the trend toward lower anxiety scores was not statistically significant after surgery . Patient education decreases preoperative anxiety and pain in patients having hip surgery The study attempted a clinical evaluation of the efficacy of stress inoculation training for postoperative pain control using patients undergoing coronary artery graft surgery . A treatment group receiving stress inoculation training was compared to attention-education and no-treatment control groups . No differences were found between the groups on two pain rating measures , analgesic intake , or measures of state anxiety and depression . The ineffectiveness of stress inoculation in this study may be due to the difference between experimental and clinical pain , the multiple dem and s of the preoperative period , possible memory difficulties which some patients may have experienced , or the possibility that the procedure is not sufficiently potent for the intensity of this type of pain OBJECTIVE The aims of the study were to assess factors responsible for the reduction of preoperative anxiety in patients undergoing breast and abdominal surgeries . In particular , we investigated whether question prompt lists ( QPL ) , patients ' knowledge , or the communication skills of surgeons had effects on anxiety reduction . METHODS Patients were r and omly assigned to QPL and control groups . Anxiety was assessed on the State Trait Anxiety Inventory . RESULTS Both groups showed significant reduction in anxiety between initial consultation and one day prior to surgery , with QPL patients showing a trend towards a greater reduction of anxiety after surgery and a significant reduction at the first outpatient follow-up . Satisfaction with consultation and the doctor 's ability to answer questions concerning diagnosis , and treatment were significantly associated with anxiety reduction . CONCLUSION Effective anxiety reduction hinged on doctors ' communication abilities and patients ' satisfaction with the consultation Objective : To evaluate the feasibility and preliminary effectiveness of therapeutic exercise before total hip replacement in frail elderly . Design : A single-blind , r and omized clinical pilot trial . Setting : Outpatient physiotherapy department . Subjects : Frail elderly with hip osteoarthritis awaiting total hip replacement . Interventions : A short ( 3—6 weeks ) tailor-made , therapeutic exercise programme was compared with usual care . Main measures : Feasibility was assessed through patient satisfaction , adherence , occurrence of adverse events and the number of eligible non-volunteers . Preliminary preoperative effectiveness was assessed with performance and self-reported measures of pain , functioning , physical activity and quality of life . Postoperatively we measured functional recovery and length of hospital stay . Results : Sixty-two eligible patients were approached of whom 21 ( mean age 76 years ) agreed to participate . Exercisers ( n = 10 ) , rated the intervention as very good 8.9 ( 8—10 ) ( 10-point rating scale ) . No serious adverse events occurred . Forty-one ( 66 % ) eligible patients did not participate , mainly because of logistic considerations , result ing in selection bias . The intervention group ( trainings sessions participated 91 % ) showed relevant preoperative improvements on the chair-rise time ( delta —2.9 seconds ; 95 % confidence interval ( CI ) —6.2 to 0.4 ) and timed-up- and -go ( delta —4.4 seconds ; 95 % CI —9.3 to 0.5 ) . Postoperatively , no significant differences were seen . Conclusions : A short , tailor-made , exercise programme is well tolerated and appreciated in elderly patients awaiting total hip replacement . However , a larger r and omized clinical trial in the same setting is not warranted , because of the high number of eligible non-volunteers Purpose To examine whether patients who received an empowerment model of education for preoperative orthopaedic teaching had improved outcomes compared to patients who received the traditional education . Design An experimental ( empowerment teaching method ) group vs. comparison ( traditional teaching method ) group posttest design . Sample Seventy-four patients undergoing elective orthopaedic surgery . Methods Following the preoperative teaching session , patients in both groups completed a question naire design ed to measure their perceptions of the teaching ( empowerment ) and self-efficacy ( belief in their ability to carry out perioperative tasks ) . A chart audit and phone interview was done after discharge to assess length of stay , pain management , complications , and patient perceptions of the ability to complete perioperative tasks . Findings Patients in the empowerment group felt the educational approach was more empowering and had significantly higher self-efficacy scores than those in the traditional teaching group . There was much less variation in empowerment and self-efficacy scores in the empowerment group . The empowerment group reported feeling greater confidence in performing perioperative tasks . There were no differences in length of stay , complications or pain control . Conclusion Use of an empowerment teaching approach enabled patients to become more confident in their ability to carry out perioperative tasks and become a more integral part of the preoperative teaching process . Implication s for Nursing Research The theoretical model will be used to structure other educational programs and guide research . More sensitive measures of complications and pain control should be considered for future studies The role of pre-operative short-term pulmonary rehabilitation in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass graft surgery has been assessed for the first time prospect ively . Forty-five patients posted for coronary artery bypass graft surgery were r and omised to receive either short-term pulmonary rehabilitation ( group I ) or no such programme ( group II ) . Patients of both the groups were evenly matched with respect to age , sex , body surface area , duration and severity of chronic obstructive pulmonary disease and coronary artery disease . Normal individuals who evenly matched with the study group were assessed for normal respiratory function parameters . Pre-operative and post-operative peak expiratory flow rate , inspiratory capacity , post-operative ventilation time , post-operative pulmonary complication and hospital stay were determined in both the groups . Peak expiratory flow rate ( 220.0 + /- 12.9 and 324.3 + /- 84.3 in group I , 218.0 + /- 16.4 and 260.5 + /- 35.2 in group II ) and inspiratory capacity ( 844.0 + /- 147.4 and 1100.0 + /- 158.1 in group I , 830.0 + /- 117.4 and 1090 + /- 137 in group II ) were significantly lower before and after surgery respectively in both groups compared to normal values . Even though both groups showed a significant rise in post-operative peak expiratory flow rate and inspiratory capacity after surgery , the post-operative peak expiratory flow rate and inspiratory capacity in group I was significantly higher than in group II . In group I , the post-operative ventilation time ( 24.5 + /- 6.00 hours ) , post-operative complications ( n = 4 ) and hospital stay ( 12.4 + /- 3.6 days ) were significantly lower than in group II ( 35.2 + /- 22.3 hours , n = 11 , 18.8 + /- 6.6 days respectively ) . These data suggest that short-term pulmonary rehabilitation is feasible and effective in improving pulmonary functions before and after surgery and in reducing surgical morbidity and cost of medical care significantly This study evaluated the relative effects of three experimental videotapes that involved different approaches for preparing coronary artery bypass graft ( CABG ) patients for surgery and the inhospital recovery period . One of the tapes conveyed information via a health care expert only . The other two featured the same health care expert and also included clips of interviews with patient models . These latter two tapes differed in the extent to which they portrayed the recovery period as a steady , forward progression or as consisting of “ ups and downs . ” Two hundred fifty-eight male CABG patients were r and omly assigned to view one of the three videotapes on the evening prior to surgery or to a control condition . Overall , patients who viewed any of the videotapes felt significantly better prepared for the recovery period , reported higher self-efficacy for using the incentive spirometer and for speeding their recovery , performed more repetitions with their incentive spirometer each time they used it postoperatively , had shorter intensive care unit stays , and were released from the hospital more quickly than patients in the control condition . There was also evidence that patients ’ self-efficacy beliefs for speeding recovery directly mediated the effects of the videotapes on length of stay both in the intensive care unit and in the hospital PURPOSE Conventional practice in colorectal surgery involves stoma education being imparted postoperatively . Proficiency in stoma management often delays patients ’ discharge following colorectal surgery . The aim of this r and omized , controlled trial was to compare preoperative intensive , community-based stoma education with conventional postoperative stoma education after elective colorectal surgery . METHODS Forty-two elective colorectal patients requiring a stoma were r and omized into an intensive preoperative teaching ( study ) or postoperative ( control ) group . Intervention for the study group included two preoperative visits in the community during which patients were taught with audiovisual aids to use and change the stoma pouching system . Goal -directed postoperative stoma education was st and ardized for both groups . Outcomes measured included time to stoma proficiency , postoperative hospital stay , unplanned stoma-related interventions in the community within six weeks of discharge , and preoperative and postoperative hospital anxiety and depression scores . Cost-effectiveness of the intervention was also evaluated . RESULTS All outcomes measured were improved in the study group , including time to stoma proficiency(5.5 vs. 9 days ; P = 0.0005 ) , hospital stay ( 8 vs. 10 days ; P = 0.029 ) , and unplanned stoma-related community interventions per patient ( median 0 vs. 0.5 ; P = 0.0309 ) . No adverse effects of the intervention were noted . The average cost saving per patient was £ 1,119 ( $ 2,104 ) for the study group compared with the control group . CONCLUSIONS Stoma education is more effective if undertaken in the preoperative setting . It results in shorter times to stoma proficiency and earlier discharge from the hospital . It also reduces stoma-related interventions in the community and has no adverse effects on patient well-being CONTEXT Postoperative pulmonary complications ( PPCs ) after coronary artery bypass graft ( CABG ) surgery are a major source of morbidity and mortality , and increase length of hospital stay and re source utilization . The prehospitalization period before CABG surgery may be used to improve a patient 's pulmonary condition . The efficacy of preoperative inspiratory muscle training ( IMT ) in reducing the incidence of PPCs in high-risk patients undergoing CABG surgery has not yet been determined . OBJECTIVE To evaluate the prophylactic efficacy of preoperative IMT on the incidence of PPCs in high-risk patients scheduled for elective CABG surgery . DESIGN , SETTING , AND PATIENTS A single-blind , r and omized clinical trial conducted at the University Medical Center Utrecht , Utrecht , the Netherl and s , with enrollment between July 2002 and August 2005 . Of 655 patients referred for elective CABG surgery , 299 ( 45.6 % ) met criteria for high risk of developing PPCs , of whom 279 were enrolled and followed up until discharge from hospital . INTERVENTION Patients were r and omly assigned to receive either preoperative IMT ( n = 140 ) or usual care ( n = 139 ) . Both groups received the same postoperative physical therapy . MAIN OUTCOME MEASURES Incidence of PPCs , especially pneumonia , and duration of postoperative hospitalization . RESULTS Both groups were comparable at baseline . After CABG surgery , PPCs were present in 25 ( 18.0 % ) of 139 patients in the IMT group and 48 ( 35.0 % ) of 137 patients in the usual care group ( odds ratio [ OR ] , 0.52 ; 95 % confidence interval [ CI ] , 0.30 - 0.92 ) . Pneumonia occurred in 9 ( 6.5 % ) of 139 patients in the IMT group and in 22 ( 16.1 % ) of 137 patients in the usual care group ( OR , 0.40 ; 95 % CI , 0.19 - 0.84 ) . Median duration of postoperative hospitalization was 7 days ( range , 5 - 41 days ) in the IMT group vs 8 days ( range , 6 - 70 days ) in the usual care group by Mann-Whitney U statistic ( z = -2.42 ; P = .02 ) . CONCLUSION Preoperative IMT reduced the incidence of PPCs and duration of postoperative hospitalization in patients at high risk of developing a pulmonary complication undergoing CABG surgery . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N17691887 Aim of this study is the evaluation of the impact of preoperative informative session using a Multimedia Health Educational Program ( MHEP ) on patients undergoing elective Laparoscopic Cholecystectomy ( LC ) for cholelithiasis , preoperative anxiety and postoperative pain and nausea . Sixty consecutive patients scheduled for elective LC were considered for enrollment in the trial . Patients were assigned r and omly to four groups : Group A included 15 patients , preoperatively informed regarding LC through the MHEP presented by a Registered Nurse ( RN ) . Group B included 15 patients preoperatively informed through a leaflet ( design ed and developed using the exact contents of the MHEP ) . In Group C , there were 15 patients who were being informed verbally from the RN . Finally , the control Group D included 15 patients , who had the conventional preoperative information about the operation and postoperative course by the attending surgeon and anesthesiologist , as every other patient included in groups A , B , C. Preoperative assessment of patient 's knowledge about cholelithiasis and LC was performed after informative session , and was based on a specifically developed " closed , true-false " question naire . Preliminary results suggest that conventional information provided by the attending surgeon ( Group D ) is inadequate . Specifically developed informative sessions with the contribution of MHEP seems to be effective on reducing preoperative anxiety and postoperative pain , in patients undergoing elective LC A 2 x 2 factorial design was employed to test the effects on various indicators of postoperative recovery of surgical patients who had received preoperative instructions . A pamphlet and /or a nurse visit were used as delivery methods . The study population consisted of 50 patients who were scheduled for cholecystectomies . Patients were given information on the expected sequence of events on the day of surgery and instructions in postoperative self-care activities . Findings indicate that a differential effect of providing information was dependent on the patient 's level of preoperative fear , with high-fear patients benefiting most from information . Patients in the high preoperative-fear group who received either the pamphlet or the pamphlet and a nurse visit had shorter postoperative hospitalizations , switched from injected to oral medication sooner , scored higher on an index of energy and movement , and rated their appetites as better when compared with patients in either the nurse-visit or control groups . However , among those who scored low in preoperative fear , patients in the control group had better recoveries from surgery than patients who received preoperative information . The study points out the need to perform an educational assessment of patients before information is provided BACKGROUND Historically , the preoperative consultation has consisted of a discussion between patient and surgeon . There is a growing literature describing efforts to integrate multimedia into surgical patient education . This study aim ed to assess the efficacy of an educational video tutorial on early learning of information specific to patients undergoing shoulder arthroscopy when it was used as an adjunct to the st and ard preoperative consultation . METHODS This study was a surgeon-blinded , r and omized controlled trial involving 40 consecutive patients requiring shoulder arthroscopy . After a preoperative consultation with an orthopaedic surgeon , patients were r and omized in a 1:1 ratio to either a control group or a treatment group . The treatment group viewed a 10-minute video , which covered the expected preoperative , intraoperative , and postoperative experience . Immediately afterward , both groups completed a question naire measuring satisfaction and recall of information received . All patients completed a second question naire at the first postoperative visit that assessed overall satisfaction with their experience . RESULTS Thirty-four patients were available for follow-up . The video group ( N = 15 ) answered 87 % of the knowledge questions correctly , whereas the control group ( N = 19 ) answered only 56 % ( P = .000 ) . There was stronger agreement in the video group that the preoperative consultation contained an appropriate amount of information ( P = .039 ) . Postoperatively , there was agreement that the video was an effective preparation tool for all stages of the surgical experience . However , there was no difference between the groups in satisfaction with their overall surgical experience . CONCLUSIONS Video can enhance patients ' operative experiences and improve their retained knowledge when it is used as an adjunct to the preoperative consultation . LEVEL OF EVIDENCE Basic science , education methodology study , devices to improve learning This study examines the impact of a preadmission telephone intervention on anxiety , knowledge , and readiness for discharge for patients attending a preadmission teaching program prior to cardiac surgery . The primary goal of the telephone intervention was to provide support by giving additional information about individual concerns . The telephone intervention did not have an effect on anxiety and knowledge . A significantly higher level of anxiety was found in the experimental group on admission , but this difference became nonsignificant when baseline level and length of waiting time were entered as covariates . The more anxious group rated their perceived knowledge level lower , despite the fact that both groups had similar scores in actual knowledge . Given the potential barrier that anxiety can pose for patient learning , nurses need to adapt their interventions to deal with the patients ' feelings of anxiety that accompany cardiac surgery to make the learning process effective BACKGROUND Breast cancer surgery is associated with side effects , including postsurgical pain , nausea , and fatigue . We carried out a r and omized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer surgery and that it would be cost effective . METHODS We r and omly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpectomy ( mean age 48.5 years ) to a 15-minute presurgery hypnosis session conducted by a psychologist or nondirective empathic listening ( attention control ) . Patients were not blinded to group assignment . Intraoperative anesthesia use ( i.e. , of the analgesics lidocaine and fentanyl and the sedatives propofol and midazolam ) was assessed . Patient-reported pain and other side effects as measured on a visual analog scale ( 0 - 100 ) were assessed at discharge , as was use of analgesics in the recovery room . Institutional costs and time in the operating room were assessed via chart review . RESULTS Patients in the hypnosis group required less propofol ( means = 64.01 versus 96.64 microg ; difference = 32.63 ; 95 % confidence interval [ CI ] = 3.95 to 61.30 ) and lidocaine ( means = 24.23 versus 31.09 mL ; difference = 6.86 ; 95 % CI = 3.05 to 10.68 ) than patients in the control group . Patients in the hypnosis group also reported less pain intensity ( means = 22.43 versus 47.83 ; difference = 25.40 ; 95 % CI = 17.56 to 33.25 ) , pain unpleasantness ( means = 21.19 versus 39.05 ; difference = 17.86 ; 95 % CI = 9.92 to 25.80 ) , nausea ( means = 6.57 versus 25.49 ; difference = 18.92 ; 95 % CI = 12.98 to 24.87 ) , fatigue ( means = 29.47 versus 54.20 ; difference = 24.73 ; 95 % CI = 16.64 to 32.83 ) , discomfort ( means = 23.01 versus 43.20 ; difference = 20.19 ; 95 % CI = 12.36 to 28.02 ) , and emotional upset ( means = 8.67 versus 33.46 ; difference = 24.79 ; 95 % CI = 18.56 to 31.03 ) . No statistically significant differences were seen in the use of fentanyl , midazolam , or recovery room analgesics . Institutional costs for surgical breast cancer procedures were $ 8561 per patient at Mount Sinai School of Medicine . Patients in the hypnosis group cost the institution $ 772.71 less per patient than those in the control group ( 95 % CI = 75.10 to 1469.89 ) , mainly due to reduced surgical time . CONCLUSIONS Hypnosis was superior to attention control regarding propofol and lidocaine use ; pain , nausea , fatigue , discomfort , and emotional upset at discharge ; and institutional cost . Overall , the present data support the use of hypnosis with breast cancer surgery patients Sixty hysterectomy patients were r and omly assigned to one of three types of psychological preparation prior to surgery , while an additional 10 patients declined psychological help . Twenty patients received information about the surgical procedure and its effects , another 20 were instructed in a cognitive coping technique , and the remainder were given general information about the ward . Interventions were shown to have different effects on a number of pre- and post-surgical measures ; notably on knowledge about hysterectomy , analgesic usage , reported days of pain after discharge , and belief in the usefulness of intervention methods . Whereas information about surgery enhanced knowledge and usefulness ratings , cognitive coping appeared to have most effect on indices of recovery . Patients declining preparation responded badly immediately after surgery , but made a satisfactory recovery after discharge . Cognitive coping methods seem to be an effective way of managing specific worries about the operation , and it is suggested that this underlies differences in patterns of recovery following surgery This study examined the effects of providing patients with selected types of information prior to surgery and the reported frequency of use of coping behaviors following surgery . The relationship of the reported frequency of coping behaviors and outcomes of surgery was also explored . A total of 111 patients were r and omly assigned to three groups . One received procedure information ; a second , procedure and sensation information ; and a third group , procedure and sensation information , plus information on selected coping strategies . Results showed no evidence that the type of information provided for patients prior to surgery increased the reported frequency of coping behaviors or that the reported frequency of coping behaviors was related to improved outcomes as evaluated by pain intensity , distress , or selected physical complications In a study of the influence of psychological preparation for surgery , the evening before their surgery 25 experimental patients participated in a small group session at which they discussed their concerns and fears and received information about what to expect and how they could aid in their recuperation . They were contrasted with a r and omly selected matched control group of 25 patients who underwent similar procedures , but received only the routine care . Verbal , interactional , and physiological variables were measured . The research hypothesis , that the extra preparation would increase patient participation , decrease tension and anxiety , and lead to a more rapid postoperative recovery , was supported . Experimental patients reported that they slept better and experienced less anxiety the morning of surgery ; they recalled more facts about their experiences on the day of surgery , and their re collection s less often involved fearful and unpleasant images ; they experienced less operative urinary retention , required less unesthesia ; they required less pain medication , returned more rapidly to oral intake , and were discharged sooner STUDY OBJECTIVE To investigate the effectiveness of a structured preoperative education program in patients receiving patient-controlled analgesia ( PCA ) . DESIGN R and omized controlled trial . SETTING University-affiliated hospital . PATIENTS 60 ASA physical status I and II women undergoing major gynecologic surgery . INTERVENTIONS Patients were r and omly allocated to receive either st and ard information given during routine preanesthetic assessment ( n = 30 ) or additional structured preoperative education on the use of PCA ( n = 30 ) . MEASUREMENTS All patients received st and ard anesthesia and PCA was provided for postoperative analgesia . Patients were review ed bid by an independent team of pain specialists and nurses . Patient satisfaction , severity of postoperative pain , nausea , dizziness , and morphine consumption were measured at discharge from recovery room , 24 , and 48 hours after operation . Recovery characteristics of patients were also measured . MAIN RESULTS Pain scores and morphine consumption decreased over time ( p < 0.01 ) , but there was no significant difference between groups . The overall analgesic efficacy , side effects , and recovery times was not affected by the education program . Patient satisfaction in the education group was better than control during early recovery ( p= 0.03 ) , but there was no additional benefit in the remaining postoperative period . CONCLUSIONS Structured preoperative PCA education did not affect patient outcome . The early improvement in patient satisfaction was minimized by continued education and pain team supervision during the rest of the postoperative period Backround . The purpose of the trial was to evaluate the effect on length of stay of individually tailored rehabilitation for clients who were undergoing hip or knee arthroplasty . Method . Clients ( n = 133 ) with complex needs ( comorbid conditions or limited social support ) were r and omly assigned to receive preoperative usual care ( UC ) or rehabilitation ( R ) . Usual care clients received a single preoperative clinic visit . Rehabilitation clients were individually assessed and received multi disciplinary rehabilitation to optimize functional capacity , education about the in-hospital phase and early discharge planning . All rehabilitation subjects received interdisciplinary counseling/education focused on preparation for discharge home . The intervention for approximately half the rehabilitation clients was a single , cost-effective session , while others received physical conditioning . Results . Clients receiving rehabilitation achieved discharge criteria earlier ( R = 5.4 , UC = 8 days ) and had a shorter actual length of stay ( R = 6.5 , UC = 10.5 days ) . Clinical Implication s. This preoperative , individually tailored , rehabilitation program reduced length of stay An anaesthetic nurse intervention was performed in order to evaluate the effects of extended preoperative information , given by anaesthetic nurses , on perioperative stress in patients operated on for breast cancer or total hip replacement ( THR ) . Forty-six consecutive patients scheduled for surgery for breast cancer , and 55 for THR , were r and omized into two groups which were given different modes of preoperative information . Patients in the control group were informed about pre- and postoperative routines by a ward nurse . Patients in the intervention group were given extended formalized information by an anaesthetic nurse . Wilcoxon rank sum test was used to show relations between variables . There were no significant differences between the intervention group and control group for patients with breast cancer or for patients with THR . Breast cancer patients in the intervention group were significantly more anxious than THR patients in the intervention group ( P < 0.01 ) . Breast cancer patients in the intervention group showed the highest anxiety scores on the Hospital Anxiety and Depression Scale ( HADS ) scale on the day of surgery . This information may reflect an increased level of anxiety due to the extended information given preoperatively . The information may thus have had a negative effect on breast cancer patients , result ing in an increased state of anxiety . The result indicates a need for individualized modes of information to provide a proper balance between enough and too much information PURPOSE The purpose of this study was to compare pain and anxiety in orthopaedic patients scheduled for elective total hip or knee arthroplasty who have received a kit of nonpharmacologic strategies for pain and anxiety in addition to their regularly prescribed analgesics to those who receive the usual pharmacologic management alone . DESIGN Descriptive comparative and correlational design using surveys and chart audits . SAMPLE Sixty-five patients r and omized to receive usual care or usual care plus a kit of nonpharmacologic strategies . FINDINGS Patients who received the kit used nonpharmacologic measures for pain and anxiety more often than patients who did not receive the kit . The kit group tended to use less opioid and have less anxiety on postoperative day 1 ( not statistically significant ) and use significantly less opioid on postoperative day 2 than the patients who did not receive the kit . There were no between-group differences in pain intensity . There were significant correlations among postoperative pain intensity , opioid use , and anxiety . The coping method of diverting attention was related to lower present ( now ) pain scores , and ignoring the pain was associated with higher worst pain . DISCUSSION Providing a kit of nonpharmacologic strategies can increase the use of these methods for postoperative pain and anxiety and decrease the amount of opioid taken . The influence of coping strategies in acute postoperative pain needs to be examined further This study was design ed to test the outcomes of a preoperative teaching program for cholecystectomy patients and to determine the appropriate time to offer the program . The hypotheses were : ( a ) Patients in a preadmission program will recover better than those in a program given the eve of surgery , and ( b ) patients in the control group will have a poorer recovery than those in the two experimental groups . The outcomes measured were state-anxiety , ventilatory function , well-being , pain , functional ability , analgesics , and length of hospitalization . There were no significant differences between the three groups except in state-anxiety the eve of surgery which was higher in the control than in the two experimental groups . State-anxiety the eve of surgery and trait-anxiety were the most important variables affecting outcomes . There was a positive and significant linear relationship between pre- and postoperative state-anxiety This study examined the effect of structured preoperative teaching on patients ' underst and ing of patient-controlled analgesia ( PCA ) and their management of pain . The experimental group received a written pamphlet and structured preoperative teaching on the use of PCA to manage their pain . The control group received the usual preoperative preparation normally provided by the physician . Both groups were later asked to complete a posttest to determine how well they understood the use of PCA and how well they managed their pain . There was no statistically significant evidence that the experimental group 's knowledge of PCA was different from that of the control group . However , there was significant evidence that the experimental group managed their pain better To test the hypothesis that educational information provided via the web would not only be accessed by our patients , but could also reduce postoperative pain following ambulatory surgery , we enrolled 195 patients into a r and omized controlled study . Fifty-two percent of our ambulatory surgery patients already knew how to use and had access to the Internet . Eighty-five percent of our study patients accessed the re sources made available to them on the web site . Patients who had access to the pain management information on the ambulatory surgery web site reported significantly less postoperative pain on arrival to their home after surgery ( p < 0.016 ) and into the night after surgery ( p < 0.013 ) . These patients also reported significantly less postoperative pain for the day immediately following surgery ( p < 0.037 ) . We conclude that using the Internet to provide just-in-time patient education can significantly effect the clinical outcome of care Background Obtaining informed consent is an essential step in the surgical pathway . Providing adequate patient education to enable informed decision making is a continued challenge of contemporary surgical practice . This study investigates whether the use of a patient information website , to augment patient education and informed consent for elective orthopaedic procedures is an effective measure . Methods A r and omised controlled trial was conducted comparing the quality of informed consent provided by a st and ard discussion with the treating surgeon compared to augmentation of this discussion with an online education re source ( www.orthoanswer.org ) . Participants were recruited from orthopaedic outpatient clinics . Patients undergoing five common orthopaedic procedures were eligible to participate in the trial . The primary outcome measure was knowledge about their operation . Satisfaction with their informed consent and anxiety relating to their operation were the secondary outcome measures . Results There was a statistically significant increase in patient knowledge for the intervention arm as compared to the control arm ( p < 0.01 ) . Patients in the intervention arm , had an average score of 69.25 % ( SD 14.91 ) correct answers as compared to 47.38 % ( SD 17.77 ) in the control arm . Satisfaction was also improved in the intervention arm ( p = 0.043 ) . There was no statistically significant difference between the control and intervention arm relating to their anxiety scores ( p = 0.195 ) . Conclusions The use of a patient education website as an augment to informed consent improves patient knowledge about their planned operation as well as satisfaction with the consent process whilst not increasing their anxiety levels . We recommend that all patients be directed to web based education tools to augment their consent . Trial registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) ACTRN12614001058662 Objective : To investigate the effects of preoperative physical therapy for patients undergoing total hip replacement . Design : Prospect i ve r and omized controlled study . Setting : Department of Orthopaedics and Traumatology in a university hospital . Subjects : Sixty patients with osteoarthritis of the hip scheduled to receive total hip replacement were r and omly assigned into two groups . Interventions : Subjects in the study group received preoperative physiotherapy design ed to strengthen the muscles of the upper and lower limbs and to improve range of motion of the hip , beginning from eight weeks before the operation . These patients also received an educational programme about living with a prosthesis . The control group received no preoperative physiotherapy or educational programme . Main outcome measures : Patients were evaluated at baseline ( study group only , eight weeks prior to operation ) , before surgery , at discharge , three months and two years postoperatively using Harris Hip Score , visual analogue scale and range at hip abduction . Results : Although patients in the study group performed transfer activities earlier than the control group , there were no significant differences between the groups at discharge with regard to the improvement in Harris Hip Score ( p < 0.48 ) and hip adduction ( p < 0.97 ) and visual analogue scale at rest ( p < 0.54 ) and activity ( p < 0.89 ) . At the latest follow-up ( two years postoperatively ) both groups had improved in Harris Hip Score , but rate of improvement between the groups was similar ( p < 0.05 ) . Conclusions : We conclude that the routine use of preoperative physiotherapy and education programme is not useful in total hip replacement surgery OBJECTIVE To determine the effectiveness of a preoperative exercise/education program on functional recovery , health related quality of life ( HRQOL ) , health service utilization , and costs following primary total knee arthroplasty ( TKA ) . METHODS One hundred thirty-one subjects were r and omized to either the control ( n = 66 ) or treatment ( n = 65 ) group 6 weeks before TKA surgery . Patients in the treatment group underwent a 4-week exercise/education program before surgery . All subjects were assessed 6 weeks preoperatively ( before the exercise/education intervention ) , immediately preoperatively ( after the exercise/education intervention ) , and 3 , 6 and 12 months after surgery utilizing the Western Ontario McMaster Osteoarthritis Index , the SF-36 , and knee range of motion ( ROM ) and strength measures . Data on length of stay , numbers of community rehabilitation or homecare visits following discharge from the surgical hospital , and the costs associated with these services were also collected . RESULTS Subjects were similar in demographic characteristics and all measurements at the baseline assessment . No differences were seen in knee measurements ( ROM and strength ) , pain , function , or HRQOL between the 2 groups following the intervention program or at any postoperative measurement point . Patients in the treatment group used fewer postoperative rehabilitation services and stayed for a shorter time in hospital than the control group , but these differences did not attain statistical significance . CONCLUSION The exercise/education intervention did not alter functional recovery or HRQOL following TKA . Health service utilization was less in the treatment group , but our study was underpowered to attain statistical significance for these measures OBJECTIVE : To determine whether preoperative inspiratory muscle training is able to attenuate the impact of surgical trauma on the respiratory muscle strength , in the lung volumes , and diaphragmatic excursion in obese women undergoing open bariatric surgery . DESIGN : R and omized controlled trial . SETTING : Meridional Hospital , Cariacica/ES , Brazil . SUBJECTS : Thirty-two obese women undergoing elective open bariatric surgery were r and omly assigned to receive preoperative inspiratory muscle training ( inspiratory muscle training group ) or usual care ( control group ) . MAIN MEASURES : Respiratory muscle strength ( maximal static respiratory pressure – maximal inspiratory pressure and maximal expiratory pressure ) , lung volumes , and diaphragmatic excursion . RESULTS : After training , there was a significant increase only in the maximal inspiratory pressure in the inspiratory muscle training group . The maximal expiratory pressure , the lung volumes and the diaphragmatic excursion did not show any significant change with training . In the postoperative period there was a significant decrease in maximal inspiratory pressure in both the groups . However , there was a decrease of 28 % in the inspiratory muscle training group , whereas it was 47 % in the control group . The decrease in maximal expiratory pressure and in lung volumes in the postoperative period was similar between the groups . There was a significant reduction in the measures of diaphragmatic excursion in both the groups . CONCLUSION : The preoperative inspiratory muscle training increased the inspiratory muscle strength ( maximal inspiratory pressure ) and attenuated the negative postoperative effects of open bariatric surgery in obese women for this variable , though not influencing the lung volumes and the diaphragmatic excursion Background Preoperative anxiety and physical unfitness have been shown to have adverse effects on recovery from cardiac surgery . This study involving cardiac surgery patients was primarily aim ed at assessing the feasibility of delivering physical conditioning and stress reduction programs within the public hospital setting . Secondary aims were to evaluate the effect of these programs on quality of life ( QOL ) , rates of postoperative atrial fibrillation ( AF ) and length of stay ( LOS ) in hospital . Methods Elective patients scheduled for coronary artery bypass graft and /or valve surgery at a public hospital in Melbourne , Australia were enrolled . Patients were r and omized to receive either holistic therapy ( HT ) or usual care ( UC ) . HT consisted of a series of light physical exercise sessions together with a mental stress reduction program administered in an outpatient setting for the first two weeks after placement on the waiting list for surgery . A self-administered SF-36 question naire was used to measure QOL and hospital records to collect data on LOS and rate of postoperative AF . Results The study population comprised 117 patients of whom 60 received HT and 57 received UC . Both programs were able to be delivered within the hospital setting but ongoing therapy beyond the two week duration of the program was not carried out due to long waiting periods and insufficient re sources . HT , as delivered in this study , compared to UC did not result in significant changes in QOL , LOS or AF incidence . Conclusions Preoperative holistic therapy can be delivered in the hospital setting , although two weeks is insufficient to provide benefits beyond usual care on QOL , LOS or postoperative AF . Further research is now required to determine whether a similar program of longer duration , or targeted to high risk patients can provide measurable benefits .Trial registration This trial was conducted as part of a larger study and according to the principles contained in the CONSORT statement 2001 Background : Few epidemiological studies have prospect ively investigated preoperative and surgical risk factors for acute postoperative pain after surgery for breast cancer . We investigated demographic , psychological , pain-related and surgical risk factors in women undergoing resectional surgery for breast cancer . Methods : Primary outcomes were pain severity , at rest ( PAR ) and movement-evoked pain ( MEP ) , in the first postoperative week . Results : In 338 women undergoing surgery , those with chronic preoperative pain were three times more likely to report moderate to severe MEP after breast cancer surgery ( OR 3.18 , 95 % CI 1.45–6.99 ) . Increased psychological ‘ robustness ’ , a composite variable representing positive affect and dispositional optimism , was associated with lower intensity acute postoperative PAR ( OR 0.63 , 95 % CI 0.48–0.82 ) and MEP ( OR 0.71 , 95 % CI 0.54–0.93 ) . Sentinel lymph node biopsy ( SLNB ) and intraoperative nerve division were associated with reduced postoperative pain . No relationship was found between preoperative neuropathic pain and acute pain outcomes ; altered sensations and numbness postoperatively were more common after axillary sample or clearance compared with SLNB . Conclusion : Chronic preoperative pain , axillary surgery and psychological robustness significantly predicted acute pain outcomes after surgery for breast cancer . Preoperative identification and targeted intervention of subgroups at risk could enhance the recovery trajectory in cancer survivors Background Many patients demonstrate psychological distress and reduced physical activity before coronary artery bypass graft surgery ( CABG ) . Here we evaluated the addition of a brief , cognitive-behavioural intervention ( the HeartOp Programme ) to routine nurse counselling for people waiting for CABG surgery . Methods R and omised controlled trial comparing nurse counselling with the HeartOp programme to routine nurse counselling in 204 patients awaiting first time elective CABG . Primary outcome measures were : anxiety and length of hospital stay ; secondary outcome measures were : depression , physical functioning , cardiac misconceptions and cost utility . Measures were collected prior to r and omisation and after 8 weeks of their intervention prior to surgery , excepting length of hospital stay which was collected after discharge following surgery . Results 100 patients were r and omised to intervention , 104 to control . At follow-up there were no differences in anxiety or length of hospital stay . There were significant differences in depression ( difference = 7.79 , p = 0.008 , 95 % CI = 2.04–13.54 ) , physical functioning ( difference = 0.82 , p = 0.001 , 95%CI = 0.34–1.3 ) and cardiac misconceptions ( difference = 2.56 , p < 0.001 , 95%CI = 1.64–3.48 ) in favour of the HeartOp Programme . The only difference to be maintained following surgery was in cardiac misconceptions . The HeartOp Programme was found to have an Incremental Cost Effectiveness Ratio ( ICER ) of £ 288.83 per Quality -Adjusted Life Year . Conclusions Nurse counselling with the HeartOp Programme reduces depression and cardiac misconceptions and improves physical functioning before bypass surgery significantly more than nurse counselling alone and meets the accepted criteria for cost efficacy OBJECTIVE To evaluate the benefits of preoperative physical therapy and instruction of patients with primary coxarthrosis to be subjected to a total hip arthroplasty . SETTING University Hospital Maastricht . DESIGN Controlled trial . MATERIAL AND METHOD During 14 months the effects were measured of preoperative physical therapy and instruction of 64 patients divided into two population s ; one group ( n = 31 ) received preoperative instruction and physical therapy , the other did not ( n = 33 ) . Effects were measured with the Visual Analog Scale , the Harris Hip Score and the days patients could st and , walk , climb a stair and be discharged . RESULTS The Harris Hip Score showed a significant difference ( p < 0.05 ) favouring the instructed group on day 14 after the operation and at the moment the patients were discharged . The other parameters showed no significant differences between the groups . Differentiation by age , gender and type of arthroplasty showed the same results . CONCLUSION Preoperative exercise and instruction is not useful for patients who in the near future will be treated with a total hip arthroplasty for primary coxarthrosis This study evaluated the efficacy of the relaxation response on the post-operative recovery of 27 cardiac surgery patients r and omly assigned to one of two groups . Thirteen experimental group patients received educational information and practice d eliciting the relaxation response before and after surgery . The 14 patients in the control group received only information . Experimental and control groups were compared before and after surgery on both physiological and psychological recovery variables . There were no initial differences between experimental and control groups on demographic , physiological , and most psychological variables . The experimental group had lower incidence of postoperative supraventricular tachycardia ( SVT ) than the control group ( p = .04 ) despite having had the same occurrence previously . Experimental and control groups did not significantly differ over the course of study on any other physiological variables . Patients practicing the relaxation response had greater decreases in psychological tension ( p = .04 ) and anger ( p = .04 ) than those who received only educational information . The decreases in psychological tension may have been a result of regression to the mean because the experimental group started with elevated tension relative to the control group ( p = .04 ) . We conclude that practicing the relaxation response before and after surgery may reduce SVT , tension , and anger The effects of complementary techniques and alternative medicine on allopathic therapies is generating much interest and research . To properly evaluate these techniques , well controlled studies are needed to corroborate the findings espoused by individuals practicing complementary medicine therapies . To this end , we evaluated the role of one of these therapies , self-hypnosis relaxation techniques , in a prospect i ve , r and omized trial to study its effects on quality of life after coronary artery bypass surgery . Subjects were r and omized to a control group or a study group . Study group patients were taught self-hypnosis relaxation techniques the night prior to surgery . The control group received no such treatment . Patients then underwent routine cardiac management and care . The main endpoint of our study was quality of life , assessed by the Profile of Moods Scale . Results demonstrated that patients undergoing self-hypnosis the night prior to coronary artery bypass surgery were significantly more relaxed than the control group ( p = 0.0317 ) . Trends toward improvement were also noted in depression , anger , and fatigue . This study demonstrates the beneficial effects of self-hypnosis relaxation techniques on coronary surgery . This study also identifies endpoints and a study design that can be used to assess complementary medicine therapies . Results of this preliminary investigation are encouraging and demonstrate a need for further well-controlled studies This is a r and omized clinical trial , aim ed to compare the frequency and intensity of symptoms of anxiety in patients of preoperative cardiac surgery who received empathic behavior from nurse or family or those who received no specific type of empathic behavior . The sample consisted of 66 patients in preoperative of cardiac surgery , which were divided in three groups : empathic behavior by nurses , without specific empathic behavior and by family . Anxiety was assessed at two points in time : before and after the intervention . The instrument used was developed and vali date d by Suriano , comprising 19 defining characteristics of the nursing diagnosis anxiety . It was observed that the reduction of anxiety symptoms was higher in the group receiving empathic behavior of relatives when compared to the other two groups . The results suggested that encouraging the participation of family members can contribute to the reduction of anxiety symptoms in patients in preoperative cardiac surgery BACKGROUND Delirium is the most common postoperative psychiatric condition in intensive care setting s and can lead to increased complications and costs . OBJECTIVES To evaluate the impact of multifaceted preoperative patient education on postoperative delirium , anxiety , and knowledge and to explore predictors of postoperative delirium , days of mechanical ventilation , and days in the intensive care unit ( ICU ) in patients undergoing pulmonary thromboendarterectomy . METHOD A prospect i ve , r and omized controlled trial was conducted on consented patients from October 2011 to April 2013 . Patients were r and omized in a 1 to 1 ratio to receive either an individualized 45-minute multifaceted preoperative education ( experimental group , n = 63 ) or st and ard education ( control group , n = 66 ) . Participants completed the State-Trait Anxiety Inventory and Knowledge Test before and after the education . Data on incidence of delirium , days of mechanical ventilation , ICU days , and cardiopulmonary parameters were collected . RESULTS The experimental group had significantly more knowledge about postoperative care ( P < .001 ) and fewer days of mechanical ventilation ( P = .04 ) than the control group . The 2 groups did not differ significantly in anxiety , incidence of delirium , or ICU days . In exploratory multivariate analyses , hearing impairment was a positive predictor for days of delirium ( P = .009 ) , days of mechanical ventilation ( P < .001 ) , and ICU days ( P= .049 ) , whereas the posttest knowledge was a negative predictor for days of mechanical ventilation ( P = .02 ) . CONCLUSION The patient education appeared to be effective in improving knowledge and reducing days of mechanical ventilation . Hearing impairment was an unexpected predictor of adverse outcomes for patients but may be amenable to nursing intervention A study of 81 cholecystectomy patients evaluated the relative contributions of instruction in a specific coping strategy and two types of informational interventions on subjective and objective indicators of recovery from surgery . The two experimental factors in the 2 × 3 × 2 factorial design were instruction in coping activities ( present or absent ) and information ( description of typical sensations , description of typical events , or no information ) . The nonexperimental factor was preoperative fear ( high or low ) . Self-report of moods , severity of pain , and bother of ambulation were the subjective indicators . Analgesics received , amount of ambulation , length of postoperative hospitalization , and time after hospital discharge before patients ventured from their homes were the objective indicators . Instruction in coping activities , description of sensations , and description of events all were found to dampen negative moods postoperatively for patients relatively fearful before surgery . Description of typical sensations significantly reduced the length of postoperative hospitalization and time after hospital discharge before patients ventured from their homes . Another sutdy of 68 herniorrhaphy patients , using the same design , result ed in only minor effects for any of the three interventions . Explanations for the different results between studies are offered The aim of this study was to investigate whether pre-operative , sensorimotor training results in improved physical function , quality of life , sensorimotor function and reduced disability in total hip replacement patients . 80 subjects awaiting total hip replacement at a Swiss hospital were recruited for this r and omised controlled trial . The intervention group participated in a pre-operative home exercise sensorimotor training programme ; the control group received no therapy . Primary outcome measure was physical function , secondary outcome measures were quality of life , disability and sensorimotor function . Outcomes were measured using generic and disease-specific question naires as well as objective ly assessed balance ability . Measurements were taken one day before surgery and 10 days , 4 and 12 months after surgery . The intervention showed improved quality of life and sensorimotor function before surgery . These effects were lost following surgery . The intervention group experienced more disability at 4 months than the control group . At one year follow-up group-membership influenced quality of life scores depending on the measurement-time-point . It can be concluded that no useful effect was identified for a pre-operative sensory-motor training-programme . The psychological aspects following total hip replacement need to be considered in order to facilitate coping-strategies , reduce unrealistic expectations and increase satisfaction Objective . To examine whether cognitive behavioral therapy ( CBT ) alleviates dysfunctional eating ( DE ) patterns and symptoms of anxiety and depression in morbidly obese patients planned for bariatric surgery . Design and Methods . A total of 98 ( 68 females ) patients with a mean ( SD ) age of 43 ( 10 ) years and BMI 43.5 ( 4.9 ) kg/m2 were r and omly assigned to a CBT-group or a control group receiving usual care ( i.e. , nutritional support and education ) . The CBT-group received ten weekly intervention sessions . DE , anxiety , and depression were assessed by the TFEQ R-21 and HADS , respectively . Results . Compared with controls , the CBT- patients showed significantly less DE , affective symptoms , and a larger weight loss at follow-up . The effect sizes were large ( DE-cognitive restraint , g = −.92 , P ≤ .001 ; DE-uncontrolled eating , g = −.90 , P ≤ .001 ) , moderate ( HADS-depression , g = −.73 , P ≤ .001 ; DE-emotional eating , g = −.67 , P ≤ .001 ; HADS-anxiety , g = −.62 , P = .003 ) , and low ( BMI , g = −.24 , P = .004 ) . Conclusion . This study supports the use of CBT in helping patients preparing for bariatric surgery to reduce DE and to improve mental health . This clinical trial is registered with NCT01403558 Objectives To determine the incidence and characteristics of r and omised controlled trials that report using the modified intention to treat approach , and how the approach is described . Design Systematic review . Data sources PubMed , Embase , Cochrane central register of controlled trials , ISI Web of Knowledge , Ovid , HighWire Press , Science-Direct , Ingenta , Medscape , BioMed Central , Springer , and Wiley , from inception to December 2006 . Main outcome measures Incidence of trials in which use of modified intention to treat was reported , and how the approach was described ( classified according to the type and number of deviations from the intention to treat approach ) . Results 475 r and omised controlled trials reported use of a modified intention to treat analysis . Of these , 76 ( 16 % ) were published in five highly cited general medical journals . The incidence of all trials that reported use of modified intention to treat published in journals indexed in Medline increased from 0.006 % in 1982 - 6 to 0.5 % in 2002 - 6 ( P<0.001 for linear trend ) . When the description of the modified intention to treat was examined in each trial , 192 ( 40 % ) reported one type of deviation from the intention to treat approach , 261 ( 55 % ) reported two or more types , and 22 ( 5 % ) did not describe any type . In 266 ( 56 % ) of the trials the deviation was related to the treatment received , in 196 ( 41 % ) to a post baseline assessment , in 118 ( 25 % ) to a baseline assessment , in 108 ( 23 % ) to a target condition , and in 23 ( 5 % ) to follow-up . Post-r and omisation exclusions occurred in 380 ( 80 % ) trials . The results reported by 270 of the 352 ( 77 % ) superiority trials favoured the drug under investigation . All of the 123 trials using equivalence or non-inferiority methods to investigate interventions reported results that favoured their assumptions . Conclusions R and omised controlled trials that report using a modified intention to treat are increasingly being published in the medical literature . The descriptions of such an approach were ambiguous , and may cover any type of descriptions for exclusion , such as missing data and deviation from protocol . Explicit statements about post-r and omisation exclusions should replace the ambiguous terminology of modified intention to treat Background Preoperative conditions may play a significant role in postoperative cognitive dysfunction ( POCD ) development in elderly patients . We aim ed to investigate whether preoperative cognitive training could lower the incidence of POCD one week after surgery . Material / Methods A total of 141 ASA I – III elderly patients who underwent gastrointestinal surgery were enrolled into the study . Patients were r and omized into either the Intervention group ( 69 analyzed ) or the Control group ( 72 analyzed ) . Patients in the intervention group were instructed and trained in a cognition mnemonic skill for a total of three 1-hour sessions with the method of loci ( MoL ) . Controls did not receive any cognitive training during hospitalization . All patients were tested using neuropsychological battery tests ( NPTs ) on admission and one week after surgery . Result The incidence of POCD in the intervention group ( 15.9 % ) was significantly lower than in the controls ( 36.1 % ) ( P<0.05 ) . Patients ’ performance in Brief Visuospatial Memory Test-Revised and Symbol-Digit Modalities Test were improved by the cognitive training . Increasing age , longer length of anesthesia and surgery , and lack of cognitive training were associated with a significantly higher risk of POCD ( P<0.05 ) . Conclusions Cognitive training with MoL can reduce the decline of early postoperative cognitive function in elderly patients undergoing major gastrointestinal surgery AIMS Research has demonstrated the beneficial impact that pre-operative education exerts on the postoperative recovery of patients having surgery but little work has focused specifically on cardiac surgery . Therefore a r and omized controlled trial was design ed to eluci date the consequences of pre-operative education , given before admission , on postoperative pain , anxiety , depression and wellbeing in the 6 months following a first episode of coronary artery surgery . METHOD AND RESULTS Three hundred and fifty-six people were r and omized into the study , with 188 in the experimental and 168 in the control arms . Patients in the experimental group received the intervention , a day of education by members of the multidisciplinary team , prior to admission for surgery . Experimental and control subjects had the usual care , which involved education on admission and throughout their stay in hospital . Measurement was conducted on entry to the study , before r and omization , and at 3 days , 6 weeks , 3 months and 6 months following operation . A variety of tools were used : the SF-36 Health Status question naire , the Hospital Anxiety and Depression scale , the General Well-Being question naire and a pain measurement tool . Analysis was done using the intention-totreat principle and non-parametric statistics . There were no significant differences between groups in the primary outcomes namely anxiety ( P=0.09 ) and pain ( P=0.48 ) , or in depression ( P=0.62 ) and wellbeing ( ' worn out ' P=0.11 ; ' tense and uptight ' P=0.29 ) 6 months after operation . This was also the case 3 days after coronary artery surgery . There was a significant difference in length of hospital stay ( P=0.01 ) with the experimental group having the longer stay . These findings contrast with much of the existing evidence . CONCLUSION The findings demonstrate that there is no benefit to be gained from this form of pre-operative education and that there is an associated increase in length of hospital stay . Future research could examine an ongoing programme of education and support , and might use alternative methods such as CD-ROM or the Internet Background Complementary therapies ( CT ) , such as relaxation technique , massage , guided imagery , and accupuncture have shown to benefit patients undergoing surgery . The aim of this study was to determine the feasibility of using audio relaxation technique ( ART ) , music intervention ( MI ) , nature video application with music ( NVAM ) , and nature video application without music ( NVA ) delivered via mobile technologies in a clinical setting . Secondary , the effects of ART , MI , NVAM and NVA on patients ’ state anxiety , pain perception , and perceived self-efficacy in healing were determined . Methods A r and omized clinical trial ( RCT ) involving 105 same day surgery ( SDS ) patients , who were assigned to an ART ( n = 25 ) , MI ( n = 25 ) , NVAM ( n = 15 ) , NVA ( n = 16 ) , or a control group ( n = 24 ) were assessed for state anxiety , self-reported pain , and self-efficacy four days prior to surgery , immediately prior and following a surgical intervention , and day five post-operative . Results ANOVA found no statistically significant differences in anxiety scores ; pain , or perceived self-efficacy between the five groups . Matched pairs t-Test revealed all participants had an increase in anxiety from pre-op to day 10 follow-up ; a significant change in pain levels from pre-op to day 10 follow-up ; and all participants had a significant increase in general self-efficacy from pre-op to day 10 follow-up . Mean pain level scores from day 1 to pre-op showed a significant decrease in pain for the ART group and NVAM group . Matched pairs t-Test for self-efficacy scores indicated the MI group and the NVA group had significant increases in self-efficacy . A significant decrease in anxiety from pre-op to day 10 for participants reporting a prior history of anxiety and for those reporting prior history of taking anti-anxiety medications . Conclusions Despite the non-significant findings between the five groups , at any measurement point , there were valuable trends toward significance and confirmed feasibility in a clinical setting . Among the groups there were statistically significant findings for all interventions on anxiety , pain , and self-efficacy . The feasability of the implementation of novel interventions of NVAM and NVAM adds to clinical practice and the CT literature .Trial registration Clinical Trials.gov Identifier : NCT02236455 ( September 4 , 2014 OBJECTIVE Occupational violence as experienced by professional nurses has been extensively research ed . However , the majority of studies have focused primarily on psychological and emotional outcomes and have not identified any interventions that may reduce the impact of aggressive behaviour on professional competence . The purpose of this study was to investigate the relationship between organisational support , occupational violence and perceived professional competence of professional nurses in Australia . DESIGN A model testing research design was used to test the hypothesis that organisational support , as experienced by nurses , would moderate the relationship between occupational violence and perceived professional competence . SETTING Nurses registered in Division 1 of the Nurses Board ( Victoria , Australia ) . PARTICIPANTS A systematic r and om sample of 380 registered nurses from the target population of nurses in Victoria was identified . MAIN OUTCOME MEASURE The relationship between organisational support , occupational violence and perceived professional competence of professional nurses in Australia . RESULTS The result showed that there was a significant effect of occupational violence on perceived competence . Analysis of the moderating effect of organisational support on the relationship between occupational violence and professional competence showed there was significant organisational support and occupational violence interaction . Overall , the data analysis demonstrated the hypothesis was upheld that the negative effects of occupational violence on perceived professional competence will be moderated by perceived organisational support . CONCLUSIONS The failure to receive appropriate organisational support may result in lowering professional nurses ' competence levels , causing a significant problem for the profession in that a reduction in professional competence has significant implication s for patient care . The findings heighten the responsibility of the nursing profession to become more aware of the needs of professional nurses BACKGROUND / AIM Hip arthroplasty is a routine operation which relieves pain in patients with osteoarthritis . The role of physical therapy after hip arthroplasty was recognized , but the importance of preoperative physical therapy and education is still to be judged . The aim of this paper was to investigate the effect of short-term preoperative program of education and physical therapy on patients ' early functional recovery immediately after total hip arthroplasty ( THA ) . METHODS This prospect i ve study included 45 patients with hip osteoarthritis scheduled to undergo primary THA and admitted to the Department of Orthopedics of Military Medical Academy . They were r and omized into 2 groups : study and control one ( with and without preoperative education and physical therapy ) . Preoperative education was conducted through conversation ( 1 appointment with physiatrist ) and brochure . The study group was instructed to perform exercises and basic activities from the postoperative rehabilitation program ( 2 practical classes with physiotherapist ) . Effects were measured with question naires ( Harris , Oxford and Japanese Orthopaedic Association ( JOA ) hip scores ) , range of motion and visual analog scale of pain . Marks showing ability to perform basic activities and endurance were from 0 ( did not perform activity ) to 5 ( independent and secure ) . Analyses examined differences between the groups over the preoperative and immediate postoperative periods and 15 months after the operation . RESULTS There were no differences between the groups at discharge according to pain , range of motion , Harris hip score and JOA hip score . Oxford hip score did not differ between the groups 15 months after the operation . The groups started to walk at the same time , but the study group walked up and down stairs ( 3.7+/-1.66 vs 5.37+/-1.46 , p < or = 0.002 ) , used toilet ( 2.3+/-0.92 vs 3.2+/-1.24 , p < or = 0.02 ) and chair ( 2.2+/-1.01 vs 3.25+/-1.21 , p < or = 0.006 ) significantly earlier than the control group . On the third day after the operation the study group was significantly more independent than the control one while performing any basic activities ( changing position in bed from supine to side lying , from supine to sitting on the edge of the bed , from sitting to st and ing , from st and ing to lying in the bad , st and ing , walking , using toilet and chair ) . At discharge the patients from the control group still needed the therapist help for walking up and down stairs ( 3+/-1.26 ) , while the patients from the study group performed there activities independently ( 4.85+/-0.37 ) ( p < or = 0.000 ) . Endurance while walking was significantly better in the study group than in the control one . The length of hospital stay after the operation was similar for both groups , but the patients from the study group needed significantly less classes with the therapist ( 5.2+/-2.35 vs 6.85+/-1.14 , p < or = 0.02 ) during hospital stay . CONCLUSION The short-term preoperative program of education with the elements of physical therapy accelerated early functional recovery of patients ( younger than 70 ) immediately after THA and we recommend it for routine use Background Images evoked immediately before the induction of anesthesia with the help of suggestions may influence dreaming during anesthesia . The aim of the study was to assess the incidence of evoked dreams and dream recalls by employing suggestions before induction of anesthesia while administering different general anesthetic combinations . Methods This is a single center , prospect i ve r and omized including 270 adult patients scheduled for maxillofacial surgical interventions . Patients were assigned to control , suggestion and dreamfilm groups according to the psychological method used . According to the anesthetic protocol there were also three subgroups : etomi date & sevoflurane , propofol & sevoflurane , propofol & propofol groups . Primary outcome measure was the incidence of postoperative dreams in the non-intervention group and in the three groups receiving different psychological interventions . Secondary endpoint was to test the effect of perioperative suggestions and dreamfilm-formation training on the occurrance of dreams and recallable dreams in different general anesthesiological techniques . Results Dream incidence rates measured in the control group did not differ significantly ( etomi date & sevoflurane : 40 % , propofol & sevoflurane : 26 % , propofol & propofol : 39 % ) . A significant increase could be observed in the incidence rate of dreams between the control and suggestion groups in the propofol & sevoflurane ( 26%-52 % ) group ( p = 0.023 ) . There was a significant difference in the incidence of dreams between the control and dreamfilm subgroup in the propofol & sevoflurane ( 26 % vs. 57 % ) , and in the propofol & propofol group ( 39 % vs.70 % ) ( p = 0.010 , and p = 0.009 , respectively ) . Similar to this , there was a significant difference in dream incidence between the dreamfilm and the suggestion subgroups ( 44 % vs. 70 % ) in the propofol & propofol group ( p = 0.019 ) . Propofol as an induction agent contributed most to dream formation and recalls ( χ2-test p value : 0.005 ) . The content of images and dreams evoked using suggestions showed great agreement using all three anesthetic protocol s. Conclusion The psychological method influenced dreaming during anesthesia . The increase of the incidence rate of dreams was dependent on the anesthetic agent used , especially the induction agent . The study was registered in Clinical Trials.gov . Identifier : NCT01839201 OBJECTIVES The objectives of this r and omised controlled study were to determine if pre-admission patient education affects post-operative pain levels , domiciliary self-care capacity and patient recall following a laparoscopic cholecystectomy ( LC ) . Participants were r and omised to receive the st and ard preadmission program ( SP ) or an individualised , education intervention ( El ) . DESIGN A pre-operative question naire was administered in the pre-admission clinic to determine participants ' knowledge of LC and post-operative management . Telephone follow-up and post-operative question naire were conducted approximately 14 days post discharge . SETTING Preadmission clinic of a Sydney , Australia , tertiary referral hospital . SAMPLE Ninety-three elective LC patients . RESULTS EI participants experienced lower pain levels and had significantly greater recall of provided information . However , no significant differences were found between the control and intervention groups for domiciliary self-care . CONCLUSION Pre-admission education intervention helps reduce post-operative pain levels following LC and significantly increases patients ' knowledge of self-care and complication management Abstract Background . Women with breast cancer experience different symptoms related to surgical or adjuvant therapy . Previous findings and theoretical models of mind – body interactions suggest that psychological wellbeing , i.e. levels of distress , influence the subjective evaluation of symptoms , which influences or determines functioning . The eight-week mindfulness-based stress reduction ( MBSR ) program significantly reduced anxiety and depression in breast cancer patients in a r and omized controlled trial ( NCT00990977 ) . In this study we tested the effect of MBSR on the burden of breast cancer related somatic symptoms , distress , mindfulness and spiritual wellbeing and evaluated possible effect modification by adjuvant therapy and baseline levels of , distress , mindfulness and spiritual wellbeing . Material and methods . A population -based sample of 336 women Danish women operated for breast cancer stages I – III were r and omized to MBSR or usual care and were followed up for somatic symptoms , distress , mindfulness skills and spiritual wellbeing post-intervention and after six and 12 months . Effect was tested by general linear regression models post-intervention , and after six and 12 months follow-up and by mixed effects models for repeated measures of continuous outcomes . Effect size ( Cohen 's d ) was calculated to explore clinical significance of effects among intervention group . Finally , modification of effect of MBSR on burden of somatic symptoms after 12 months ’ follow-up by adjuvant therapy and baseline levels of , distress , mindfulness and spiritual wellbeing were estimated . Results . General linear regression showed a significant effect of MBSR on the burden of somatic symptoms post-intervention and after 6 months ’ follow-up . After 12 months ’ follow-up , no significant effect of MBSR on the burden of somatic symptoms was found in mixed effect models . A statistically significant effect of MBSR on distress was found at all time-points and in the mixed effect models . Significant effects on mindfulness were seen after six and 12 months and no significant effect was observed for spiritual wellbeing . No significant modification of MBSR effect on somatic symptom burden was identified . Conclusion . This first report from a r and omized clinical trial on the long-term effect of MBSR finds an effect on somatic symptom burden related to breast cancer after six but not 12 months follow-up providing support for MBSR in this patient group The basic assumption underlying the present study was that emotional factors may influence not only recovery but also blood loss and blood pressure in maxillofacial surgery patients , where the surgery was performed under general anesthesia . Eighteen patients were administered a hypnosis tape containing preoperative therapeutic suggestions , 18 patients were administered hypnosis tapes containing pre- and perioperative suggestions , and 24 patients were administered a hypnosis tape containing perioperative suggestions only . The patients who received taped suggestions were compared to a group of matched control patients . The patients who received preoperative suggestions exhibited a 30 % reduction in blood loss . A 26 % reduction in blood loss was shown in the group of patients receiving pre- and perioperative suggestions , and the group of patients receiving perioperative suggestions only showed a 9 % reduction in blood loss . Lower blood pressure was found in the groups that received pre- and perioperative and perioperative suggestions only . Rehabilitation was facilitated in the group of patients receiving perioperative suggestions only Abstract Purpose Patients undergoing surgery can be impaired in several health-related quality of life areas . As a result , a modern and effective presentation of medical information before elective surgery is of great importance . Thorough preoperative education of the patient could possibly lead to an improvement of postoperative quality of life . Material s and methods In a prospect i ve r and omized study we examined the influence of a preoperative informative video on the postoperative quality of life of patients undergoing elective surgery for inguinal hernia . Quality of life was assessed with a short form question naire ( SF-36 ) preoperatively , on the first postoperative day and 3 , 6 , and 12 months after surgery . Results From January 2004 until January 2005 , 100 patients were included in the study ( video group n = 50 patients , control group n = 50 patients ) . Quality of life was measured higher in the video group soon after surgery and until 3 months afterwards . In the same group other aspects evaluated such as “ global health ” and “ social role ” showed higher values postoperatively and resumption of preoperative activities took place earlier . No difference was detectable 6 months after surgery . Conclusion Informative video presents a modern and cost-effective method for the justified and detailed education of the patient about the several pre- , intra- , and postoperative steps of an elective groin hernia operation . The higher information level and the better conditions of surgical care , as the patients perceive these , lead to a better postoperative quality of life The aim of this study was to examine the impact of a brief psychoeducation group intervention on fear and anxiety in patients undergoing the coronary artery bypass grafting ( CABG ) . Sixty consecutive patients undergoing CABG for the first time were recruited for a clinical trial and r and omized into two groups . The control group received routine care . The study group received a brief psychoeducation group intervention combined with routine care . The psychoeducation session consisted of a discussion of fear and anxiety in a psychotherapeutic atmosphere and relaxation techniques . Fear was scored with the Bypass Grafting Fear Scale ( BGFS ) and anxiety was scored with the Spielberger State Inventory ( STAI ) Question naire . The BGFS and the STAI were given to the patients the day after hospital admission and a day before the operation to measure fear and anxiety . Fear scores decreased in the psychoeducation group . Of the 29 patients treated with psychoeducation , the mean ( SD ) fear score decreased from 4.6 ( 1.7 ) at baseline to 2.8 ( 1.2 ) before the operation ( p < .001 ) . In the 31 patients who received routine care , there was a nonsignificant trend from 3.7 ( 1.9 ) to 4.1 ( 2.1 ) ( p > .05 ) . The mean difference in fear score before the operation was significantly lower in the psychoeducation group than the routine care group ( mean difference −1.3 ; 95 % CI , −2.1 , −.2 ; p < .05 ) . There were no differences in anxiety scores before the operation between the psychoeducation and routine care groups . In patients undergoing CABG , adding psychoeducation to routine care had a significant positive effect on fear but not on anxiety scores . A larger study of psychoeducation in these patients is warranted to assess the efficacy of this intervention in greater detail Objective : To determine in a pilot study the feasibility and effects of preoperative inspiratory muscle training in patients at high risk of postoperative pulmonary complications who were scheduled for coronary artery bypass graft surgery . Design : Single-blind , r and omized controlled pilot study . Setting : University Medical Centre Utrecht , the Netherl and s. Subjects : Twenty-six patients at high risk of postoperative pulmonary complications were selected . Intervention : The intervention group ( N = 14 ) received 2 - 4 weeks of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group . Main measures : Primary outcome variables of feasibility were the occurrence of adverse events , and patient satisfaction and motivation . Secondary outcome variables were postoperative pulmonary complications and length of hospital stay . Results : The feasibility of inspiratory muscle training was good and no adverse events were observed . Treatment satisfaction and motivation , scored on 10-point scales , were 7.9 ( ± 0.7 ) and 8.2 ( ± 1.0 ) , respectively . Postoperative atelectasis occurred in significantly fewer patients in the intervention group than in the control group ( ϰ2 DF1 = 3.85 ; P = 0.05 ) : Length of hospital stay was 7.93 ( ± 1.94 ) days in the intervention group and 9.92 ( ± 5.78 ) days in the control group ( P = 0.24 ) . Conclusion : Inspiratory muscle training for 2 - 4 weeks before coronary artery bypass graft surgery was well tolerated by patients at risk of postoperative pulmonary complications and prevented the occurrence of atelectasis in these patients . A larger r and omized clinical trial is warranted The objective of this study was to examine the effects of a brief and economical procedure in the preparation of surgical patients . More specifically , the study was intended to test whether patient 's monitoring style ( high vs. low ) makes any difference to the benefits of a relaxation technique . Ninety-two patients scheduled for hysterectomy with double oophorectomy were assessed for preferred coping style and r and omly assigned to one of two conditions : ( a ) relaxation training and ( b ) attention control . It was hypothesized that low monitors would report less pain , less analgesic use and a higher activity level when trained in relaxation than low monitor controls or than high monitors trained in relaxation . Results showed no differences between individuals with different coping styles . On the other h and , however , statistically significant differences were observed between trained patients and controls . Namely , individuals trained in relaxation experienced less pain along the surgical process , pain interfered less with their daily activities , and performed a higher activity level three weeks after surgery , compared to non trained patients The goal of the current study was to investigate whether preoperative rehabilitation advice reinforced by a patient information booklet can aid recovery after total hip arthroplasty in terms of pain , function , satisfaction , and quality of life . Thirty-five patients awaiting primary total hip arthroplasty were recruited into this study and r and omly allocated before admission to receive either the st and ard pathway of care or the rehabilitation program and booklet . All patients showed increases in function and psychological variables with time . The preoperative class and booklet , however , seemed to have the greatest impact on length of hospital stay , reducing the hospital stay by 3 days , and therapy input required , significantly influencing the cost of the procedure ( the rehabilitation class led to a cost saving of 587 British pounds ; approximately 810 dollars , per patient ) . In addition , patients attending the class reported higher levels of satisfaction ( 99 % satisfied in the preoperative rehabilitation class compared with 80 % in the control group 3 months postoperatively ) and had more realistic expectations of surgery OBJECTIVE To compare the efficacy of two modes of delivery of information for patients undergoing functional endoscopic sinus surgery : website and printed leaflet . METHODS A two-centre , prospect i ve , single-blinded , r and omised , controlled trial was conducted , comparing mode of information delivery . Adult patients were r and omly allocated to receive pre-operative information regarding functional endoscopic sinus surgery , either via a website or a printed leaflet . Primary outcomes , measured by question naire , were : readability , usability and recall of complications . RESULTS Fifty-eight patients were recruited . Fifty met the inclusion criteria , of which 40 were analysed in the study ( 20 patients per group ) , meeting the power criteria set . There were 18 male and 22 female patients , ranging in age from 21 to 76 years ( mean , 47 years ) . Patients found both the printed leaflet and the website readable , and were satisfied with the usability of both modes . There were similar rates for recall of complications in both study arms . CONCLUSION Patient information on functional endoscopic sinus surgery can be provided either as a printed leaflet or a website , with similar rates for usability , readability and recall of complications . These findings could help tailor the provision of pre-operative information for patients undergoing functional endoscopic sinus surgery , based on patient preference Study Design . Multicenter , r and omized , controlled trial on preoperative pain neuroscience education ( NE ) for lumbar radiculopathy . Objective . To determine if the addition of NE to usual preoperative education would result in superior outcomes with regard to pain , function , surgical experience , and health care utilization postsurgery . Summary of Background Data . One in 4 patients after lumbar surgery ( LS ) for radiculopathy experience persistent pain and disability , which is nonresponsive to perioperative treatments . NE focusing on the neurophysiology of pain has been shown to decrease pain and disability in population s with chronic low back pain . Methods . Eligible patients scheduled for LS for radiculopathy were r and omized to receive either preoperative usual care ( UC ) or a combination of UC plus 1 session of NE delivered by a physical therapist ( verbal one-on-one format ) and a NE booklet . Sixty-seven patients completed the following outcomes prior to LS ( baseline ) , and 1 , 3 , 6 , and 12 months after LS : low back pain ( numeric rating scale ) , leg pain ( numeric rating scale ) , function ( Oswestry Disability Index ) , various beliefs and experiences related to LS ( 10-item survey with Likert scale responses ) , and postoperative utilization of health care ( utilization of health care question naire ) . Results . At 1-year follow-up , there were no statistical differences between the experimental and control groups with regard to primary outcome measure of low back pain ( P = 0.183 ) , leg pain ( P = 0.075 ) , and function ( P = 0.365 ) . In a majority of the categories regarding surgical experience , the NE group scored significantly better : better prepared for LS ( P = 0.001 ) ; preoperative session preparing them for LS ( P < 0.001 ) and LS meeting their expectations ( P = 0.021 ) . Health care utilization post-LS also favored the NE group ( P = 0.007 ) result ing in 45 % less health care expenditure compared with the control group in the 1-year follow-up period . Conclusion . NE result ed in significant behavior change . Despite a similar pain and functional trajectory during the 1-year trial , patients with LS who received NE viewed their surgical experience more favorably and used less health care facility in the form of medical tests and treatments . Level of Evidence : UNLABELLED In patients with severe knee osteoarthritis ( OA ) , total knee arthroplasty ( TKA ) is performed for both symptom relief and to achieve better function in daily life . Implementation of efficient TKA rehabilitation programs with shorter length of stay ( LOS ) and reduced medical expenditures is an important issue in clinical practice . However , the effectiveness of preoperative rehabilitation programs is still under debate . Most preoperative rehabilitation programs last many weeks and may be more expensive than TKA . The purpose of this study was to investigate the effects of a simplified , easy-to-learn , and less time-consuming preoperative rehabilitation education program on TKA patients . PATIENTS AND METHODS In this r and omized controlled study , we allocated all the patients into study and control group according to chart number . The study group , which comprised 126 patients , participated in a 40-min preoperative home rehabilitation education program 4 weeks prior to TKA . One hundred seventeen patients in the control group did not participate in this preoperative program . RESULTS The study group required a shorter hospital LOS ( mean : 7.12 days ; P=0.027 ) and had less hospitalization-related medical expenditures ( mean : 123726 New Taiwan dollars [ NTD ] , equivalent to 4266.4 United States dollars [ USD ] or 3022.1 [ Euros ] ) , ( P=0.001 ) than the control group . However , the study group showed no significant improvement in function when compared to the control group . DISCUSSION Our study demonstrates that a simplified preoperative rehabilitation program can reduce LOS and increase cost savings . This program was recommended as a routine protocol for OA patients before admission for TKA The objective of this study was to investigate the effect of a cognitive intervention ( distraction and re appraisal ) with information given pre-operatively on post-operative outcomes of Chinese women having an abdominal hysterectomy . Using a controlled trial , 48 Chinese women having elective hysterectomy received the cognitive intervention with information ( experimental group ) . A control group ( n=48 ) received information alone . Outcome measures used in the study were post-operative anxiety and pain , requests for analgesia and patient satisfaction . The results show that women in the experimental group reported lower post-operative anxiety scores , lower pain scores and higher levels of satisfaction than women in the control group . There were no statistically significant differences in post-operative requests for analgesia between the groups . It is concluded that a cognitive intervention such as distraction and re appraisal may have significant clinical benefits and improve the care of women having an elective hysterectomy Background : Coronary artery bypass grafting ( CABG ) in high-risk patients is associated with significant perioperative complications and anxiety . Prevention of these postoperative complications and anxiety is important in the improvement of clinical outcomes following CABG . Objective : The objective of the study was to evaluate the effect of nurse-initiated preoperative education and counseling on postoperative complications and anxiety symptoms following CABG . Methods : In this prospect i ve and r and omized trial , 40 patients were divided into the study and control groups . All patients received st and ard preoperative and postoperative care , but the study group patients also completed a structured education and counseling course supervised by design ated nurses 3 days before the surgery . Anxiety symptoms were assessed by Zung ’s self-rating anxiety scale ( SAS ) on the day of admission and at 3 days after the surgery . Results : There was no statistically significant difference in the baseline characteristics or operational data between the 2 groups ( P > .05 ) . Following the surgery , the rate of complications such as lower extremity edema , urinary retention , constipation , respiratory infection , and deep venous thrombosis in the study group was lower than in the control group ( P < .05 ) . The mean postoperative SAS scores in the study group was lower than in the control group ( 40.1 [ SD , 6.5 ] vs 48.9 [ SD , 7.3 ] ; P = .01 ) , and the proportion of patients with a SAS score greater than 40 in the study group was also lower than in the control group ( 15 % vs 45 % , P = .041 ) . Conclusions : Nurse-initiated preoperational education and counseling were associated with a reduced rate of perioperative complications and a reduced level of anxiety following CABG PURPOSE : The purpose of this study was to determine the influence of clean dressing technique in a home-care setting following a patient education program and telephone follow-up in a group of adult patients to wound healing in patients managed by sterile dressing changes by professional nurses in a general care outpatient clinic . DESIGN : R and omized controlled trial . SUBJECTS AND SETTING : The sample comprised adult patients with clean wounds who attended a general outpatient clinic in the Kowloon East district , a densely populated urban area in Hong Kong . Sixty-five subjects were r and omly allocated to the intervention group and 61 were allocated to the control group . INSTRUMENT : The Bates-Jensen Wound Assessment Tool ( BWAT ) was used to measure progress toward wound healing . METHODS : We compared a control group of patients who received normal wound care ( sterile dressing changes by professional nurses in a nonspecialized outpatient clinic ) to a group of adult patients who managed their wounds using clean technique for dressing changes in their home following education on wound care . The intervention group also received follow-up telephone calls on days 1 and 3 . The BWAT was completed to assess the wounds of both groups on the patients ' first attendance and once a week until their wounds had healed . RESULTS : Analysis revealed no significant differences between groups based on demographic or pertinent clinical characteristics . The mean BWAT score decreased in 2 weeks , from 27.26 to 15.15 ( Freidman test , & khgr;2= 26.00 , P < .000 ) for the intervention group and from 27.11 to 17.15 ( Freidman test , & khgr;2= 24.15 , P < .000 ) for the control group . A Mann-Whitney U test was used to compare the differences between the 2 groups based on total BWAT score . No statistically significant differences were found when groups were compared at baseline ( Z = −0.416 , P = .678 ) , week 1 ( Z = −1.313 , P = .189 ) , or week 2 ( Z = −0.905 , P = .418 ) . CONCLUSION : No differences in wound healing were found when patients who dressed their wounds at home using clean techniques versus patients who had their wounds dressed with sterile technique by professional nurses in a general outpatient clinic A r and omized 2 X 3 X 2 factorial design was used to evaluate the short- and long-term effects of interventions that provided different means of exerting personal control over postoperative experiences in a sample of 121 black and 47 white hysterectomy patients . One variable was the presence or absence of the description of the experience in concrete sensory terms ; the second variable was instruction in a cognitive-coping strategy , instruction in a behavior-coping strategy , or no instruction ; and the third variable was experimental or control information about the posthospital experience . There was support for the coping processes that concrete sensory information was expected to stimulate , but no significant effects on resumption of usual life activities as was expected . The behavioral-coping technique was associated with a reduction in pain medication . The cognitive-coping technique was associated with reports of better physical recovery during hospitalization , but longer hospitalization . Posthospitalization recovery data , collected 2 , 4 , and 12 weeks after discharge , showed a different pattern of effects for the interventions than observed during hospitalization Introduction : Most cancer patients want to be informed as much as possible . We conducted a r and omized trial comparing the impact of additional written information to oral information only on quality of life ( QoL ) and satisfaction of non-small cell lung cancer patients . Patients and Methods : Non-small cell lung cancer patients undergoing thoracic surgery were eligible . Patients were r and omized to receive oral information only or oral plus written information describing the disease and its associated surgery and outcomes . QoL was assessed by Psychologic Global Well-Being Index . Patients ’ satisfaction was assessed by question naire of satisfaction of hospitalized patients . Results : One-hundred two patients were included , full data were available for 75 of them ( 10 early deaths , 4 lost to follow-up , and 13 with incomplete question naires ) . QoL scores ( baseline , 3 months ) were comparable between both groups . In contrast , patients receiving oral plus written information were significantly dissatisfied with regard to several aspects of care regarding staffs as well as the structure . The information group significantly influenced satisfaction levels at multivariate analysis ( st and ardized beta coefficient , −0.26 , p = 0.04 ) . Conclusions : Unexpectedly , at the end of their hospital stay , patients receiving both oral and written information experienced a statistically significant lower level of satisfaction , whereas no difference in QoL between both groups were highlighted . Further research is needed on patient ’s information Objectives : This study was a prospect i ve investigation of the extent to which psychologic variables could be predictive of postoperative pain . Study aims were : 1 ) to evaluate whether an assessment of pre-operative distress factors could predict the intensity of postoperative pain ; and 2 ) to characterize the unique pattern in which anxiety and pain catastrophizing scores relate to postoperative pain . Methods : The Pain Catastrophizing Scale and the State-Trait Anxiety Inventory were administered to 38 patients scheduled for elective abdominal surgery . The question naires were completed on the day of admission , a day before the operation . On day 1 and day 2 following the operation , perception of pain intensity at the surgical wound was assessed by visual analog scale . Results : The Pain Catastrophizing Scale and State-Trait Anxiety Inventory scores were significantly correlated with the postoperative pain scores . A linear regression analysis showed that Pain Catastrophizing Scale predicted the level of postoperative pain intensity even after controlling for state anxiety and that trait anxiety was not a significant predictor . In addition , analysis of the unique pattern of each predictor related to postoperative pain intensity indicated a linear curve for the Pain Catastrophizing Scale and curvilinear curve for the state anxiety . Discussion : The results are discussed in light of appraisal and coping theories . It is suggested that a simple assessment of preoperative catastrophizing tendency and anxiety scores may assist medical teams in postoperative pain management OBJECTIVE To determine whether it is possible to increase patients ' knowledge and certainty about care-related issues , to reach a more empowering learning experience and to exercise a more positive impact on selected clinical outcomes by means of additional preadmission education ( education using the concept map method added to st and ard preadmission education ) than by means of st and ard preadmission education ( written educational material with non- systematic oral education ) . METHODS Elective hip arthroplasty patients were r and omized into group A ( n=62 ) , who received preadmission education using the concept map method with written educational material ; and group B ( n=61 ) , who received the written educational material and non- systematic oral education . Data were collected from both groups 4 weeks prior to hospital admission , at admission and at discharge using question naires . RESULTS In the first post-test at admission , group A had significantly better knowledge and certainty of care-related issues than group B. Group A also reported a significantly more positive learning experience than patients in group B. In the second post-test at discharge , patients in group A still had better knowledge and certainty of care-related issues than patients in group B. CONCLUSION Preadmission education using the concept map method and written educational material seems to yield better learning results than the use of written educational material with non- systematic oral education . PRACTICE IMPLICATION S Empowering preadmission education using the concept map method is beneficial for patients Objective Elective surgery represents a considerable source of stress for the patient . Many attempts have been made to prepare patients before surgery with the aim of reducing stress and improving outcome . This study used a novel approach to fulfill this aim by showing a videotape of a patient undergoing total hip replacement surgery , covering the time period from hospital admission to discharge , that strictly keeps to the patient ’s perspective . Methods Before elective total hip replacement surgery , 100 patients were r and omly assigned to a control group or a preparation group ; the latter group was shown the videotape on the evening before surgery . Anxiety and pain were evaluated daily for 5 days , beginning with the preoperative day , by means of the State-Trait Anxiety Inventory and a visual analog scale . Intraoperative heart rate and blood pressure , as well as postoperative intake of analgesics and sedatives , were recorded . Urinary levels of cortisol , epinephrine , and norepinephrine were determined in 12-hour sample s collected at night for 5 nights , beginning with the preoperative night . Results Compared with the control group , the preparation group showed significantly less anxiety on the morning before surgery and the mornings of the first 2 postoperative days , and significantly fewer of them had an intraoperative systolic blood pressure increase of more than 15 % . The pain ratings did not differ significantly between the two groups , but the prepared patients needed less analgesic medication after surgery . Prepared patients had significantly lower cortisol excretion during the preoperative night and the first 2 postoperative nights . Excretion of catecholamines did not differ significantly between groups . Conclusions We conclude that use of the videotape decreased anxiety and stress , measured in terms of urinary cortisol excretion and intraoperative systolic blood pressure increase , in patients undergoing hip replacement surgery and prepared them to cope better with postoperative pain Introduction and hypothesisThe purpose of this study was to determine if a clean intermittent self-catheterization ( CISC ) instructional video could improve anxiety in women undergoing prolapse and /or incontinence surgery . Methods A total of 199 women were r and omized to preoperative CISC video or routine counseling prior to prolapse/incontinence surgery . Patient anxiety , satisfaction , and concerns about CISC were evaluated using the State-Trait Anxiety Inventory-State ( STAI-S ) and study -specific visual analog scale ( VAS ) questions at four perioperative time points . Results STAI-S and VAS anxiety measures were similar at baseline between groups ; no significant differences were seen by group at any time point . STAI-S scores varied considerably over time , with highest scores at voiding trial failure and lowest scores at postoperative visit . Women in the video group had improved STAI-S scores and reported less worry and more comfort with CISC immediately following video viewing . Women with anxiety/depression had higher STAI-S scores at voiding trial failure and discharge and reported less anxiety reduction following video viewing compared to non-anxious/non-depressed peers . Conclusions Women undergoing prolapse/incontinence surgery have significant perioperative anxiety , which is exacerbated by voiding trial failure . Preoperative CISC video viewing decreases anxiety scores immediately following viewing , but this effect is not sustained at voiding trial failure . Women with baseline anxiety/depression exhibit less anxiety score improvement after video viewing and have overall higher anxiety scores perioperatively UNLABELLED This r and omized controlled trial aims to evaluate the influence of preoperative relaxation techniques on postoperative outcomes . From January 1997 to June 1998 208 patients were operated on for primary inguinal hernia or goiter . The patients were r and omized into two groups : Group A ( n = 103 ) underwent the surgical treatment with a preoperative visualization therapy . Group B ( n = 105 ) underwent the surgical treatment without a preoperative therapy . Patients with age under 18 years , ASA-status IV-V , recurrent inguinal hernia or recurrent goiter and malignant neoplasms were excluded from the study . There were no differences in age , sex , duration of the operation , training of the surgeon , and preoperative blood parameters between the two groups . RESULTS During the postoperative follow-up we observed more hematomas ( group A with visualization therapy : 30.3 % , group B without visualization therapy : 44.4 % ) as well as more pain ( group A : 4.2 , group B : 5.2 ) and analgesic consumption ( group A : 59.7 mg Tramadol HCL , group B : 72.5 mg Tramadol HCL ) in group B ( p < 0.05 ) . There were no significant differences in infections , nausea , hypocalcemia , tetania , recurrent nerve palsy , fever . CONCLUSIONS Preoperative visualization therapy reduces significantly the number of postoperative hematomas after inguinal hernia repair . Furthermore a decrease of analgesic requirements after surgical treatment was observed In order to underst and the effects of relaxation training on surgical stress response , a study was conducted among patients with abdominal surgery . Fifty-one patients were r and omly divided into two groups . Experimental group ( n = 25 ) : patients received preoperative instruction and relaxation training , control group ( n = 26 ) : patients received only preoperative instruction . Anxiety state ( state anxiety and physical symptoms of anxiety ) , blood pressure , heart rate , serum cortisone and postoperative pain of two groups were assessed and compared respectively on the third preoperative day , operation day , the first and the fourth postoperative day . Results showed that ( 1 ) there were significant differences between two groups ( P < 0.05 ) in state anxiety scores on each day , physical symptoms on the first and fourth day after operation and severity of pain on the first postoperative day . ( 2 ) responses of systolic pressure , diastolic pressure and heart rate decreased in the experimental group . ( 3 ) Serum cortisone level decreased significantly in the experimental group on the first postoperative day ( P < 0.05 ) . This study shows that relaxation training has positive effects on surgical stress responses , especially in reducing the psychological anxiety response . Relaxation training can be served as an easy and effective method in nursing practice Psychological stress has been shown to impair wound healing , but experimental research in surgical patients is lacking . This study investigated whether a brief psychological intervention could reduce stress and improve wound healing in surgical patients . This r and omised controlled trial was conducted at a surgical centre . Inclusion criteria were English-speaking patients over 18 years booked to undergo elective laparoscopic cholecystectomy ; exclusion criteria were cancellation of surgery , medical complications , and refusal of consent . Seventy five patients were r and omised and 15 patients were excluded ; 60 patients completed the study ( 15 male , 45 female ) . Participants were r and omised to receive st and ard care or st and ard care plus a 45-min psychological intervention that included relaxation and guided imagery with take-home relaxation CDs for listening to for 3 days before and 7 days after surgery . In both groups ePTFE tubes were inserted during surgery and removed at 7 days after surgery and analysed for hydroxyproline as a measure of collagen deposition and wound healing . Change in perceived stress from before surgery to 7-day follow-up was assessed using question naires . Intervention group patients showed a reduction in perceived stress compared with the control group , controlling for age . Patients in the intervention group had higher hydroxyproline deposition in the wound than did control group patients ( difference in means 0.35 , 95 % CI 0.66 - 0.03 ; t(43)=2.23 , p=0.03 ) . Changes in perceived stress were not associated with hydroxyproline deposition . A brief relaxation intervention prior to surgery can reduce stress and improve the wound healing response in surgical patients . The intervention may have particular clinical application for those at risk of poor healing following surgery Background : Post-operative anxiety is common and may have significant impact on the post-operative recovery of the patients . Theatre nurse visits before surgery has been shown to reduce patient ’s anxiety levels following general surgery . Aim : To investigate the effect of pre-operative visits and counselling by intensive care unit ( ICU ) nurses on patient ’s anxiety levels following carotid endarterectomy . Methods : This is an open-label and r and omized clinical trial . Patients undergoing carotid endarterectomy were divided into study ( n=60 ) and control group ( n=60 ) . For the study group , in addition to routine pre-operational counselling by the surgeons , ICU nurses visited the patients and provided a structured counselling the day before surgery . For the control group , only routine pre-operative counselling was provided . Anxiety levels were assessed by Zung self-rating anxiety scale ( SAS ) the day before surgery and on the day after being discharged from ICU to the ward . Results : The two groups were comparable in age , sex , surgical methods , and duration of ICU stays . Following the surgery , the mean SAS score in the control group increased from 50.5±5.4 to 58.5±7.3 ( p=0.03 ) , whereas the mean SAS score in the study group reduced from 51.5±4.3 to 45.1±6.5 ( p=0.02 ) . The proportion of patients with anxiety symptoms in the control group was higher than in the study group following the surgery ( 58.3 % vs. 33.3 % , p=0.001 ) . Conclusions : Pre-operative visits and counselling by ICU nurses could reduce patient ’s anxiety levels following carotid endarterectomy STUDY OBJECTIVE Surgical paients have been known to benefit immensely from psychological interventions . This study set out to assess the pre and postoperative anxiety levels and depression and the effect of cognitive therapy among Nigerian surgical patients . The effects of gender and educational status on perioperative anxiety and depression were also evaluated . STUDY DESIGN The study utilized a controlled outcome design to evaluate the efficacy of self-instructional training ( SIT ) and rational emotive therapy ( RET ) in surgical patients . Preoperative anxiety and depression scores were used as co-variants . PATIENTS Thirty-three ( 33 ) elective surgical patients were sample d r and omly , divided into 3 groups of eleven ( 11 ) patients each . Eight ( 8) subjects underwent gynaecological procedures while the remaining 25 subjects had general surgical procedures . The mean age was 32.72 + /- 15.83 years ( range = 17 - 16 years . ) MEASUREMENTS The major instruments used in the study were the State Anxiety Subscale of the Speilberger State Trait Anxiety Inventory ( STAI ) and Hospital Anxiety and Depression Inventory . MAIN RESULTS SIT had the potential to reduce anxiety level among subjects postoperatively ( t = 2.06 ; df = 10 ; p < 0.05 ) . The use of RET reduced depression among surgical patients ( t = 1.23 ; df = 10 ; p < 0.05 ) . CONCLUSIONS It was concluded that surgical patients manifest varying degrees of anxiety preoperatively and postoperatively . Patient 's pre and postoperative anxiety and depression can be reduced by the introduction of SIT and RET Wang AW , Gilbey HJ , Ackl and TR : Perioperative exercise programs improve early return of ambulatory function after total hip arthroplasty : A r and omized , controlled trial . Am J Phys Med Rehabil 2002;81:801–806 . Objective Patients with endstage hip arthritis have poor ambulatory function . The aim of this study was to determine if perioperative exercise programs are well tolerated by these elderly patients and if a customized program can achieve an earlier recovery of normal ambulatory function after total hip arthroplasty . Design Twenty-eight subjects scheduled for total hip arthroplasty were r and omized to either the exercise group and received a perioperative customized exercise program or the control group and received the routine perioperative care . Ambulatory function was assessed by measurement of gait parameters during a 25-m walk test , and walking endurance was assessed by a 6-min walk test . Results Exercise group subjects attended 97.3 % of scheduled exercise sessions with no training injuries . Exercise group subjects demonstrated greater stride length and gait velocity at 3 wk postsurgery . At 12 and 24 wk postsurgery , gait velocity was greater , and the 6-min walking distance was significantly greater than the control group . Conclusion The study indicates that perioperative customized exercise program are well tolerated in the elderly patient with endstage hip arthritis and are effective in improving the rate of recovery in ambulatory function in the first 6 mo after total hip arthroplasty This study examined the effect of psychoeducational preparation 1–2 days prior to surgery on postoperative state anxiety among Egyption bladder cancer patients with urinary diversion . The theoretical rationale was based upon the Betty Neuman Health-Care Systems Model . State anxiety was measured by the A-state form of the State Trait Anxiety Inventory . A total of 30 patients were assigned r and omly to experimental and control groups . Fifteen patients were included in each category . Preoperatively , the total sample was interviewed about their “ worries ” at that time , and data from this qualitative part were categorized into three subconcepts . Results revealed that their main anxieties are related to stress associated with being cancer patients followed by stress related to the impact of surgery on their bodies and on their social and marital life . Results from the quantitative part of the study showed that psychoeducational preparation lowered significantly state anxiety on the third day post-operatively and before discharge for those patients who had the intervention The investigators examined whether elders who have been taught pain management communication skills and pain management information obtain greater postoperative pain relief than elders not taught this information . Thirty-one elders were r and omly assigned preoperatively to a control or communication group in this posttest-only experiment with repeated measures . Communication group participants were taught pain management , pain communication skills , and the use of two pain-intensity scales . Control group participants were taught to use the two pain-intensity scales . Pain was measured with the McGill Pain Question naire Short Form . The communication group elders reported less postoperative pain over the course of their hospital stay . Pain management knowledge alone may have enabled the elders to obtain greater pain relief . Nurses may want to incorporate similar pain management information and pain communication skills when teaching elders how to obtain greater postoperative pain relief Background : The ‘ Fit For Surgery ’ programme was based on previous studies suggesting improvement in risk factors contributing to coronary disease while patients wait for cardiac surgery . Aim : To evaluate our nurse-led programme in a r and omised controlled trial with 188 patients . Methods : Patients listed for coronary artery bypass surgery with at least one poorly controlled risk factor were r and omised to st and ard care or the intervention which provided lifestyle counselling and preparation for surgery at monthly intervals . Primary outcome measurements were anxiety , blood pressure , cholesterol , length of stay and body mass index . Costs of the intervention were also collected . Results : For both groups blood pressure and total cholesterol improved ( Blood pressure mm Hg ( Control − 9.11 ( CI − 4.89 , − 13.33 ) ; Intervention − 13.02 ( CI − 8.76 , − U17.29 ) both p < 0.01 ) ; total cholesterol ( Control − 0.20 ( CI − 0.03 , − 0.37 ) p = 0.02 , Intervention − 0.18 ( CI − 0.02 , − 0.34 ) p = 0.03 ) . However there were no significant differences between the groups . Cost minimization analysis showed that the total costs were less in the intervention group due to fewer admissions ( total costs £ 10,754 ( 3746 ) v £ 13,047 ( 5835 ) , CI − 3743 , − 843 ; p = 0.002 ) . Conclusions : The nurse-led programme did not appear to reduce risk factors prior to coronary artery bypass surgery . However , the intervention appears to reduce overall healthcare utilization OBJECTIVE The present study was design ed to test the hypotheses that response expectancies and emotional distress mediate the effects of an empirically vali date d presurgical hypnosis intervention on postsurgical side effects ( i.e. , pain , nausea , and fatigue ) . METHOD Women ( n = 200 ) undergoing breast-conserving surgery ( mean age = 48.50 years ; 63 % White , 15 % Hispanic , 13 % African American , and 9 % other ) were r and omized to a hypnosis or to an attention control group . Prior to surgery , patients completed assessment s of hypothesized mediators ( response expectancies and emotional distress ) , and following surgery , patients completed assessment s of outcome variables ( pain , nausea , and fatigue ) . RESULTS Structural equation modeling revealed the following : ( a ) Hypnotic effects on postsurgical pain were partially mediated by pain expectancy ( p < .0001 ) but not by distress ( p = .12 ) ; ( b ) hypnotic effects on postsurgical nausea were partially mediated by presurgical distress ( p = .02 ) but not by nausea expectancy ( p = .10 ) ; and ( c ) hypnotic effects on postsurgical fatigue were partially mediated by both fatigue expectancy ( p = .0001 ) and presurgical distress ( p = .02 ) . CONCLUSIONS The results demonstrate the mediational roles of response expectancies and emotional distress in clinical benefits associated with a hypnotic intervention for breast cancer surgical patients . More broadly , the results improve underst and ing of the underlying mechanisms responsible for hypnotic phenomena and suggest that future hypnotic interventions target patient expectancies and distress to improve postsurgical recovery AIM This paper reports on a study which aim ed to evaluate the effects of structured written preoperative information on patients ' postoperative psychological and physical wellbeing after surgery for abdominal aortic aneurysm ( AAA ) . BACKGROUND The possible benefits of current booklets written by professionals on postoperative psychological and physical wellbeing in patients with AAA are unknown . Previous studies have shown that preoperative information has a favourable effect on both mood state and physical mobilization . METHOD Fifty-two patients admitted for elective repair of AAA were selected consecutively and r and omized to receive only verbal ( control group ) , or verbal and written information in booklet form ( experimental group ) . The booklet contained procedural and sensory information about the disease and its treatment . Two question naires were used to establish whether the booklet had any effect on perceived health , psychological and physical wellbeing postoperatively . RESULTS The two groups were similar regarding their perceived health but differed significantly regarding psychological wellbeing pre- and postoperatively . Patients in the experimental group were significantly sadder both pre- and postoperatively compared with those in the control group . Both groups were similar in postoperative physical wellbeing . CONCLUSION This group of patients often has asymptomatic disease , with a short interval between diagnosis and major surgery . When patients receive an information booklet during this period , this seems to cause more worries than anticipated . Hence , a more supportive educational programme might benefit this patient group , both pre- and postoperatively Within the context of a double blind r and omized controlled parallel trial of 2 nonsteroidal antiinflammatory drugs , we vali date d WOMAC , a new multidimensional , self-administered health status instrument for patients with osteoarthritis of the hip or knee . The pain , stiffness and physical function subscales fulfil conventional criteria for face , content and construct validity , reliability , responsiveness and relative efficiency . WOMAC is a disease-specific purpose built high performance instrument for evaluative research in osteoarthritis clinical trials OBJECTIVES To evaluate the verbal and written preoperative information in patients undergoing surgery for malignant gynaecologic disease , in terms of satisfaction about preoperative received informations , hospitalization days , postoperative pain experienced using visual analogue scale ( VAS ) and number of pain drugs used daily . STUDY DESIGN From January 2008 to December 2012 , consecutive patients with diagnosis of endometrial cancer , referred to the Division of Gynecology of University Campus Bio-Medico of Rome , were enrolled . Eligible subjects were r and omized into two groups : Group V ( Verbal information ward ) consisted of patients who had verbal preoperative information about surgical procedure and postoperative management and Group W ( Written Information ward ) consisted of patients who had written preoperative information . All preoperative and postoperative data were recorded . Concerning satisfaction about preoperative received informations , patients were asked to complete the QLQ-C30 and the EORTC INFO25 . RESULTS 190 patients were considered in this study . Group W ( n=92 ) has a better info satisfaction ( p=0.0008 , statistically significant ) , a mean VAS value lower ( p=0.02 , statistically significant ) and also a lower number of hospitalization days ( p=0.0265 , statistically significant ) and pain medications used daily , ( p=0.0120 , statistically significant ) , comparing with group V ( n=98 ) . CONCLUSIONS We support the use of preoperative information leaflet to better prepare patients for a surgical procedure , showing a faster recovery , low medications use and a better quality of life outcome BACKGROUND ( Extreme ) obesity is a chronic harmful condition with high risk of medical comorbidities and negative social and emotional consequences . Bariatric surgery is an effective intervention for obesity , but approximately 20 to 30 % of the patients experience adverse outcomes after surgery and there is a need for augmentation of current treatment strategies . This study examines the added value of pre-operative cognitive behavioral therapy ( CBT ) focused on modification of thoughts and behaviors in terms of eating behavior and physical exercise as well as preparation for surgery and postoperative life style . We hypothesize that pre-operative CBT will result in better weight loss maintenance , reduction of maladaptive eating behavior and better adherence to postoperative lifestyle on the long term as compared to bariatric surgery alone . METHODS One hundred and twenty eight patients that are on a waiting list for bariatric surgery are r and omly assigned to the control or treatment condition . Patients in the treatment condition receive 10 sessions of CBT before surgery aim ed at modifying dysfunctional eating habits and behaviors and developing more rational weight and body-related beliefs in order to enable long term maintenance of a healthier lifestyle after surgery . Weight loss , eating behavior , eating disorders , depression , quality of life and psychological distress are assessed before and after treatment , as well as 1 , 3 , and 5 year following surgery PURPOSE OF THE RESEARCH This study aim ed to test the feasibility of implementing a psychoeducational intervention program for gynecological cancer patients . METHODS AND SAMPLE A single-blinded r and omized controlled trial and mixed- method design were used . Study subjects were newly diagnosed gynecological cancer patients with surgery as the first-line treatment . They were r and omly assigned to the intervention group , in which a psychoeducational intervention program based on a thematic counseling model was offered , or to the attention control group . Quantitative data on sexual functioning , quality of life , uncertainty , anxiety , depression and social support were collected at recruitment , post-operative and during the in-hospital period , and eight weeks after the operation . Participants in the intervention group and three nurses working in the clinical setting were invited to have semi-structured interviews . KEY RESULTS Of the 30 eligible subjects , 26 were successfully recruited into the study . Following the psychoeducational intervention program , there was significant improvement in the level of inconsistent information about the illness within the category of uncertainty among participants in the intervention group . In addition , trends towards improvement were demonstrated in quality of life , uncertainty , depression and perceived social support with the provision of the interventions . Qualitative data indicated the interventions were desired and appreciated by the participants , as well as being feasible and practical to implement in Hong Kong clinical setting s. CONCLUSIONS The findings suggest that it is feasible to deliver the psychoeducational intervention program and it may have beneficial effects in gynecological cancer patients . A full-scale study is warranted to confirm the results The purpose of this study was to assess the effectiveness of two different relaxation techniques in the management of postoperative pain . The sample consisted of 40 women between the ages of 21 and 65 years who were undergoing elective cholecystectomy . Using an experimental design , participants were r and omly assigned to four groups : an experimental group who received a taped recording of a rhythmic breathing exercise ( RB ) ; an experimental group who received a taped recording of Benson 's Relaxation Technique ( BRT ) ; an attention-distraction control group ( CA ) who received a taped recording of a history of the hospital ; and a st and ard control ( CB ) group who had only the routine perioperative care which all groups received . Data were collected on postoperative sensation and distress at five time points during the first 72 postoperative hours , number of doses of analgesic medication during the same time period , and number of postoperative hospital days . Data were analysed using multivariate and univariate analyses of variance . The BRT group was significantly different from the CA group on a combined sensation and distress factor ( P = 0.011 ) . No significant differences were found among groups for doses of analgesics ( P = 0.068 ) or postoperative hospital days ( P = 0.56 ) OBJECTIVE Psychoeducational preparation is known to improve postoperative outcome . We tested two common psychoeducational procedures in elderly orthopedic patients , examining how best to match interventions to patients by psychological type . METHODS Two hundred twenty-two elderly patients undergoing total hip or knee replacement were r and omly assigned to 1 ) a slide-tape with information on the postoperative , in-hospital rehabilitation experience , or 2 ) training in Benson 's Relaxation Response with a bedside audiotape , in a 2 x 2 factorial design . RESULTS The relaxation response did not influence postoperative outcomes . The educational intervention reduced length of stay and pain medication use for patients who exhibited most denial ( tendency to avoid thinking about unpleasant events ) , and reduced postoperative anxiety and cognitive errors on the Mini-Mental State Exam for patients with most baseline anxiety . There was no effect on postoperative pain . CONCLUSIONS The importance of attending to the patient 's psychological state and level of preparation before orthopedic surgery is reinforced . Patients who exhibit most denial and highest anxiety may benefit from educational interventions , but patients ' directly expressing desire for information may be a poor guide in deciding which patients would benefit , compared with more formal psychological testing for denial and anxiety STUDY OBJECTIVE To determine whether providing additional information to the st and ard consent process , in the form of a multimedia module ( MM ) , improves patient knowledge about operative laparoscopy without increasing anxiety . DESIGN R and omized controlled trial ( Canadian Task Force classification I ) . SETTING Two outpatient gynecologic clinics , one in a private hospital and the other in a public teaching hospital . PATIENTS Forty-one women aged 19 to 51 years ( median , 35.6 years ) requiring operative laparoscopy for investigation and treatment of pelvic pain . INTERVENTION Following the st and ard informed consent process , patients were r and omized to watch the MM ( intervention group , n = 21 ) or not ( control group , n = 20 ) . The surgeon was blinded to the group assignments . All patients completed a knowledge question naire and the Spielberger short-form State-Trait Anxiety Inventory . Six weeks after recruitment , patients completed the knowledge question naire and the State-Trait Anxiety Inventory a second time to assess knowledge retention and anxiety scores . MEASUREMENTS AND MAIN RESULTS Patient knowledge of operative laparoscopy , anxiety level , and acceptance of the MM were recorded . The MM intervention group demonstrated superior knowledge scores . Mean ( SE ) score in the MM group was 11.3 ( 0.49 ) , and in the control group was 7.9 ( 0.50 ) ( p < .001 ) ( maximum score , 14 ) . This did not translate into improved knowledge scores 6 weeks later ; the score in the MM group was 8.4 ( 0.53 ) vs. 7.8 ( 0.50 ) in the control group ( p = .44 ) . There was no difference in anxiety levels between the groups at intervention or after 6 weeks . Overall , patients found the MM acceptable , and 18 women ( 86 % ) in the intervention group and 12 ( 60 % ) in the control group stated they would prefer this style of informed consent in the future . CONCLUSION Use of an MM enhances the informed consent process by improving patient knowledge , in the short term , without increasing anxiety OBJECTIVE To investigate the feasibility and preliminary effectiveness of a home-based intensive exercise program to improve physical health of frail elderly patients scheduled for elective total hip arthroplasty ( THA ) . DESIGN Single-blind pilot r and omized controlled trial . SETTING Patients ' homes and a general hospital in The Netherl and s. PARTICIPANTS Frail patients ( N=30 ) older than 65 years . INTERVENTION A preoperative , home-based program supervised by an experienced physical therapist to train functional activities and walking capacity . The control group received usual care consisting of 1 session of instructions . MAIN OUTCOME MEASURES Feasibility was determined on the basis of adherence to treatment , patient satisfaction , adverse events , walking distance ( measured with a pedometer ) , and intensity of exercise ( evaluated with the Borg scale ) . Preliminary pre- and postoperative effectiveness was determined by the Timed Up & Go ( TUG ) test , 6-minute walk test ( 6MWT ) , Chair Rise Time , and self-reported measures of functions , activities , and participation . RESULTS Patient satisfaction and adherence to the training were good ( median=5 on a 5-point Likert scale ) and no serious adverse events occurred . The Borg score during training was 14 ( range , 13 - 16 ) . Preoperative clinical relevant differences on the TUG test ( 2.9 s ; 95 % confidence interval [ CI ] , -0.9 to 6.6 ) and significant differences on the 6MWT ( 41 m ; 95 % CI , 8 to 74 ) were found between groups . CONCLUSIONS Intensive preoperative training at home is feasible for frail elderly patients waiting for THA and produces relevant changes in functional health . A larger multicenter r and omized controlled trial is in progress to investigate the (cost-)effectiveness of preoperative training Objective : To examine the effect of pre-operative physiotherapy before hip arthroplasty in patients with end-stage hip osteoarthritis . Design : A prospect i ve r and omized controlled study . Setting : Physical medicine and rehabilitation and orthopaedic departments of Policlinico Gemelli of Rome . Subjects : Twenty-three patients r and omized in study and control groups . Intervention : The study group took part in an educational and physiotherapy programme one month before surgery . Both groups took part in the same inpatient rehabilitation programme after surgery . Main outcome measures : Both groups were evaluated one month ( T0 ) and the day before arthroplasty ( T1 ) , after 15 days ( T2 ) , four weeks ( T3 ) and three months ( T4 ) post surgery , using the Barthel Index , the Short Form-36 ( SF-36 ) , the Western Ontario and McMaster Osteoarthritis Index ( WOMAC ) , the Hip Harris Score ( HHS ) , visual analogue scale ( VAS ) , the British Medical Research Council ( BMRC ) measures of hip abductor and quadriceps strength and range of hip abduction and external rotation . Results : There were no significant differences between groups with regard to the Barthel Index , SF-36 , WOMAC and HHS at T4 . The study group presented significant improvements of the SF-36 physical composite score at T1 . The hip external rotation was significantly higher in the study group at each evaluation and the visual analogue scale values were lower at T1 , T3 and T4 . Conclusion : Pre-operative physiotherapy in patients undergoing hip arthroplasty does not improve impairment and health-related quality of life after intervention . Physiotherapy and educational therapy may be useful for end-stage osteoarthritis AIM This paper is a report of a study to determine the effectiveness of jaw and total body relaxation for postoperative pain , anxiety and level of relaxation , and to determine any patient expectancy effects . BACKGROUND Relaxation is increasingly suggested as a pain control technique that can be used by nurses in daily practice . A systematic review of the effectiveness of relaxation for postoperative pain relief revealed many poorly design ed studies and only some weak evidence supporting the use of relaxation for postoperative pain . METHOD A r and omized controlled trial ( n = 118 ) was conducted between 2002 and 2003 to compare total body relaxation , jaw relaxation , attention control and usual care . Consenting patients admitted for elective orthopaedic surgery aged 18 or over , able to speak English and able to tense and relax more than two muscle groups were included . Pain at rest and on movement , anxiety and relaxation were assessed at pre-admission clinic , pre-intervention , immediately post-intervention and 1 , 2 , 3 and 4 hours later . However , the trial was under-powered . FINDINGS There were statistically significant reductions in pain at rest from pre- to post-intervention for both the relaxation groups and the attention control group . The usual care group had a small increase in pain , whilst the other three groups had similar small decreases in pain . There was no statistically significant difference in anxiety or relaxation scores pre- to post-intervention between groups . CONCLUSION Jaw relaxation could give these orthopaedic patients a small , very short-lasting additional amount of pain relief , and it may be that staff and patients feel this small benefit to be worthwhile The purpose of this investigation was to evaluate the effects of guided imagery on postoperative outcomes in patients undergoing same-day surgical procedures . Forty-four adults scheduled for head and neck procedures were r and omly assigned into 2 groups for this single-blind investigation . Anxiety and baseline pain levels were documented preoperatively . Both groups received 28 minutes of privacy , during which subjects in the experimental group listened to a guided imagery compact disk ( CD ) , but control group patients received no intervention . Data were collected on pain and narcotic consumption at 1- and 2-hour postoperative intervals . In addition , discharge times from the postoperative anesthesia care unit ( PACU ) and the ambulatory procedure unit and patient satisfaction scores were collected . The change in anxiety levels decreased significantly in the guided imagery group ( P = .002 ) . At 2 hours , the guided imagery group reported significantly less pain ( P = .041 ) . In addition , length of stay in PACU in the guided imagery group was an average of 9 minutes less than in the control group ( P = .055 ) . The use of guided imagery in the ambulatory surgery setting can significantly reduce preoperative anxiety , which can result in less postoperative pain and earlier PACU discharge times This study tested the effect of a preoperative pain communication intervention on older adults ’ ability to obtain pain relief after a total knee arthroplasty . A posttest-only experimental design was used to compare older adults r and omly assigned to ( a ) view a pain management and pain communication film , ( b ) view the pain management film only , or ( c ) receive st and ard care only . Initial method adjustments decreased potential error in the study . Adjustments included testing only total knee arthroplasty patients receiving st and ard physical therapy and omitting unreliable measures from the analyses . Recruitment of the st and ard care group was halted when differences emerged between the remaining groups . Older adults in the communication group reported significantly less sensory pain on postoperative Day 1 than older adults in the pain management only group . Teaching older adults both pain communication skills and pain management information before surgery might result in greater pain relief during the early postoperative period Purpose Laparoscopic Cholecystectomy ( LC ) is common practice in treatment of symptomatic gall stones . LC is often associatedwith preoperative anxiety and stress which maynegatively impact postoperative pain perception and recovery from surgery . The aim of the present study wasto investigate whether a “ non-pharmacological ” interventionwith guided imagery can reduce preoperative anxiety , postoperative pain perception and medication comparedto st and ard care in patients undergoing LC . Methods In a pragmatic multi-centre r and omized controlled study 140 patients were r and omized to a Guided Imagery (GI)group or control group . The GI group was provided witha CD to practice guided imagery once a day , 7 days priorto surgery . Patients in the control group received st and ardcare instructions only . Primary outcome measurement wasthe use of postoperative analgesics . Secondary outcome parameters were preoperative anxiety levels using theAmsterdam Preoperative Anxiety and Information Scale(APAIS ) , postoperative pain perception ( VAS-scale ) , generalpatient satisfaction ( PSQ ) and safety ( adverse events)with treatment . Results 95 out of 140 r and omized patients completed the study , 43 in the GI and 52 in the control group . The major reasons for dropping out were acute LCs or cancellation ofLC . Both groups were highly comparable with respect todemographic data . The majority was female ( GI : 77%,Control : 75 % ) . Postoperative morphine use was not significantlydifferent between the GI ( 15.8±18.5 mg ) and control group ( 12.5±13.6 mg , p=0.34 ) . No significant differenceswere observed in anxiety and postoperative VASscores . Twenty-three percent of patients did exercises1 - 3 times , 65 % 4 - 7 times and 12 % > 7 times . Within GIgroup analysis showed significantly less postoperativemorphine use upon better compliance to GI exercises(p=0.02 ) . Conclusion It is not as simple as replacing a pill with a CD . GuidedImagery seems to reduce postoperative pain medicationonce compliance to imagery exercises is achieved We studied 32 coronary bypass patients to examine the effect of hypnosis on recovery from surgery . The patients were assessed for hypnotizability with the Hypnotic Induction Profile ( HIP ) and assigned to experimental groups with a r and om stratification procedure to equate for differences in hypnotizability , age , and severity of illness . We taught patients in groups one and two formal hypnosis with different treatment strategies ; patients in group three were not taught formal hypnosis or a treatment strategy . Scores on the HIP were significant predictors of recovery , independent of experimental treatment with formal hypnosis . Patients who scored " Midrange " stabilized more quickly in the intensive care unit ( ICU ) than those who scored " High " or " Low " ( p = < .05 ) . Patients who scored " High " had more labile blood pressure in the ICU compared to the " Midrange " and " Lows " ( p = < .05 ) . Measured hypnotizability was associated with the recovery sequence from surgery Background : The preoperative period ( prehabilitation ) may represent a more appropriate time than the postoperative period to implement an intervention . The impact of prehabilitation on recovery of function al exercise capacity was thus studied in patients undergoing colorectal resection for cancer . Methods : A parallel-arm single-blind superiority r and omized controlled trial was conducted . Seventy-seven patients were r and omized to receive either prehabilitation ( n = 38 ) or rehabilitation ( n = 39 ) . Both groups received a home-based intervention of moderate aerobic and resistance exercises , nutritional counseling with protein supplementation , and relaxation exercises initiated either 4 weeks before surgery ( prehabilitation ) or immediately after surgery ( rehabilitation ) , and continued for 8 weeks after surgery . Patients were managed with an enhanced recovery pathway . Primary outcome was functional exercise capacity measured using the vali date d 6-min walk test . Results : Median duration of prehabilitation was 24.5 days . While awaiting surgery , functional walking capacity increased ( ≥20 m ) in a higher proportion of the prehabilitation group compared with the rehabilitation group ( 53 vs. 15 % , adjusted P = 0.006 ) . Complication rates and duration of hospital stay were similar . The difference between baseline and 8-week 6-min walking test was significantly higher in the prehabilitation compared with the rehabilitation group ( + 23.7 m [ SD , 54.8 ] vs. −21.8 m [ SD , 80.7 ] ; mean difference 45.4 m [ 95 % CI , 13.9 to 77.0 ] ) . A higher proportion of the prehabilitation group were also recovered to or above baseline exercise capacity at 8 weeks compared with the rehabilitation group ( 84 vs. 62 % , adjusted P = 0.049 ) . Conclusion : Meaningful changes in postoperative functional exercise capacity can be achieved with a prehabilitation program In a prospect i ve , r and omized , single-blind trial , we assessed the effectiveness of a preoperative video as a source of additional patient information before ambulatory surgery . One hundred twenty-seven patients were allocated to either treatment ( video ) or control ( nonvideo ) groups . Of the 127 , 17 ( 13 % ) patients correctly answered all process , risk , and misconception statements using a question naire . Overall , the video group was 2 - 16 times more likely to recall all knowledge questions correctly than the non-video group after adjusting for previous general anesthesia experience , state ( how one feels at the moment ) , and trait ( how one generally feels ) anxiety levels ( relative risk 6.36 , 95 % confidence interval 2.01 - 15.82 ) . The predictors of correct risk knowledge were those who had a video intervention ( relative risk 7.12 , 95 % confidence interval 3.70 to 10.07 ) and low trait anxiety scores ( relative risk 5.88 , 95 % confidence interval 1.69 to 25.00 ) . A video could be an important additional component of the preoperative interview , but anesthesiologists will still need to provide patient-specific information . Implication s : This study r and omly allocated adults to see a video about anesthesia before scheduled ambulatory surgery . The video group had better recall of information . The video was a useful adjunct to routine preoperative consultations . ( Anesth Analg 1998;87:531 - 6 The efficacy of the regular elicitation of the relaxation response in reducing surgical anxiety and pain in an ambulatory surgery setting was studied in a population of patients scheduled for the surgical removal of a skin cancer . Forty-nine patients with skin cancer were enrolled in the study immediately after being informed of the ned for surgery ; 21 of these patients elicited the relaxation response 20 minutes per day until the day of surgery , 21 read for 20 minutes per day , and 7 were noncompliant and were excluded from the study . Contrary to expectations , neither group of patients showed any increase in anxiety immediately before or after surgery on either psychological or physiological measures . Thus , there were no differences between the two groups on any of the psychological or physiological measures of anxiety , nor were there any differences in pain perception . There were statistically significant subjective differences ; the experimental patients stated that the relaxation-response technique had reduced their anxiety several days before surgery and reportedly experienced their highest levels of anxiety prior to entering the study , while the controls experienced their highest levels of anxiety during and after surgery . This suggests that ( 1 ) minor outpatient surgery does not lead to detectable increased anxiety levels on the day of surgery and ( 2 ) regular elicitation of the relaxation response can alter subjective reports of distress associated with surgery BACKGROUND : Nonpharmacological interventions , including combinations of music , education , coping skills , and relaxation techniques , have been found to have a positive effect on patients ' perceived anxiety in many setting s. However , few research studies have assessed and compared the effectiveness of music and relaxation interventions in reducing the anxiety levels of orthopaedic and oncology patients . PURPOSE : We conducted a prospect i ve , r and omized , controlled study to examine the effectiveness of music and relaxation interventions on perceived anxiety during initial hospitalization for patients receiving orthopaedic or cancer care treatment at a Midwestern teaching hospital . METHOD : This was a pre-test/post-test study design utilizing the State-Trait Anxiety Inventory . One hundred twelve patients were r and omized into 3 study groups . Thirty-eight subjects ( 34 % ) were r and omized in the music-focused relaxation group , 35 subjects ( 31 % ) in the music and video group , and 39 ( 35 % ) subjects in the control group . Fifty-seven ( 51 % ) were orthopaedic patients and 55 ( 49 % ) were oncology patients . RESULTS : Comparison of the 3 study groups showed no statistically significant differences with regard to patients ' demographics . Although reduced anxiety levels were reported for all 3 groups postintervention , the differences were not statistically significant ( p > .05 ) . Also , there was no significant difference found between the perceived anxiety levels of patients admitted to the orthopaedic and oncology care units ( p > .05 ) . Finally , the results of the intragroup comparisons ( regardless of the group assignment ) showed a significant decrease in anxiety levels reported by all patients postintervention ( p < .001 ) . CONCLUSIONS : Music and relaxation interventions could be an additional tool in assisting patients to become less anxious during their hospital stay . Music focused relaxation and music and video are both valuable and cost-effective strategies that can assist the orthopaedic and oncology patient population . Identifying opportunities to make these interventions easily accessible to healthcare professionals can assist in the management of patient anxiety during hospitalization The effects of pre-surgery intervention messages on postsurgical pain and recovery in 42 female patients were compared . Each participant was scheduled for at least two periodontal surgeries and exposed to one of four messages before each surgery . Auditory and visual messages classified as " control enhancement " were associated with reduction of pain after the second surgery with no effect after the first surgery Cardiac surgery correlates with increased perioperative stress and anxiety . We tested whether preoperative extensive oral information in combination with more personal attention by the surgeon is associated with any effect on patients ’ perioperative stress , anxiety , and well-being . Sixty patients awaiting open heart surgery were divided into two groups . Group I consisted of 30 patients who received routine medical information through an informative pamphlet . In Group II ( n = 30 patients ) , additional , extensive oral medical information and more personal attention by the surgeon was provided before surgery . Salivary cortisol , plasma cortisol , state anxiety , and patients ’ well-being were measured perioperatively . Extensive preoperative oral information in combination with more personal attention by the physician did not have any significant influence on the perioperative psychoendocrinologic course of stress . During transport to the operating room , salivary cortisol increased significantly ( P < 0.001 ) in both groups ( ranges are 95 % confidence intervals ) ( Group I , 23.2 nmol/L [ 17.1–31.5 ] ; Group II , 14.6 nmol/L [ 9.9–21.3 ] ) versus the first day in the hospital ( Group I , 8.4 nmol/L [ 6.2–11.4 ] ; Group II , 6.7 nmol/L [ 5.3–8.6 ] ) . After the induction of anesthesia , plasma cortisol decreased significantly ( P < 0.001 ) in both groups ( Group I , 170.1 nmol/L [ 143.6–201.4 ] ; Group II , 172.0 nmol/L [ 142.2–208.1 ] ) versus preoperative levels . After surgery , well-being decreased ( P = 0.003 ) in all patients , and patients ’ state anxiety was reduced ( P = 0.001 ) after surgery . Our data demonstrate a lack of effect of extensive oral medical information that was presented as part of clinical routine on the perioperative psychoendocrinologic course of stress . High levels of stress during transport to the operating room were detected Eighty women undergoing multimodality treatment for large ( > 4 cm ) or locally advanced ( T3 , T4 , Tx , N2 ) , breast cancers participated in a r and omised controlled trial ( RCT ) to evaluate the immuno-modulatory effects of relaxation training and guided imagery . Patients underwent chemotherapy followed by surgery , radiotherapy , and hormone therapy . Those in the intervention group were taught relaxation and guided imagery . Patients kept diaries of the frequency of relaxation practice and imagery vividness . On 10 occasions during the 37 weeks following the diagnosis , blood was taken for immunological assays CD phenotyping : T cell subsets ( helper , cytotoxic ) , natural killer ( NK ) and lymphokine activated killer ( LAK ) cells , B lymphocytes and monocytes ; cytotoxicity : NK and LAK cell activities ; cytokines interleukin 1 beta ( 1beta ) , 2 , 4 and 6 and tumour necrosis factor alpha . Significant between-group differences were found in the number of CD25 + ( activated T cells ) and CD56 + ( LAK cell ) subsets . The number of CD3 + ( mature ) T cells was significantly higher following chemotherapy and radiotherapy , in patients r and omised to relaxation and guided imagery . Using a median split , women who rated their imagery ratings highly had elevated levels of NK cell activity at the end of chemotherapy and at follow-up . Significant correlations were obtained between imagery ratings and baseline corrected values for NK and LAK cell activity , and IL1beta . Relaxation frequency correlated with the number of CD4 + ( T helper ) cells , the CD4+:8 + ( helper : cytotoxic ) ratio , and IL1beta levels . Relaxation training and guided imagery beneficially altered putative anti-cancer host defences during and after multimodality therapy . Such changes , to the best of our knowledge , have not been previously documented in a RCT AIM This paper reports a study examining the effects of preoperative nursing intervention for pain on abdominal surgery preoperative anxiety and attitude to pain , and postoperative pain . METHOD In a r and omized controlled study conducted between January and August 2001 , patients undergoing abdominal surgery in a medical center in southern Taiwan were r and omly assigned to an experimental ( n = 32 ) or control group ( n = 30 ) . The experimental group received routine care and preoperative nursing intervention for pain , while the control group received routine care only . A structured question naire including an anxiety scale , pain attitude scale , and Brief Pain Inventory was used to assess the results . RESULTS Participants in the experimental group experienced a significant decrease in preoperative anxiety and a significant improvement in preoperative pain attitude . They also had statistically significantly lower postoperative pain intensity for 4 hours after surgery and lower highest pain intensity within the first 24 hours after surgery . Perceived pain interference during position changes , deep breathing/coughing , and moments of emotion in the experimental group was statistically significantly lower than that of the control group in the same situations . The experimental group also started out-of-bed activities 1.5 days earlier . CONCLUSION Preoperative nursing intervention for pain has positive effects for patients undergoing abdominal surgery . The intervention used in this study could serve as a guide for nurses to improve the pain care of these patients Elective surgery patients were prepared for surgery with training in muscle relaxation or with information about sensations they would experience . Relaxation reduced hospital stay , pain , and medication for pain and increased strength , energy , and postoperative epinephrine levels . Information reduced hospital stay . Personality variables ( denial , fear , aggressiveness ) were associated with recovery and influenced patients ' responses to preparation . Less frightened patients benefited more from relaxation than did very frightened patients . Nonaggressive patients reacted to information with decreased hospital stay along with increased pain , medication , and epinephrine . Aggressive patients responded to information with decreased hospital stay along with decreased pain , medication , and epinephrine . Patients using denial were not harmed by preparation . A catharsis/moderation model is proposed to explain how information benefits patients . An active coping model is proposed to explain the benefits of relaxation . This study suggests that behavioral preparation benefits even frightened , aggressive , or denying elective surgical patients OBJECTIVE To test the proposal that external health locus of control and self-efficacy would moderate the effects of a psychological preparation for surgery on outcomes for surgical heart patients . MAIN OUTCOME MEASURES Psychological distress , pain , serum cortisol , and tumor necrosis factor alpha . DESIGN A total of 80 coronary artery bypass graft patients were given st and ard care plus a psychological preparation or st and ard care alone using a single-blind methodology with r and om assignment . Data on psychological and biological functioning were collected at admission ( baseline ) and discharge . RESULTS As predicted , external health locus of control and self-efficacy moderated the effect of the preparation on all outcomes . Results indicated that for high external health locus of control , the preparation was related to lower distress for people with high self-efficacy compared with those with low self-efficacy . When external health locus of control was low , the preparation was related to lower distress for those with lower self-efficacy . CONCLUSION These findings caution against the use of preparations and education for surgical patients without accounting for control appraisal PURPOSE This study examined the effects of preoperative incentive spirometry ( IS ) education ( POISE ) on postoperative outcomes for knee and hip total joint replacement patients . DESIGN In this prospect i ve study , 140 patients were r and omized to Group 1 ( POISE intervention = 50 completing ) or Group 2 ( no intervention = 56 completing ) ( 34 dropped ) . METHODS The Group 1 intervention consisted of formal instruction preoperatively for IS home use , postoperative use , and IS volumes documentation . Group 2 patients received no intervention . Patients recorded postoperative IS volumes , which were used to determine return to baseline volume . FINDINGS One hundred six patients completed the study . Most were Caucasian females averaging 64 years . Although IS return to baseline volume time was not significantly different between groups , POISE patients had fewer postoperative complications , hospital days , and charges . POISE patients ranked the intervention as helpful . CONCLUSIONS Although IS volumes were not significantly different between groups , POISE patients had better outcomes and ranked the intervention as helpful An intervention assisting older adults to communicate their pain was tested in a posttest-only experiment . Thirty-eight preoperative older adults were r and omly assigned to a communication group watching a videotape about communicating and managing postoperative pain or a comparison group watching a videotape about managing postoperative pain only . Pain was measured on Postoperative Days 1 and 2 , and 1 and 7 days after hospital discharge by a data collector blind to the condition . The communication group reported greater pain relief and less pain interference on Postoperative Day 1 . The comparison group reported greater pain relief on Postoperative Day 2 after attaining a pain interference level similar to the pain communication group . The pain communication intervention had modest effects for reducing pain interference with activities on Postoperative Day 1 . Greater pain relief might be achieved when older adults and their health care providers are more knowledgeable about both pain communication and pain management & NA ; The effect of emotions on pain perception is generally recognized but the underlying mechanisms remain unclear . Here , emotions related to pain were induced in healthy volunteers using hypnosis , during 1‐min immersions of the h and in painfully hot water . In Experiment 1 , hypnotic suggestions were design ed to induce various positive or negative emotions . Compared to a control condition with hypnotic‐relaxation , negative emotions produced robust increases in pain . In Experiment 2 , induction of pain‐related anger and sadness were found to increase pain . Pain increases were associated with increases in self‐rated desire for relief and decreases in expectation of relief , and with increases in arousal , negative affective valence and decreases in perceived control . In Experiment 3 , hypnotic suggestions specifically design ed to increase and decrease the desire for relief produced increases and decreases in pain , respectively . In all three experiments , emotion‐induced changes in pain were most consistently found on ratings of pain unpleasantness compared to pain intensity . Changes in pain‐evoked cardiac responses ( R – R interval decrease ) , measured in experiments 2 and 3 , were consistent with changes in pain unpleasantness . Correlation and multiple regression analyses suggest that negative emotions and desire for relief influence primarily pain affect and that pain‐evoked autonomic responses are strongly associated with pain affect . These results confirm the hypothesized influence of the desire for relief on pain perception , and particularly on pain affect , and support the functional relation between pain affect and autonomic nociceptive responses . This study provides further experimental confirmation that pain‐related emotions influence pain perception and pain‐related physiological responses Investigated the effects of psychologically preparing patients for minor gynaecological surgery . A total of 59 women who were undergoing elective laparoscopy were assigned r and omly to three experimental conditions : Preparation , in which an informative preoperative interview was conducted ; placebo , in which a reassuring preoperative interview was held ; and control , in which no contact was made prior to surgery . The women were assessed postoperatively in terms of pain , anxiety and attitudes and required to complete a follow-up question naire that followed a 3-week interval , which assessed subjective report of recovery rate . The results showed similar levels of pain report for all groups , although significantly fewer prepared patients requested postoperative analgesia . No differences in pain reports emerged at follow-up , although there was a tread for prepared patients to report a more rapid return to full health . The results are considered in the context of explanatory models that have been proposed to account for the effects of psychological preparation Patients have been found to receive inadequate analgesia despite moderate to severe pain after coronary artery bypass graft ( CABG ) surgery . The purpose of this pilot study was to evaluate a preadmission educational booklet for patients undergoing their first uncomplicated CABG . A r and omized controlled trial ( RCT ) was undertaken at the largest cardiovascular centre in Canada . Repeated measures were used to compare data from 3 interviews : at baseline , day 3 , and day 5 . Patients were r and omly assigned to one of 3 groups at the preadmission clinic 2 to 7 days before surgery : ( 1 ) generic hospital booklet and videotape ( control ) , ( 2 ) control + pain booklet , or ( 3 ) control + pain booklet and interview ; 45 subjects completed all 3 interviews . Measures were the McGill Pain Question naire-Short Form and the American Pain Society Patient Outcome Question naire . For all groups , analgesic administration was inadequate ( 19.89[13.37 ] mg morphine equivalents/24 hours ) despite unrelieved pain ( 6.63[2.46 ] , 0 - 10 ) . However , patients receiving the interventions in addition to control care received 46 % more analgesia than patients receiving control care alone and had fewer concerns about asking for help and taking analgesia . Changes were not required in the intervention booklet or measures 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 One of the most frequently used methods for the diagnosis and treatment of heart diseases is cardiac catheterization which increases the anxiety level in patients before surgery . In this r and om clinical study , 62 people undergoing coronary angiography were r and omly assigned to experimental and control groups . The necessary data were collected through a hemodynamic variable sheet , the STAI anxiety question naire and a pain scale . The experimental group subjects were asked to listen to a Guided Imagery CD for 18 min . The mean level of anxiety for the Guided Imagery group after the intervention decreased significantly . The comparison of the means of hemodynamic parameters before and after the intervention showed a small decrease after the intervention , but this reduction was not statistically significant . Moreover , the means of pain as measured by pain scale showed that the control group had slower level of pain but , again , this difference was not statistically significant The purpose of this prospect i ve , r and omized study was to apply an 8-week customized exercise program to patients ( Group E ) scheduled for total hip arthroplasty , followed by a postsurgery exercise program , and show the effect on functional recovery compared with control subjects ( Group C ) who received no additional exercise apart from routine in-hospital physical therapy . Strength , range of motion , and physical function tests were completed by 57 patients at Week 8 and Week 1 before surgery and at Weeks 3 , 12 , and 24 postoperatively . No differences between the exercise and control groups were observed at baseline . By 1 week before surgery , patients in Group E had shown significant improvements for Western Ontario and McMaster Universities Osteoarthritis Index ( total score , stiffness , and physical function components ) , and combined hip strength . Patients in Group E had improved hip flexion range of motion in the diseased hip compared with patients in Group C. Significant differences in outcome measures between Group E and Group C were observed throughout the postoperative phase from Weeks 3 to 24 . The current study showed that customized perioperative exercise programs are well tolerated by patients with end-stage hip arthritis , and are effective in improving early recovery of physical function after total hip arthroplasty Twenty patients undergoing cardiac surgery were seen one or more times by a psychiatrist who performed two functions . In a supportive fashion he cleared up any misconceptions the patient had about the forthcoming surgery and he taught him a simple autohypnotic technique . Twenty controls , matched for relevant variables , received routine preoperative care . Contrary to the report of others , a single visit by the psychiatrist did not influence the incidence of postoperative delirium , anxiety , depression , pain , or medication requirements . However , there was a trend for patients receiving a greater number of preoperative visits to have a lower incidence of detected delirium . Age was the only factor in this study that differed significantly between delirious and nondelirious patients INTRODUCTION The aim of this pilot study was to assess the effect of pre-operative inspiratory muscle training ( IMT ) on respiratory variables in patients undergoing major abdominal surgery . PATIENTS AND METHODS Respiratory muscle strength ( maximum inspiratory [ MIP ] and expiratory [ MEP ] mouth pressure ) and pulmonary functions were measured at least 2 weeks before surgery in 80 patients awaiting major abdominal surgery . Patients were then allocated r and omly to one of four groups ( Group A , control ; Group B , deep breathing exercises ; Group C , incentive spirometry ; Group D , specific IMT ) . Patients in groups B , C and D were asked to train twice daily , each session lasting 15 min , for at least 2 weeks up to the day before surgery . Outcome measurements were made immediately pre-operatively and postoperatively . RESULTS In groups A , B and C , MIP did not increase from baseline to pre-operative assessment s. In group D , MIP increased from 51.5 cmH(2)O ( median ) pre-training to 68.5 cmH(2)O ( median ) post-training pre-operatively ( P < 0.01 ) . Postoperatively , groups A , B and C showed a fall in MIP from baseline ( P < 0.01 , P < 0.01 ) and P = 0.06 , respectively ) . No such significant reduction in postoperative MIP was seen in group D ( P = 0.36 ) . CONCLUSIONS Pre-operative specific IMT improves MIP pre-operatively and preserves it postoperatively . Further studies are required to establish if this is associated with reduced pulmonary complications We studied the effect of an instructional video in Spanish on self-reported anxiety , knowledge about general anesthesia procedures , and satisfaction with the preoperative anesthesia process in patients requiring a Spanish interpreter . This prospect i ve , r and omized , nonblinded pilot study took place at Massachusetts General Hospital ( MGH ) , a university-affiliated tertiary-care hospital . Twenty adult , ASA physical status 1 , 2 , and 3 patients , scheduled for elective surgery ( gynecological , orthopedic , and intrabdominal surgery ) during general anesthesia were studied . Anxiety , knowledge , and patient satisfaction were assessed using a visual analog scale ( VAS ) . There was a significant reduction in anxiety score in patients who viewed the video compared with those who did not ( median reduction 2 vs 0 ; P = 0.020 ) . There was an increase in satisfaction score in the video group ( median increase 2 vs 0 ; P = 0.046 ) . There was no difference in reported knowledge-improvement scores between the two groups ( 3.5 vs 4 ; P = 0.908 ) . In Spanish-speaking patients , the addition of an instructional video in Spanish to a preanesthesia interview decreased anxiety and increased patient satisfaction Existing evidence suggests that preoperative psychological preparation that is design ed to reduce anxiety may sensitize cortisol and adrenaline responses to surgery . In a controlled trial of abdominal surgery patients , we therefore tested the effects of a preoperative preparation that used guided imagery , not to reduce anxiety , but to increase patients ' feelings of being able to cope with surgical stress ; 26 imagery patients were compared with 25 controls who received , instead , background information about the hospital . State-anxiety was similar in each group , but imagery patients experienced less postoperative pain than did the controls , were less distressed by it , felt that they coped with it better , and requested less analgesia . Hormone levels measured in peripheral venous blood did not differ on the afternoon of admission , before preparation . Cortisol levels were , however , lower in imagery patients than in controls immediately before and after surgery . Noradrenaline levels were greater on these occasions in imagery patients than controls . The results are interpreted in relation to two theories . One states that preoperative " worry " reduces surgical stress . The other concerns the influence of active and passive coping on endocrine responses to stress Purpose To determine the effect of intensive preoperative education on the outcome of Patient Controlled Analgesia ( PCA ) postoperatively . Methods This prospect i ve r and omised study was carried out in a single teaching hospital over three months . One group of patients ( n = 42 ) received a 20 min st and ardised tutorial regarding PCA use from a single investigator and the other group ( n = 43 ) received no additional education apart from the routine preoperative anaesthetic consultation . A blinded investigator assessed the patients following surgery . Pain scores and morphine consumption , patient satisfaction , side-effect profile and anti-emetic use were recorded at six , 24 and 48 hr post-operatively . Results Pain scores , satisfaction scores and morphine consumption were similar in both groups throughout the study period . Fewer patients in the tutored group complained of nausea from 6 to 24 hr than did untutored patients ( 28%vs 51 % ; P < 0.05 ) . More tutored patients used antiemetic medication from 0 to 6 ( 28%vs 12%;P < 0.05 ) and 6 to 24 hr ( 37%vs 19%;P < 0.05 ) . Side effect profile and requirement for rescue analgesia was otherwise similar in both groups . Conclusion Our results suggest that specific preoperative education of patients using PCA does not alter pain scores , morphine consumption or patient satisfaction but may result in earlier and more effective use of anti-emetic medication . RésuméObjectifDéterminer l’effet d’un enseignement préopératoire intensif sur l’évolution postopératoire de l’analgésie contrôlée par le patient (ACP).MéthodeOn a réalisé une étude prospect i ve et r and omisée dans un seul hôpital d’enseignement pendant trois mois . Un groupe de patients ( n = 42 ) a reçu d’un unique expérimentateur un cours individuel st and ardisé concernant l’utilisation de l’ACP et l’autre groupe ( n = 43 ) n’a reçu aucun enseignement additionnel après la visite de routine de l’anesthésiste avant l’intervention . Un expérimentateur impartial a évalué les patients après la chirurgie . Les scores de douleur et la consommation de morphine , la satisfaction du patient , le profil des effets secondaires et l’utilisation d’antiémétique ont été enregistrés six , 24 et 48 h après l’opération . RésultatLes scores de douleur et de satisfaction et la consommation de morphine étaient similaires dans les deux groupes tout au long de l’expérience . Il y a eu moins de plaintes de nausée entre 6 et 24 h chez les patients qui ont reçu un enseignement que chez ceux qui n’en ont pas eu ( 28 % vs 51 % ; P < 0,05 ) . Un plus gr and nombre de patients informés a utilisé des médicaments antiémétiques de 0 à 6 ( 28 % vs 12 % ; P < 0,05 ) et de 6 à 24 h ( 37 % vs 19 % ; P < 0,05 ) . Le profil des effets secondaires et la dem and e d’analgésie supplémentaire ont été , par ailleurs , similaires dans les deux groupes . Conclusion Nos résultats laissent croire qu’un enseignement préopératoire spécifique dispensé aux patients qui utilisent l’ACP n’a pas d’effet sur les scores de douleur , la consommation de morphine ou la satisfaction du patient , mais qu’il peut entraîner un usage précoce et plus efficace de médicaments antiémétiques This study of 58 cholecystectomy and 57 herniorrhaphy patients was design ed to determine the reliability of the effects of preoperative preparation on postoperative recovery that were observed in a previous study . The preoperative preparation consisted of information that focused on the typical subjective sensory experiences of surgical patients in combination with instruction in postoperative exercises . The effects of prehospital admission preparation , restatement postoperatively of preparatory information , and adding temporal orienting information to the preparatory information on postoperative course were also examined . The main results of the original study were replicated . In the cholecystectomy sample , the preoperative information intervention significantly reduced length of postoperative hospitalization and length of time posthospital discharge before patients ventured from home . Temporal orienting information reduced feelings of helplessness postoperatively in the cholecystectomy sample . Consistent with the original study , only trends for effects were observed in the herniorrhaphy sample Complementary and Alternative Therapies ( CAT ) are increasingly being utilized in conjunction with conventional medicine . Health Information Technology ( HIT ) and CAT are being scrutinized for evidence based health outcomes . The aim of this r and omized controlled trial ( RCT ) is to determine if the use of mobile technologies delivering CAT , specifically relaxation technique ( RT ) , medical music intervention ( MMI ) , nature l and scape applications with ( NLAM ) and without music ( NLAWM ) compared with no intervention ( control group ) will assist in decreasing pre- and post-surgical patients ' anxiety and pain levels while increasing post-operative healing self-efficacy levels The experience of pain has cognitive and emotional components as well as sensory and physical factors ; hence , psychological variables often play a key role in the control of pain ( 2 ) . Recent review s ( 4 ) have shown the effectiveness of procedures such as cognitive modification , hypnosis , and relaxation training for increasing subjects ' tolerance of laborstory pain , e.g. , cold-pressor stimulation . In the present investigation , we sought to determine the effectiveness of one of these procedures , relaxation training , as a method for coping with the dinicaL pain which follows surgery . Subjects were 26 women , ages 30 to 62 yr . , who were scheduled to undergo vaginal hysterectomies . Subjects were r and omly assigned to either experimental or control groups . During the 10-day periods prior to their scheduled operations , the 13 women in the experimental group each received two 90-min , individual sessions of training in progressive muscle relaxation . The relaxation procedures involved ( a ) instructions to focus attention on pleasant , relatively monotonous internal feelings , e.g. , deep breathing , and ( b ) systematic tension-release of gross muscle systems ; see Bernstein and Borkovec ( 1 ) for detailed instructions . In keeping with ethical guidelines , the investigators informed subjects that the use of relaxation for pain control was an experimental procedure and , as such , its effectiveness could not be guaranteed . Subjects were instructed to practice the relaxation exercises twice daily and to use them as a means of coping with post-operative pain . In the control group were 13 women who underwent vaginal hysterectomies but had no contact with the experimenters prior to surgery . Subjects ' pain was assessed one and three days post-operatively via the following dependent measures : ( a ) subjects ' self-reports of pain , i.e. , the McGill-Melzack Pain Question naire , ( b ) behavioral observations made by two independent raters , i.e. , the Chambers-Price Rating Scales for Pain , and ( c ) the number of pain medications received by the subject . Statistical analyses showed that differences between the experimental and control groups on the dependent measures were not significant at either one or three days following subjects ' surgeries ( ps > .05 ) ; see Petri ( 3 ) for details regarding design , analysis , and a discussion of the results . Relaxation training was not sufficient procedure for the reduction of clinical pain , perhaps as a result of ( a ) insufficient training in the relaxation procedures , ( b ) a lack of staff reinforcement for subjects ' post-operative use of the relaxation exercises , and ( c ) the ready availability of alternative , " easier " methods of pain control , e.g. , medication The authors ' repeated measures experimental study at a 359-bed community medical center located in California compared the effect of preadmission structured education with postadmission unstructured education on the outcomes of patient satisfaction , postoperative recovery , and return to functional status . Power analysis for a large effect size was used to determine the sample size of 50 adult females scheduled for open abdominal surgery . The authors used valid and reliable tools to measure the dependent variables and their findings suggest that same-day admission surgical patients who receive preadmission structured education have improved clinical outcomes , are more satisfied , are more likely to meet the targeted discharge date , and return to prior functional status sooner We examined whether pre‐operative information benefited patients receiving patient‐controlled analgesia ( PCA ) after major surgery . We investigated whether patients felt better informed about PCA and also whether pre‐operative information altered the use of PCA , the adequacy of pain relief , worries about addiction and safety , and knowledge of side‐effects . We investigated the effectiveness of information provided in two ways , namely by a patient‐determined leaflet or an interview by a trained nurse from the pain team , compared with routine pre‐operative information . We studied 225 patients , 75 in each group . Patients in the leaflet group were better informed about PCA , became familiar with using PCA more quickly and were less confused about PCA than the control group . However , there were no effects on pain relief , worries about addiction and safety , and knowledge of side effects . The pre‐operative interview result ed in no benefits . Our findings indicate that the detailed provision of pre‐operative information failed to improve patients ' experiences of PCA Pur#ose of the trial A PROGRAM of structured preoperative patient education preceding elective surgery ( Programme d’enseignement preoperatoire dispense a des patients de chirurgie elective-PEPCE ) has been instituted in a large Montreal hospital . The SacreCoeur of Cartierville ( SCC ) Hospital is a community institution with 644 primarily active treatment beds serving a francophone population in the northern suburbs of Montreal . The purpose of the trial reported here was to evaluate the efficacy and the efficiency of a nursing intervention in the management of selected and representative elective surgical patients . Efficacy was assessed by study ing the effect of the new program on physical functional capacity on the comfort and on the satisfaction of patients . Efficiency was evaluated by determining the impact of the program on length of hospitalization and on length of delay before patients resumed normal activities of life . The r and omized controlled trial was planned to provide the best possible evidence to clinical and administrative professionals of the hospital . The evidence was focused on the appropriateness of instituting an on-going structured preoperative educational program for elective surgical patients . The education was included as part of already established pre-admission procedures . A subordinate but important objective of the study reported here was to adapt , develop and vali date data -gathering instruments suitable for the evaluation of patients ’ physical functional capacity BACKGROUND Patients who undergo cardiac catheterization or percutaneous coronary intervention ( PCI ) often have a poor underst and ing of their disease and of related therapeutic risks , benefits , and alternatives . This pilot study was undertaken to compare the effectiveness of 2 preprocedural educational approaches to enhance patients ' knowledge of st and ard consent elements . METHODS Patients undergoing first-time elective , outpatient cardiac catheterization and possible PCI were r and omly assigned to a scripted verbal or written consent process ( group I ) or a web-based , audiovisual presentation ( group II ) . Preconsent and postconsent question naires were administered to evaluate changes in patients ' self-reported underst and ing of st and ard consent elements . RESULTS One hundred and two patients enrolled at a single institution completed the pre- and postconsent surveys ( group I=48 ; group II=54 ) . Changes in patient comprehension rates were similar between groups for risk and benefit consent elements , but group II had significantly greater improvement in the identification of treatment alternatives than group I ( p=0.028 ) . Independent of intervention , correct identification of all risks and alternatives increased significantly after consent ( p<0.05 ) ; 4 of 5 queried risks were correctly identified by greater than 90 % of respondents . However , misperceptions of benefits persisted after consent ; increased survival and prevention of future myocardial infa rct ion were identified as PCI-related benefits by 83 % and 46 % of respondents , respectively . CONCLUSIONS Although both scripted verbal and audiovisual informed consent improved patient comprehension , important patient misperceptions regarding PCI-related outcomes and alternatives persist , independent of informed consent approach , and considerable challenges still exist in educating patients about contemplated medical procedures . Future research appears warranted to improve patient comprehension This study tests for the impact of client-nurse interaction , an essential element lacking in earlier research on preoperative instruction . An experimental design compared the effects of three models of intervention : Facilitator , Informational and Routine Treatment on postoperative pain and anxiety in 91 cholecystectomy patients . Planned comparisons showed that subjects in both experimental conditions reported significantly less postoperative anxiety than subjects who received the routine treatment . There were no differences in anxiety levels between the two experimental groups or in pain scores among the three groups . Refinements in the facilitator model are recommended to enhance the problem-solving nature of the interaction and to strengthen future research . The findings support the importance of providing the patient with sensation information and postoperative exercise instruction The purpose of this study was to investigate the efficiency of preoperative pain management education and the role of analgesics administration before the onset of pain postoperatively . The study was a prospect i ve , r and omized , and single-blind clinical trial , which was conducted January 1 , 2008 through October 1 , 2008 in the Thoracic Surgery Unit of Akdeniz University Hospital . A total of 70 patients who underwent thoracotomy ( 35 in the control group and 35 in the study group ) were included in the study . Of the patients , 70 % ( n = 49 ) were male and 30 % ( n = 21 ) were female . Mean age was 51 ± 10 years ( range = 25 - 65 ) . The same analgesia method was used for all patients ; the same surgical team performed each operation . Methods , including preemptive analgesia and placement of pleural or thoracic catheter for using analgesics , that were likely to affect pain level , were not used . The same analgesia medication was used for both patient groups . But the study group , additionally , was educated on how to deal with pain preoperatively and on the pharmacological methods to be used after surgery . An intramuscular diclofenac Na 75 mg was administered to the study group regardless of whether or not they reported pain in the first two postoperative hours . The control group did not receive preoperative education , and analgesics were not administered to them unless they reported pain in the postoperative period . The routine analgesics protocol was as follows : diclofenac Na 75 mg ( once a day ) intramuscular administered upon the complaint of pain following extubation in the postoperative period and 20 mg mepederin intravenously ( maximum dose , 100 mg/day ) , in addition , when the patient expressed pain . Pain severity was assessed during the second , fourth , eighth , 16th , 24th , and 48th hours , and marked using the Verbal Category Scale and the Behavioral Pain Assessment Scale . Additionally , the total dose of daily analgesics was calculated . The demographic characteristics showed a homogeneous distribution in both patient groups . The rate of pain , which was defined as sharp , stabbing , and exhausting , was higher in the control group than in the study group , and the difference between the two groups was statistically significant ( p < .05 ) . As the doses of analgesics used for pain management in both groups were compared , it was determined that analgesic consumption was lower in the study group than in the control group , and the difference was statistically significant ( p < .05 ) . As a result , it was determined that preoperative thoracic pain management education and analgesics administered postoperatively , before the onset of pain , reduced the amount of analgesics used in the first postoperative 48 hours OBJECTIVE The role of complementary medicine techniques has generated increasing interest in today 's society . The purpose of our study was to evaluate the effects of one technique , self-hypnosis , and its role in coronary artery bypass surgery . We hypotesize that self-hypnosis relaxation techniques will have a positive effect on the patient 's mental and physical condition following coronary artery bypass surgery . EXPERIMENTAL DESIGN A prospect i ve , r and omized trial was conducted . Patients were followed beginning one day prior to surgery until the time of discharge from the hospital . SETTING The study was conducted at Columbia Presbyterian Medical Center , a large tertiary care teaching institution . PATIENTS All patients undergoing first-time elective coronary artery bypass surgery were eligible . A total of 32 patients were r and omized into two groups . INTERVENTIONS The study group was taught self-hypnosis relaxation techniques preoperatively , with no therapy in the control group . MEASURES Outcome variables studied included anesthetic requirements , operative parameters , postoperative pain medication requirements , quality of life , hospital stay , major morbidity and mortality . RESULTS Patients who were taught self-hypnosis relaxation techniques were significantly more relaxed postoperatively compared to the control group ( p=0.032 ) . Pain medication requirements were also significantly less in patients practising the self-hypnosis relaxation techniques that those who were noncompliant ( p=0.046 ) . No differences were noted in intraoperative parameters , morbidity or mortality . CONCLUSION This study demonstrates the beneficial effects self-hypnosis relaxation techniques on patients undergoing coronary artery bypass surgery . It also provides a framework to study complementary techniques and the limitations encountered Background : Postoperative nausea and vomiting ( PONV ) after general anesthesia and surgery may have an incidence as high as 70 % irrespective of antiemetic drug therapy . The use of preoperative hypnosis and mental preparation by means of an audio tape was investigated in the prophylaxis of nausea and vomiting before elective breast reduction surgery . Similar interventions have not been found in the literature BACKGROUND Patients awaiting cardiac surgery typically experience significant physical and psychological stress . However , although there is evidence that preoperative education interventions can lead to positive postoperative outcomes for surgical patients in general , less is known about the effectiveness among patients undergoing cardiac surgery , especially Chinese cardiac patients . OBJECTIVES To determine whether a preoperative education intervention design ed for Chinese cardiac patients can reduce anxiety and improve recovery . DESIGN R and omized controlled trial . SETTING S Cardiac surgical wards of two public hospitals in Luoyang , China . METHODS 153 adult patients undergoing cardiac surgery were r and omized into the trial , 77 to a usual care control group and 76 to preoperative education group comprising usual care plus an information leaflet and verbal advice . Measurement was conducted before r and omization and at seven days following surgery . The primary outcome was change in anxiety measured by the Hospital Anxiety and Depression Scale ( HADS ) . Secondary outcomes were change in depression ( HADS ) , change in pain as measured by subscales of the Brief Pain Inventory-short form ( BPI-sf ) , length of Intensive Care Unit stay and postoperative hospital stay . RESULTS Of 153 participants r and omized , 135 ( 88.2 % ) completed the trial . Participants who received preoperative education experienced a greater decrease in anxiety score ( mean difference -3.6 points , 95 % confidence interval -4.62 to -2.57 ; P<0.001 ) and a greater decrease in depression score ( mean difference -2.1 points , 95 % CI -3.19 to -0.92 ; P<0.001 ) compared with those who did not . There was no difference between groups in average pain , current pain , and interference in general activity , mood and walking ability . Patients r and omized to the preoperative education group reported less interference from pain in sleeping ( mean difference -0.9 points , 95 % CI -1.63 to -0.16 ; P=0.02 ) . There was some evidence to suggest a reduced number of hours spent in the Intensive Care Unit among preoperative education patients ( P=0.05 ) but no difference in length of postoperative hospital stay ( P=0.17 ) . CONCLUSIONS This form of preoperative education is effective in reducing anxiety and depression among Chinese cardiac surgery patients . Based upon existing evidence and international practice , preoperative education should be incorporated into routine practice to prepare Chinese cardiac patients for surgery This study compared the effects of preoperative physical therapy or general cardiovascular conditioning exercises with the routine procedure of no preoperative physical therapy on patients undergoing primary total knee replacement . Thirty patients were r and omly assigned to 1 of 3 groups . Group 1 was the control group . Group 2 participated in a physical therapy program design ed to strengthen the upper and lower limbs and improve knee range of motion . Group 3 participated in a cardiovascular conditioning program , consisting of arm ergometry , cycle ergometry , aquatic exercises , and aerobic activity . All patients were evaluated preoperatively and postoperatively using the Hospital for Special Surgery Knee Rating , the Arthritis Impact Measurement Scale , and the Quality of Well Being instrument . Both experimental groups tolerated their respective exercise protocol s extremely well . All 3 groups showed significant improvement postoperatively as measured by the Hospital for Special Surgery Knee Rating , the Arthritis Impact Measurement Scale and the Quality of Well Being measurement scales . However , neither type of preoperative exercise added to the degree of improvement after surgery at any of the postoperative evaluations AIMS To test an educational programme with telephone follow-up to improve self-care in Brazilian patients who underwent percutaneous coronary intervention . BACKGROUND Percutaneous coronary intervention has been established as a treatment for coronary disease . However , additional intervention is needed to improve self-care for individuals who undergo this procedure to reduce further disease . Telephone follow-up is one strategy that has been used to improve chronic disease self-care . DESIGN R and omized controlled trial . TRIAL REGISTRATION Clinical Trials.gov , NCT01341093 . METHODS Sixty patients who were preparing for their first percutaneous coronary intervention between 2011 - 2012 were r and omly allocated to an educational programme with telephone follow-up ( N = 30 ) or a control group ( N = 30 ) . Perceived health status was assessed with the Medical Outcomes Study 36-Item Short Form . Self-efficacy , symptoms of anxiety and depression and medication adherence were also assessed . Measures were collected before intervention ( baseline ) and 6 months later . RESULTS Both groups improved from baseline to 6 months in the ' Physical Component Summary ' and in the domains of ' Physical Functioning ' , ' Role-Emotional ' and ' Role-Physical ' . The educational programme group showed a reduction in anxiety from baseline to 6-month follow-up , while the control group showed a slight increase . No differences in symptoms in depression and self-efficacy were found and both groups reported high levels of medication adherence . CONCLUSION The educational programme with telephone follow-up is a promising intervention as it led to reduction in anxiety for those receiving the educational programme . Further improvements in timing and focus of the educational programme , such as targeting emotional and social lifestyle changes , might be warranted This study was carried out on volunteers to evaluate a newly developed interactive software package aim ed at informing prospect i ve Le Fort I osteotomy patients regarding the surgical technique and possible complications . The aim of the study was to compare two methods of information delivery ; a multi-media tablet device delivering both graphic and verbal information , and an audio device delivering essentially the same information in verbal form only . The null hypothesis was that there would be no difference between the efficiencies of the two methods . The subjects ' ability to recall the information delivered by both devices was assessed using a question naire . The tablet device participants scored an average of 15.48 points , while the audio device participants scored an average of 268 points . The difference was statistically significant ( p < 0.001 ) , suggesting that the multi-media tablet device was more effective method OBJECTIVE To establish whether the provision of commercially produced written information in addition to routine hospital information can improve patients ' knowledge and satisfaction and affect their health-related quality of life . METHODS Elective surgical patients were r and omised into an experimental group ( N = 54 ) who received three commercially produced information booklets at pre- assessment , before surgery and at discharge , and a control group ( N = 55 ) who received st and ard hospital information only . RESULTS The experimental group were significantly less anxious immediately before their operation , and reported greater perceived control compared to controls post-operatively . Two weeks after discharge , health status for the two groups was similar except the experimental group reported significantly less pain . Overall satisfaction was fairly high and similar in both groups . The experimental group demonstrated greater knowledge at pre-admission , but not at discharge or follow-up . DISCUSSION Patients increasingly expect written information ; however amount , quality and timeliness vary considerably . Combining commercially produced information with st and ard hospital information may be to the patient 's benefit . PRACTICE IMPLICATION S Providing patients with commercially produced st and ardised information in addition to internally produced hospital information could have an additional , though limited , benefit to patients ' health outcomes . This could be a way of incorporating the expertise of both providers to the patient 's benefit Previous studies offer contradictory evidence regarding the effects of cortisol changes on health outcomes for surgical heart patients . Increased cortisol and inflammation have been related to psychological stress while separate studies have found an inverse relation between cortisol and inflammation . Psychological preparations for surgery can reduce stress and improve outcomes and may interact with cortisol changes . Following from these relationships , we hypothesised that a preparation for surgery will interact with changes in cortisol to affect outcomes . Measures were the SF 36 General Health and Activities , medical visits and satisfaction . Eighty-five patients were r and omly assigned to st and ard care plus a psychological preparation or st and ard care alone using a single-blind methodology . Data on psychological and biological functioning were collected at admission , 1 day prior and 5 days post-surgery , and 12-months after hospital discharge . General health and activities , and medical visits were related to the interaction of cortisol change and psychological preparation in support of the hypothesis . Patients were more satisfied in the preparation group than controls . Based on these findings , some outcomes from psychological preparations may be affected by changes in levels of cortisol . These results caution against a one-size-fits-all approach to psychological preparations Aim . This study determined the usefulness of an interactive , individualized online patient pathway to patients undergoing elective operation for nonmalignant disease . Methods . An exploratory double-blind , prospect i ve r and omized controlled trial was established involving consecutive patients undergoing minimally invasive radioguided parathyroidectomy ( MIRP ) . A total of 64 patients were r and omly assigned to either a st and ard or an enhanced Web site ( interactive with detailed , personalized timeline ) . Each patient completed vali date d Hospital Anxiety and Depression Scale question naires preoperatively and pain assessment s and question naires concerning Web site usefulness postoperatively . Results . All patients found their Web site useful , although patient satisfaction was significantly higher with the enhanced Web site in regard to overall impression as well as ease , organization , usefulness , and specificity of information . There were no significant differences in mean anxiety or pain scores , in analgesia requirements , or adequacy of informed consent . Conclusion . Providing education and information through a tailored Web server is viewed positively by patients PURPOSE To evaluate the effects of a tailored information package for rectal cancer patients on satisfaction with information , anxiety and depression and readjustment . METHOD The study used a r and omised control trial method . Seventy six patients undergoing surgery and treatment for rectal cancer were r and omly assigned to an intervention ( n = 43 ) or control group ( n = 33 ) . The intervention group received an information pack tailored according to their treatment plan and preferred information . The control group received the information currently given to these patients . Satisfaction with information was measured using the Patient Satisfaction with Cancer Treatment Education ( PSCaTE ) scale , anxiety and depression were measured using the Hospital Anxiety and Depression Scale ( HADS ) and readjustment was measured using the Reintegration to Normal Living Index , at three time points . RESULTS There was a statistically significant difference between the intervention and control group on pre and post intervention scores with patients in the intervention group expressing a higher level of satisfaction with information than those in the control group at Times 2 and 3 ( p = 0.00 for both ) . The intervention group also had a significantly lower anxiety score than the control group at Time 3 ( p = 0.03 ) . There was no difference between depression and readjustment scores in the two groups . CONCLUSION The results support the hypothesis that a tailored information pack for patients with rectal cancer will positively affect satisfaction with information . These results will enhance the knowledge base surrounding the provision of tailored information to specific patient groups |
2,453 | 23,449,768 | Cyclosporine and mycophenolate mofetil failed to show superiority over alkylating agents .
Tacrolimus and adrenocorticotropic hormone significantly reduced proteinuria .
CONCLUSIONS Alkylating agents plus corticosteroids had long-term and short-term benefits for adult IMN , but result ed in more withdrawals or hospitalizations | BACKGROUND AND OBJECTIVES The efficacy and safety of immunosuppression for idiopathic membranous nephropathy ( IMN ) with nephrotic syndrome are still controversial . | Background A previous double-blind 24-week clinical trial of mizoribine ( MZ ) vs placebo in steroid-resistant primary nephrotic syndrome ( SRPNS ) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function . The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years ’ treatment . Methods A multicenter r and omized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospect i ve postmarketing study . Results There was a significant imbalance in the baseline serum albumin level ( s-Alb ) between the conventional therapy ( CT ) and MZ onlay therapy groups . Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb ≤3 g/dl . Therefore , the primary analysis ( urinary protein level (UP)-improving effect ) was performed using a mixed-effects model , with stratification according to the baseline s-Alb value . The analysis revealed that , in the subset of 34 patients with membranous nephropathy ( MN ) within the stratum of patients with baseline s-Alb ≤3 g/dl ( n = 52 ) , the rate of change ( slope of change in the UP level/month ) , in terms of the log ( UP+0.2 ) , was −0.0577 in those allocated to the MZ group and −0.0227 in those allocated to the CT group ( P = 0.058 ) . In the stratum of patients with a baseline s-Alb > 3 g/dl ( n = 97 ) , there were no significant differences in the UP between the two treatment groups . Hence , MZ onlay therapy was not considered to be efficacious in this group of patients . No serious adverse reactions to the drug were observed . Conclusions The present study yielded significant results , in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP , in addition to that obtained following CT , in particular , in MN patients in a severe nephrotic state To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy , we compared two regimens based on a 6-mo treatment , alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide . Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were r and omized to be given methylprednisolone ( 1 g intravenously for 3 consecutive days followed by oral methylprednisolone , 0.4 mg/kg per d for 27 d ) alternated every other month either with chlorambucil ( 0.2 mg/kg per d for 30 d ) or cyclophosphamide ( 2.5 mg/kg per d for 30 d ) . The whole treatment lasted 6 mo ; 3 mo with corticosteroids and 3 mo with one cytotoxic drug . Among 87 patients followed for at least 1 yr , 36 of 44 ( 82 % ; 95 % confidence interval [ CI ] , 67.3 to 91.8 % ) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome , versus 40 of 43 ( 93 % ; 95 % CI , 80.9 to 98.5 % ) assigned to methylprednisolone and cyclophosphamide ( P = 0.116 ) . Of patients who attained remission of the nephrotic syndrome , 11 of 36 in the chlorambucil group ( 30.5 % ) and 10 of 40 in the cyclophosphamide group ( 25 % ) had a relapse of the nephrotic syndrome between 6 and 30 mo . The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups ( P < 0.01 ) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr . Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects . Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster . One patient per group developed cancer . It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr BACKGROUND We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome . METHODS To vali date the hypothesis that the 2 treatments were equivalent , patients with biopsy-proven membranous nephropathy and nephrotic syndrome were r and omly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months ( group A ) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year ( group B ) . RESULTS The primary outcome measure is cumulative number of remissions as a first event . Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event . After a median follow-up of 24 months ( interquartile range , 15 to 25 months ) , there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d ( interquartile range , 4.0 to 7.3 g/d ) to 2.1 g/d ( interquartile range , 0.4 to 3.8 g/d ; P = 0.004 ) in group A and 6.0 g/d ( interquartile range , 4.4 to 8.5 g/d ) to 0.3 g/d ( interquartile range , 0.2 to 1.9 g/d ; P = 0.049 ) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy . CONCLUSION Most nephrotic patients with membranous nephropathy responded to either treatment . Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone , without significant differences between these 2 therapies Controlled trial of cyclophosphamide in idiopathic membranous nephropathy . We evaluated cyclophosphamide treatment in a controlled prospect i ve study of 22 adult patients with clinical ly and histologically defined idiopathic membranous nephropathy . By r and om assignment , 11 patients received no drug and 11 patients received cyclophosphamide orally , 1.5 to 2.5 mg/kg/day ( mean , 1.8 ) , for one year . Before treatment , the two groups were similar in age and sex distributions , duration of illness , blood pressure , degree of proteinuria , renal function and histologic staging . After treatment , a downward trend in proteinuria was noted , with no significant difference in the quantity and rate of decrease between groups . Renal function ( C in and C PAH ) was stable in all patients , with no difference between groups . On comparing pretreatment and one-year renal biopsy specimens in eight patients in each group , regardless of treatment or clinical outcome , the appearance of the renal lesions remained the same or progressed in terms of basement membrane thickening and incorporation of subepithelial deposits , and immunofluorescence with IgG and C3 remained positive in glomerular capillaries . Cyclophosphamide dosage was decreased in five patients because of recurrent leukopenia ; no other major toxicity was observed . Beyond one year of treatment , renal function has decreased in two of eight patients in the no-drug group and in one of seven patients in the cyclophosphamide-treated group . We conclude that treatment with cyclophosphamide for one year did not have a favorable effect on proteinuria , renal function or morphologic aspects of the glomerular lesion . Essai controle du cyclophosphamide dans la nephropathie membraneuse idiopathique . Nous avons evalue le traitement par le cyclophosphamide dans une etude prospect i ve controlee de 22 malades adultes atteints de nephropathie membraneuse idiopathique cliniquement et anatomiquement definie . Au hasard , onze malade n'ont recu aucun traitement et onze autres ont eu du cyclophosphamide par voie orale a raison de 1,5 a 2,5 mg/kg par jour ( 1,8 en moyenne ) pendant un an . Avant le traitement les deux groupes etaient semblables en distribution d'âge et de sexe , duree de la maladie , pression arterielle , importance de la proteinurie , fonction renale et etat histologique . Apres traitement , une tendance a la diminution de la proteinurie a ete observee sans difference significative entre les groupes dans le debit de proteine ou la vitesse de diminution . La fonction renale ( C in et C PAH ) etait stable chez tous les malades , sans difference entre les groupes . La comparaison des biopsies avant traitement et apres un an chez huit malades de chaque groupe , independamment du traitement ou de l'evolution clinique , a montre que les lesions renales sont restees les memes ou ont progresse , sous la forme d'un epaississement de la membrane basale et de l'incorporation de depots sous-epitheliaux , et que l'immunofluorescence avec IgG et C3 reste positive dans les capillaires glomerulaires . La posologie du cyclophosphamide a ete diminuee chez cinq malades en raison d'une leucopenie recidivante ; aucune autre toxicite majeure n'a ete observee . Au-dela d'un an de traitement , la fonction renale a diminue chez deux des huit malades du groupe ne recevant pas de medicament et chez l'un des sept malades du groupe traite par le cyclophosphamide . Nous concluons que le traitement par le cyclophosphamide pendant un an n'a pas eu d'effet favorable sur la proteinurie , la fonction renale ou les lesions histologiques glomerulaires BACKGROUND Retrospective and anecdotal data suggest that mycophenolate mofetil ( MMF ) might be effective when given as rescue therapy for membranous nephropathy ( MN ) . Prospect i ve controlled data on MMF and prednisolone as primary therapy are lacking . METHODS A prospect i ve , r and omized , controlled , open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome . MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients , with follow up of 15 months . RESULTS MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction , despite a lower cumulative prednisolone dose in the MMF group ( 3.80 + /- 0.28 vs 9.93 + /- 0.25 g , P < 0.001 ) . Remission ( composite of ' complete ' and ' partial ' ) rates were 63.6 % and 66.7 % in the MMF group and control group , respectively ( P = 1.000 ) . Serum creatinine and creatinine clearance remained stable during follow up . Cumulative relapse rate was 23.1 % at 2 years . Chlorambucil result ed in more leucopenia compared with MMF . CONCLUSION Data from this pilot study indicate that more than 60 % of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment , and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents BACKGROUND The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy ( MN ) and focal segmental glomerulosclerosis ( FSGS ) are based on steroids and /or cytotoxic agents . Data on the effect of mycophenolate mofetil ( MMF ) for these conditions are scarce and confounding . METHODS We compared the efficacy of an MMF-based therapy with st and ard therapies in inducing remission in adult nephrotics with MN and FSGS in a r and omized pilot study . MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2 - 3 months . Conventional therapy was prednisolone 1 mg/kg/day for 3 - 6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN . The primary end point was change in urinary protein/creatinine ratio . RESULTS A total of 54 patients ( 21 MN and 33 FSGS ) were recruited ; 28 were r and omized to receive MMF ( group A ) and 26 were on conventional treatment ( group B ) . There was no difference in the proportion of patients achieving remission in two groups ( 64 and 80 % in MN and 70 and 69 % in FSGS ) . The frequency of relapses and incidence of infections was also similar . FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose . CONCLUSIONS A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term . It induces remission faster and reduces steroid exposure in FSGS patients . Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function We have assessed the medium-term effect of a short course of high-dose , alternate-day prednisolone on adult nephrotic patients with membranous nephropathy , using a r and omized , prospect i ve , double-blind , controlled trial . Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years . One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial . One hundred and sixty further patients , excluded from the trial , but with membranous nephropathy were identified , followed and assessed retrospectively at the end of the trial . At 36 months there was no significant difference between control and treatment groups in plasma creatinine , creatinine clearance or 24-h excretion of protein . At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls . No significant benefit was therefore observed on renal function in the medium term Selective depletion of B cells with the mAb rituximab may benefit the autoimmune glomerular disease idiopathic membranous nephropathy ( IMN ) . Here , we describe our experience treating 100 consecutive IMN patients with persistent nephrotic syndrome with rituximab . We defined complete remission as persistent proteinuria < 0.3 g/24 h and partial remission as persistent proteinuria <3 g/24 h , each also having > 50 % reduction in proteinuria from baseline . During a median follow-up of 29 months after rituximab administration , 65 patients achieved complete or partial remission . The median time to remission was 7.1 months . All 24 patients who had at least 4 years of follow-up achieved complete or partial remission . Rates of remission were similar between patients with or without previous immunosuppressive treatment . Four patients died and four progressed to ESRD . Measured GFR increased by a mean 13.2 ( SD 19.6 ) ml/min per 1.73 m(2 ) among those who achieved complete remission . Serum albumin significantly increased and albumin fractional clearance decreased among those achieving complete or partial remission . Proteinuria at baseline and the follow-up duration each independently predicted the decline of proteinuria . Furthermore , the magnitude of proteinuria reduction significantly correlated with slower GFR decline ( P=0.0001 ) . No treatment-related serious adverse events occurred . In summary , rituximab achieved disease remission and stabilized or improved renal function in a large cohort of high-risk patients with IMN The natural course of idiopathic membranous nephropathy is variable , with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time . Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment . We up date d at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were r and omly assigned to receive symptomatic therapy ( 39 patients ) or a treatment of six months with methylprednisolone and chlorambucil ( 42 patients ) . The probability of surviving without developing end-stage renal disease at 10 years was 92 % in patients given methylprednisolone and chlorambucil versus 60 % in controls ( P = 0.0038 ) . The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls ( P = 0.035 ) . The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients ( P = 0.000 ) . Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients ( P = 0.0001 ) . Four patients had to stop treatment because of reversible side-effects . In the long-term one treated patient developed diabetes and another one became obese . In conclusion , a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term . This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy Membranous nephropathy is a common cause of nephrotic syndrome in adults . Although some patients with membranous nephropathy achieve a spontaneous remission , renal function continues to deteriorate in others . We conducted a prospect i ve r and omized trial evaluating monotherapy with tacrolimus to achieve complete or partial remission in patients with biopsy-proven membranous nephropathy . Twenty-five patients received tacrolimus ( 0.05 mg/kg/day ) over 12 months with a 6-month taper , whereas 23 patients were in the control group . The probability of remission in the treatment group was 58 , 82 , and 94 % after 6 , 12 , and 18 months but only 10 , 24 , and 35 % , respectively in the control group . The decrease in proteinuria was significantly greater in the treatment group . Notably , six patients in the control group and only one in the treatment group reached the secondary end point of a 50 % increase in their serum creatinine . No patient in the tacrolimus group showed a relapse during the taper period . Nephrotic syndrome reappeared in almost half of the patients who were in remission by the 18th month after tacrolimus withdrawal . We conclude that tacrolimus is a very useful therapeutic option for patients with membranous nephropathy and preserved renal function . The majority of patients experienced remission with a significant reduction in the risk for deteriorating renal function We conducted a prospect i ve r and omized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days ( 45 mg per square meter of body-surface area ; n = 81 ) or no specific treatment ( n = 77 ) . The mean duration of follow-up was 48 months . Patients in the prednisone group ( median age , 46 years ) entered with a mean disease duration of 15 months , a median creatinine clearance of 1.2 ml per second per 1.73 m2 ( range , 0.25 to 2.6 ) , and a median rate of urinary protein excretion of 6.8 g per day ( 0.3 to 26 ) . The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group ( 0.10 vs. 0.06 ml per second ; P = 0.8 ) , or at the last follow-up evaluation ( -0.07 vs. -0.02 ml per second ; P = 0.2 ; 95 percent confidence interval on the difference , -0.03 to 0.13 ) . The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months . Outcomes were similar in the two groups with respect to progression to renal failure ( 3 vs. 4 patients ) , death ( 3 vs. 1 patient ) , complete remission of proteinuria at 36 months ( 16 vs. 19 patients ) , and a decline of 25 percent or more in the creatinine clearance at 60 months ( 32 vs. 25 percent of patients ) . A multivariate analysis , which adjusted for differences at entry in sex distribution , urinary protein excretion , and creatinine concentration , as well as other prognostic variables , failed to provide an explanation for the lack of effect of prednisone . We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy There is no consensus regarding the modality of therapy for idiopathic membranous nephropathy ( IMN ) , especially for patients who did not react to treatment with cytotoxic drugs . This study followed prospect ively for 3-year IMN patients who did not react to Ponticelli protocol comparing effects of 2-year course of cyclosporine ( CsA ) with azathioprine ( Aza ) treatment both with small doses of prednisolone . Twenty-three patients were r and omly assigned to receive either cyclosporine at 3mg/kg per day ( 10 patients ) or azathioprine at 1.5 to 2mg/kg ( 13 patients ) . Both groups were comparable regarding age , sex and renal function , except for proteinuria , which was significantly greater in CsA group ( P=0.003 ) . Similar rate of remission of nephrotic syndrome ( NS ) have been noted at the end of treatment ( 80 % CsA versus 93 % Aza ) . During last year , follow-up relapses of NS were more frequent in Aza group ( 5 versus 1 ) . A fall in proteinuria was recorded in both groups during treatment , but it rose significantly in Aza group ( 1.5g/day versus 3.1g/day , P=0.04 ) and remained unchanged in CsA group ( 3.9g/day versus 4.1g/day ) after treatment cessation . Renal function deteriorated in Aza group ( sCr 120.5 versus 269.8μmol/L ; P<0.01 ) and was stable in CsA group . In conclusion , CsA and steroids may be a very important option in the management of high-risk IMN patients . Long-term treatment is necessary for achievement of full therapeutic effect . Treatment with Aza did not have long-term benefits particularly regarding renal function preservation In this prospect i ve r and omized trial , we compared the effects of cyclosporine- and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy . Twenty-eight patients were r and omized to receive treatment with one of the three therapeutic regimens : cyclosporine with methylprednisolone , cyclophosphamide with methylprednisolone or lisinopril ( control ) . Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period . At the end of the study period , renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group . Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group . Total cholesterol levels and proteinuria were significantly reduced in all groups . In the comparison between the groups , serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study . Six patients from the cyclosporine group ( 1/10 complete and 5/10 partial ) , all cyclophosphamide-treated ( 4/8 complete and 4/8 partial ) and all 10 lisinopril-treated patients ( 10/10 partial ) were on remission at the end of the study . In conclusion , cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens . Cyclophosphamide is associated with more complete remissions after 9 months of treatment . Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions BACKGROUND Treatment of patients with membranous glomerulonephritis ( MGN ) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival . The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil ( MMF ) for patients with MGN . STUDY DESIGN 1-year prospect i ve , r and omized , and controlled clinical trial . SETTING & PARTICIPANTS 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome . INTERVENTION 19 patients received MMF ( 2 g/d ) for 12 months and 17 patients were in the control group . All patients had the same conservative treatment based on renin-angiotensin blockers , statins , low-salt and low-protein diet , and diuretics in case of edema . OUTCOMES & MEASUREMENTS End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year ( month 12 ) . Data were analyzed on an intention-to-treat analysis . RESULTS Mean proteinuria over creatinuria ratio was stable in both groups throughout the study ( P = 0.1 ) . Mean proteinuria over creatinuria ratio was 4,690 + /- 2,212 mg/g in the MMF group and 6,548 + /- 4,601 mg/g in the control group ( 95 % confidence interval of the difference , -619 to + 4,247 ; P = 0.1 ) . Remission was complete in 3 patients ( 1 in the MMF group , 2 in the control group ; P = 0.5 ) and partial in 11 patients ( 6 in the MMF group , 5 in the control group ; P = 0.9 ) . The probability of complete or partial remission did not differ between the 2 groups after 12 months ( relative risk , 0.92 ; 95 % confidence interval , 0.48 to 1.75 ; P = 0.7 ) . Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level . LIMITATIONS The small number of patients and short follow-up prevent generalizations . CONCLUSIONS A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions . Serious adverse effects were observed in 4 patients ( 20 % ) receiving MMF 40 patients with idiopathic membranous glomerulonephritis were r and omized to receive either no treatment or a regime of cyclophosphamide for 6 months , and warfarin and dipyridamole for two years . During the two years of the trial there was no significant deterioration in renal function in either group . A significantly greater improvement in urinary protein excretion was , however , observed at all time points in the treatment group . Plasma albumin was also significantly higher in the treatment group at 18 and 24 months . As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment In most patients with membranous nephropathy , the disease follows a benign course ; only one fourth of the patients develop renal insufficiency [ 1 - 4 ] . Results of r and omized clinical trials assessing the efficacy of corticosteroids [ 5 - 7 ] and chlorambucil [ 8 , 9 ] in patients with membranous nephropathy and normal renal function are controversial . Because in most untreated patients renal function remains normal and spontaneous remissions of proteinuria develop , it does not seem justified to use potentially toxic immunosuppressive drugs in these patients . Such treatment should be limited to patients at risk for disease progression [ 10 ] . It is well known that patients with membranous nephropathy and established renal insufficiency are at high risk for developing end-stage renal disease [ 11 ] . Uncontrolled studies in patients with deteriorating renal function have shown beneficial effects of intravenous pulses of methylprednisolone followed by oral prednisone [ 12 ] , of prednisone and cyclophosphamide [ 13 - 15 ] , of prednisone and chlorambucil [ 16 ] , and of prednisone combined with azathioprine [ 17 ] . In a pilot study , we observed that chlorambucil and prednisone reversed the deterioration of renal function in some patients with membranous nephropathy [ 18 ] . Both chlorambucil and cyclophosphamide have major side effects . In patients with lupus nephritis , it has been shown that the use of intravenous pulses of cyclophosphamide is effective and is associated with fewer side effects than is daily oral cyclophosphamide [ 19 ] . We therefore did a r and omized trial comparing the efficacy of chlorambucil , methylprednisolone , and prednisone with pulses of cyclophosphamide and methylprednisolone in patients with membranous nephropathy and deteriorating renal function . Our data show that treatment with chlorambucil can retard progression of renal failure , whereas monthly intravenous cyclophosphamide is ineffective . Methods Patient Selection To be eligible for the study , patients were required to have a nephrotic syndrome with biopsy-proven membranous nephropathy and deteriorating renal function . Exclusion criteria were as follows : age younger than 18 years , serum creatinine levels lower than 150 mol/L , evidence for secondary types of membranous nephropathy ( such as malignancy , hepatitis infection , positive test results for anti-DNA antibodies , or the use of drugs that could induce membranous nephropathy ) , child wish , diabetes mellitus , or clinical evidence of renal vein thrombosis . Renal biopsy specimens were taken from all patients at presentation and were re-evaluated by one investigator . Histologic staging was done according to the criteria of Ehrenreich and Churg [ 20 ] . All patients gave informed consent . Study Design and Intervention Patients were r and omly assigned to one of two treatment protocol s. Patients assigned to receive chlorambucil were given three cycles of treatment with steroids ( intravenous pulses of methylprednisolone , 1 g on 3 consecutive days , followed by oral prednisone , 0.5 mg/kg of body weight per day for 27 days ) , and each cycle was followed by 1 month of treatment with oral chlorambucil ( 0.15 mg/kg per day ) . We used a lower dose of chlorambucil than that used by Ponticelli and colleagues [ 9 ] because in our previous study using chlorambucil at 0.2 mg/kg per day , leukopenia developed in more than half of the patients [ 18 ] . Patients assigned to receive cyclophosphamide were given intravenous pulses of cyclophosphamide , 750 mg/m2 , at monthly intervals for 6 months . They also received three intravenous pulses of methylprednisolone of 1 g for 3 consecutive days every 2 months . Cyclophosphamide was administered under forced saline diuresis . All patients received intravenous metoclopramide or ondansetron to avoid or reduce symptoms of nausea and vomiting . The patients received diuretics and antihypertensive drugs if required . Clinical examinations , biochemical profiles , and full blood counts were done at weekly intervals during immunosuppressive therapy and at regular intervals thereafter . The trial was stopped when the serum creatinine levels doubled . For calculations of renal survival , renal death was defined as a doubling of the serum creatinine level or the start of renal replacement therapy . We have used the reciprocal of serum creatinine ( 1000/serum creatinine level ) to assess the effect of the therapeutic interventions on the progression of renal insufficiency . Changes in this ratio parallel changes in endogenous creatinine clearance ( [ urinary creatinine concentration x V]/serum creatinine , where V = 24-h urine volume ) because in a given patient , creatinine excretion ( urinary creatinine concentration x V ) is generally constant over time . For calculations , 1000 mol/L ( 8.85 mg/dL ) was taken as the creatinine level in patients who received hemodialysis . Complete remission was defined as a reduction of proteinuria to less than 0.3 g/24 h , and partial remission was defined as when proteinuria ranged between 0.3 and 3.0 g/24 h. To correct for inappropriate 24-hour urine collection s , the amount of urinary protein per 10 mmol of creatinine ( protein-creatinine index ) was used for calculation . At the start of the therapy , an interim analysis was planned after 20 patients were enrolled . By the end of 1992 , we became aware of the study of Falk and colleagues [ 21 ] , which showed no additional benefit of intravenous pulses of cyclophosphamide plus steroid treatment . Analysis of our patients ' data also showed no effect of treatment with pulses of cyclophosphamide . It therefore seemed unjustified to continue the study protocol , and no more patients were enrolled . Statistical Analysis Results are given as the mean SD or as the median with range . Average changes in time from baseline values are given with 95 % confidence intervals . Changes in serum creatinine levels were compared using repeated measures of analysis of variance . The Gehan log-rank test was used for survival analysis . The Wilcoxon test was used for all other statistical comparisons . A probability value of less than 0.05 was considered statistically significant . Results Clinical Findings Between June 1989 and November 1992 , 20 patients met the entrance criteria of the study and were r and omly assigned to either treatment regimen . Two of the 20 patients ( 1 from each treatment group ) immediately withdrew after assignment . One had to receive regular dialysis before treatment with methylprednisolone and cyclophosphamide had begun , and the other became psychotic 2 weeks after starting prednisone treatment . Because these 2 patients received neither chlorambucil nor cyclophosphamide , their data are not used for analysis . Of the remaining 18 patients , 9 were assigned to receive chlorambucil and 9 to receive cyclophosphamide . The clinical details are given in Table 1 . All patients but 1 were men , and all had a nephrotic syndrome ( proteinuria , 3.5 g/d ) and renal insufficiency . In the 6 months before the start of treatment , the serum creatinine levels of patients in the chlorambucil group increased from a mean of 146 69 mol/L to 260 112 mol/L ; in the cyclophosphamide group , the levels increased from 141 87 mol/L to 218 85 mol/L ( P > 0.2 between the two groups ) . Six patients in the chlorambucil group and 5 patients in the cyclophosphamide group had been treated previously with short-term , high-dose prednisone according to a previously published schedule [ 5 ] . In the group assigned to receive chlorambucil , 7 of the 9 patients received antihypertensive treatment consisting of one drug ( 3 patients received an angiotensin-converting enzyme inhibitor and 4 patients , a -blocker ) , and in the group assigned to receive cyclophosphamide , 5 of the 9 patients received an antihypertensive drug , an angiotensin-converting enzyme inhibitor . Patients were followed for 6 to 36 months after the start of immunosuppressive therapy . Table 1 . Clinical Characteristics of Patients at Study Entry Pathologic Findings In both treatment groups , six patients had stage I or II membranous nephropathy . In the chlorambucil group , two patients had stage III nephropathy . The biopsy specimen of one patient could not be re-evaluated . Three of the patients treated with pulse cyclophosphamide had stage III nephropathy . Response to Immunosuppressive Therapy The course of renal function as reflected by 1000/serum creatinine for the individual patients is shown in Figures 1 and 2 . During the 6 months of treatment , the serum creatinine level had decreased in all patients treated with chlorambucil by an average of 74 mol/L ( range , 19 to 175mol/L ; P = 0.003 ) . In contrast , we observed an uninterrupted increase of the serum creatinine level in seven of the nine patients treated with cyclophosphamide , with an average increase of 79 mol/L ( range , 67 to 204 mol/L ; P = 0.02 ; difference between both groups , P < 0.001 ) . The difference in the course of the serum creatinine level between the treatment groups was already apparent 3 months after therapy was started ( P = 0.02 compared with the baseline creatinine level ) , and it persisted during the subsequent years of follow-up . Renal survival differed significantly between the two treatment groups ( P = 0.03 ) in favor of the patients treated with chlorambucil . Both groups had similar increases of serum albumin levels and decreases of proteinuria and serum cholesterol levels ( Table 2 ) . Table 2 . Changes in Biochemical Variables from Baseline during the First Year after Start of Treatment * Figure 1 . Renal function as shown by 1000/serum creatinine level in individual patients treated with chlorambucil , methylprednisolone , and prednisone . Figure 2 . Renal function as shown by 1000/serum creatinine level in individual patients treated with intravenous pulses of cyclophosphamide and methylprednisolone . Follow-up Follow-up data for each patient are given in Table 3 . In the chlorambucil group , one patient had a complete remission of proteinuria , and three had a partial remission of proteinuria after Seventy-two adults with the nephrotic syndrome without renal insufficiency had a membranous type of renal histology on biopsy . These patients were r and omly allocated to at least eight weeks of alternate-day treatment with prednisone or placebo in a multicenter study . Deterioration of glomerular filtration rate was significantly more rapid in placebo-treated than in prednisone-treated patients , and ultimately 10 of 38 given placebo but only one of 34 given prednisone were in renal failure ( creatinine more than 5 mg per deciliter [ 440 mumol per liter ] ) or dead ( P less than 0.02 ) . In male patients and in those with nonselective initial proteinuria , there was a trend ( not reaching statistical significance ) toward more rapid deterioration of renal function . Age , admission blood pressure , serum creatinine , daily total protein excretion , and severity of histologic changes did not predict the subsequent course . We conclude that a short course of alternate-day prednisone therapy was beneficial in our group of patients with idiopathic membranous nephropathy OBJECTIVE To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy . DESIGN R and omized , controlled treatment trial . Patients were followed for a mean of 29.2 + /- 17.1 months . SETTING Collaborative network of 120 university and private- practice nephrologists . PARTICIPANTS Patients with membranous glomerulopathy whose renal function deteriorated ( as evidence d by doubling of the serum creatinine level , a 50 % fall in the glomerular filtration rate , or a sustained serum creatinine level of greater than 2.0 mg/dL [ reciprocal creatinine value , 0.5 ] , or whose nephrotic range proteinuria persisted in association with morbid complications . Of 156 patients with biopsy-proven membranous glomerulopathy , 36 became eligible for r and omization . Twenty-six of these 36 patients were r and omly assigned to receive one of the two treatments . INTERVENTIONS Pulse methylprednisolone , oral corticosteroids , and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone . MAIN RESULTS At entry , no statistical differences were found between the treatment groups in duration of renal disease , age , gender , serum creatinine level , 24-hour urine protein excretion , or biopsy stage . The groups showed no difference in mean arterial blood pressure during follow-up . Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up . Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point . The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment . The power to detect a substantial improvement in renal function , defined as a doubling of the reciprocal of the serum creatinine , at the 0.05 significance level was 0.92 . CONCLUSIONS Combination therapy with intravenous cyclophosphamide and corticosteroids , when compared with corticosteroid therapy alone , does not improve renal function in patients with progressive membranous glomerulopathy BACKGROUND A clinical trial of cyclosporine in patients with steroid-resistant membranous nephropathy ( MGN ) was conducted . Although MGN remains the most common cause of adult-onset nephrotic syndrome , its management is still controversial . Cyclosporine has been shown to be effective in cases of progressive MGN , but it has not been used in controlled studies at an early stage of the disease . METHODS We conducted a r and omized trial in 51 biopsy-proven idiopathic MGN patients with nephrotic-range proteinuria comparing 26 weeks of cyclosporine treatment plus low-dose prednisone to placebo plus prednisone . All patients were followed for an average of 78 weeks , and the short- and long-term effects on renal function were assessed . RESULTS Seventy-five percent of the treatment group versus 22 % of the control group ( P < 0.001 ) had a partial or complete remission of their proteinuria by 26 weeks . Relapse occurred in 43 % ( N = 9 ) of the cyclosporine remission group and 40 % ( N = 2 ) of the placebo group by week 52 . The fraction of the total population in remission then remained almost unchanged and significant different between the groups until the end of the study ( cyclosporine 39 % , placebo 13 % , P = 0.007 ) . Renal function was unchanged and equal in the two groups over the test medication period . In the subsequent follow-up , renal insufficiency , defined as doubling of baseline creatinine , was seen in two patients in each group , but remained equal and stable in all of the other patients . CONCLUSION This study suggests that cyclosporine is an effective therapeutic agent in the treatment of steroid-resistant cases of MGN . Although a high relapse does occur , 39 % of the treated patients remained in remission and were subnephrotic for at least one-year post-treatment , with no adverse effect on filtration function BACKGROUND AND METHODS Treatment with methylprednisolone and chlorambucil may protect renal function and increase the chance of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy . To determine whether similar results might be obtained with methylprednisolone alone , we compared the effects of methylprednisolone and chlorambucil with those of methylprednisolone alone in 92 patients with the nephrotic syndrome caused by idiopathic membranous nephropathy . The patients were r and omly assigned to receive either alternating one-month courses of methylprednisolone and then chlorambucil for a total of six months ( group 1 ) or methylprednisolone alone for six months at the same cumulative dosage ( group 2 ) . RESULTS Four of the 45 patients in group 1 ( 9 percent ) and 1 of the 47 in group 2 ( 2 percent ) stopped treatment because of side effects . At one , two , and three years , the percentage of patients who did not have the nephrotic syndrome was significantly higher in group 1 than in group 2 . It was 58 , 54 , and 66 percent , respectively , in group 1 , as compared with 26 , 32 , and 40 percent in group 2 ( P = 0.002 , 0.029 , and 0.011 ) . By year 4 , the difference was no longer statistically significant : 62 percent of the patients in group 1 and 42 percent of those in group 2 did not have the nephrotic syndrome ( P = 0.102 ) . The patients in group 1 were in remission longer than those in group 2 ( P = 0.008 ) . CONCLUSIONS In patients with the nephrotic syndrome caused by idiopathic membranous nephropathy , treatment with methylprednisolone and chlorambucil for six months induces an earlier remission of the nephrotic syndrome than methylprednisolone alone , but the difference may diminish with time Rituximab effectively reduces proteinuria in patients with idiopathic membranous nephropathy ( IMN ) , but response to treatment may vary from patient to patient . The association between baseline clinical , laboratory , and histology covariates and proteinuria reduction was evaluated retrospectively by multiple linear regression analysis at 3 mo after rituximab therapy in 14 patients with IMN with proteinuria > 3.5 g/24 h while on angiotensin-converting enzyme inhibition for at least 6 mo and no previous remissions . The association strength was expressed by st and ardized beta coefficients ( SbetaC ) . Glomerular ( SbetaC = 0.48 , P = 0.049 ) and tubulointerstitial ( TI ) scores ( SbetaC = 0.61 , P = 0.003 ) predicted the outcome . Among glomerular and TI score components , tubular atrophy ( SbetaC = 0.59 , P = 0.003 ) and interstitial fibrosis ( SbetaC = 0.60 , P = 0.001 ) were significantly associated with 3-mo proteinuria . Urinary protein excretion decreased from 9.1 + /- 4.0 to 4.6 + /- 3.5 g/24 h ( P < 0.001 ) in eight patients with TI score 1.7 but did not change in six with a score > or = 1.7 . Nine additional patients with IMN then were allocated prospect ively to rituximab treatment on the basis of a TI score < 1.7 . Three-month proteinuria decreased in all patients from 8.9 + /- 5.3 to 4.9 + /- 3.9 g/24 h ( P < 0.001 ) and serum albumin increased from 2.2 + /- 0.6 to 2.8 + /- 0.5 mg/dl ( P < 0.01 ) . Changes in serum albumin and cholesterol were inversely correlated ( P < 0.02 , r = -0.44 ) . Rituximab achieved CD20 and CD19 depletion in all patients . In patients with IMN and nephrotic proteinuria despite angiotensin-converting enzyme inhibition therapy , renal biopsy findings may help in predicting response to rituximab and defining selection criteria for r and omized trials that aim to assess the risk/benefit profile of B cell target therapy as compared with aspecific immunosuppressants and /or conservative therapy alone Idiopathic membranous nephropathy ( IMN ) is the most common cause of nephrotic syndrome in adults . Universal consensus regarding the need for and the modality of therapy has not been formed because of a lack of controlled trials of sufficient size , quality , and duration . This study compared the effect of a 6-mo course of alternating prednisolone and cyclophosphamide with supportive treatment in adults with nephrotic syndrome caused by IMN on doubling of serum creatinine , development of ESRD , and quality of life in a r and omized , controlled trial . Patients were followed up for 10 yr . Data were analyzed on an intention-to-treat basis . A total of 93 patients completed the study . Of the 47 patients who received the experimental protocol , 34 achieved remission ( 15 complete and 19 partial ) , compared with 16 ( five complete , 11 partial ) of 46 in the control group ( P < 0.0001 ) . The 10-yr dialysis-free survival was 89 and 65 % ( P = 0.016 ) , and the likelihood of survival without death , dialysis , and doubling of serum creatinine were 79 and 44 % ( P = 0.0006 ) in the two groups . Treated patients exhibited significantly lower prevalence of edema , hypertension , hypoalbuminemia , hyperlipidemia that required therapy , angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use , and better quality of life on follow-up . The incidence of infections was similar in the two groups . In conclusion , untreated IMN with nephrotic syndrome is associated with a high risk for deterioration of renal function . A 6-mo regimen of cyclophosphamide and steroids induces remissions in a high proportion , arrests progression of renal insufficiency , and improves quality of life In a controlled double-blind trial five patients with the nephrotic syndrome due to idiopathic membranous glomerulonephritis received azathioprine , 2.5 mg/kg-d , while four others received placebo . After 1 year of treatment there was no significant difference between the two groups with regard to the changes in leukocyte count , values for hemoglobin , serum creatinine , blood urea nitrogen or serum albumin , 24-hour excretion of protein in the urine , or creatinine clearance . In this study azathiprine appeared not to be useful in the treatment of idiopathic membranous glomerulonephritis We treated patients with idiopathic membranous nephropathy ( iMGN ) and renal insufficiency , using : ( i ) ( n = 15 ) monthly cycles of steroids ( 1 g methyl-prednisolone i.v . on three consecutive days , followed by oral prednisone 0.5 mg/kg/day months 1 , 3 and 5 ) and chlorambucil ( 0.15 mg/kg/day months 2 , 4 and 6 ) ; or ( ii ) ( n = 17 ) oral cyclophosphamide ( 1.5 - 2.0 mg/kg/day for 1 year ) and steroids in a comparable dose . The groups were comparable in age , renal function and levels of proteinuria . During the 6 months preceding treatment , serum creatinine levels increased from 148 + /- 50 to 219 + /- 73 mumol/l in the chlorambucil group and from 164 + /- 86 to 274 + /- 126 mumol/l in the cyclophosphamide group . Median ( range ) follow-ups were : chlorambucil 38 months ( 8 - 71 ) ; cyclophosphamide 26 months ( 5 - 68 ) ( NS ) . Renal function improved in both groups , but the improvement was short-lived in the chlorambucil group ; 12 months after starting treatment , mean serum creatinine was 6.3 mumol/l lower in the chlorambucil group and 121 mumol/l lower in the cyclophosphamide group ( p < 0.01 ) . Four chlorambucil-treated patients developed ESRD , and five needed a second course of therapy , whereas only one cyclophosphamide-treated patient developed ESRD ( p < 0.05 ) . Remissions of proteinuria occurred more frequently after cyclophosphamide treatment ( 15/17 vs. 5/15 ; p < 0.01 ) . Side-effects necessitated interruption of treatment in six patients on cyclophosphamide and in 11 on chlorambucil ( p < 0.05 ) . In our patients , oral cyclophosphamide was better tolerated than oral chlorambucil . The suggested greater efficacy of the oral cyclophosphamide regimen needs to be ascertained by longer follow-up Patients of idiopathic membranous nephropathy ( MGN ) were r and omly assigned to received steroid and cyclophosphamide every other month ( Gr-I ) and steroid alone ( Gr-II ) . Of 36 patients in Gr . I , 33 patients achieved complete remissions , 2 had relapsing course with remission on further courses of therapy and only one has reached end stage renal failure . In contrast , of the 35 patients in Gr . II , 15 ( P < 0.001 ) achieved complete remission , 7 are in partial remission , 5 have no response , another 5 have deterioration of renal function of which two required dialysis , and 3 have relapsing course after the initial remission . Mean follow up period was 46 + /- 10.2 months . We conclude that steroid and cyclophosphamide every other month is highly effective in achieving remission in patients with membranous nephropathy Background : Idiopathic membranous nephropathy ( IMN ) , a common cause of nephrotic syndrome in adults , is usually treated with corticosteroids in combination with cyclophosphamide or cyclosporine . A recent placebo-controlled study suggested that tacrolimus monotherapy was effective in IMN . However , the effectiveness of tacrolimus versus classic regimen and its potential nephrotoxicity remain inconclusive . This study evaluated the efficacy and safety of tacrolimus plus prednisone in patients with nephrotic IMN . Methods : Seventy-three patients with nephrotic IMN were recruited in this multicenter r and omized controlled trial , 39 receiving tacrolimus and prednisone , while 34 receiving cyclophosphamide and prednisone . Tacrolimus was given at 0.1 mg/kg/d initially and adjusted to a blood trough level at 5 to 10 ng/mL for 6 months and then reduced to 2 to 5 ng/mL in the subsequent 3 months . Results : Intention-to-treat analysis suggested that the remission rate at the end of the sixth month was significantly higher in tacrolimus group than that in cyclophosphamide group ( 85 % versus 65 % , P < 0.05 ) . The decrease of proteinuria was significantly greater in tacrolimus group . At the end of the 12th month , the remission rates were comparable between these 2 groups . Patients treated with tacrolimus were more likely to develop glucose intolerance ( or diabetes mellitus ) , infection , and hypertension . No obvious nephrotoxicity of calcineurin inhibitor was found in repeat renal biopsy . Conclusions : Tacrolimus plus corticosteroids is an alternative therapeutic regimen for nephrotic IMN . The short-term efficacy might be better than cyclophosphamide plus prednisone |
2,454 | 21,326,002 | Studies in curative treatments for oesophagogastric cancer show that surgery and chemoradiation therapy has a major short-term detrimental effect on HRQL , but recovery occurs within 6 months in long-term survivors but those not achieving a survival benefit report very poor HRQL .
In advanced oesophageal cancer , 18 mm self-exp and able metal stents and nonstent therapies lead to better short-term HRQL scores than nonexp and able stents and are the recommended st and ard of care .
A small survival advantage and improved HRQL is conferred by adjuvant and palliative gemcitabine chemotherapy in patients with pancreatic cancer .
SUMMARY This review identified few well- design ed studies that also included a robust assessment of HRQL . | PURPOSE OF REVIEW The aim of this systematic review is to scrutinize and summarize the design , conduct and reporting st and ards of articles recently published describing health-related quality of life ( HRQL ) outcomes of treatment of upper gastrointestinal cancer . | The European Study Group for Pancreatic Cancer ( ESPAC-1 ) study is the largest study of adjuvant treatment for pancreatic ductal adenocarcinoma to date and confirmed a survival advantage for adjuvant chemotherapy but not for chemoradiation . The importance of parallel evaluation of survival and quality of life ( QoL ) has been recognized as fundamental and the aim was to assess QoL and quality adjusted survival . A longitudinal QoL study on a subset of ESPAC-1 patients who prospect ively completed the EORTC QLQ C-30 question naire during treatment and follow-up . An integrated quality -survival product method was used to adjust any treatment effect on survival by a function of measured QoL , calculated over a restricted 24-month-period ( QALM-24 ) . Three hundred and sixteen patients completed 1,201 question naires . There were no differences between treatment groups in dimension scores at baseline ( r and omization ) . For the chemotherapy group , the mean Quality Adjusted Life Months over 24 months ( QALM-24 ) was 9.6 ( 95 % CI : 8.7 , 11.2 ) months compared with the mean QALM-24 of 8.6 ( 95 % CI : 7.6 , 10.5 ) months for the no chemotherapy group . For the chemoradiation group , the mean QALM-24 was 7.1 ( 95 % CI : 6.0 , 9.0 ) months compared with the mean QALM-24 of 8.1 ( 95 % CI : 7.0 , 10.0 ) months for the no chemoradiation group . The previously reported survival advantage supporting the use of adjuvant chemotherapy is maintained when adjusted using quality adjusted survival methodology . Chemotherapy provided on average an additional 1.0 quality -adjusted life months within a restricted 2-year time period from the time of resection PURPOSE To determine the effects of primary chemoembolization on the health-related quality of life ( HRQOL ) of patients with hepatocellular carcinoma ( HCC ) . MATERIAL S AND METHODS Single-center prospect i ve data collection with longitudinal analysis of HRQOL scores obtained via the Short Form-36 ( SF-36 ) assessment tool was performed before and during serial chemoembolization procedures in 73 patients with HCC . Baseline HRQOL scores were evaluated for significant ( P < .05 ) change within the total patient population during 4 , 8 , and 12 months of treatment , and separately within a subset of 23 patients who underwent three or more chemoembolization procedures . RESULTS Patients had decreased pretreatment baseline scores within all eight scales of the SF-36 compared with healthy age-adjusted norms . Within the total population , mental health scores improved after 4 months of chemoembolization ( rate of change , 5.6 ; P = .05 ; n = 48 ) , but no significant change was present at 8 or 12 months . Subset patients experienced improvements of mental health scores after the first ( score change , 13 ; P = .008 ; n = 21 ) and second procedures ( score change , 12.2 ; P = .002 ; n = 23 ) and improvements of bodily pain scores ( score change , 9.9 ; P = .047 ; n = 21 ) after the initial procedure . Vitality scores worsened ( score change , -7.8 ; P = .044 ; n = 21 ) in the subset after the first chemoembolization . CONCLUSIONS Patients with HCC are likely to perceive improved mental health during the first 4 months of primary treatment with chemoembolization . In addition , if patients ultimately undergo more than two procedures , they are likely to perceive improved mental health during the first two sessions , with decreased bodily pain during the initial session . Patient-perceived vitality will likely worsen after the initial procedure OBJECTIVES : A dramatic rise in incidence , an aging population , and expensive palliative treatments have led to an escalating burden on clinicians managing inoperable esophageal cancer with only limited evidence of effectiveness . This study compares the clinical effectiveness and cost-effectiveness of self-exp and ing metal stents ( SEMSs ) with other palliative therapies to aid clinicians in making an evidence -based treatment choice . METHODS : We conducted a prospect i ve , multicenter , r and omized , controlled , clinical trial with 215 patients followed until death or study closure . The primary outcome measures were dysphagia , quality of life ( QL ) 6 weeks following treatment , and total cost of treatment . Secondary outcome measures included treatment-associated morbidity , mortality , survival , and cost-effectiveness . An intention-to-treat analysis was carried out . RESULTS : There was a significant difference in mean dysphagia grade between treatment arms 6 weeks following treatment ( P=0.046 ) , with worse swallowing reported by rigid stent – treated patients ( mean dysphagia score difference=−0.49 ; 95 % confidence interval ( CI ) −0.10 to −0.89 , P=0.014 ) . Global QL scores were lower at both 1 and 6 weeks following treatment for patients treated by SEMSs ( mean difference QL index week 1=−0.66 ; 95 % CI : −0.02 to −1.30 , P=0.04 ; mean difference QL index week 6=−1.01 ; 95 % CI −0.30 to −1.72 , P=0.006 ) . These findings were associated with higher post-procedure pain scores in the SEMS patient group ( mean difference of the European Organisation for Research and Treatment of Cancer QLQ C-30 pain symptom score at week 1=11.13 ; 95 % CI : 2.89–19.4 ; P=0.01 ) . Although mean EQ-5D QL values differed between the treatments ( P<0.001 ) , this difference dissipated following generation of quality -adjusted life year values . Total costs varied between treatment arms but these findings canceled out when SEMSs were compared with non-SEMS therapies ( 95 % CI −845.15–1,332.62 ) . These results were robust to sensitivity analysis . There were no differences in the in-hospital mortality or early complication rates , but late complications were more frequent after rigid stenting ( risk ratio=2.47 ; 95 % CI 1.88–3.04 ) . There was a survival advantage for non-stent-treated patients ( log-rank statistic=4.21 , P=0.04 ) . CONCLUSIONS : The treatment choice for patients with inoperable esophageal cancer should be between a SEMS or a non-stent treatment after consideration has been given to both patient and tumor characteristics and clinician and patient preferences BACKGROUND AND OBJECTIVES This pilot study prospect ively evaluates the impact of esophageal resection on health-related quality of life ( HRQL ) and mood states at diagnosis and during the first year after surgery . METHODS Participants included 38 patients with planned esophageal resection . Two instruments were used : the Functional Assessment in Cancer Therapy core instrument with the esophageal subscale ( FACT-E ) , and the Profile of Mood States ( POMS ) . Subjects were evaluated after diagnosis and at 1 , 3 , 6 , 9 , and 12 months after surgical resection . RESULTS All subjects demonstrated a decrease in overall HRQL after resection with a gradual return toward baseline by month 9 . The functional and physical subscales of the FACT-E demonstrated the largest decrease at 1 month with a gradual return toward baseline . The POMS subscales that demonstrated the highest amount of disorder after surgery were tension , fatigue , and vigor . Although the trends were similar between patients undergoing surgery alone ( n = 18 ) and those with neoadjuvant therapy ( n = 20 ) , the group that had received surgery alone demonstrated a higher HRQL and less mood disorder during the postoperative period , as compared with the neoadjuvant group . CONCLUSIONS Patient perceptions of HRQL and mood states change over the first 12 months after esophageal resection . Although no statistically significant differences were found in this study , several trends were identified . Ongoing assessment s of these changes are important , and interventions need to be developed and implemented to produce an effective decrease in the impact of esophageal resection on HRQL and mood states , particularly after trimodality therapy Purpose Gemcitabine is the only drug approved for single-agent therapy in advanced pancreatic carcinoma ( APC ) . Gemcitabine-based combination chemotherapy has not yet shown promising results . Methods This multicenter phase II study enrolled previously untreated patients with locally advanced and /or metastatic pancreatic adenocarcinoma . Patients received 1,000 mg/m2 gemcitabine , 100-min infusion , day 1 and 100 mg/m2 oxaliplatin , 2-h infusion , day 2 ; q2w . The primary end point was response rate ( RR ) . Results Thirteen study centers enrolled 48 eligible patients of which 44 were evaluable . The RR , median overall survival , and median time to progression were 18.2 % , 9.4 and 5.6 months , respectively . Sixteen patients ( 36.4 % ) experienced clinical benefit . The global quality of life scores improved by 11.71 . Grade 3/4 peripheral sensory neuropathy was noted ( 2.1 % ) , while the most common hematologic toxicity was anemia ( grade 3/4 , 6.3 % ) . Conclusions Gemcitabine and oxaliplatin combination chemotherapy showed a promising activity in APC patients and was well tolerated Purpose The quality of life ( QL ) of advanced gastric cancer patients receiving irinotecan , folinic acid and 5-fluorouracil ( 5-FU ) ( IF arm ) or cisplatin with 5-FU ( CF arm ) is presented . Methods Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks . QL was assessed using the EORTC QLQ-C30 at baseline , subsequently every 8 weeks until progression and thereafter every 3 months until death . The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling . Results A total of 333 patients were r and omised and treated ( IF 170 , CF 163 ) . The time-to-progression for IF and CF was 5.0 and 4.2 months ( P = 0.088 ) , respectively . The overall compliance rates for QL question naire completion were 60 and 56 % in the IF and CF arms , respectively . Significant treatment differences were observed for the physical functioning scale ( P = 0.024 ) , nausea\vomiting ( P = 0.001 ) and EQ-5D thermometer ( P = 0.020 ) in favour of the IF treatment arm . Conclusion There was a trend in favour of IF over CF in time-to-progression . The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales , suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer BACKGROUND Previous work highlighted a number of method ological constraints when reporting health-related quality of life ( HRQOL ) outcomes from r and omized controlled trials ( RCTs ) . Given this , the objective of this study was to investigate whether the quality of such HRQOL reports has improved over time . MATERIAL S AND METHODS On the basis of a predefined set of criteria , 159 RCTs with a HRQOL end point , published between 1990 and 2004 were identified and analyzed . Each study was evaluated by a number of issues ( e.g. sample size and industry sponsorship ) and by the " minimum st and ard checklist for evaluating HRQOL outcomes in cancer clinical trials " . RESULTS The quality of HRQOL reports , as measured by the overall checklist score , was independently related to more recently published studies ( P < 0.0001 ) . This relationship was independent of industry funded , HRQOL end point ( primary versus secondary ) , cancer disease site , size of the study and HRQOL difference between treatment arms . While only 39.3 % of studies published between 1990 and 2000 ( 89/159 RCTs ) were identified as being probably robust , thus likely to support clinical decision making , this percentage was 64.3 % for studies published after 2000 ( 70/159 RCTs ) . CONCLUSION Since we found a significant learning curve in HRQOL trial reporting since 1990 , it can be expected that HRQOL data will increasingly impact on clinical decision making and treatment policies in the near future BACKGROUND A previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma ( HCC ) . This was investigated further in this multicentre study . PATIENTS AND METHODS Two hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were r and omised to receive long-acting octreotide , 30 mg as an intramuscular injection once every 4 weeks for up to 2 years , or placebo . RESULTS At the time of the final analysis , median overall survival ( OS ) was 6.53 months ( 95 % confidence interval [ CI ] , 4.8 - 8.3 ) for octreotide versus 7.03 months ( 95 % CI , 5.43 - 8.53 ) for placebo ( p=0.34 ) . Progression-free survival ( p=0.26 ) also did not differ significantly between the two treatment groups . No objective responses were achieved in the octreotide group but 33 % of patients achieved disease stabilisation for a mean time of 5.5 months ( 95 % CI , 1.1 - 9.9 ) . The median time until definitive global health score deterioration ( according to QLQ-C30 ) was 2.3 months ( 95 % CI , 1.4 - 3.7 ) in the octreotide and 4 months ( 95 % CI , 2.2 - 5.7 ) in the placebo group ( p=0.09 ) . There were four objective responses in the placebo group . Octreotide was well tolerated ; seven patients reported severe adverse events possibly related to octreotide and there were no cases of haematoma or cholecystitis . CONCLUSIONS In patients with advanced HCC , octreotide has a favourable safety profile but does not improve OS and could have a negative impact on quality of life PURPOSE To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil ( FU ) and leucovorin ( Folfirinox ) in advanced pancreatic adenocarcinoma ( APA ) . PATIENTS AND METHODS Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks , which comprised oxaliplatin 85 mg/m(2 ) and irinotecan 180 mg/m(2 ) plus leucovorin 400 mg/m(2 ) followed by bolus FU 400 mg/m(2 ) on day 1 , then FU 2,400 mg/m(2 ) as a 46-hour continuous infusion . Quality of life ( QOL ) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) . RESULTS Forty-seven patients were entered , and 46 received treatment . Thirty-five patients ( 76 % ) had metastatic disease . A total of 356 cycles were delivered , with a median of eight cycles per patient ( range , one to 24 cycles ) . All patients were assessable for safety . No toxic death occurred . Grade 3 to 4 neutropenia occurred in 52 % of patients , including two patients with febrile neutropenia . Other relevant toxicities included grade 3 to 4 nausea ( 20 % ) , vomiting ( 17 % ) , and diarrhea ( 17 % ) and grade 3 neuropathy ( 15 % ; Levi 's scale ) . The confirmed response rate was 26 % ( 95 % CI , 13 % to 39 % ) , including 4 % complete responses . Median time to progression was 8.2 months ( 95 % CI , 5.3 to 11.6 months ) , and median overall survival was 10.2 months ( 95 % CI , 8.1 to 14.4 months ) . Between baseline and end of treatment , patients had improvement in all functional scales of the EORTC QLQ-C30 , except cognitive functioning . Responders had major improvement in global QOL . CONCLUSION With a good safety profile , a promising response rate , and an improvement in QOL , Folfirinox will be further assessed in a phase III trial The feasibility , safety , and efficacy of planned sequential administration of docetaxel and irinotecan with 5-fluorouracil (5-FU)/leucovorin in advanced upper gastrointestinal adenocarcinoma ( UGIA ) are unknown . Seventy-three patients with gastric ( GC ; n = 22 ) , pancreatic ( PC ; n = 28 ) or biliary cancer ( BC ; n = 23 ) were r and omised to start with 45 mg/m2 docetaxel or 180 mg/m2 irinotecan combined with 5-FU/leucovorin every 2nd week . After every 2nd course , the patients were crossed over to the other combination . Treatment was given for a maximum of 12 courses . Quality -of-life ( QoL ) was evaluated during the first two months using the EORTC QLQ-C30 . Eighteen patients ( 25 % ; GC 32 % , PC 21 % , BC 22 % ) demonstrated partial response ( PR ) and 21 ( 29 % ) had prolonged stable disease . Mean QoL scores were low at baseline . Twenty-three ( 32 % ) patients had improved QoL using a summary measure and 13 were stable . Median time to progression was 4.4 months and overall survival 8.2 months . The treatments were reasonably well tolerated . Grade 3–4 toxicities were slightly more common for the docetaxel combination . There were two treatment-related deaths . Planned sequential treatment with docetaxel or irinotecan with 5-FU/leucovorin is feasible , reasonably tolerable and appears active in advanced UGIA 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 Health‐related quality of life ( HRQL ) outcomes are important in assessing new approaches to the treatment of cancer . Neoadjuvant therapy is being used increasingly before surgery in patients with localized oesophageal cancer . This prospect i ve non‐r and omized study evaluated HRQL in patients treated by preoperative chemotherapy and radiation therapy followed by surgery ( multimodal therapy ) or by surgery alone BACKGROUND Both gastrojejunostomy ( GJJ ) and stent placement are commonly used palliative treatments of obstructive symptoms caused by malignant gastric outlet obstruction ( GOO ) . OBJECTIVE Compare GJJ and stent placement . DESIGN Multicenter , r and omized trial . SETTING Twenty-one centers in The Netherl and s. PATIENTS Patients with GOO . INTERVENTIONS GJJ and stent placement . MAIN OUTCOME MEASUREMENTS Outcomes were medical effects , quality of life , and costs . Analysis was by intent to treat . RESULTS Eighteen patients were r and omized to GJJ and 21 to stent placement . Food intake improved more rapidly after stent placement than after GJJ ( GOO Scoring System score > or = 2 : median 5 vs 8 days , respectively ; P < .01 ) but long-term relief was better after GJJ , with more patients living more days with a GOO Scoring System score of 2 or more than after stent placement ( 72 vs 50 days , respectively ; P = .05 ) . More major complications ( stent : 6 in 4 patients vs GJJ : 0 ; P = .02 ) , recurrent obstructive symptoms ( stent : 8 in 5 patients vs GJJ : 1 in 1 patient ; P = .02 ) , and re interventions ( stent : 10 in 7 patients vs GJJ : 2 in 2 patients ; P < .01 ) were observed after stent placement compared with GJJ . When stent obstruction was not regarded as a major complication , no differences in complications were found ( P = .4 ) . There were also no differences in median survival ( stent : 56 days vs GJJ : 78 days ) and quality of life . Mean total costs of GJJ were higher compared with stent placement ( $ 16,535 vs $ 11,720 , respectively ; P = .049 [ comparing medians ] ) . Because of the small study population , only initial hospital costs would have been statistically significant if the Bonferroni correction for multiple testing had been applied . LIMITATIONS Relatively small patient population . CONCLUSIONS Despite slow initial symptom improvement , GJJ was associated with better long-term results and is therefore the treatment of choice in patients with a life expectancy of 2 months or longer . Because stent placement was associated with better short-term outcomes , this treatment is preferable for patients expected to live less than 2 months . ( CLINICAL TRIAL REGISTRATION NUMBER IS RCT N 06702358 . ) Abstract Objective . Patients with incurable distal esophageal or cardia cancer often need palliative stenting to relieve their dysphagia but stents passing through the cardia can cause reflux and aspiration , leading to a reduced health-related quality of life ( HRQL ) . This study addressed the hypothesis that antireflux stenting improves HRQL compared to conventional stenting . Material and methods . In a single-blind , multicenter , r and omized trial in patients with inoperable esophageal or cardia cancer requiring palliative stenting passing through the cardia , 65 patients were stented . Patients received either an antireflux stent ( Esophageal Z-Stent with Dua antireflux valve ; n = 28 ) or a conventional stent ( Esophageal Z-stent , Ultraflex or Wallstent ; n = 37 ) . Vali date d question naires ( European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-OES18 ) were used to collect information on HRQL at baseline and 1 and 3 months after stenting . Main outcome measurements were differences in HRQL scores between baseline and 1 and 3 months after stenting . Results . Scores for most aspects of HRQL were similar in the two groups , and no statistically significant differences were found . Some general symptoms however showed clinical ly relevant improvement in the antireflux stent group , while esophageal-specific symptoms such as dysphagia seemed clinical ly better , and symptoms of reflux were clinical ly reduced in the conventional stent group but not in the antireflux stent group . Conclusion . This study , although limited in size , provided no obvious support for using the antireflux stent in preference to the conventional stent in the palliation of distal esophageal or cardia cancer from an HRQL perspective BACKGROUND Gastric outlet obstruction ( GOO ) is most commonly a complication of advanced distal gastric , periampullary , or duodenal malignancy . Palliation of obstruction is the primary aim of treatment in most of these patients . Self-exp and able metal stents have emerged as an effective treatment option . OBJECTIVE Our purpose was to investigate the efficacy and safety of a newly developed enteral metal stent ( WallFlex ) . DESIGN Prospect i ve multicenter cohort study . SETTING Three tertiary referral centers ( 2 academic ) . PATIENTS Fifty-one consecutive patients with symptomatic malignant GOO from January 2005 to February 2006 . INTERVENTION Placement of a self-exp and able metallic stent ( WallFlex ) . MAIN OUTCOME MEASUREMENTS The primary end point was defined as improvement of the GOO scoring system for the remainder of the patients ' lives . Secondary end points focused on efficacy and safety and global quality of life . RESULTS The Gastric Outlet Obstruction Scoring System score improved ( P < .001 ) , the body mass index decreased ( P < .001 ) , and the World Health Organization performance score improved ( P = .002 ) when the score before stenting was compared with the mean score until death . Global quality of life did not improve . Technical and clinical success was achieved in 98 % and 84 % of the patients . Median survival was 62 days ( 75 % alive at 35 days , 25 % alive at 156 days ) . Median stent patency was 307 days ( 75 % functional at 135 days , 25 % functional at 470 days ) . Stent dysfunction was proved in 7 patients ( 14 % ) , migration in 1 ( 2 % ) , and tumor overgrowth or ingrowth in 6 ( 12 % ) . LIMITATIONS Lack of a control group . CONCLUSION Placement of a WallFlex enteral stent in patients with nonresectable malignant GOO is safe and provides a statistically significant and clinical ly relevant relief of obstructive symptoms with a low need for reintervention Adjuvant therapies for pancreatic and periampullary cancer reportedly achieve only a marginal survival benefit . In this r and omized controlled trial , 120 patients with resected pancreatic or periampullary cancer received either adjuvant celiac axis infusion chemotherapy combined with radiotherapy ( CAI/RT ) or no adjuvant treatment . The objective of the study was to compare the quality of life ( QoL ) in patients who received CAI/RT after pancreatoduodenectomy with the QoL in patients who did not receive adjuvant treatment PURPOSE To determine which formats for presenting health-related quality of life ( HRQL ) data are interpreted most accurately and are most preferred by cancer patients . Patients often want a great deal of information about cancer treatments , including information relevant to HRQL . Clinical trials provide method ologically sound HRQL data that may be useful to patients . PATIENTS AND METHODS In a multicenter study , 198 patients with previously treated cancer participated in a structured interview . Participants judged HRQL information presented in one textual and five graphical formats . Outcome measures included the accuracy of patients ' interpretations and ease-of-use and helpfulness ratings for each format . RESULTS Correct interpretations ranged from 85 % to 98 % across formats ( F = 10.3 , P < .0001 ) with line graphs of mean HRQL scores over time being interpreted correctly most often . Older patients and less-educated patients were less likely to interpret graphs accurately ( F = 7.3 , P = .008 ; and F = 10.6 , P = .001 , respectively ) , but all groups were most accurate on simple line graphs . Multivariate analysis revealed that format type , participant age and education were independent predictors of accuracy rates . Patients ' ratings also varied across formats both for ease of underst and ing scores ( F = 12.1 , P < .0001 ) and for helpfulness scores ( F = 13.2 , P < .0001 ) , with line graphs being rated highest on both outcomes . CONCLUSION Patients generally prefer a simple linear representation of group mean HRQL scores , and can accurately interpret data presented in this format more than 98 % of the time irrespective of their age group and educational level . The findings have important implication s for the communication of clinical trial HRQL results BACKGROUND Controversy exists about the best surgical treatment for esophageal carcinoma . METHODS We r and omly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy . Principal end points were overall survival and disease-free survival . Early morbidity and mortality , the number of quality -adjusted life-years gained , and cost effectiveness were also determined . RESULTS A total of 106 patients were assigned to undergo transhiatal esophagectomy , and 114 to undergo transthoracic esophagectomy . Demographic characteristics and characteristics of the tumor were similar in the two groups . Perioperative morbidity was higher after transthoracic esophagectomy , but there was no significant difference in in-hospital mortality ( P=0.45 ) . After a median follow-up of 4.7 years , 142 patients had died--74 ( 70 percent ) after transhiatal resection and 68 ( 60 percent ) after transthoracic resection ( P=0.12 ) . Although the difference in survival was not statistically significant , there was a trend toward a survival benefit with the extended approach at five years : disease-free survival was 27 percent in the transhiatal-esophagectomy group , as compared with 39 percent in the transthoracic-esophagectomy group ( 95 percent confidence interval for the difference , -1 to 24 percent [ the negative value indicates better survival with transhiatal resection ] ) , whereas overall survival was 29 percent as compared with 39 percent ( 95 percent confidence interval for the difference , -3 to 23 percent ) . CONCLUSIONS Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy . Although median overall , disease-free , and quality -adjusted survival did not differ statistically between the groups , there was a trend toward improved long-term survival at five years with the extended transthoracic approach Background : A phase III trial suggested that a PEFG ( cisplatin , epirubicin , 5-fluorouracil , gemcitabine ) regimen might improve the outcome compared to gemcitabine in advanced pancreatic adenocarcinoma . The analysis of treatment impact on quality of life ( QOL ) is reported . Method : Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and PAN-26 question naires at baseline and every second month of treatment until disease progression . Results : The largest differences between arms favored PEFG . Expressed as improvement ≧10 points from baseline ( PEFG/gemcitabine ) , these were : emotional function ( 43/18 % ) , fatigue ( 41/17 % ) , QOL ( 55/29 % ) , pain ( 64/41 % ) , and flatulence ( 50/26 % ) . Only change in sexual function favored gemcitabine ( 19/42 % ) . Physical function , fatigue , appetite , and satisfaction with healthcare improved in 40–46 % of partial responders compared with 0–12 % of patients with stable disease . Conclusion : Clinical ly relevant improvement in QOL from baseline was observed more often after PEFG than after gemcitabine , suggesting that the PEFG regimen did not impair QOL , Partial response was associated with improved QOL suggesting that effective treatment of pancreatic adenocarcinoma may have an important role in these patients OBJECTIVE We sought to determine the effect of neoadjuvant chemoradiotherapy followed by surgical intervention on health-related quality of life in patients with esophageal cancer . METHODS Health-related quality of life was evaluated in a prospect i ve phase II study of neoadjuvant chemoradiotherapy followed by esophagectomy in 52 patients with carcinoma of the esophagus . Esophagectomy was performed 6 weeks after completion of induction . Functional Assessment of Cancer Therapy-Esophageal scoring was performed before treatment , 7 weeks after initiation of neoadjuvant therapy , before resection , and at 1 , 3 , and 6 months and 1 year after resection . RESULTS Forty-three patients completed the entire treatment protocol . Functional Assessment of Cancer Therapy-Esophageal scores decreased significantly after chemoradiation at week 7 ( 120 vs 127 at baseline , P = .04 ) but returned to baseline levels before surgical intervention ( 127 ) . Similarly , scores decreased significantly after surgical intervention ( 115 at 1 month , P = .02 ) but returned to baseline levels by 3 months postoperatively ( 127 ) . At 1 year postoperatively , there was a statistically significant improvement in scores compared with those at baseline ( 139 , P = .003 ) . Functional Assessment of Cancer Therapy-Esophageal scores continued to increase over time for patients who were alive at least 1 year after the operation with or without disease but were observed to significantly decrease in those who died within 1 year after the operation ( P = .0001 ) . An increase in quality of life was associated with a significantly lower risk of death ( P = .04 ) . CONCLUSION Neoadjuvant therapy has a significant effect on health-related quality of life , but this is transient , with recovery to baseline within 5 to 7 weeks after completion of induction therapy . Health-related quality of life decreases again after surgical intervention but returns to baseline levels within 3 months BACKGROUND The aim of the study was to compare the longitudinal quality of life ( QoL ) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a r and omized multicenter phase III trial ( FFCD 9102 ) . MATERIAL S AND METHODS All patients with locally advanced resectable ( T3 - 4 N0 - 1 M0 ) epidermoid or gl and ular esophageal cancer ( n = 451 ) received induction chemoradiation . Responders ( n = 259 ) were r and omized between surgery ( arm A ) and continuation of chemoradiation ( arm B ) . The Spitzer QoL Index was scored ( 0 - 10 ) at inclusion and at each follow-up , every 3 months during 2 years . QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements . The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up . RESULTS The squamous histology was predominant in both arms . The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups . QoL scores at the first follow-up were comparatively worse in arm A than in arm B ( 7.52 versus 8.45 , P < 0.01 ) , whereas the longitudinal QoL study showed no difference between treatments ( adjusted P = 0.26 ) . Furthermore , the longitudinal QoL was not different ( adjusted P = 0.23 ) among survivors with 2 years of follow-up . CONCLUSIONS Among patients responding to induction chemoradiation , surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced , resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period BACKGROUND This prospect i ve study examined health-related quality of life ( HRQL ) and survival in patients with potentially curable gastric cancer . METHODS Consecutive patients ( n=58 ) selected for curative surgery completed a vali date d question naire ( EORTC QLQ-C30 ) and site-specific module ( QLQ-STO22 ) before surgery and regularly for 2 years afterwards . Changes of 10 or more points on a 0 - 100 scale were considered clinical ly significant . RESULTS Some 30 patients were alive after 2 years ( 52 % ) . In the first 3 months after surgery , HRQL was significantly reduced across all dimensions except emotional and cognitive functioning ( mean reduction of 10 or more points ) . Functional aspects of HRQL recovered by 6 months in patients who subsequently were alive at 2 years , although at least a third of patients experienced specific symptoms , even 6 months after surgery , especially diarrhoea . For those dying within 2 years , some postoperative functional HRQL recovery occurred , but many symptoms were common . CONCLUSIONS Potentially curative gastrectomy for cancer has a detrimental impact on HRQL that mostly recovers in patients surviving some 2 years . Patients who die within 2 years may experience limited postoperative recovery . It is recommended that patients receive HRQL information about the outcomes of surgery for gastric cancer PURPOSE S0205 was a r and omized clinical trial that compared the therapeutic impact of gemcitabine versus gemcitabine plus cetuximab . Study results for patient-reported health-related quality of life ( HRQL ) outcomes are reported . PATIENTS AND METHODS Patients completed the Brief Pain Inventory and a measure of emotional well-being ( each measured on a 0 to 10 scale ) at baseline and at weeks 5 , 9 , 13 , and 17 postr and om assignment . Worst pain status was classified as palliated ( worst pain scores < 5 maintained for 2 consecutive cycles ) or not palliated ( remaining patients ) and tested with a chi(2 ) test . Change in emotional well-being and worst pain ( exploratory analysis ) were assessed over 17 weeks using generalized estimating equations with inverse probability of censoring weights . RESULTS Seven hundred twenty of 766 enrolled patients contributed baseline HRQL data . The two treatment arms did not differ statistically in the percentage of patients with successful worst pain palliation . Longitudinal analyses showed significantly improved emotional well-being for patients on both arms by weeks 13 and 17 ( P < .01 and P < .001 ) . An exploratory longitudinal analysis of worst pain showed significant decreases at all time points for both arms ( P < .01 and P < .001 ) . Significant treatment arm differences for either worst pain or emotional well-being were not observed at any of the assessment times . CONCLUSION We observed palliated pain and improved well-being for patients on this trial . However , these improvements were similar in both treatment arms , suggesting that the addition of cetuximab did not contribute to improvement in these HRQL outcomes It is not known whether pylorus‐preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours . A prospect i ve r and omized trial was undertaken to compare the results of the two procedures PURPOSE Conventional medicine has had little to offer patients with inoperable pancreatic adenocarcinoma ; thus , many patients seek alternative treatments . The National Cancer Institute , in 1998 , sponsored a r and omized , phase III , controlled trial of proteolytic enzyme therapy versus chemotherapy . Because most eligible patients refused r and om assignment , the trial was changed in 2001 to a controlled , observational study . METHODS All patients were seen by one of the investigators at Columbia University , and patients who received enzyme therapy were seen by the participating alternative practitioner . Of 55 patients who had inoperable pancreatic cancer , 23 elected gemcitabine-based chemotherapy , and 32 elected enzyme treatment , which included pancreatic enzymes , nutritional supplements , detoxification , and an organic diet . Primary and secondary outcomes were overall survival and quality of life , respectively . Results At enrollment , the treatment groups had no statistically significant differences in patient characteristics , pathology , quality of life , or clinical ly meaningful laboratory values . Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group ( median survival , 14 months ) and enzyme treatment groups ( median survival , 4.3 months ) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 ( P < .001 ) . At 1 year , 56 % of chemotherapy-group patients were alive , and 16 % of enzyme-therapy patients were alive . The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group ( P < .01 ) . CONCLUSION Among patients who have pancreatic cancer , those who chose gemcitabine-based chemotherapy survived more than three times as long ( 14.0 v 4.3 months ) and had better quality of life than those who chose proteolytic enzyme treatment PURPOSE Evidence suggests that patient-reported outcomes ( PROs ) from r and omized trials in oncology may not influence clinical decision making and patient choice . Reasons for this are currently unclear and little is known about patients ' interpretation of PROs . This study assessed patients ' underst and ing of multidimensional PROs in a graphical format . PATIENTS AND METHODS Semistructured interviews in which patients interpreted a series of graphs depicting simple , then multiple different hypothetical PROs associated with two treatments with identical chances of survival were audio recorded . The interviewer and a blinded observer ( listening to audio recordings ) scored patients ' underst and ing of the graphs . Logistic regression examined the associations between patient underst and ing of the graphs and clinical and sociodemographic details . Results One hundred thirty-two patients with esophageal and gastric cancer were interviewed and 115 understood the first two graphs depicting different PROs of two treatments ( 87 % ; 95 % CI,81 to 93 ) . Simultaneous interpretation of adverse and beneficial treatment effects was achieved by 74 ( 66 % ; 95 % CI , 57 to 75 ) . Graphs showing complex , longitudinal data were correctly interpreted by 97 ( 73 % ; 95 % CI , 66 to 81 ) and 108 ( 81 % ; 95 % CI , 75 to 88 ) , respectively . Univariable analyses demonstrated associations between patient underst and ing and patient age , educational level , and cancer site ( P < or = .02 for all ) ; however , in a multivariable model each of these associations was attenuated . CONCLUSION Most patients underst and graphical multidimensional PROs , although a smaller majority were able to interpret more complex , or simultaneous , presentations . Additional work is needed to define methods for communicating clinical and PRO data from trials to allow patients to make informed treatment choices |
2,455 | 28,786,336 | Conclusions : Five-session rTMS treatment could best improve stroke-induced upper limb dyskinesia acutely and in a long-lasting manner .
Intermittent theta burst stimulation is more beneficial than continuous theta burst stimulation .
rTMS applied in the acute phase of stroke is more effective than rTMS applied in the chronic phase .
Subcortical lesion benefit more from rTMS than other lesion site | Objective : The aim of this study was to evaluate the short- and long-term effects as well as other parameters of repetitive transcranial magnetic stimulation ( rTMS ) on upper limb motor functional recovery after stroke . | The authors investigated the use of slow-frequency repetitive transcranial magnetic stimulation ( rTMS ) to the unaffected hemisphere to decrease interhemispheric inhibition of the lesioned hemisphere and improve motor function in patients within 12 months of a stroke . Patients showed a significant decrease in simple and choice reaction time and improved performance of the Purdue Pegboard test with their affected h and after rTMS of the motor cortex in the intact hemisphere as compared with sham rTMS Objective : To investigate the long-term behavioral and neurophysiologic effects of combined time-locked repetitive transcranial magnetic stimulation ( rTMS ) and physical therapy ( PT ) intervention in chronic stroke patients with mild motor disabilities . Methods : Thirty patients were enrolled in a double-blind , r and omized , single-center clinical trial . Patients received 10 daily sessions of 1 Hz rTMS over the intact motor cortex . In different groups , stimulation was either real ( rTMSR ) or sham ( rTMSS ) and was administered either immediately before or after PT . Outcome measures included dexterity , force , interhemispheric inhibition , and corticospinal excitability and were assessed for 3 months after the end of treatment . Results : Treatment induced cumulative rebalance of excitability in the 2 hemispheres and a reduction of interhemispheric inhibition in the rTMSR groups . Use-dependent improvements were detected in all groups . Improvements in trained abilities were small and transitory in rTMSS patients . Greater behavioral and neurophysiologic outcomes were found after rTMSR , with the group receiving rTMSR before PT ( rTMSR-PT ) showing robust and stable improvements and the other group ( PT-rTMSR ) showing a slight improvement decline over time . Conclusion : Our findings indicate that priming PT with inhibitory rTMS is optimal to boost use-dependent plasticity and rebalance motor excitability and suggest that time-locked rTMS is a valid and promising approach for chronic stroke patients with mild motor impairment . Classification of evidence : This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke . Neurology ® Malcolm MP , Triggs WJ , Light KE , Gonzalez Rothi LJ , Wu S , Reid K , Nadeau SE : Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy : an exploratory r and omized controlled trial . Am J Phys Med Rehabil 2007;86:707–715 . Objective : To test the potential adjuvant effect of repetitive transcranial magnetic stimulation ( rTMS ) on motor learning in a group of stroke survivors undergoing constraint-induced therapy ( CIT ) for upper-limb hemiparesis . Design : This was a prospect i ve r and omized , double-blind , sham-controlled , parallel group study . Nineteen individuals , one or more years poststroke , were r and omized to either a rTMS + CIT ( n = 9 ) or a sham rTMS + CIT ( n = 10 ) group and participated in the 2-wk intervention . Results : Regardless of group assignment , participants demonstrated significant gains on the primary outcome measures : the Wolf Motor Function Test ( WMFT ) and the Motor Activity Log (MAL)–Amount of Use , and on secondary outcome measures including the Box and Block Test ( BBT ) and the MAL – How Well . Participants receiving rTMS failed to show differential improvement on either primary outcome measure . Conclusions : Although this study provided further evidence that even relatively brief sessions of CIT can have a substantial effect , it provided no support for adjuvant use of rTMS OBJECTIVE Repetitive transcranial magnetic stimulation ( rTMS ) has been recognized as a promising intervention for treatment of stroke patients . However , most previous reports have described the short-term effects of rTMS on motor performance . We conducted a sham-controlled trial to evaluate long-term effects of high-frequency rTMS on motor recovery in subacute stroke patients . METHODS Twenty-eight patients were r and omly divided into two groups , and received either real or control rTMS . Both treatments were accompanied by motor practice . A daily dose of 1000 pulses of subthreshold 10 Hz rTMS was applied over the primary motor cortex of the affected hemisphere for 10 days within one month after onset of stroke . Motor function was assessed before and after treatment , and 3 months after the stroke . RESULTS Motor function improved in both groups after treatment ; however , patients who received real rTMS experienced additional improvement in motor function of the affected upper limb . Over 3 months after the stroke , the time and type of intervention for the Motoricity Index of the affected upper extremity showed significant interaction . CONCLUSION Positive long-term effects on motor recovery could be achieved after 10 daily sessions of high-frequency rTMS in conjunction with motor practice during the sub-acute period of stroke Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can enhance function of the paretic h and in patients with mild motor impairment . Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown . In this pilot , r and omized , double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation , in 30 patients within 5–45 days after ischemic stroke , and mild to severe h and paresis . The primary feasibility outcome was compliance with the interventions . The primary safety outcome was the proportion of intervention-related adverse events . Performance of the paretic h and in the Jebsen – Taylor test and pinch strength were secondary outcomes . Outcomes were assessed at baseline , after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment . Baseline clinical features were comparable across groups . For the primary feasibility outcome , compliance with treatment was 100 % in the active group and 94 % in the sham group . There were no serious intervention-related adverse events . There were significant improvements in performance in the Jebsen – Taylor test ( mean , 12.3 % 1 month after treatment ) and pinch force ( mean , 0.5 Newtons ) in the active group , but not in the sham group . Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible , safe and potentially effective to improve function of the paretic h and , in patients with mild to severe hemiparesis . These promising results will be valuable to design larger r and omized clinical trials Background and Purpose — Although there has been extensive research on the effectiveness of repetitive transcranial magnetic stimulation ( rTMS ) to improve patients ’ motor performance after experiencing chronic stroke , explicit findings on the coupling of different rTMS protocol s are meager . We design ed this sham-controlled r and omized study to investigate the potential for a consecutive suppressive-facilitatory TMS protocol to improve motor outcomes after chronic stroke . Methods — Fifty-four chronic hemiplegic stroke patients were allocated across 4 groups to undergo 20 daily sessions of ( 1 ) 1 Hz rTMS over the contralesional primary motor cortex ( M1 ) and then intermittent theta burst stimulation over the ipsilesional M1 ( group A ) ; ( 2 ) contralesional sham stimulation and then ipsilesional real intermittent theta burst stimulation ( group B ) ; ( 3 ) contralesional real 1 Hz rTMS and then ipsilesional sham stimulation ( group C ) ; or ( 4 ) bilateral sham-control procedures ( group D ) . We tested cortical excitability and motor activity assessment s at the baseline , postpriming rTMS , and postconsequent rTMS periods . Results — At post , group A showed greater muscle strength , Fugl-Meyer Assessment ( FMA ) , Wolf Motor Function test , and reaction time improvement in comparison with group B ( P<0.001≈0.003 ) and group C ( P=0.001≈0.003 ) . Correlation analyses in group A revealed a close relation between contralesional map area decrement and Wolf Motor Function test gain ( P=0.005 ; r=−0.75 ) , and also revealed ipsilesional map area increment and reaction time decrement ( P=0.02 ; r=−0.87 ) . We detected no such relations in the other 3 groups . Conclusions — Our clinical trials established an extended timeframe during which conditioning could be safely continued and produced more favorable outcomes in facilitating motor performance and ameliorating interhemispheric imbalance than those obtained from single-course rTMS modulation alone Introduction . Repetitive transcranial magnetic stimulation ( rTMS ) is a promising technique for promoting rehabilitation of arm function after stroke . The feasibility and impact of rTMS as an adjunct to traditional task-oriented training to improve arm function have not yet been demonstrated . Objective . Evaluate the feasibility of a r and omized controlled trial aim ed at determining the efficacy of rTMS as an adjunct to task-oriented therapy in facilitating restoration of arm function after stroke . Methods . Stratified block-r and omized controlled trial set in the general community . Eleven stroke persons with mild to severe arm deficits were recruited and r and omized to receive 8 sessions of real-rTMS or sham-rTMS followed by ninety minutes of arm tasks design ed to improve function . Results . Medium to large , statistically significant effect sizes ( 0.49 to 1.63 ) were observed in both groups on several measures of arm function at the postintervention evaluation . Three out of four subjects in the real-TMS condition showed increased levels of corticomotor excitability after the first stimulation session . Conclusions . Preliminary evidence suggests that an rTMS protocol potent enough to induce transient increases in cortical excitability of the lesioned hemisphere is feasible but did not show promising results as an adjunct to task-specific training . This trial is registration with Clinical Trials.gov NCT00850408 Background and Purpose — It has been recently shown that a single session of repetitive transcranial magnetic stimulation ( rTMS ) of the unaffected hemisphere can improve motor function in stroke patients ; however , this improvement is short-lasting . We therefore conducted a r and omized , sham-controlled , phase II trial to evaluate whether five sessions of low-frequency rTMS can increase the magnitude and duration of these effects and whether this approach is safe . Methods — Fifteen patients with chronic stroke were r and omized to receive active or sham rTMS of the unaffected hemisphere . A blinded rater assessed motor function and corticospinal excitability at baseline , during and after 2 weeks of treatment . Safety was assessed using a neuropsychologic battery and electroencephalogram . Results — Active rTMS result ed in a significant improvement of the motor function performance in the affected h and that lasted for 2 weeks . These effects were not observed in the sham rTMS group ( affected and unaffected h and ) and in the unaffected h and in the active rTMS group . Corticospinal excitability decreased in the stimulated , unaffected hemisphere and increased in the affected hemisphere . There was a significant correlation between motor function improvement and corticospinal excitability change in the affected hemisphere . Cognitive performance and electroencephalogram were not changed significantly throughout the trial in both groups of treatment . Conclusions — These results support and extend the findings of previous studies on rTMS in stroke patients because five consecutive sessions of rTMS increased the magnitude and duration of the motor effects . Furthermore , this increased dose of rTMS is not associated with cognitive adverse effects and /or epileptogenic activity Background and Purpose — A recent report has demonstrated that the contralesional primary motor cortex ( M1 ) inhibited the ipsilesional M1 via an abnormal transcallosal inhibition ( TCI ) in stroke patients . We studied whether a decreased excitability of the contralesional M1 induced by 1 Hz repetitive transcranial magnetic stimulation ( rTMS ) caused an improved motor performance of the affected h and in stroke patients by releasing the TCI . Methods — We conducted a double-blind study of real versus sham rTMS in stroke patients . After patients had well- performed motor training to minimize the possibility of motor training during the motor measurement , they were r and omly assigned to receive a subthreshold rTMS at the contralesional M1 ( 1 Hz , 25 minutes ) or sham stimulation . Results — When compared with sham stimulation , rTMS reduced the amplitude of motor-evoked potentials in contralesional M1 and the TCI duration , and rTMS immediately induced an improvement in pinch acceleration of the affected h and , although a plateau in motor performance had been reached by the previous motor training . This improvement in motor function after rTMS was significantly correlated with a reduced TCI duration . Conclusions — We have demonstrated that a disruption of the TCI by the contralesional M1 virtual lesion caused a paradoxical functional facilitation of the affected h and in stroke patients ; this suggests a new neurorehabilitative strategy for stroke patients BACKGROUND AND PURPOSE Repetitive transcranial magnetic stimulation ( rTMS ) may enhance plastic changes in the human cortex and modulation of behavior . However , the underlying neural mechanisms have not been sufficiently investigated . We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke . METHODS Twenty-one patients were r and omly divided into two groups , and received either real or sham rTMS . Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere , coupled with sequential finger motor training of the paretic h and . Functional MRIs were obtained before and after training using sequential finger motor tasks , and performances were assessed . RESULTS Following rTMS intervention , movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group ( p < 0.05 ) . Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex , thalamus , and cau date nucleus . Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group . CONCLUSION According to these results , a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits It has been 30 years since the discovery that repeated electrical stimulation of neural pathways can lead to long-term potentiation in hippocampal slices . With its relevance to processes such as learning and memory , the technique has produced a vast literature on mechanisms of synaptic plasticity in animal models . To date , the most promising method for transferring these methods to humans is repetitive transcranial magnetic stimulation ( rTMS ) , a noninvasive method of stimulating neural pathways in the brain of conscious subjects through the intact scalp . However , effects on synaptic plasticity reported are often weak , highly variable between individuals , and rarely last longer than 30 min . Here we describe a very rapid method of conditioning the human motor cortex using rTMS that produces a controllable , consistent , long-lasting , and powerful effect on motor cortex physiology and behavior after an application period of only 20 - 190 Background . Initially developed to excite peripheral nerves , magnetic stimulation was quickly recognized as a valuable tool to noninvasively activate the cerebral cortex . The subsequent discovery that repetitive transcranial magnetic stimulation ( rTMS ) could have long-lasting effects on cortical excitability spawned a broad interest in the use of this technique as a new therapeutic method in a variety of neuropsychiatric disorders . Although the current outcomes from initial trials include some conflicting results , initial evidence supports that rTMS might have a therapeutic value in different neurologic conditions . Methods . We review ed the results of clinical trials of rTMS on four different disorders : stroke , Parkinson 's disease , chronic refractory pain , and epilepsy . We review ed r and omized , controlled studies only in order to obtain the strongest evidence for the clinical effects of rTMS . Results . An extensive literature review revealed 32 articles that met our criteria . From these studies , we found evidence for the therapeutic efficacy of rTMS , particularly in the relief of chronic pain and motor neurorehabilitation in single hemisphere stroke patients . Repetitive TMS also seems to have a therapeutic effect on motor function in Parkinson 's disease , but the evidence is somewhat confounded by the uncontrolled variability of multiple factors . Lastly , only two r and omized , sham-controlled studies have been performed for epilepsy ; although evidence indicates rTMS may reduce seizure frequency in patients with neocortical foci , more research is needed to confirm these initial findings . Conclusions . There is mounting evidence for the efficacy of rTMS in the short-term treatment of certain neurologic conditions . More long-term research is needed in order to properly evaluate the effects of this method in a clinical setting Introduction . Restoration of upper extremity ( UE ) functional use remains a challenge for individuals following stroke . Repetitive transcranial magnetic stimulation ( rTMS ) is a noninvasive modality that modulates cortical excitability and is being explored as a means to potentially ameliorate these deficits . The purpose of this study was to evaluate , in the presence of chronic stroke , the effects of low-frequency rTMS to the contralesional hemisphere as an adjuvant to functional task practice ( FTP ) , to improve UE functional ability . Methods . Twenty-two individuals with chronic stroke and subsequent moderate UE deficits were r and omized to receive 16 sessions ( 4 times/week for 4 weeks ) of either real-rTMS or sham-rTMS followed by 1-hour of paretic UE FTP . Results . No differences in UE outcomes were revealed between the real-rTMS and sham-rTMS intervention groups . After adjusting for baseline differences , no differences were revealed in contralesional cortical excitability postintervention . In a secondary analysis , data pooled across both groups revealed small , but statistically significant , improvements in UE behavioral measures . Conclusions . rTMS did not augment changes in UE motor ability in this population of individuals with chronic stroke . The chronicity of our participant cohort and their degree of UE motor impairment may have contributed to inability to produce marked effects using rTMS Rationale : Repetitive transcranial magnetic stimulation ( rTMS ) is used alone or in combination with physiotherapy for rehabilitation of stroke patients . TMS mapping can also quantify the excitability of the motor area in both the ipsilesional ( IL ) and contralateral ( CL ) hemisphere . Objective : This study is the first to measure the dynamics of cortical excitability by TMS mapping before and after treatment with low-frequency ( LF ) rTMS in the contralesional hemisphere at three different timepoints . Furthermore , the patients were clinical ly evaluated during the same visit as the mapping to establish both short and long-term outcomes after rTMS treatment . Methods and Results : A total of 16 participants with acute ischemic stroke were assessed 10 days post-stroke by TMS mapping . The patients were r and omized into two equal groups : a real rTMS group and a sham group . The rTMS group received LF-rTMS to the contralesional hemisphere for 10 days , starting on the first day after the first mapping . Each subject was also evaluated by mapping on days 45 and 90 after stroke onset . The primary clinical outcome measured was the Fugl-Meyer Assessment for Upper Extremity ( FMA-UE ) on days 10 , 45 and 90 post-stroke . At 10 days after stroke onset , both groups presented low excitability in the lesion side and high excitability in the non-affected side . In the real rTMS group , at 45 days after stroke , a downward trend in the excitability of the contralesional hemisphere and an upward trend in the excitability of the lesioned side were observed . At 90 days after stroke , a tendency toward balanced excitability between both hemispheres was observed . In the sham group , at both 45 and 90 days , we observed increased excitability in the non-affected side compared to the side with the lesioned motor area . At 45 days , the real rTMS group demonstrated a better recovery of the upper limb motor function than the sham group , but at 90 days , there was no significant difference between the two groups . Discussion : These results demonstrated that LF-rTMS treatment enhances rebalance of the excitability patterns in both hemispheres and led us to question the “ one size fits all ” approach widely used in rTMS interventions . Abbreviations : Amax = maximum amplitude , Amean = AM = averaged amplitude , APB = abductor pollicis brevis , CL = contralesional , DTI = diffusion tensor imaging , EEG = electroencephalography , EMG = electromyography , FMA-UE = Fugl-Meyer Assessment for Upper Extremity , HS = hot spot , IHC = interhemispheric functional connectivity , IL = ipsilesional , LF-rTMS = low-frequency repetitive transcranial magnetic stimulation , MCA = middle cerebral artery , MEP(s ) = motor evoked potential(s ) , NIBS = non-invasive brain stimulation , rMT = resting motor threshold , RP = responsive points , rTMS = repetitive transcranial magnetic stimulation , TMS = transcranial magnetic Low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere ( UH-LF-rTMS ) in patients with stroke can decrease interhemispheric inhibition from the unaffected to the affected hemisphere and improve h and dexterity and strength of the paretic h and . The objective of this proof-of-principle study was to explore , for the first time , effects of UH-LF-rTMS as add-on therapy to motor rehabilitation on short-term intracortical inhibition ( SICI ) and intracortical facilitation ( ICF ) of the motor cortex of the unaffected hemisphere ( M1UH ) in patients with ischemic stroke . Eighteen patients were r and omized to receive , immediately before rehabilitation treatment , either active or sham UH-LF-rTMS , during two weeks . Resting motor threshold ( rMT ) , SICI , and ICF were measured in M1UH before the first session and after the last session of treatment . There was a significant increase in ICF in the active group compared to the sham group after treatment , and there was no significant differences in changes in rMT or SICI . ICF is a measure of intracortical synaptic excitability , with a relative contribution of spinal mechanisms . ICF is typically upregulated by glutamatergic agonists and downregulated by gabaergic antagonists . The observed increase in ICF in the active group , in this hypothesis-generating study , may be related to M1UH reorganization induced by UH-LF-rTMS BACKGROUND Repetitive transcranial magnetic stimulation ( rTMS ) is a simple and non-invasive method of augmenting motor recovery after stroke , probably mediated by restoring inter-hemispheric activation balance . This placebo-controlled pilot study examined the possible benefit of stimulating the lesioned hemisphere ( 5-Hz rTMS ) or inhibiting the contra-lesional hemisphere ( 1-Hz rTMS ) on clinical recovery of motor function in patients with ischaemic stroke and assessed the sustainability of the response . METHODS Sixty patients with ischaemic stroke ( > 1 month from onset ) with mild-to-moderate hemiparesis were r and omized to receive 10 daily sessions of either sham rTMS , 5-Hz ipsi-lesional rTMS or 1-Hz contra-lesional rTMS , in addition to a st and ard physical therapy protocol . Serial assessment s were made over a period of 12 weeks by the thumb-index finger tapping test ( FT ) , Activity Index ( AI ) score and the modified Rankin Scale ( mRS ) . RESULTS In contrast to control patients , those receiving active rTMS as ipsi-lesional 5-Hz stimulation or 1-Hz contra-lesional stimulation showed statistically significant improvement on the FT test , AI scores and mRS score at 2 weeks , and the effect was sustained over the 12-week observation period . No significant adverse events were observed during treatment in either group . CONCLUSIONS Repetitive TMS has beneficial effects on motor recovery that can be translated to clinical ly meaningful improvement in disability in patients with post-stroke hemiparesis , with a well-sustained effect . The similarity of inhibitory and stimulatory rTMS in producing these effects supports the inter-hemispheric balance hypothesis and encourages further research into their use in long-term neurorehabilitation programmes of patients with stroke Lately it has been indicated that the stimulation of both sides of the motor cortices with different frequencies of rTMS can improve the behaviour of a paretic arm . We studied the effect of rTMS in severe cases of post-stroke after nearly 10 years . They had wide hemispheric lesion and their paresis had not changed for more than 5 years . The majority of patients could not move their fingers on the affected side . In our study we examined whether the active movement could be induced by rTMS even several years after stroke and which hemisphere ( affected or unaffected ) stimulated by rTMS would be the best location for attenuating the spasticity and for developing movement in the paretic arm . Sixty-four patients ( more than 5 years after stroke in a stable state ) were followed for 3 months . They were treated with rTMS with 1 Hz at 30 % of 2.3 T 100 stimuli per session twice a day for a week . The area to be stimulated was chosen according to the evoked movement by TMS in the paretic arm . That way , four groups were created and compared . In group A , where both hemispheres were stimulated ( because of the single stimulation of TMS could induce movement from both sides of hemispheres ) the spasticity decreased but the movement could not be influenced . A highly significant improvement in spasticity , in movement induction and in the behaviour of paresis was observed in group B , where before treatment , there was no evoked movement in the paretic arm from stimulating either hemispheres of the brain . For treatment we stimulated the unaffected hemisphere from where the intact arm is moved ( ipsilateral to the paretic side ) . In both groups C ( contralateral hemisphere to the paretic arm ) and D ( ipsilaterally evoked movement in the paretic arm ) , the spasticity decreased during the first week , but the movement of the paretic arm improved only in group C. It seems that spasticity can be modified by the stimulation either the affected or the unaffected hemisphere , but the induction of movement can be achieved only by the stimulation of an intact motor pathway and its surrounding area ( groups B and C ) . The improvement in paretic extremities can be achieved with rTMS even after years of stroke when the traditional rehabilitation has failed BACKGROUND We demonstrated that prolonged transcranial magnetic intermittent theta burst stimulation ( iTBS , 1200 pulses/session = iTBS1200 ) produces longer-lasting facilitation in corticospinal excitability than ordinary form of iTBS in healthy subjects . OBJECTIVE Here we show the safety and small-scale efficacy of iTBS1200 over ipsilesional primary motor cortex ( M1 ) in subacute stroke patients . METHODS Twelve patients with first-time , subacute ischemic stroke of the middle cerebral artery were r and omized into two groups that received 10 daily-sessions of either iTBS1200 or sham stimulation ( n=6/group ) over ipsilesional M1 h and region in addition to medical and rehabilitation treatments . The primary outcome measures were safety and tolerability . The secondary outcome measures included the National Institute of Health Stroke Scale ( NIHSS ) , Upper Extremity Fugl-Meyer Test ( UE-FMT ) , Action Research Arm Test ( ARAT ) , active motor thresholds (aMTs)/motor-evoked potentials ( MEPs ) from the extensor carpi radialis ( ECR ) , and magnetoencephalography on post-intervention day 1 and post-stroke day 60 . RESULTS iTBS or sham stimulation was well tolerated by all patients without seizures or significant adverse effects . Compared with the matched controls , the iTBS group showed measurable improvements in the NIHSS and the proximal UE-FMT scores on post-intervention day 1 and post-stroke day 60 . Nevertheless , the h and ARAT scores , aMT and MEPs from the paretic ECR were not different between groups . Post-movement beta synchronization increased over iTBS-conditioned M1 on post-intervention day 1 in testable patients . CONCLUSIONS Repetitive sessions of iTBS1200 over ipsilesional M1 of subacute stroke patients are safe and the potential benefits encourage a larger trial to determine the efficacy in stroke patients . ( Clinical Trials.gov : NCT-01323881 ) Background . Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the unaffected motor cortex may improve motor function of the paretic h and after stroke . However , low-frequency rTMS might adversely affect bimanual movement by decreasing transcallosal function . Objective . The authors investigated whether combined administration of rTMS and transcranial direct current stimulation ( tDCS ) prevents deterioration of bimanual movement induced by low-frequency rTMS over the unaffected hemisphere . Methods . A total of 27 participants with chronic subcortical stroke were r and omly assigned to receive either 1 Hz rTMS over the unaffected hemisphere , anodal tDCS over the affected hemisphere , or a combination of rTMS and tDCS . All patients performed a pinching motor-training task after stimulation . Bimanual movement and transcallosal inhibition ( TCI ) were evaluated after stimulation . Results . rTMS and rTMS-tDCS enhanced the motor training effect on the paretic h and . rTMS decreased bimanual coordination and reduced TCI from the unaffected to the affected hemisphere ( TCIunaff-aff ) . rTMS-tDCS changed TCI balance of both hemispheres but did not affect bimanual coordination or TCIunaff-aff . The change in bimanual coordination was negatively correlated with TCIunaff-aff . Following stimulation , improvement in the pinch force in the paretic h and was negatively correlated with TCI balance . Conclusions . Inhibitory rTMS over the unaffected hemisphere transiently caused deterioration of bimanual movements for the current task in stroke patients . This short-term decline was prevented by combined administration of low-frequency rTMS over the unaffected hemisphere and anodal tDCS over the affected hemisphere . These responses to bihemispheric stimulation suggest possible caution and opportunities for the rehabilitation of h and function after stroke Background . Noninvasive cortical stimulation could represent an add-on treatment to enhance motor recovery after stroke . However , its clinical value , including anticipated size and duration of the treatment effects , remains largely unknown . Objective . The authors design ed a small semi-r and omized clinical trial to explore whether long-lasting clinical ly important gains can be achieved by adding theta burst stimulation ( TBS ) , a form of repetitive transcranial magnetic stimulation ( TMS ) , to a rehabilitation program for the h and . Methods . A total of 41 chronic stroke patients received excitatory TBS to the ipsilesional hemisphere or inhibitory TBS to the contralesional hemisphere in 2 centers ; each active group was compared with a group receiving sham TBS . TBS was followed by physical therapy for 10 working days . Patients and therapists were blinded to the type of TBS . Primary outcome measures ( 9-hole Peg Test [ 9HPT ] , Jebsen Taylor Test [ JTT ] , and grip and pinch-grip dynamometry ) were assessed 4 , 30 , and 90 days post treatment . The clinical ly important difference was defined as 10 % of the maximum score . Results . There were no differences between the active treatment and sham groups in any of the outcome measures . All patients achieved small sustainable improvements—9HPT , 5 % of maximum ( confidence interval [ CI ] = 3%-7 % ) ; JTT , 5.7 % ( CI = 3%-8 % ) ; and grip strength , 6 % ( CI = 2%-10%)—all below the defined clinical ly important level . Conclusions . Cortical stimulation did not augment the gains from a late rehabilitation program . The effect size anticipated by the authors was overestimated . These results can improve the design of future work on therapeutic uses of TMS BACKGROUND AND PURPOSE The purpose of this study was to compare the long-term effect of five daily sessions of 1 vs. 3 Hz repetitive transcranial magnetic stimulation ( rTMS ) on motor recovery in acute stroke . METHODS A total of 36 patients with acute ischaemic stroke participated in the study . The patients were r and omly assigned into one of three groups ; the first and second groups received real rTMS ; 1 and 3 Hz and third group received sham stimulation , daily for 5 days . Motor disability was assessed before and after the last session , and then after first , second and third month . Cortical excitability was assessed before and after the second and fifth session . The outcome measure was clinical disability at 3 months post-rTMS . RESULTS No significant differences were found in basal rating scales between the three groups . At the 3-month time point , both of the real rTMS groups had improved significantly more in different rating scales than the sham group ; in addition , the 1 Hz group performed better than the 3 Hz group . Measures of cortical excitability immediately after the last session showed that the 1 Hz group had reduced excitability of the non-stroke hemisphere and increased excitability of the stroke hemisphere , whereas the 3 Hz group only showed increased excitability of the stroke hemisphere . CONCLUSION These results confirm that five daily sessions of rTMS over motor cortex using either 1 Hz over the unaffected hemisphere or 3 Hz over the affected hemisphere can enhance recovery . At 3 months , the improvement was more pronounced in 1 Hz group Abstract Background : High- and low-frequency repetitive transcranial magnetic stimulation ( HF-rTMS and LF-rTMS ) has been shown to be beneficial for upper limb hemiparesis in patients with acute stroke . However , no study has examined the usefulness of bilateral application of HF- and LF-rTMS ( BL-rTMS ) . Methods : Fifty-eight hemiparetic patients with acute stroke were r and omly assigned into two groups : HF-rTMS group and BL-rTMS group . All patients were scheduled to receive five sessions of either HF-rTMS over the lesional hemisphere or BL-rTMS over both hemispheres for 5 days . Motor function of the affected upper limb was evaluated using the Brunnstrom Recovery Stage ( BRS ) for upper-limb and h and -fingers , grip strength and tapping frequency , before the first session and after the last session of rTMS . Results : Improvement of BRS for the upper limb and h and /finger was significantly greater in the BL-rTMS group than the HF-rTMS group ( p < 0.01 ) . Improvement in grip strength and tapping frequency was also greater in the BL-rTMS group , although the differences were not statistically significant . Conclusions : The proposed BL-rTMS is safe and feasible and showed a greater improvement of BRS of the affected upper limb compared to HF-rTMS . This novel rTMS approach may be a useful intervention for hemiparetic patients with acute stroke OBJECTIVE To assess the efficacy of inhibitory repetitive transcranial magnetic stimulation ( rTMS ) for decreasing upper-limb muscle tone after chronic stroke . DESIGN A r and omized sham-controlled trial with a 4-week follow-up . SETTING Research hospital . PARTICIPANTS Patients with stroke ( N=20 ) with poststroke upper limb spasticity . INTERVENTIONS The experimental group received rTMS to the primary motor cortex of the unaffected side ( 1500 pulses ; 1Hz ; 90 % of resting motor threshold for the first dorsal interosseous muscle ) in 10 sessions , 3d/wk , and physical therapy ( PT ) . The control group received sham stimulation and PT . MAIN OUTCOME MEASURES Modified Ashworth scale ( MAS ) , upper-extremity Fugl-Meyer assessment , FIM , range of motion , and stroke-specific quality -of-life scale . All outcomes were measured at baseline , after treatment ( postintervention ) , and at a 4-week follow-up . A clinical ly important difference was defined as a reduction of ≥1 in the MAS score . RESULTS Friedman test revealed that PT is efficient for significantly reducing the upper limb spasticity of patients only when it is associated with rTMS . In the experimental group , 90 % of the patients at postintervention and 55.5 % at follow-up showed a decrease of ≥1 in the MAS score , representing clinical ly important differences . In the control group , 30 % of the patients at postintervention and 22.2 % at follow-up experienced clinical ly meaningful changes . There were no differences between the groups at any time for any of the other outcome measures , indicating that both groups demonstrated similar behaviors over time for all variables . CONCLUSIONS rTMS associated with PT can be beneficial in reducing poststroke spasticity . However , more studies are needed to clarify the clinical changes underlying the reduction in spasticity induced by noninvasive brain stimulations OBJECTIVE Changes in cerebral cortex excitability have been demonstrated after a stroke and are considered relevant for recovery . Repetitive transcranial magnetic stimulation ( rTMS ) of the brain can modulate cerebral cortex excitability and , when rTMS is given as theta burst stimulation ( TBS ) , LTP- or LTD-like changes can be induced . The aim of present study was to evaluate the effects of TBS on cortical excitability in acute stroke . METHODS In 12 acute stroke patients , we explored the effects of facilitatory TBS of the affected hemisphere and of inhibitory TBS of the unaffected hemisphere on cortical excitability to single-pulse transcranial magnetic stimulation ( TMS ) on both sides . The effects produced by TBS in patients were compared with those observed in a control group of age-matched healthy individuals . RESULTS In patients , both the facilitatory TBS of the affected motor cortex and the inhibitory TBS of the unaffected motor cortex produced a significant increase of the amplitude of MEPs evoked by stimulation of the affected hemisphere . The effects observed in patients were comparable to those observed in controls . CONCLUSIONS Facilitatory TBS over the stroke hemisphere and inhibitory TBS over the intact hemisphere in acute phase enhance the excitability of the lesioned motor cortex . SIGNIFICANCE TBS might be useful to promote cortical plasticity in stroke patients OBJECTIVE Recent reports demonstrated that low-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the unaffected hemisphere improved the affected h and function in chronic stroke patients . We investigated whether 1 Hz rTMS improved the motor learning of the affected h and in patients after stroke . DESIGN A double-blind study . PATIENTS Twenty patients with chronic subcortical stroke . METHODS The patients were r and omly assigned to receive either a sub-threshold rTMS over the unaffected hemisphere ( 1 Hz , 25 minutes ) or sham stimulation , and all patients performed a pinching task after stimulation . We evaluated the motor function of the affected h and and the excitatory and inhibitory function of the affected motor cortex by transcranial magnetic stimulation . RESULTS Compared with sham stimulation , rTMS induced an increase in the excitability of the affected motor cortex(p < 0.001 ) and an improvement in acceleration of the affected h and ( p = 0.006 ) . Moreover , the effect of motor training on pinch force was enhanced by rTMS ( p < 0.001 ) . These improvement in the motor function lasted for one week after rTMS and motor training ( p < 0.001 ) . CONCLUSION rTMS improved the motor learning of the affected h and in patients after stroke ; thus , it can apply as anew rehabilitation strategy for patients after stroke BACKGROUND Recently , high-frequency repetitive transcranial magnetic stimulation ( HF-rTMS ) and low-frequency rTMS ( LF-rTMS ) are reported to improve motor function significantly in chronic hemiparetic stroke patients . However , few studies have investigated the safety and efficacy of these rTMS modalities introduced during the early phase of stroke . The purpose of this study was to clarify the rTMS modality that is more beneficial for upper limb hemiparesis in the early phase of stroke using a r and omized controlled trial . METHODS Twenty-nine patients with a hemispheric stroke lesion in the early phase of stroke were examined . Patients were r and omly assigned into 3 groups : the HF-rTMS group ( 10 Hz rTMS to the lesional hemisphere [ n = 9 ] ) , the LF-rTMS group ( 1 Hz rTMS to the nonlesional hemisphere [ n = 11 ] ) , and the sham stimulation group [ n = 9 ] ) . Patients received sessions for 5 consecutive days . Grip strength and tapping frequency were assessed before and after the intervention . Motor improvement of the affected upper limb after intervention was compared among the 3 groups . RESULTS All patients completed the 5-day protocol . Both the HF-rTMS and LF-rTMS groups had significant increases in both grip strength and tapping frequency . Comparison of the extent of improvement showed a more significant increase in grip strength and tapping frequency in the HF-rTMS group compared to the sham stimulation group ( each P < .05 ) , and no difference between the LF-rTMS group and the sham stimulation group . CONCLUSIONS HF-rTMS applied to the lesional hemisphere in the early phase of stroke was more beneficial for motor improvement of the affected upper limb than LF-rTMS OBJECTIVE The aim of this study was to evaluate the effects of transcranial magnetic stimulation synchronized with maximal effort to make a target movement in patients with chronic hemiplegia involving the h and . DESIGN Non-r and omized double-blinded controlled trial . SUBJECTS Nine chronic patients with hemiplegia who were unable to fully extend the affected fingers following stroke . METHODS Patients were assigned to receive 100 pulses of active or sham transcranial magnetic stimulation of the affected hemisphere per session . Each active or sham pulse was delivered during maximal effort at thumb and finger extension as a target movement . A blinded rater assessed stroke impairments at baseline , immediately after , and one week after 4 weekly transcranial magnetic stimulation sessions . Motor evoked potential amplitudes were measured at each session . RESULTS All sessions were completed without adverse effects . Immediately after the fourth transcranial magnetic stimulation session , 4 of 5 patients in the active transcranial magnetic stimulation group ( 80 % ) had either reduced wrist flexor spasticity or improved manual performance ; no such change occurred in the sham group ( Fisher 's exact test , p < 0.05 ) . Effects persisted one week later . In the active transcranial magnetic stimulation group , 3 patients who showed an increase in motor evoked potential amplitudes all had improvement in clinical assessment s. CONCLUSION Transcranial magnetic stimulation synchronized with maximum effort to make a target movement improved h and motor function in patients with chronic hemiplegia BACKGROUND We conducted a r and omized , double-blind , sham-controlled study to assess the efficacy in motor recovery and safety of daily repetitive transcranial magnetic stimulation ( rTMS ) in subacute stroke patients . METHODS Forty-one patients were r and omly assigned to a real or sham stimulation group . Each patient underwent regular rehabilitation accompanied by a series of 10 daily 5-Hz rTMS of the ipsilesional primary motor cortex ( M1 ) or sham stimulation . The primary outcome was motor recovery evaluated by the Brunnstrom stages ( BS ) . The secondary outcomes were improvement in the Fugl-Meyer Assessment ( FMA ) , grip power , National Institutes of Health Stroke Scale ( NIHSS ) , Functional Independence Measure ( FIM ) , a quantitative measurement of finger tapping movement , and the incidence of adverse events . RESULTS Thirty-nine patients completed the study and were included in the analyses . The real rTMS group demonstrated additional improvement in the BS h and score at the last follow-up compared to the sham . The grip power , the NIHSS motor score , and the number of finger taps in the affected h and improved in the real stimulation group but not in the sham group . The BS upper limb scores , the FMA distal upper limb score , the NIHSS total score , and the FIM motor score showed improvement from baseline at the earlier time points after the real rTMS . There were no additional improvements in the other scores after the real rTMS compared to the sham . No serious adverse events were observed . CONCLUSIONS Our results suggest that dailyhigh-frequency rTMS of the ipsilesional M1 is tolerable and modestly facilitates motor recovery in the paralytic h and of subacute stroke patients OBJECTIVE The interhemispheric competition model proposes that the functional recovery of motor deficits in patients after stroke can be achieved by increasing the excitability of the affected hemisphere or decreasing the excitability of the unaffected hemisphere . We investigated whether bilateral repetitive transcranial magnetic stimulation might improve the paretic h and in patients after stroke . DESIGN A double-blind study . PATIENTS Thirty patients with chronic subcortical stroke . METHODS The patients were r and omly assigned to receive 1 Hz repetitive transcranial magnetic stimulation over the unaffected hemisphere , 10 Hz repetitive transcranial magnetic stimulation over the affected hemisphere , or bilateral repetitive transcranial magnetic stimulation comprising both the 1 Hz and 10 Hz repetitive transcranial magnetic stimulation . All patients underwent motor training following repetitive transcranial magnetic stimulation . RESULTS Bilateral repetitive transcranial magnetic stimulation and 1 Hz repetitive transcranial magnetic stimulation immediately improved acceleration in the paretic h and . Compared with 1 Hz repetitive transcranial magnetic stimulation , bilateral repetitive transcranial magnetic stimulation decreased the inhibitory function of the affected motor cortex and enhanced the effect of motor training on pinch force . Moreover , this effect of motor training lasted for one week . On the other h and , 10 Hz repetitive transcranial magnetic stimulation had no effect on the motor function . CONCLUSION Bilateral repetitive transcranial magnetic stimulation improved the motor training effect on the paretic h and of patients after stroke more than unilateral stimulation in pinch force ; this might indicate a new neurorehabilitative strategy for stroke PURPOSE Increasing evidence suggests that the contralesional motor cortex ( M1 ) inhibits the ipsilesional M1 in stroke patients . This inhibition could impair motor function of the affected h and . We investigated if inhibitory 1~Hz repetitive transcranial magnetic stimulation ( rTMS ) over the contralesional M1 improved motor performance of the affected h and in acute stroke . METHODS A double-blind study of real versus placebo rTMS was conducted . Twelve patients early after subcortical stroke ( mean : 7 days ) received 1200 stimuli of real and placebo rTMS in a crossover design . The sequence of stimulations was counterbalanced across subjects . Stimulus intensity was subthreshold ( 90 % of motor threshold at rest ) . Motor function was tested by grip strength recordings and Nine Hole Peg Test ( NHPT ) executions before and after each rTMS session . RESULTS Compared to sham stimulation , real rTMS improved NHPT results but not grip strength in the affected h and . No change of performance was observed for the unaffected h and . NHPT baseline repetitions in a subgroup of patients indicated stable motor performance prior to the rTMS sessions . CONCLUSIONS The study suggests that therapeutic rTMS applications over the contralesional hemisphere are feasible in acute stroke patients and can transiently improve dexterity of the affected h and . RTMS may become an additional tool for early neurorehabilitation Summary The effect of combined low-frequency repetitive transcranial magnetic stimulation ( LF rTMS ) and virtual reality ( VR ) training in patients after stroke was assessed . In a double-blind r and omized controlled trial , 112 patients with hemiplegia after stroke were r and omly divided into two groups : experimental and control . In experimental group , the patients received LF rTMS and VR training treatment , and those in control group received sham rTMS and VR training treatment . Participants in both groups received therapy of 6 days per week for 4 weeks . The primary endpoint including the upper limb motor function test of Fugl-meyer assessment ( U-FMA ) and wolf motor function test ( WMFT ) , and the secondary endpoint including modified Barthel index ( MBI ) and 36-item Short Form Health Survey Question naire ( SF-36 ) were assessed before and 4 weeks after treatment . Totally , 108 subjects completed the study ( 55 in experimental group and 53 in control group respectively ) . After 4-week treatment , the U-FMA scores [ mean difference of 13.2 , 95 % confidence interval ( CI ) 3.6 to 22.7 , P<0.01 ] , WMFT scores ( mean difference of 2.9 , 95 % CI 2.7 to 12.3 , P<0.01 ) , and MBI scores ( mean difference 16.1 , 95 % CI 3.8 to 9.4 , P<0.05 ) were significantly increased in the experimental group as compared with the control group . The results suggested the combined use of LF rTMS with VR training could effectively improve the upper limb function , the living activity , and the quality of life in patients with hemiplegia following subacute stroke , which may provide a better rehabilitation treatment for subacute stroke BACKGROUND AND PURPOSE Repetitive transcranial magnetic stimulation ( rTMS ) changes the excitability of the motor cortex and thereby has the potential to enhance motor recovery after stroke . This r and omized , sham-controlled , double-blind study was to compare the effects of high-frequency versus low-frequency rTMS on motor recovery during the early phase of stroke and to identify the neurophysiological correlates of motor improvements . METHODS A total of 69 first-ever ischemic stroke patients with motor deficits were r and omly allocated to receive five daily sessions of 3-Hz ipsilesional rTMS , 1-Hz contralesional rTMS or sham rTMS in addition to st and ard physical therapy . Outcome measures included motor deficits , neurological scores and cortical excitability , which were assessed at baseline , after the intervention and at 3-month follow-up . RESULTS The rTMS groups manifested greater motor improvements than the control group , which were sustained for at least 3 months after the end of the treatment sessions . 1-Hz rTMS over the unaffected hemisphere produced more profound effects than 3-Hz rTMS in facilitating upper limb motor performance . There was a significant correlation between motor function improvement and motor cortex excitability change in the affected hemisphere . CONCLUSIONS Repetitive transcranial magnetic stimulation is a beneficial neurorehabilitative strategy for enhancing motor recovery in the acute and subacute phase after stroke OBJECTIVE Inhibition of motor cortex excitability of the contralesional hemisphere may improve dexterity of the affected h and after stroke . METHODS 40 patients ( 17 dominant hemispheric stroke , 23 non-dominant hemispheric stroke ) with a mild to moderate upper limb motor impairment were enrolled in a double-blind , r and omized , placebo-controlled trial with two parallel-groups . Both groups received 15 daily sessions of motor training preceded by either 1 Hz rTMS or sham rTMS . Behavioral and neurophysiological evaluations were performed at baseline , after the first week and after the third week of treatment , and after a 6 months follow-up . RESULTS In both groups motor function of the affected h and improved significantly . Patients with stroke of the non-dominant hemisphere made a similar improvement , regardless of whether the motor training was preceded by sham or 1 Hz rTMS . Patients with stroke of the dominant hemisphere had a less favorable improvement than those with stroke of the non-dominant hemisphere after motor training preceded by sham rTMS . However , when 1 Hz rTMS preceded the motor training , patients with stroke of the dominant hemisphere made a similar improvement as those with stroke of the non-dominant hemisphere . INTERPRETATION Motor recovery of the affected upper limb after stroke is determined by dominance of the affected hemisphere . Stroke of the dominant hemisphere is associated with per se poorer improvement of the affected h and . 1 Hz rTMS over the contralesional M1 significantly improves dexterity of the affected h and in patients with stroke of the dominant hemisphere , but not in those with stroke of the non-dominant hemisphere Background . Low-frequency repetitive transcranial magnetic stimulation ( rTMS ) of the contralesional primary motor cortex ( M1 ) may improve recovery in patients with hemiparetic stroke . Objective . To evaluate the effectiveness of applying 1 Hz rTMS to the contralesional M1 in addition to physiotherapy during early rehabilitation for stroke patients with h and hemiparesis in a r and omized , sham-controlled , double-blind study . Methods . Forty patients with moderate upper extremity hemiparesis were r and omized to receive 3 weeks of motor training ( 45 minutes daily ) preceded by 30 minutes of 1 Hz rTMS applied to the contralesional M1 or 30 minutes of sham rTMS . Functional assessment of the paretic h and using the Wolf Motor Function Test was performed before , immediately after , and 3 months after completing treatment . Results . No statistically significant differences were found between the experimental and the control group for h and function ( Wolf Motor Function Test ; P = .92 ) or the level of neurological deficit ( National Institutes of Health Stroke Scale [ NIHSS ] ; P = .82 ) after treatment . Effect sizes for the experimental ( d = 0.5 ) and the control group ( d = 0.47 ) were small . Similar results were observed at the 3-month follow-up . Conclusions . The findings did not suggest that rTMS suppression of the contralesional motor cortex augments the effect of early neurorehabilitation for upper limb hemiparesis . Larger trials that stratify subjects based on residual motor function or physiological measures of excitation and inhibition may identify responders in the future |
2,456 | 29,992,191 | Barriers challenging the sustainability of the CHWs led projects were transportation , nature of official support , quantity and quality of CHWs , training of CHWs , incentives for CHWs , and maintaining a good rapport between CHWs and target population .
Conclusion CHWs appear to frequently engage in implementing diverse public health intervention programs in China .
Facilitators and barriers identified are comparable to those identified in high income countries . | Background Community Health Workers ( CHWs ) have been widely used in response to the shortage of skilled health workers especially in re source limited areas .
China has a long history of involving CHWs in public health intervention project .
CHWs in China called village doctors who have both treatment and public health responsibilities .
This systematic review aim ed to identify the types of public health services provided by CHWs and summarized potential barriers and facilitating factors in the delivery of these services . | Background Type 2 diabetes ( T2DM ) affects 113.9 million people in China , the largest number of any country in the world ( JAMA 310:948–59 , 2013 ) . T2DM prevalence has risen dramatically from around 1 % in the 1980s to now over 10 % and is expected to continue rising . Despite the growing disease burden , few people with T2DM are achieving adequate management targets to prevent complications . Health system infrastructure in China is struggling to meet these gaps in care , and innovative , cost-effective and affordable solutions are needed . One promising strategy that may be particularly relevant to the Chinese context is improving support for lay family members to care for their relatives with T2DM . Methods We hypothesise that an interactive mobile health management system can support lay family health promoters ( FHP ) and healthcare staff to improve clinical outcomes for family members with T2DM through medical assessment , regular monitoring , lifestyle advice and the prescribing of guidelines recommended medications . This intervention will be implemented as a cluster r and omised controlled trial involving 80 communities ( 40 communities in Beijing and 40 rural villages in Hebei province ) and 2000 people with T2DM . Outcome analyses will be conducted blinded to intervention allocation . The primary outcome is the proportion of patients achieving ≥2 “ ABC ” goals ( HbA1c < 7.0 % , blood pressure ( BP ) < 140/80 mmHg and LDL cholesterol < 100 mg/dl or 2.6 mmol/L ) at the end of follow-up ( Diabetes Care 36(Supplement 1):S11-S66 , 2013 ) . Secondary outcomes include the proportion of patients achieving individual ABC targets ; mean changes in HbA1c , BP , LDL , renal function ( serum creatinine and urinary albumin ) , body mass index , quality of life ( QOL , EQ-5D ) , and healthcare utilisation from baseline ; and cost-effectiveness/utility of intervention . Trial outcomes will be accompanied by detailed process and economic evaluations . Discussion The Chinese government has prioritised prevention and treatment of diabetes as 1 of 11 National Basic Public Health Services . Despite great promise for mHealth interventions to improve access to effective health care , there remains uncertainty about how this can be successfully achieved . The findings are likely to inform policy on a scalable strategy to overcome sub-optimal access to effective health care in China . Trial registration Clinical trials.gov In China , one of the major problems in upgrading rural health services is the difficulty of communicating between the rural and urban areas . Enabling local agencies to access the Internet in re source -poor areas can provide an efficient means of diffusing current training and information and will have far-reaching policy implication s. To test the feasibility of using the Internet to deliver needed health information to the countryside , the UCLA School of Public Health and the Institute of Health Studies of Kunming Medical College ( IHS-KMC ) collaborated in an experimental website project to improve the quality of reproductive health services to promote women 's health in three rural counties of Yunnan . The project involved the county government and the Bureau of Public Health , the Bureau of Family Planning ; the Bureau of Education , Women 's Federation , and the Maternal and Child Health Station targeting village health workers and teachers ; women 's cadres . Three counties , matched on socioeconomic status , participated in the study and were r and omized to receive three programs . Nanhua County received computer skill training and logistic support including a planning workshop for information diffusion . Mouding County received computers only . Dayao , the control county , did not receive the full program until the conclusion of the project . The study demonstrated that the use of a website to disseminate health information in remote rural areas is not only feasible but that it also will be enthusiastically adopted by local health workers and interested parties . Moreover , the knowledge was diffused from the primary population of village doctors , family planning workers , women 's cadres , and teachers to the secondary population of villagers and students Background Latin America , China and India are experiencing unprecedentedly rapid demographic ageing with an increasing number of people with dementia . The 10/66 Dementia Research Group 's title refers to the 66 % of people with dementia that live in developing countries and the less than one tenth of population -based research carried out in those setting s. This paper describes the protocol s for the 10/66 population -based and intervention studies that aim to redress this imbalance . Methods / design Cross-sectional comprehensive one phase surveys have been conducted of all residents aged 65 and over of geographically defined catchment areas in ten low and middle income countries ( India , China , Nigeria , Cuba , Dominican Republic , Brazil , Venezuela , Mexico , Peru and Argentina ) , with a sample size of between 1000 and 3000 ( generally 2000 ) . Each of the studies uses the same core minimum data set with cross-culturally vali date d assessment s ( dementia diagnosis and subtypes , mental disorders , physical health , anthropometry , demographics , extensive non communicable disease risk factor question naires , disability/functioning , health service utilisation , care arrangements and caregiver strain ) . Nested within the population based studies is a r and omised controlled trial of a caregiver intervention for people with dementia and their families ( IS RCT N41039907 ; IS RCT N41062011 ; IS RCT N95135433 ; IS RCT N66355402 ; IS RCT N93378627 ; IS RCT N94921815 ) . A follow up of 2.5 to 3.5 years will be conducted in 7 countries ( China , Cuba , Dominican Republic , Venezuela , Mexico , Peru and Argentina ) to assess risk factors for incident dementia , stroke and all cause and cause-specific mortality ; verbal autopsy will be used to identify causes of death . Discussion The 10/66 DRG baseline population -based studies are nearly complete . The incidence phase will be completed in 2009 . All investigators are committed to establish an anonymised file sharing archive with monitored public access . Our aim is to create an evidence base to empower advocacy , raise awareness about dementia , and ensure that the health and social care needs of older people are anticipated and met Pregnancy is a condition exhibiting increased susceptibility to oxidative stress , and Fe plays a central role in generating harmful oxygen species . The objective of the present study is to investigate the changes in haematological status , oxidative stress and erythrocyte membrane fluidity in anaemic pregnant women after Fe supplementation with and without combined vitamins . The study was a 2 months double-blind , r and omised trial . Pregnant women ( n 164 ) were allocated to four groups : group C was the placebo control group ; group I was supplemented daily with 60 mg Fe ( ferrous sulphate ) daily ; group IF was supplemented daily with Fe plus 400 μg folic acid ; group IM was supplemented daily with Fe plus 2 mg retinol and 1 mg riboflavin , respectively . After the 2-month trial , Hb significantly increased by 15.8 , 17.3 and 21.8 g/l , and ferritin by 2.8 , 3.6 and 11.0 μg/l , in the I , IF and IM groups compared with placebo . Polarisation ( ρ ) and microviscosity ( η ) decreased significantly in other groups compared with placebo , indicating an increase in membrane fluidity . Significant decreases of ρ and η values compared with group C were 0.033 and 0.959 for group I , 0.037 and 1.074 for group IF and 0.064 and 1.865 for group IM , respectively . In addition , significant increases of glutathione peroxidase activities and decreases of malondialdehyde were shown in all treated groups , as well as increases of plasma retinol and urine riboflavin in group IM . The findings show that supplementation with Fe and particularly in combination with vitamins could improve the haematological status as well as oxidative stress and erythrocyte membrane fluidity Background Being an intermediate stage in the development of diabetes , pre-diabetics were estimated as high as 14 % to 63 % in China and one to three quarters of them will develop into diabetes within 10 years . It is well established that the risk of diabetes progression can be modified substantially and a whole range of proven guidelines , protocol s and method ologies are available . Unfortunately , most proven interventions are seldom used in daily practice and this is especially true in re source poor rural China . This project aims at demonstrating that an evolutionary intervention package featuring low cost , integration with routine services , cultural sensitization and self-optimization , is effective and sustainable in preventing diabetes . Methods / design This project utilizes a quasi cluster r and omized controlled trial and a batched implementation strategy in which villages are recruited in 7 blocks within 7 consecutive years respectively . Block 0 involves 3 villages and provides an opportunity for piloting and refining primitive intervention method ologies and protocol s. The following 6 blocks consist of 14 villages each and serve as intervention arm ; while all the villages not yet started intervention form the control arm . For each block , measurement happens at baseline and every 12 months ( for plasma glucose ) or monthly ( for body weight and blood pressure ) after baseline . These arrangements enable documentation of up to 6 years of consecutive measures and detection of lower incidence of progression into diabetes , improved body max index and blood pressure , and increased service use and involvement in healthy dietary and physical activities among pre-diabetics receiving the experimental intervention compared to themselves at baseline or those in the delayed-intervention control condition . Discussion China has a long history of separating disease prevention and treatment systems and there is a clear need to leverages key success factors in a synergetic way toward integrated and sustainable diabetes prevention . This project is owned and managed by local health authorities and utilizes available re sources . It introduces a package of long-term incentives , establishes ongoing mechanisms for continuous capacity building and quality improvement , and builds up an operational cycle for catalyzing similar efforts in the local prefecture even throughout rural China . Trial registration Current Controlled Trials : IS RCT N66772711 Introduction Schizophrenia is a severe , chronic and disabling mental illness . Non-adherence to medication and relapse may lead to poorer patient function . This r and omised controlled study , under the acronym LEAN ( Lay health supporter , e-platform , award , and iNtegration ) , is design ed to improve medication adherence and high relapse among people with schizophrenia in re source poor setting s. Methods / analysis The community-based LEAN has four parts : ( 1 ) Lay health supporters ( LHSs ) , mostly family members who will help supervise patient medication , monitor relapse and side effects , and facilitate access to care , ( 2 ) an E-platform to support two-way mobile text and voice messaging to remind patients to take medication ; and alert LHSs when patients are non-adherent , ( 3 ) an Award system to motivate patients and strengthen LHS support , and ( 4 ) iNtegration of the efforts of patients and LHSs with those of village doctors , township mental health administrators and psychiatrists via the e-platform . A r and om sample of 258 villagers with schizophrenia will be drawn from the schizophrenic ‘ 686 ’ Program registry for the 9 Xiang dialect towns of the Liuyang municipality in China . The sample will be further r and omised into a control group and a treatment group of equal sizes , and each group will be followed for 6 months after launch of the intervention . The primary outcome will be medication adherence as measured by pill counts and supplemented by pharmacy records . Other outcomes include symptoms and level of function . Outcomes will be assessed primarily when patients present for medication refill visits scheduled every 2 months over the 6-month follow-up period . Data from the study will be analysed using analysis of covariance for the programme effect and an intent-to-treat approach . Ethics and dissemination University of Washington : 49464 G ; Central South University : CTXY-150002 - 6 . Results will be published in peer- review ed journals with deidentified data made available on FigShare . Trial registration number ChiCTR-ICR-15006053 ; Pre- results OBJECTIVE To prevent perinatal transmission of hepatitis B virus ( HBV ) , WHO recommends that the first dose of hepatitis B ( HepB ) vaccine be given within 24 hours after birth . This presents a challenge in remote areas with limited cold-chain infrastructure and where many children are born at home . METHODS Rural townships in three counties in China 's Hunan Province were r and omized into three groups with different strategies for delivery of the first dose of HepB vaccine . In group 1 , vaccine was stored within the cold chain and administered in township hospitals . In group 2 , vaccine was stored out of the cold chain in villages and administered by village-based health workers to infants at home . Group 3 used the same strategy as group 2 , but vaccine was packaged in a prefilled injection device . Training of immunization providers and public communication conveying the importance of the birth dose was performed for all groups . FINDINGS Among children born at home , timely administration ( within 24 hours after birth ) of the first dose of HepB vaccine increased in all groups after the study : group 1 , from 2.4 % to 25.2 % ; group 2 , from 2.6 % to 51.8 % ; and group 3 , from 0.6 % to 66.7 % ; P < 0.001 in each case . No significant difference in antibody response to vaccine was observed between the groups . CONCLUSION Timely administration of the first dose of HepB vaccine was improved by communication and training activities , and by out-of-cold-chain storage of vaccine and administration at the village level , especially among children born at home Background Currently there are two main sources of mortality data with cause of death assignments in China . Both sources –the Ministry of Health-Vital Registration system and the Chinese Disease Surveillance Point system – present their own challenges . A new approach to cause of death assignment is a smartphone-based shortened version of a verbal autopsy survey . This study evaluates the feasibility and acceptability of this new method conducted by township health care providers ( THP ) and village doctors ( VD ) in rural China , where a large proportion of deaths occur in homes and cause of death data are inaccurate or lacking . Methods The Population Health Metrics Research Consortium mobile phone-based shortened verbal autopsy question naire was made available on an And roid system-based application , and cause of death was derived using the Tariff method ( Tariff 2.0 ) ; we called this set of tools “ msVA . ” msVA was administered to relatives of the deceased by six THPs and six VDs in 24 villages located in six townships of Luquan County , Hebei Province , China . Subsequently , interviews were conducted among 12 interviewers , 12 r and omly selected respondents , and five study staff to assess the feasibility and acceptability of using msVA for mortality data collection . Results Between July 2013 and August 2013 , 268 deaths took place in the study villages . Among the 268 deaths , 227 VAs were completed ( nine refusals , 31 migrations and one loss of data due to breakdown of the smartphone ) . The average time for a VA interview was 21.5 ± 3.4 min ( 20.1 ± 3.5 min for THP and 23.2 ± 4.1 min for VD ) . Both THPs and VDs could be successful interviewers ; the latter needed more training but had more willingness to implement msVA in the future . The interviews revealed that both interviewers and relatives of the deceased found msVA to be feasible , acceptable , and more desirable than traditional methods . The cost of conducting a new VA was $ 8.87 per death . Conclusions Conduction of msVA by VDs in their own villages was feasible and acceptable in rural northern China . Broader implementation of msVA across rural China could potentially improve the coverage and quality of cause of death data , allowing for better national health evaluation and program planning Background Effective prevention against cancers depends heavily on sustained individual efforts practicing protective behaviors and avoiding risk factors in a complex sociocultural context , which requires continuous and personalized supports . Contemporary prevention relies primarily on strategies targeting general population with limited attention being paid to individualized approaches . This study tests a novel package called , in acronym of core intervention components , eCROPS-CA that leverages protective behaviors against over 80 % leading cancers among high risk individuals via continuous and tailored counseling by village doctors . Methods / Design The study utilizes a quesi- RCT design involving 4320 high risk individuals selected , via rapid and detailed risk assessment s , from about 72,000 farmers aged 35 + in 36 administrative villages r and omized into equal intervention and delayed intervention arms . The intervention arm receives baseline and semiannual follow up evaluations plus eCROPS-CA for 5 years ; while the control arm , only the baseline and follow-up evaluations for the first 5 years and eCROPS-CA starting from the 6th year if the intervention is proved effective . eCROPS-CA comprises electronic supports and supervision ( e ) , counseling cancer prevention ( C ) , recipe for objective behaviors ( R ) , operational toolkit ( O ) , performance-based incentives ( P ) , and screening and assessment ( S ) . Evaluation measures include : incidence and stage of the leading cancers , cancer-related knowledge , attitudes and practice s ; easy biophysical indicators ( e.g. , body mass index , blood pressure ) ; intervention compliance , acceptance of the package . Discussion The prevention package incorporates key success factors in a synergetic way toward cost-effectiveness and long-term sustainability . It targets a set rather than any single cancer ; choses village doctors as key solution to the widespread lack of professional manpower in implementing personalized and thus relatively sophisticated prevention ; adopts real-time monitoring in reaching continuous improvement ; utilizes smart web aids to enable prioritizing complex determinants of objective behaviors , linking counseling sessions happened at different time points and hence delivering highly coordinated prevention ; uses 2-stage risk assessment models in identifying high risk individuals so as to focus on the most needed ; applies st and ardized operation procedures in simplifying and smoothing behavior intervention yet ensuring delivery of essential steps and key elements . Trials registryIS RCT Background Many community dwelling individuals with schizophrenia do not take medications regularly and , thus , are prone to frequent relapses . Aim Evaluate the effectiveness of self-management training on adherence to medications and relapse among individuals with chronic schizophrenia living in the community . Methods A total of 201 individuals with chronic schizophrenia living in the urban and rural communities of Shanghai Municipality were r and omized into a treatment as usual control group ( n=98 ) or a selfmanagement intervention group ( n=103 ) that received weekly self-management skills training for 6 months followed by 24 months of monthly group booster sessions in which a community health worker review ed patients ’ self-management checklists . Two psychiatrists blind to the treatment status of patients , assessed adherence to medications using the Morisky Medication Adherence Scale and patients ’ insight into their illness using the Scale to Assess Unawareness of Mental Disorders ( SAUMD ) at baseline and 30 months after baseline . A total of 194 individuals ( 95.6 % ) completed the study . Results There were no differences between groups at baseline , but after 30 months the intervention group had significantly better medication compliance , significantly greater insight into their illness , and ( by self-report ) were using significantly higher dosages of antipsychotic medication . Only 2 ( 1.9 % ) of the 103 intervention group participants relapsed ( i.e. , experienced one or more re-hospitalizations ) over the 30 months of follow-up , but 14 ( 14.3 % ) of the 98 control group subjects relapsed ( X2=8.83 , p=0.003 ) . Conclusions Given the large sample size , relatively long follow-up , r and omized design , and single-blind evaluation of outcomes the dramatic reduction in relapse and improvements in medication adherence and insight identified in this study are robust findings . These results extended our previous findings , which demonstrated the benefit of self-management training on improving the symptoms and social functioning of individuals with chronic schizophrenia living in the community . Cost-benefit studies are now needed to assess the feasibility of up-scaling this self-management intervention to a wide range of communities Introduction This study analyzes the factors that influence the turnover intention of village doctors by investigating village clinic workers in rural areas , particularly in Xiangyang City , Hubei Province . Methods A total of 1184 village clinics were sample d r and omly in Xiangyang City . The research assistants distributed 1930 question naires to village doctors . This study had a response rate of 97.88 % . A total of 1889 village doctors completed the question naires . Results The results of the investigation conducted in Xiangyang City indicated that 63.2 % of the village doctors did not plan to leave the organization where they were currently employed . However , more than one-third ( 36.8 % ) of the village doctors considered leaving their posts voluntarily . Some job satisfaction indexes affect their intention to resign . The results showed that income satisfaction and the way organization policies are put into practice , in addition , my pay and the amount of work I do , the chances for advancement on this job and the work conditions are significant factors that contribute to the turnover intention of village doctors . Conclusions This study may interest heath care management administrator and highlight the influence of job satisfaction on turnover intention of village doctors . Our findings outline some issues that contribute to these problems and suggest an approach for health care policy maker to implement a broader national process and organizational strategies to improve the job satisfaction and stability of the village doctors Background The aim of this study was to assess the effectiveness of an EPI smartphone application ( EPI app ) on improving vaccination coverage in rural Sichuan Province , China . Methods This matched-pair cluster r and omized controlled study included 32 village doctors , matched in 16 pairs , and took place from 2013 to 2015 . Village doctors in the intervention group used the EPI app and reminder text messages while village doctors in the control group used their usual procedures and text messages . The primary outcome was full vaccination coverage with all five vaccines ( 1 dose of BCG , 3 doses of hepatitis B , 3 doses of OPV , 3 doses of DPT and 1 dose of measles vaccine ) , and the secondary outcome was coverage with each dose of the five individual vaccines . We also conducted qualitative interviews with village doctors to underst and perceptions on using the EPI app and how this changed their vaccination work . Results The full vaccination coverage increased statistically significant from baseline to end-line in both the intervention ( 67 % [ 95 % CI:58 - 75 % ] to 84 % [ 95 % CI:76 - 90 % ] , P = 0.028 ) and control group ( 71 % [ 95 % CI:62 - 79 % ] to 82 % [ 95 % CI:74 - 88 % ] , P = 0.014 ) . The intervention group had higher increase in full vaccination coverage from baseline to end-line compared to the control group ( 17 % vs 10 % ) , but this was not statistically significant ( P = 0.164 ) . Village doctors found it more convenient to use the EPI app to manage child vaccination and also reported saving time by looking up information of caregivers and contacting caregivers for overdue vaccinations quicker . However , village doctors found it hard to manage children who migrated out of the counties . Conclusions This study showed that an app and text messages can be used by village doctors to improve full vaccination coverage , though no significant increase in vaccination coverage was found when assessing the effect of the app on its own . Village doctors using EPI app reported having improved their working efficiency of managing childhood vaccination . Future studies should be conducted to evaluate the impact of more integrated approach of mHealth intervention on child immunization . Trial registration Chinese Clinical Trials Registry ( ChiCTR ) : ChiCTR-TRC-13003960 , registered on December 6 , 2013 Background In re source -poor areas of China and India , the cardiovascular disease burden is high , but availability of and access to quality healthcare is limited . Establishing a management scheme that utilizes the local infrastructure and builds healthcare capacity is essential for cardiovascular disease prevention and management . The study aims to develop , implement , and evaluate the feasibility and effectiveness of a simplified , evidence -based cardiovascular management program delivered by community healthcare workers in re source -constrained areas in Tibet , China and Haryana , India . Methods / design This yearlong cluster-r and omized controlled trial will be conducted in 20 villages in Tibet and 20 villages in Haryana . R and omization of villages to usual care or intervention will be stratified by country . High cardiovascular disease risk individuals ( aged 40 years or older , history of heart disease , stroke , diabetes , or measured systolic blood pressure of 160 mmHg or higher ) will be screened at baseline . Community health workers in the intervention villages will be trained to manage and follow up high-risk patients on a monthly basis following a simplified ‘ 2 + 2 ’ intervention model involving two lifestyle recommendations and the appropriate prescription of two medications . A customized electronic decision support system based on the intervention strategy will be developed to assist the community health workers with patient management . Baseline and follow-up surveys will be conducted in a st and ardized fashion in all villages . The primary outcome will be the net difference between-group in the proportion of high-risk patients taking antihypertensive medication pre- and post-intervention . Secondary outcomes will include the proportion of patients taking aspirin and changes in blood pressure . Process and economic evaluations will also be conducted . Discussion To our knowledge , this will be the first study to evaluate the effect of a simplified management program delivered by community health workers with the help of electronic decision support system on improving the health of high cardiovascular disease risk patients . If effective , this intervention strategy can serve as a model that can be implemented , where applicable , in rural China , India , and other re source -constrained areas .Trial registration The trial was registered in the clinical trials.gov data base on 30 December , 2011 and the registration number is NCT01503814 Background The high-risk strategy has been proven effective in preventing cardiovascular disease ; however , the population benefits from these interventions remain unknown . This study aims to assess , at the population level , the effects of an evidence -based high cardiovascular risk management program delivered by village doctors in rural China . Methods The study will employ a cluster-r and omized controlled trial in which a total of 120 villages in five northern provinces of China , will be assigned to either intervention ( 60 villages ) or control ( 60 villages ) . Village doctors in intervention villages will be trained to implement a simple evidence -based management program design ed to identify , treat and follow-up as many as possible individuals at high-risk of cardiovascular disease in the village . The intervention will also include performance feedback as well as a performance-based incentive payment scheme and will last for 2 years . We will draw two different ( independent ) r and om sample s , before and after the intervention , 20 men aged ≥ 50 years and 20 women aged ≥60 years from each village in each sample and a total of 9,600 participants from 2 sample s to measure the study outcomes at the population level . The primary outcome will be the pre-post difference in mean systolic blood pressure , analyzed with a generalized estimating equations extension of linear regression model to account for cluster effect . Secondary outcomes will include monthly clinic visits , provision of lifestyle advice , use of antihypertensive medications and use of aspirin . Process and economic evaluations will also be conducted . Discussion This trial will be the first implementation trial in the world to evaluate the population impact of the high-risk strategy in prevention and control of cardiovascular disease . The results are expected to provide important information ( effectiveness , cost-effectiveness , feasibility and acceptability ) to guide policy making for rural China as well as other re source -limited countries . Trial registration The trial is registered at Clinical Trials.gov ( NCT01259700 ) . Date of initial registration is December 13 , 2010 To report on the design and basic outcomes of three interventions aim ed at improving the use and quality of maternity care in rural China : financial interventions , training in clinical skills , and training in health education . Community-based cluster r and omized trials were carried out in one central and two western provinces between 2007 and 2009 : ( 1 ) financial interventions covered part of women ’s costs for prenatal and postnatal care , ( 2 ) training of midwives in clinical skills was given by local maternity care experts in two- or three-group training courses , ( 3 ) health education training for midwives and village doctors were given by local experts in health education in two- or three-group training courses . A survey was conducted in a stratified r and om sample of women who had been pregnant in the study period . 73 % of women ( n = 3,673 ) were interviewed within 1–10 months of giving birth . Outcomes were compared by the different intervention and control groups . Adjusted odds ratios were calculated by logistic regression to adjust for varying maternal characteristics . Most of the differences found between the groups were small and some varied between provinces . The financial intervention did not influence the number of visits , but was associated with increased caesarean sections and a decrease in many ultrasound tests . The clinical intervention influenced some indicators of care content . There was no consistent finding for the health education intervention . Financial and training interventions have the potential to improve maternity care , but better implementation is required . Unintended consequences , including overuse of technology , are possible OBJECTIVE To study the feasibility of the programme " Focusing on early childhood development " in impoverished rural areas in China . METHODS A question naire survey was conducted among 100 mothers , about half with junior middle school education , 18 % with grade -school education , and 29 % being illiterate , of children aged under two years in 7 villages in Changfeng County , Anhui Province , a native impoverished county , to underst and their knowledge and attitudes about child healthcare . Then these mothers were r and omly divided into 2 equal groups : experimental group , receiving face-to-face guidance in the practice of early healthcare for children at home with a pamphlet developed by WHO as teaching material ; and control group without receiving guidance . Two months later the mothers received the second session of guidance . Six months after the same question naire survey was conducted among the 100 mothers to investigate the changes in knowledge and practice and Gesell development test was made to observe the changes in mental development . Two-days ' training on the technique of early child healthcare in the form of reading , videotape presenting , and exercise , was given to 29 village doctors . Question naire survey was conducted among them before and 1 month after the training to underst and the changes of their knowledge and attitudes towards early child healthcare . RESULTS After the guidance the knowledge and fostering skills in terms of early child healthcare were improved significantly among the mothers of the experimental group in comparison with the mothers of the control group ( P < 0.01 ) . After the training most of the village doctors managed put the knowledge they had learned into practice , however , the percentage of those who lacked confidence in the smooth implementation of the programme remained unchanged ( 38 % vs. 41 % ) . Before the experiment the abilities in different fields were not significantly different between the children in these 2 groups . Six months after the implementation of the programme the abilities in fine motion , speech , and interpersonal communication were improved significantly among the children of the experimental group ( all P < 0.05 ) . CONCLUSION Economic , simple , and effective , the programme " Focusing on early childhood development " is suitable for the impoverished rural areas in China Objective To assess the effectiveness of a coach-led motivational interviewing ( MI ) intervention in improving glycaemic control , as well as clinical , psychosocial and self-care outcomes of individuals with type 2 diabetes mellitus ( T2DM ) compared with usual care . Design Pragmatic cluster r and omised controlled trial ( RCT ) . Setting Community Health Stations ( CHSs ) in Fengtai district , Beijing , China . Participants Of the 41 r and omised CHSs ( 21 intervention and 20 control ) , 21 intervention CHSs ( 372 participants ) and 18 control CHSs ( 296 participants ) started participation . Intervention Intervention participants received telephone and face-to-face MI health coaching in addition to usual care from their CHS . Control participants received usual care only . Medical fees were waived for both groups . Outcome measures Outcomes were assessed at baseline , 6 and 12 months . Primary outcome measure was glycated haemoglobin ( HbA1c ) . Secondary outcomes included a suite of anthropometric , blood pressure ( BP ) , fasting blood , psychosocial and self-care measures . Results At 12 months , no differential treatment effect was found for HbA1c ( adjusted difference 0.02 , 95 % CI −0.40 to 0.44 , p=0.929 ) , with both treatment and control groups showing significant improvements . However , two secondary outcomes : psychological distress ( adjusted difference −2.38 , 95 % CI −4.64 to −0.12 , p=0.039 ) and systolic BP ( adjusted difference −3.57 , 95 % CI −6.08 to −1.05 , p=0.005 ) were robust outcomes consistent with significant differential treatment effects , as supported in sensitivity analyses . Interestingly , in addition to HbA1c , both groups displayed significant improvements in triglycerides , LDL cholesterol and HDL cholesterol . Conclusions In line with the current Chinese primary healthcare reform , this study is the first large-scale cluster RCT to be implemented within real-world CHSs in China , specifically addressing T2DM . Although a differential treatment effect was not observed for HbA1c , numerous outcomes ( including HbA1c ) improved in both groups , supporting the establishment of regular , free clinical health checks for people with T2DM in China . Trial registration number IS RCT N01010526 ; Pre- results OBJECTIVE To assess whether a theory-based , community health worker-delivered intervention for household smokers will lead to reduced secondh and smoke exposure to children in Chinese families . METHODS Smoking parents or caregivers who had a child aged 5 years or younger at home were r and omized to the intervention group ( n = 164 ) to receive smoking hygiene intervention or to the comparison group ( n = 154 ) . The intervention was delivered by trained community health workers . Outcomes were assessed at 2- and 6- month follow-up . RESULTS Of the 318 families r and omized , 98 ( 60 % ) of 164 intervention group and 82 ( 53 % ) of 154 of controls completed 6-month follow-up assessment . At the 6-month follow-up , 62 % of intervention and 45 % of comparison group households adopted complete smoking restrictions at home ( P = .022 ) ; total exposure ( mean number of cigarettes per week ± st and ard deviation ) from all smokers at home in the past 7 days was significantly lower among children in the intervention ( 3.29 ± 9.06 ) than the comparison ( 7.41 ± 14.63 ) group ( P = .021 ) ; and mean urine cotinine level ( ng/mL ) was significantly lower in the intervention ( 0.030 ± .065 ) than the comparison ( 0.087 ± .027 ) group , P < .001 ) . Participants rating of the overall usefulness of the intervention was 4.8 + 0.8 ( 1 st and ard deviation ) on the 5 point scale ( 1 not at all and 5 = very useful ) . CONCLUSIONS The findings of this very first study in China showed that smoking hygiene intervention was effective in reducing children 's exposure to secondh and smoke . These findings have implication s for the development of primary health care-based secondh and smoke exposure reduction and family oriented smoking cessation interventions as China moves toward a smoke-free society Background Increasing cases of diabetes , a general lack of routinely operational prevention , and a long history of separating disease prevention and treatment call for immediate engagement of frontier clinicians . This applies especially to village doctors who work in rural China where the majority of the nation ’s vast population lives . Objective This study aims to develop and test an online Smart Web Aid for Preventing Type 2 Diabetes ( SWAP-DM2 ) capable of addressing major barriers to applying proven interventions and integrating diabetes prevention into routine medical care . Methods Development of SWAP-DM2 used evolutionary prototyping . The design of the initial system was followed by refinement cycles featuring dynamic interaction between development of practical and effective st and ardized operation procedures ( SOPs ) for diabetes prevention and Web-based assistance for implementing the SOPs . The result ing SOPs incorporated proven diabetes prevention practice s in a synergetic way . SWAP-DM2 provided support to village doctors ranging from simple educational webpages and record maintenance to relatively sophisticated risk scoring and personalized counseling . Evaluation of SWAP-DM2 used data collected at baseline and 6-month follow-up assessment : ( 1 ) audio recordings of service encounters ; ( 2 ) structured exit surveys of patients ’ knowledge , self-efficacy , and satisfaction ; ( 3 ) measurement of fasting glucose , body mass index , and blood pressure ; and ( 4 ) qualitative interviews with doctors and patients . Data analysis included ( 1 ) descriptive statistics of patients who received SWAP-DM2–assisted prevention and those newly diagnosed with prediabetes and diabetes ; ( 2 ) comparison of the variables assessed between baseline and follow-up assessment ; and ( 3 ) narratives of qualitative data . Results The 17 participating village doctors identified 2219 patients with elevated diabetes risk . Of these , 84.85 % ( 1885/2219 ) consented to a fasting glucose test with 1022 new prediabetes and 113 new diabetes diagnoses made within 6 months . The prediabetic patients showed substantial improvement from baseline to 6-month follow-up in vegetable intake ( 17.0 % , 43/253 vs 88.7 % , 205/231 ) , calorie intake ( 1.6 % , 4/253 vs 71.4 % , 165/231 ) , leisure-time exercises ( 6.3 % , 16/253 vs 21.2 % , 49/231 ) , body weight ( mean 62.12 kg , SD 9.85 vs mean 58.33 kg , SD 9.18 ) , and body mass index ( mean 24.80 kg/m2 , SD 3.21 vs mean 23.36 kg/m2 , SD 2.95 ) . The prediabetic patients showed improvement in self-efficacy for modifying diet ( mean 5.31 , SD 2.81 vs mean 8.53 , SD 2.25 ) , increasing physical activities ( mean 4.52 , SD 3.35 vs mean 8.06 , SD 2.38 ) , engaging relatives ( mean 3.93 , SD 3.54 vs mean 6.93 , SD 2.67 ) , and knowledge about diabetes and risks of an imbalanced diet and inadequate physical activity . Most participating doctors and patients viewed SWAP-DM2 as useful and effective . Conclusions SWAP-DM2 is helpful to village doctors , acceptable to patients , and effective in modifying immediate determinants of diabetes at least in the short term , and may provide a useful solution to the general lack of participation in diabetes prevention by frontier clinicians in rural China . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 66772711 ; http://www.controlled-trials.com/IS RCT N66772711 ( Archived by WebCite at http://www.webcitation.org/6OMkAqyEy ) BACKGROUND Iron and vitamin A deficiencies impact anemia and the immune system . OBJECTIVE to investigate the effect of iron combined with retinol supplementation on iron status , IL-2 level and lymphocyte proliferation . METHODS a double-blind r and omized trial conducted over 2 months . We r and omly allocated 186 anemic pregnant women with 80 ≤ Hb 0 < 110 g/L into four groups . Group I ( n=47 ) was supplemented daily with 60 mg iron as ferrous sulfate , IF ( n=46 ) with 60 mg iron and 0.4 mg folic acid , IR ( n=46 ) with 60 mg iron , 2.0 mg retinol and 0.4 mg folic acid and C ( n=47 ) was the placebo group , . RESULTS after the 2 months trial , there were considerable increases of iron status in Hb , plasma iron and ferritin in the I , IF and IR groups compared with Group C. Increases in plasma iron and ferritin in the IR group were also significantly greater than in Groups I and IF . Compared with group C , increases of IL-2 levels were 119 , 184 and 206 ng/L ; and lymphocyte proliferation increased by 0.095 , 0.112 and 0.219 in Groups I , IF and IR , respectively . Increases of IL-2 were 65.3 ng/L and 87.5 ng/L in Groups IF and IR , greater than in Group I ( both p values < 0.01 ) ; and lymphocyte proliferation in Group IR were 0.124 and 0.107 , also greater than in Groups I and IF , respectively . CONCLUSION iron combined retinol supplementation was more beneficial to improving iron status and lymphocyte proliferation during pregnancy than iron alone PURPOSE We evaluated a peer leader – support program ( PLSP ) for diabetes self-management in China in terms of acceptability and feasibility ; implementation ; perceived advantages ; disadvantages and barriers ; reach and recruitment ; effectiveness in terms of diabetes knowledge and clinical impacts ; adoption ; and sustainability . METHODS Within each of 3 cities in Anhui Province , 2 subcommunities were r and omly assigned to usual care or PLSP . Peer leaders and staff of Community Health Service Centers ( CHSCs ) co-led biweekly educational meetings . Peer leaders also led biweekly discussion meetings , promoted regular care through the CHSCs , organized informal health promotion activities ( eg , walking and tai chi groups ) , and provided informal individual support to participants through casual contact . RESULTS Qualitative evaluations indicated acceptance of and positive responses to the program among patients , peer leaders , and CHSC staff . Implementation was successful in 2 of 3 subcommunities , the third failing for lack of staff re sources . Reported advantages included peer support as a bridge between CHSCs and their patients . In 2 sites where the PLSP was implemented , analyses controlling for baseline differences and site showed significant benefits for PLSP relative to controls ( P < 0.05 ) for knowledge , self-efficacy , BMI , systolic blood pressure , diastolic blood pressure , and both fasting and 2-hour post-pr and ial blood glucose . The Anhui Provincial Health Bureau has extended the PLSP model to other communities and to cardiovascular disease prevention and management . CONCLUSION The PLSP was well accepted , feasible given sufficient administrative and staff re sources , effective for those who participated , and generalizable to other sites and health problems Background — In rural areas in China and India , the cardiovascular disease burden is high but economic and healthcare re sources are limited . This study ( the Simplified Cardiovascular Management Study [ SimCard ] ) aims to develop and evaluate a simplified cardiovascular management program delivered by community health workers with the aid of a smartphone-based electronic decision support system . Methods and Results — The SimCard study was a yearlong cluster-r and omized , controlled trial conducted in 47 villages ( 27 in China and 20 in India ) . Recruited for the study were 2086 individuals with high cardiovascular risk ( aged ≥40 years with self-reported history of coronary heart disease , stroke , diabetes mellitus , and /or measured systolic blood pressure ≥160 mm Hg ) . Participants in the intervention villages were managed by community health workers through an And roid-powered app on a monthly basis focusing on 2 medication use and 2 lifestyle modifications . In comparison with the control group , the intervention group had a 25.5 % ( P<0.001 ) higher net increase in the primary outcome of the proportion of patient-reported antihypertensive medication use pre- and post-intervention . There were also significant differences in certain secondary outcomes : aspirin use ( net difference : 17.1 % ; P<0.001 ) and systolic blood pressure ( –2.7 mm Hg ; P=0.04 ) . However , no significant changes were observed in the lifestyle factors . The intervention was culturally tailored , and country-specific results revealed important differences between the regions . Conclusions — The results indicate that the simplified cardiovascular management program improved quality of primary care and clinical outcomes in re source -poor setting s in China and India . Larger trials in more places are needed to ascertain the potential impacts on mortality and morbidity outcomes . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01503814 |
2,457 | 30,556,217 | None of the instruments review ed appeared to have been developed for use in clinical practice and specifically for patients with HM , except MyPOS .
Furthermore , measurement properties were established , largely , in clinical trial scenarios . | The wide range of health-related quality -of-life ( HRQoL ) instruments used in haematology makes it challenging for haematologists and other care team members in practice to select , use and underst and the scoring system and finally interpret the results .
The main objectives of this study were to : ( a ) provide a comprehensive list of quality -of-life issues important to patients suffering from haematological malignancies , identified through the literature ; ( b ) provide a list of health-related quality -of-life ( HRQoL ) instruments used in haematological malignancies in both daily clinical practice and research ; and ( c ) evaluate the relevance and comprehensibility of the identified instruments in haematological malignancies . | Intensification of treatment for acute myeloid leukemia ( AML ) in adult patients result ed in a substantial improvement in long-term prognosis . Therefore , the assessment of quality of life ( QL ) of patients undergoing treatment is of growing interest . This study was design ed to evaluate QL in patients with AML treated according to the protocol of the German AML-Cooperative Group ( Münster , Germany ) . The EORTC QLQ-C 30 question naire was used to analyze QL throughout therapy , evaluating defined specific parameters at 12 different time-points . Sixty-one patients were recruited within the first 30 months of the study . Those 28 patients who have completed the course of inpatient treatment ( n = 28 ) are evaluated for changes in the conceptually distinct QL domains : Physical Functioning ( P < 0.001 ) , role functioning ( P = 0.001 ) , Emotional Functioning ( P < 0.001 ) and social functioning ( P = 0.007 ) improve significantly from beginning of chemotherapy to the end of inpatient treatment . Individual assessment of Global Health Status and Subjective QL improves significantly over the same time ( P < 0.001 ) . at the end of inpatient treatment patients suffer significantly less from fatigue , nausea/emesis , loss of appetite and sleep disturbance ( P < 0.001 ) . although most patients with aml eventually relapse , the evaluation of ql in patients undergoing treatment shows that subjective benefit outweights the adverse effects of antileukemic therapy Fatigue is a major complaint among advanced cancer patients . Several instruments are available for measuring fatigue . The EORTC QLQ-C30 is one of the most frequently used health-related quality of life ( HRQOL ) instruments , and it includes a three-item fatigue subscale . Limited knowledge exists about the validity , performance and sensitivity of EORTC QLQ-C30 fatigue scale as compared with a fatigue-specific instrument . The aim of the present study was to vali date the EORTC QLQ-C30 fatigue scale ( FA ) against the Fatigue Question naire ( FQ ) . The FQ is frequently used and was developed to measure fatigue in both cancer and noncancer population s. The FQ measures physical ( PF , seven items ) and mental fatigue ( MF , four items ) . The study population included two different cohorts : A ) patients with advanced metastatic cancer included in a prospect i ve r and omized study of palliative radiotherapy ( n = 238 ) ; B ) patients with leukaemia and malignant lymphoma curatively treated with stem-cell transplantation and high-dose chemotherapy ( n = 128 ) . The analysis demonstrated that the FA correlated higher with the PF scale ( r = 0.67–0.75 ) as compared with the MF scale ( r = 0.49–0.61 ) . The item – scale correlations between FA items and the PF scale were consistently higher than between FA items and the MF scale . A factor analysis including all the items within the FA and the FQ identified two factors . All FA items loaded on a PF factor ( 0.70–0.85 ) . A floor/ ceiling effect , indicating a high number of respondents with lowest , respectively , highest scores was observed more frequently in the FA as compared with the FQ . The PF discriminated better between diagnostic groups with different levels of fatigue than the FA did . In conclusion , the EORTC QLQ-C30 fatigue scale is measuring physical fatigue . A floor/ ceiling effect seems to appear for the EORTC QLQ-C30 fatigue scale . The validity of the EORTC QLQ-C30 fatigue scale is to be question ed for use in palliative care patients . In studies with fatigue as a defined end point , a domain-specific instrument should , therefore , be added When a r and omized trial ( NMSG 4/90 ) comparing treatment with melphalan/prednisone to melphalan/prednisone + interferon α‐2b in newly diagnosed multiple myeloma was inititated in 1990 , a quality ‐of‐life assessment was integrated into the study . We used the question naire ( QLQ‐C30 ) developed by the European Organization of Research and Treatment of Cancer ( EORTC ) Study Group on Quality of Life . The QLQ‐C30 incorporates five functional scales , three symptom scales , a global health and quality ‐of‐life scale and some single symptom measures . The question naire was completed prior to treatment and after 1 , 6 , 12 , 24 , 36 and 48 months . 524 ( 90.2 % ) of 581 patients enrolled in the NMSG 4/90 completed the first question naire , and 484 ( 83.3 % ) completed all question naires given to them . All but one of the scales met the minimum criteria of reliability ( Cronbach ’s alpha ≥0.70 ) . Validity was shown by ( 1 ) the ability of the scales to discriminate clearly between patients differing in clinical status as defined by pre‐treatment W.H.O. performance index and Durie & Salmon stage , and ( 2 ) the sensitivity to changes in objective disease status ( response and relapse ) . This is the first report of the measurement of health‐related quality of life in a prospect i ve clinical trial in multiple myeloma . The results demonstrate that the QLQ‐C30 is a reliable and valid instrument for the measurement of quality of life in these patients . The data will be used for a cost – utility analysis of the results of the NMSG 4/90 trial Measurement of health-related quality of life was integrated into a r and omized trial ( NMSG 4/90 ) comparing melphalan/prednisone to melphalan/prednisone + interferon alpha-2b in newly diagnosed multiple myeloma . One of the aims of the study was to assess the prognostic significance of quality -of-life scores , using the EORTC QLQ-C30 question naire . Univariate analysis showed a highly significant association with survival from the start of therapy for physical functioning as well as role and cognitive functioning , global quality of life , fatigue and pain . In multivariate analysis , physical functioning and W.H.O. performance status were independent prognostic factors ( P values = 0.001 for both ) when analysed in a Cox regression model with the somatic variables beta-2 microglobulin , skeletal disease and age . The best prediction for survival from the start of therapy was obtained by combining the beta-2 microglobulin and physical functioning scores in a variable consisting of three risk factor levels with an estimated median survival of 17 , 29 and 49 months , respectively . At a 12 months l and mark analysis , the relative risk for patients with physical functioning score 0 - 20 v 80 - 100 was 5.63 ( 99 % CI 2.76 - 11.49 ) , whereas the relative risk for patients without an objective response to chemotherapy compared to those with at least a minor response was 2.32 ( 99 % CI 1.44 - 3.74 ) . Quality -of-life assessment may be an independent and valuable addition to the known prognostic factors in multiple myeloma Patients who undergo hematopoietic SCT ( HSCT ) often experience physical and psychological problems , even long after treatment has been completed . This study was performed to evaluate the effects of a 12-week outpatient physical exercise ( PE ) program , incorporating aerobic and strength exercises , as compared with a usual care control condition on patients ’ physical performance and psychosocial well-being . Patients who had completed HSCT up to 6 months earlier were r and omly assigned to a supervised PE program ( n=64 ) or a usual care control group ( n=67 ) . Primary outcomes were quantified physical performance and self-reported physical functioning . Secondary outcomes were body composition measurement , quantified walking activity and patient-reported outcomes ( physical activity , fatigue and health-related quality of life ) . Assessment s were at baseline , immediately after program completion and at 3-month follow-up . Significant intervention effects were observed at both posttreatment and follow-up on physical performance measures . No other outcomes yielded statistically significant group differences . PE should be considered in the management of HSCT recipients to improve physical performance after discharge from the hospital . Further research is needed to determine how the program can be enhanced so that improved physical performance also translates into improved physical and psychosocial functioning in daily life Few studies have evaluated long-term health-related quality of life ( HRQL ) in patients during auto-SCT . This prospect i ve study examined HRQL in 96 eligible patients before , during and up to 3 years after auto-SCT . The aim of the study was to make a comprehensive assessment of the frequency and severity of different symptoms in patients undergoing auto-SCT . The European Organization for Treatment and Research of Cancer Quality of Life Question naire ( EORTC QLQ C-30 ) was administered 13 times . The second week during treatment was the period when patients had the lowest HRQL regarding both total quality of life and function and symptom scales . The patients recovered quickly and just two months after transplantation the baseline values were restored . Three years after transplantation most of the items in the question naire had stabilized , except role function and dyspnea , which had improved . There were significant differences between multiple myeloma ( MM ) and lymphoma patients ’ physical function , quality of life , fatigue and pain during week 2 . At the 3-year follow-up , lymphoma patients indicated a better HRQL than MM patients . The quick recovery of patients after transplantation suggests that treatment is well tolerated ; however , the supportive care could be improved at week 2 , especially for the lymphoma patients Objective Long-term health-related quality of life ( HRQoL ) was determined for patients admitted to the haematology ward who needed intensive care treatment ( H-IC+ ) and compared with those who did not ( H-IC− ) as well as with that for patients admitted to the general ICU ( nH-IC+ ) . Methods A cross-sectional study was carried out median 18 months after admission by employing the short form-36 , checklist for individual strength , cognitive failure question naire and hospital anxiety and depression scale . Results 27 ( 79 % ) of the 34 H-IC+ patients approached , and 93 ( 85 % ) of the 109 H-IC− patients approached replied . Data were adjusted for relevant covariates and matched with those of 149 patients in the general ICU . Apart from the lower role-physical functioning score for H-IC+ ( P = 0.04 ) no other differences were found between H-IC+ and H-IC−. Groups H-IC+ and nH-IC+ evaluated their HRQoL on SF-36 similarly , except for the lower aggregated physical component summary ( PCS ) for H-IC+ ( P<0.0001 ) . After adjusting for PCS , no significant differences in CIS , CFQ and HADS were observed between the groups . Conclusions Eighteen months after admission , patients treated for haematological malignancies reported similar HRQoL , whether or not they had received intensive care treatment , but reported a lower PCS than those of patients in the general ICU . Hence , there is no reason to assume that admission to the ICU has a negative impact on long-term HRQoL , so this should not affect the decision whether or not to transfer patients with haematological malignancies to the ICU Allogeneic haematopoietic stem cell transplantation ( HSCT ) is an increasingly widespread therapy method . It is associated with many socio-psychological and physical risks . Forty-four subjects , who were clinical ly monitored at the Bolzano BMT Centre including a follow-up period of at least 3 months , completed the question naire Functional Assessment of Chronic Illness Therapy-Bone Marrow Transplantation ( version 4 ) . Semi-structured , problem-oriented interviews were conducted with seven r and omly selected subjects , the results of which were subjected to a summarising content analysis according to Mayring . The results from the quantitative and qualitative parts were compared based on triangulation . In the r and om sample , 22.7 % stated that they were highly satisfied with their current quality of life ( QOL ) . Throughout all dimensions of the question naire , women showed lower scores than men . The results revealed a positive correlation between the post-HSCT period and QOL ( r(s)=0.338 , P=0.025 ) , especially regarding the social/family ( r(s)=0.411 , P=0.006 ) and emotional well-being ( r(s)=0.306 , P=0.043 ) . The interviews primarily revealed dependence and inability to work . The support received from family , friends and hospital staff and the shift in priorities because of the transplantation were perceived as positive . The comparison mainly leads to corresponding results of the quantitative and qualitative parts of the study . Patient self-rating using question naires and interviews plays a direct and relevant role in the assessment of the QOL after allogeneic HSCT AIM The aim of this study was to compare the effect of two methods of rehabilitation after stem cell transplantation on health and quality of life . BACKGROUND Stem cell transplantation is routinely used in the treatment of haematological malignancy . However , it is an intensive treatment often associated with deterioration in wellbeing and the need for prolonged recovery . METHODS During a 14-month data collection period ( August 2005 to October 2006 ) , patients who had had a stem cell transplant ( n = 58 ) were r and omly allocated to either a healthcare professional-led rehabilitation programme or a self-managed rehabilitation programme . The primary outcome measure , physical functioning as measured by the 36-item Short Form Health Survey , was recorded at baseline and 6 months after r and omization . Secondary health and quality of life measures included the seven other dimensions of the 36-item Short Form Health Survey , General Health Question naire , Graham and Longman Quality of Life Scale and a Shuttle Walk Test . FINDINGS There was no difference in change in Short Form 36 physical functioning scores between the two groups at follow-up ( mean difference 0.19 points , 95 % confidence interval 10.77 - 11.16 ) . No evidence of a difference between the two modes of rehabilitation was observed for any of the trial outcomes . CONCLUSION One approach for providing a flexible service may be for staff and individual patients to work together , selecting from a series of specified options a programme with the appropriate content and duration to meet that individual 's needs PURPOSE To investigate the effect of recombinant human erythropoietin ( epoetin beta ) on anemia , transfusion need , and quality of life ( QOL ) in severely anemic patients with low- grade non-Hodgkin 's lymphoma ( NHL ) , chronic lymphocytic leukemia ( CLL ) , or multiple myeloma ( MM ) . PATIENTS AND METHODS Transfusion-dependent patients with NHL ( n = 106 ) , CLL ( n = 126 ) , or MM ( n = 117 ) and a low serum erythropoietin concentration were r and omized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks . Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival ( hemoglobin [ Hb ] > 8.5 g/dL ) between weeks 5 to 16 . Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need . QOL was assessed by the Functional Assessment of Cancer Therapy scale . RESULTS Transfusion-free ( P = .0012 ) survival and transfusion- and severe anemia-free survival ( P = .0001 ) were significantly greater in the epoetin beta group versus placebo ( Wald chi(2 ) test ) , giving a relative risk reduction of 43 % and 51 % , respectively . The response rate was 67 % and 27 % in the epoetin beta versus the placebo group , respectively ( P < .0001 ) . After 12 and 16 weeks of treatment , QOL significantly improved in the epoetin beta group compared with placebo ( P < .05 ) ; this improvement correlated with an increase in Hb concentration ( > or = 2 g/dL ) . A target Hb that could be generally recommended could not be identified . CONCLUSION Many severely anemic and transfusion-dependent patients with advanced MM , NHL , and CLL and a low performance status benefited from epoetin therapy , with elimination of severe anemia and transfusion need , and improvement in QOL Symptoms of traumatic stress are common in acute leukemia . The goal of the present qualitative study was to underst and this traumatic stress , as perceived by patients . Participants were 43 patients with acute leukemia in Toronto , Canada . Participants were asked in serial interviews about their experience of diagnosis and treatment . A total of 65 interviews were analyzed utilizing the grounded theory method . Our findings provide insight into the traumatic experience of the diagnosis and treatment , as well as the initial psychological response to this trauma . Patients coped by surrendering control to the medical team , in whom they felt great trust . Patients also expressed a strong preference for limited information , with a preference to avoid discussion s about overall prognosis . These results may inform interventions to relieve traumatic stress in this high risk population CONTEXT There are few r and omized controlled trials on the effectiveness of palliative care interventions to improve the care of patients with advanced cancer . OBJECTIVE To determine the effect of a nursing-led intervention on quality of life , symptom intensity , mood , and re source use in patients with advanced cancer . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted from November 2003 through May 2008 of 322 patients with advanced cancer in a rural , National Cancer Institute- design ated comprehensive cancer center in New Hampshire and affiliated outreach clinics and a VA medical center in Vermont . INTERVENTIONS A multicomponent , psychoeducational intervention ( Project ENABLE [ Educate , Nurture , Advise , Before Life Ends ] ) conducted by advanced practice nurses consisting of 4 weekly educational sessions and monthly follow-up sessions until death or study completion ( n = 161 ) vs usual care ( n = 161 ) . MAIN OUTCOME MEASURES Quality of life was measured by the Functional Assessment of Chronic Illness Therapy for Palliative Care ( score range , 0 - 184 ) . Symptom intensity was measured by the Edmonton Symptom Assessment Scale ( score range , 0 - 900 ) . Mood was measured by the Center for Epidemiological Studies Depression Scale ( range , 0 - 60 ) . These measures were assessed at baseline , 1 month , and every 3 months until death or study completion . Intensity of service was measured as the number of days in the hospital and in the intensive care unit ( ICU ) and the number of emergency department visits recorded in the electronic medical record . RESULTS A total of 322 participants with cancer of the gastrointestinal tract ( 41 % ; 67 in the usual care group vs 66 in the intervention group ) , lung ( 36 % ; 58 vs 59 ) , genitourinary tract ( 12 % ; 20 vs 19 ) , and breast ( 10 % ; 16 vs 17 ) were r and omized . The estimated treatment effects ( intervention minus usual care ) for all participants were a mean ( SE ) of 4.6 ( 2 ) for quality of life ( P = .02 ) , -27.8 ( 15 ) for symptom intensity ( P = .06 ) , and -1.8 ( 0.81 ) for depressed mood ( P = .02 ) . The estimated treatment effects in participants who died during the study were a mean ( SE ) of 8.6 ( 3.6 ) for quality of life ( P = .02 ) , -24.2 ( 20.5 ) for symptom intensity ( P = .24 ) , and -2.7 ( 1.2 ) for depressed mood ( P = .03 ) . Intensity of service did not differ between the 2 groups . CONCLUSION Compared with participants receiving usual oncology care , those receiving a nurse-led , palliative care-focused intervention addressing physical , psychosocial , and care coordination provided concurrently with oncology care had higher scores for quality of life and mood , but did not have improvements in symptom intensity scores or reduced days in the hospital or ICU or emergency department visits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00253383 Abstract In lower-risk myelodysplastic syndromes ( MDS ) with del(5q ) , lenalidomide induces erythroid responses associated with better survival . In a phase II , single-arm trial , 45 patients with anemia and lower-risk del(5q ) MDS received lenalidomide 10 mg/day to evaluate quality of life ( QoL ) changes , measured by QOL-E , safety , responses and survival . Lenalidomide was well tolerated , with 80 % completing ≥ 24 weeks of treatment . Earlier study discontinuation was related to disease progression ( n = 5 ) , death ( n = 1 ) and withdrawal of consent ( n = 3 ) . Within 24 weeks , 82 % obtained erythroid responses , durable in 69 % at 52 weeks . Cytogenetic responses occurred in 29 patients ( 64 % ) , with 10 patients achieving a complete cytogenetic response . QoL-E scores correlated with hemoglobin levels and improved in erythroid responders . Erythroid responders had an 86 % reduced risk of disease progression and an 80 % reduction in mortality risk compared with non-responders . These findings corroborate earlier studies and give further support to the use of lenalidomide in lower-risk MDS and del(5q ) OBJECTIVES To investigate the subjective well-being of patients with newly diagnosed multiple myeloma who were treated in a t and em transplantation programme . METHODS Fifty-one patients participated in the prospect i ve , longitudinal question naire study . The EORTC QLQ-C30 and the EuroQol-5D were administered 2 wk after completion of vincristine , adriamycin and dexamethason/vincristine , adriamycin and methyl prednison ( VAD/VAMP ) chemotherapy , both at hospital discharge after treatment with high-dose melphalan ( HDM ) and 1 month after this hospital discharge , at hospital admission , at the day of hospital discharge for peripheral stem cell transplantation ( PSCT ) and at 6 and 12 months following discharge after PSCT . RESULTS Overall , patients ' functioning improved during treatment and follow-up , with significant decreases shortly following PSCT . Shortly after HDM and PSCT , patients reported a considerable increase in levels of soreness in the mouth ( + 26/+36 points on a scale ranging form 0 to 100 ; P < 0.01 ) , change of taste ( + 23/+21 points ; P < 0.05/NS ) , nausea/vomiting ( + 26/+27 points ; P < 0.01/ < 0.05 ) , appetite loss ( + 40/+43 points ; P < 0.001 ) and diarrhoea ( + 25/+36 points ; P < 0.01 ) . However , none of these symptoms persisted during follow-up . CONCLUSION The intensive treatment programme was subjectively being well tolerated by the majority of patients . The duration of declined quality of life after administration of HDM seemed to be short . The duration of subjective recovery after PSCT remained uncertain , but in any case was present at the 6 month follow-up . Together with the rather good results in survival , the evaluation of quality of life invites further exploration of double transplantations in multiple myeloma BACKGROUND Compared with placebo , prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma . However , because of toxicity associated with long-term bisphosphonate treatment , establishing the lowest effective dose is important . This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma . METHODS This double-blind , r and omised , phase 3 trial was undertaken at 37 clinics in Denmark , Norway , and Sweden . Patients with multiple myeloma who were starting antimyeloma treatment were r and omly assigned in a 1:1 ratio to receive one of two doses of pamidronate ( 30 mg or 90 mg ) given by intravenous infusion once a month for at least 3 years . R and omisation was done by use of a central , computerised minimisation system . Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire ( scale 0 - 100 ) . All patients who returned question naires at 12 months and were still on study treatment were included in the analysis of the primary endpoint . This study is registered with Clinical Trials.gov , number NCT00376883 . FINDINGS From January , 2001 , until August , 2005 , 504 patients were r and omly assigned to pamidronate 30 mg or 90 mg ( 252 in each group ) . 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis . Mean physical function at 12 months was 66 points ( 95 % CI 62·9 - 70·0 ) in the 90 mg group and 68 points ( 64·6 - 71·4 ) in the 30 mg group ( 95 % CI of difference -6·6 to 3·3 ; p=0·52 ) . Median time to first skeletal-related event in patients who had such an event was 9·2 months ( 8·1 - 10·7 ) in the 90 mg group and 10·2 months ( 7·3 - 14·0 ) in the 30 mg group ( p=0·63 ) . In a retrospective analysis , eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group . INTERPRETATION Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma . FUNDING Nordic Cancer Union and Novartis Healthcare OBJECTIVE The aim was to prospect ively measure quality of life in patients with malignant blood disorders following stem cell transplantation ( SCT ) using an individualized and a st and ardized measure . METHODS Twenty-two consecutive patients were assessed before and one year following SCT , using a generic and disease-related version of the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting ( SEIQoL-DW ) and the EORTC QLQ-C30 . Results of the QLQ-C30 were compared with Swedish norm values . RESULTS A majority of the patients reported concerns related to health before as well as one year after SCT , recorded by both instruments . Mean scores produced by the SEIQoL-DW , and four scales of the EORTC QLQ-C30 , showed a change over time , indicating improved quality of life one year after SCT . In comparison with Swedish norm values for the EORTC QLQ-C30 , SCT recipients reported a worse functioning . CONCLUSIONS In addition to well-known disease and treatment-related problems , areas not typically included in st and ardized instruments were nominated in the disease-related SEIQoL-DW . Such areas included positive aspects , e.g. a changed view of life and oneself . The results support the use of the generic and disease-related SEIQoL-DW to achieve a comprehensive picture of patient 's clinical situation under treatment or when recovering from illness BACKGROUND Anemia is common in myeloproliferative neoplasm (MPN)-associated myelofibrosis . The Functional Assessment of Cancer Therapy ( FACT ) measurement system is a patient-reported outcomes instrument that documents symptoms of the diverse aspects of cancer treatment . One FACT version , FACT-Anemia ( FACT-An ) , documents symptoms of anemia related to cancer . The FACT-An has been vali date d in diverse cancer population s , but not in MPN-associated myelofibrosis . OBJECTIVE Our aim was to evaluate the relationship between anemia response to therapy with pomalidomide with or without corticosteroids and patient-reported outcomes using the FACT-An instrument . METHODS Data were obtained from a Phase II , r and omized , double-blind Bayesian pick-the-winner trial of prednisone and pomalidomide in patients with MPN-associated myelofibrosis and anemia ( red blood cell-transfusion dependence ) . Details of the study , including definitions of anemia , anemia response , red blood cell-transfusion , red blood cell-transfusion dependence , and red blood cell-transfusion independence , are reported . Change in quality of life from r and omization to the last cycle of therapy was evaluated using the FACT-An Physical Well Being , Functional Well Being , Trial Outcome Index , and Anemia domains . Clinical ly important differences were used to determine the smallest difference in scores that patients perceived as beneficial in the FACT-An domains of interest . Patients were classified as meeting clinical ly important differences for responsiveness if their change score from baseline was > 1 SEM , indicating improvement . RESULTS Eighty-five patients were studied . Thirty-one patients ( 37 % ) were classified as anemia responders by prospect ively defined criteria . Across all FACT-An domains , anemia responders showed greater improvement in Physical Well Being , Functional Well Being , and Trial Outcome Index scores than did nonresponders . This improvement began at the second 28-day cycle of therapy and was sustained . CONCLUSIONS We show a correlation between anemia response and improved quality of life measured by the FACT-An instrument in patients with MPN-associated myelofibrosis and anemia Background Precisely defining the different applications of patient-reported outcome measures ( PROs ) in clinical practice can be difficult . This is because the intervention is complex and varies amongst different studies in terms of the type of PRO used , how the PRO is fed back , and to whom it is fed back . Methods A theory-driven approach is used to describe six different applications of PROs in clinical practice . The evidence for the impact of these applications on the process and outcomes of care are summarised . Possible explanations for the limited impact of PROs on patient management are then discussed and directions for future research are highlighted . Results The applications of PROs in clinical practice include screening tools , monitoring tools , as a method of promoting patient-centred care , as a decision aid , as a method of facilitating communication amongst multidisciplinary teams ( MDTs ) , and as a means of monitoring the quality of patient care . Evidence from r and omised controlled trials suggests that the use of PROs in clinical practice is valuable in improving the discussion and detection of HRQoL problems but has less of an impact on how clinicians manage patient problems or on subsequent patient outcomes . Many of the reasons for this may lie in the ways in which PROs fit ( or do not fit ) into the routine ways in which patients and clinicians communicate with each other , how clinicians make decisions , and how healthcare as a whole is organised . Conclusions Future research needs to identify ways in with PROs can be better incorporated into the routine care of patients by combining qualitative and quantitative methods and adopting appropriate trial design CONTEXT Multiple myeloma ( MM ) is a common hematologic malignancy and is associated with symptom burden and impairments in health-related quality of life ( HRQL ) . OBJECTIVES To develop a disease-specific , patient-reported outcome ( PRO ) measure for the assessment of HRQL among patients with MM as part of the Functional Assessment of Cancer Therapy ( FACT ) measurement system . METHODS HRQL concerns and symptoms associated with MM were tabulated based on a literature review , and 52 c and i date PRO items were identified . Expert clinicians ( n=13 ) rated 52 items on relevance to HRQL for MM patients ( 0 - 3 scale ) . Experts added 11 items for comprehensive PRO assessment in MM . A list of 63 c and i date items was rated ( 0 - 3 scale ) by 13 MM patients enrolled through the International Myeloma Foundation website . Qualitative data and quantitative item ratings were review ed to select FACT-MM scale items . RESULTS Expert clinicians provided the highest HRQL relevance ratings for bone pain , bodily pain , difficulty walking ( 2.9 ) , tiring easily ( 2.6 ) , feeling discouraged ( 2.5 ) , interference with activities and difficulty with self-care as a result of bone pain ( 2.5 ) , and fatigue ( 2.5 ) . Mean age of patients was 57 years ; Eastern Cooperative Oncology Group performance status was 0 ( 38 % ) , 1 ( 31 % ) , or 2 ( 31 % ) . Quantitative ratings by patients identified sexual function ( 1.3 ) , uncertainty about health ( 1.2 ) , fatigue ( 1.0 ) , weight gain ( 1.0 ) , and emotional concerns , such as worry about new symptoms and difficulty planning for the future ( 1.0 ) as most relevant to HRQL . CONCLUSION The 14-item FACT-MM PRO measure was developed based on expert clinician and patient data , ensuring relevance to HRQL for MM patients In a population -based study , the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age ( risk ratio : 1.62 ; confidence interval [ CI ] 1.22–2.15 ; p=0.001 ) . A study of health-related quality of life ( HRQoL ) was integrated in the trial , using the EORTC QLQ-C30 question naire . Of the 274 patients receiving intensive therapy 221 ( 81 % ) were compared to 113 ( 94 % ) of 120 patients receiving conventional melphalan-prednisone treatment . Prior to treatment , there were no statistically significant differences in any HRQoL score between the two groups . One month after the start of induction chemotherapy , the patients on intensive treatment had more sleep disturbance than the control patients . At 6 mo , corresponding to a mean of 52 d after high-dose melphalan , the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss . At 12 and 24 mo , the HRQoL was similar to that of the control patients . At 36 mo , there was a trend toward less fatigue , pain , nausea , and appetite loss in the intensive-treatment group . Thus , the 18 mo of prolonged survival seem to be associated with a good health-related quality of life . Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase , this treatment modality must be regarded as an important step forward in the care of multiple myeloma PURPOSE / OBJECTIVES To examine the patterns of fatigue , physical activity , health status , and quality of life before and after high-dose chemotherapy and hematopoietic stem cell transplantation ( HSCT ) and to examine the feasibility of obtaining real-time fatigue and physical activity data . DESIGN Prospect i ve , repeated measures . SETTING Two midwestern academic medical centers . SAMPLE Convenience sample of autologous or allogeneic patients undergoing HSCT ( N = 20 baseline , N = 17 post-transplant ) . METHODS Subjects were assessed over a five-day period before and after HSCT for a total of 10 days . Subjects rated fatigue intensity three times daily and wore a wrist actigraph to measure physical activity . At the end of both five-day periods , subjects completed measures of perceived health status ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ) and life satisfaction Quality of Life Index ) . MAIN RESEARCH VARIABLES Fatigue , physical activity , perceived health status , and quality of life . FINDINGS Study results indicate that fatigue significantly increased and physical activity decreased following high-dose chemotherapy and HSCT . The decline coincided with diminished physical , emotional , role , and cognitive functioning . The symptoms that patients experienced ( i.e. , fatigue , pain , nausea and vomiting , sleep disturbances , appetite loss , and diarrhea ) increased during the acute post-transplant period . No significant changes in life satisfaction were found . CONCLUSIONS The study findings suggest that patients receiving high-dose chemotherapy followed by HSCT experience increased fatigue , reduced physical activity , diminished functioning , and poorer quality of life immediately after transplant . Findings demonstrate that real-time fatigue and physical activity data can feasibly be collected in acutely ill patients . IMPLICATION S FOR NURSING Patients undergoing HSCT require considerable supportive nursing care immediately following transplant . Clinicians and research ers need to strive for effective symptom management to improve the likelihood of successful outcomes Abstract Quality of life ( QoL ) is an important outcome in patients with non-Hodgkin lymphoma ( NHL ) . We assessed the validity of administering the Functional Assessment of Cancer Therapy – General ( FACT-G ) at 12-month intervals over 3 years in a longitudinal study of 611 prospect ively enrolled , newly diagnosed patients with NHL . We evaluated corrected item-total correlation and percent missing to identify items that may be less useful in certain NHL patient subgroups . The FACT-G subscales and total score demonstrated good internal consistency reliability , convergent validity and known-groups validity . Most scores also demonstrated good responsiveness to change . Questions that could be problematic included GE3 ( losing hope ) and GP2 ( nausea ) for patients in remission , and GP5 ( bothered by side effects ) for patients being observed . Overall , the FACT-G was a valid measure for monitoring QoL over time in patients with NHL . However , sensitivity analyses based on subscale scoring that excludes potentially problematic items may be warranted High-dose melphalan and autologous hematopoietic stem cell transplantation ( HSCT ) is a st and ard treatment for myeloma , but very little is known about the psychosocial or quality -of-life difficulties that these patients encounter during treatment . Data regarding older patients is particularly scarce . Using a prospect i ve design , this investigation evaluated 94 patients at stem cell collection and again after high-dose therapy and transplantation . Outcomes included quality -of-life ( FACT-BMT ) and psychosocial adjustment ( ie , Brief Symptom Inventory , Impact of Events Scale , and Satisfaction with Life Scale ) . Findings were compared with age- and sex-adjusted population norms and with transplantation patient norms . At stem cell collection , physical deficits were common , with most patients scoring 1 st and ard deviation below population norms for physical well-being ( 70.2 % ) and functional well-being ( 57.5 % ) , and many reporting at least moderate fatigue ( 94.7 % ) and pain ( 39.4 % ) . Clinical ly meaningful levels of anxiety ( 39.4 % ) , depression ( 40.4 % ) , and cancer-related distress ( 37.0 % ) were evident in a notable proportion of patients . After transplantation , there was a worsening of transplant-related concerns ( P < .05 ) , depression ( P < .05 ) , and life-satisfaction ( P < .001 ) ; however , pain improved ( P < .01 ) , and social functioning was well preserved . Overall , the declines in functioning after transplantation were less pronounced than anticipated . Older patients were not more compromised than younger ones ; in multivariate analyses , they reported better overall quality of life ( P < .01 ) and less depression ( P < .05 ) before transplantation . Our findings emphasize the importance of early screening and intervention |
2,458 | 20,556,758 | We conclude that at present there is insufficient evidence for the effectiveness of most of the interventions used in the primary prevention of OIHD . | BACKGROUND Occupational irritant h and dermatitis ( OIHD ) is an important cause of discomfort in the working population .
Different preventive measures are in place but it is not clear how effective these are .
OBJECTIVES To assess the effect of interventions for preventing OIHD in healthy people who work in occupations where the skin is at risk of damage . | Background Workers in wet work occupations have a risk for developing h and eczema . Prevention strategies exist , but compliance to the proposed recommendations is poor . Therefore , a multifaceted implementation strategy ( MIS ) is developed to implement these recommendations to reduce h and eczema among health care workers performing wet work . Methods / Design This study is a r and omised controlled trial in three university hospitals in the Netherl and s. R and omisation to the control or intervention group is performed at department level . The control group receives a leaflet containing the recommendations only . The intervention group receives the MIS which consists of five parts : 1 ) within a department , a participatory working group is formed to identify problems with the implementation of the recommendations , to find solutions for it and implement these solutions ; 2 ) role models will help their colleagues in performing the desired behaviour ; 3 ) education to all workers will enhance knowledge about ( the prevention of ) h and eczema ; 4 ) reminders will be placed at the department reminding workers to use the recommendations ; 5 ) workers receive the same leaflet as the control group containing the recommendations . Data are collected by question naires at baseline and after 3 , 6 , 9 and 12 months . The primary outcome measure is self-reported h and eczema . The most important secondary outcome measures are symptoms of h and eczema ; actual use of the recommendations ; sick leave ; work productivity ; and health care costs . Analyses will be performed according to the intention to treat principle . Cost-effectiveness of the MIS will be evaluated from both the societal and the employer 's perspective . Discussion The prevention of h and eczema is important for the hospital environment . If the MIS has proven to be effective , a major improvement in the health of health care workers can be obtained . Results are expected in 2014.Trial registration The object of this study was to compare the protective action of a new barrier cream ( Excipial Protect ® , Spirig Pharma AG , Egerkingen , Switzerl and ) to its vehicle in the context of h and irritation of apprentice hairdressers caused by repeated shampooing and exposure to hair‐care products . This was a double‐blind cross‐over comparing Excipial Protect ® ( containing aluminium chlorohydrate 5 % as active ingredient ) against its vehicle alone . The efficacy of the creams was evaluated taking into account : ( 1 ) clinical scores by research ers , ( 2 ) biometric measurements , ( 3 ) subjective opinions of the subjects . An analysis of variance was performed considering order of application , degree of atopy , and reported number of shampoos . We observed very little difference in efficacy between the protective cream and its vehicle . The presence , however , of aluminium chlorhydrate in the protective cream was shown to have a positive effect against work‐related irritation . The cosmetic qualities of the creams seemed , to the participants , to be as important as their real protective and hydrating properties , an important factor in compliance issues The purpose of this study was to develop a new model for the induction of chronic irritant contact dermatitis , which would reflect well the conditions of daily practice . Various weak irritant agents were tested for irritating potency on the skin and the sensitivity of transepidermal water loss ( TEWL ) measurements in the detection of early skin changes was also studied . 10 widely used surfactants and 1 solubilizer were applied to the skin of the forearms of healthy volunteers in aqueous solutions of 12.5 millimoles/1 for 45 min twice daily for 3 weeks . The effect on the skin was evaluated daily by means of TEWL measurements and by a visual scoring system . Each solution caused an increase in TEWL value over time due to the cumulative irritating action on the epidermal barrier . This increase in TEWL was different for the various solutions , result ing in different mean TEWL values on the last day of the experiment . Thus , it was possible to rank the agents according to irritating potency . This ranking order was the same in almost every individual and remained constant during the 3 weeks . In comparison with the visual scoring system , the TEWL measurements were more sensitive in the detection of early changes in the skin A cohort of initially 111 office apprentices was prospect ively followed for the duration of their training ( 2 and 3 years , respectively ) . The point prevalence of ( slight ) irritant or atopic h and eczema was 18.9 % in the initial and 25.0 % in the final examinations . Altogether , 37 cases of ( slight ) h and eczema were noted within the study period ; of these , 10 qualified for a more conservative definition of " h and eczema " . Expressed in a person-time-model , the incidence rates were 18.4 and 4.1 cases per 100 persons per year , respectively . The only significant risk factor for the development of ( slight ) irritant or atopic h and eczema within the study period was previous h and eczema -- partly as a child , partly during a preceding occupation ( e.g. hairdressing ) . Compared to one retrospective study in a cohort of older office employees and to a study sampling the general population , incidence rates were slightly higher in this study . Such differences may partly be due to different definitions of what has to be considered " a case of h and eczema " . The necessity to ( i ) communicate on the method of case definition and ( ii ) develop guidelines for case definition in epidemiological studies is emphasised An in vivo method was developed to measure the effectiveness of skin protective creams against 2 dye indicator solutions : methylene blue in water and oil red O in ethanol , representative of model hydrophilic and lipophilic compounds , 3 representative barrier creams commercialized as effective against lipophilic , hydrophilic , or lipophilic and hydrophilic substances were assayed by measurements of the dye in cyanoacrylate strips of protected skin sample s after various application limes . The flexural surfaces of the forearms of 6 normal volunteers ( 3 female and 3 male , mean age 26.8±4.1 years ) were treated . The method was as follows : solutions of 5 % methylene blue in water and 5 % oil red O in ethanol were prepared , and applied to untreated skin and protective‐cream‐pretreated skin with the aid of aluminum occlusive chambers , for 0 h and 4 h , respectively . At the end of the application time , the creams were removed . Consecutive skin surface biopsies ( SSB ) from 1 to 4 strips were taken . The amount of stain in each strip was determined by colorimetry , and the cumulative amount of stain from 1 to 4 strips in each measurement was calculated . The cumulative amount represents the amount of permeation of each solution at each time point , and the efficacy of skin barrier cream . The results showed one formulation at both 0 h and 4 h reduced the amount of permeation of melhylene blue ( p<0.0l ) and oil red O ( p<0.01 ) compared with the control group . Another formulation was protective against the permeation of oil red O ( p < 0.0l ) . but not against methylene blue at 0 h and 4 h ; it was not significantly different at 0 h versus 4 h. The 3rd formulation produced increased cumulative amounts to oil red O at both 0 h and 4 h ( p<0.05 ) ; it also increased permeation amounts to methylene blue ( p<0.05 ) after 4 h. This model appears a facile , rapid and objective early screen to evaluate the efficacy of skin barrier creams in vivo , as well as their individual ingredients Objective . The objective of this controlled intervention study was to quantify the efficacy of skin protection ( SP ) measures and ultraviolet B ( UVB ) hardening in the prevention of h and dermatitis in bakers ' apprentices . Method . SP measures were compared against UVB hardening in a controlled clinical trial of 94 apprentices . The apprentices were assigned to the intervention arms class-wise . Bakers ' apprentices involved in a previous follow-up study served as additional controls representing no intervention . The apprentices were interviewed and examined in a st and ardised way at the beginning of the training and at 4 monthly follow-ups . Transepidermal water loss ( TEWL ) was measured at the back of the h and s. Results . Demographic profile and atopy criteria were equally distributed in the two intervention arms and the control group . Point prevalence of h and dermatitis after 6 months was highest in the controls ( 29.1 % ) followed by the UVB ( 19.4 % ) and the SP group ( 13.3 % ) . UVB hardening and SP measures reduced h and dermatitis prevalence by 9.7 % ( 95%CI : –8.5 to 28.1 ) and 15.7 % ( 95%CI : –2.4 to 33.9 ) , respectively . Application of SP measures reduced the odds ratios ( ORs ) for h and dermatitis 0.8-fold ( 95%CI : 0.17–3.70 ) and 0.33-fold ( 95%CI : 0.09–1.23 ) compared with the UVB group and the controls , respectively . These clinical trends were confirmed by statistically significant differences in TEWL values . TEWL values were consistently higher in the UVB group than in the SP group ( P=0.002 ) . Conclusions . This study provided evidence , based on significant differences in TEWL levels , that general SP measures may be more effective than UV light hardening of the skin , which in turn was more effective than no intervention . This trend was supported by the frequency of development of clinical h and dermatitis , although differences did not reach statistical significance . A multi-centre trial is recommended to confirm the efficacy of SP measures in a larger r and omised study An improved human model for the quantification of skin barrier creams ( BCs ) is described . In contrast to the previously published procedure , the back , instead of the forearm , and a total of 4 irritants are used . Due to the larger area , 3 BC formulations can be simultaneously compared to the control field , which receives the irritant only , without BC‐pretreatment . On 10 human volunteers , the irritants 10 % sodium lauryl sulfate ( SLS ) , 1 % sodium hydroxide ( NaOH ) , 30 % lactic acid ( LA ) and undiluted toluene ( TOL ) were applied via large Finn Chambers for 30 min , 5 × during the 1st week and 4 × during the 2nd week . Taktosan Salbe ( water‐in‐oil emulsion ) and RAWI Speerschutzcreme ( oil‐in‐water emulsion ) were applied 30 min before contact with the irritants . In order to asses reproducibility and interindividual variation , the BC RAWI was tested in duplicate . Irritant cutaneous reactions were quantified by 4 parameters : erythema score , transepidermal water loss , blood flow volume and stratum corneum hydration by measuring capacitance . The results showed marked differences in efficacy . Taktosan significantly suppressed irritation by SLS , NaOH and LA , which was apparent in nearly all parameters . RAWI caused significant inhibition of SLS irritation , and a positive trend against NaOH and LA was observed . Both BCs failed against TOL . The results of duplicate testing with RAWI showed good reproducibility . The dogma that oil‐in‐water emulsions are primarily effective against lipophilic irritants , and water‐in‐oil emulsions against hydrophilic irritants , needs to be re‐evaluated on the basis of our findings . This model seems to have potential for further studies on BCs and might eluci date the complex interaction of BCs with irritants Skin harrier function was studied after use of occlusive gloves on normal and compromised skin . 2 studies were performed ( Study A and B ) , and the effects were evaluated by non‐invasive methods . Participants in the studies were instructed to wear an occlusive glove on one h and , while the other h and served as control . The gloves used were hypoallergenic , non‐latex . Study A : 20 volunteers wore a glove on normal skin 6 h/day for 3 days . Study B : 20 volunteers wore a glove on sodium fauryl sulfa lei S LSI‐compromised skin 6 h/day for 3 days . Skin harrier function was evaluated by measurement of transepidermal water loss ( TEWL ) ( Evaporimeter ) , skin hydration by electrical capacitance ( Corneometer ) and inflammation was evaluated by erythema index ( DermaSpetrometer ) . Results : Study A. Glove occlusion on normal skin 6 h/day for 3 days caused no significant influence on the water barrier function . Study B : Glove occlusion on SLS‐compromised skin for the same period of time had a significantly negative effect on the water barrier function . It is concluded that occlusion may be an additional factor in the pathogenesis of cumulative irritant contact dermatitis Moisturizers are used daily by many people to alleviate symptoms of clinical ly and subjectively dry skin . Recent studies suggest that certain ingredients in creams may accelerate the recovery of a disrupted barrier and decrease the skin susceptibility to irritant stimuli . In the present single‐blind study , a moisturizing cream was tested for its influence both on barrier recovery in surfuctant‐damaged skin and on the susceptibility of normal skin to exposure to the irritant sodium lauryl sulphate ( SLS ) . Parameters measured were transepidermal water loss ( TEWL ) and skin corneometer values , indicating degree of hydration . Treatment of surfactant‐damaged skin with the test cream for 14 days promoted barrier recovery , as observed as a decrease in TEWL . Skin corneometer values also normalized more rapidly during the treatment . In normal skin , use or the test cream significantly reduced TFWL after 14 days of treatment , and irritant reactions to SLS were , significantly decreased . Skin corneometer values increased after only 1 application and remained elevated after 14 days . In conclusion , the accelerated rate of recovery of surfactant‐damaged skin and the lower degree of SLS‐induced irritation in normal skin treated with the test cream may be of clinical relevance in attempts to reduce contact dermatitis due to irritant stimuli The occurrence of h and eczema in an industrial city was studied . Question naires were sent to 20000 individuals aged 20–65 years , r and omly selected from the population register of the city . After two reminders , a response rate of 83 % was obtained . Analysis of the drop‐outs did not indicate that the presence of h and eczema was an important selection factor for response to the question naire . Those subjects considering themselves to have had h and eczema within the previous 12 months were invited to a dermatological examination to verify the diagnosis and for further investigation . Seventy‐one per cent accepted the invitation . Analysis of drop‐outs showed that willingness to attend the dermatological examination was to some extent dependent on the severity of the h and eczema Aims : To evaluate the effect of an intervention to reduce work related skin problems in gut cleaning departments in Danish swine slaughterhouses . The intervention consisted of an evidence based prevention programme and a documented method for implementation . Methods : R and omised controlled intervention study with a one year follow up . The intervention included educational activities and evidence based recommendations . The effect of the intervention was evaluated by telephone interviews using a st and ardised question naire based on the Nordic Occupational Skin Question naire ( NOSQ-2002 ) with modified and additional questions on exposure , preventive measures , information , and discussion s on prevention of skin problems , etc . Results : A total of 644 ( 87.5 % ) responded at the baseline interview and 622 ( 71.6 % ) at the one year follow up interview . A total of 495 participated in both interviews ( 67.3 % ) . In the intervention departments the frequency of eczema on h and s or forearms within the past three months at follow up was reduced significantly from 56.2 % at baseline to 41.0 % at follow up , while a slight non-significant increase was observed in the comparison departments ( from 45.9 % to 50.2 % ) . The intervention activities result ed in more frequent use of protective gloves in general and the use of cotton gloves worn underneath rubber and plastic gloves . At follow up three times as many in the intervention departments used the recommended high fat skin care products introduced as part of the intervention activities . At follow up , discussion of skin problems was increased in the intervention group while no changes were observed in the comparison group . Conclusions : A significant 27 % relative reduction of occupational eczema in a high risk group was feasible through implementation of an evidence based prevention programme Eczematous skin disease is a serious work-related illness . Since 1995 , reimbursement by insurance companies for treatment of skin diseases has become the largest cost source in some countries . This study was a r and omized controlled trial ( N = 20 ) of the efficacy of Pro-Q , a skin protectant product , in the prevention of contact dermatitis from sodium lauryl sulfate and urushiol , the resinous sap of poison ivy and poison oak . Pro-Q was significantly effective in reducing the irritation from sodium lauryl sulfate but did not prevent the allergic reaction to urushiol In the present work a practical cl aim substantiation study is shown by the example of 5 commercially available body lotions . Their efficacy with respect to effects on transepidermal water loss ( TEWL ) and stratum corneum ( SC ) hydration of ageing skin has been examined . Results were obtained after single and repeated application ( 14 days , 2 × a day ) . The best performing product was then selected and further tested for its potential effects on sodium lauryl sulfate (SLS)‐damaged skin . This was done in a younger population and the recovery of the impaired barrier function was followed by TEWL measurements . The selected body lotion had a high efficacy , improving both the TEWL and SC hydration of ageing skin by more than 30 % . When applied to SLS‐damaged skin , the product was able to improve skin barrier repair in comparison with physiological barrier repair . The results of this study show that a combination of non‐invasive objective measurements can be used to substantiate product cl aims . Cl aims can be made with respect to protective and preventive properties of products , but also as to effectiveness of topical skin treatment in the case of abnormal barrier function or barrier restoration The effect of a moisturizer was tested on experimentally irritated human skin in two studies . In a prevention study , 12 volunteers had both h and s immersed into a 0.375 % sodium lauryl sulphate solution , 10 min twice daily for 2 days . Before each immersion one h and was treated with the moisturizer ; the other h and served as control . In a therapeutic study , 12 volunteers had both h and s immersed in the same way as mentioned above . After the last immersion one h and was treated for 5 days with the moisturizer ; the other h and served as control . Skin barrier function was evaluated by transepidermal water loss ( Evaporimeter ) , and blood flow was evaluated by laser Doppler flowmetry and skin hydration by electrical capacitance ( Corneometer ) . A significant preventive effect was obtained on the treated h and , compared to the control h and , judged by all measured parameters . A significant therapeutic effect was observed on skin barrier function and on skin hydration on the treated h and , compared to the control h and , while no difference between the h and s in blood flow was observed after the end of treatment . The moisturizer could prevent irritant skin reactions induced by a detergent , and it could also accelerate regeneration of the barrier function of irritated skin Objectives The aim of the trial was to investigate whether the publicized effects of skin protection creams can be replicated in a real occupational setting during activities that expose the skin . Methods A prospect i ve , r and omized , four-tailed controlled pilot trial was performed to compare the effect of skin protection and skin care alone or in combination with cleansing against a control group ( only cleansing ) . Two branches were selected for the investigation : the building industry and the timber industry . A total of 1,006 workers from these two branches were recruited , and out of these 485 workers were examined longitudinally for at least three time points over 1 year ( lost for follow-up : 430 workers , exclusion : 91 workers ) . At each time point , as a primary outcome measure , we assessed the condition of the skin at both h and s in a blinded manner and the individual was assigned to one of the following categories : no eczema , mild , moderate and severe eczema . As a secondary outcome measure , the worker ’s transepidermal water loss ( TEWL ) was measured under st and ardized conditions at the back of both h and s. In addition , the workers were asked to evaluate their skin condition during the study . Results With regard to differences in the occurrence of eczemas , we found only in workers in building industry without application of skin protection or skin care creams a statistical significant increase in the incidence between the first and the second visit and a statistical significant decrease in the incidence between the second and third visit . When evaluating the secondary outcome -measurement changes in the TEWL values , an improvement was found for the group skin protection and skin care in combination and by skin care alone . Females in the timber industry started with better TEWL values than males , which may be due to better overall skin care . In this group we found an improvement for the group skin protection and skin care in combination and by skin protection alone . For skin protection alone , we noted a slight , but not significant improvement in all other groups . The subjective improvement of skin condition was reported from the participants who used skin protection and skin care in combination . Conclusions Taking all these secondary - outcome measurements together , the main result of this study was that skin protection creams alone have a small effect on the skin barrier in workers in the building and timber industries compared with skin care alone or in combination with skin protection OBJECTIVES The role of atopic constitution , contact sensitization , transepidermal water loss , and dry skin in the development of h and dermatitis was investigated in a prospect i ve study of 74 apprentice hairdressers and 111 apprentice nurses . METHODS Base-line measurements included a question naire on personal characteristics and anamnestic information , examination of h and skin , measurements of transepidermal water loss , patch tests , and prick tests . The condition of the h and s , previous exposure , and transepidermal water loss were followed at intervals of four to six weeks . Cox proportional hazard models were used in the statistical analysis . RESULTS The average incidence rate of h and dermatitis was 32.8 cases per 100 person-years for the hairdressers and 14.5 cases per 100 person-years for the nurses . The rate ratio of having a dry versus normal skin type was 7.3 for the hairdressers [ 95 % confidence interval ( 95 % CI ) 2.2 - 24.3 ] and 1.7 for the nurses ( 95 % CI 0.5 - 6.4 ) . Apprentice nurses with a history of ( atopic ) mucosal symptoms had a 3.4-fold increased incidence rate of h and dermatitis ( 95 % CI 1.05 - 11.2 ) . The rate ratio of mucosal atopy for the apprentice hairdressers was 2.2 ( 95 % CI 0.7 - 6.7 ) . Graphic display of the results suggested an increased risk of h and dermatitis among the apprentice hairdressers with transepidermal water loss on the h and greater than 15 g.m-2.h , but the relative risk of increased transepidermal water loss was not statistically significant . CONCLUSION The most important endogenous risk factors for h and dermatitis among the apprentice hairdressers and nurses were the presence of dry skin and a history of mucosal atopy . No relationship between increased transepidermal water loss and the risk of h and dermatitis was observed OBJECTIVE Occupational skin changes in hairdressers are very common . Morbidity , however , has not yet been quantified precisely . METHODS A cohort of 2,352 hairdressing apprentices ( of the 2,570 invited to participate , i.e. , 91.5 % response ) was prospect ively followed for the duration of their vocational training ( 3 years ) by three examinations . Three waves ( years ) were recruited in 1992 , 1993 , and 1994 from 15 vocational training schools in northwestern Germany . RESULTS The point prevalence of ( mostly slight ) irritant skin changes of the h and s increased from 35.4 % in the initial examination to 47.5 % in the intermediate examination and to 55.1 % in the final examination . Given a more conservative definition of a case of " h and dermatitis , " these estimates were 12.9 % , 23.5 % , and 23.9 % , respectively . Altogether , 34.3 and 15.2 cases of " skin changes ( any degree ) " and " h and dermatitis , " respectively , in 100 person-years were observed during the study period . The incidence rate , i.e. , the number of newly diseased study participants in relation to the person-time at risk contributed , decreased in the course of the study . The proportion of dropouts until final follow-up was 51.8 % . CONCLUSION The present results appear to lie in a range with those found in other , much smaller cohort studies . However , comparison of the results is hampered either by the lack of a clear definition or by a different definition of " person-time at risk " or " a case of h and dermatitis . " As compared with an external control group of office apprentices , the incidence was several times higher in hairdressing apprentices , which points to the high risk for skin damage in this occupation |
2,459 | 27,007,216 | Dietary advice has been shown to improve the dietary intake of the general population .
Research is needed to determine whether dietary advice can have a similar benefit in people with serious mental illness | BACKGROUND People with serious mental illness have consistently higher levels of mortality and morbidity than the general population .
They have greater levels of cardiovascular disease , metabolic disease , diabetes , and respiratory illness .
Although genetics may have a role in the physical health problems of these people , lifestyle and environmental factors such as smoking , obesity , poor diet , and low levels of physical activity play a prominent part .
OBJECTIVES To review the effects of dietary advice for schizophrenia and schizophrenia-like psychosis . | 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 This r and omized controlled trial examined benefits of adding active health promotion to basic primary care ( BPC ) services for SMI adults . It compared BPC with BPC plus wellness training ( WT ) , a 12 months intervention promoting individual skills in self-management . Three hundred nine participants enrolled during short-term residential treatment completed baseline assessment s and were assigned to treatment groups , before discharge . Outcomes of perceived health status ( SF-36 ) , global assessment of function , and ratings of self-efficacy were assessed at follow-up interviews at 6 , 12 , and 18 months . The intent-to-treat analysis employed multilevel regression to examine differences by group on outcomes across time , controlling for health related covariates . The WT group showed significantly better outcomes on the SF-36 physical functioning and general health scales . Findings affirm ability of SMI adults to benefit from active health promotion A recent meta- analysis of prospect i ve cohort studies suggests that high dietary intakes of flavonols are associated with a significantly lower risk of coronary heart disease mortality.1 The major dietary sources of flavonols such as quercetin , kaempferol , and isorhamnetin are tomatoes , onions , kale , broccoli , celery , apples , and cherries , while catechins are concentrated in tea and red wine.2,3 No clinical trials have examined the effect of interventions to increase habitual fruit and vegetable intake on plasma flavonol concentrations in free living population s. As the principal dietary sources of flavonols are restricted to a few specific food types , it is uncertain whether general dietary advice to increase fruit and vegetable consumption will increase plasma flavonol concentrations . We conducted a r and omised controlled trial to investigate the effect over six months of an intervention to increase fruit and vegetable intake in a free living population and investigated what impact this intervention had on plasma concentrations of flavonols.4 The methods are outlined in more detail elsewhere.4 In brief , we undertook a r and omised six month parallel group controlled trial using a brief negotiation model to encourage increased consumption of fruit and vegetables to at least five portions per BACKGROUND People with schizophrenia make poor dietary choices . AIMS To measure the impact of giving free fruit and vegetables for 6 months on eating habits in schizophrenia . METHOD We r and omly allocated 102 people with schizophrenia in two areas of Scotl and to receive free fruit and vegetables for 6 months , supported by instruction in meal planning and food preparation ; free fruit and vegetables alone ; or to continue as before . Diet was assessed using the Scottish Health Survey question naire . Blood sample s to measure micronutrients were taken and mental state , body mass index , level of physical activity and future risk of coronary heart disease ( CHD ) were assessed . RESULTS After the intervention , those who received free fruit and vegetables , or free fruit and vegetables and associated instruction , were consuming significantly more fruit and vegetables than those in the treatment as usual group . Consumption fell to pre-intervention levels 12 months after the intervention stopped . There was no between-group difference at any time in blood micronutrients , body mass index , physical activity or risk of CHD . CONCLUSIONS The diet of people with schizophrenia improved when they were given free fruit and vegetables but this was given free fruit and vegetables but this was not sustained after withdrawal of the intervention . A support programme added no benefit Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents . The prevalence of obesity , insulin resistance , impaired glucose tolerance , type 2 diabetes mellitus , dyslipidemia , and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population . Risk reduction studies for persons with obesity , diabetes , and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction . In the l and mark multi-center r and omized-controlled trial study , the Diabetes Prevention Project ( DPP ) , a cognitive/behavioral intervention , was more successful in producing weight loss and preventing diabetes than the drugs metformin , troglitazone or placebo . This pilot study examined the effectiveness of a cognitive/behavioral group intervention , modified after the DPP program , in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system . Outcome measures included body weight , body mass index , waist-hip ratios , and fasting glucose levels . Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33 . The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group . The CB group participants lost an average of 5.4 lb or 2.9 % of body weight , and those in the control group lost 1.3 lb or 0.6 % body weight . The range of weight loss for the treatment group was from 1 to 20 lb . This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder 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 Objective : To assess the long-term effect of dietary advice on diet and mortality after a r and omised trial of men with a recent history of myocardial infa rct ion . Design : Question naire survey and mortality follow-up after a trial of dietary advice . Setting : Twenty-one hospitals in south Wales and south-west Engl and .Subjects : Former participants in the Diet and Reinfa rct ion Trial . Main outcome measures : Current fish intake and cereal fibre intake . All-cause mortality , stroke mortality and coronary mortality . Results : By February 2000 , after 21147 person years of follow-up , 1083 ( 53 % ) of the men had died . Completed question naires were obtained from 879 ( 85 % ) of the 1030 men alive at the beginning of 1999 . Relative increases in fish and fibre intake were still present at 10 y but were much smaller . The early reduction in all-cause mortality observed in those given fish advice ( unadjusted hazard 0.70 ( 95 % CI 0.54 , 0.92 ) ) was followed by an increased risk over the next 3 y ( unadjusted hazard 1.31 ( 95 % CI 1.01 , 1.70 ) . Fat and fibre advice had no clear effect on coronary or all-cause mortality . The risk of stroke death was increased in the fat advice group – the overall unadjusted hazard was 2.03 ( 95 % CI 1.14 , 3.63 ) . Conclusions : In this follow-up of a trial of intensive dietary advice following myocardial infa rct ion we did not observe any substantial long-term survival benefit . Further trials of fish and fibre advice are feasible and necessary to clarify the role of these foods in coronary disease In several studies , many nutrients in fruits and vegetables , such as dietary fiber , potassium , and antioxidants , have been associated with reduced risk for cardiovascular disease ( 1 - 5 ) . However , as review ed elsewhere ( 6 ) , most prospect i ve studies that have specifically examined intake of fruits and vegetables in relation to risk for cardiovascular disease have been small , and their results have been inconsistent . Dietary assessment s were often crude and available only at baseline , and few studies have examined the effects of specific types of vegetables or fruits . In a recent report ( 7 ) , we evaluated the association between fruit and vegetable intake and risk for ischemic stroke . We found that persons in the highest quintile of fruit and vegetable intake had a relative risk of 0.69 ( 95 % CI , 0.52 to 0.92 ) compared with the lowest quintile of intake ; moreover , a 1-serving/d increase in fruit or vegetable intake was associated with a 6 % lower risk for ischemic stroke , after controlling for st and ard cardiovascular risk factors . In the current study , we sought to evaluate the association between intake of overall and specific fruits and vegetables and incidence of coronary heart disease . Methods Study Sample The sample s for this analysis consisted of participants in the Nurses ' Health Study ( 8) and Health Professionals ' Follow-Up Study ( 1 ) . The two studies have similar design s ; in both , participants complete mailed question naires about medical history , health behaviors , and occurrence of cardiovascular and other outcomes every 2 years . The Nurses ' Health Study began in 1976 , when 121 700 female registered nurses 30 to 55 years of age were recruited ; diet was first assessed in 1980 . Health Professionals ' Follow-up Study participants were recruited in 1986 and comprise 51 529 male health professionals , including dentists , veterinarians , pharmacists , optometrists , osteopaths , and podiatrists , 40 to 75 years of age . Sample for Analysis We excluded participants with incomplete dietary assessment s or with previously diagnosed cancer , diabetes or cardiovascular disease that was reported before the first dietary assessment . We followed 84 251 eligible women during 14 years of follow-up and 42 148 eligible men during 8 years follow-up for incidence of coronary heart disease . The rate of follow-up for nonfatal events was 97 % of the total potential person-years of follow-up in both cohorts . Assessment of Coronary Heart Disease End Points Our primary end point was nonfatal myocardial infa rct ion or fatal coronary disease occurring after return of the 1980 question naire but before 1 June 1994 in women and after return of the 1986 question naire but before 1 January 1994 in men . We sought to review medical records for all such reports . Records were review ed by physicians who were blinded to the participants ' risk factor status . Myocardial infa rct ion was confirmed by using World Health Organization criteria : symptoms plus either diagnostic electrocardiographic changes or elevated levels of cardiac enzymes ( 9 ) . Infa rct ions that required hospital admission and for which confirmatory information was obtained by interview or letter , but for which no medical records were available , were design ated as probable . We included all confirmed and probable cases in our analyses because results were the same after probable cases were excluded . Deaths were identified by using state vital records and the National Death Index or were reported by next of kin and the U.S. postal system . Follow-up for deaths was more than 98 % complete [ 10 ] . Death certificates along with medical records were used to ascertain cause of death . Fatal coronary disease was categorized as definite if 1 ) it was confirmed by hospital record or autopsy or 2 ) coronary disease was listed as the cause of death on the certificate , this was the underlying and most plausible cause , and evidence of previous coronary disease was available . We did not rely on the statement of the cause of death on the death certificate alone as providing sufficient confirmation of death due to coronary heart disease . If no medical records were available , we categorized persons in whom coronary heart disease was the underlying cause on the death certificate as presumed coronary heart disease . Analyses limited to confirmed cases yielded results very similar to those obtained when all cases were included , although with less precision . Persons who experienced sudden death within 1 hour of onset of symptoms and had no plausible cause other than coronary disease were categorized as coronary heart disease cases . Fatal cases of coronary heart disease constituted 30 % of all cases of coronary heart disease among women and 33 % among men . Dietary Assessment Diet was assessed in the Nurses ' Health Study in 1980 , 1984 , 1986 , and 1990 . A 61-item semi-quantitative food-frequency question naire that included 6 fruit items , 11 vegetable items , and 3 potato items was used in 1980 . In 1984 , the question naire was exp and ed to 126 items that covered 15 fruit items and 28 vegetable items plus potatoes ; similar question naires were repeated in 1986 and 1990 . In the Health Professionals ' Follow-up Study , diet was assessed in 1986 and 1990 by using food-frequency question naires very similar to those in the 1984 Nurses ' Health Study question naire . We excluded women who left 10 or more of the 61 items blank or who had implausible scores for total food intake ( < 500 or > 3500 kcal/d ) . Men who left 70 or more of the 131 dietary questions blank or who reported daily caloric intake outside the plausible range of 800 to 4200 calories were also excluded . For each food item , a st and ard serving size was specified . Natural portion sizesfor example , one banana or a small glass of tomato juicewere used whenever possible ; otherwise a weight or volume of that item commonly consumed by the U.S. population at one meal was used . On dietary question naires , participants reported their average intake of the specified portion size ( serving ) for each food over the past year . For each food item on the question naire , nine responses were possible , ranging from never or less than once per month to six or more times per day . Detailed descriptions of the reproducibility and validity of the food frequency question naire for men and women have been published elsewhere ( 11 - 13 ) . Frequencies and portions for the individual food items were converted to average daily intake of each fruit and vegetable item for each participant . The average daily intakes of individual food items were combined to compute total fruit and vegetable intake and intakes of composite fruit and vegetable groups . Definitions of the composite groups ( all fruits , all vegetables , citrus fruit , citrus fruit juice , cruciferous vegetables , green leafy vegetables , vitamin Crich fruits and vegetables , legumes , and potatoes ) were modified for our previous study ( 7 ) by using a report by Steinmetz and colleagues ( 14 ) . Vitamin Crich fruits and vegetables were defined as those containing more than 30 mg of vitamin C per serving . We did not include potatoes , tofu and soybeans , dried beans , and lentils as vegetables ; in addition , condiments such as chili sauce and garlic that had very small portion sizes were not counted in total vegetables . When aggregating items to compute the composite items , we assumed that individual foods for which values were missing implied no intake ( 15 ) . Statistical Analysis We found 1063 incident cases of coronary heart disease among men and 1127 among women . Person-time for each participant was calculated from the date of return of the 1980 question naire in the Nurses ' Health Study or the 1986 question naire in the Health Professionals ' Follow-up Study to the first coronary heart disease event , death , or the cutoff date ( 1 June 1994 for women and 31 January 1994 for men ) , whichever occurred first . We excluded participants who reported cardiovascular disease or cancer or diabetes before completion of the baseline dietary question naires . Each participant contributed only one end point , and the cohort at risk for each 2-year follow-up period included only those who remained free of reported coronary heart disease at the beginning of each follow-up period . The study hypotheses were defined before data were collected . The analyses were performed separately in each cohort because of differences in sex and the question naires administered to the two cohorts . This approach was selected to achieve better control of confounding . We used pooled logistic regression with 2-year follow-up increments ( 16 ) to estimate relative risks ( incidence rate ratios ) and 95 % CIs within each cohort . Analyses were adjusted for age ( 5-year categories ) , smoking ( never , former , or current [ 1 to 14 cigarettes/d , 15 to 24 cigarettes/d , or 25 cigarettes/d ] ) , alcohol consumption ( five categories in women and seven categories in men ) , family history of myocardial infa rct ion ( before 65 years of age in women and before 60 years of age in men ) , body mass index ( quintiles ) ; use of multivitamin supplements , use of vitamin E , use of aspirin , physical activity ( two categories in women and quintiles in men ) , reported hypertension and hypercholesterolemia , total daily caloric intake ( 17 ) , and time period ( each 2-year follow-up period ) . Among women , we also controlled for postmenopausal hormone use . We up date d information on diet and risk factors for coronary heart disease over time to better represent long-term patterns ( 8 , 18 ) . In the Nurses ' Health Study , we used data from the 1980 , 1984 , 1986 , and 1990 question naires , and in the Health Professionals ' Follow-up Study , we used data from the 1986 and 1990 question naires . For each 2-year follow-up period in which events were reported , we computed intake for each composite item as a cumulative average of intake from all available food-frequency question naires up to the start of the follow-up period . For participants who experienced angina , coronary artery bypass graft surgery or BACKGROUND The main objective was to assess the efficacy of a weight management program design ed for out patients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a r and omized control group . The effects of the weight management program were also assessed with regard to safety and quality of life . METHOD Forty-eight patients were enrolled in a 12-week , r and omized , multicenter weight management study . Thirty-three patients were r and omly allocated to an intervention group in which they received olanzapine within a weight management program . Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual out patients . Weight , body mass index ( BMI ) , and measurements of safety and quality of life were evaluated . The study was conducted from January 7 , 2003 , to September 16 , 2003 . RESULTS Thirty-six patients ( 75 % ) completed this study . We found significant differences in weight ( -3.94 + /- 3.63 kg vs. -1.48 + /- 1.88 kg , p = .006 ) and BMI ( -1.50 + /- 1.34 vs. -0.59 + /- 0.73 , p = .007 ) change from baseline to endpoint between the intervention and control groups , respectively . Significant differences in weight reduction were initially observed at week 8 ( p = .040 ) . No significant differences were found with regard to the safety outcomes . When the ratio of low-density lipoproteins to high-density lipoproteins was calculated , change from baseline was greater in the intervention group than the control group ( -0.19 vs. -0.04 ) , but the difference was not statistically significant ( p = .556 ) . After the completion of the weight management program , there was a trend toward statistical difference in the physical health score changes between the weight management and control groups ( 1.12 in the intervention group vs. -0.93 in the control group , p = .067 ) . CONCLUSION The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms , vital signs , and laboratory data . In addition , such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being OBJECTIVE St and ardized mortality rates are elevated in schizophrenia compared to the general population . The incidence of coronary heart disease ( CHD ) and the relative contribution of CHD to increased mortality in schizophrenia patients are not clear , despite recent concerns about metabolic complications of certain atypical antipsychotics . METHOD Ten-year risk for CHD was calculated for 689 subjects who participated in the Clinical Trials of Antipsychotic Treatment Effectiveness ( CATIE ) Schizophrenia Trial at baseline using the Framingham CHD risk function and were compared with age- , race- and gender-matched controls from the National Health and Nutrition Examination Survey ( NHANES ) III . RESULTS Ten-year CHD risk was significantly elevated in male ( 9.4 % vs. 7.0 % ) and female ( 6.3 % vs. 4.2 % ) schizophrenia patients compared to controls ( p = 0.0001 ) . Schizophrenia patients had significantly higher rates of smoking ( 68 % vs. 35 % ) , diabetes ( 13 % vs. 3 % ) , and hypertension ( 27 % vs. 17 % ) and lower HDL cholesterol levels ( 43.7 vs. 49.3 mg/dl ) compared to controls ( p < 0.001 ) . Only total cholesterol levels did not differ between groups . Ten-year CHD risk remained significantly elevated in schizophrenia patients after controlling for body mass index ( p = 0.0001 ) . CONCLUSIONS These results are consistent with recent evidence of increased cardiac mortality in schizophrenia patients . While the impact of cigarette smoking is clear , the relative contributions to cardiac risk of specific antipsychotic agents , diet , exercise , and quality of medical care remain to be clarified Obesity is a major problem nationwide and even more prevalent among people with psychiatric disabilities . This study examined the efficacy of a psychiatric rehabilitation weight loss program . Twenty-one individuals participated in the 12-week intervention . Another 15 individuals served as matched controls . Results indicate the intervention group improved more than the control group for weight , body mass index , waist circumference and physical activity . The intervention group lost 2.7 kg ( 6 lbs ) and the control group gained 0.5 kg ( 1 lb ) . A weight loss program incorporating psychiatric rehabilitation principles was effective for people with psychiatric disabilities at a community based program BACKGROUND Overweight and obesity are epidemic among persons with serious mental illness , yet weight-loss trials systematic ally exclude this vulnerable population . Lifestyle interventions require adaptation in this group because psychiatric symptoms and cognitive impairment are highly prevalent . Our objective was to determine the effectiveness of an 18-month tailored behavioral weight-loss intervention in adults with serious mental illness . METHODS We recruited overweight or obese adults from 10 community psychiatric rehabilitation outpatient programs and r and omly assigned them to an intervention or a control group . Participants in the intervention group received tailored group and individual weight-management sessions and group exercise sessions . Weight change was assessed at 6 , 12 , and 18 months . RESULTS Of 291 participants who underwent r and omization , 58.1 % had schizophrenia or a schizoaffective disorder , 22.0 % had bipolar disorder , and 12.0 % had major depression . At baseline , the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 36.3 , and the mean weight was 102.7 kg ( 225.9 lb ) . Data on weight at 18 months were obtained from 279 participants . Weight loss in the intervention group increased progressively over the 18-month study period and differed significantly from the control group at each follow-up visit . At 18 months , the mean between-group difference in weight ( change in intervention group minus change in control group ) was -3.2 kg ( -7.0 lb , P=0.002 ) ; 37.8 % of the participants in the intervention group lost 5 % or more of their initial weight , as compared with 22.7 % of those in the control group ( P=0.009 ) . There were no significant between-group differences in adverse events . CONCLUSIONS A behavioral weight-loss intervention significantly reduced weight over a period of 18 months in overweight and obese adults with serious mental illness . Given the epidemic of obesity and weight-related disease among persons with serious mental illness , our findings support implementation of targeted behavioral weight-loss interventions in this high-risk population . ( Funded by the National Institute of Mental Health ; ACHIEVE Clinical Trials.gov number , NCT00902694 . ) BACKGROUND Obesity is common in persons with schizophrenia . Besides its adverse health effects , obesity reduces quality of life and contributes to the social stigma of schizophrenia . METHOD This 14-week , multicenter , open-label , rater-blinded , r and omized study evaluated the effects of a group-based behavioral treatment ( BT ) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone . Participants were r and omly assigned to receive BT or usual clinical care ( UC ) . BT included 20 sessions during which patients were taught to reduce caloric intake . In UC , patients were encouraged to lose weight but received no special advice about weight reduction . The primary outcome measure was change in body weight . RESULTS Seventy-two patients were enrolled . The mean + /- SD weight loss at endpoint was significant in both groups ( p < .05 ) and numerically greater in patients receiving BT than in those receiving UC ( -2.0 + /- 3.79 and -1.1 + /- 3.11 kg , respectively ) . More patients in the BT group than in the UC group had lost > or = 5 % of their body weight at endpoint ( 26.5 % [ 9/34 ] and 10.8 % [ 4/37 ] , respectively ; p = .082 ) . A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5 % of their body weight at endpoint ( 32.1 % [ 9/28 ] vs. 10.8 % [ 4/37 ] , respectively , p = .038 ) and at week 14 ( complete population ; 40.9 % [ 9/22 ] and 14.3 % [ 4/28 ] , respectively , p = .027 ) . CONCLUSION BT may be an effective method for weight reduction in patients with chronic psychotic illness BACKGROUND Overweight and obesity are common concerns in individuals with severe mental disorders . In particular , antipsychotic drugs ( AP ) frequently induce weight gain . This phenomenon lacks current management and no previous controlled studies seem to use cognitive therapy to modify eating and weight-related cognitions . Moreover , none of these studies considered binge eating or eating and weight-related cognitions as possible outcomes . AIM The main aim of this study is to assess the effectivity of cognitive and behavioural treatment ( CBT ) on eating and weight-related cognitions , binge eating symptomatology and weight loss in patients who reported weight gain during AP treatment . METHOD A r and omized controlled study ( 12-week CBT vs. Brief Nutritional Education ) was carried out on 61 patients treated with an antipsychotic drug who reported weight gain following treatment . Binge eating symptomatology , eating and weight-related cognitions , as well as weight and body mass index were assessed before treatment , at 12 weeks and at 24 weeks . RESULTS The CBT group showed some improvement with respect to binge eating symptomatology and weight-related cognitions , whereas the control group did not . Weight loss occurred more progressively and was greater in the CBT group at 24 weeks . CONCLUSION The proposed CBT treatment is particularly interesting for patients suffering from weight gain associated with antipsychotic treatment OBJECTIVE Olanzapine is the most commonly prescribed atypical antipsychotic medication in Australia . Research reports an average weight gain of between 4.5 and 7 kg in the 3 months following its commencement . Trying to minimize this weight gain in a population with an already high prevalence of obesity , mortality and morbidity is of clinical and social importance . This r and omized controlled trial investigated the impact of individual nutrition education provided by a dietitian on weight gain in the 3 and 6 months following the commencement of olanzapine . METHOD Fifty-one individuals ( 29 females , 22 males ) who had started on olanzapine in the previous 3 months ( mean length of 27 days + /- 20 ) were recruited through Peninsula Health Psychiatric Services and were r and omly assigned to either the intervention ( n = 29 ) or the control group ( n = 22 ) . Individuals in the intervention group received six 1 hour nutrition education sessions over a 3-month period . Weight , waist circumference , body mass index ( BMI ) and qualitative measures of exercise levels , quality of life , health and body image were collected at baseline at 3 and 6 months . RESULTS After 3 months , the control group had gained significantly more weight than the treatment group ( 6.0 kg vs 2.0 kg , p < or = 0.002 ) . Weight gain of more than 7 % of initial weight occurred in 64 % of the control group compared to 13 % of the treatment group . The control group 's BMI increased significantly more than the treatment group 's ( 2 kg/m(2)vs 0.7 kg/m(2 ) , p < or = 0.03 ) . The treatment group reported significantly greater improvements in moderate exercise levels , quality of life , health and body image compared to the controls . At 6 months , the control group continued to show significantly more weight gain since baseline than the treatment group ( 9.9 kg vs 2.0 kg , p < or = 0.013 ) and consequently had significantly greater increases in BMI ( 3.2 kg/m(2)vs 0.8 kg/m(2 ) , p < or = 0.017 ) . CONCLUSION Individual nutritional intervention provided by a dietitian is highly successful at preventing olanzapine-induced weight gain AIM To produce dietetic guidelines summarizing the systematic review evidence on dietary advice for secondary prevention of cardiovascular disease . METHODS The Cochrane Library , MEDLINE and EMBASE were comprehensively search ed for systematic review s on aspects of diet and heart health . Review s were included if they search ed systematic ally for r and omised controlled trials relating to diet and secondary prevention of cardiovascular disease . Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review . The quality and results of each review were discussed and summarized in a whole group meeting . The guidelines were trialled in seven dietetic departments and modified where necessary . RESULTS Providing evidence -based dietary information ( including increasing omega-3 fat plus fruit and vegetable intake ) to all people after myocardial infa rct ion will save more lives than concentrating dietary advice on those in need of weight loss or lipid lowering . The practice of prioritizing dietetic time to those with raised lipids is out of date since the advent of statin therapy . CONCLUSION There is good systematic review evidence that dietary advice to those with cardiovascular disease can reduce mortality and morbidity as well as modify risk factors . Dietary advice that does this most effectively should be prioritized 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 Food is known to increase the bioavailability of ziprasidone . Therefore , we evaluated the effects of meals of differing caloric and fat content on steady-state ziprasidone exposure in a stable , treated group of subjects with DSM-IV diagnoses of schizophrenia , schizoaffective disorder , bipolar disorder , or psychotic disorder ( not otherwise specified ) who were already receiving oral ziprasidone as their st and ard therapy . METHOD Patients took ziprasidone under 6 meal conditions in r and omized sequences ( fasted , low calorie/low fat , low calorie/high fat , medium calorie/high fat , high calorie/low fat , and high calorie/high fat ) ; each crossover period was separated by at least 3 days for washout of the previous meal condition . Serial blood sample s were obtained over the 12 hours postdose . The study was conducted from July 27 to September 28 of 2006 . RESULTS Maximum ziprasidone exposures in this study were observed with high-calorie meals ( 1000 kcal ) , which were nearly twice those observed under fasting conditions . The medium-calorie meal ( 500 kcal ) was associated with exposures similar to the high-calorie meals . Low-calorie meals ( 250 kcal ) were associated with exposures that were approximately 60 % to 90 % lower than those of medium- and high-calorie meals , and approached exposures seen under fasting conditions . Fat content of the meal had no significant effect on ziprasidone absorption . The ziprasidone exposures observed with medium- and high-calorie meals had less variability than those with low-calorie meals and under fasting conditions . CONCLUSIONS These results confirm that ziprasidone should be taken with food and that a meal equal to or greater than 500 kcal , irrespective of fat content , is required for optimal and reproducible bioavailability of the administered dose CONTEXT Clinical trials using antihyperglycemic medications to improve glycemic control have not demonstrated the anticipated cardiovascular benefits . Low-glycemic index diets may improve both glycemic control and cardiovascular risk factors for patients with type 2 diabetes but debate over their effectiveness continues due to trial limitations . OBJECTIVE To test the effects of low-glycemic index diets on glycemic control and cardiovascular risk factors in patients with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS A r and omized , parallel study design at a Canadian university hospital research center of 210 participants with type 2 diabetes treated with antihyperglycemic medications who were recruited by newspaper advertisement and r and omly assigned to receive 1 of 2 diet treatments each for 6 months between September 16 , 2004 , and May 22 , 2007 . INTERVENTION High-cereal fiber or low-glycemic index dietary advice . MAIN OUTCOME MEASURES Absolute change in glycated hemoglobin A(1c ) ( HbA(1c ) ) , with fasting blood glucose and cardiovascular disease risk factors as secondary measures . RESULTS In the intention-to-treat analysis , HbA(1c ) decreased by -0.18 % absolute HbA(1c ) units ( 95 % confidence interval [ CI ] , -0.29 % to -0.07 % ) in the high-cereal fiber diet compared with -0.50 % absolute HbA(1c ) units ( 95 % CI , -0.61 % to -0.39 % ) in the low-glycemic index diet ( P < .001 ) . There was also an increase of high-density lipoprotein cholesterol in the low-glycemic index diet by 1.7 mg/dL ( 95 % CI , 0.8 - 2.6 mg/dL ) compared with a decrease of high-density lipoprotein cholesterol by -0.2 mg/dL ( 95 % CI , -0.9 to 0.5 mg/dL ) in the high-cereal fiber diet ( P = .005 ) . The reduction in dietary glycemic index related positively to the reduction in HbA(1c ) concentration ( r = 0.35 , P < .001 ) and negatively to the increase in high-density lipoprotein cholesterol ( r = -0.19 , P = .009 ) . CONCLUSION In patients with type 2 diabetes , 6-month treatment with a low-glycemic index diet result ed in moderately lower HbA(1c ) levels compared with a high-cereal fiber diet . Trial Registration clinical trials.gov identifier : NCT00438698 |
2,460 | 21,392,371 | Conclusions Despite 35 RCTs there has been little improvement in outcomes over the last few decades .
No clear correlation has been demonstrated between transfusion requirements and mortality . | Introduction Worldwide , trauma is a leading cause of death and disability .
Haemorrhage is responsible for up to 40 % of trauma deaths .
Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy .
We undertook a systematic review of r and omized controlled trials ( RCT ) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes : bleeding and /or transfusion requirements ; correction of trauma induced coagulopathy and mortality . | BACKGROUND Human polymerized hemoglobin ( PolyHeme , Northfield Laboratories ) is a universally compatible oxygen carrier developed to treat life-threatening anemia . This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury . STUDY DESIGN Injured patients with a systolic blood pressure</=90 mmHg were r and omized to receive field resuscitation with PolyHeme or crystalloid . Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood . Control patients received blood on arrival in the trauma center . This trial was conducted as a dual superiority/noninferiority primary end point . RESULTS Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers ( 79 % men ; mean age 37.1 years ) . Injury mechanism was blunt trauma in 48 % , and median transport time was 26 minutes . There was no significant difference between day 30 mortality in the as-r and omized ( 13.4 % PolyHeme versus 9.6 % control ) or per- protocol ( 11.1 % PolyHeme versus 9.3 % control ) cohorts . Allogeneic blood use was lower in the PolyHeme group ( 68 % versus 50 % in the first 12 hours ) . The incidence of multiple organ failure was similar ( 7.4 % PolyHeme versus 5.5 % control ) . Adverse events ( 93 % versus 88 % ; p=0.04 ) and serious adverse events ( 40 % versus 35 % ; p=0.12 ) , as anticipated , were frequent in the PolyHeme and control groups , respectively . Although myocardial infa rct ion was reported by the investigators more frequently in the PolyHeme group ( 3 % PolyHeme versus 1 % control ) , a blinded committee of experts review ed records of all enrolled patients and found no discernable difference between groups . CONCLUSIONS Patients resuscitated with PolyHeme , without stored blood for up to 6 U in 12 hours postinjury , had outcomes comparable with those for the st and ard of care . Although there were more adverse events in the PolyHeme group , the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available Background Studies have confirmed adverse outcome associated with transfusion of packed red blood cells ( PRBCs ) in trauma ; however , little data are available regarding other blood product transfusion , such as fresh frozen plasma ( FFP ) and platelets . The objective of this study was to examine risk-adjusted outcome in trauma with stratification by blood product type . Methods Prospect i ve data were collected daily for 1,172 consecutive trauma patients admitted to the intensive care unit ( ICU ) during a 2-year period , including transfusion rates of blood products ( PRBCs , FFP , platelets ) . Outcome assessment included infection rate , ventilator days ( Vdays ) , ICU and hospital length of stay ( LOS ) , and mortality . Results Blood products were transfused in 786 ( 67 % ) patients . The study cohort had a mean age of 43 ± 21 years and Injury Severity Score ( ISS ) of 24 ± 13 . Although the majority of patients were men , women were more likely to be transfused ( p < 0.001 ) . Mean transfusion rates of PRBCs ( 5.5 ± 9.6 U ) , FFP ( 5.4 ± 11.4 ) , and platelets ( 3.7 ± 11.1 ) were high . Univariate analysis identified that blood product transfusion ( any type ) was associated with a significantly greater infection rate ( 34 % vs. 9.4 % ; p < 0.001 ) , hospital LOS ( 18.6 vs. 9 days ; p < 0.001 ) , ICU LOS ( 13.7 vs. 7.4 days ; p < 0.001 ) , Vdays ( 12.9 vs. 6.3 days ; p < 0.001 ) , and mortality ( 19 % vs. 8.3 % ; p < 0.001 ) . Multivariate analysis ( risk-adjusted for severity of injury by ISS , age , sex , and race , and stratified by blood product type ) confirmed that risk of infection increased by 5 % , and hospital LOS , ICU LOS , and Vdays increased by 0.64 , 0.42 , and 0.47 days , respectively , for every unit of PRBCs given . Risk of death increased by 3.5 % for every unit of FFP transfused . Conclusion There is a dose-dependent correlation between blood product transfusion and adverse outcome ( increased mortality and infection ) in trauma patients BACKGROUND Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure ( SBP ) . One human trial has demonstrated improved survival when fluid resuscitation is restricted , whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure . We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock . METHODS Patients presenting in hemorrhagic shock were r and omized to one of two fluid resuscitation protocol s : target SBP > 100 mm Hg ( conventional ) or target SBP of 70 mm Hg ( low ) . Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved . In-hospital mortality , injury severity , and probability of survival were determined for each patient . RESULTS One hundred ten patients were enrolled over 20 months , 55 in each group . The study cohort had a mean age of 31 years , and consisted of 79 % male patients and 51 % penetrating trauma victims . There was a significant difference in SBP observed during the study period ( 114 mm Hg vs. 100 mm Hg , p < 0.001 ) . Injury Severity Score ( 19.65 + /- 11.8 vs. 23.64 + /- 13.8 , p = 0.11 ) and the duration of active hemorrhage ( 2.97 + /- 1.75 hours vs. 2.57 + /- 1.46 hours , p = 0.20 ) were not different between groups . Overall survival was 92.7 % , with four deaths in each group . CONCLUSION Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study . Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology , the heterogeneous nature of human traumatic injuries , and the imprecision of SBP as a marker for tissue oxygen delivery Hypertonic solutions effectively improve hemodynamic parameters in patients admitted to the emergency room . However , no significant differences in outcome were observed compared with st and ard isotonic treatment in most previously published studies . This study evaluates pretreatment prognostic factors that predict a beneficial effect of hypertonic solution in patients admitted to the emergency room with hemorrhagic hypovolemia in a prospect i ve double-blind fashion . The patients ( n = 212 ) were r and omized upon admission to receive 250 mL intravenous ( i.v . ) bolus of hypertonic 7.5 % NaCl + 6 % dextran ( HSD , n = 101 ) , or isotonic 0.9 % NaCl solutions ( IS , n = 111 ) as the first treatment , followed by st and ard resuscitation . Pretreatment factors assessed were sex , age , cause of hypovolemia , revised trauma score ( RTS ) , Glasgow index , and mean arterial pressure ( MAP ) on admission . Both groups were compared for survival at 24 h and 30 days postadmission . Infused volumes were registered . HSD administration significantly increased MAP and reduced i.v . crystalloid infusions to maintain hemodynamic parameters , compared with IS . There was no difference between groups in the number of blood transfusions administered . Overall complication rates in both groups were similar ( 24 % ) . There was a significant difference ( p < .03 ) in overall ( 30 days ) survival rate between HSD ( 73 % ) and IS ( 64 % ) groups . The 24 h survival rate was significantly lower in IS ( 72 % ) compared with HSD ( 87 % ) ; p < .01 . Multivariate analyses showed that RTS and MAP were identified as independent predictors for 24 h survival in the group that received HSD . When evaluated for overall survival rate , hypertonic infusion benefited significantly only patients with MAP < 70 mmHg ( p < .01 ) Background Blood is a scarce and costly re source . Transfusion is often required after major trauma but blood may not be readily available , and concerns remain over the potential adverse consequences of allogeneic blood transfusion . Intraoperative blood salvage ( IBS ) is used extensively after blunt abdominal trauma , but when blood is contaminated by enteric contents its use has been considered contraindicated . Methods This was a r and omised , controlled trial conducted with Ethical Review Board approval in an inner city trauma unit . Patients with penetrating torso injury requiring a laparotomy and who had exhibited hypotension either pre-hospital or on arrival and in whom there was considered to be significant blood loss were r and omly assigned to 2 groups . The control group was given allogeneic blood transfusion at the discretion of the attending medical staff . The cell save ( CS ) group underwent IBS with transfusion of both allogeneic and autologous blood . All patients received prophylactic antibiotics . The primary outcome was exposure to allogeneic blood up to the first 24 hours postinjury . Results Twenty-three patients were entered into the control group and 21 into the CS group . The groups were equivalent in demographic details , injury patterns and injury severity . The mean volume of salvaged blood re-infused in the CS group was 1,493 ml ( range 0–2,690 ml ) . The mean number of units of allogeneic blood transfused in the first 24 hours in the control group was 11.17 compared to 6.47 in the CS group ( P = 0.008 ) . Enteric injury had been sustained in 17/23 ( 75 % ) of the control group and 18/21 ( 85 % ) of the CS group ( P = NS ) . Survival in the control group was 8/23 ( 35 % ) compared to 7/21 ( 33.3 % ) in the CS arm ( P = NS ) . Patients with documented postoperative sepsis were significantly more likely to die compared to those without sepsis ( P = 0.04 ) ; however , those patients in the CS arm were no more likely to develop sepsis compared to those who received allogeneic blood alone . Conclusion In this r and omised , controlled trial for patients with penetrating abdominal injuries , IBS led to a significant reduction in allogeneic blood usage with no discernable effect on rates of postoperative infection or mortality BACKGROUND Fluid resuscitation may be detrimental when given before bleeding is controlled in patients with trauma . The purpose of this study was to determine the effects of delaying fluid resuscitation until the time of operative intervention in hypotensive patients with penetrating injuries to the torso . METHODS We conducted a prospect i ve trial comparing immediate and delayed fluid resuscitation in 598 adults with penetrating torso injuries who presented with a pre-hospital systolic blood pressure of < or = 90 mm Hg . The study setting was a city with a single central ized system of pre-hospital emergency care and a single receiving facility for patients with major trauma . Patients assigned to the immediate-resuscitation group received st and ard fluid resuscitation before they reached the hospital and in the trauma center , and those assigned to the delayed-resuscitation group received intravenous cannulation but no fluid resuscitation until they reached the operating room . RESULTS Among the 289 patients who received delayed fluid resuscitation , 203 ( 70 percent ) survived and were discharged from the hospital , as compared with 193 of the 309 patients ( 62 percent ) who received immediate fluid resuscitation ( P = 0.04 ) . The mean estimated intraoperative blood loss was similar in the two groups . Among the 238 patients in the delayed-resuscitation group who survived to the postoperative period , 55 ( 23 percent ) had one or more complications ( adult respiratory distress syndrome , sepsis syndrome , acute renal failure , coagulopathy , wound infection , and pneumonia ) , as compared with 69 of the 227 patients ( 30 percent ) in the immediate-resuscitation group ( P = 0.08 ) . The duration of hospitalization was shorter in the delayed-resuscitation group . CONCLUSIONS For hypotensive patients with penetrating torso injuries , delay of aggressive fluid resuscitation until operative intervention improves the outcome A prospect i ve trial of 6 % hetastarch ( HES ) v 5 % plasma protein fraction ( PPF ) as the colloid component of intravenous ( IV ) fluid resuscitation was conducted in 32 patients with multisystem trauma and /or hemorrhagic shock . Patient age , mechanism and pattern of injury , and IV fluid requirements were similar in both groups . No intergroup differences were noted in indexes of hepatic , pulmonary , or renal function or in the incidence of infection . The frequency of other complications , including bleeding diatheses , and mortality were identical in the two groups . Although this investigation should be viewed as a pilot study , our results suggest that , compared with PPF , HES in large volumes is a safe , effective colloid solution in the resuscitation of patients with multisystem trauma and /or hemorrhagic shock . Further study of HES in a larger number of patients is warranted by these findings BACKGROUND Tranexamic acid can reduce bleeding in patients undergoing elective surgery . We assessed the effects of early administration of a short course of tranexamic acid on death , vascular occlusive events , and the receipt of blood transfusion in trauma patients . METHODS This r and omised controlled trial was undertaken in 274 hospitals in 40 countries . 20 211 adult trauma patients with , or at risk of significant bleeding were r and omly assigned within 8 h of injury to either tranexamic acid ( loading dose 1 g over 10 min then infusion of 1 g over 8 h ) or matching placebo . R and omisation was balanced by centre , with an allocation sequence based on a block size of eight , generated with a computer r and om number generator Both participants and study staff ( site investigators and trial coordinating centre staff ) were masked to treatment allocation . The primary outcome was death in hospital within 4 weeks of injury , and was described with the following categories : bleeding , vascular occlusion ( myocardial infa rct ion , stroke and pulmonary embolism ) , multiorgan failure , head injury , and other AL analyses were by intention to treat . This study is registered as IS RCT N86750102 , Clinical trials.gov NCT00375258 , and South African Clinical Trial Register DOH-27 - 0607 - 1919 . RESULTS 10096 patients were allocated to tranexamic acid and 10 115 to placebo , of whom 10060 and 10067 , respectively , were analysed . All-cause mortality was significantly reduced with tranexamic acid ( 1463 [ 14.5 % ] tranexamic acid group vs 1613 [ 160 % ] placebo group ; relative risk 0.91 , 95 % CI 085 - 097 ; p = 00035 ) . The risk of death due to bleeding was significantly reduced ( 489 [ 49 % ] vs 574 [ 5 - 7 % ] ; relative risk 0 - 85 , 95 % CI 0.76 - 0.96 ; p = 0 - 0077 ) . CONCLUSION Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study On the basis of these results , tranexamic acid should be considered for use in bleeding trauma patients Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock , and seem to be effective in resuscitating trauma patients with severe injuries . In this study , the contribution of the dextran component was investigated in a prospect i ve , three-armed , double-blind , r and omized trial . Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of ( 1 ) normal saline ( NS ) ; ( 2 ) 7.5 % NaCl ( HS , for hypertonic saline ) ; or ( 3 ) 7.5 % NaCl in 6 % dextran 70 ( HSD ) . Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients ' conditions indicated . By predetermined hypothesis , the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology . The 7.5 % NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology . The addition of a colloid , in the form of 6 % dextran 70 , did not offer any additional benefit , at least in this setting of rapid urban transport OBJECTIVE To assess in a r and omized prospect i ve manner nephrectomy rate , transfusion rate , blood loss , and time of operation in penetrating renal trauma patients r and omized to vascular control or no vascular control before opening Gerota 's fascia . METHOD During a 53-month period from January of 1994 to May of 1998 , 56 patients with penetrating renal injuries were entered into a r and omized prospect i ve study at an urban Level I trauma center . The patients were r and omized to a preliminary vascular control group or no vascular control group . R and omization was performed intraoperatively before opening Gerota 's fascia . All renal injuries were identified and diagnosed intraoperatively . Intravenous pyelography was not performed preoperatively . If the patient was r and omized to the no control group and significant bleeding ensued after opening of Gerota 's fascia , the renal hilum was cross-clamped . All injuries were included regardless of patient age , associated injuries , blood loss , severity of renal injury , or other abdominal organs injured . All injuries that required renorrhaphy or partial nephrectomy underwent drainage with closed Jackson-Pratt drainage . RESULTS Twenty-nine patients were r and omized to the preliminary vascular control group , and 27 patients were r and omized to the no vascular control group . The average age in the vascular control group was 25.3 years ( SD , 10.9 ) and 23.4 years ( SD , 8.2 ) in the no control group . The average penetrating abdominal trauma index in the vascular control group was 22.9 ( SD , 10.9 ) and in the no control group 23.7 ( SD , 13.7 ) . Nine nephrectomies ( 31 % ) were performed in the vascular control group , and eight nephrectomies ( 30 % ) were performed in the no vascular control group ( p > 0.05 ) . The average operative time for the vascular control group was 127 minutes and for the no control group was 113 minutes ( p > 0.05 ) . Eleven patients ( 38 % ) required intraoperative blood transfusion in the vascular control group ( average , 5.5 U/patient transfused ) versus eight patients ( 30 % ) in the no vascular control group ( average , 5.2 U/patient transfused ) ( p > 0.05 ) . The average blood loss in the vascular control group was 1.06 liters versus 0.91 liters in the no control ( p > 0.05 ) . There was one mortality in the study population . CONCLUSION Vascular control of the renal hilum before opening Gerota 's fascia has no impact on nephrectomy rate , transfusion requirements , or blood loss . Operative time may be increased with the vascular control technique BACKGROUND Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation . Of the many possible causes of these complications , bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage . Recombinant human bactericidal/permeability-increasing protein ( rBPI21 ) has antibacterial and antiendotoxin properties , reduces cytokine levels , and increases survival in animal models of hemorrhagic shock . The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI21 infusion in patients with hemorrhage due to trauma . METHODS This was a phase II , multicenter , r and omized , double-blind , placebo-controlled trial . Patients who required at least 2 U of blood were r and omized to receive rBPI21 ( 4 mg x kg(-1 ) x d(-1 ) for 2 consecutive days ) or an equivalent volume of placebo by continuous infusion within 12 hours of injury . The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study . Safety was monitored clinical ly and by laboratory panels during the study period . RESULTS A total of 401 patients were treated ( 202 in the rBPI21 group and 199 in the placebo group ) . The composite end point rate of mortality or serious complication through day 15 was 46 % in the placebo group and 39 % in the rBPI21 group ( hazard ratio = 0.79 ; p = 0.13 ) . Secondary analysis , which adjusted for age , mechanism of injury , Injury Severity Score ( 1990 version ) , and units of blood received before study drug infusion showed similar results ( hazard ratio = 0.79 ; p = 0.14 ) . The proportion of patients who developed at least one serious organ dysfunction was 22 % in the placebo group and 16 % in the rBPI21 group ( hazard ratio = 0.71 ; p = 0.14 ) . The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32 % in the placebo group and 22 % in the rBPI21 group ( hazard ratio = 0.66 ; post hocp = 0.03 ) . The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups , Injury Severity Scores , and units of blood transfused . No treatment difference was observed in mortality or re source utilization in this phase II study . CONCLUSION rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15 , especially respiratory complications , in patients with hemorrhage due to trauma . A phase III study is currently in progress To evaluate the use of hypertonic saline/dextran solutions in the prehospital resuscitation of severely injured patients , we administered 250 mL of either 7.5 % sodium chloride/dextran 70 ( HSD ) ( n = 83 ) or lactated Ringer 's solution ( n = 83 ) , followed by conventional isotonic fluids , to 166 trauma patients with systolic blood pressures less than or equal to 100 mm Hg , in a prospect i ve , r and omized , double-blinded clinical trial . Patients in the sodium chloride/dextran 70 group required less fluid before hospitalization and arrived in the emergency department with higher systolic blood pressures than patients in the lactated Ringer 's solution group . The rate of survival to hospital discharge for the entire cohort was 64 % for patients in the sodium chloride/dextran 70 group vs 59 % for patients in the lactated Ringer 's solution group . The rate of survival to hospital discharge for the patients with severe head injuries was 32 % for the sodium chloride/dextran 70 group vs 16 % for the lactated Ringer 's solution group . Actuarial survival for patients with severe head injuries in the sodium chloride/dextran 70 group compared with patients with severe head injuries in the lactated Ringer 's solution group did not quite reach statistical significance . There were no adverse side effects associated with sodium chloride/dextran 70 administration . Administration of small volumes of sodium chloride/dextran 70 before hospitalization increased the blood pressure of severely injured patients more effectively than did lactated Ringer 's solution and showed tendencies toward improving survival in the patients with severe head injuries Introduction Mortality is the most widely accepted outcome measure in r and omized controlled trials of therapies for critically ill adults , but most of these trials fail to show a statistically significant mortality benefit . The reasons for this are unknown . Methods We search ed five high impact journals ( Annals of Internal Medicine , British Medical Journal , JAMA , The Lancet , New Engl and Journal of Medicine ) for r and omized controlled trials comparing mortality of therapies for critically ill adults over a ten year period . We abstract ed data on the statistical design and results of these trials to compare the predicted delta ( delta ; the effect size of the therapy compared to control expressed as an absolute mortality reduction ) to the observed delta to determine if there is a systematic overestimation of predicted delta that might explain the high prevalence of negative results in these trials . Results We found 38 trials meeting our inclusion criteria . Only 5/38 ( 13.2 % ) of the trials provided justification for the predicted delta . The mean predicted delta among the 38 trials was 10.1 % and the mean observed delta was 1.4 % ( P < 0.0001 ) , result ing in a delta-gap of 8.7 % . In only 2/38 ( 5.3 % ) of the trials did the observed delta exceed the predicted delta and only 7/38 ( 18.4 % ) of the trials demonstrated statistically significant results in the hypothesized direction ; these trials had smaller delta-gaps than the remainder of the trials ( delta-gap 0.9 % versus 10.5 % ; P < 0.0001 ) . For trials showing non-significant trends toward benefit greater than 3 % , large increases in sample size ( 380 % - 1100 % ) would be required if repeat trials use the observed delta from the index trial as the predicted delta for a follow-up study . Conclusions Investigators of therapies for critical illness systematic ally overestimate treatment effect size ( delta ) during the design of r and omized controlled trials . This bias , which we refer to as " delta inflation " , is a potential reason that these trials have a high rate of negative results ."Absence of evidence is not evidence of absence . Background To assess , whether arterial blood gas measurements during trauma patient 's pre-hospital shock resuscitation yield useful information on haemodynamic response to fluid resuscitation by comparing haemodynamic and blood gas variables in patients undergoing two different fluid resuscitation regimens . Methods In a prospect i ve r and omised study of 37 trauma patients at risk for severe hypovolaemia , arterial blood gas values were analyzed at the accident site and on admission to hospital . Patients were r and omised to receive either conventional fluid therapy or 300 ml of hypertonic saline . The groups were compared for demographic , injury severity , physiological and outcome variables . Results 37 patients were included . Mean ( SD ) Revised Trauma Score ( RTS ) was 7.3427 ( 0.98 ) and Injury Severity Score ( ISS ) 15.1 ( 11.7 ) . Seventeen ( 46 % ) patients received hypertonic fluid resuscitation and 20 ( 54 % ) received conventional fluid therapy , with no significant differences between the groups concerning demographic data or outcome . Base excess ( BE ) values decreased significantly more within the hypertonic saline ( HS ) group compared to the conventional fluid therapy group ( mean BE difference -2.1 mmol/l vs. -0.5 mmol/l , p = 0.003 ) . The pH values on admission were significantly lower within the HS group ( mean 7.31 vs. 7.40 , p = 0.000 ) . Haemoglobin levels were in both groups lower on admission compared with accident site . Lactate levels on admission did not differ significantly between the groups . Conclusion Pre-hospital use of small-volume resuscitation led to significantly greater decrease of BE and pH values . A portable blood gas analyzer was found to be a useful tool in pre-hospital monitoring for trauma resuscitation OBJECTIVE The purpose of this r and omized , prospect i ve clinical trial was to determine whether hypothermia during resuscitation is protective or harmful to critically injured trauma patients . SUMMARY BACKGROUND DATA Hypothermia has both protective and harmful clinical effects . Retrospective studies show higher mortality in patients with hypothermia ; however , hypothermia is more common in more severely injured patients , which makes it difficult to determine whether hypothermia contributes to mortality independently of injury severity . There are no r and omized , prospect i ve treatment studies to assess hypothermia 's impact as an independent variable . METHODS Fifty-seven hypothermic ( T < or = 34.5 C ) , critically injured patients requiring a pulmonary artery catheter were r and omized to a rapid rewarming protocol using continuous arteriovenous rewarming ( CAVR ) or to a st and ard rewarming ( SR ) control group . The primary outcome of interest was first 24-hour blood product and fluid resuscitation requirements . Other comparative analyses included coagulation assays , hemodynamic and oxygen transport measurements , length of stay , and mortality . RESULTS The two groups were well matched for demographic and injury severity characteristics . CAVR rewarmed significantly faster than did SR ( p < 0.01 ) , producing two groups with different amounts of hypothermia exposure . The patients who underwent CAVR required less fluid during resuscitation to the same hemodynamic goals ( 24,702 mL vs. 32,540 mL , p = 0.05 ) and were significantly more likely to rewarm ( p = 0.002 ) . Only 2 ( 7 % ) of 29 patients who underwent CAVR failed to warm to 36 C and both died , whereas 12 ( 43 % ) of 28 patients who underwent SR failed to reach 36 C , and all 12 died . Patients who underwent CAVR had significantly less early mortality ( p = 0.047 ) . CONCLUSION Hypothermia increases fluid requirements and independently increases acute mortality after major trauma The rapid infusion system ( RIS ) , which can deliver fluids/blood products rapidly at precise rates and normothermic conditions , was compared with conventional fluid administration ( CFA ) in a r and omized study of 36 hypovolemic trauma patients . Admission stratification criteria of the groups were similar relative to age , Glasgow Coma Score ( GCS ) , Injury Severity Score ( ISS ) and plasma lactate . Despite the lack of difference in blood loss between the 24-h survivors of the two groups , the CFA group required greater total fluids ( 23.6/20.21 ) , red blood cells ( 5.5/4.61 ) , fresh frozen plasma ( FFP ) ( 2.8/1.91 ) , platelets ( 523/204 ml ) , and crystalloids ( 12.9/10.61 ) . Lactate levels were lower in the RIS group at virtually all times from hours 1 to 24 ( 4.3/5.3 mM/l , t-value = 3.3 , DF = 279 , P = 0.001 ) . Post-admission hypothermia was greater in the CFA group at all times during the first 24 h ( 35.2/36.4 degrees C , t-value = 5.6 , DF = 250 , P = 0.001 ) . The mean partial thromboplastin time was significantly higher in the CFA group ( 47.3/35.1 s , t-value = 3.1 , DF = 279 , P = 0.002 ) . The PTT and PT were related to the degree of lactic acidosis ( P = 0.0001 ) and hypothermia ( P = 0.001 ) but not to the amount of FFP given ( P = 0.14 ) . The hospital costs , days in the ICU , and days on the ventilator were greater for the CFA group , as was the incidence of pneumonia ( 0/11 vs. 6/17 ; P = 0.03 ) . Hypovolemic trauma patients resuscitated with the RIS needed fewer fluid/blood products and had less coagulopathy ; more rapid resolution of hypoperfusion acidosis ; better temperature preservation ; and fewer hospital complications than those resuscitated with conventional methods of fluid/blood product administration We report the results of the first clinical study on the use of a hypertonic saline-dextran solution for the prehospital management of hypotensive victims of penetrating trauma . During a 4-month period , 48 trauma patients with penetrating injuries and a prehospital systolic blood pressure of 90 mm Hg or less were infused in-field with 250 ml of either a hypertonic saline-dextran solution or the crystalloid plasmalyte A. There were no complications associated with the infusion of the hypertonic saline-dextran solution , and execution of the protocol by paramedic personnel was both safe and uniformly successful . The potential impact of this solution on medical care and the results of this feasibility study justify the initiation of a larger prospect i ve , r and omized clinical trial on the efficacy of this solution in the prehospital setting OBJECTIVE To evaluate the use of 250 mL of a 7.5 % sodium chloride solution , both with and without added dextran 70 , for the prehospital resuscitation of hypotensive trauma patients . DESIGN Double-blind r and omized trial . SETTING Six trauma systems served by helicopter transport . PATIENTS Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport . INTERVENTIONS Infusion of study solution , in the field or during transport , followed by conventional isotonic solutions as needed . Solutions studied in four cohorts were as follows : ( 1 ) lactated Ringer 's ; ( 2 ) 7.5 % sodium chloride ( hypertonic saline ) ; ( 3 ) 7.5 % sodium chloride combined with 6 % dextran 70 ; and ( 4 ) 7.5 % sodium chloride combined with 12 % dextran 70 . MAIN OUTCOME MEASURES Blood pressure response ; survival to time of hospital discharge among the treatment groups ; and survival compared with that predicted by norms from the Major Trauma Outcome Study ( MTOS ) . RESULTS The mean ( + /- SD ) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer 's solution group ( 34 + /- 46 vs 11 + /- 49 mm Hg , P < .03 ) . Overall survival in the four treatment groups was 49 % , 60 % , 56 % , and 45 % ( not statistically significant ) . Survival in the hypertonic saline solution group , however , was significantly higher than that predicted by the MTOS norms ( 60 % vs 48 % , P < .001 ) . Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group ( P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis ; with survival in the hypertonic saline solution group [ 34 % ] vs lactated Ringer 's solution group [ 12 % ] ) . CONCLUSIONS Prehospital infusion of 250 mL of 7.5 % sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms . Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5 % sodium chloride resuscitation . Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70 BACKGROUND In trauma patients with significant hemorrhage , it is hypothesized that failure to normalize prothrombin time ( PT ) after recombinant activated factor VII ( rFVIIa ) treatment predicts poor clinical outcomes and potentially indicates a need for additional therapeutic interventions . METHODS To assess the value of PT to predict outcomes after rFVIIa or placebo therapy , we performed a post hoc analysis of data from 169 severely injured , critically bleeding trauma patients who had 1-hour postdose PT measurements from two r and omized clinical trials . Baseline characteristics and outcome parameters were compared between subjects with 1-hour postdose PT > or=18 seconds and PT < 18 seconds . RESULTS In rFVIIa-treated subjects , prolonged postdose PT values > or=18 seconds were associated with significantly higher 24-hour mortality ( 60 % vs. 3 % ; p < 0.001 ) and 30-day mortality , increased incidence of massive transfusion , and fewer intensive care unit-free days compared with postdose PT values < 18 seconds . Recombinant rFVIIa-treated subjects with postdose PT > or=18 seconds had significantly lower baseline hemoglobin levels , fibrinogen levels , and platelet counts than subjects with postdose PT values < 18 seconds even though they received similar amounts of blood products before rFVIIa dosing . Placebo-treated subjects with postdose PT > or=18 seconds had significantly increased incidence of massive transfusion , significantly decreased intensive care unit-free days , and significantly lower levels of fibrinogen and platelets at baseline compared with subjects with postdose PT values < 18 seconds . CONCLUSIONS The presence of prolonged PT after rFVIIa or placebo therapy was associated with poor clinical outcomes . Because subjects with postdosing PT > or=18 seconds had low levels of hemoglobin , fibrinogen , and platelets , this group may benefit from additional blood component therapy OBJECTIVE To determine the safety and possible efficacy of diaspirin cross-linked hemoglobin ( DCLHb ) in the treatment of patients in Class II-IV hemorrhagic , hypovolemic shock . DESIGN Multicenter , r and omized , normal saline-controlled , dose-escalation study . SETTING Eleven hospitals in the U.S. and Belgium . SUBJECTS One hundred and thirty-nine ( 139 ) hospitalized patients with Class II-IV hemorrhagic , hypovolemic shock within the previous 4 hours who still were requiring therapy for shock . INTERVENTIONS Beginning with the lowest dose , patients were r and omized to receive 50 , 100 , or 200 mL of either 10 % DCLHb or normal saline infused intravenously over 15 minutes . Following infusion of either treatment , further fluid resuscitation could be given , as necessary , to maintain perfusion . Vital signs , laboratory assessment s , blood and fluid administration , complications , and adverse events were recorded at various times from the end of infusion through 72 hours after infusion . RESULTS A total of 29 ( 13 DCLHb- and 16 saline-treated ) patients died during the study period . Adverse events were experienced by 61 % of patients in the DCLHb group and 53 % of patients in the saline group ; serious adverse events occurred in 28 % of DCLHb-treated patients and 30 % of saline-treated patients . The incidence of prospect ively defined , clinical complications , including renal insufficiency and renal failure , was similar between the treatment groups except for the occurrence of dysrhythmias/conduction disorders , which occurred significantly more frequently in the saline-treated patients than the DCLHb-treated patients ( p = 0.041 ) . At the highest dose level ( 200 mL ) , statistically significant between-group differences were observed with greater increases in serum amylase , LDH , the isoenzymes LD1,2,4 and 5 , and CK-MB in the DCLHb group compared to the control group ; none were of clinical significance . The volume of blood administered did not differ between the groups . Overall 24- and 72-hour survival rates were similar between treatment groups , although the hospital discharge rate was slightly higher in the DCLHb-treated patients ( 80 % ) compared with the saline-treated patients ( 74 % ) . CONCLUSION Administration of 50 to 200 mL of DCLHb to patients in hemorrhagic , hypovolemic shock was not associated with evidence of end organ toxicity or significant adverse events . Further studies involving larger doses and , perhaps , earlier administration of DCLHb are warranted Prior studies at Harborview Medical Center have suggested that dilutional thrombocytopenia is a major etiology of microvascular , nonmechanical bleeding ( MVB ) . We undertook a prospect i ve r and omized double-blind clinical study to compare the prophylactic effects of 6 units of platelet concentrates ( PLT ) versus 2 units of fresh frozen plasma ( FFP ) administered with every 12 units of modified whole blood in patients undergoing massive transfusion ( 12 or more units in 12 hours ) . After exclusions , three of 17 patients who received PLT and three of 16 patients who received FFP developed MVB , an incidence no different from our previous findings . Regression lines of platelet counts during transfusion were no different between groups , and both groups had higher platelet counts than predicted from a st and ard washout equation . Only one patient had evidence of dilutional thrombocytopenia as a cause for MVB . Prophylactic platelet administration is not warranted as a routine measure to prevent MVB ABSTRACT Allogeneic blood transfusions in surgical patients have been associated with an increased risk of infectious complications and organ dysfunction . Residual leukocytes contaminating units of packed red blood cells have been incriminated through the induction of anergy and /or a potentiated inflammatory response , leading to the possibility that leukoreduced red blood cell transfusion might mitigate these effects . We set out to evaluate the effect of leukoreduced red cell transfusion on the risk of infections complications in patients requiring transfusion following injury . We conducted a single-center , double-blinded r and omized controlled trial of leukoreduced versus st and ard , nonleukoreduced red blood cell transfusions in injured patients receiving transfusion within 24 hrs of injury . The primary endpoint was infectious complications within 28 days of r and omization . Secondary end points were multiple organ failure , length of stay , febrile episodes , and mortality . Two hundred sixty eight subjects were eligible for analysis . Rates of infectious complications were similar in subjects receiving leukoreduced transfusions ( 30 % ) or st and ard transfusions ( 36 % ) ( [ RR ] , 0.84 [ 0.55 - 1.3 ] ) and there was no statistically significant effect of leukoreduced blood transfusion on mortality [ RR , 1.20 ( 0.74 - 1.9 ) ] , febrile episodes [ RR , 1.01 ( 0.89 - 1.2 ) ] , or organ dysfunction scores ( 5.9 vs. 6.6 ; P = 0.29 ) . Thus , pre-storage leukoreduction of allogeneic red blood cells had a small , but non-significant effect on the rate of infectious complication in this high-risk population requiring transfusion . There was no effect on the rates of febrile episodes , mortality , length of stay , or severity of organ dysfunction BACKGROUND Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure . Recombinant Factor VIIa ( rFVIIa , NovoSeven ) is a procoagulant that might limit bleeding and improve trauma outcomes . METHODS We performed a phase 3 r and omized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma . We studied 573 patients ( 481 blunt and 92 penetrating ) who bled 4 to 8 red blood cell ( RBC ) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management . Patients were assigned to rFVIIa ( 200 μg/kg initially ; 100 μg/kg at 1 hour and 3 hours ) or placebo . Intensive care unit management was st and ardized using evidence -based trauma " bundles " with formal oversight of compliance . Primary outcome was 30-day mortality . Predefined secondary outcomes included blood products used . Safety was assessed through 90 days . Study powering was based on prior r and omized controlled trials and large trauma center data bases . RESULTS Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis ( 10.8 % vs. 27.5 % planned/predicted ) and difficulties consenting and enrolling sicker patients . Mortality was 11.0 % ( rFVIIa ) versus 10.7 % ( placebo ) ( p = 0.93 , blunt ) and 18.2 % ( rFVIIa ) versus 13.2 % ( placebo ) ( p = 0.40 , penetrating ) . Blunt trauma rFVIIa patients received ( mean ± SD ) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours , and placebo patients received 9.1 ± 11.3 RBC units ( p = 0.04 ) and 23.5 ± 28.0 total allogeneic units ( p = 0.04 ) . Thrombotic adverse events were similar across study cohorts . CONCLUSIONS rFVIIa reduced blood product use but did not affect mortality compared with placebo . Modern evidence -based trauma lowers mortality , paradoxically making outcomes studies increasingly difficult Objective To evaluate the effect of early optimization in the survival of severely injured patients . Summary Background Data It is unclear whether supranormal ( “ optimal ” ) hemodynamic values should serve as endpoints of resuscitation or simply as markers of the physiologic reserve of critically injured patients . The failure of optimization to produce improved survival in some r and omized controlled trials may be associated with delays in starting the attempt to reach optimal goals . There are limited controlled data on trauma patients . Methods Seventy-five consecutive severely injured patients with shock result ing from bleeding and without major intracranial or spinal cord trauma were r and omized to resuscitation , starting immediately after admission , to either normal values of systolic blood pressure , urine output , base deficit , hemoglobin , and cardiac index ( control group , 35 patients ) or optimal values ( cardiac index > 4.5 L/min/m2 , ratio of transcutaneous oxygen tension to fractional inspired oxygen > 200 , oxygen delivery index > 600 mL/min/m2 , and oxygen consumption index > 170 mL/min/m2 ; optimal group , 40 patients ) . Initial cardiac output monitoring was done noninvasively by bioimpedance and , subsequently , invasively by thermodilution . Crystalloids , colloids , blood , inotropes , and vasopressors were used by predetermined algorithms . Results Optimal values were reached intentionally by 70 % of the optimal patients and spontaneously by 40 % of the control patients . There was no difference in rates of death ( 15 % optimal vs. 11 % control ) , organ failure , sepsis , or the length of intensive care unit or hospital stay between the two groups . Patients from both groups who achieved optimal values had better outcomes than patients who did not . The death rate was 0 % among patients who achieved optimal values compared with 30 % among patients who did not . Age younger than 40 years was the only independent predictive factor of the ability to reach optimal values . Conclusions Severely injured patients who can achieve optimal hemodynamic values are more likely to survive than those who can not , regardless of the resuscitation technique . In this study , attempts at early optimization did not improve the outcome of the examined subgroup of severely injured patients The object of this article is to assess the value of human serum albumin ( HSA ) in the initial resuscitation of hypotensive trauma victims . Thirty-six patients ( mean age = 30 years ) in shock from trauma who underwent laparotomies were r and omly assigned to either Ringer 's lactate solution ( RL ) resuscitation or 4 % HSA in RL resuscitation . Both groups received approximately 8L of test fluid and 6U of washed red cells . The only death in the study occurred in a patient assigned to the RL group . Two patients in each group required mechanical ventilation for longer than 24 hours . No differences were noted in a battery of pulmonary function tests performed daily for 5 days . These results demonstrate that HSA is not essential in this clinical setting for safe and effective resuscitation BACKGROUND Human polymerized hemoglobin ( PolyHeme ) is a universally compatible , disease-free , oxygen-carrying resuscitative fluid . This is the first prospect i ve , r and omized trial to compare directly the therapeutic benefit of PolyHeme with that of allogeneic red blood cells ( RBCs ) in the treatment of acute blood loss . STUDY DESIGN Forty-four trauma patients ( 33 male , 11 female ) aged 19 - 75 years with an average Injury Severity Score ( ISS ) score of 21+/-10 were r and omized to receive red cells ( n = 23 ) or up to 6 U ( 300 g ) of PolyHeme ( n = 21 ) as their initial blood replacement after trauma and during emergent operations . RESULTS There were no serious or unexpected adverse events related to PolyHeme . The PolyHeme infusion of 4.4+/-2.0 units ( mean + /- SD ) result ed in a plasma [ Hb ] of 3.9+/-1.3 g/dL , which accounted for 40 % of the total circulating [ Hb ] . There was no difference in total [ Hb ] between the groups before infusion ( 10.4+/-2.3 g/dL control vs. 9.4+/-1.9 g/dL experimental ) . At end-infusion the experimental RBC [ Hb ] fell to 5.8+/-2.8 g/dL vs. 10.6+/-1.8 g/dL ( p < 0.05 ) in the control , although the total [ Hb ] was not different between the groups or from pre-infusion . The total number of allogeneic red cell transfusions for the control and experimental groups was 10.4+/-4.2 units vs. 6.8+/-3.9 units ( p < 0.05 ) through day 1 , and 11.3+/-4.1 units vs. 7.8 + /-4.2 units ( p = 0.06 ) through day 3 . CONCLUSIONS PolyHeme is safe in acute blood loss , maintains total [ Hb ] in lieu of red cells despite the marked fall in RBC [ Hb ] , and reduces the use of allogeneic blood . PolyHeme appears to be a clinical ly useful blood substitute Pentastarch is a colloid that is chemically similar to Hetastarch . It has a shorter half-life ( 12 hr ) , and produces volume expansion at least 1.5 times the administered volume . We compared Pentastarch to Ringer 's lactate in 41 patients ( 21 Pentastarch , 20 Ringer 's lactate ) presenting with hemorrhagic shock . The groups were similar in age , sex , race , and type of injury . Significantly less volume of Pentastarch was required initially to resuscitate to a normal blood pressure and urine output than Ringer 's lactate ( P < 0.005 ) . Coagulation parameters ( prothrombin time , partial thromboplastin time , fibrinogen , and factor VIII ) were measured for 48 hr post-resuscitation , and no abnormalities were noted in the Pentastarch group . Serum albumin was the same in both groups throughout the study period ; however , serum colloid oncotic pressure was elevated at 1 hr post-resuscitation in the Pentastarch group ( P < 0.005 ) . There was no difference in ventilatory parameters , blood gases , pulmonary function tests , ventilator days , or hospital days between the two groups . We conclude that Pentastarch is safe and effective for the initial resuscitation from hemorrhagic shock RESULTS In total 1309 patients were entered in the study : 699 ( 53.4 % ) were treated by paramedics operating protocol A and 610 ( 46.6 % ) were treated by paramedics operating protocol B. The r and omisation worked well and there were no significant differences between treatment groups in incident characteristics , ambulance performance times , or patient or injury characteristics , apart from slightly more moderate or severe head injuries in the protocol A group ( 25.3 % versus 20.3 % ) . Protocol compliance was poor , with only 31 % of protocol A patients receiving prehospital fluids and only 80 % of protocol B patients not given fluids . The estimated odds ratio for being given prehospital fluids when treated by protocol A compared to protocol B was 2.09 ( 95 % confidence interval ( CI ) , 1.53 to 2.81 ) . MORTALITY There were 73 deaths within 6 months in the 699 patients in the protocol A group ( 10.4 % ) , and 60/610 ( 9.8 % ) in the protocol B group . Thus the crude odds ratio for deaths when managed by protocol A was 1.07 ( 95 % CI , 0.73 to 1.54 ) . Excluding 26 patients whose cause of death may not have been trauma related , the odds ratio was 1.04 ( 95 % CI , 0.69 to 1.55 ) . Excluding 17 patients who may have been dead on arrival of the ambulance at the scene the odds ratio was 1.04 ( 95 % CI , 0.70 to 1.53 ) . Adjustment for age , injury severity and whether the patient was unconscious at the scene did not significantly alter these odds ratios . COMPLICATIONS A total of 106 patients were identified from hospital notes as having at least one of eight major complications ( adult respiratory distress syndrome , sepsis , acute renal failure , coagulopathy , wound infection , pneumonia , fat embolism or pulmonary embolism ) . The proportions with recorded complications were similar in the two groups : 60/699 ( 8.5 % ) in the protocol A group versus 46/610 ( 7.5 % ) in the protocol B group . HEALTH STATUS : A total of 878 question naires were sent to patients , and 559 ( 64 % ) usable replies were received . The response rate was similar in the two groups ( 62.9 % versus 64.6 % ) . In all eight dimensions of the SF-36 health status measure patients who had been managed by paramedics operating protocol A reported better average health than did patients in the protocol B group . However , none of the differences were at a level considered clinical ly important and only for one of the eight dimensions was the difference statistically significant . COMPOSITE OUTCOMES : No significant differences in outcome were found between the two protocol groups in terms of patients who either died or had serious complications , nor for patients who either died or had known poor health . SUBGROUPS : Subgroups of patients were defined on eight characteristics ( ambulance service area , whether a doctor was on scene , paramedic-patient contact time , injury severity , whether taken to theatre for emergency surgery , type of injuries , type of area , and whether the patient was treated before or after protocol cross-over ) . There was no evidence of any difference in mortality rates or composite outcomes between any subgroups , or between protocol s within any subgroup . Time to A&E department The analysis suggests that patients given fluids spent 12 - 13 minutes longer at the accident scene than did patients not given fluids . However , because only one-quarter of patients were given fluids , and the specific protocol used made little difference to this , average on-scene times were largely unaffected by protocol s. COSTS In the prehospital and immediate-care phase ( including A&E treatment ) , the mean costs of the protocol A and protocol B groups were ¿ 419 and ¿ 416 , respectively . This small difference reflects two small and off setting effects of protocol B : reduced on-scene time ( p = 0.08 ) and increased use of blood in the A&E department ( p = 0.03 ) . There were no other statistically significant differences in costs , with the mean total costs being ¿ 2706 and ¿ 2678 in the protocol A and protocol B groups , respectively ( p = 0.52 ) . ( ABSTRACT BACKGROUND Transfusion of trauma patients can result in long-term survival of donor white blood cells ( WBCs ) or " transfusion-associated microchimerism " ( TA-MC ) . The aim was to determine whether leukoreduction of blood transfusions , advocated to reduce the immunomodulatory effect of transfusion , decreases the likelihood of developing TA-MC . STUDY DESIGN AND METHODS A subgroup of trauma patients from a r and omized trial was examined , evaluating the risk of infection following leukoreduced versus nonleukoreduced blood transfusion . Patients ' blood was sample d at least 1 month after hospital discharge , and TA-MC was assessed with quantitative allele-specific polymerase chain reaction detection of differences at the HLA-DR locus or a panel of insertion-deletion polymorphism loci distributed throughout the chromosomal complement . At the time of blood sampling , a scripted interview was used to ascertain symptoms suggestive of chronic graft-versus host disease ( cGVHD ) . RESULTS For 67 patients evaluated , the mean age was 43 + /- 17 years and mean Injury Severity Score was 24 + /- 12 . Median time from injury to blood sampling for TA-MC was 240 ( interquartile range , 116 - 360 ) days . Nine of 32 patients ( 28 % ) in the nonleukoreduced transfusion group developed TA-MC compared to 13 of 35 patients ( 37 % ) in the leukoreduced group ( p = 0.43 ) . Subjects with TA-MC were no more likely than subjects without TA-MC to have at least one symptom suggestive of cGVHD ( 64 % vs. 76 % , respectively ) . CONCLUSIONS TA-MC seems to be a prevalent condition among injured patients at the second of two regional trauma centers evaluated , suggesting that it is a common phenomenon after transfusion in the setting of injury . Although leukoreduction removes greater than 99.9 percent of donor WBCs , it fails to prevent or even substantially reduce the likelihood of developing TA-MC . TA-MC does not appear to be strongly associated with symptoms suggestive of cGVHD several months after transfusion In a prospect i ve , r and omized study 35 patients with multiple injuries were examined for early changes of blood coagulation . Parameters suggesting a consumption coagulopathy were lower in patients who died subsequently than in survivors . No therapeutic influence of low dose Heparin therapy or of the proteinase inhibiting substance TrasylolR could be demonstrated Abstract . This study evaluates the hemodynamic effects of the administration of 10 % pentastarch solution ( PS ) during the initial treatment of hypovolemia in trauma patients . This prospect i ve r and omized phase II study included trauma patients admitted to the emergency room with hemorrhagic hypovolemia : systolic blood pressure ( SBP ) < 90 mmHg . Upon admission , the patients were r and omized to receive 10 % PS ( n= 12 ) or isotonic 0.9 % NaCl solution ( IS ) ( n= 11 ) , infused intravenously in 250-ml boluses , repeated until SBP > 100 mmHg . Blood pressure , infused volumes necessary to maintain SBP , and overall survival rates were determined and compared between groups . SBP increased significantly following either IS ( from 64.4 ± 9.2 mmHg to 111.1 ± 6.3 mmHg ) , or PS ( from 63.7 ± 10.6 mmHg to 108.1 ± 9.8 mmHg ) when compared to admission values ( p < 0.05 ) . Endovenous volumes infused were greater ( p= 0.001 ) in IS patients ( 1420 ± 298 ml ) than in PS patients ( 356 ± 64 ml ) . No blood was transfused into PS patients , compared to 370 ± 140 ml of red blood cells transfused into IS patients ( p= 0.015 ) . Mortality rates were similar in the two groups ( p= 0.725 ) . We concluded that PS is a safe , efficient method for inducing hemodynamic recovery of hypovolemic trauma patients , with a clear reduction in the intravenous volumes required for acute resuscitation BACKGROUND The secret with any alternative to transfusion is to minimize the need for transfusion in the first place . This can be done by reducing the volume of blood loss . The volume of blood being lost can be reduced by direct methods where possible ( i.e. , hemostasis at the point of bleeding ) , or by improving the coagulation profile of the patient , thereby improving the extrinsic coagulation . Recombinant activated factor VII ( rFVIIa ) offers theoretical possibilities of improving the coagulation profile . STUDY DESIGN AND METHODS The efficacy and safety of rFVIIa for the treatment of bleeding in patients with severe blunt and penetrating trauma has been investigated in two double-blind , placebo-controlled studies within a single trial-one on patients with blunt injury and the other in similar patients with penetrating injury . RESULTS In patients with blunt trauma alive at 48 hours , treatment with rFVIIa effected a significant reduction in the primary endpoint of 48-hour red blood cell ( RBC ) transfusion requirement ( p = 0.02 ) , and the safety of the dosing regimen was established . Similar trends were observed in patients with penetrating injuries . Across both studies and treatment arms , the 48-hour mortality rate ranged from 16 to 19 percent . In the blunt trauma study , this equated to 13 patients from each arm who died before the benefits of treatment could be adequately assessed . Analysis of data for the 117 blunt trauma patients who survived at least 48 hours after receiving study treatment shows that , in addition to reducing RBC requirement , rFVIIa significantly reduced the need for massive transfusion over 48 hours ( > 20 RBC units ) ( relative risk reduction of 56 % [ 95 % confidence interval : 9%-79 % ] ; p = 0.03 ) , and the fresh-frozen plasma ( p = 0.036 ) , platelet ( p = 0.023 ) , and cryoprecipitate ( p = 0.053 ) requirements within 48 hours , and was associated with a significant reduction in the 30-day risk of acute respiratory distress syndrome ( ARDS ) ( p = 0.05 ) and multiple organ failure and /or ARDS ( p = 0.05 ) . CONCLUSION Treatment with adjunctive rFVIIa significantly reduces transfusion requirements in the 48 hours after severe injury and these procoagulant effects may improve clinical outcome at 30 days BACKGROUND Uncontrolled bleeding is a leading cause of death in trauma . Two r and omized , placebo-controlled , double-blind trials ( one in blunt trauma and one in penetrating trauma ) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa ( rFVIIa ) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma . METHODS Severely bleeding trauma patients were r and omized to rFVIIa ( 200 , 100 , and 100 microg/kg ) or placebo in addition to st and ard treatment . The first dose followed transfusion of the eighth red blood cell ( RBC ) unit , with additional doses 1 and 3 hours later . The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose . RESULTS Among 301 patients r and omized , 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis . In blunt trauma , RBC transfusion was significantly reduced with rFVIIa relative to placebo ( estimated reduction of 2.6 RBC units , p = 0.02 ) , and the need for massive transfusion ( > 20 units of RBCs ) was reduced ( 14 % vs. 33 % of patients ; p = 0.03 ) . In penetrating trauma , similar analyses showed trends toward rFVIIa reducing RBC transfusion ( estimated reduction of 1.0 RBC units , p = 0.10 ) and massive transfusion ( 7 % vs. 19 % ; p = 0.08 ) . Trends toward a reduction in mortality and critical complications were observed . Adverse events including thromboembolic events were evenly distributed between treatment groups . CONCLUSION Recombinant FVIIa result ed in a significant reduction in RBC transfusion in severe blunt trauma . Similar trends were observed in penetrating trauma . The safety of rFVIIa was established in these trauma population s within the investigated dose range BACKGROUND Activated neutrophils have been shown to play a pivotal role in resuscitation injury after traumatic hemorrhagic shock . Blocking the adhesion of neutrophils with a recombinant humanized monoclonal antibody against CD18 ( rhuMAb CD18 ) may reduce resuscitation injury but increase the risk of infection . This was a dose-finding phase II study to determine safety , pharmacokinetics , pharmacodynamics , and clinical outcome parameters for additional studies . METHODS This was a prospect i ve , placebo-controlled , r and omized ( 3:1 ) , double-blind phase II trial enrolling 116 blunt and penetrating trauma patients from 14 trauma centers over a 9-month period . Patients with hypotension ( blood pressure < or = 90 mm Hg ) from hemorrhagic shock were given a single intravenous dose of rhuMAb CD18 or placebo . The three doses tested were 0.5 , 1 , and 2 mg/kg . The drug was administered within 4 hours of the hypotensive episode and no later than 6 hours from time of injury . Exclusion criteria included head injury result ing in Glasgow Coma Scale score less than 8 or a history of cardiopulmonary resuscitation in the trauma center . An independent Drug Safety and Monitoring Review Board periodically review ed unblinded data for safety issues and to give approval for dose escalation . RESULTS Minor and major infection rates in rhuMAb CD18 groups were comparable to placebo . There was no evidence of antibody formation against rhuMAb CD18 . Linear PK was observed within the dose range studied . Duration of neutrophil binding was dose-dependent , with 2 mg/kg result ing in greater than 90 % neutrophil CD18 receptor saturation for approximately 48 hours . The mortality was 6.7 % ( 2 of 30 ) in the placebo group , 4.8 % ( 1 of 21 ) in the 0.5-mg/kg group , 8.5 % ( 4 of 47 ) in the 1-mg/kg group , and 0 % ( 0 of 18 ) in the 2-mg/kg group . The study was not powered for efficacy , and none of the efficacy variables demonstrated statistical significance . Favorable trends were seen in the 2-mg/kg group as compared with placebo in median intensive care unit length of stay ( 5 vs. 9 days ) and median time on ventilator ( 34 vs. 72 hours ) . CONCLUSIONS A single 2-mg/kg dose of rhuMAb CD18 maintains greater than 90 % saturation of neutrophil CD18 receptors for approximately 48 hours in patients with traumatic hemorrhagic shock undergoing resuscitation . There was no trend toward increased infection . A larger trial is needed to demonstrate the clinical efficacy of rhuMAb CD18 , perhaps using more reliable endpoints BACKGROUND We have previously shown that blood transfusion in the first 24 hours is an independent predictor of mortality , intensive care unit ( ICU ) admission , and increased ICU length of stay in the acute trauma setting when controlling for Injury Severity Score , Glasgow Coma Scale score , and age . Indices of shock such as base deficit , serum lactate level , and admission hemodynamic status ( systolic blood pressure , heart rate ) and admission hematocrit were considered potential confounding variables in that study . The objectives of this study were to evaluate admission anemia and blood transfusion within the first 24 hours as independent predictors of mortality , ICU admission , ICU length of stay ( LOS ) , and hospital LOS , with serum lactate level , base deficit , and shock index ( heart rate/systolic blood pressure ) as covariates . METHODS Prospect i ve data were collected on 15,534 patients admitted to a Level I trauma center over a 3-year period ( 1998 - 2000 ) and stratified by age , gender , race , Glasgow Coma Scale score , and Injury Severity Score . Admission anemia and blood transfusion were assessed as independent predictors of mortality , ICU admission , ICU LOS , and hospital LOS by logistic regression analysis , with base deficit , serum lactate , and shock index as covariates . RESULTS Blood transfusion was a strong independent predictor of mortality ( odds ratio [ OR ] , 2.83 ; 95 % confidence interval [ CI ] , 1.82 - 4.40 ; p < 0.001 ) , ICU admission ( OR , 3.27 ; 95 % CI , 2.69 - 3.99 ; p < 0.001 ) , ICU LOS ( p < 0.001 ) , and hospital LOS ( Coef , 4.37 ; 95 % CI , 2.79 - 5.94 ; p < 0.001 ) when stratified by indices of shock ( base deficit , serum lactate , shock index , and anemia ) . Patients who underwent blood transfusion were almost three times more likely to die and greater than three times more likely to be admitted to the ICU . Admission anemia ( hematocrit < 36 % ) was an independent predictor of ICU admission ( p = 0.008 ) , ICU LOS ( p = 0.012 ) , and hospital LOS ( p < 0.001 ) . CONCLUSION Blood transfusion is confirmed as an independent predictor of mortality , ICU admission , ICU LOS , and hospital LOS in trauma after controlling for severity of shock by admission base deficit , lactate , shock index , and anemia . The use of other hemoglobin-based oxygen-carrying resuscitation fluids ( such as human or bovine hemoglobin substitutes ) in the acute postinjury period warrants further investigation In a prospect i ve double blind clinical study of 70 patients with bony trauma and shock , 35 patients were allocated into each group receiving either a placebo or Aprotinin . In both groups there was a high incidence of pulmonary insufficiency and thrombocytopaenia . In the placebo group there was a higher incidence of pulmonary insufficiency , but not its severity , with greater volumes of blood transufsion and the most severe form occurred only after decompensated shock . Thrombocytopaenia showed a similar pattern in all patients from both groups falling to a mean minimum on the 2nd day and rising thereafter . In the placebo group counts were lower in those with decompensated shock , and the fall was more profound , rapid and earlier in patients developing severe pulmonary insufficiency . Counts of less than 100,000 on the first day were associated with a high probability of severe pulmonary insufficiency subsequently occurring and this finding was not associated with greater volumes of blood transfusion . In those patients receiving Aprotinin , the subsequent incidence of severity of pulmonary insufficiency was less and not associated with increased volumes of blood transfusion . The platelet counts were not lower in decompensated shock and there was a more rapid rise from the minimum level BACKGROUND The infusion of small volumes of hypertonic saline solution or hypertonic saline plus dextran 70 is remarkably effective in restoring adequate hemodynamic conditions after hypovolemic shock . This prospect i ve double-blind study compares the immediate hemodynamic effects of a bolus infusion of 7.5 % NaCl or 7.5 % NaCl plus 6 % dextran 70 ( both 2400 mOsm/L ) in severe hypovolemia . METHODS One hundred five adult patients admitted in hypovolemic shock ( systolic blood pressure less than 80 mm Hg ) were revived on arrival to the emergency room and administration of a 250 ml intravenous bolus of hypertonic saline solution ( n = 35 ) , hypertonic saline plus dextran ( n = 35 ) , or isotonic saline solution ( n = 35 ) . This infusion was immediately followed by st and ard crystalloid and blood replacement until systolic pressure reached 100 mm Hg . Mean arterial pressure ( MAP ) was measured every 5 minutes , and all intravenous infusions were registered . Plasma volume expansion was calculated from plasma protein concentration measurements . Patients were followed up throughout their hospital course , and results of treatment were recorded . RESULTS At the end of the infusion period , and 5 and 10 minutes after infusion , MAP was significantly higher in patients receiving either hypertonic solution , compared with the group receiving isotonic solution . All groups showed similar trends toward restoration of hemodynamic parameters thereafter . The calculated plasma volume expansion , immediately after the bolus infusion , was significantly higher ( 24.1 % + /- 1.8 % and 24.9 % + /- 1.1 % ) in the hypertonic groups , compared with isotonic groups ( 7.9 % + /- 1.3 % ) . Significantly greater volumes of fluids were required to restore systolic pressure in the patients receiving isotonic saline solution than in the groups receiving hypertonic solution . There were no significant differences between the groups receiving hypertonic solutions . The incidence of complications was low , and the mortality rate was similar in all groups . CONCLUSIONS Infusion of 250 ml hypertonic saline solution in patients with severe hypovolemia was not related to any complications , nor did it affect mortality rates ; it improved MAP significantly , acutely exp and ed plasma volume by 24 % , and reduced significantly the volumes of crystalloids and blood required in their resuscitation Objectives : Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors . Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity . We hypothesized that early coagulopathy is due to tissue hypoperfusion , and investigated derangements in coagulation associated with this . Methods : This was a prospect i ve cohort study of major trauma patients admitted to a single trauma center . Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times , prothrombin fragments 1 + 2 , fibrinogen , thrombomodulin , protein C , plasminogen activator inhibitor-1 , and d-dimers . Base deficit ( BD ) was used as a measure of tissue hypoperfusion . Results : A total of 208 patients were enrolled . Patients without tissue hypoperfusion were not coagulopathic , irrespective of the amount of thrombin generated . Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD . An increasing BD was associated with high soluble thrombomodulin and low protein C levels . Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high d-dimer levels . High thrombomodulin and low protein C levels were significantly associated with increased mortality , blood transfusion requirements , acute renal injury , and reduced ventilator-free days . Conclusions : Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors . Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation . Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma Experimental data have suggested that pneumatic external counterpressure improves outcome in intra-abdominal hemorrhage by either a tamponade effect and /or elevation in central systemic blood pressure . As a result , the empiric use of the pneumatic antishock garment ( PASG ) has become a st and ard of care , even to the point where the device has been legislated as required equipment on emergency medical rescue vehicles . However , the effect of the PASG on intra-abdominal hemorrhage has not been evaluated in r and omized clinical trials . The purpose of this study was to evaluate the effect of the PASG on the survival of hypotensive patients with penetrating abdominal injuries . During a 2 1/2-year period , 201 consecutive patients presenting with penetrating anterior abdominal injuries and an initial prehospital systolic blood pressure of 90 mm Hg or less were entered into the study . All prehospital care was delivered by the same municipal emergency medical services system , and all patients subsequently were transported to the same regional trauma facility . The patients were r and omized into control and pneumatic external counterpressure groups by an alternate-day assignment of PASG use . The result ing study population s ( control , n = 104 ; PASG , n = 97 ) were found to be well matched for survival probability indices , prehospital response and transport times , and the volume of IV fluids received . The results demonstrated no significant difference in the survival rates of the control and PASG treatment groups ( 81 of 104 vs 67 of 97 ) . From these data we conclude that , contrary to previous cl aims , the PASG provides no significant advantage in improving survival in the urban prehospital management of penetrating abdominal injuries 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 Introduction We conducted a post-hoc analysis on the effect of recombinant factor VIIa ( rFVIIa ) on coagulopathic patients from two r and omized , placebo-controlled , double-blind trials of rFVIIa as an adjunctive therapy for bleeding in patients with severe trauma . Methods Blunt and penetrating trauma patients were r and omly assigned to rFVIIa ( 200 + 100 + 100 μg/kg ) at 0 , 1 , and 3 hours after transfusion of 8 units of red blood cells ( RBCs ) or to placebo . Subjects were monitored for 48 hours post-dosing and followed for 30 days . Coagulopathy was retrospectively defined as transfusion of fresh frozen plasma ( FFP ) ( > 1 unit of FFP per 4 units of RBCs ) , FFP in addition to whole blood , and transfusion of platelets and /or cryoprecipitate . Results Sixty rFVIIa-treated and 76 placebo subjects were retrospectively identified as being coagulopathic . No significant differences were noted in baseline characteristics . The rFVIIa-treated coagulopathic subgroup consumed significantly less blood product : RBC transfusion decreased by 2.6 units for the whole study population ( P = 0.02 ) and by 3.5 units among patients surviving more than 48 hours ( P < 0.001 ) . Transfusion of FFP ( 1,400 versus 660 ml , P < 0.01 ) , platelet ( 300 versus 100 ml , P = 0.01 ) , and massive transfusions ( 29 % versus 6 % , P < 0.01 ) also dropped significantly . rFVIIa reduced multi-organ failure and /or acute respiratory distress syndrome in the coagulopathic patients ( 3 % versus 20 % , P = 0.004 ) , whereas thromboembolic events were equally present in both groups ( 3 % versus 4 % , P = 1.00 ) . Conclusion Coagulopathic trauma patients appear to derive particular benefit from early adjunctive rFVIIa therapy |
2,461 | 17,054,131 | All shunts result ed in a significantly lower rebleeding rate at the expense of a higher incidence of encephalopathy .
TIPS was complicated by a high incidence of shunt dysfunction .
No survival advantage was demonstrated with any shunt | BACKGROUND R and omised clinical trials have compared portosystemic shunting procedures with endoscopic therapy for variceal haemorrhage , but there is no consensus as to which approach is preferable .
OBJECTIVES To compare the effects of shunts ( total surgical shunt ( TS ) ; distal spleno-renal shunts ( DSRS ) or transjugular intrahepatic porto-systemic shunts ( TIPS ) with endoscopic therapy ( ET , sclerotherapy and /or b and ing ) for prevention of variceal rebleeding in patients with cirrhosis . | Seventy consecutive cirrhotic patients with persistent or recurrent variceal bleeding were included in a clinical trial to compare the efficacy and safety of portacaval shunt ( PCS ) and stapler transection ( ST ) in patients with low surgical risk , and of stapler transection and endoscopic sclerotherapy ( ES ) in patients with high surgical risk . To classify the patients into low- and high-risk groups a new scoring system was used , based on an analysis of factors influencing operative mortality in an earlier series of emergency portacaval shunt . Thirty-eight low-risk patients were r and omly allocated for treatment with portacaval shunt ( 19 patients ) or stapler transection ( 19 patients ) , and 32 high-risk patients for stapler transection ( 17 patients ) or ES ( 15 patients ) . The operative mortality of patients treated by PCS was close to that expected according to retrospective data , this indicating that the proposed scoring system is highly discriminant . In low-risk patients , portacaval shunt evidence d greater haemostatic efficacy and fewer complications than stapler transection . However , hepatic encephalopathy during follow-up was more frequent in the portacaval shunt group and there were no significant differences in operative mortality and long-term survival between the two groups . In high-risk patients , stapler transection and sclerotherapy had a similar haemostatic efficacy , operative mortality and long-term survival . However , sclerotherapy occasioned fewer complications than stapler transection . Our results motivate us to recommend stapler transection for low-risk patients and to consider sclerotherapy as an alternative for high-risk patients in the emergency treatment of uncontrolled variceal bleeding Portosystemic encephalopathy is a common complication of surgical portacaval shunts . Recently , transjugular intrahepatic portosystemic shunts have been proposed to produce portal decompression in a manner analogous to a side-to-side portacaval shunt , but with less morbidity . The incidence and clinical spectrum of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts , however , had not been previously prospect ively defined . We therefore prospect ively studied portosystemic encephalopathy in 30 patients undergoing transjugular intrahepatic portosystemic shunts and compared these findings with 25 patients concurrently undergoing sclerotherapy ( controls ) . At entry , both study groups were comparable . Portosystemic encephalopathy was assessed by examining and grading mental status , asterixis , plasma ammonia and trail making tests . The portosystemic encephalopathy index was calculated from these parameters . Nine of 30 patients with transjugular intrahepatic portosystemic shunts experienced 24 episodes of acute portosystemic encephalopathy during follow-up ; 6 of 9 had a history of portosystemic encephalopathy before transjugular intrahepatic portosystemic shunts and 5 of these 6 patients had Child C cirrhosis . Mental status and asterixis scores as well as portosystemic encephalopathy index worsened significantly in the first month after transjugular intrahepatic portosystemic shunts but showed some improvement thereafter . Increasing age , a medical history of portosystemic encephalopathy and trail scores for part B greater than 100 sec were predictors of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts . Portosystemic encephalopathy could be managed medically in all but one patient who underwent liver transplant . In contrast , there were no significant changes in mental status , asterixis , ammonia or trail scores over time in sclerotherapy controls . Only six episodes of encephalopathy occurred in endoscopic sclerotherapy patients over the duration of the study . Thus , overall risk of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts was higher than during sclerotherapy A prospect i ve r and omized trial was conducted in unselected , consecutive patients with bleeding esophageal varices result ing from cirrhosis comparing ( 1 ) emergency portacaval shunt performed within 8 hr of initial contact ( 21 patients ) with ( 2 ) emergency medical therapy ( intravenous vasopressin and esophageal balloon tamponade ) followed in 9 to 30 days by elective portacaval shunt in survivors ( 22 patients ) . All patients underwent the same diagnostic workup within 3 to 6 hr of initial contact , and received identical supportive therapy initially . All patients were followed up for at least 10 yr . The protocol contained no escape or crossover provisions . There were no statistically significant differences between the two treatment groups in the incidence of any of the clinical variables , results of laboratory tests or degree of portal hypertension . Child 's risk classes in the shunt group were A—2 patients , B—8 patients and C—11 patients , whereas in the medical group they were A—10 patients , B—5 patients , and C—7 patients , a significant difference ( p < 0.01 ) that might have favored emergency medical treatment . Bleeding was controlled initially and permanently by emergency shunt in every patient , but by medical therapy in only 45 % ( p < 0.001 ) . Mean requirement for blood transfusion was 7.1 ± 2.6 units in the shunt group and 21.4 ± 2.6 units in the medical group ( p < 0.001 ) . Eighty‐one percent of the patients in the shunt group were discharged alive compared with 45 % in the medical group ( p = 0.027 ) . Five‐ and 10‐yr observed survival rates were 67 % and 57 % , respectively , after emergency shunt compared with 18 % and 18 % , respectively , after the combination of emergency medical therapy and elective shunt ( p < 0.01 ) . These survival rates produced by emergency shunt performed within 8 hr of initial contact confirm the effectiveness of this procedure observed in our previous unr and omized studies . ( Hepatology 1994;20:863–872 ) BACKGROUND The transjugular-intrahepatic-portosystemic shunt is a new interventional treatment for portal hypertension . The aim of our study was to compare the transjugular shunt with endoscopic treatment for the prophylaxis of recurrent variceal bleeding . METHODS Between March , 1993 , and March , 1996 , 126 patients with variceal bleeding were r and omly assigned either transjugular shunt ( n = 61 ) or endoscopic treatment ( n = 65 ) . Patients were followed up for a median of 14 ( IQR 8 - 25 ) months and 13 ( 8 - 25 ) months , respectively . In 31 ( 51 % ) of the shunted patients , simultaneous transjugular-variceal embolisation was done at the time of shunt placement . Endoscopic treatment consisted of sclerotherapy and /or b and ing ligation and was combined with propranolol medication . FINDINGS Technical success was achieved in all patients assigned to the shunt group . During follow-up , the cumulative 1-year variceal rebleeding rates in the shunted and endoscopically treated patients were 15 % and 41 % and the 2-year rates were 21 % and 52 % ( p = 0.001 ) , respectively . In nine ( 12 % ) patients from the endoscopic group treatment failed and the patients received the transjugular-shunt treatment . A total of 19 bleeding episodes from any source occurred in 15 patients in the shunt group compared with 100 episodes in 33 patients in the endoscopic group . There was no difference in survival with estimated 1-year survival rates for shunted and endoscopically treated patients of 90 % and 89 % , and 2-year survival rates of 79 % and 82 % , respectively . The incidence of clinical ly significant hepatic encephalopathy after 1 year was higher in the shunt group ( 36 % vs 18 % , p = 0.011 ) . INTERPRETATION These results suggest , that the transjugular shunt is more effective than endoscopic treatment in prevention of variceal rebleeding but has a considerable risk of hepatic encephalopathy . Survival is similar in the two groups OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND AND METHODS We compared propranolol therapy and endoscopic ligation for the primary prevention of bleeding from esophageal varices . This prospect i ve , controlled trial included consecutive eligible patients who had large varices ( > 5 mm in diameter ) that were at high risk for bleeding . The patients were assigned to either propranolol therapy , at a dose sufficient to decrease the base-line heart rate by 25 percent , or variceal ligation , to be performed weekly until the varices were obliterated or so reduced in size that it was not possible to continue treatment . RESULTS Of the 89 patients , 82 of whom had cirrhosis of the liver , 44 received propranolol and 45 underwent variceal ligation . The mean ( + /-SD ) duration of follow-up in each group was 14+/-9 and 13+/-10 months , respectively . The mean time required to achieve an adequate reduction in the heart rate was 2.5+/-1.7 days ; the mean number of sessions needed to complete variceal ligation was 3.2+/-1.1 . After 18 months , the actuarial probability of bleeding was 43 percent in the propranolol group and 15 percent in the ligation group ( P=0.04 ) . Twelve patients in the propranolol group and four in the ligation group had bleeding . Three of the four in the ligation group had bleeding before their varices had been obliterated . Nine patients in the ligation group had recurrent varices , a mean of 3.7 months after the initial treatment . Five patients in each group died ; bleeding from the varices was the cause of death of four patients in the propranolol group and of three in the ligation group . There were no serious complications of variceal ligation ; in the propranolol group , treatment was stopped in two patients because of side effects . CONCLUSIONS In patients with high-risk esophageal varices , endoscopic ligation of the varices is safe and more effective than propranolol for the primary prevention of variceal bleeding Fifty-two patients with severe cirrhosis ( Child Class C ) and variceal hemorrhage requiring six or more units of blood were r and omly assigned to either sclerotherapy or portacaval shunt . Of 38 pretreatment characteristics , only the frequency of active alcoholism differed significantly between the groups . During the initial hospitalization , the patients in the shunt group required significantly more blood ( 21.5 + /- 3.1 units ) than did those in the sclerotherapy group ( 12.3 + /- 1.3 units ) , although the latter had significantly more rebleeding during hospitalization after the procedure ( 14 of 28 vs. 5 of 24 patients ) . There was no difference in short-term survival , with 13 patients in the sclerotherapy group discharged alive , as compared with 10 patients in the shunt group . Patients were followed for a mean of 263 days after the initial discharge ( range , 8 to 1117 ) . The sclerotherapy group required significantly more days of hospitalization for rebleeding , but we failed to demonstrate any significant difference in long-term survival between the sclerotherapy and shunt groups . Total health-care costs per patient were significantly higher for the shunt group ( + 23,957 + /- + 3,111 ) than for the sclerotherapy group ( + 15,364 + /- + 2,220 ) . We conclude that sclerotherapy is less costly than portacaval shunt and as effective for the treatment of esophageal varices associated with severe cirrhosis In a continuation of a trial for which preliminary results were reported in the Journal two years ago , a total of 64 patients with Child Class C cirrhosis and variceal hemorrhage requiring six or more units of blood were r and omly assigned to receive either a portacaval shunt ( 32 patients ) or endoscopic sclerotherapy ( 32 patients ) . The duration of initial hospitalization and the total amount of blood transfused during hospitalization were significantly less in the patients receiving sclerotherapy ( P less than 0.001 ) . There was no difference in short-term survival ( 50 percent of the sclerotherapy group were discharged alive , as compared with 44 percent of the shunt-surgery group ) . Both groups were followed for a mean of 530 days after r and omization . Rebleeding from varices , the duration of rehospitalization for hemorrhage , and transfusions received after discharge were all significantly greater in the sclerotherapy group ( P less than 0.001 ) . Forty percent of the sclerotherapy-treated patients discharged alive ( 7 of 16 patients ) ultimately required surgical treatment for bleeding varices , despite a mean of 6.1 treatment sessions . Health care costs and long-term survival did not differ significantly between the groups ( P greater than 0.05 ) . We conclude that although endoscopic sclerotherapy is as good as surgical shunting for the acute management of variceal hemorrhage in poor-risk patients with massive bleeding , sclerotherapy-treated patients in whom varices are not obliterated and bleeding continues should be considered for elective shunt surgery BACKGROUND AND AIMS The transjugular intrahepatic portosystemic shunt ( TIPS ) is a new therapeutic modality for variceal bleeding . In this study we compared the two year survival and rebleeding rates in cirrhotic patients treated by either variceal b and ligation or TIPS for variceal bleeding . METHODS Eighty cirrhotic patients ( Pugh score 7–12 ) with variceal bleeding were r and omly allocated to TIPS ( n=41 ) or ligation ( n=39 ) , 24 hours after control of bleeding . RESULTS Mean follow up was 581 days in the ligation group and 678 days in the TIPS group . The two year survival rate was 57 % in the TIPS group and 56 % in the ligation group ( NS ) ; the incidence of variceal rebleeding after two years was 18 % in the TIPS group and 66 % in the ligation group ( p<0.001 ) . Uncontrolled rebleeding occurred in 11 patients in the ligation group ( eight were rescued by emergency TIPS ) but in none of the TIPS group . The incidence of encephalopathy at two years was 47 % in the TIPS group and 44 % in the ligation group ( NS ) . CONCLUSIONS TIPS did not increase the two year survival rate compared with variceal b and ligation after variceal bleeding in cirrhotic patients with moderate or severe liver failure . It significantly reduced the incidence of variceal rebleeding without increasing the rate of encephalopathy Between September 1982 and April 1988 , 60 cirrhotic patients with prior variceal hemorrhage were r and omized to undergo the placement of an elective shunt ( distal splenorenal : 26 ; nonselective : 4 ) or long-term endoscopic sclerotherapy ( n = 30 ) . Eighty-six percent of patients had alcoholic cirrhosis , and 33 % were classified as Child 's class C. After a mean follow-up of 87 months , 60 % of patients undergoing sclerotherapy and 17 % of shunt patients experienced rebleeding ( p < 0.001 ) . Shunt patients have survived longer than those who had sclerotherapy ( 6-year survival rates of 53 % and 26 % , respectively ; p < 0.05 ) . In part because of the wide geographic distribution of patients , only 4 of 13 patients in whom sclerotherapy failed ( 31 % ) could undergo salvage by shunt surgery . Although hepatic portal perfusion was better maintained after sclerotherapy , there were no major differences between the groups in terms of post-therapy hepatic or psychoneurologic function . In a predominantly alcoholic cirrhotic patient population ( half non-urban ) , the results of elective shunt surgery were superior to those of chronic endoscopic sclerotherapy with respect to the prevention of recurrent variceal hemorrhage and survival Five hundred four shunt procedures have been done at Emory University Hospitals between 1971 and 1981 to decompress bleeding esophageal varices . This paper review s how far the experiences of a prospect i ve r and omized study ( 55 patients ) of distal splenorenal shunts against total shunts is supported by the nonr and omized experience ( 449 patients ) , and outlines our current methods of management dictated by this experience . The overall operative mortality for 348 selective shunts is 4.1 % , and for 156 nonselective shunts , 14.1 % . The five-year survival following selective shunt is 59 % , and following nonselective shunt is 49 % : more than half the selective shunt patients are alive , in contrast to the median survival of 44.5 months for patients having nonselective shunts . Following selective shunt , the survival in nonalcoholic patients is significantly better than the median survival of alcoholic patients of 57 months . Encephalopathy , reported at three years after surgery in the r and omized patients was significantly ( p < 0.001 ) lower after selective shunt ( 12 % ) compared to nonselective shunt ( 52 % ) : in the same population at seven years , all patients with patent nonselective shunts have clinical or sub clinical encephalopathy , but only 30 % of the selective shunt patients have sub clinical encephalopathy . Shunt patency , immediately after surgery , is 93 % following selective shunt , with only two documented late thromboses : nine of nine patients , at a mean of seven years , retain patency in the r and omized study . Shunt occlusion increases with time after interposition nonselective shunts : seven of 13 are occluded at a mean follow-up of seven years in the r and omized study . Portal venous perfusion is retained in 93 % of patients seven to ten days after selective shunt , but in no patient with a patent nonselective shunt . Late portal perfusion is maintained in nine of the eleven patients in the r and omized group studied at a mean of seven years after selective shunt . Restoration of portal perfusion has led to clearing of encephalopathy and improvement in hepatic function in six patients . The following conclusions are made ; ( 1 ) selective shunts can be done with low operative mortality , and long-term patency with excellent control of bleeding ; ( 2 ) hepatic portal venous perfusion has been maintained after selective shunt for ten years , and this is vital for preventing encephalopathy and maintaining hepatic function ; ( 3 ) long-term survival after selective shunt is better than any reported series for nonselective shunt ; and ( 4 ) selective shunts are the operative procedure of choice for variceal decompression and nonselective shunts should rarely be performed for elective decompression BACKGROUND & AIMS In patients with cirrhosis of the liver , after the first variceal bleeding episode , transjugular intrahepatic portosystemic stent shunting ( TIPS ) and endoscopic sclerotherapy plus propranolol ( ES ) were compared regarding prevention of variceal rebleeding and mortality . METHODS Eighty-three patients with cirrhosis of the liver were r and omized to undergo TIPS ( n = 42 ) or ES ( n = 41 ) . RESULTS Median observation time was in 1.6 years in the TIPS group and 1.45 years in the ES group . Cumulative rates of rebleeding were 23 % in the TIPS group and 57 % in the ES group ( P = 0.0001 ) . Hepatic encephalopathy was observed in 29 % of the patients in the TIPS group and in 13 % of those in the ES group ( P = 0.041 ) . Cumulative rates of survival were 69 % in the TIPS group and 67 % in the ES group ( P = 0.62 ) . Mortality rates in both groups were positively correlated with a higher Child 's classification . CONCLUSIONS Although TIPS significantly reduced the rate of rebleeding , survival rates were not improved . Because TIPS is associated with an increased risk of encephalopathy and high rates of shunt dysfunction , which requires reintervention , the procedure can not be recommended for elective treatment after the first variceal bleeding episode , but it is an effective therapy in patients in whom endoscopic sclerotherapy fails to control bleeding OBJECTIVES To compare endoscopic sclerotherapy , propranolol and distal splenorenal shunt in the prevention of rebleeding esophageal varices and mortality in alcoholic cirrhotics . METHODS Forty-three alcoholic cirrhotics that had bled from esophageal varices were r and omized to sclerotherapy ( 13 ) , shunt ( 15 ) or propranolol(15 ) . Outcomes measured were rebleeding from varices and death . RESULTS There was no significant difference between the three treatment groups in relation to rebleeding rate or death . Continued alcohol consumption did not influence outcome . CONCLUSIONS All three therapies were equally effective in preventing rebleeding from varices STUDY OBJECTIVE To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis . DESIGN A prospect i ve , r and omized clinical trial with crossover for those failing therapy . The median follow-up was 61 months . SETTING A private , tertiary-referral university hospital . PATIENTS Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval . TREATMENTS Endoscopic variceal sclerosis or distal splenorenal shunt . MEASUREMENTS AND MAIN RESULTS Survival was significantly ( P = 0.02 ) improved in patients r and omly assigned to receive sclerotherapy : 13 of these 37 ( 35 % ) patients failed sclerotherapy and required surgical rescue . A survival advantage ( P = 0.01 ) was seen in patients with alcoholic cirrhosis who had this combined therapy ; however , in patients with nonalcoholic cirrhosis , survival for those receiving sclerotherapy and surgical rescue was not significantly ( P = 0.36 ) different from that of patients receiving distal splenorenal shunt . Control of variceal bleeding was significantly ( P less than 0.001 ) better in the distal splenorenal shunt group ( 34 of 35 [ 97 % ] compared with 15 of 37 [ 41 % ] in the sclerotherapy group ) . Using death , uncontrolled rebleeding , or shunt thrombosis as the endpoints result ed in no significant difference between treatment groups . Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt ( P = 0.01 and P = 0.001 , respectively ) . CONCLUSIONS Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding . Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy , but shunting provides better control of variceal bleeding BACKGROUND Sclerotherapy is usually effective in controlling acutely bleeding esophageal varices . It may not be as effective as shunt surgery for prevention of rebleeding ; therefore we undertook a prospect i ve study comparing interposition mesocaval shunt ( MCS ) and repeated sclerotherapy . METHODS Forty-five patients ( mean age , 52.6 + /- 9.8 years ) with variceal bleeding were r and omized after emergency endoscopic sclerotherapy either to repeat variceal obliteration followed by regular check endoscopy ( n = 21 ) or to elective interposition mesocaval shunting by use of 14 mm polytetrafluoroethylene graft ( n = 24 ) . There was an equal distribution of Child 's classes in the two groups . RESULTS In the sclerotherapy group 12 patients had recurrent hemorrhages causing five deaths compared with the shunt group , in which four patients had postoperative bleeding but without associated death . No difference was noted in the incidence of encephalopathy despite the development of total shunting 1 year after MCS . The median hospital stay was similar ; 34.5 days ( MCS ) and 33 days ( sclerotherapy ) . The number of intensive care unit days was also similar in the two groups . No difference was noted in survival in patients with Child 's A and Child 's B disease in the treatment groups . In patients with Child 's C cirrhosis there was a statistically significant longer survival in patients undergoing MCS compared with patients undergoing sclerotherapy . CONCLUSIONS The results of the study show that the rate of rebleeding is significantly higher after sclerotherapy than after mesocaval shunting . In patients with Child 's C cirrhosis MCS may be an alternative to sclerotherapy for the prevention of rebleeding from esophageal varices in patients not suitable for transplantation The role of sclerotherapy in long-term management after oesophageal variceal bleeding was assessed by comparing repeated sclerotherapy by means of a rigid oesophagoscope in 37 patients with control medical management in 38 patients . Varices were eradicated in 21 of the 22 patients analysed ( 95 % ) in the sclerotherapy group , but recurred in 13 of the 21 patients ( average 21.5 months ) . Varices persisted in 13 of 14 surviving controls . The sclerotherapy patients had fewer recurrent bleeds than control patients ( 43 versus 73 ) ; the majority occurred before variceal eradication and were mild . However , there was no difference in survival in the two groups . The commonest cause of death was liver failure ( 37 patients ) . 32 complications occurred in 24 patients during 258 injections . Repeated sclerotherapy failed to improve survival in this trial , although varices were eradicated and recurrent variceal bleeds were prevented with adequate follow-up The aim of this study was to compare the efficacy of transjugular intrahepatic portosystemic shunt ( TIPS ) with that of endoscopic sclerotherapy ( ES ) in the long-term management of patients with cirrhosis after variceal bleeding . Seventy-eight consecutive cirrhotic patients with recent variceal bleeding were r and omly allocated to either TIPS ( n=38 ) or ES ( n=40 ) . All patients were in good condition at r and omization . The mean follow-up was 1116+/-92 days in the TIPS group and 1047+/-102 days in the ES group . Differences in rebleeding from any source ( 18.4 % vs. 32.5 % ) and esophageal variceal rebleeding ( 15.7 % vs. 27.5 % ) were not significantly different between the two groups ( P>0.05 ) . The mortality rates were similar in both treatment groups . Shunt dysfunction was noted in 27 patients ( 71 % ) in the TIPS group . There were more numbers of rehospitalization during follow-up in the TIPS group than in the ES group ( 2.6+/-0.4 vs. 1.1+/-0.2 ) ( P<0.01 ) . TIPS and ES are equally effective in the prevention of variceal rebleeding . However , TIPS is associated with high incidence of shunt dysfunction , which lead to more rehospitalization . Therefore , TIPS may not be a first-line treatment for the prevention of variceal rebleeding in cirrhotic patients who are in stable condition In 1984 we started a prospect i ve controlled trial comparing endoscopic sclerotherapy ( ES ) with the distal splenorenal shunt ( DSRS ) in the elective treatment of variceal hemorrhage in cirrhotic patients . The study population included 40 patients with cirrhosis and portal hypertension referred to our department from October 1984 to March 1988 . These patients were drawn from a pool of 173 patients who underwent either elective surgery or endoscopic sclerotherapy during this time . Patients were assigned to one of the two groups according to a r and om-number table : 20 to DSRS and 20 to ES . During the postoperative period , no DSRS patient died , while one ES patient died of uncontrolled hemorrhage . One DSRS patient had mild recurrent variceal hemorrhage despite an angiographically patent DSRS . Four ES patients suffered at least one episode of gastrointestinal bleeding : two from varices and two from esophageal ulcerations . Five ES patients developed transitory dysphagia . Long-term follow-up was complete in all patients . Two-year survival rates for shunt ( 95 % ) and ES ( 90 % ) groups were similar . One DSRS patient rebled from duodenal ulcer , while three ES patients had recurrent bleeding from esophagogastric sources ( two from varices and one from hypertensive gastropathy ) . One DSRS and two ES patients have evolved a mild chronic encephalopathy ; four DSRS and two ES patients suffered at least one episode of acute encephalopathy . Two ES patients had esophageal stenoses , which were successfully dilated . Preliminary data from this trial seem to indicate that DSRS , in a subgroup of patients with good liver function and a correct portal-azygos disconnection , more effectively prevents variceal rebleeding than ES . However no significant difference in the survival of the two treatment groups was noted This paper reports the preliminary results of a prospect i ve r and omized trial comparing endoscopic variceal sclerosis and distal splenorenal shunt ( DSRS ) in the management of patients with cirrhosis and variceal bleeding . Seventy-one patients have been entered ; 36 have received sclerosis and 35 DSRS . R and omization of the study population was stratified on Child 's A/B ( 56 % ) and Child 's C ( 44 % ) . Sixty-one per cent had alcoholic and 39 % nonalcoholic cirrhosis . No patients have been lost to follow-up , which currently st and s at a median of 26 months . Rebleeding occurred significantly ( p < 0.05 ) more frequently in patients in the sclerosis group ( 19 of 36 : 53 % ) compared to DSRS ( 1 of 35 : 3 % ) , but only 11 of 36 ( 31 % ) were not controlled by further sclerosis and failed that therapy . Patients in whom sclerosis failed underwent surgery . Survival was significantly ( p < 0.01 ) improved in the sclerosis group ( + surgery in 31 % ) , with an 84 % 2-year survival compared to a 59 % 2-year survival in the DSRS group . Portal perfusion was significantly ( p < 0.05 ) better maintained in the sclerosis ( 95 % ) compared to the DSRS ( 53 % ) group . Galactose elimination capacity improved significantly ( p < 0.05 ) in 21 patients successfully managed by sclerosis at 1 year and was significantly ( p < 0.01 ) better maintained in the sclerosis compared to DSRS group . The authors conclude that endoscopic sclerosis : ( 1 ) has a higher rebleeding rate than DSRS , with one third of patients failing therapy from rebleeding ; ( 2 ) allows significant improvement in liver function when successful ; and ( 3 ) gives significantly improved survival in the management of variceal bleeding when backed up by surgical therapy for patients with uncontrolled rebleeding BACKGROUND / AIMS Deterioration of hepatic encephalopathy is a major concern with the transjugular intrahepatic portosystemic shunt procedure . Symmetric hyperintense globus pallidus on T1-weighted cranial magnetic resonance imaging in patients with liver cirrhosis anticipates hepatocerebral disease . It is hypothesized that hepatic encephalopathy and basal ganglia signal intensity progress in patients with cirrhosis of the liver undergoing transjugular intrahepatic portosystemic shunt . METHODS Twenty-four patients were r and omized to undergo either transjugular intrahepatic portosystemic shunt or elective sclerotherapy . At study entry and 6 months after r and omization , neurologic assessment , psychometric tests , st and ard EEG , and magnetic resonance imaging were performed . The severity of liver failure was grade d using Child-Pugh 's classification . The signal intensity of the globus pallidus was determined on sagittal T1-weighted magnetic resonance imaging . RESULTS The T1-weighted signal intensity of the globus pallidus on magnetic resonance imaging significantly increased after transjugular intrahepatic portosystemic shunt placement ( p<0.01 ) , but not with elective sclerotherapy . At follow-up , neurological symptoms indicating decline of mental status and motor performance were somewhat more prevalent in transjugular intrahepatic portosystemic shunt patients . Significant deterioration of EEG abnormalities occurred in patients treated with transjugular intrahepatic portosystemic shunt as opposed to elective sclerotherapy ( p<0.01 ) . CONCLUSIONS Transjugular intrahepatic portosystemic shunt procedure increases hyperresonant globus pallidus on magnetic resonance imaging . Neuropsychiatric evaluation shows advancing hepatic encephalopathy , in particular with transjugular intrahepatic portosystemic shunt ; however , it does not parallel the augmentation of pallidal signal intensity on magnetic resonance imaging Thirteen Child 's class C patients with variceal hemorrhage requiring 6 or more units of blood were r and omly assigned to groups receiving either flexible endoscopic sclerotherapy using 5 % sodium morrhuate or esophageal transection/reanastomosis employing the EEA Auto Suture stapling instrument . One patient with a previous hiatus hernia repair was assigned to the transection group and had a mesocaval shunt . The r and omization groups compared favorably with each other and with a retrospective shunt group ( 20 patients ) . Although transection patients required significantly less operative time and fewer blood transfusions , the outcome of the transection group was significantly worse than that of the shunt group . The trend in survival likewise favored the shunt group rather than the sclerotherapy group . Although the reported operative mortality rates of transection and sclerotherapy are less than that of portal decompression , the results of this study --the first controlled trial of these procedures --would warrant distinct caution in using either of these new techniques in high-risk patients . Portal decompression may still be the procedure of choice in class C patients with substantial variceal hemorrhage The aim of this study was to compare transjugular intrahepatic portosystemic stent-shunt ( TIPSS ) with variceal b and ligation ( VBL ) in the secondary prophylaxis of esophageal variceal hemorrhage in patients with cirrhosis . Fifty-eight patients with cirrhosis who presented with the first episode of esophageal variceal hemorrhage were r and omized to TIPSS ( 31 ) or VBL ( 27 ) , 24 hours after control of bleeding . Shunt function was assessed after 1 month and then at 6 monthly intervals thereafter . VBL was performed weekly until variceal eradication , and then at 3 months , 6 months , and yearly thereafter . Mean follow-up in the TIPSS group was 15.7 ( + /-10.2 ) months ; in the VBL group , it was 16.8 ( + /-10.9 ) months . Results for rebleeding and mortality were analyzed on an intention-to-treat basis and using the Kaplan-Meier method . The frequency and the severity of variceal rebleeding was significantly lower in the TIPSS group ( 9.8 % ) , compared with the VBL group ( 51.9 % ) ( P < .0006 ) . Although mortality rates were not significantly different , 8 of the patients who rebled in the VBL group required TIPSS therapy for uncontrolled bleeding . No significant differences were found in the frequency of other complications such as encephalopathy and sepsis . Patients in the VBL group required significantly greater time in the intensive care unit during the period of this study ( < 0.03 ) . The total direct cost of treatment incurred was pound sterling 1,373 ( $ 2,200 ) per patient , the cost being less in the patients treated with TIPSS compared with VBL . The results of this study show that TIPSS is superior to VBL for the secondary prophylaxis of variceal hemorrhage in patients with cirrhosis One hundred and twelve consecutive Child Class A and B cirrhotic patients were included in a prospect i ve controlled trial aim ed at investigating the efficacy and safety of endoscopic sclerotherapy vs. distal splenorenal shunt in the elective treatment of hemorrhage from esophagogastric varices . Fifty-seven patients were r and omly allocated to splenorenal shunt and 55 to endoscopic sclerotherapy . Since only 4 of the 55 patients assigned to endoscopic sclerotherapy had to be excluded after r and omization and before treatment as compared to 14 of the 57 patients assigned to splenorenal shunt , it is suggested that the applicability of endoscopic sclerotherapy is greater than that of splenorenal shunt . One patient in each group died within 30 days of the procedure and two in the endoscopic sclerotherapy group were lost to follow-up just after discharge . Variceal rebleeding during follow-up occurred in 37.5 % ( 18/48 ) of patients in the endoscopic sclerotherapy group and in 14.3 % of those in the splenorenal shunt group ( 6/42 ) ( p less than 0.02 ) , whereas hepatic encephalopathy was more frequent in patients su bmi tted to splenorenal shunt ( 10/42 , 24 % ) than in those treated by endoscopic sclerotherapy ( 4/48 , 8 % ) ( p less than 0.05 ) . The therapeutic modality was the only variable with independent predictive value for rebleeding during follow-up , whereas for hepatic encephalopathy , the therapeutic modality , and the presence of encephalopathy related to the bleeding episode each showed independent predictive value . Early and long-term mortality , did not differ between the two therapeutic groups , being the 2-year survival was 71 % for splenorenal shunt and 68 % for endoscopic sclerotherapy . ( ABSTRACT TRUNCATED AT 250 WORDS December 1991 through November 1993 , fifty-five patients underwent TIPS with the following indications : failed sclerotherapy or surgery ( 25 patients ) , bleeding from gastric varices ( 3 patients ) , patients waiting for liver transplantation ( 11 patients ) and refractory ascites ( 9 patients ) . Seven patients were included in a r and omized TIPS vs sclerotherapy trial . The average follow-up of living patients is 4.6 months ( range : 1 - 16 months ) . The technical success rate was 100 % . The portosystemic gradient decreased from 22 mmHg to 10.7 mmHg . After TIPS all patients were followed-up with endoscopic , angiographic and color Doppler examinations and underwent periodic clinical checks . Early ( 5-day ) angiographic follow-up exams showed partial stent thrombosis in 5/32 cases ( 15.5 % ) and complete stent thrombosis in 3 cases ( 9.3 % ) . Late angiographic follow-up exams ( 1 - 9 months ) showed complete stent occlusion in 2 cases , stent stenosis in 8 cases and hepatic vein stenosis in 5 cases . At present , 37 patients are alive ( 67 % ) ; 5 patients have undergone liver transplantation ( 9 % ) , and 13 patients died (24%)--3 within 48 - 72 hours after the procedure and 10 in 1 - 8 months . Five patients had recurrent bleeding ( 9 % ) . Ascites was reduced or disappeared in 8/9 cases . Early clinical complications occurred in 12 % of cases and were treated with medical therapy . Within one year , signs of encephalopathy developed in 13 patients ( 23 % ) and were successfully treated with medical therapy BACKGROUND & AIMS Uncontrolled studies suggest that placement of a transjugular intrahepatic portosystemic shunt ( TIPS ) could be useful in the treatment of variceal bleeding . The aim of this study was to evaluate the efficacy and safety of TIPS in the elective treatment of hemorrhage from esophageal varices in a r and omized controlled study that compared the effects of TIPS with those of endoscopic sclerotherapy ( ES ) . METHODS Sixty-three consecutive cirrhotic patients with hemorrhage from esophageal varices were included . Thirty-two patients were r and omly allocated to ES and 31 to TIPS groups . RESULTS One patient in each group died before the therapeutic procedure could be performed . During a mean follow-up period of 15 months , variceal rebleeding occurred in 51.6 % of the patients in the ES group and 23 % of those in the TIPS group . Uncontrolled rebleeding occurred in 10 of 31 patients in the ES group , whereas rebleeding did not occur in any patient of the TIPS group . Hepatic encephalopathy was more frequent in TIPS patients ( 33.3 % ) than in those treated by ES ( 13 % ) . However , mortality was similar in both treatment groups . CONCLUSIONS These preliminary results suggest that TIPS is more effective than ES in the prevention of variceal rebleeding in cirrhotic patients , even though no difference in survival was observed A prospect i ve controlled trial of the therapeutic portacaval shunt was conducted with 79 patients r and omized for medical , end-side or side-side anastomosis . At 5 years no significant differences in survival were established among the groups , although a trend favoring end-side shunt was discernible . In the medical series , 70 % have experienced variceal bleeding and about two-thirds of these have died . Fatality related to liver failure , however , was significantly more common after surgery . No substantial differences between the two surgical shunts were observed with regard to bleeding , encephalopathy , or hepatic function , although the side-side shunt provided better control of ascites . Retrospective analysis on the basis of special clinical features did not identify subgroup(s ) of patients for whom surgical treatment would be advantageous . Nevertheless , published data do not exclude the possibility that a therapeutic portacaval shunt may allow longer survival for the patient with a single major variceal hemorrhage BACKGROUND / AIMS Terlipressin is a long-acting vasopressin analogue that has been proved useful in the treatment of variceal haemorrhage . This study investigates the time profile of the haemodynamic effects of terlipressin on portal hypertension as well as the efficacy in decreasing portal-pressure and collateral blood flow of reduced doses , suitable for longer therapy to prevent early rebleeding . METHODS Splanchnic and systemic haemodynamics were measured in 23 patients with cirrhosis and portal hypertension in baseline conditions and at 30 min , 1 , 2 , 3 and /or 4 h after the double-blind administration of a single intravenous injection of 1 mg ( n=8 ) or 2 mg ( n=8 ) of terlipressin , or placebo ( n=7 ) . RESULTS Placebo caused no significant effects . At 30 min of terlipressin administration , the hepatic venous pressure gradient ( 1 mg : -16+/-9 % , 2 mg : -21+/-11 % ; p<0.01 ) and azygos blood flow ( 1 mg : -19+/-13 % , 2 mg : -25+/-17 % ; p<0.05 ) were significantly reduced . These effects were still significant at 4 h ( 2 mg ) or 3 h ( 1 mg ) . Both doses moderately increased arterial pressure at 1 h. At 4 h , neither arterial pressure nor peripheral vascular resistance was significantly modified by either dose of terlipressin . Terlipressin caused no significant changes in hepatic blood flow . CONCLUSIONS In patients with cirrhosis , a single injection of 2 mg of terlipressin significantly and markedly reduces portal pressure and azygos blood flow for up to 4 h. The effects of a reduced dose ( 1 mg ) were almost as pronounced and prolonged , suggesting that after the initial control of variceal bleeding , terlipressin therapy could be maintained for several days at low dosage to reduce the risk of early rebleeding Treatment of variceal hemorrhage is one of the most controversial subjects in medicine . The resurgence of old therapies ( endoscopic sclerotherapy ) and the introduction of new modalities ( obliterative angiotherapy ) has exacerbated the controversy . No widely accepted controlled therapeutic trial is available . The problem related to survival analysis has been studied in the light of the available information concerning the natural history of variceal bleeding . It is believed that controlled trials can be design ed which will prove the efficacy , or lack of it , for any proposed treatment ; however , valid conclusions based on previous studies are limited , largely because of the many confounding variables . Time , as a variable factor both for r and omization and therapeutic intervention , has been largely ignored , yet , we believe it is the major variable in this setting . For the population of variceal bleeders , risk of rebleeding or death rapidly diminishes over the first few days after a bleed , and early survival may be the best marker for later survival . Neither presentation nor treatment seems to alter this fundamental behavior . Variceal hemorrhage may serve as a prototype for problems of survival analysis of diseases with early high mortality Eighty-two consecutive Child-Campbell class A and B cirrhotic patients were included in a prospect i ve controlled trial to assess the efficacy and safety of portacaval anastomosis vs. endoscopic sclerotherapy as elective treatment of variceal hemorrhage . Forty-one patients were r and omized to portacaval anastomosis and 41 to sclerotherapy . After excluding dropouts , 34 patients were treated with portacaval anastomosis and 35 with sclerotherapy . The incidence of variceal rebleeding during follow-up ( mean + /- SD , 20.6 + /- 14.2 months ) was significantly higher in the sclerotherapy than in the portacaval groups , either considering the overall treated group or only patients completing sclerotherapy ( 40 % and 25 % vs. 2.9 % ; P = 0.0002 and P = 0.01 , respectively ) . The 2-year probability of suffering from at least one episode of hepatic encephalopathy was significantly higher in patients su bmi tted to portacaval anastomosis than in those treated with endoscopic sclerotherapy ( 40 % vs. 12 % ; P = 0.04 ) . However , disabling encephalopathy only appeared in 3 of 34 patients who underwent surgery ( 8.8 % ) . Early and long-term mortality did not differ between the therapeutic groups ; 2-year survival rates were 83 % for portacaval anastomosis and 79 % for sclerotherapy . It is concluded that portacaval anastomosis is more effective than endoscopic sclerotherapy in preventing variceal rebleeding in spite of the greater incidence of hepatic encephalopathy . The role of portacaval anastomosis in the elective treatment of variceal rebleeding should be reassessed Ninety‐six patients with good liver function ( Child class A or B ) and esophageal varices were r and omly assigned to one of three groups given different treatments : endoscopic injection sclerotherapy ( n = 32 ) , esophageal transection ( n = 32 ) or distal splenorenal shunt ( n = 32 ) . Five patients ( 5.2 % ) had to be excluded from this study because severe chronic pancreatitis made separation of the distal splenic vein from the pancreatic bed difficult . Esophageal transection was performed for these patients BACKGROUND Emergency treatment of acute bleeding is of singular and paramount importance in the therapy of portal hypertension and esophagogastric varices . Accordingly , for more than three decades we have conducted prospect i ve studies of emergency therapy , and particularly of emergency portacaval shunt ( EPCS ) . STUDY DESIGN Emergency portacaval shunt was performed upon 400 patients with cirrhosis of the liver and acutely bleeding esophagogastric varices according to three principles : operation within eight hours of initial contact ; unselected patients , meaning that no patient with variceal bleeding caused by hepatic disease was excluded from EPCS , and prospect i ve study , meaning that a well-defined protocol was consistently used and data were collected on-line . Patients were divided into an early group of 180 treated from 1963 to 1978 and a recent group of 220 treated from 1978 to July , 1990 , with similar characteristics , but strikingly different outcome . Follow-up rates at one , five , and ten years were 100 , 98 , and 97 percent , respectively ; 96 percent of patients underwent EPCS five or more years ago . Proof of acute variceal bleeding and of cirrhosis of the liver ( alcoholic in 95 percent ) was obtained in every patient . Child 's risk classes determined quantitatively were A in 11 percent of the patients , B in 65 percent , and C in 24 percent . All patients had a direct portacaval shunt , side-to-side in 85 percent , which reduced the mean portal vein to inferior vena cava pressure gradient from 271 to 21 mm saline solution . RESULTS All but four patients ( 99 percent ) had immediate and permanent control of variceal bleeding . Thrombosis of the shunt occurred in only two patients ( 0.5 percent ) . Survival rates at 30 days , five years , ten years , and 15 years in the early group were 58 , 40 , 30 , and 30 percent , respectively , while in the recent group they were 85 , 78 , 71 , and 57 percent , respectively ( p < 0.0001 ) . Other striking gains in the recent group were abstention from alcohol , improvement in liver function and improvement in Child 's class , all in 70 percent of patients . Recurrent portal-systemic encephalopathy occurred in 9 percent of the early group and 8 percent of the recent group . CONCLUSIONS Emergency portacaval shunt substantially improved survival and quality of life of patients with cirrhosis of the liver and bleeding varices . Our results are attributable to rapid and simplified diagnosis , prompt operation , an organized system of care , and rigorous , lifelong follow-up evaluation that emphasized abstinence from alcohol and dietary protein control . Transplantation of the liver is infrequently required in patients whose bleeding is permanently controlled This presentation draws upon the experience of the O.M.G.E. Multi-national Upper G.I. Bleeding Survey , using data collected during 1980 - 1982 by 185 clinicians from 44 centres in 21 countries to discuss two questions . First , can prognostic factors be identified in patients presenting to hospital with upper G.I. bleeding , and if so what are they ? Second , is it possible - by combining the two technologies of endoscopy and computers - to provide an individual patient with a short-term prognostic prediction sufficiently accurate to affect patient management . Amongst 4,010 patients , a number of clinical factors were found to affect short-term prognosis . These included patient age , previous history of heart or liver disease , confusion and dehydration on admission , jaundice , and ascites . Identification of the bleeding source via endoscopy was shown to aid short-term prognosis - especially in the period of the 2nd to 10th days post-admission . Use of computer analysis enabled " high risk " patients to be defined ( of whom 63.8 % suffered further bleeding and 30.0 % died ) , and also a comparable " low risk " group ( of whom only 4 % suffered further bleeding and none died ) . Finally , " time-dependence " studies have been used to identify a group of patients who ( by the 2nd day post-admission ) have a residual risk of further bleeding sufficiently low ( well under 1 % ) to suggest that considerable re sources can be saved by the judicious use of endoscopy and computer science BACKGROUND & AIMS Transjugular intrahepatic portosystemic shunt ( TIPS ) procedures are increasingly being used , but the relationship between the hemodynamic effects of TIPS and the clinical events on follow-up remains undefined . Hence , we have investigated the hemodynamic correlations of portal hypertension-related events after a TIPS procedure . METHODS Prospect i ve follow-up of 122 cirrhotic patients who had a TIPS procedure performed because of variceal hemorrhage was conducted . RESULTS The portacaval pressure gradient ( PPG ) significantly decreased after the TIPS procedure ( from 19.7 + /- 4.6 to 8.6 + /- 2.7 mm Hg ; P > 0.001 ) , but increased thereafter and at rebleeding ( n = 25 ) was > 12 mm Hg in all patients ( 18.4 + /- 4.6 mm Hg ) . Twenty-six patients developed ascites ; the PPG ( measured in 19 ) was always > 12 mm Hg . Increasing the PPG to > 12 mm Hg occurred very frequently ( 83 % at 1 year ) . Within 1 year , 77 % of patients underwent balloon angioplasty or restenting . However , 80 % had again a PPG of > 12 mm Hg 1 year after reintervention . Hepatic encephalopathy developed in 31 % of patients at 1 year ; 21 of 23 patients had a PPG of < 12 mm Hg . CONCLUSIONS Total protection from the risk of recurrent complications of portal hypertension after a TIPS procedure requires that the PPG be decreased and maintained < 12 mm Hg . However , reintervention will be required in most patients within 1 year and again the second year . On the other h and , such portal decompression is associated with an increased risk of hepatic encephalopathy Background : The aim of the present study was to compare the transjugular intrahepatic portosystemic shunt ( TIPS ) with variceal b and ligation ( VBL ) in the prophylaxis of variceal rebleeding in patients with cirrhosis of the liver . Methods : Fifty-four cirrhotic patients ( 21 Child-Pugh class A , 27 class B , 6 class C ) were r and omized to TIPS ( n = 28 ) or VBL ( n = 26 ) within 2 months after control of esophageal variceal hemorrhage . Statistical analysis was performed on the intention-to-treat principle . Results : Mean follow-up was 2 years . Mortality risk at 1 and 2 years of follow-up was 7.8 % ± 5.3 % and 19.9 % ± 8.8 % in the TIPS group and 16.5 % ± 7.6 % and 16.5 % ± 7.6 % in the VBL group , respectively ( n.s . ) ; actuarial probability of remaining free from rebleeding was 83.7 % ± 7.4 % and 71.4 % ± 10.4 % in the TIPS group and 83.9 % ± 7.3 % and 78.1 % ± 8.8 % in the VBL group at 1 and 2 years , respectively ( n.s . ) . Hepatic encephalopathy within 1 month after r and omization was observed in 2 patients in the TIPS group and in 1 in the VBL group . Conclusion : TIPS is not superior to VBL in the prevention of variceal rebleeding . Furthermore , similar mortality rates in patients treated with TIPS or VBL negate TIPS as the preferred strategy for prevention of variceal rebleeding BACKGROUND Transjugular intrahepatic portosystemic shunt ( TIPS ) is popular in treating portal hypertension because of its perceived efficacy and cost benefits , although it has never been compared with surgical shunting in a cost-benefit analysis . This study was undertaken to determine the cost benefit of TIPS versus small-diameter prosthetic H-graft portacaval shunt ( HGPCS ) . METHODS Cost of care was determined in 80 patients prospect ively r and omized to receive TIPS or HGPCS as definitive treatment for bleeding varices , beginning with shunt placement and including subsequent admissions for complications or follow-up related to shunting . RESULTS Patients were similar in age , gender , severity of illness/liver dysfunction , and urgency of shunting . After TIPS or HGPCS , variceal rehemorrhage ( 8 versus O , respectively ; p = 0.03 ) , shunt occlusion ( 13 versus 4 ; p = 0.03 ) , shunt revision ( 16 versus 4 ; p < 0.005 ) , and shunt failure ( 18 versus 10 ; p = 0.10 ) were compared ; all were more common after TIPS . Through the index admission , TIPS cost $ 48,188 + /- $ 43,355 whereas HGPCS cost $ 61,552 + /- $ 47,615 . With follow-up , TIPS cost $ 69,276 + /- $ 52,712 and HGPCS cost $ 66,034 + /- $ 49,118 . CONCLUSIONS Early cost of TIPS was less than , though not different from , cost of HGPCS . With follow-up , costs after TIPS mounted . The initially lower cost of TIPS is offset by higher rates of subsequent occlusion and rehemorrhage The aim of the present study was to compare the cumulative cost of the first 18‐month period in a selected group of Italian cirrhotic patients treated with transjugular intrahepatic portosystemic shunt ( TIPS ) versus endoscopic sclerotherapy ( ES ) to prevent variceal rebleeding . Thirty‐eight patients enrolled in a controlled trial were considered ( 18 TIPS and 20 sclerotherapy ) . The number of days spent in the hospital for the initial treatment and during the follow‐up period were defined as the costs of hospitalization . ES sessions , TIPS procedures , angioplasty or addition of a second stent to maintain the shunt patency , were defined as the costs of therapeutic procedures . The two groups were comparable for age , sex , and Child‐Pugh score . During the observation period 4 patients died in the TIPS group , and 2 died and 1 was transplanted in the sclerotherapy group . The rebleeding rate was significantly higher in the sclerotherapy group . Despite this , the number of days spent in the hospital was similar in the two groups . This was because of a higher number of hospital admissions for the treatment of hepatic encephalopathy and shunt insufficiency in the TIPS group . The therapeutic procedures were more expensive for TIPS . Consequently , the cumulative cost was higher for patients treated with TIPS than for those treated with sclerotherapy . The extra cost was because of the initial higher cost of the procedure and the difference was still maintained at the end of the 18‐month follow‐up . When the cumulative costs were expressed per month free of rebleeding , the disadvantage of TIPS disappeared . In conclusion , a program of prevention of variceal rebleeding with TIPS , despite the longer interval free of rebleeding , is not a cost‐saving strategy in comparison with BACKGROUND AND STUDY AIMS After a first variceal bleeding episode in patients with cirrhosis of the liver , treatment with transjugular intrahepatic portosystemic stent shunt ( TIPS ) and endoscopic variceal ligation ( EVL ) plus propranolol were compared , with regard to prevention of variceal rebleeding , complications , and mortality . PATIENTS AND METHODS 85 patients were r and omly allocated to receive TIPS ( n = 43 ) or EVL ( n = 42 ) . The groups were comparable regarding age , sex , etiology of liver cirrhosis , and liver function . RESULTS The mean observation times were 4.1 years in the TIPS group and 3.6 years in the EVL group . Although the probability of rebleeding was higher in the EVL group ( 29.9 % ) than in the TIPS group ( 19.4 % ) , the difference was not statistically significant . Three of five patients of the EVL group successfully underwent TIPS placement after treatment failure . The probability of TIPS dysfunction requiring shunt revision was 89 % . Hepatic encephalopathy was observed more often in the TIPS group ( 40.5 % ) than in the EVL group ( 20.5 % ; P < 0.05 ) . The probability of survival was similar in both groups ( TIPS group 75.9 % , EVL group 82.2 % ; n.s . ) . CONCLUSIONS In view of its good efficacy and the lower cost of treatment , endoscopic ligation plus propranolol may be recommended as initial procedure for prevention of recurrent variceal hemorrhage , whereas TIPS seems to be the preferable procedure in patients with recurrent bleeding after adequate endoscopic and pharmacological treatment BACKGROUND & AIMS Variceal bleeding refractory to medical treatment with beta-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts ( TIPS ) . This prospect i ve r and omized trial tested the hypothesis that patients receiving distal splenorenal shunts ( DSRS ) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding . METHODS A prospect i ve r and omized controlled clinical trial at 5 centers was conducted . One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were r and omized to DSRS or TIPS . Protocol and event follow-up for 2 - 8 years ( mean , 46 + /- 26 months ) for primary end points of variceal bleeding and encephalopathy and secondary end points of death , ascites , thrombosis and stenosis , liver function , need for transplant , quality of life , and cost were evaluated . RESULTS There was no significant difference in rebleeding ( DSRS , 5.5 % ; TIPS , 10.5 % ; P = .29 ) or first encephalopathy event ( DSRS , 50 % ; TIPS , 50 % ) . Survival at 2 and 5 years ( DSRS , 81 % and 62 % ; TIPS , 88 % and 61 % , respectively ) were not significantly different ( P = .87 ) . Thrombosis , stenosis , and reintervention rates ( DSRS , 11 % ; TIPS , 82 % ) were significantly ( P < .001 ) higher in the TIPS group . Ascites , need for transplant , quality of life , and costs were not significantly different . CONCLUSIONS DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients . Reintervention is significantly greater for TIPS compared with DSRS . Because both procedures have equivalent outcomes , the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed During the past 15 years , endoscopic sclerotherapy and , more recently , b and ligation and such pharmacologic agents as octreotide have eclipsed surgical shunting as the preferred method for controlling acute variceal hemorrhage . The status of sclerotherapy for the long-term management of patients with bleeding varices , however , remains controversial . In a previous controlled clinical trial comparing endoscopic sclerotherapy with surgical portacaval shunting [ 1 ] , we enrolled 64 adult patients with Child class C cirrhosis and active hemorrhage from esophageal varices . At the index hospitalization , patients r and omly assigned to sclerotherapy required less blood transfusion and fewer days of hospitalization than did those r and omly assigned to shunt surgery . During the initial follow-up period , which extended for a mean of 530 days after r and omization , 75 % of the patients treated with sclerotherapy were hospitalized for recurrent variceal hemorrhage but none of the patients who had had shunt surgery were rehospitalized [ 1 ] . Although patients treated with sclerotherapy had longer hospital stays and received more blood transfusions during short-term follow-up , a longer follow-up study [ 2 ] showed no difference in survival or overall health care costs between patients treated with sclerotherapy and those treated with surgical shunt . The transjugular intrahepatic portosystemic shunt ( TIPS ) procedure is a nonsurgical procedure in which an exp and able metal prosthesis is used to connect an intrahepatic portal vein with an adjacent hepatic vein [ 3 , 4 ] . In our initial report on 100 patients having this procedure [ 3 ] , TIPS stent placement was technically successful in 96 patients and variceal hemorrhage was controlled in 88 of 94 patients [ 3 ] . Furthermore , the 30-day mortality rate was only 13 % in patients treated with TIPS . These data , as well as those of other research ers who used radiographically placed portosystemic stents , suggest that TIPS might be more cost-effective than sclerotherapy ; however , data comparing the two procedures are limited [ 5 - 10 ] . Therefore , we did a r and omized , controlled trial in patients with massive acute variceal hemorrhage in an effort to compare the two therapies for the prevention of recurrent variceal hemorrhage . Methods From November 1991 through December 1995 , we enrolled 49 adults who had cirrhosis and endoscopically documented bleeding from esophageal varices . We excluded an estimated additional 250 patients with bleeding varices whom we had seen during the study period ( vide infra ) . Our study protocol was approved by the Committee on Human Research of the University of California , San Francisco . Patients who were admitted to San Francisco General Hospital , University of California Medical Center , and Veterans Affairs Medical Center ( all located in San Francisco , California ) with massive or submassive acute gastrointestinal tract hemorrhage from large esophageal varices were approached for consent and r and omization within 24 hours of admission . Massive hemorrhage was defined as bleeding associated with shock ( systolic blood pressure < 80 mm Hg ) . Submassive hemorrhage was defined as hemorrhage associated with postural vital sign changes ( upright pulse rate increased by 20 beats per minute compared with supine pulse rate ; upright systolic blood pressure decreased by 20 mm Hg compared with supine blood pressure ) . The 250 excluded patients were excluded for the following reasons : They were prisoners ; they were younger than 18 or older than 75 years of age ; they had had a cerebrovascular accident within 3 months before the onset of bleeding ; they refused to accept blood products ; or they had gastric variceal hemorrhage , electrocardiographic changes compatible with acute myocardial infa rct ion , a Po 2 less than 70 mm Hg or an arterial pH of 7.20 or less on room air at the time of evaluation for eligibility , a serum creatinine level of 221 mol/L or more , a prothrombin time at least 5 seconds longer than control ( despite the use of fresh frozen plasma ) , a platelet count less than 50 109/L , stage IV hepatic encephalopathy , cancer other than skin cancer , the acquired immunodeficiency syndrome ( AIDS ) or advanced AIDS-related complex , sepsis , pneumonia , peritonitis , clinical evidence of alcoholic hepatitis , a serum bilirubin concentration of 7 mg/dL or more , thrombosis of the portal vein , thrombosis of the hepatic veins , or thrombosis of the inferior vena cava as determined by Doppler ultrasonography . All patients received endoscopic sclerotherapy at the time of the initial endoscopic procedure that established the source of hemorrhage as esophageal varices . Patients were deemed eligible for participation if they presented with hemodynamically submassive or massive hemorrhage and were found to have large ( > 1 cm across ) distal esophageal varices with cherry red spots , hematocystic spots , or red wale signs . Before r and omization , all patients had patency of the portal venous system ( main , right , and left portal veins and the splenic vein ) and hepatic veins determined by real-time color and pulse-wave Doppler ultrasonography . After we obtained informed consent , we used serially numbered , sealed , opaque envelopes to r and omly assign patients either to repeated sclerotherapy or to TIPS . If neither the patient nor the patient 's next of kin was able to give informed consent , a patient advocate was design ated to consider the invitation to participate . Patients r and omly assigned to sclerotherapy received treatment every 2 to 7 days during the initial hospitalization ; treatment consisted of 0.5- to 2.0-mL injections of ethanolamine oleate solution per varix . Repeated endoscopy and sclerotherapy treatments were done weekly after discharge from the initial hospitalization . As much as 30 mL of ethanolamine oleate solution was used per treatment session . All visible varices were injected within the distal 7 to 10 cm of the esophagus . In patients who developed sclerotherapy-associated ulcers , repeated endoscopy was scheduled to be done 2 to 7 days after the notation of ulcers to assess interval healing . Patients assigned to the TIPS group had the procedure within 48 hours of r and omization ; the procedure was performed by one of six radiologists skilled in this procedure , as described elsewhere [ 3 ] . Catheterization of the hepatic vein was done through the right internal jugular vein . A tract between a suitable hepatic vein and a suitable portal vein was established by needle set ( Ring TIPS set , Cook , Inc. , Bloomington , Indiana ) , dilated with a balloon over a guidewire , and then maintained by one or more exp and able metal mesh stents ( Wallstent , Schneider , Inc. , Minneapolis , Minnesota ) . The adequacy of the portosystemic shunt was documented by contrast injection and manometric measurement at the time of the initial procedure . A target portal vein-to-hepatic vein pressure gradient of 12 mm Hg or less was achieved in all cases . Persistent varices opacified at portal venography after adequate stenting were occluded by using embolization coils . Preprocedural data recorded prospect ively included sex , age , vital signs at admission , physical examination findings at admission ( including presence of encephalopathy and ascites ) , nutritional status , results of laboratory tests , and Child-Pugh score [ 11 ] . Prospect ively identified outcome variables after r and omization included death , rebleeding , liver transplantation , total transfusion requirements , onset and presence of encephalopathy , cost of managing variceal hemorrhage after r and omization , total duration of hospitalization for variceal hemorrhage and any related encephalopathy , and complications of therapy . Nutritional status was defined as malnourished if the patient had gross muscle wasting , had cachexia , or had lost at least 10 % of body weight during the previous 6 months . Bleeding after r and omization was defined as bloody or coffee grounds emesis ( hemetemesis , melenemesis ) or liquid black stools ( melena ) with a decrease in hematocrit sufficient to warrant transfusion . Hepatic encephalopathy was defined clinical ly by the presence of asterixis , gross disorientation or agitation , or frank somnolence or coma in the absence of another identifiable cause . Presence of ascites was determined by both ultrasonography and clinical assessment ( shifting dullness , fluid wave , gross distention ) for all patients initially and for patients in the TIPS group having follow-up Doppler ultrasonography . For patients assigned to sclerotherapy , presence of ascites was subsequently determined by clinical criteria alone . Follow-up information was obtained through face-to-face interviews , telephone interviews , or chart review s and was obtained from the patient , family , physician , or all three sources . The total cost of health care per patient was calculated as the sum of all real costs for inpatient and outpatient hospital care , including hospital expenditures and costs for professional services from the day of r and omization until death or the last follow-up visit . In addition , all outpatient costs for endoscopic sclerotherapy , Doppler ultrasonography , and stent revision during the follow-up period were included . We used the actual cost to the hospital or medical staff , or both , of providing a service or procedure ( rather than billing charges or collection s ) . For example , the cost of an endoscopic sclerotherapy session was determined by summating the following : 1 hour of a gastroenterologist 's time plus benefits ( derived from personnel pay records ) ; 2 hours of a registered nurse 's time plus benefits ; the invoice cost of disposable sclerotherapy catheters , bite blocks , and intravenous tubing ; the pharmacy costs of all drugs , including the sclerosant agent ; the estimated depreciation of an Olympus GIT-IT100 videoendoscope ( Lake Success , New York ) ; endoscopic processing costs ; 1 hour of recovery room personnel time ; and costs of recovery supplies . Outcome variables were compared , using the In September 1982 , a prospect i ve r and omized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated . Twenty-seven patients have received shunts ( distal splenorenal = 23 , nonselective = 4 ) and 30 patients have had chronic sclerotherapy . Eighty-six per cent of patients had alcoholic cirrhosis and 33 % were Child 's class C. After a mean follow-up of 25 months , 19 % of shunt and 57 % of sclerotherapy patients have had rebleeding ( p = 0.003 ) . Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt ( 65 % ) and sclerotherapy ( 61 % ) groups . Only two of 10 sclerotherapy failures have been salvaged by surgery . Posttherapy quantitative hepatic function , frequency of encephalopathy , and cumulative medical costs were similar for both groups . Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt . In conclusion , endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival , hepatic function , frequency of encephalopathy , and costs . Sclerotherapy is an acceptable , but not superior , alternative to shunt surgery for treatment of variceal hemorrhage |
2,462 | 29,788,164 | Trial evidence also suggests a benefit of combining celecoxib ( Cel ) with ZA and ADT .
Our results support the use of AAP or Doc with ADT in men with metastatic hormone-naive prostate cancer .
AAP appears to be the most effective treatment , but it is not clear to what extent and whether this is due to a true increased benefit with AAP or the variable features of the individual trials . | Background Our prior Systemic Treatment Options for Cancer of the Prostate systematic review s showed improved survival for men with metastatic hormone-naive prostate cancer when abiraterone acetate plus prednisolone/prednisone ( AAP ) or docetaxel ( Doc ) , but not zoledronic acid ( ZA ) , were added to and rogen-deprivation therapy ( ADT ) . | Abstract Background Adding abiraterone acetate with prednisolone ( AAP ) or docetaxel with prednisolone ( DocP ) to st and ard-of-care ( SOC ) each improved survival in systemic therapy for advanced or metastatic prostate cancer : evaluation of drug efficacy : a multi-arm multi-stage platform r and omised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term and rogen deprivation therapy ( ADT ) . The protocol provides the only direct , r and omised comparative data of SOC + AAP versus SOC + DocP. Method Recruitment to SOC + DocP and SOC + AAP overlapped November 2011 to March 2013 . SOC was long-term ADT or , for most non-metastatic cases , ADT for ≥2 years and RT to the primary tumour . Stratified r and omisation allocated pts 2 : 1 : 2 to SOC ; SOC + docetaxel 75 mg/m2 3-weekly × 6 + prednisolone 10 mg daily ; or SOC + abiraterone acetate 1000 mg + prednisolone 5 mg daily . AAP duration depended on stage and intent to give radical RT . The primary outcome measure was death from any cause . Analyses used Cox proportional hazards and flexible parametric models , adjusted for stratification factors . This was not a formally powered comparison . A hazard ratio ( HR ) < 1 favours SOC + AAP , and HR > 1 favours SOC + DocP. Results A total of 566 consenting patients were contemporaneously r and omised : 189 SOC + DocP and 377 SOC + AAP . The patients , balanced by allocated treatment were : 342 ( 60 % ) M1 ; 429 ( 76 % ) Gleason 8–10 ; 449 ( 79 % ) WHO performance status 0 ; median age 66 years and median PSA 56 ng/ml . With median follow-up 4 years , 149 deaths were reported . For overall survival , HR = 1.16 ( 95 % CI 0.82–1.65 ) ; failure-free survival HR = 0.51 ( 95 % CI 0.39–0.67 ) ; progression-free survival HR = 0.65 ( 95 % CI 0.48–0.88 ) ; metastasis-free survival HR = 0.77 ( 95 % CI 0.57–1.03 ) ; prostate cancer-specific survival HR = 1.02 ( 0.70–1.49 ) ; and symptomatic skeletal events HR = 0.83 ( 95 % CI 0.55–1.25 ) . In the safety population , the proportion reporting ≥1 grade 3 , 4 or 5 adverse events ever was 36 % , 13 % and 1 % SOC + DocP , and 40 % , 7 % and 1 % SOC + AAP ; prevalence 11 % at 1 and 2 years on both arms . Relapse treatment patterns varied by arm . Conclusions This direct , r and omised comparative analysis of two new treatment st and ards for hormone-naïve prostate cancer showed no evidence of a difference in overall or prostate cancer-specific survival , nor in other important outcomes such as symptomatic skeletal events . Worst toxicity grade over entire time on trial was similar but comprised different toxicities in line with the known properties of the drugs . Trial registration Clinical trials.gov : NCT00268476 Purpose Systemic Therapy for Advanced or Metastatic Prostate Cancer : Evaluation of Drug Efficacy is a r and omized controlled trial using a multiarm , multistage , platform design . It recruits men with high-risk , locally advanced or metastatic prostate cancer who were initiating long-term hormone therapy . We report survival data for two celecoxib (Cel)-containing comparisons , which stopped accrual early at interim analysis on the basis of failure-free survival . Patients and Methods St and ard of care ( SOC ) was hormone therapy continuously ( metastatic ) or for ≥ 2 years ( nonmetastatic ) ; prostate ( ± pelvic node ) radiotherapy was encouraged for men without metastases . Cel 400 mg was administered twice a day for 1 year . Zoledronic acid ( ZA ) 4 mg was administered for six 3-weekly cycles , then 4-weekly for 2 years . Stratified r and om assignment allocated patients 2:1:1 to SOC ( control ) , SOC + Cel , or SOC + ZA + Cel . The primary outcome measure was all-cause mortality . Results were analyzed with Cox proportional hazards and flexible parametric models adjusted for stratification factors . Results A total of 1,245 men were r and omly assigned ( Oct 2005 to April 2011 ) . Groups were balanced : median age , 65 years ; 61 % metastatic , 14 % N+/X M0 , 25 % N0M0 ; 94 % newly diagnosed ; median prostate-specific antigen , 66 ng/mL. Median follow-up was 69 months . Grade 3 to 5 adverse events were seen in 36 % SOC-only , 33 % SOC + Cel , and 32 % SOC + ZA + Cel patients . There were 303 control arm deaths ( 83 % prostate cancer ) , and median survival was 66 months . Compared with SOC , the adjusted hazard ratio was 0.98 ( 95 % CI , 0.80 to 1.20 ; P = .847 ; median survival , 70 months ) for SOC + Cel and 0.86 ( 95 % CI , 0.70 to 1.05 ; P = .130 ; median survival , 76 months ) for SOC + ZA + Cel . Preplanned subgroup analyses in men with metastatic disease showed a hazard ratio of 0.78 ( 95 % CI , 0.62 to 0.98 ; P = .033 ) for SOC + ZA + Cel . Conclusion These data show no overall evidence of improved survival with Cel . Preplanned subgroup analyses provide hypotheses for future studies 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 Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Objective To evaluate the reliability of risk of bias assessment s based on published trial reports , for determining trial inclusion in meta-analyses . Design Reliability evaluation of risk of bias assessment s. Data sources 13 published individual participant data ( IPD ) meta-analyses in cancer were used to source 95 r and omised controlled trials . Review methods Risk of bias was assessed using the Cochrane risk of bias tool ( RevMan5.1 ) and accompanying guidance . Assessment s were made for individual risk of bias domains and overall for each trial , using information from either trial reports alone or trial reports with additional information collected for IPD meta-analyses . Percentage agreements were calculated for individual domains and overall ( < 66%=low , ≥66%=fair , ≥90%=good ) . The two approaches were considered similarly reliable only when agreement was good . Results Percentage agreement between the two methods for sequence generation and incomplete outcome data was fair ( 69.5 % ( 95 % confidence interval 60.2 % to 78.7 % ) and 80.0 % ( 72.0 % to 88.0 % ) , respectively ) . However , percentage agreement was low for allocation concealment , selective outcome reporting , and overall risk of bias ( 48.4 % ( 38.4 % to 58.5 % ) , 42.1 % ( 32.2 % to 52.0 % ) , and 54.7 % ( 44.7 % to 64.7 % ) , respectively ) . Supplementary information reduced the proportion of unclear assessment s for all individual domains , consequently increasing the number of trials assessed as low risk of bias ( and therefore available for inclusion in meta-analyses ) from 23 ( 23 % ) based on publications alone to 66 ( 66 % ) based on publications with additional information . Conclusions Using cancer trial publications alone to assess risk of bias could be unreliable ; thus , review ers should be cautious about using them as a basis for trial inclusion , particularly for those trials assessed as unclear risk . Supplementary information from trialists should be sought to enable appropriate assessment s and potentially reduce or overcome some risks of bias . Furthermore , guidance should ensure clarity on what constitutes risk of bias , particularly for the more subjective domains Background The multi-arm multi-stage ( MAMS ) trial is a new paradigm for conducting r and omised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm . MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally design ed trials . Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive , advanced disease as quickly as possible . The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases . Methods STAMPEDE is an open-label , 5-stage , 6-arm r and omised controlled trial using MAMS methodology for men with prostate cancer . It is the first trial of this design to use multiple arms and stages synchronously . Results The practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials . These issues include the choice of intermediate and final outcome measures , sample size calculations and the impact of varying the assumptions , the process for moving between trial stages , stopping accrual to each trial arm and overall , and issues around perceived trial complexity . Conclusion It is possible to use the MAMS design to initiate and undertake large scale cancer trials . The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other research ers will use this exciting and efficient method to perform further r and omised controlled trials . Trial registration IS RCT N78818544 , Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . |
2,463 | 17,619,914 | As a conclusion , the effect of treatments for LBP is only small to moderate . | Numerous r and omized trials have been published investigating the effectiveness of treatments for non-specific low-back pain ( LBP ) either by trials comparing interventions with a no-treatment group or comparing different interventions .
In trials comparing two interventions , often no differences are found and it raises questions about the basic benefit of each treatment . | Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain Study Design . Two replicate , 4-week , r and omized , double-blind , placebo-controlled , trials of rofecoxib 25 and 50 mg versus placebo for chronic low back pain . Objectives . To determine the efficacy and safety of two doses of rofecoxib compared to placebo in the treatment of chronic low back pain . Summary of Background Data . Although nonsteroidal anti-inflammatory drugs are commonly prescribed for chronic low back pain , their efficacy is unproven and toxicity can be serious . These studies evaluated the efficacy and tolerability of rofecoxib , a selective COX-2 inhibitor , in the treatment of chronic low back pain . Methods . Patients with chronic low back pain were r and omized 1:1:1 to rofecoxib 25 mg , 50 mg , or placebo once daily . Primary endpoint : Low Back Pain Intensity . Secondary endpoints : Pain Bothersomeness , Global Assessment s of Response to Therapy , Global Assessment of Disease Status , Rol and -Morris Disability Question naire , SF-12 Health Survey , Use of Rescue Acetaminophen , and Discontinuations Due to Lack of Efficacy . Results . Combining both studies , 690 patients were r and omized to placebo ( N = 228 ) , rofecoxib 25 mg ( N = 233 ) , or rofecoxib 50 mg ( N = 229 ) . Mean ( ± SD ) age was 53.4 ( ± 12.9 ) years , pain duration 12.1 ( ± 11.8 ) years , 62.3 % female . Both rofecoxib groups improved significantly . Mean differences from placebo in pain intensity were −13.50 mm , −13.81 mm ( 25 , 50 mg doses ) respectively ( P < 0.001 ) . Both regimens were superior to placebo in eight of nine secondary endpoints . Fifty mg provided no advantage over 25 mg . Both rofecoxib regimens were well tolerated , although 25 mg had a slightly better safety profile . Conclusions . Rofecoxib significantly reduced chronic low back pain in adults and was well tolerated & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreatment , with no statistically significant differences between treatments BACKGROUND The effectiveness of massage therapy for low-back pain has not been documented . This r and omized controlled trial compared comprehensive massage therapy ( soft-tissue manipulation , remedial exercise and posture education ) , 2 components of massage therapy and placebo in the treatment of subacute ( between 1 week and 8 months ) low-back pain . METHODS Subjects with subacute low-back pain were r and omly assigned to 1 of 4 groups : comprehensive massage therapy ( n = 25 ) , soft-tissue manipulation only ( n = 25 ) , remedial exercise with posture education only ( n = 22 ) or a placebo of sham laser therapy ( n = 26 ) . Each subject received 6 treatments within approximately 1 month . Outcome measures obtained at baseline , after treatment and at 1-month follow-up consisted of the Rol and Disability Question naire ( RDQ ) , the McGill Pain Question naire ( PPI and PRI ) , the State Anxiety Index and the Modified Schober test ( lumbar range of motion ) . RESULTS Of the 107 subjects who passed screening , 98 ( 92 % ) completed post-treatment tests and 91 ( 85 % ) completed follow-up tests . Statistically significant differences were noted after treatment and at follow-up . The comprehensive massage therapy group had improved function ( mean RDQ score 1.54 v. 2.86 - 6.5 , p < 0.001 ) , less intense pain ( mean PPI score 0.42 v. 1.18 - 1.75 , p < 0.001 ) and a decrease in the quality of pain ( mean PRI score 2.29 v. 4.55 - 7.71 , p = 0.006 ) compared with the other 3 groups . Clinical significance was evident for the comprehensive massage therapy group and the soft-tissue manipulation group on the measure of function . At 1-month follow-up 63 % of subjects in the comprehensive massage therapy group reported no pain as compared with 27 % of the soft-tissue manipulation group , 14 % of the remedial exercise group and 0 % of the sham laser therapy group . INTERPRETATION Patients with subacute low-back pain were shown to benefit from massage therapy , as regulated by the College of Massage Therapists of Ontario and delivered by experienced massage therapists STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition BACKGROUND CONTEXT Restorative exercise and palliative modalities are frequently used together for the treatment of acute low back pain . However , little is known about the effects of combining these treatments . PURPOSE To evaluate the efficacy of combining continuous low-level heat wrap therapy with directional preference-based exercise on the functional ability of patients with acute low back pain . STUDY DESIGN / SETTING A r and omized controlled trial was conducted at three outpatient medical facilities . PATIENT SAMPLE One hundred individuals ( age 31.2+/-10.6 years ) with low back pain of less than 3 months duration . OUTCOME MEASURES The primary outcome measure was functional ability assessed by the Multidimensional Task Ability Profile question naire . Secondary outcomes were disability assessed by the Rol and -Morris Disability Question naire and pain relief assessed by a 6-point verbal rating scale . METHODS Participants were r and omized to one of four groups : Heat wrap therapy alone ( heat wrap , n=25 ) ; directional preference-based exercise alone ( exercise , n=25 ) ; combination of heat wrap therapy and exercise ( heat+exercise , n=24 ) ; or control ( booklet , n=26 ) . Treatment was administered for five consecutive days and included four visits to the study center over 1 week . RESULTS At 2 days after the conclusion of treatment ( Day 7 ) , functional improvement for heat+exercise was 84 % , 95 % , and 175 % greater than heat wrap , exercise , and booklet , respectively ( p<.05 ) . Seventy-two percent of the subjects in the heat+exercise group demonstrated a return to pre-injury function compared with 20 % , 20 % , and 19 % for heat wrap , exercise , and booklet , respectively ( p<.05 ) . Disability reduction for heat+exercise was 93 % , 139 % , and 400 % greater than heat wrap , exercise , and booklet , respectively ( p<.05 ) . Pain relief for heat+exercise was 70 % and 143 % greater than exercise and booklet , respectively ( p<.05 ) . CONCLUSIONS Combining continuous low-level heat wrap therapy with directional preference-based exercise during the treatment of acute low back pain significantly improves functional outcomes compared with either intervention alone or control . Either intervention alone tends to be more effective than control A controlled study of different modes of acupuncture stimulation was conducted on patients fulfilling clinical criteria for chronic low back pain of nociceptive origin . Forty patients were r and omly entered into the study . Thirty had three trial treatments with manual stimulation of needles ( MS ) , electrical low frequency stimulation at 2 Hz ( LF ) , and high – frequency stimulation at 80 Hz ( HF ) , and then continued treatment with the mode they felt most benefitted them . Ten patients were put on the waiting list for treatment but served as the untreated control group . The results were evaluated after 6 weeks and at 6 months for : activity related to pain ; mobility ; verbal descriptors of pain and the patient 's subjective assessment of his condition . After 6 weeks , patients receiving treatment showed significant improvement ( P < 0.05 to P < 0.001 ) on three of the four measures compared to the untreated controls . After 6 months a similar measure of significant improvement was seen in patients continuing with low – frequency ( LF ) acupuncture , but not in those groups continuing with manual stimulation ( MS ) or high – frequency ( HF ) acupunture . The results suggest that 2 Hz electrical stimulation is the mode of choice when using acupuncture in the treatment of chronic nociceptive low back pain Two hundred and sixty patients with lumbago or sciatic pain participated in a multicenter observer-blind r and omized trial to compare the efficacy and tolerability of dipyrone 2.5 g , diclofenac 75 mg , and placebo administered as an intramuscular injection once daily for the duration of one to two days . The effectiveness of the test treatments in relieving sciatic pain was measured by a visual analog scale ( VAS ) before and 30 minutes , 1 , 2 , 3 , 6 and 24 hours after each injection . In addition , the patient 's general well-being was measured on a 5-point rating scale on day 0 , 1 and 2 . At the end of the trial , the patients evaluated the overall efficacy of the study drugs on a 5-point rating scale . Minimal finger-toe distance was measured every day of the trial . Pain intensity on VAS ( primary endpoint ) showed a significantly greater reduction with dipyrone than with diclofenac or placebo between 1 and 6 hours after application ( p < 0.01 ) and at the end of the trial ( after 48 hours ) . Improvement in general well-being and minimal finger-toe distance was greatest in the dipyrone group . 59 % of the patients with dipyrone assessed the overall efficacy as " excellent " or " very good " , compared with 30 % with diclofenac , and 18 % with placebo . Adverse reactions were reported in only 7 patients ( 3 % ) , 4 ( 5 % ) in the dipyrone , 1 ( 1 % ) in the diclofenac , and 2 ( 2 % ) in the placebo group & NA ; There is some evidence for the efficacy of acupuncture in chronic low‐back pain ( LBP ) , but it remains unclear whether acupuncture is superior to placebo . In a r and omized , blinded , placebo‐controlled trial , we evaluated the effect of traditional acupuncture in chronic LBP . A total of 131 consecutive out‐ patients of the Department of Orthopaedics , University Goettingen , Germany , ( age=48.1 years , 58.5 % female , duration of pain : 9.6 years ) with non‐radiating LBP for at least 6 months and a normal neurological examination were r and omized to one of three groups over 12 weeks . Each group received active physiotherapy over 12 weeks . The control group ( n=46 ) received no further treatment , the acupuncture group ( n=40 ) received 20 sessions of traditional acupuncture and the sham‐acupuncture group ( n=45 ) 20 sessions of minimal acupuncture . Changes from baseline to the end of treatment and to 9‐month follow‐up were assessed in pain intensity and in pain disability , and secondary in psychological distress and in spine flexion , compared by intervention groups . Acupuncture was superior to the control condition ( physiotherapy ) regarding pain intensity ( P=0.000 ) , pain disability ( P=0.000 ) , and psychological distress ( P=0.020 ) at the end of treatment . Compared to sham‐acupuncture , acupuncture reduced psychological distress ( P=0.040 ) only . At 9‐month follow‐up , the superiority of acupuncture compared to the control condition became less and acupuncture was not different to sham‐acupuncture . We found a significant improvement by traditional acupuncture in chronic LBP compared to routine care ( physiotherapy ) but not compared to sham‐acupuncture . The trial demonstrated a placebo effect of traditional acupuncture in chronic LBP The acupuncture treatment situation was beneficial to the majority of people with low back pain . This was shown by the use of short-term controls and long-term controls , although the latter were not intended in the study design . After acupuncture , there was a 51 % pain reduction in the average pain score in the Immediate Treatment Group . The short-term controls , the Delayed Treatment Group , had no reduction whatsoever in their pain scores at the comparable followup period . Later , the Delayed Treatment Group bere also treated by acupuncturists , and reported 62 % less pain . When these two treatment groups were compared at 40 weeks with long-term controls ( Inadequate Treatment Group ) , the Inadequate Treatment Group still had the same pain scores , on the average , as when they enrolled in the study . Both treatment groups , on the average , had 30 % lower pain scores . Furthermore , 58 % of the treatment groups felt that they were definitely improved at 40 weeks , while only 11 % of the Inadequate Treatment Group felt definitely improved at 40 weeks Study Design . A single blind r and omized controlled trial comparing two models of care for patients with acute simple low back pain . Objectives . To compare two research -based models of care for acute low back pain and investigate the effect of the timing of physical intervention . Summary of Background Data . National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain . The guidelines suggest two different models of care . Direct comparisons between these models are lacking in the literature . The present study aims to compare these approaches to the management of acute low back pain . Methods . Among 804 referred patients , 102 subjects met the specific admission criteria and were r and omly assigned to an “ assess/advise/treat ” group or an “ assess/advise/wait ” group . The intervention consisted of biopsychosocial education , manual therapy , and exercise . Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active . Assessment of long-term outcome enables comparison to be made between early and late intervention . Study outcomes of reported pain ( Visual Analogue Scale ) , functional disability ( the Rol and and Morris Disability Question naire ) , mood ( Modified Zung Self Rated Depression Score , Modified Somatic Perception Question naire , State-Trait Anxiety Inventory ) , general health ( Euroqol ) , and quality of life ( Short Form 36 ) were assessed at baseline , 6 weeks , 3 months , and 6 months . Results . At 6 weeks , the assess/advise/treat group demonstrated greater improvements in disability , mood , general health , and quality of life than patients in the assess/advise/wait group ( P < 0.05 ) . Disability and pain were not significantly different between the groups at long-term follow up ( P > 0.05 ) . However , mood , general health , and quality of life remained significantly better in the assess/advise/treat group ( P < 0.05 ) . Conclusions . At short-term , intervention is more effective than advice on staying active , leading to more rapid improvement in function , mood , quality of life , and general health . The timing of intervention affects the development of psychosocial features . If treatment is provided later , the same psychosocial benefits are not achieved . Therefore , an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care Study Design . A r and omized controlled multicenter study with a 2-year follow-up by an independent observer . Objectives . To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain ( CLBP ) . Summary of Background Data . The reported results after fusion surgery on patients with CLBP vary considerably , and the evidence of treatment efficacy is weak in the absence of r and omized controlled studies . Patients and Methods . A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were r and omized blindly into four treatment groups . Patients aged 25–65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4–L5 , L5-S1 , or both were eligible to participate in the study . The surgical group ( n=222 ) included three different fusion techniques , not analyzed separately in this study . Patients in the nonsurgical group ( n=72 ) were treated with different kinds of physical therapy . The surgical group comprised 49.5 % men , and the mean age was 43 years . The corresponding figures for the nonsurgical group were 48.6 % and 44 years . The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years , respectively . The Visual Analogue Scale ( VAS ) was used to measure pain . The Oswestry Low Back Pain Question naire , the Million Score and the General Function Score ( GFS ) were used to measure disability . The Zung Depression Scale was used to measure depressive symptoms . The overall result was assessed by the patient and by an independent observer . Records from the Swedish Social Insurance were used to evaluate work disability . Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle . Results . At the 2-year follow-up 289 of 294 ( 98 % ) patients , including 25 who had changed groups , were examined . Back pain was reduced in the surgical group by 33 % ( 64 to 43 ) , compared with 7 % ( 63 to 58 ) in the nonsurgical group ( P = 0.0002 ) . Pain improved most during the first 6 months and then gradually deteriorated . Disability according to Oswestry was reduced by 25 % ( 47 to 36 ) compared with 6 % ( 48 to 46 ) among nonsurgical patients ( P = 0.015 ) , according to Million by 28 % ( 64 to 46 ) compared with 8 % ( 66 to 60 ) ( P = 0.004 ) , and accordingtoGFS by 31 % ( 49 to 34 ) compared with 4 % ( 48 to 46 ) ( P = 0.005 ) . The depressive symptoms , according to Zung , were reduced by 20 % ( 39 to 31 ) in the surgical group compared with 7 % ( 39 to 36 ) in the nonsurgical group ( P = 0.123 ) . In the surgical group 63 % ( 122/195 ) rated themselves as “ much better ” or “ better ” compared with 29 % ( 18/62 ) in the nonsurgical group ( P < 0.0001 ) . The “ net back to work rate ” was significantly in favor of surgical treatment , or 36 % vs. 13 % ( P = 0.002 ) . The early complication rate in the surgical group was 17 % . Conclusion . Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment OBJECTIVE To evaluate the efficacy of intramuscular injection of thiocolchicoside ( 4 mg-2 ml ) compared to placebo administered twice daily for 5 days in patients suffering from acute low back pain . PATIENTS AND METHODS Multicenter , r and omized , double-blinded , placebo-controlled trial . The study was conducted between July 1998 and March 2000 in five centers . Hospitalized patients with acute low back pain were included . The primary evaluation criterion was spontaneous pain at rest assessed by visual analog scale ( VAS ) . H and -to-floor distance , muscle spasm intensity , patients ' global evaluation and analgesic tablet ( paracetamol ) consumption were used as secondary evaluation criteria . RESULTS One hundred and forty nine patients were included . Both groups showed improvement on spontaneous pain assessed by VAS at the end of day 1 ; however , improvement was statistically significant in thiocolchicoside group on day 3 ( P < 0.001 ) . H and -to-floor distance and muscle spasm determined by palpation decreased significantly on day 5 in thiocolchicoside group ( P < 0.0005 for both ) . According to the patients ' global evaluation , 76.8 % of patients in thiocolchicoside group evaluated the treatment as very good/good ( P < 0.0005 ) . Also a significant difference was observed in favor of the thiocolchicoside group in the total paracetamol consumption ( P < 0.001 ) . Treatment was well tolerated in both groups and none of the patients was withdrawn from the study due to an adverse effect . CONCLUSION Twice daily administration of 4 mg thiocolchicoside for 5 days provides an efficient and safe treatment for patients with acute low back pain accompanied by muscle spasm The effects of exercise for isolated lumbar extensor muscles were examined in 54 chronic low-back pain patients . Subjects were r and omly assigned to a 10-week exercise program ( N = 31 ) or a wait-list control group ( N = 23 ) . Results indicated a significant increase in isometric lumbar extension strength for the treatment group and a significant reduction in reported pain compared with the control group ( P 0.05 ) . Treated subjects reported less physical and psychosocial dysfunction whereas the control group increased in pain , and physical and psychosocial dysfunction . There were no concomitant changes in reported daily activity levels . These results show that lumbar extension exercise is beneficial for strengthening the lumbar extensors and results in decreased pain and improved perceptions of physical and psychosocial functioning in chronic back pain patients . However , these improvements were not related to changes in activities or psychological distress BACKGROUND AND PURPOSE Clinicians treating patients with low back pain often use exercise to reduce pain and improve function . The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain ( ie , onset of back pain within 7 days to 7 weeks ) . SUBJECTS AND METHODS Patients were r and omly assigned to either an experimental group or a control group . A visual analog scale and the pain rating index ( PRI ) of the McGill Pain Question naire ( MPQ ) were used to obtain baseline measurements of pain . The Rol and Morris Disability Question naire ( RMDQ ) was used to measure disability , and the Sorensen Test was used to measure trunk extensor endurance . Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks . Subjects in the control group did not do exercises . Both groups were given back care advice and hot packs for 15 minutes , 3 to 5 times per week . Re assessment s were carried out at 3 and 6 weeks . RESULTS There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours , the total MPQ PRI , the sensory component of the MPQ PRI , and the RMDQ . At 6 weeks , no differences were found for pain measurements , disability scores , and holding time on the Sorensen Test . CONCLUSION AND DISCUSSION Trunk extensor endurance training reduced pain and improved function at 3 weeks but result ed in no improvement at 6 weeks when compared with the control group . Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain STUDY DESIGN A prospect i ve , r and omized , controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group . OBJECTIVE To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working . SUMMARY OF BACKGROUND DATA One episode of low back pain increases the risk of further episodes of the condition . The Mensendieck approach combines education and exercise . This approach has been used for many years in Sc and inavia and the Netherl and s. However , the effects on low back pain have not been evaluated previously in a r and omized , controlled trial . METHODS A total of 77 men and women , mean age 39.6 years ( range , 21.2 - 49.8 years ) , who had finished treatment for a low back pain episode , were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years . The patients were assigned at r and om to either the Mensendieck program or a control group . The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks . At 5- and 12-month follow-up examinations , the patients were assessed for recurrence of low back pain , days of sick leave , low back pain , and functional scores . RESULTS After 12 months , there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group ( P < 0.05 ) . There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group , but no significant differences between the groups . There was reduction in pain and improvement in function in both groups , with no significant differences between the groups . CONCLUSIONS A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition . However , there were no differences between the groups with regard to days of sick leave , low back pain , and function A number of treatments are widely prescribed for chronic back pain , but few have been rigorously evaluated . We examined the effectiveness of transcutaneous electrical nerve stimulation ( TENS ) , a program of stretching exercises , or a combination of both for low back pain . Patients with chronic low back pain ( median duration , 4.1 years ) were r and omly assigned to receive daily treatment with TENS ( n = 36 ) , sham TENS ( n = 36 ) , TENS plus a program of exercises ( n = 37 ) , or sham TENS plus exercises ( n = 36 ) . After one month no clinical ly or statistically significant treatment effect of TENS was found on any of 11 indicators of outcome measuring pain , function , and back flexion ; there was no interactive effect of TENS with exercise . Overall improvement in pain indicators was 47 percent with TENS and 42 percent with sham TENS ( P not significant ) . The 95 percent confidence intervals for group differences excluded a major clinical benefit of TENS for most outcomes . By contrast , after one month patients in the exercise groups had significant improvement in self-rated pain scores , reduction in the frequency of pain , and greater levels of activity as compared with patients in the groups that did not exercise . The mean reported improvement in pain scores was 52 percent in the exercise groups and 37 percent in the nonexercise groups ( P = 0.02 ) . Two months after the active intervention , however , most patients had discontinued the exercises , and the initial improvements were gone . We conclude that for patients with chronic low back pain , treatment with TENS is no more effective than treatment with a placebo , and TENS adds no apparent benefit to that of exercise alone BACKGROUND AND PURPOSE Spinal and muscle flexibility have been studied intensively and used clinical ly as outcome measurements in the rehabilitation of subjects with low back pain . The results of previous studies are contradictory and there is a lack of longitudinal data on the effects of long term therapeutic exercise on flexibility . METHOD A controlled experimental study was conducted to determine the effects of progressive therapeutic exercise on spinal and muscle flexibility . Eighty-six chronic low back pain subjects fulfilled the inclusion criteria and were divided into three study groups : ( 1 ) intensive training group , ( 2 ) home exercise group and ( 3 ) control group . The intervention period lasted three months and measurements were performed at both the beginning of the study and immediately after intervention . Follow-up measurements were carried out six and 12 months after baseline . Spinal flexibility was measured with lumbar flexion , extension , spinal lateral flexion and rotation , and muscle flexibility was measured with measurements of erector spinae , hamstring and iliopsoas muscles . Also self-reported outcomes of the Oswestry Index and Borg Scale -- Back Pain Intensity were used . Associations between change ( pre- to post-treatment ) were determined for the dependent variables . RESULTS The results showed no correlation between flexibility , the Oswestry Index or back pain intensity . After the first three-month period lumbar flexion , extension and spinal rotation decreased among all subjects . Spinal rotation and erector spinae muscle flexibility improved significantly with intensive training . At the nine-month follow-up , erector spine flexibility was still greater than at baseline . Hamstring flexibility increased among the intensive training and home exercise groups from pre- to post-intervention . However , the degree of hamstring flexibility gained during training was subsequently lost following the period without programmed exercise in both training groups . Self-reported outcome variables showed positive changes among the three study groups after the completion of intervention period , but these changes were only able to be maintained during subsequent follow-ups for the intensive training and home exercise groups . CONCLUSIONS The findings suggest that flexibility does not play an important role in coping with chronic low back pain for subjects whose functional limitations are not severe . Also , it appears that the achieved gains in spinal and muscle flexibility may not be able to be maintained without continued exercise In a r and omized , blinded study , we compared the outcome from a full-time functional restoration program with the outcome from shorter active rehabilitation programs for patients with chronic , disabling low back pain . The study initially included 132 patients , r and omized into one of three treatment programs : ( 1 ) an intensive 3-week multidisciplinary program ; ( 2 ) active physical training and back school ; or ( 3 ) psychological pain management and active physical training . Nine of the r and omized patients never started in any program , so the studied population consisted of 123 patients . Of these , 14 patients ( 11 % ) dropped out . The results presented here are at 1 year following treatment , where we achieved a 92 % response rate , including the drop-outs . The functional restoration program was superior to the shorter programs as to work-ready rate , health care contacts , back pain level , disability level , staying physically active , and reduction in analgesics . There was no significant difference between Programs 2 and 3 in most of these parameters . As for sick leave and leg pain , there was no significant difference between Programs 1 and 2 , although a difference was observed when comparing Program 3 with each of the other two . Conclusively , it seems that there is human , as well as economical , benefit from a functional restoration program compared to less intensive programs for these patients Study Design A r and omized trial was conducted on a representative sample of patients with untreated low back pain lasting 7 weeks or longer , or having more than 6 episodes in 12 months . Objectives To contrast the effectiveness of manipulation , a manipulation mimic , and a back education program . Method ologic criticisms of earlier studies were addressed . Summary of Background Data Published meta-anal-yses suggest clinical benefit from manipulation for acute patients . Data are inconclusive for patients having symptoms for longer than 1 month . Methods A total of 1267 consecutive patients were screened . Block r and omization was used to assign 209 qualifying patients to treatment groups . Self-reported pain and activity tolerance served as primary outcome measures . Patients were assessed at enrollment , after 2 weeks of treatment , and again after 2 weeks without treatment . Multiple teams conducted recruitment , r and omization , assessment , treatment , and data analysis independently without sharing information . Treatments were carefully described , monitored , and balanced for physician attention and physical contact effects . Results A total of 81.3 % of subjects completed the study . Confounding factors and missing data were identified in approximately 20 % of those completing the final follow-up . Analysis of the remaining data was carried out . A strong time effect under treatment was observed . Greater improvement was noted in pain and activity tolerance in the manipulation group . Immediate benefit from pain relief continued to accrue after manipulation , even for the last encounter at the end of the 2-week treatment interval . Conclusion Time is a strong ally of the low back pain patient . In human terms , however , there appears to be clinical value to treatment according to a defined plan using manipulation even in low back pain exceeding 7 weeks ' duration Patients ( 112 ) with acute low-back pain of recent onset were recruited to this double-blind , r and omized , placebo-controlled parallel group study in general practice to evaluate the efficacy and tolerability of the muscle relaxant , tizanidine . They were treated for 7 days with tizanidine ( 4 mg three times daily ) or matching placebo . Aspirin tablets ( 300 mg ) were taken as required as ‘ rescue ’ medication . Symptoms were assessed by the patient and doctor before treatment , and after 3 and 7 days . Patients recorded pain and aspirin consumption in a daily diary . Both treatments were effective . In patients who had taken no medication prior to entry , aspirin consumption was almost halved in the first 3 days of taking tizanidine compared with placebo ( P = 0.037 ) . Results for pain at rest , pain at night , restriction of movement and pain on movement suggest that tizanidine may give greater improvement , earlier . No serious drug-related adverse events or abnormal biochemistry or haematology were observed in either group . Drowsiness occurred in 22 % of patients taking tizanidine although , in patients with severe acute low-back pain , sedation , analgesia and bed rest might be beneficial and desired . Considerably more patients given aspirin/placebo had gastro-intestinal side-effects ( P = 0.018 ) . In conclusion , tizanidine may reduce the need for analgesics and be useful in the treatment of acute low-back pain & NA ; The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem . A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods . The treatment group received an intervention design ed to reduce current problems , but above all to prevent reinjury and minor pains from becoming chronic medical problems , and it included a physical and behavioral therapy package . The control group was placed on a waiting‐list . Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity , anxiety , sleep quality and fatigue ratings , observed pain behavior , activities , mood , and helplessness . These differences were generally maintained at the 6 month follow‐up . In addition , the treatment group broke a trend for increasing amounts of pain‐related absenteeism , while the control group did not . Taken as a whole , the results suggest that a secondary prevention program aim ed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases Study Design . A r and omized controlled trial was conducted . Objective . To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain . Summary of Background Data . Osteopathic manipulative treatment may be useful for acute or subacute low back pain . However , its role in chronic low back pain is unclear . Methods . This trial was conducted in a university-based clinic from 2000 through 2001 . Of the 199 subjects who responded to recruitment procedures , 91 met the eligibility criteria . They were r and omized , with 82 patients completing the 1-month follow-up evaluation , 71 completing the 3-month evaluation , and 66 completing the 6-month evaluation . The subjects were r and omized to osteopathic manipulative treatment , sham manipulation , or a no-intervention control group , and they were allowed to continue their usual care for low back pain . The main outcomes included the SF-36 Health Survey , a 10-cm visual analog scale for overall back pain , the Rol and –Morris Disability Question naire , lost work or school days because of back pain , and satisfaction with back care . Results . As compared with the no-intervention control subjects , the patients who received osteopathic manipulative treatment reported greater improvements in back pain , greater satisfaction with back care throughout the trial , better physical functioning and mental health at 1 month , and fewer cotreatments at 6 months . The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects . There were no significant benefits with osteopathic manipulative treatment , as compared with sham manipulation . Conclusions . Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain . It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment , such as range of motion activities or time spent interacting with patients , which may represent placebo effects Glover , J. R. , Morris , Jean G. , and Khosla , T. (1974).British Journal of Industrial Medicine,31 , 59 - 64 . Back pain : a r and omized clinical trial of rotational manipulation of the trunk . A therapeutic trial was conducted in a medium-sized engineering works on patients suffering from back pain with its accompanying tenderness and hyperaesthesia . The patients were r and omly allocated to two treatment groups , ( a ) manipulation , and ( b ) de-tuned ( i.e. , simulated ) short-wave diathermy , the latter acting as a placebo . The manipulated group were given one lumbar rotational manipulation session of 15 minutes or less and this was followed by four daily detuned short-wave diathermy sessions of 15 minutes . The control group were given five 15-minute daily sessions of detuned short-wave diathermy only . The patients ' own subjective assessment of relief from pain was recorded in the range 0 % ( no relief ) to 100 % ( complete relief ) . The responses were measured at three stages , ( 1 ) within 15 minutes , ( 2 ) three days after treatment , and ( 3 ) seven days after treatment . Although each of the two treatment groups showed progressive and marked improvement in the percentage of relief from pain during the seven-day period , there was no demonstrable difference between the two , except that at the 15-minute stage the relief from pain in the manipulated group was always greater than in the controls Dissatisfaction with current nonsurgical treatment of acute soft tissue and back injuries initiated a search for more effective treatment . A multicenter trial , involving 12 clinics , treated 1,072 patients . Treatment consisted of intensive , time-limited exercises emphasizing mobility , muscle strengthening , work conditioning , sequence training , and appropriate education sessions . Return to full-time work was proof that the patient had recovered fully . Time off work and compensation costs were parameters used to evaluate results . A detailed study of 703 patients treated at five clinics , operational for more than 12 months , showed superior results when compared with the comparison group of 2,172 matched control subjects . The treatment group returned to work earlier and realized substantial cost savings . This treatment program has proved to be superior to the miscellaneous variety of treatment modalities used for acute soft tissue and back injuries provided to the comparison group We evaluated etoricoxib , a novel COX-2-specific inhibitor , in 319 patients with chronic low back pain ( LBP ) in this double-blind , placebo-controlled trial . Patients were r and omized to a 60 mg dose ( n = 103 ) or 90 mg dose ( n = 107 ) of etoricoxib , or placebo ( n = 109 ) , daily for 12 weeks . The primary endpoint was low back pain intensity scale ( Visual Analog Scale of 0- to 100-mm ) time-weighted average change from baseline over 4 weeks . Other endpoints included evaluation over 3 months of low back pain intensity scale , Rol and -Morris Disability Question naire ( RMDQ ) , low back pain bothersomeness scale , patient- and investigator-global assessment s , Patient Health Survey ( MOS SF-12 ) , rescue acetaminophen use , and discontinuation due to lack of efficacy . Etoricoxib provided significant improvement from baseline versus placebo in pain intensity ( 4 weeks : 12.9 mm and 10.3 mm for 60-mg and 90-mg doses , P < .001 for each ; 12 weeks : 10.5 mm and 7.5 mm for 60-mg and 90-mg doses , P = .001 and .018 , respectively ) . Etoricoxib at either dose led to significant improvement in other endpoints , including RMDQ scores , bothersomeness scores and global assessment s. Etoricoxib given once daily provided significant relief of symptoms , and disability associated with chronic LBP that was observed 1 week after initiating therapy , was maximal at 4 weeks , and was maintained over 3 months Abstract Twenty chronic low back pain ( LBP ) patients with relatively high st and ing paraspinal EMG levels ( > 5 gmV ) were r and omly assigned to 2 groups . One group ( N = 10 ) received EMG biofeedback training to reduce st and ing paraspinal EMG levels , the other group ( N = 10 ) served as a waiting list control group . Changes in perceived pain ( duration × intensity ) and paraspinal EMG in st and ing position were measured at a 3 week pretreatment baseline , during the 3 week treatment period , and at a 3 week post‐treatment baseline . Compared to patients in the waiting list control group , those who received EMG biofeedback showed a significant decrease in st and ing paraspinal EMG from pretreatment to post‐treatment baseline . However , no significant differences in reported pain were found during these periods . It is concluded that reduction of st and ing paraspinal EMG does not lead to reduction in pain 81 patients with chronic low back pain ( average duration 10 years ) were r and omised to two treatment groups . 40 received an empirically devised regimen of forceful spinal manipulation and injections of a dextrose-glycerine-phenol ( " proliferant " ) solution into soft-tissue structures , as part of a programme to decrease pain and disability . The other 41 patients received parallel treatment in which the main differences were less extensive initial local anaesthesia and manipulation , and substitution of saline for proliferant . Neither patients nor assessors knew which treatment had been given . When assessed by disability scores the experimental group had greater improvement than the control group at one ( p less than 0.001 ) , three ( p less than 0.004 ) , and six ( p less than 0.001 ) months from the end of treatment ; at six months an improvement of more than 50 % was recorded in 35 of the experimental group versus 16 of the control group and the numbers free from disability were 15 and 4 , respectively ( p less than 0.003 ) . Visual analogue pain scores and pain diagrams likewise showed significant advantages for the experimental regimen The efficacy of an NSAID ( tenoxicam ) in the treatment of acute low back pain ( LBP ) was assessed in a double blind controlled study by using an objective functional evaluation . Seventy-three patients consulting for acute LBP were r and omized into two groups : Group I was treated with tenoxicam for 14 days and Group II was given a placebo . Trunk function was measured with a computerized isoinertial dynamometric trunk testing device ( Isostation B200 ) . Isometric and dynamic torques , range of motion and movement velocities were measured before treatment and after 14 days . Clinical evaluation was realized by the patient on a pain visual analogue scale ( VAS ) on days 1 , 8 and 15 and by the investigator on a five-point scale on days 8 and 15 . The functional evaluation showed significant differences in favour of the tenoxicam treatment for velocity and extension isometric torque . VAS and investigator evaluations showed a significant difference in favour of tenoxicam on day 8 but no difference on day 15 . This study shows that the use of tenoxicam in acute LBP is of interest . Tenoxicam has an effect on pain during the first part of the treatment and may help to restore full function even if the symptoms have disappeared 24 patients with chronic low back pain were r and omly assigned to three treatment conditions : ( a ) EMG biofeedback , ( b ) relaxation training , and ( c ) a placebo condition . Patients were seen for eight sessions and were evaluated before Session 1 and after Session 8 . Eight analyses of covariance which were adjusted for age and pretest scores were computed on the final scores to find which variables could detect significant difference between treatments . Age was included as a covariate because the differences in age between conditions were significant . Four variables with significant and nearly significant differences were chosen for analysis . The second set of analyses identified the nature of the differences among the three conditions . These included a priori planned comparisons among conditions , and paired t tests . Relaxation-trained subjects were significantly superior to subjects in the placebo condition , in decreasing pain during the function test , increasing relaxation , and decreasing Upper Trapezius EMG . They were superior to EMG Biofeedback training in increasing reported activity . Both Relaxation and EMG trained subjects were able to reduce Upper Trapezius EMG by Session 8 Relaxation-trained subjects showed significant change on eight of the 14 possible comparisons for each treatment condition . EMG biofeedback training showed significant favorable results in only one condition ; the placebo condition showed no significant results . Relaxation training gave better results in reducing EMG and pain , and in increasing relaxation and activity than either EMG biofeedback alone or a placebo condition BACKGROUND Bed rest and back-extension exercises are often prescribed for patients with acute low back pain , but the effectiveness of these two competing treatments remains controversial . METHODS We conducted a controlled trial among employees of the city of Helsinki , Finl and , who presented to an occupational health care center with acute , nonspecific low back pain . The patients were r and omly assigned to one of three treatments : bed rest for two days ( 67 patients ) , back-mobilizing exercises ( 52 patients ) , or the continuation of ordinary activities as tolerated ( the control group ; 67 patients ) . Outcomes and costs were assessed after 3 and 12 weeks . RESULTS After 3 and 12 weeks , the patients in the control group had better recovery than those prescribed either bed rest or exercises . There were statistically significant differences favoring the control group in the duration of pain , pain intensity , lumbar flexion , ability to work as measured subjectively , the Oswestry back-disability index , and number of days absent from work . Recovery was slowest among the patients assigned to bed rest . The overall costs of care did not differ significantly among the three groups . CONCLUSIONS Among patients with acute low back pain , continuing ordinary activities within the limits permitted by the pain leads to more rapid recovery than either bed rest or back-mobilizing exercises Objective The authors sought to determine whether a series of needle acupuncture treatments produced long-term relief of chronic low back pain . Design A blinded placebo-controlled study with an independent observer . The patients were r and omized to receive manual acupuncture , electroacupuncture , or active placebo ( mock transcutaneous electrical nerve stimulation ) . Subjects were examined and monitored by an investigator who was blinded to the treatment given . Setting A tertiary-level pain clinic at a Swedish university hospital . Patients Fifty consecutive patients ( 33 women , 17 men ; mean age , 49.8 years ) with chronic low back pain ( mean pain duration , 9.5 years ) and without rhizopathy or history of acupuncture treatment were included in the study . Interventions Treatments were given once per week for 8 weeks . Two further treatments were given during the follow-up assessment period of 6 months or longer . Outcome Measures The independent observer made a global assessment of the patients 1 , 3 , and 6 months after treatment . The patients kept pain diaries to score pain intensity twice daily , analgesic intake , and quality of sleep daily , and activity level weekly . Results At the 1-month independent assessment , 16 of 34 patients in the acupuncture groups and 2 of 16 patients in the placebo group showed improvement ( p < 0.05 ) . At the 6-month follow-up assessment , 14 of 34 patients in the acupuncture groups and 2 of 16 patients in the placebo group showed improvement ( p < 0.05 ) . A significant decrease in pain intensities occurred at 1 and 3 months in the acupuncture groups compared with the placebo group . There was a significant improvement in return to work , quality of sleep , and analgesic intake in subjects treated with acupuncture . Conclusions The authors found a long-term pain-relieving effect of needle acupuncture compared with true placebo in some patients with chronic nociceptive low back pain Study Design . A multicenter assessor-blinded r and omized clinical trial was conducted . Objectives . To investigate the difference in effectiveness of manipulative therapy and interferential therapy for patients with acute low back pain when used as sole treatments and in combination . Summary of Background Data . Both manipulative therapy and interferential therapy are commonly used treatments for low back pain . Evidence for the effectiveness of manipulative therapy is available only for the short-term . There is limited evidence for interferential therapy , and no study has investigated the effectiveness of manipulative therapy combined with interferential therapy . Methods . Consenting subjects ( n = 240 ) recruited following referral by physicians to physiotherapy departments in the ( government-funded ) National Health Service in Northern Irel and were r and omly assigned to receive a copy of the Back Book and either manipulative therapy ( MT ; n = 80 ) , interferential therapy ( IFT ; n = 80 ) , or a combination of manipulative therapy and interferential therapy ( CT ; n = 80 ) . The primary outcome was a change in functional disability on the Rol and Morris Disability Question naire . Follow-up question naires were posted at discharge and at 6 and 12 months . Results . The groups were balanced at baseline for low back pain and demographic characteristics . At discharge all interventions significantly reduced functional disability ( Rol and Morris scale , MT : −4.53 ; 95 % CI , −5.7 to −3.3 vs. IFT : −3.56 ; 95 % CI , −4.8 to −2.4 vs. CT : −4.65 ; 95 % CI , −5.8 to −3.5 ; P = 0.38 ) and pain ( McGill question naire , MT : −5.12 ; 95 % CI , −7.7 to −2.5 vs. IFT : −5.87 ; 95 % CI , −8.5 to −3.3 vs. CT : −6.64 ; 95 % CI , −9.2 to −4.1 ; P = 0.72 ) and increased quality of life ( SF-36 Role-Physical , MT : 28.6 ; 95 % CI , 18.3 to 38.9 vs. IFT : 31.4 ; 95 % CI , 21.2 to 41.5 vs. CT : 30 ; 95 % CI , 19.9 to 40 ; P = 0.93 ) to the same degree and maintained these improvements at 6 and 12 months . No significant differences were found between groups for reported LBP recurrence , work absenteeism , medication consumption , exercise participation , or healthcare use at 12 months ( P > 0.05 ) . Conclusions . For acute low back pain , there was no difference between the effects of a combined manipulative therapy and interferential therapy package and either manipulative therapy or interferential therapy alone Acupuncture treatment of chronic low back pain was studied in a placebo-controlled double-blind crossover trial completed by 77 patients . The patients had significantly increased depression , neuroticism , and hypochondriasis scores . Initial pain levels correlated with state-anxiety , depression , pain duration , and abnormal illness behavior measures , as well as with the intake of psychotropic but not analgesic medication . Overall reduction in pain score was 26 percent for acupuncture and 22 percent for placebo treatment ; the difference was not significant ( p greater than 0.6 ) . Analgesic drug intake was reduced to a similar extent in both groups . During the first phase of treatment , patients receiving acupuncture had a greater but not significantly different reduction in pain rating scores compared with those receiving placebo ( t = 0.52 ; p greater than 0.6 ) . This group showed significantly lower pain scores ( p less than 0.05 ) in the second phase of the trial while receiving placebo treatment . Overall reduction in individual patient 's pain score was best predicted by initial pain severity ( r = 0.43 ; p less than 0.001 ) and psychotropic drug intake ( r = 0.37 ; p less than 0.001 ) . None of the variables tested predicted which patients would specifically respond to acupuncture or placebo Design . Cross-sectional analysis of the factors influencing self-rated disability associated with chronic low back pain and prospect i ve study of the relationship between changes in each of these factors and in disability following active therapy . Objectives . To examine the relative influences of pain , psychological factors , and physiological factors on self-rated disability . Summary of Background Data . In chronic LBP , the interrelationship between physical impairment , pain , and disability is particularly complicated , due to the influence of various psychological factors and the lack of unequivocal methods for assessing impairment . Investigations using new “ belief ” question naires and “ sophisticated ” performance tests , which have shown promise as discriminating measures of impairment , may assist in clarifying the situation . Previous studies have rarely investigated all these factors simultaneously . Methods . One hundred forty-eight patients with cLBP completed question naires and underwent tests of mobility , strength , muscle activation , and fatigability , and ( in a subgroup ) erector spinae size and fiber size/type distribution . All measures were repeated after 3 months active therapy . Relationships between each factor and self-rated disability ( Rol and and Morris question naire ) at baseline , and between the changes in each factor and changes in disability following therapy , were examined . Results . Stepwise linear regression showed that the most significant predictors of disability at baseline were , in decreasing order of importance : pain ; psychological distress ; fear-avoidance beliefs ; muscle activation levels ; lumbar range of motion ; gender . Only changes in pain , psychological distress , and fear-avoidance beliefs significantly accounted for the changes in disability following therapy . Conclusion . A combination of pain , psychological and physiological factors was best able to predict baseline disability , although its decrease following therapy was determined only by reductions in pain and psychological variables . The active therapy programm — in addition to improving physical function — appeared capable of modifying important psychological factors , possibly as a result of the positive experience of completing the prescribed exercises without undue harm & NA ; Although high‐frequency low‐intensity transcutaneous electric nerve stimulation ( TENS ) has been extensively used to relieve low back pain , experimental studies of its effectiveness have yielded contradictory findings mainly due to method ological problems in pain evaluation and placebo control . In the present study , separate visual analog scales ( VAS ) were used to measure the sensory‐discriminative and motivational‐affective components of low back pain . Forty‐two subjects were r and omly assigned to 1 of 3 groups : TENS , placebo‐TENS , and no treatment ( control ) . In order to measure the short‐term effect of TENS , VAS pain ratings were taken before and after each treatment session . Also , to measure long‐term effects , patients rated their pain at home every 2 h throughout a 3‐day period before and 1 week , 3 months and 6 months after the treatment sessions . In comparing the pain evaluations made immediately before and after each treatment session , TENS and placebo‐TENS significantly reduced both the intensity and unpleasantness of chronic low back pain . TENS was significantly more efficient than placebo‐TENS in reducing pain intensity but not pain unpleasantness . TENS also produced a significant additive effect over repetitive treatment sessions for pain intensity and relative pain unpleasantness . This additive effect was not found for placebo‐TENS . When evaluated at home , pain intensity was significantly reduced more by TENS than placebo‐TENS 1 week after the end of treatment , but not 3 months and 6 months later . At home evaluation of pain unpleasantness in the TENS group was never different from the placebo‐TENS group . These results suggest that TENS reduces both the sensory‐discriminative and motivational‐af‐fective components of low back pain in the short term but that much of the reduction in the affective component may be a placebo effect . We conclude that TENS should be used as a short‐term analgesic procedure in a multidisciplinary program for low back pain rather than as an exclusive or long‐term treatment Background : Chronic low back pain ( LBP ) is a growing health problem . Non‐steroidal anti‐inflammatory drugs ( NSAIDs ) are used to treat this condition , but have not demonstrated efficacy beyond 2 weeks , and no studies have shown that NSAIDs produce durable improvements in disability . Methods : To evaluate the efficacy and durability of effect of etoricoxib for chronic LBP , a r and omized , double blind , placebo‐controlled trial was conducted at 46 centres . Three hundred and twenty‐five patients with chronic LBP requiring treatment with an NSAID or paracetamol were r and omized 1:1:1 to etoricoxib 60 mg ( n=109 ) , 90 mg ( n=106 ) , or placebo ( n=110 ) , daily for 3 months . Pre‐specified endpoints over 3 months included LBP intensity scale ( visual analog scale 0–100 mm ) time‐weighted average change from baseline , the Rol and –Morris Disability Question naire ( RMDQ ) , the LBP bothersomeness scale , patient and investigator global assessment s , and measures of quality of life . Results : Both etoricoxib groups experienced significant reductions in LBP intensity at 4 weeks versus placebo [ −15.15 mm and −13.03 mm for 60 and 90 mg , respectively , probability (p)<0.001 for each ] , which was maintained over 3 months . Treatment result ed in significant improvement from baseline compared to placebo in RMDQ scores ( etoricoxib 60 mg , −2.82 and 90 mg , −2.38 , p<0.001 for each ) over 12 weeks and most other efficacy endpoints . There were no significant differences between treatments in incidence of adverse events ( AEs ) or discontinuations due to AEs . Conclusion : Etoricoxib provided significant relief of symptoms and disability associated with chronic LBP detected at 1 week , confirmed at 4 weeks , and maintained over 3 months . Reductions in chronic LBP severity corresponded to improvements in physical functioning and quality of life . All treatments were generally well tolerated OBJECTIVE To assess efficacy and safety of diclofenac-K 12.5 mg tablets in the treatment of acute low back pain ( low back pain ) . MATERIAL / METHOD A multiple dose , double-blind , double-dummy , r and omized , placebo-controlled , parallel group trial compared diclofenac-K ( 12.5 mg ; n = 124 ) with ibuprofen ( 200 mg ; n = 122 ) and placebo ( n = 126 ) in patients with moderate-to-severe acute low back pain . The treatment consisted of an initial dose of 2 tablets followed by 1 or 2 tablets every 4 - 6 hours as needed ( maximum 6 tablets/day ) for 7 days . The primary efficacy outcome for the initial dose was TOTPAR-3 , the summed total pain relief over the first 3 hours . Secondary initial dose outcomes included TOTPAR-6 , summed pain intensity differences SPID-3 and SPID-6 , time to rescue medication or remedicate , and the End of First Dose global efficacy assessment . The primary efficacy outcome for the flexible multiple dosing regimen was the End of Study global efficacy assessment . Secondary outcomes for multiple dosing included time to rescue medication over the entire study , the End of Day global efficacy assessment s ( daily over Days 1 - 7 ) , pain intensity differences on the VAS measured at Visit 2 and 3 , and change in Eifel algofunctional index . Safety/tolerability was assessed by recording adverse events . RESULTS Diclofenac-K 12.5 mg demonstrated superiority vs placebo on the primary efficacy parameter and almost all secondary initial dose outcomes . With respect to the initial dose , diclofenac-K 12.5 mg was also significantly superior to ibuprofen 200 mg on SPID-3 . Ibuprofen 200 mg was superior to placebo only on the End of First Dose global efficacy assessment . The flexible multiple dosing regimens of diclofenac-K and ibuprofen were both significantly superior to placebo on the End of Study global efficacy assessment , time to rescue medication over the entire study period , the End of Day global efficacy assessment on Days 1 - 2 , pain intensity difference on the VAS at Visit 3 and the Eifel algofunctional index at Visit 3 ( also at Visit 2 in diclofenac-K 12.5 mg group ) . Both active treatments were as well tolerated as placebo . CONCLUSIONS The flexible multiple dosing regimen of diclofenac-K 12.5 mg ( initial dose of 2 tablets followed by 1 - 2 tablets every 4 - 6 hours , max . 75 mg/day ) is an effective and safe treatment of acute low back pain & NA ; This prospect i ve , r and omised controlled trial , with three parallel groups , patient and observer blinded for verum and sham acupuncture and a follow up of 3 months raises the question : “ Does a combination of acupuncture and conservative orthopedic treatment improve conservative orthopedic treatment in chronic low back pain ( LBP ) . 186 in‐ patients of a LBP rehabilitation center with a history of LBP ≥6 weeks , VAS ≥50 mm , and no pending compensation cl aims , were selected ; for the three r and om group 4 weeks of treatment was applied . 174 patients met the protocol criteria and reported after treatment , 124 reported after 3 months follow up . Patients were assorted 4 strata : chronic LBP , ≤0.5 years , 0.5–2 years , 2–5 years , ≥5 years . Analysis was by intention to treat . Group 1 ( Verum+COT ) recieved 12 treatments of verum acupuncture and conservative orthopedic treatment ( COT ) . Group 2 ( Sham+COT ) recieved 12 treatments of non‐specific needling and COT . Group 3 ( nil+COT ) recieved COT alone . Verum‐ and Sham acupuncture were blinded against patient and examiner . The primary endpoints were pain reduction ≥50 % on VAS 3 months after the end of the treatment protocol . Secondary endpoints were pain reduction ≥50 % on VAS and treatment efficacy on a four‐point box scale directly after the end of the treatment protocol and treatment efficacy after 3 months . In the whole sample a pain relief of ≥50 % on VAS was reported directly after the end of treatment protocol : Verum+COT 65 % ( 95%CI 51–77 % ) , Sham+COT 34 % ( 95%ci 22–49 % ) , nil+COT 43 % ( 95%ci 29–58 % ) – results are significant for Verum+COT over Sham+COT ( P≤0.02 ) . The results after 3 months are : Verum+COT 77 % ( 95%ci 62–88 % ) , Sham+COT 29 % ( 95%ci 16–46 % ) , nil+Cot 14 % ( 95%ci 4–30 % ) – effects are significant for Verum+COT over Sham+COT ( P≤0.001 ) and for Verum+COT over nil+COT ( P<0.001 ) . No difference was found in the mobility of the patients nor in the intake of NSAID diclofenac . Our conclusion is that acupuncture can be an important supplement of conservative orthopedic treatment in the management of chronic LBP Study Design . A multicenter , r and omized , controlled trial with 1-year follow-up . Objectives . To compare the effect of manual therapy to exercise therapy in sick-listed patients with chronic low back pain ( > 8 wks ) . Summary and Background Data . The effect of exercise therapy and manual therapy on chronic low back pain with respect to pain , function , and sick leave have been investigated in a number of studies . The results are , however , conflicting . Methods . Patients with chronic low back pain or radicular pain sick-listed for more than 8 weeks and less than 6 months were included . A total of 49 patients were r and omized to either manual therapy ( n = 27 ) or to exercise therapy ( n = 22 ) . Sixteen treatments were given over the course of 2 months . Pain intensity , functional disability ( Oswestry disability index ) , general health ( Dartmouth COOP function charts ) , and return to work were recorded before , immediately after , at 4 weeks , 6 months , and 12 months after the treatment period . Spinal range of motion ( Schober test ) was measured before and immediately after the treatment period only . Results . Although significant improvements were observed in both groups , the manual therapy group showed significantly larger improvements than the exercise therapy group on all outcome variables throughout the entire experimental period . Immediately after the 2-month treatment period , 67 % in the manual therapy and 27 % in the exercise therapy group had returned to work ( P < 0.01 ) , a relative difference that was maintained throughout the follow-up period . Conclusions . Improvements were found in both intervention groups , but manual therapy showed significantly greater improvement than exercise therapy in patients with chronic low back pain . The effects were reflected on all outcome measures , both on short and long-term follow-up BACKGROUND Valdecoxib , a cyclooxygenase (COX)-2 specific inhibitor , is indicated for relief of the signs and symptoms of rheumatoid arthritis , osteoarthritis , and primary dysmenorrhea . Therapeutic doses of COX-2 specific inhibitors are as effective as nonspecific nonsteroidal anti-inflammatory drugs in reducing inflammatory pain while sparing the gastrointestinal and platelet toxicity associated with nonspecific COX-1 inhibition . OBJECTIVE The aim of this study was to assess the analgesic efficacy and tolerability of valdecoxib 40 mg/d compared with placebo in the treatment of chronic low back pain . METHODS This 4-week , prospect i ve , r and omized , double-blind placebo-controlled , parallel-group study was conducted at 37 centers across the United States and 5 centers in Canada . Patients aged > or = 18 years with chronic low back pain in flare were enrolled . Patients were r and omized to receive valdecoxib 40-mg/d or placebo tablets , once daily for 4 weeks . Patients rated low back pain intensity on a visual analog scale and completed the Rol and -Morris Disability Question naire and the modified Brief Pain Inventory-Short Form ( mBPI-SF ) at each visit . RESULTS Two hundred ninety-three patients were enrolled . The valdecoxib group comprised 148 patients ( 81 women , 67 men ; mean [ SD ] age , 48.6 [ 13.3 ] years ; mean [ SD ] body weight , 86.6 [ 20.9 ] kg ) , and the placebo group included 145 patients ( 85 women , 60 men ; mean [ SD ] age , 48.7 [ 12.6 ] years ; mean [ SD ] body weight , 85.6 [ 19.9 ] kg ) . Of the enrolled patients , 249 completed the study : 134 patients ( 91 % ) who received valdecoxib and 115 patients ( 79 % ) who received placebo . No statistically significant differences in patient baseline characteristics were noted between treatment groups , except in response to 1 mBPI-SF question ; patients in the valdecoxib group reported significantly greater interference in relations with other people due to pain than did those in the placebo group ( P = 0.048 ) . Changes from baseline in low back pain intensity were significantly greater in valdecoxib-treated patients at each assessment ( all , P < 0.001 vs placebo ) . Pain scores on the mBPI-SF indicated significantly greater pain relief with valdecoxib at each assessment ( all , P < or = 0.014 vs placebo ) . Improvements in mean Rol and -Morris Disability Question naire score with valdecoxib were significantly greater than with placebo at each assessment ( all , P < or = 0.003 ) . Although the overall incidence of adverse events ( AEs ) was significantly higher among patients receiving valdecoxib than those receiving placebo ( 35.1 % vs 24.1 % , respectively ; P = 0.042 ) , no significant differences were found between groups for the incidence of any individual AE . Most AEs ( 89 % [ 77/87 total events ] ) were mild or moderate in severity . CONCLUSIONS In this study of patients with chronic low back pain , valdecoxib 40 mg/d provided rapid relief ( within 1 week ) and consistent relief ( over 4 weeks ) . In addition , significant improvement in function and decreased disability were found with valdecoxib compared with placebo |
2,464 | 23,887,534 | It would also suggest that there is currently a poor evidence base to support the use of the current patient reported outcome measures as indicators of patient centredness | This paper explores the concept of patient-centred care as a dimension of quality as applied to dentistry and provides a systematic review of the literature .
The new NHS dental contract , which is currently being piloted in Engl and , is committed to delivering improvements in quality . | Background Precisely defining the different applications of patient-reported outcome measures ( PROs ) in clinical practice can be difficult . This is because the intervention is complex and varies amongst different studies in terms of the type of PRO used , how the PRO is fed back , and to whom it is fed back . Methods A theory-driven approach is used to describe six different applications of PROs in clinical practice . The evidence for the impact of these applications on the process and outcomes of care are summarised . Possible explanations for the limited impact of PROs on patient management are then discussed and directions for future research are highlighted . Results The applications of PROs in clinical practice include screening tools , monitoring tools , as a method of promoting patient-centred care , as a decision aid , as a method of facilitating communication amongst multidisciplinary teams ( MDTs ) , and as a means of monitoring the quality of patient care . Evidence from r and omised controlled trials suggests that the use of PROs in clinical practice is valuable in improving the discussion and detection of HRQoL problems but has less of an impact on how clinicians manage patient problems or on subsequent patient outcomes . Many of the reasons for this may lie in the ways in which PROs fit ( or do not fit ) into the routine ways in which patients and clinicians communicate with each other , how clinicians make decisions , and how healthcare as a whole is organised . Conclusions Future research needs to identify ways in with PROs can be better incorporated into the routine care of patients by combining qualitative and quantitative methods and adopting appropriate trial design BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals OBJECTIVE This paper defines an interactional analysis instrument to characterize patient-centered care and identify associated variables . METHODS In this study , 509 new adult patients were r and omized to care by family physicians and general internists . An adaption of the Davis Observation Code was used to measure a patient-centered practice style . The main outcome measures were visit-specific satisfaction and healthcare re source utilization . RESULTS In initial primary care visits , patient-centered practice style was positively associated with higher patient self-reported physical health status ( p=0.0328 ) , higher educational level ( p=0.0050 ) , and non-smoking status ( p=0.0108 ) ; it was also observed more often in the interactions of family physicians compared to internists ( p=0.0003 ) . Controlling for patient sociodemographic variables , self-reported health status , pain , health risk behaviors ( obesity , alcohol abuse , and smoking ) , and clinic assignment , patient satisfaction was not related to the provision of patient-centered care . Moreover , a higher average amount of patient-centered care recorded in visits throughout the one-year study period was significantly related to lower annual medical charges ( p=0.0003 ) . CONCLUSIONS Patient-centered care was observed more often with family physician caring for healthier , more educated patients , and was associated with lower charges . PRACTICE IMPLICATION S Reduced annual medical care charges are an important outcome of patient-centered medical visits Purpose : This article uses an interactional analysis instrument to characterize patient-centered care in the primary care setting and to examine its relationship with health care utilization . Methods : Five hundred nine new adult patients were r and omized to care by family physicians and general internists . An adaption of the Davis Observation Code was used to measure a patient-centered practice style . The main outcome measures were their use of medical services and related charges monitored over 1 year . Results : Controlling for patient sex , age , education , income , self-reported health status , and health risk behaviors ( obesity , alcohol abuse , and smoking ) , a higher average amount of patient-centered care recorded in visits throughout the 1-year study period was related to a significantly decreased annual number of visits for specialty care ( P = .0209 ) , less frequent hospitalizations ( P = .0033 ) , and fewer laboratory and diagnostic tests ( P = .0027 ) . Total medical charges for the 1-year study were also significantly reduced ( P = .0002 ) , as were charges for specialty care clinic visits ( P = .0005 ) , for all patients who had a greater average amount of patient-centered visits during that same time period . For female patients , the regression equation predicted 15.47 % of the variation in total annual medical charges compared with male patients , for whom 31.18 % of the variation was explained by the average percent of patient-centered care , controlling for sociodemographic variables , health status , and health risk behaviors . Conclusions : Patient-centered care was associated with decreased utilization of health care services and lower total annual charges . Reduced annual medical care charges may be an important outcome of medical visits that are patient-centered |
2,465 | 30,183,763 | Most comparisons did not show group differences .
Conclusions Most comparisons did not show group differences in automaticity .
The remaining comparisons leaned more toward a greater degree of movement automaticity after implicit learning than explicit learning . | Background Implicit motor learning is considered to be particularly effective for learning sports-related motor skills .
It should foster movement automaticity and thereby facilitate performance in multitasking and high-pressure environments . | Purpose Adding external focus of attention ( EF , focus on the movement effect ) may optimize current anterior cruciate ligament ( ACL ) injury prevention programmes . The purpose of the current study was to investigate the effects of an EF , by a visual stimulus and an internal focus , by a verbal stimulus during unexpected sidestep cutting in female and male athletes and how these effects remained over time . Methods Ninety experienced basketball athletes performed sidestep cutting manoeuvres in three sessions ( S1 , S2 and S3 ) . In this r and omized controlled trial , athletes were allocated to three groups : visual ( VIS ) , verbal ( VER ) and control ( CTRL ) . Kinematics and kinetics were collected at the time of peak knee frontal plane moment . Results Males in the VIS group showed a larger vertical ground reaction force ( S1 : 25.4 ± 3.1 N/kg , S2 : 25.8 ± 2.9 N/kg , S3 : 25.2 ± 3.2 N/kg ) and knee flexion moments ( S1 : −3.8 ± 0.9 Nm/kg , S2 : −4.0 ± 1.2 Nm/kg , S3 : −3.9 ± 1.3 Nm/kg ) compared to the males in the VER and CTRL groups and to the females in the VIS group ( p < 0.05 ) . Additionally , the males in the VIS group reduced knee valgus moment and the females in the VER group reduced knee varus moment over time ( n.s . ) . Conclusion Male subjects clearly benefit from visual feedback . Females may need different feedback modes to learn a correct movement pattern . Sex-specific learning preferences may have to be acknowledged in day by day practice . Adding video instruction or feedback to regular training regimens when teaching athletes safe movement patterns and providing individual feedback might target suboptimal long-term results and optimize ACL injury prevention programmes . Level of evidence The aim of this study was to ascertain whether the performances of implicit and explicit learners would converge over an extended period of learning . Participants practised a complex motor skill - golf putting - for 3000 trials , either with a concurrent secondary , tone-counting task ( implicit learning ) or without such a task ( explicit learning ) . The cognitive dem and s of the secondary task were predicted to prevent the accumulation of verbalizable rules about the motor task . The implicit group reported significantly fewer rules than the explicit group on subsequent verbal protocol s. The performance of the implicit group remained below that of the explicit group throughout the learning phase . However , no significant differences were found between groups during a delayed retention test . Additionally , for the participants in the explicit group only , a Reinvestment Scale score correlated positively with the number of rules accrued and negatively with overall putting performance during the learning phase . We use the results to argue against the excessive use of verbal instruction during skill acquisition , which might be unnecessary and ultimately might hamper performance under stressful conditions Accumulating evidence suggests that instructions inducing an " external " focus ofattention by directing learners ' attention toward the effects of their movements enhance learning , compared to instructions directing attention to the movements themselves ( " internal " focus ; for a review , see Wulf & Prinz , 2001 ) . Wulf , HoB , and Prinz ( 1998 ) first demonstrated external relative to internal focus advantages using ski-simulator and stabilometer tasks . In subsequent studies , this effect proved to be quite robust ( e.g. , Shea & Wulf , 1999 ; Wulf , McNevin , & Shea , 2001 ) and generalizable to sports-related tasks , including golf ( Wulf , Lauterbach , & Toole , 1999 ) , tennis ( Wulf , McNevin , Fuchs , Ritter , & Toole , 2000 ) , soccer , and volleyball skills ( Wulf , McConnel , Gartner , & Schwarz , 2002 ) . A " constrained action hypothesis " ( Wulfet aI. , 2001 ) was proposed to account for the greater effectiveness of an external compared to internal focus ofattention . According to this hypothesis , attempts to control one 's own movements consciously ( internal focus ) disrupt functioningofthe motor system by interferingwith automatic control processes . In contrast , focusing on the effects ofone 's movements promotes the use of automatic control processes , allowing the motor system to self-organize more naturally . The study by Wulf et al. ( 2001 ) supported this viewby demonstrating not only faster and more frequent adjustments of the balance movements but also Implicit processes almost certainly preceded explicit processes in our evolutionary history , so they are likely to be more resistant to disruption according to the principles of evolutionary biology [ Reber , A. S. ( 1992 ) . The cognitive unconscious : An evolutionary perspective . Consciousness and Cognition , 1 , 93 - 133 . ] . Previous work ( e.g. , [ Masters , R. S. W. ( 1992 ) . Knowledge , (k)nerves and know-how : The role of explicit versus implicit knowledge in the breakdown of a complex motor skill under pressure . British Journal of Psychology , 83 , 343 - 358 . ] ) has shown that implicitly learned motor skills remain stable under psychological pressure and concurrent cognitive dem and s , and recently [ Poolton , J. M. , Masters , R. S. W. , & Maxwell , J. P. ( 2007 ) . Passing thoughts on the evolutionary stability of implicit motor behaviour : Performance retention under physiological fatigue . Consciousness and Cognition , 16(2 ) , 456 - 468 . ] showed that they also remain stable under conditions of anaerobic fatigue that would have significantly challenged the survival skills of our ancestors . Here we examine the stability of an implicitly learned motor skill under fatigue conditions that primarily tax a different physiological system ( the aerobic system ) , but which have equally strong evolutionary connotations . Participants acquired a throwing task by means of an errorless ( implicit ) learning method or an errorful ( explicit ) method . Motor performance in the errorless condition , but not the errorful condition , remained stable following an exhaustive VO2 max . running test . Our findings replicate and extend the work of Poolton et al. , providing further support for Reber 's evolutionary distinction between implicit and explicit processes OBJECTIVES A growing number of publications describe cerebellar abnormalities in patients with bipolar disorder ( BD ) . The aim of the following paper was to examine the functional aspects of that issue by focusing on implicit learning - a cognitive function with significant cerebellar underpinnings . METHODS 27 patients with BD and 26 healthy controls ( HC ) , matched for age and sex took part in the study . Implicit motor learning was assessed by the serial reaction time task ( SRTT ) , in which participants were unconsciously learning a sequence of motor reactions . The indicators of procedural learning were the decrease of reaction time ( RT ) across the repetition of the sequence and the rebound of RT when the sequence changed into a r and om set of stimuli . RESULTS BD patients did not present any indicators of the implicit learning , their RT increased across repetitions of the sequence and it decreased when the sequence changed to r and om . Contrary , in the control group RT decreased across the sequence repetitions and increased when the stimuli begun to appear r and omly . LIMITATIONS A low subject count and a non-drug naïve patients group , medicated with atypical antipsychotic and mood stabilizers , are the most significant limitations of this study . CONCLUSIONS BD patients did not acquire procedural knowledge while performing the task , whereas HC did . To our knowledge this is the first study that shows the impairment of implicit motor learning in patients with BD . This indicates the possible cerebellar dysfunction in this disease and may provide a new neuropsychiatric approach to bipolar disorder Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Abstract We investigated the attention dem and s associated with implicit and explicit ( motor ) learning and performance using a probe reaction time paradigm . Two groups of participants learned a golf putting task over eight blocks of 50 trials performed from different distances . One group ( errorless learning ) began putting from the shortest distance ( 25 cm ) and moved progressively back to the furthest distance ( 200 cm ) . A second group ( errorful learning ) began putting from the furthest distance ( 200 cm ) and moved progressively closer ( 25 cm ) . Retention tests were used to assess learning in the two conditions , followed by transfer tests in which participants used either an unusual putter or a very unusual putter . Transfer to the unusual putters had an equivalent effect on the performance of both errorless and errorful learners , but probe reaction times were unaffected in the errorless learners , suggesting that execution of their movements was associated with reduced attention dem and s. Reducing errors during initial learning trials may encourage an implicit mode of learning and lower the dem and for cognitive re sources in subsequent performance |
2,466 | 31,244,687 | Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration , low sleep quality /efficiency , and circadian sleep desynchronization such as delayed phases and /or eveningness .
Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms .
Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD .
Conclusions : Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms .
These subjects have shown polymorphisms in clock genes expression and in genes involved in melatonin production .
The impairment of circadian sleep regulation may increase the individual 's vulnerability to develop symptoms of ASD by altering the sleep regulation in toto , which plays a key role in normal brain development .
Even though controversies and " research gaps " are present in literature at this point , we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD .
In particular , circadian sleep dysrhythmicity may predispose to develop ASD symptoms and vice versa within a self-reinforcing feedback loop .
By targeting sleep disturbances and circadian sleep dysrhythmicity , we may improve treatment strategies for both children and adults with ASD | Background : A compelling number of studies , conducted in both children and adults , have reported an association between sleep disturbances/circadian sleep alterations and autism spectrum disorder ( ASD ) ; however , the data are sparse and the nature of this link is still unclear .
The present review aim ed to systematic ally collect the literature data relevant on sleep disturbances and circadian sleep dysrhythmicity related to ASD across all ages and to provide an integrative theoretical framework of their association . | A high prevalence of subjective insomnia in adults with Asperger syndrome has been reported . In the present study the sleep quality of these patients was studied using wrist actigraphy . Nineteen adults with Asperger syndrome and frequent feelings of insomnia were compared with 10 controls devoid of neuropsychiatric disorders and subjective sleep problems during six consecutive nights . The patients had similar actigraphic sleep profile to the controls . The subjective low sleep quality in patients was not reflected in actigraphic assessment of sleep . This finding suggests that pervasive anxiety inherent in persons with Asperger syndrome predisposes them to insomnia complaints Although melatonin and cognitive-behavioural therapy have shown efficacy in treating sleep disorders in children with autism spectrum disorders , little is known about their relative or combined efficacy . One hundred and sixty children with autism spectrum disorders , aged 4 - 10 years , suffering from sleep onset insomnia and impaired sleep maintenance , were assigned r and omly to either ( 1 ) combination of controlled-release melatonin and cognitive-behavioural therapy ; ( 2 ) controlled-release melatonin ; ( 3 ) four sessions of cognitive-behavioural therapy ; or ( 4 ) placebo drug treatment condition for 12 weeks in a 1 : 1 : 1 : 1 ratio . Children were studied at baseline and after 12 weeks of treatment . Treatment response was assessed with 1-week actigraphic monitoring , sleep diary and sleep question naire . Main outcome measures , derived actigraphically , were sleep latency , total sleep time , wake after sleep onset and number of awakenings . The active treatment groups all result ed in improvements across all outcome measures , with moderate-to-large effect sizes from baseline to a 12-week assessment . Melatonin treatment was mainly effective in reducing insomnia symptoms , while cognitive-behavioural therapy had a light positive impact mainly on sleep latency , suggesting that some behavioural aspects might play a role in determining initial insomnia . The combination treatment group showed a trend to outperform other active treatment groups , with fewer dropouts and a greater proportion of treatment responders achieving clinical ly significant changes ( 63.38 % normative sleep efficiency criterion of > 85 % and 84.62 % , sleep onset latency < 30 min ) . This study demonstrates that adding behavioural intervention to melatonin treatment seems to result in a better treatment response , at least in the short term BACKGROUND Many studies in autistic disorder report sleep problems and altered circadian rhythms , suggesting abnormalities in melatonin physiology . Additionally , melatonin , a pineal gl and hormone produced from serotonin , is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology . METHODS Nocturnal urinary excretion of 6-sulphatoxymelatonin was measured by radioimmunoassay in groups of children and adolescents with autistic disorder ( n = 49 ) and normal control individuals ( n = 88 ) matched on age , sex , and Tanner stage of puberty . RESULTS Nocturnal 6-sulphatoxymelatonin excretion rate was significantly and substantially lower in patients with autism than in normal controls ( mean + /- SEM , .75 + /- .11 vs. 1.80 + /- .17 microg/hr , p = .0001 ) , and was significantly negatively correlated with severity of autistic impairments in verbal communication and play ( p < .05 ) . CONCLUSIONS These findings indicate clearly that nocturnal production of melatonin is reduced in autism . Further research is warranted in order to underst and the mechanisms underlying the lower melatonin production , to assess the impact of altered melatonin on the pathophysiology and behavioral expression of autistic disorder , and to determine the utility of melatonin administration in individuals with autism STUDY OBJECTIVES ( 1 ) Compare sleep behaviors of children with autism spectrum disorders ( ASD ) with sleep behaviors of typically developing ( TD ) children using the Children 's Sleep Habits Question naire ( CSHQ ) ; ( 2 ) compare sleep quality --defined as mean activity , sleep latency , number of awakenings , sleep efficiency and total sleep time -- of the cohort of children with ASD and TD , as measured by 10 nights of actigraphy ; and ( 3 ) estimate the prevalence of sleep disturbances in the ASD and TD cohorts . DESIGN Descriptive cross-sectional study . SETTING The Children 's Hospital of Philadelphia . PARTICIPANTS R and omly selected children from the Regional Autism Center . The ASD cohort of 59 children , aged 4 to 10 years , ( 26 with autism , 21 with pervasive developmental disorder-not otherwise specified [ PDD-NOS ] , and 12 with Asperger disorder ) were compared with 40 TD control subjects . MEASUREMENTS AND RESULTS The CSHQ , sleep diaries , and 10 nights of actigraphy using the Sadeh algorithm of children with ASD and TD control subjects were compared . CSHQ showed 66.1 % of parents of children with ASD ( 62.5 % autism , 76.2 % PDD-NOS , 58.3 % Asperger disorder ) and 45 % of parents of the control subjects reported that their children had sleep problems . Actigraphic data showed that 66.7 % of children with ASD ( 75 % autism , 52.4 % PDD-NOS , 75 % Asperger disorder ) and 45.9 % of the control subjects had disturbed sleep . CONCLUSIONS The prevalence estimate of 45 % for mild sleep disturbances in the TD cohort highlights pediatric sleep debt as a public health problem of concern . The prevalence estimate of 66 % for moderate sleep disturbances in the ASD cohort underscores the significant sleep problems that the families of these children face . The predominant sleep disorders in the ASD cohort were behavioral insomnia sleep-onset type and insomnia due to PDD Asperger syndrome ( AS ) is a neurodevelopmental disorder belonging to autism spectrum disorders . Both children and adults with AS have subjective impairment in the initiation and continuity of sleep , and studies using objective assessment are sparse . Twenty young AS adults with frequent complaints of low sleep quality were compared to 10 age- , gender- and education-matched controls without sleep complaints using polysomnography and spectral power analysis of slow-wave sleep . AS subjects displayed a similar polysomnographic profile as compared with controls . In spectral power analysis , a statistically nonsignificant trend towards decreased relative delta power and increased theta power in slow-wave sleep was found in the AS group . It seems that nonorganic insomnia , due to anxiety inherent in AS , is responsible for the low sleep quality in these subjects Background Sleep difficulties are prevalent in children with autism spectrum disorder ( ASD ) . The temporal nature of the association between sleep problems and ASD is unclear because longitudinal studies are lacking . Our aim is to clarify whether sleep problems precede and worsen autistic traits and ASD or occur as a consequence of the disorder . Methods Repeated sleep measures were available at 1.5 , 3 , 6 , and 9 years of age in 5151 children participating in the Generation R Study , a large prospect i ve birth cohort in the Netherl and s. Autistic traits were determined with the Pervasive Developmental Problems score ( PDP ) of the Child Behavior Checklist ( CBCL ) at 1.5 and 3 years and the Social Responsiveness Scale ( SRS ) at 6 years . This cohort included 81 children diagnosed with ASD . Results Sleep problems in early childhood were prospect ively associated with a higher SRS score , but not when correcting for baseline PDP score . By contrast , a higher SRS score and an ASD diagnosis were associated with more sleep problems at later ages , even when adjusting for baseline sleep problems . Likewise , a trajectory of increasing sleep problems was associated with ASD . Conclusions Sleep problems and ASD are not bidirectionally associated . Sleep problems do not precede and worsen autistic behavior but rather co-occur with autistic traits in early childhood . Over time , children with ASD have an increase in sleep problems , whereas typically developing children have a decrease in sleep problems . Our findings suggest that sleep problems are part of the construct ASD We describe our experience in using melatonin to treat insomnia , a common sleep concern , in children with autism spectrum disorders . One hundred seven children ( 2—18 years of age ) with a confirmed diagnosis of autism spectrum disorders who received melatonin were identified by review ing the electronic medical records of a single pediatrician . All parents were counseled on sleep hygiene techniques . Clinical response to melatonin , based on parental report , was categorized as ( 1 ) sleep no longer a concern , ( 2 ) improved sleep but continued parental concerns , ( 3 ) sleep continues to be a major concern , and ( 4 ) worsened sleep . The melatonin dose varied from 0.75 to 6 mg . After initiation of melatonin , parents of 27 children ( 25 % ) no longer reported sleep concerns at follow-up visits . Parents of 64 children ( 60 % ) reported improved sleep , although continued to have concerns regarding sleep . Parents of 14 children ( 13 % ) continued to report sleep problems as a major concern , with only 1 child having worse sleep after starting melatonin ( 1 % ) , and 1 child having undetermined response ( 1 % ) . Only 3 children had mild side-effects after starting melatonin , which included morning sleepiness and increased enuresis . There was no reported increase in seizures after starting melatonin in children with pre-existing epilepsy and no new-onset seizures . The majority of children were taking psychotropic medications . Melatonin appears to be a safe and well-tolerated treatment for insomnia in children with autism spectrum disorders . Controlled trials to determine efficacy appear warranted The purpose of this study was to determine the efficacy of controlled-release ( CR ) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders . A r and omized double-blind , placebo-controlled crossover trial of CR melatonin ( 5 mg ) followed by a 3-month open-label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects . Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs . Clinician rating of severity of the sleep disorder and improvement from baseline , along with caregiver ratings of global functioning and family stress were also obtained . Fifty-one children ( age range 2 - 18 years ) who did not respond to sleep hygiene intervention were enrolled . Fifty patients completed the crossover trial and 47 completed the open-label phase . Recordings of total night-time sleep and sleep latency showed significant improvement of approximately 30 min . Similarly , significant improvement was observed in clinician and parent ratings . There was additional improvement in the open-label somnolog measures of sleep efficiency and the longest sleep episode in the open-label phase . Overall , the therapy improved the sleep of 47 children and was effective in reducing family stress . Children with neurodevelopmental disabilities , who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance , showed improvement in melatonin therapy Objective To investigate longitudinal sleep patterns in children with autistic spectrum disorders ( ASDs ) . Study design Prospect i ve longitudinal study using Avon Longitudinal Study of Parents and Children , an English cohort born in 1991–1992 . Parental reports of sleep duration were collected by question naires at 8 time points from 6 months to 11 years . Children with an ASD diagnosis at age 11 years ( n=73 ) were identified from health and education records . Results From aged 30 months to 11 years old , children with ASD slept for 17–43 min less each day than contemporary controls . No significant difference in total sleep duration was found in infancy , but from 30 months of age children with ASD slept less than their peers , a difference that remained significant after adjusting for sex , ethnicity , high parity and epilepsy . The reduction in total sleep was wholly due to changes in night rather than daytime sleep duration . Night-time sleep duration was shortened by later bedtimes and earlier waking times . Frequent waking ( 3 or more times a night ) was also evident among the children with ASD from 30 months of age . Age-specific decreases of > 1SD within individuals in sleep duration across adjacent time points was a predictor of ASD between 18 months and 30 months of age ( p=0.04 ) and from 30 months to 42 months ( p=0.02 ) . Conclusions Sleep duration in children with ASD is reduced from 30 months of age and persists until adolescence Supplemental melatonin has shown promise in treating sleep onset insomnia in children with autism spectrum disorders ( ASD ) . Twenty-four children , free of psychotropic medications , completed an open-label dose-escalation study to assess dose – response , tolerability , safety , feasibility of collecting actigraphy data , and ability of outcome measures to detect change during a 14-week intervention . Supplemental melatonin improved sleep latency , as measured by actigraphy , in most children at 1 or 3 mg dosages . It was effective in week 1 of treatment , maintained effects over several months , was well tolerated and safe , and showed improvement in sleep , behavior , and parenting stress . Our findings contribute to the growing literature on supplemental melatonin for insomnia in ASD and inform planning for a large r and omized trial in this population Sleep disturbances are common in patients with Asperger disorder . Although these sleep problems are often persistent and may significantly impair the child 's daytime well-being , no treatment studies have been reported . In this open clinical trial , the effectiveness of melatonin was studied in a sample of 15 children with Asperger disorder ( 13 boys , 2 girls ) aged 6 - 17 years using several question naires and actigraph measurements . They included assessment s of sleep quality , tiredness , and behavior . Melatonin ( 3 mg/day ) was used for 14 days . All the measurements were made three times : before the treatment period , during the treatment ( days 12 - 14 ) , and 3 weeks after the discontinuation of the treatment . The sleep patterns of all the children improved , and half of them displayed excellent responses to melatonin . In particular , actigraphically measured sleep latency decreased from 40.02 + /- 24.09 minutes to 21.82 + /- 9.64 minutes ( p = 0.002 ) , whereas sleep duration remained steady at 477.40 + /- 55.56 minutes and 480.48 + /- 50.71 minutes . Despite the short duration of the treatment , behavioral measures also displayed a significant improvement , and most of the effect disappeared after the discontinuation of the melatonin ( p = 0.001 ) . In conclusion , melatonin may provide an interesting new and well-tolerated treatment option for children with Asperger disorder suffering from chronic insomnia . However , these results must be confirmed in a controlled study OBJECTIVE To assess the efficacy and safety of novel pediatric-appropriate , prolonged-release melatonin minitablets ( PedPRM ) versus placebo for insomnia in children and adolescents with autism spectrum disorder ( ASD ) , with or without attention-deficit/hyperactivity disorder ( ADHD ) comorbidity , and neurogenetic disorders ( NGD ) . METHOD A total of 125 children and adolescents ( 2 - 17.5 years of age ; 96.8 % ASD , 3.2 % Smith-Magenis syndrome [ SMS ] ) whose sleep failed to improve on behavioral intervention alone were r and omized ( 1:1 ratio ) , double-blind , to receive PedPRM ( 2 mg escalated to 5 mg ) or placebo for 13 weeks . Sleep measures included the vali date d caregivers ' Sleep and Nap Diary ( SND ) and Composite Sleep Disturbance Index ( CSDI ) . The a priori primary endpoint was SND-reported total sleep time ( TST ) after 13 weeks of treatment . RESULTS The study met the primary endpoint : after 13 weeks of double-blind treatment , participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 minutes with placebo ( adjusted mean treatment difference PedPRM-placebo -32.43 minutes ; p = .034 ) . Sleep latency ( SL ) decreased by 39.6 minutes on average with PedPRM and 12.5 minutes with placebo ( adjusted mean treatment difference -25.30 minutes ; p = .011 ) without causing earlier wakeup time . The rate of participants attaining clinical ly meaningful responses in TST and /or SL was significantly higher with PedPRM than with placebo ( 68.9 % versus 39.3 % respectively ; p = .001 ) corresponding to a number needed to treat ( NNT ) of 3.38 . Overall sleep disturbance ( CSDI ) tended to decrease . PedPRM was generally safe ; somnolence was more commonly reported with PedPRM than placebo . CONCLUSION PedPRM was efficacious and safe for treatment of insomnia in children and adolescents with ASD with/without ADHD and NGD . The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high . Clinical trial registration information-Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities ; http:// clinical trials.gov/ ; NCT01906866 Asperger 's syndrome ( AS ) is a pervasive developmental disorder that may fall along the autistic spectrum . We compared the sleep of eight patients with AS with that of participants matched for age and gender . Patients with AS showed decreased sleep time in the first two-thirds of the night , increased number of shifts into REM sleep from a waking epoch , and all but one patient showed signs of REM sleep disruption . EEG sleep spindles were significantly decreased while K complexes and REM sleep rapid eye movements were normal . Three patients with AS , but none of the comparison participants , showed a pathological index of periodic leg movements in sleep . These observations show that sleep disorders are associated with AS and suggest that defective sleep control systems may be associated with the clinical picture of AS BACKGROUND Melatonin is often used for autistic children with sleep disorders , despite a lack of published evidence in this population . METHODS A r and omized , placebo-controlled double-blind crossover trial of melatonin was undertaken in 11 children with autistic spectrum disorder ( ASD ) . RESULTS Seven children completed the trial . Sleep latency was 2.6 h [ 95 % confidence intervals ( CI ) 2.28 - 2.93 ] baseline , 1.91 h ( 95 % CI 1.78 - 2.03 ) with placebo and 1.06 h ( 95 % CI 0.98 - 1.13 ) with melatonin . Wakings per night were 0.35 ( 95 % CI 0.18 - 0.53 ) baseline , 0.26 ( 95 % CI 0.20 - 0.34 ) with placebo and 0.08 ( 95 % CI 0.04 - 0.12 ) with melatonin . Total sleep duration was 8.05 h ( 95 % CI 7.65 - 8.44 ) baseline , 8.75 h ( 95 % CI 8.56 - 8.98 ) with placebo and 9.84 h ( 95 % CI 9.68 - 9.99 ) with melatonin . CONCLUSIONS Although the study was small owing to recruitment difficulties , it still provides evidence of effectiveness of melatonin in children with sleep difficulties and ASD , which we predict a larger study would confirm Twenty-two children with autism spectrum disorders who had not responded to supported behaviour management strategies for severe dysomnias entered a double blind , r and omised , controlled crossover trial involving 3 months of placebo versus 3 months of melatonin to a maximum dose of 10 mg . 17 children completed the study . There were no significant differences between sleep variables at baseline . Melatonin significantly improved sleep latency ( by an average of 47 min ) and total sleep ( by an average of 52 min ) compared to placebo , but not number of night wakenings . The side effect profile was low and not significantly different between the two arms STUDY OBJECTIVE To determine the efficacy of melatonin on sleep problems in children with autistic spectrum disorder ( ASD ) and fragile X syndrome ( FXS ) . METHODS A 4-week , r and omized , double blind , placebo-controlled , crossover design was conducted following a 1-week baseline period . Either melatonin , 3 mg , or placebo was given to participants for 2 weeks and then alternated for another 2 weeks . Sleep variables , including sleep duration , sleep-onset time , sleep-onset latency time , and the number of night awakenings , were recorded using an Actiwatch and from sleep diaries completed by parents . All participants had been thoroughly assessed for ASD and also had DNA testing for the diagnosis of FXS . RESULTS Data were successfully obtained from the 12 of 18 subjects who completed the study ( 11 males , age range 2 to 15.25 years , mean 5.47 , SD 3.6 ) . Five participants met diagnostic criteria for ASD , 3 for FXS alone , 3 for FXS and ASD , and 1 for fragile X premutation . Eight out of 12 had melatonin first . The conclusions from a nonparametric repeated- measures technique indicate that mean night sleep duration was longer on melatonin than placebo by 21 minutes ( p = .02 ) , mean sleep-onset latency was shorter by 28 minutes ( p = .0001 ) , and mean sleep-onset time was earlier by 42 minutes ( p = .02 ) . CONCLUSION The results of this study support the efficacy and tolerability of melatonin treatment for sleep problems in children with ASD and FXS Sleep disturbances are regarded as a common clinical feature in autistic children . This concept is based primarily on informal observations or studies conducted with question naires . In this study we compared data obtained by question naires to that obtained with actigraphy . Among 22 autistic children , 12 were reported as having sleep problems and 8 patients completed 72 hours actigraphy . While the employment of question naires disclosed that autistic children had an earlier morning awakening time and multiple and early night arousals , actigraphic monitoring showed that with the exception of an earlier morning arousal time ( p = .045 ) , sleep patterns of autistic children were similar to that of normal children . Parental over-sensitivity to sleep disturbances of the autistic children may explain this phenomenon |
2,467 | 31,404,063 | Baseline demographic reporting was high for age and sex in CRTs , but was uncommon for race and ethnicity .
HTE analyses were uncommon and was rare for demographic subgroups , which limits the ability to examine the extent of benefits or risks for treatments tested with CRT design | BACKGROUND Cluster-r and omized trials ( CRTs ) are being increasingly used to test a range of interventions , including medical interventions commonly used in clinical practice .
Policies created by the NIH and the Food and Drug Administration ( FDA ) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect ( HTE ) for individually r and omized trials .
Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs .
OBJECTIVES We sought to underst and the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease , cancer , and chronic lower respiratory diseases .
Additionally , we also report on the proportion of CRTs that reported on baseline demographics of its population s and conducted demographic HTE analyses . | Cluster r and omized trials are frequently used in health service evaluation . It is common practice to use an analysis model with a r and om effect to allow for clustering at the analysis stage . In design s where clusters are exposed to both control and treatment conditions , it may be of interest to examine treatment effect heterogeneity across clusters . In design s where clusters are not exposed to both control and treatment conditions , it can also be of interest to allow heterogeneity in the degree of clustering between arms . These two types of heterogeneity are related . It has been proposed in both parallel cluster trials , stepped‐wedge , and other cross‐over design s that this heterogeneity can be allowed for by incorporating additional r and om effect(s ) into the model . Here , we show that the choice of model parameterization needs careful consideration as some parameterizations for additional heterogeneity induce unnecessary or implausible assumptions . We suggest more appropriate parameterizations , discuss their relative advantages , and demonstrate the implication s of these model choices using a real example of a parallel cluster trial and a simulated stepped‐wedge trial BACKGROUND During cardiopulmonary resuscitation ( CPR ) in patients with out-of-hospital cardiac arrest , the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival . We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations . METHODS This cluster-r and omized trial with crossover included 114 emergency medical service ( EMS ) agencies . Adults with non-trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions ( intervention group ) or interrupted chest compressions ( control group ) . The primary outcome was the rate of survival to hospital discharge . Secondary outcomes included the modified Rankin scale score ( on a scale from 0 to 6 , with a score of ≤3 indicating favorable neurologic function ) . CPR process was measured to assess compliance . RESULTS Of 23,711 patients included in the primary analysis , 12,653 were assigned to the intervention group and 11,058 to the control group . A total of 1129 of 12,613 patients with available data ( 9.0 % ) in the intervention group and 1072 of 11,035 with available data ( 9.7 % ) in the control group survived until discharge ( difference , -0.7 percentage points ; 95 % confidence interval [ CI ] , -1.5 to 0.1 ; P=0.07 ) ; 7.0 % of the patients in the intervention group and 7.7 % of those in the control group survived with favorable neurologic function at discharge ( difference , -0.6 percentage points ; 95 % CI , -1.4 to 0.1 , P=0.09 ) . Hospital-free survival was significantly shorter in the intervention group than in the control group ( mean difference , -0.2 days ; 95 % CI , -0.3 to -0.1 ; P=0.004 ) . CONCLUSIONS In patients with out-of-hospital cardiac arrest , continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC CCC Clinical Trials.gov number , NCT01372748 . ) Objective To investigate whether real-time audio and visual feedback during cardiopulmonary resuscitation outside hospital increases the proportion of subjects who achieved prehospital return of spontaneous circulation . Design A cluster-r and omised trial . Subjects 1586 people having cardiac arrest outside hospital in whom resuscitation was attempted by emergency medical services ( 771 procedures without feedback , 815 with feedback ) . Setting Emergency medical services from three sites within the Resuscitation Outcomes Consortium in the United States and Canada . Intervention Real-time audio and visual feedback on cardiopulmonary resuscitation ( CPR ) provided by the monitor-defibrillator . Main outcome measure Prehospital return of spontaneous circulation after CPR . Results Baseline patient and emergency medical service characteristics did not differ between groups . Emergency medical services muted the audible feedback in 14 % of cases during the period with feedback . Compared with CPR clusters lacking feedback , clusters assigned to feedback were associated with increased proportion of time in which chest compressions were provided ( 64 % v 66 % , cluster-adjusted difference 1.9 ( 95 % CI 0.4 to 3.4 ) ) , increased compression depth ( 38 v 40 mm , adjusted difference 1.6 ( 0.5 to 2.7 ) ) , and decreased proportion of compressions with incomplete release ( 15 % v 10 % , adjusted difference −3.4 ( −5.2 to −1.5 ) ) . However , frequency of prehospital return of spontaneous circulation did not differ according to feedback status ( 45 % v 44 % , adjusted difference 0.1 % ( −4.4 % to 4.6 % ) ) , nor did the presence of a pulse at hospital arrival ( 32 % v 32 % , adjusted difference −0.8 ( −4.9 to 3.4 ) ) , survival to discharge ( 12 % v 11 % , adjusted difference −1.5 ( −3.9 to 0.9 ) ) , or awake at hospital discharge ( 10 % v 10 % , adjusted difference −0.2 ( −2.5 to 2.1 ) ) . Conclusions Real-time visual and audible feedback during CPR altered performance to more closely conform with guidelines . However , these changes in CPR performance were not associated with improvements in return of spontaneous circulation or other clinical outcomes . Trial Registration Clinical Trials Background Computer-based decision support has been effective in providing alerts for preventive care . Our objective was to determine whether a personalized asthma management computer-based decision support increases the quality of asthma management and reduces the rate of out-of-control episodes . Methods A cluster-r and omized trial was conducted in Quebec , Canada among 81 primary care physicians and 4447 of their asthmatic patients . Patients were followed from the first visit for 3–33 months . The physician control group used the Medical Office of the 21st century ( MOXXI ) system , an integrated electronic health record . A custom-developed asthma decision support system was integrated within MOXXI and was activated for physicians in the intervention group . Results At the first visit , 9.8 % ( intervention ) to 12.9 % ( control ) of patients had out-of-control asthma , which was defined as a patient having had an emergency room visit or hospitalization for respiratory-related problems and /or more than 250 doses of fast-acting β-agonist ( FABA ) dispensed in the past 3 months . By the end of the trial , there was a significant increase in the ratio of doses of inhaled corticosteroid use to fast-acting β-agonist ( 0.93 vs. 0.69 : difference : 0.27 ; 95 % CI : 0.02–0.51 ; P = 0.03 ) in the intervention group . The overall out-of-control asthma rate was 54.7 ( control ) and 46.2 ( intervention ) per 100 patients per year ( 100 PY ) , a non-significant rate difference of −8.7 ( 95 % CI : −24.7 , 7.3 ; P = 0.29 ) . The intervention ’s effect was greater for patients with out-of-control asthma at the beginning of the study , a group who accounted for 44.7 % of the 5597 out-of-control asthma events during follow-up , as there was a reduction in the event rate of −28.4 per 100 PY ( 95 % CI : −55.6 , −1.2 ; P = 0.04 ) compared to patients with in-control asthma at the beginning of the study ( −0.08 [ 95 % CI : −10.3 , 8.6 ; P = 0.86 ] ) . Discussion This study evaluated the effectiveness of a novel computer-assisted ADS system that facilitates systematic monitoring of asthma control status , follow-up of patients with out of control asthma , and evidence -based , patient-specific treatment recommendations . We found that physicians were more likely to use ADS for out-of-control patients , that in the majority of these patients , they were advised to add an inhaled corticosteroid or a leukotriene inhibitor to the patient s treatment regimen , and the intervention significantly increased the mean ratio of inhaled corticosteroids to FABA during follow-up . It also reduced the rate of out-of-control episodes during follow up among patients whose asthma was out-of-control at the time of study entry . Future research should assess whether coupling patient-specific treatment recommendations , automated follow-up , and home care with comparative feedback on quality and outcomes of care can improve guideline adoption and care outcomes . Conclusions A primary care-personalized asthma management system reduced the rate of out-of-control asthma episodes among patients whose asthma was poorly controlled at the study ’s onset . Trial Registration Clinical trials.gov Identifier : NCT00170248 http:// clinical 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 Patients at risk of severe exacerbations contribute disproportionally to asthma mortality , morbidity and costs . We evaluated the effectiveness and costs of using ‘ asthma risk registers ’ for these patients in primary care . Methods In a cluster-r and omised trial , 29 primary care practice s identified 911 at-risk asthma patients using British asthma guideline criteria ( severe asthma plus adverse psychosocial characteristics ) . Intervention practice s added electronic alerts to identified patients ' records to flag their at-risk status and received practice -based training about using the alerts to improve patient access and opportunistic management . Control practice s continued routine care . Numbers of patients experiencing the primary outcome of a moderate-severe exacerbation ( result ing in death , hospitalisation , accident and emergency attendance , out-of-hours contact , or a course/boost in oral prednisolone for asthma ) , other healthcare and medication usage , and costs over 1 year were derived from practice -based records . Results There was no significant effect on exacerbations ( control : 46.5 % ; intervention : 53.6 % , OR , 95 % CI 1.30 , 0.93 to 1.80 ) . However , this composite outcome masked relative reductions in intervention patients experiencing hospitalisations ( OR 0.50 , 95 % CI 0.26 to 0.94 ) , accident and emergency ( OR 0.74 , 95 % CI 0.42 to 1.31 ) and out-of-hours contacts ( OR 0.79 , 95 % CI 0.45 to 1.37 ) ; and a relative increase in prednisolone prescription for exacerbations ( OR 1.31 , 95 % CI 0.92 to 1.85 ) . Furthermore , prescription of nebulised short-acting β-agonists reduced and long-acting β-agonists increased for intervention relative to control patients . The adjusted mean per patient healthcare cost was £ 138.21 lower ( p=0.837 ) among intervention practice s. Conclusion Using asthma risk registers in primary care did not reduce treated exacerbations , but reduced hospitalisations and increased prescriptions of recommended preventative therapies without increasing costs Objective To evaluate the effectiveness of a structured education pulmonary rehabilitation programme on the health status of people with chronic obstructive pulmonary disease ( COPD ) . Design Two-arm , cluster r and omised controlled trial . Setting 32 general practice s in the Republic of Irel and . Participants 350 participants with a diagnosis of moderate or severe COPD . Intervention Experimental group received a structured education pulmonary rehabilitation programme , delivered by the practice nurse and physiotherapist . Control group received usual care . Main outcome measure Health status as measured by the Chronic Respiratory Question naire ( CRQ ) at baseline and at 12–14 weeks postcompletion of the programme . Results Participants allocated to the intervention group had statistically significant higher mean change total CRQ scores ( adjusted mean difference ( MD ) 1.11 , 95 % CI 0.35 to 1.87 ) . However , the CI does not exclude a smaller difference than the one that was prespecified as clinical ly important . Participants allocated to the intervention group also had statistically significant higher mean CRQ Dyspnoea scores after intervention ( adjusted MD 0.49 , 95 % CI 0.20 to 0.78 ) and CRQ Physical scores ( adjusted MD 0.37 , 95 % CI 0.14 to 0.60 ) . However , CIs for both the CRQ Dyspnoea and CRQ Physical subscales do not exclude smaller differences as prespecified as clinical ly important . No other statistically significant differences between groups were seen . Conclusions A primary care based structured education pulmonary rehabilitation programme is feasible and may increase local accessibility to people with moderate and severe COPD . Trial registration IS RCT N52403063 The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. BACKGROUND In a departure from the previous strategy of immediate defibrillation , the 2005 resuscitation guidelines from the American Heart Association-International Liaison Committee on Resuscitation suggested that emergency medical service ( EMS ) personnel could provide 2 minutes of cardiopulmonary resuscitation ( CPR ) before the first analysis of cardiac rhythm . We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm . METHODS We conducted a cluster-r and omized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada . Patients in the early- analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later- analysis group were assigned to receive 180 seconds of CPR , before the initial electrocardiographic analysis . The primary outcome was survival to hospital discharge with satisfactory functional status ( a modified Rankin scale score of ≤3 , on a scale of 0 to 6 , with higher scores indicating greater disability ) . RESULTS We included 9933 patients , of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis . A total of 273 patients ( 5.9 % ) in the later- analysis group and 310 patients ( 5.9 % ) in the early- analysis group met the criteria for the primary outcome , with a cluster-adjusted difference of -0.2 percentage points ( 95 % confidence interval , -1.1 to 0.7 ; P=0.59 ) . Analyses of the data with adjustment for confounding factors , as well as subgroup analyses , also showed no survival benefit for either study group . CONCLUSIONS Among patients who had an out-of-hospital cardiac arrest , we found no difference in the outcomes with a brief period , as compared with a longer period , of EMS-administered CPR before the first analysis of cardiac rhythm . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC PRIMED Clinical Trials.gov number , NCT00394706 . ) BACKGROUND Mechanical chest compression devices have the potential to help maintain high- quality cardiopulmonary resuscitation ( CPR ) , but despite their increasing use , little evidence exists for their effectiveness . We aim ed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest . METHODS The pre-hospital r and omised assessment of a mechanical compression device in cardiac arrest ( PARAMEDIC ) trial was a pragmatic , cluster-r and omised open-label trial including adults with non-traumatic , out-of-hospital cardiac arrest from four UK Ambulance Services ( West Midl and s , North East Engl and , Wales , South Central ) . 91 urban and semi-urban ambulance stations were selected for participation . Clusters were ambulance service vehicles , which were r and omly assigned ( 1:2 ) to LUCAS-2 or manual CPR . Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene . The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat . Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation . Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible . The study is registered with Current Controlled Trials , number IS RCT N08233942 . FINDINGS We enrolled 4471 eligible patients ( 1652 assigned to the LUCAS-2 group , 2819 assigned to the control group ) between April 15 , 2010 and June 10 , 2013 . 985 ( 60 % ) patients in the LUCAS-2 group received mechanical chest compression , and 11 ( < 1 % ) patients in the control group received LUCAS-2 . In the intention-to-treat analysis , 30 day survival was similar in the LUCAS-2 group ( 104 [ 6 % ] of 1652 patients ) and in the manual CPR group ( 193 [ 7 % ] of 2819 patients ; adjusted odds ratio [ OR ] 0·86 , 95 % CI 0·64 - 1·15 ) . No serious adverse events were noted . Seven clinical adverse events were reported in the LUCAS-2 group ( three patients with chest bruising , two with chest lacerations , and two with blood in mouth ) . 15 device incidents occurred during operational use . No adverse or serious adverse events were reported in the manual group . INTERPRETATION We noted no evidence of improvement in 30 day survival with LUCAS-2 compared with manual compressions . On the basis of ours and other recent r and omised trials , widespread adoption of mechanical CPR devices for routine use does not improve survival . FUNDING National Institute for Health Research HTA - 07/37/69 BACKGROUND Meta- analysis of small trials suggests that pharmacist-led collaborative review and revision of medical treatment may improve outcomes in heart failure . METHODS AND RESULTS We studied patients with left ventricular systolic dysfunction in a cluster-r and omized controlled , event driven , trial in primary care . We allocated 87 practice s ( 1090 patients ) to pharmacist intervention and 87 practice s ( 1074 patients ) to usual care . The intervention was delivered by non-specialist pharmacists working with family doctors to optimize medical treatment . The primary outcome was a composite of death or hospital admission for worsening heart failure . This trial is registered , number IS RCT N70118765 . The median follow-up was 4.7 years . At baseline , 86 % of patients in both groups were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker . In patients not receiving one or other of these medications , or receiving less than the recommended dose , treatment was started , or the dose increased , in 33.1 % of patients in the intervention group and in 18.5 % of the usual care group [ odds ratio ( OR ) 2.26 , 95 % CI 1.64 - 3.10 ; P < 0.001 ] . At baseline , 62 % of each group were treated with a β-blocker and the proportions starting or having an increase in the dose were 17.9 % in the intervention group and 11.1 % in the usual care group ( OR 1.76 , 95 % CI 1.31 - 2.35 ; P < 0.001 ) . The primary outcome occurred in 35.8 % of patients in the intervention group and 35.4 % in the usual care group ( hazard ratio 0.97 , 95 % CI 0.83 - 1.14 ; P = 0.72 ) . There was no difference in any secondary outcome . CONCLUSION A low-intensity , pharmacist-led collaborative intervention in primary care result ed in modest improvements in prescribing of disease-modifying medications but did not improve clinical outcomes in a population that was relatively well treated at baseline INTRODUCTION Achievement and maintenance of good asthma control is a major objective in asthma management . However , asthma control in many patients is suboptimal , due to improper use of asthma medications and non-adherence . The aim of this study was to evaluate the effect of a pharmacist intervention on asthma control in adult patients . METHODS A 6-month cluster r and omized controlled trial was undertaken with allocation of community pharmacies to intervention or control group . Adult asthma patients in the intervention group received a protocol -based intervention addressing individual needs related to asthma control , inhaler technique and medication adherence . Patients in the control group received usual care . Main variables were measured at baseline , 3 and 6 months . RESULTS 336 patients completed the study , 150 in the control group and 186 in the intervention group . The intervention result ed in enhanced asthma control : Patients receiving the intervention had an Odds ratio of 3.06 ( 95 % CI:1.63 - 5.73 ; p < 0.001 ) of having controlled asthma six months later . In the intervention group mean ACQ scores significantly improved [ 0.66 points ( SD : 0.78 ) ; p < 0.001 ] and the number of controlled asthma patients increased by 30.1 % ( p < 0.001 ) after 6 months . The intervention also result ed in improved medication adherence ( by 40.3 % , p < 0.001 ) and inhaler technique ( by 56.2 % , p < 0.001 ) . No significant changes for any of these variables were observed in the control group . CONCLUSION The AFasma study focused on the important outcomes of asthma management , and showed that through the design ed intervention , community pharmacists can increase controlled asthma patients compared to usual care . Trial registration NCT01085474 BACKGROUND Childhood asthma morbidity remains significant , especially in low-income children . Most often , asthma management is provided by the child 's primary care provider . OBJECTIVE We sought to evaluate whether enhancing primary care management for persistent asthma with telephone-based peer coaching for parents reduced asthma impairment and risk in children 3 to 12 years old . METHODS Over 12 months , peer trainers provided parents with asthma management training by telephone ( median , 18 calls ) and encouraged physician partnership . The intervention was evaluated in a cluster-r and omized trial of 11 intervention and 11 usual care pediatric practice s ( 462 and 486 families , respectively ) . Patient outcomes were assessed by means of telephone interviews at 12 and 24 months conducted by observers blinded to intervention assignment and compared by using mixed-effects models , controlling for baseline values and clustering within practice s. In a planned subgroup analysis we examined the heterogeneity of the intervention effect by insurance type ( Medicaid vs other ) . RESULTS After 12 months , intervention participation result ed in 20.9 ( 95 % CI , 9.1 - 32.7 ) more symptom-free days per child than in the control group , and there was no difference in emergency department ( ED ) visits . After 24 months , ED visits were reduced ( difference in mean visits/child , -0.28 ; 95 % CI , -0.5 to -0.02 ) , indicating a delayed intervention effect . In the Medicaid subgroup , after 12 months , intervention participation result ed in 42 % fewer ED visits ( difference in mean visits/child , -0.50 ; 95 % CI , -0.81 to -0.18 ) and 62 % fewer hospitalizations ( difference in mean hospitalizations/child , -0.16 ; 95 % CI , -0.30 to -0.014 ) . Reductions in health care use endured through 24 months . CONCLUSIONS This pragmatic telephone-based peer-training intervention reduced asthma impairment . Asthma risk was reduced in children with Medicaid insurance BACKGROUND The quality of care provided to patients with cancer who are dying in hospital and their families is suboptimum . The UK Liverpool Care Pathway ( LCP ) for patients who are dying was developed with the aim of transferring the best practice of hospices to hospitals . We therefore assessed the effectiveness of LCP in the Italian context ( LCP-I ) in improving the quality of end-of-life care for patients with cancer in hospitals and for their family . METHODS In this pragmatic cluster r and omised trial , 16 Italian general medicine hospital wards were r and omly assigned to implement the LCP-I programme or st and ard health-care practice . For each ward , we identified all patients who died from cancer in the 3 months before r and omisation ( preintervention ) and in the 6 months after the completion of the LCP-I training programme . The primary endpoint was the overall quality of care toolkit scale . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT01081899 . FINDINGS During the postintervention assessment , data were gathered for 308 patients who died from cancer ( 147 in LCP-I programme wards and 161 in control wards ) . 232 ( 75 % ) of 308 family members were interviewed , 119 ( 81 % ) of 147 with relatives cared for in the LCP-I wards ( mean cluster size 14·9 [ range eight to 22 ] ) and 113 ( 70 % ) of 161 in the control wards ( 14·1 [ eight to 22 ] ) . After implementation of the LCP-I programme , no significant difference was noted in the distribution of the overall quality of care toolkit scores between the wards in which the LCP-I programme was implemented and the control wards ( score 70·5 of 100 vs 63·0 of 100 ; cluster-adjusted mean difference 7·6 [ 95 % CI -3·6 to 18·7 ] ; p=0·186 ) . INTERPRETATION The effect of the LCP-I programme in our study is less than the effects noted in earlier phase 2 trials . However , if the programme is implemented well it has the potential to reduce the gap in quality of care between hospices and hospitals . Further research is needed to ascertain what components of the LCP-I programme might be effective and to develop and assess a wider range of approaches to quality improvement in hospital care for people at the end of their lives and for their families . FUNDING Italian Ministry of Health and Maruzza Lefebvre D'Ovidio Foundation-Onlus Cluster r and omized trials r and omly assign groups of individuals to examine research questions or test interventions and measure their effects on individuals . Recent emphasis on quality improvement , comparative effectiveness , and learning health systems has prompted exp and ed use of pragmatic cluster r and omized trials in routine health-care setting s , which in turn poses practical and ethical challenges that current oversight frameworks may not adequately address . The 2012 Ottawa Statement provides a basis for considering many issues related to pragmatic cluster r and omized trials but challenges remain , including some arising from the current US research and health-care regulations . In order to examine the ethical , regulatory , and practical questions facing pragmatic cluster r and omized trials in health-care setting s , the National Institutes of Health Health Care Systems Research Collaboratory convened a workshop in Bethesda , Maryl and , in July 2013 . Attendees included experts in clinical trials , patient advocacy , research ethics , and research regulations from academia , industry , the National Institutes of Health Collaboratory , and other federal agencies . Workshop participants identified substantial barriers to implementing these types of cluster r and omized trials , including issues related to research design , gatekeepers and governance in health systems , consent , institutional review boards , data monitoring , privacy , and special population s. We describe these barriers and suggest means for underst and ing and overcoming them to facilitate pragmatic cluster r and omized trials in health-care setting Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease ( COPD ) compared with usual care . Design 24 month , multicentre , pragmatic cluster r and omised controlled trial Setting 40 general practice s in the western part of the Netherl and s Participants Patients with COPD according to GOLD ( Global Initiative for COPD ) criteria . Exclusion criteria were terminal illness , cognitive impairment , alcohol or drug misuse , and inability to fill in Dutch question naires . Practice s were included if they were willing to create a multidisciplinary COPD team . Intervention General practitioners , practice nurses , and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice , including early recognition of exacerbations and self management , smoking cessation , physiotherapeutic reactivation , optimal diagnosis , and drug adherence . Additionally , the course served as a network platform and collaborating healthcare providers design ed an individual practice plan to integrate integrated disease management into daily practice . The control group continued usual care ( based on international guidelines ) . Main outcome measures The primary outcome was difference in health status at 12 months , measured by the Clinical COPD Question naire ( CCQ ) ; quality of life , Medical Research Council dyspnoea , exacerbation related outcomes , self management , physical activity , and level of integrated care ( PACIC ) were also assessed as secondary outcomes . Results Of a total of 1086 patients from 40 clusters , 20 practice s ( 554 patients ) were r and omly assigned to the intervention group and 20 clusters ( 532 patients ) to the usual care group . No difference was seen between groups in the CCQ at 12 months ( mean difference –0.01 , 95 % confidence interval –0.10 to 0.08 ; P=0.8 ) . After 12 months , no differences were seen in secondary outcomes between groups , except for the PACIC domain “ follow-up/coordination ” ( indicating improved integration of care ) and proportion of physically active patients . Exacerbation rates as well as number of days in hospital did not differ between groups . After 24 months , no differences were seen in outcomes , except for the PACIC follow-up/coordination domain . Conclusion In this pragmatic study , an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care , except improved level of integrated care and a self reported higher degree of daily activities . The contradictory findings to earlier positive studies could be explained by differences between interventions ( provider versus patient targeted ) , selective reporting of positive trials , or little room for improvement in the already well developed Dutch healthcare system . Trial registration Netherl and s Trial Register NTR2268 Background —Substantial evidence - practice gaps exist in the management of acute coronary syndromes ( ACS ) in China . Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated . Methods and Results —Between October 2007 and August 2010 , a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster r and omized , controlled trial . Eligible hospitals were level 2 or level 3 centers routinely admitting > 100 patients with ACS per year . Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later . Outcomes were several key performance indicators reflecting the management of ACS . The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals , using data collected from 50 consecutive patients in each hospital . Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy , with nonsignificant improvements or absence of effects on other key performance indicators . Conclusions —Among hospitals in China , the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments , but effectiveness was otherwise limited . An accompanying process evaluation identified several health system barriers to more successful implementation . Clinical Trial Registration —URL : http://www.anzctr.org.au/default.aspx . Unique identifier : ACTRN12609000491268 CONTEXT Studies have found that patients with acute coronary syndromes ( ACS ) often do not receive evidence -based therapies in community practice . This is particularly true in low- and middle-income countries . OBJECTIVE To evaluate whether a multifaceted quality improvement ( QI ) intervention can improve the use of evidence -based therapies and reduce the incidence of major cardiovascular events among patients with ACS in a middle-income country . DESIGN , SETTING , AND PARTICIPANTS The BRIDGE-ACS ( Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes ) trial , a cluster-r and omized ( concealed allocation ) trial conducted among 34 clusters ( public hospitals ) in Brazil and enrolling a total of 1150 patients with ACS from March 15 , 2011 , through November 2 , 2011 , with follow-up through January 27 , 2012 . INTERVENTION Multifaceted QI intervention including educational material s for clinicians , reminders , algorithms , and case manager training , vs routine practice ( control ) . MAIN OUTCOME MEASURES Primary end point was the percentage of eligible patients who received all evidence -based therapies ( aspirin , clopidogrel , anticoagulants , and statins ) during the first 24 hours in patients without contraindications . RESULTS Mean age of the patients enrolled was 62 ( SD , 13 ) years ; 68.6 % were men , and 40 % presented with ST-segment elevation myocardial infa rct ion , 35.6 % with non-ST-segment elevation myocardial infa rct ion , and 23.6 % with unstable angina . The r and omized clusters included 79.5 % teaching hospitals , all from major urban areas and 41.2 % with 24-hour percutaneous coronary intervention capabilities . Among eligible patients ( 923/1150 [ 80.3 % ] ) , 67.9 % in the intervention vs 49.5 % in the control group received all eligible acute therapies ( population average odds ratio [ OR(PA ) ] , 2.64 [ 95 % CI , 1.28 - 5.45 ] ) . Similarly , among eligible patients ( 801/1150 [ 69.7 % ] ) , those in the intervention group were more likely to receive all eligible acute and discharge medications ( 50.9 % vs 31.9 % ; OR(PA ) , , 2.49 [ 95 % CI , 1.08 - 5.74 ] ) . Overall composite adherence scores were higher in the intervention clusters ( 89 % vs 81.4 % ; mean difference , 8.6 % [ 95 % CI , 2.2%-15.0 % ] ) . In-hospital cardiovascular event rates were 5.5 % in the intervention group vs 7.0 % in the control group ( OR(PA ) , 0.72 [ 95 % CI , 0.36 - 1.43 ] ) ; 30-day all-cause mortality was 7.0 % vs 8.4 % ( ORPA , 0.79 [ 95 % CI , 0.46 - 1.34 ] ) . CONCLUSION Among patients with ACS treated in Brazil , a multifaceted educational intervention result ed in significant improvement in the use of evidence -based therapies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00958958 BACKGROUND Registries have shown that quality of care for acute coronary syndromes ( ACS ) often falls below the st and ards recommended in professional guidelines . Quality improvement ( QI ) is a strategy to improve st and ards of clinical care for patients , but the efficacy of QI for ACS has not been tested in r and omized trials . METHODS We undertook a prospect i ve , cluster-r and omized , multicenter , multinational study to evaluate the efficacy of a QI program for ACS . Participating centers collected data on consecutive admissions for non-ST-elevation ACS for 4 months before the QI intervention and 3 months after . Thirty-eight hospitals in France , Italy , Pol and , Spain , and the United Kingdom were r and omized to receive the QI program or not , 19 in each group . We measured 8 in-hospital quality indicators ( risk stratification , coronary angiography , anticoagulation , β-blockers , statins , angiotensin-converting enzyme inhibitors , and clopidogrel loading and maintenance ) before and after the intervention and compared composite changes between the QI and non-QI groups . RESULTS A total of 2604 patients were enrolled . The absolute overall change in use of quality indicators in the QI group was 8.5 % compared with 0.8 % in the non-QI group ( odds ratio for achieving a quality indicator in QI versus non-QI 1.66 , 95 % CI 1.43 - 1.94 ; P < .001 ) . The main changes were observed in the use of risk stratification and clopidogrel loading dose . CONCLUSIONS The QI strategy result ed in a significant improvement in the quality indicators measured . This type of QI intervention can lead to useful changes in health care practice for ACS in a wide range of setting |
2,468 | 31,618,991 | IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events , whilst the relationship with IgG is more complex and difficult to eluci date , with studies reporting divergent results .
In this systematic review , there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD , especially for the IgM subclass . | Antibodies to oxidized LDL ( oxLDL ) may be associated with improved outcomes in cardiovascular disease .
However , analysis is restricted by heterogenous study design and endpoints .
Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease ( CAD ) . | Aims We aim ed to determine whether the levels of total serum IgM and IgG , together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein ( MDA-LDL ) , can improve cardiovascular risk discrimination . Methods and Results The Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ) r and omized 9098 patients in the UK and Irel and into the Blood Pressure-Lowering Arm . 485 patients that had cardiovascular ( CV ) events over 5.5 years were age and sex matched with 1367 controls . Higher baseline total serum IgG , and to a lesser extent IgM , were associated with decreased risk of CV events ( IgG odds ratio ( OR ) per one st and ard deviation ( SD ) 0.80 [ 95 % confidence interval , CI 0.72,0.89 ] , p < 0.0001 ; IgM 0.83[0.75,0.93 ] , p = 0.001 ) , and particularly events due to coronary heart disease ( CHD ) ( IgG OR 0.66 ( 0.57,0.76 ) ; p < 0.0001 , IgM OR 0.81 ( 0.71,0.93 ) ; p = 0.002 ) . The association persisted after adjustment for a basic model with variables in the Framingham Risk Score ( FRS ) as well as following inclusion of C-reactive protein ( CRP ) and N-terminal pro-B-type natriuretic peptide ( NtProBNP ) . IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively . The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG , and there was improvement in continuous and categorical net reclassification ( 17.6 % and 7.5 % respectively ) as well as in the integrated discrimination index . Conclusion High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events , particularly those attributed to CHD , in patients with hypertension Objective — Previous smaller studies have indicated inverse associations between autoantibodies to oxidized low-density lipoprotein epitopes , and cardiovascular disease . The present study investigated associations between autoantibodies against the apolipoprotein B-100 peptides p45 and p210 , respectively , and risk of incident cardiovascular disease in a large population -based cohort . Approach and Results — Apolipoprotein B-100 autoantibodies were analyzed by ELISA in a prospect i ve study , including 5393 individuals ( aged 46–68 years ) belonging to the cardiovascular arm of the Malmö Diet and Cancer study with a follow-up time of > 15 years . Subjects that suffered an acute coronary event during follow-up ( n=382 ) had lower levels at baseline of IgM autoantibodies recognizing the native and malondialdehyde-modified apolipoprotein B-100 peptides p45 and p210 and also lower IgG levels recognizing native p210 , whereas no association was found with risk for stroke ( n=317 ) . Subjects in the highest compared with lowest tertile of IgM-p45MDA ( hazard ratio [ 95 % confidence interval ] : 0.72 [ 0.55 , 0.94 ] ; P=0.017 ) and IgG-p210native ( hazard ratio [ 95 % confidence interval ] : 0.73 [ 0.56 , 0.97 ] ; P=0.029 ) had lower risk for incident coronary events after adjustment for cardiovascular risk factors in Cox proportional hazard regression models . Moreover , subjects with high levels of IgG-p210native were less likely to have carotid plaques as assessed by ultrasonography at baseline ( odds ratio=0.81 , 95 % confidence interval 0.70–0.95 , P=0.008 after adjustment for risk factors ) . Conclusions — This large prospect i ve study demonstrates that subjects with high levels of apolipoprotein B-100 autoantibodies have a lower risk of coronary events supporting a protective role of these autoantibodies in cardiovascular disease BACKGROUND Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking . OBJECTIVES This study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 ( OxPL-apoB ) , but without prior coronary artery disease ( CAD ) , are at risk for recurrent stroke and CAD events following high-dose statin therapy . METHODS In the SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels ) trial , OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following r and omization to placebo or 80 mg atorvastatin . The primary endpoint was the time from r and omization to a second nonfatal or fatal stroke . Secondary endpoints included first major coronary events and any cardiovascular event . RESULTS Patients with recurrent stroke had higher baseline median OxPL-apoB levels than patients without ( 15.5 nmol/l vs. 11.6 nmol/l ; p < 0.0001 ) . After multivariable adjustment , elevated baseline OxPL-apoB predicted recurrent stroke ( hazard ratio [ HR ] : 4.3 ; p < 0.0001 ) , first major coronary events ( HR : 4.0 ; p < 0.0001 ) , and any cardiovascular event ( HR : 4.4 ; p < 0.0001 ) . These comparisons for any endpoint did not differ by treatment , shown as a nonsignificant interaction test . The net reclassification improvement , integrated discrimination improvement , and area under the receiver-operating characteristic curve ( AUC ) were all significantly improved by adding OxPL-apoB to the models , with ΔAUC + 0.0505 ( p < 0.0001 ) for recurrent stroke , ΔAUC + 0.0409 ( p < 0.0001 ) for first major coronary event , and ΔAUC + 0.0791 ( p < 0.0001 ) for any cardiovascular event . CONCLUSIONS Elevated OxPL-apoB levels predicted recurrent stroke and first major coronary events in patients with prior stroke or transient ischemic attack . The lack of statin-OxPL-apoB treatment interaction suggested that OxPLs might be statin-independent therapeutic targets to reduce risk of cardiovascular events . ( Lipitor in the Prevention of Stroke , for Patients Who Have Had a Previous Stroke [ SPARCL ] ; NCT00147602 ) AIMS Antibodies to oxidized low-density lipoproteins ( oxLDLAbs ) are detectable in the serum of patients with and without atherosclerosis , but it is unclear if they play a pathogenic or a protective role in atherogenesis or if they are simply a marker of atherosclerosis . Therefore , in a prospect i ve cohort study we investigated if oxLDLAbs titer predicts cardiovascular ( CV ) events in high-risk coronary artery disease patients . METHODS AND RESULTS The titer of IgG antibodies to malondialdehyde modified oxidized low-density lipoproteins was measured in 748 r and omly selected patients of the GENICA study who underwent coronary angiography and assessment of incident CV events at follow-up . Patients were classified by oxLDLAbs into a low and a high titer group , corresponding to the first three and the last quartile , respectively . Cardiovascular event-free survival was compared between oxLDLAbs groups by Kaplan-Meier and multivariate technique including propensity score matching analysis . During long-term follow-up ( median 7.2 years ) CV deaths were observed in 65 patients ( 11.6 % ) , more commonly in the high than in the low oxLDLAbs group ( patients free from CV death 83.1 % vs. 89 % respectively , p=0.025 ) . The incidence of CV events was also higher in the former than in latter ( event-free survival 69.2 % vs. 77.7 % respectively , p=0.030 ) . CONCLUSIONS An oxLDLAbs titer above the 75th percentile is a marker of LDL oxidation which predicts a worse CV prognosis at long term follow-up in high-risk Caucasian patients referred for coronary angiography BACKGROUND The relation between measures of oxidation of lipid particles and cardiovascular disease has not been extensively investigated prospect ively on a population basis . METHODS A community cohort of 1192 men and 1427 women with measures of IgG antibodies to oxidized LDL were followed 8 years for the development of initial coronary heart disease ( CHD ) and cardiovascular disease ( CVD ) events . RESULTS Levels of IgG autoantibodies to a form of oxidized LDL were significantly associated with age in both sexes , positively with fibrinogen in men and negatively with HDL cholesterol in women . In sex-specific models that adjusted for age alone or those that adjusted for age , cholesterol , HDL cholesterol , smoking , and diabetes mellitus , there was no relation between level of antibodies to oxidized LDL and the development of CHD or CVD . CONCLUSION Autoantibodies to oxidized LDL were strongly related to age and were not related to incident CHD or CVD over 8 years of follow up Background Certain immunoglobulins ( Ig ) are proposed to have protective functions in atherosclerosis . Objectives We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein ( MDA-LDL ) are associated with clinical coronary heart disease ( CHD ) and unfavorable plaque characteristics . Methods NORDIL was a prospect i ve study investigating adverse cardiovascular outcomes in hypertensive patients . IBIS-3 analyzed lesions in a non-culprit coronary artery with < 50 % stenosis using radiofrequency intravascular ultrasound ( RF-IVUS ) and near-infrared spectroscopy ( NIRS ) . Imaging was repeated after a median of 386 days on rosuvastatin . Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub- studies respectively . Findings From 10,881 NORDIL patients , 87 had serum sample d at baseline and developed CHD over 4.5 years , matched to 227 controls . Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes , with odds ratio 0.29 ( 0.11 , 0.76 ; p = 0.012 ; p = 0.016 for trend ) . Therefore , the effect was explored at the lesional level in IBIS-3 . 143 patients had blood sample s and RF-IVUS measurements available , and NIRS was performed in 90 of these . At baseline , IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume ( p = 0.027 ) and percentage of plaque occupied by necrotic core ( p = 0.011 ) , as well as lipid core burden index ( p = 0.024 ) in the worst 4 mm segment . Interpretation Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development , and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability AIMS Acute coronary syndromes ( ACS ) are mostly caused by plaque rupture . This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound ( IVUS ) in patients undergoing coronary angiography . METHODS AND RESULTS Between November 2008 and January 2011 , IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS ( n = 318 ) or stable angina ( n = 263 ) . Primary endpoint was major adverse cardiac events ( MACEs ) defined as mortality , ACS , or unplanned coronary revascularization . Culprit lesion-related events were not counted . Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8 % . The presence of IVUS virtual histology-derived thin-cap fibroatheroma ( TCFA ) lesions ( present 10.8 % vs. absent 5.6 % ; adjusted HR : 1.98 , 95 % CI : 1.09 - 3.60 ; P = 0.026 ) and lesions with a plaque burden of ≥70 % ( present 16.2 % vs. absent 5.5 % ; adjusted HR : 2.90 , 95 % CI : 1.60 - 5.25 ; P < 0.001 ) were independently associated with a higher MACE rate . Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only ( present 7.5 % vs. absent 3.0 % ; adjusted HR : 2.51 , 95 % CI : 1.15 - 5.49 ; P = 0.021 ) . Thin-cap fibroatheroma lesions with a plaque burden of ≥70 % were associated with a higher MACE rate within ( P = 0.011 ) and after ( P < 0.001 ) 6 months of follow-up , while smaller TCFA lesions were only associated with a higher MACE rate after 6 months ( P = 0.033 ) . CONCLUSION In patients undergoing coronary angiography , the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year , particularly of death and ACS . Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions , especially on the short term OBJECTIVES The goal of this study was to examine the prospect i ve association between oxidation-specific biomarkers , primarily oxidized phospholipids ( OxPL ) on apolipoprotein B-100-containing lipoproteins ( OxPL/apoB ) and lipoprotein ( a ) [ Lp(a ) ] , and risk of peripheral artery disease ( PAD ) . We examined , as secondary analyses , indirect measures of oxidized lipoproteins , including autoantibodies to malondialdehyde-modified low-density lipoprotein ( MDA-LDL ) and apolipoprotein B-100 immune complexes ( ApoB-IC ) . BACKGROUND Biomarkers to predict the development of PAD are lacking . OxPL circulate in plasma , are transported by Lp(a ) , and deposit in the vascular wall and induce local inflammation . METHODS The study population included 2 parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study ( 1994 to 2008 ) and 144 women within the Nurses ' Health Study ( 1990 to 2010 ) with incident confirmed cases of clinical ly significant PAD , matched 1:3 to control subjects . RESULTS Levels of OxPL/apoB were positively associated with risk of PAD in men and women : pooled relative risk : 1.37 , 95 % confidence interval : 1.19 to 1.58 for each 1-SD increase after adjusting age , smoking , fasting status , month of blood draw , lipids , body mass index , and other cardiovascular disease risk factors . Lp(a ) was similarly associated with risk of PAD ( pooled adjusted relative risk : 1.36 ; 95 % confidence interval : 1.18 to 1.57 for each 1-SD increase ) . Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD . CONCLUSIONS OxPL/apoB were positively associated with risk of PAD in men and women . The major lipoprotein carrier of OxPL , Lp(a ) , was also associated with risk of PAD , reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a ) |
2,469 | 26,633,262 | Heterogeneity was related in part to the dosing strategy .
Overall , low- quality evidence indicates that corticosteroids reduce mortality among patients with sepsis .
Moderate- quality evidence suggests that a long course of low-dose corticosteroids reduced 28-day mortality without inducing major complications and led to an increase in metabolic disorders | BACKGROUND Sepsis occurs when an infection is complicated by organ failures as defined by a sequential organ failure assessment ( SOFA ) score of two or higher .
Sepsis may be complicated by impaired corticosteroid metabolism .
Giving corticosteroids may benefit patients .
The original review was published in 2004 and was up date d in 2010 and again in 2015 .
OBJECTIVES To examine the effects of corticosteroids on death at one month in patients with sepsis , and to examine whether dose and duration of corticosteroids influence patient response to this treatment . | Objective To determine the population incidence and outcome of severe sepsis occurring in adult patients treated in Australian and New Zeal and intensive care units ( ICUs ) , and compare with recent retrospective estimates from the USA and UK . Design Inception cohort study . Setting Twenty-three closed multi-disciplinary ICUs of 21 hospitals ( 16 tertiary and 5 university affiliated ) in Australia and New Zeal and . Patients A total of 5878 consecutive ICU admission episodes . Measurements and results Main outcome measures were population -based incidence of severe sepsis , mortality at ICU discharge , mortality at 28 days after onset of severe sepsis , and mortality at hospital discharge . A total of 691 patients , 11.8 ( 95 % confidence intervals 10.9–12.6 ) per 100 ICU admissions , were diagnosed with 752 episodes of severe sepsis . Site of infection was pulmonary in 50.3 % of episodes and abdominal in 19.3 % of episodes . The calculated incidence of severe sepsis in adults treated in Australian and New Zeal and ICUs is 0.77 ( 0.76–0.79 ) per 1000 of population . 26.5 % of patients with severe sepsis died in ICU , 32.4 % died within 28 days of the diagnosis of severe sepsis and 37.5 % died in hospital . Conclusion In this prospect i ve study , 11.8 patients per 100 ICU admissions were diagnosed with severe sepsis and the calculated annual incidence of severe sepsis in adult patients treated in Australian and New Zeal and ICUs is 0.77 per 1000 of population . This figure for the population incidence falls in the lower range of recent estimates from retrospective studies in the U.S. and the Abstract Introduction Low-dose hydrocortisone treatment is widely accepted therapy for the treatment of vasopressor-dependent septic shock . The question of whether corticosteroids should be given to septic shock patients by continuous or by bolus infusion is still unanswered . Hydrocortisone induces hyperglycemia and it is possible that continuous hydrocortisone infusion would reduce the fluctuations in blood glucose levels and that tight blood glucose control could be better achieved with this approach . Methods In this prospect i ve r and omized study , we compared the blood glucose profiles , insulin requirements , amount of nursing workload needed , and shock reversal in 48 septic shock patients who received hydrocortisone treatment either by bolus or by continuous infusion with equivalent dose ( 200 mg/day ) . Duration of hydrocortisone treatment was five days . Results The mean blood glucose levels were similar in the two groups , but the number of hyperglycemic episodes was significantly higher in those patients who received bolus therapy ( 15.7 ± 8.5 versus 10.5 ± 8.6 episodes per patient , p = 0.039 ) . Also , more changes in insulin infusion rate were needed to maintain strict normoglycemia in the bolus group ( 4.7 ± 2.2 versus 3.4 ± 1.9 adjustments per patient per day , p = 0.038 ) . Hypoglycemic episodes were rare in both groups . No difference was seen in shock reversal . ConclusionS trict normoglycemia is more easily achieved if the hydrocortisone therapy is given to septic shock patients by continuous infusion . This approach also reduces nursing workload needed to maintain tight blood glucose control . Trial Registration Number IS RCT CONTEXT AND OBJECTIVE Sepsis and septic shock are very common conditions among critically ill patients that lead to multiple organ dysfunction syndrome ( MODS ) and death . Our purpose was to investigate the efficacy of early administration of dexamethasone for patients with septic shock , with the aim of halting the progression towards MODS and death . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study , developed in a surgical intensive care unit at Hospital das Clínicas , Faculdade de Medicina da Universidade de São Paulo . METHODS The study involved 29 patients with septic shock . All eligible patients were prospect ively r and omized to receive either a dose of 0.2 mg/kg of dexamethasone ( group D ) or placebo ( group P ) , given three times at intervals of 36 hours . The patients were monitored over a seven-day period by means of the sequential organ failure assessment score . RESULTS Patients treated with dexamethasone did not require vasopressor therapy for as much time over the seven-day period as did the placebo group ( p = 0.043 ) . Seven-day mortality was 67 % in group P ( 10 out of 15 ) and 21 % in group D ( 3 out of 14 ) ( relative risk = 0.31 , 95 % confidence interval 0.11 to 0.88 ) . Dexamethasone enhanced the effects of vasopressor drugs . CONCLUSIONS Early treatment with dexamethasone reduced the seven-day mortality among septic shock patients and showed a trend towards reduction of 28-day mortality CONTEXT Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock . In addition , the benefit of adding fludrocortisone in this setting is unclear . OBJECTIVES To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess , as a secondary objective , the benefit of fludrocortisone . DESIGN , SETTING , AND PATIENTS A multicenter , 2 x 2 factorial , r and omized trial , involving 509 adults with septic shock who presented with multiple organ dysfunction , as defined by a Sequential Organ Failure Assessment score of 8 or more , and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France . INTERVENTIONS Patients were r and omly assigned to 1 of 4 groups : continuous intravenous insulin infusion with hydrocortisone alone , continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone , conventional insulin therapy with hydrocortisone alone , or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone . Hydrocortisone was administered in a 50-mg bolus every 6 hours , and fludrocortisone was administered orally in 50-microg tablets once a day , each for 7 days . MAIN OUTCOME MEASURE In-hospital mortality . RESULTS Of the 255 patients treated with intensive insulin , 117 ( 45.9 % ) , and 109 of 254 ( 42.9 % ) treated with conventional insulin therapy died ( relative risk [ RR ] , 1.07 ; 95 % confidence interval [ CI ] , 0.88 - 1.30 ; P = .50 ) . Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia ( < 40 mg/dL ) than those in the conventional-treatment group , with a difference in mean number of episodes per patient of 0.15 ( 95 % CI , 0.02 - 0.28 ; P = .003 ) . At hospital discharge , 105 of 245 patients treated with fludrocortisone ( 42.9 % ) died and 121 of 264 ( 45.8 % ) in the control group died ( RR , 0.94 ; 95 % CI , 0.77 - 1.14 ; P = .50 ) . CONCLUSIONS Compared with conventional insulin therapy , intensive insulin therapy did not improve in-hospital mortality among patients who were treated with hydrocortisone for septic shock . The addition of oral fludrocortisone did not result in a statistically significant improvement in in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00320099 BACKGROUND Clinical trials yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of community-acquired pneumonia . We assessed whether short-term corticosteroid treatment reduces time to clinical stability in patients admitted to hospital for community-acquired pneumonia . METHODS In this double-blind , multicentre , r and omised , placebo-controlled trial , we recruited patients aged 18 years or older with community-acquired pneumonia from seven tertiary care hospitals in Switzerl and within 24 h of presentation . Patients were r and omly assigned ( 1:1 ratio ) to receive either prednisone 50 mg daily for 7 days or placebo . The computer-generated r and omisation was done with variable block sizes of four to six and stratified by study centre . The primary endpoint was time to clinical stability defined as time ( days ) until stable vital signs for at least 24 h , and analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00973154 . FINDINGS From Dec 1 , 2009 , to May 21 , 2014 , of 2911 patients assessed for eligibility , 785 patients were r and omly assigned to either the prednisone group ( n=392 ) or the placebo group ( n=393 ) . Median time to clinical stability was shorter in the prednisone group ( 3·0 days , IQR 2·5 - 3·4 ) than in the placebo group ( 4·4 days , 4·0 - 5·0 ; hazard ratio [ HR ] 1·33 , 95 % CI 1·15 - 1·50 , p<0·0001 ) . Pneumonia-associated complications until day 30 did not differ between groups ( 11 [ 3 % ] in the prednisone group and 22 [ 6 % ] in the placebo group ; odds ratio [ OR ] 0·49 [ 95 % CI 0·23 - 1·02 ] ; p=0·056 ) . The prednisone group had a higher incidence of in-hospital hyperglycaemia needing insulin treatment ( 76 [ 19 % ] vs 43 [ 11 % ] ; OR 1·96 , 95 % CI 1·31 - 2·93 , p=0·0010 ) . Other adverse events compatible with corticosteroid use were rare and similar in both groups . INTERPRETATION Prednisone treatment for 7 days in patients with community-acquired pneumonia admitted to hospital shortens time to clinical stability without an increase in complications . This finding is relevant from a patient perspective and an important determinant of hospital costs and efficiency . FUNDING Swiss National Science Foundation , Viollier AG , Nora van Meeuwen Haefliger Stiftung , Julia und Gottfried Bangerter-Rhyner Stiftung Background Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis . However , the effect of corticosteroid replacement on mortality in this high-risk group remains unclear . We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock . Methods We enrolled patients with cirrhosis and septic shock aged 18 years or older in a r and omized double-blind placebo-controlled trial . Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin . Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved , followed by steroid tapering over eight days . The primary outcome was 28-day all-cause mortality . Results The trial was stopped for futility at interim analysis after 75 patients were enrolled . Relative adrenal insufficiency was diagnosed in 76 % of patients . Compared with the placebo group ( n = 36 ) , patients in the hydrocortisone group ( n = 39 ) had a significant reduction in vasopressor doses and higher rates of shock reversal ( relative risk [ RR ] 1.58 , 95 % confidence interval [ CI ] 0.98–2.55 , p = 0.05 ) . Hydrocortisone use was not associated with a reduction in 28-day mortality ( RR 1.17 , 95 % CI 0.92–1.49 , p = 0.19 ) but was associated with an increase in shock relapse ( RR 2.58 , 95 % CI 1.04–6.45 , p = 0.03 ) and gastrointestinal bleeding ( RR 3.00 , 95 % CI 1.08–8.36 , p = 0.02 ) . Interpretation Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock . Despite initial favourable effects on hemodynamic parameters , hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects . ( Current Controlled Trials registry no. IS RCT N99675218 . There is increasing evidence that the hypercortisolemia in inflammatory diseases suppresses the elaboration of proinflammatory cytokines , thus protecting the host from its own defence reactions . In severe sepsis and septic shock cortisol levels are usually elevated , but some patients may have relative adrenal insufficiency . This may contribute to the overwhelming systemic inflammatory response syndrome . We evaluated the impact of low-dose hydrocortisone infusion ( 10 mg/h ) on the course of the systemic inflammatory response syndrome . This dose corresponds to a maximum secretory rate of cortisol achieved in corticotropin-stimulated healthy humans . In a prospect i ve observational study 57 surgical patients with severe sepsis or septic shock were studied , of which in addition to the conventional treatment 12 patients were infused with low-dose hydrocortisone , and 45 were treated without any corticosteroid . In the longitudinal analysis the systemic inflammatory response — as judged by body temperature , cardiovascular response , and kinetics of inflammatory mediators such as phospholipase A2 , C-reactive protein , and neutrophil elastase — started to differ in favor of the hydrocortisone-treated patients after 2 days of treatment ( P < 0.05 , Mann-Whitney U test ) . The difference disappeared after withdrawal of exogenous cortisol . Shock reversal was achieved in all patients treated with low-dose hydrocortisone . The data provide evidence that low-dose hydrocortisone infusion attenuates the systemic inflammatory response in human septic shock . From an immunological point of view a relative cortisol deficiency may contribute to the amplified immune response in systemic inflammatory diseases . A r and omized clinical trial must clarify the impact of low-dose hydrocortisone infusion on the clinical course and outcome of septic shock patients Introduction Vasopressin is an alternative vasopressor in the management of septic shock . It spares catecholamine use but whether it improves outcome remains uncertain . Current evidence suggests that it may be most effective if used early and possibly in conjunction with corticosteroids . This trial will compare vasopressin to noradrenaline as initial vasopressor in the management of adult septic shock and investigate whether there is an interaction of vasopressin with corticosteroids . Methods and analysis This is a multicentre , factorial ( 2 × 2 ) , r and omised , double-blind , placebo-controlled trial . 412 patients will be recruited from multiple UK intensive care units and r and omised to receive vasopressin ( 0–0.06 U/min ) or noradrenaline ( 0–12 µg/min ) as a continuous intravenous infusion as initial vasopressor therapy . If maximum infusion rates of this first study drug are reached , the patient will be treated with either hydrocortisone ( initially 50 mg intravenous bolus six-hourly ) or placebo , before additional open-label catecholamine vasopressors are prescribed . The primary outcome of the trial will be the difference in renal failure-free days between treatment groups . Secondary outcomes include need for renal replacement therapy , survival rates , other organ failures and re source utilisation . Ethics and dissemination The trial protocol and information sheets have received a favourable opinion from the Oxford A Research Ethics Committee ( 12/SC/0014 ) . There is an independent Data Monitoring and Ethics Committee and independent membership of the Trial Steering Committee including patient and public involvement . The trial results will be published in peer- review ed journals and presented at national and international scientific meetings . Trial registration number : IS RCT N 20769191 and EudraCT 2011 - 005363 - 24 Introduction The aim of the study was to assess the prognostic importance of basal cortisol concentrations and cortisol response to corticotropin , and to determine the effects of physiological dose steroid therapy on mortality in patients with sepsis . Methods Basal cortisol level and corticotropin stimulation test were performed within 24 hours in all patients . One group ( 20 patients ) received st and ard therapy for sepsis and physiological-dose steroid therapy for 10 days ; the other group ( 20 patients ) received only st and ard therapy for sepsis . Basal cortisol level was measured on the 14th day in patients who recovered . The outcome of sepsis was compared . Results Only Sequential Organ Failure Assessment ( SOFA ) score was found related to mortality , independent from other factors in multivariate analysis . No significant difference was found between the changes in the percentage of SOFA scores of the steroid therapy group and the st and ard therapy group in survivors , nor between the groups in basal and peak cortisol levels , cortisol response to corticotropin test and mortality . The mortality rates among patients with occult adrenal insufficiencies were 40 % in the steroid therapy group and 55.6 % in the st and ard therapy group . Discussion There was a trend towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy . In the advancing process from sepsis to septic shock , adrenal insufficiency was not frequent as supposed . There was a trend ( that did not reach significance ) towards a decrease in the mortality rates of the patients with sepsis who received physiological-dose steroid therapy Objective : To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients . Participants : A multidisciplinary , multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine . In addition , international experts in endocrinology were invited to participate . Design / Methods : The task force members review ed published literature and provided expert opinion from which the consensus was derived . The consensus statements were developed using a modified Delphi methodology . The strength of each recommendation was quantified using the Modified GRADE system , which classifies recommendations as strong ( grade 1 ) or weak ( grade 2 ) and the quality of evidence as high ( grade A ) , moderate ( grade B ) , or low ( grade C ) based on factors that include the study design , the consistency of the results , and the directness of the evidence . Results : The task force coined the term critical illness – related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness . Critical illness – related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response . Critical illness – related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents , particularly in the setting of sepsis . At this time , the diagnosis of tissue corticosteroid resistance remains problematic . Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 & mgr;g/dL after adrenocorticotrophic hormone ( 250 & mgr;g ) administration or a r and om total cortisol of < 10 & mgr;g/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome ( Pao2/Fio2 of < 200 and within 14 days of onset ) . The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids . Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day ( 10 mg/hr ) for ≥7 days is recommended for septic shock . Methylprednisolone in a dose of 1 mg·kg−1·day−1 for ≥14 days is recommended in patients with severe early acute respiratory distress syndrome . Glucocorticoids should be weaned and not stopped abruptly . Reinstitution of treatment should be considered with recurrence of signs of sepsis , hypotension , or worsening oxygenation . Dexamethasone is not recommended to treat critical illness – related corticosteroid insufficiency . The role of glucocorticoids in the management of patients with community-acquired pneumonia , liver failure , pancreatitis , those undergoing cardiac surgery , and other groups of critically ill patients requires further investigation . Conclusion : Evidence -linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary , multispecialty task force Background Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia . Objectives The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia ( CAP ) requiring hospitalization . Design and Setting An open label , prospect i ve , r and omized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan . Patients Thirty-one adult CAP patients who required hospitalization were enrolled . Measurements and Results Fifteen patients received 40 mg of prednisolone intravenously for 3 days ( steroid group ) . Sixteen patients did not receive prednisolone ( control group ) . Both groups were also evaluated for their adrenal function . The primary endpoint was length of hospital stay . Secondary endpoints were duration of intravenous ( IV ) antibiotics and time required to stabilize vital signs . Both groups demonstrated similar baseline characteristics and length of hospital stay , and yet a shorter duration of IV antibiotics was observed in the steroid group ( p < 0.05 ) . In addition , vital signs were stabilized earlier in the steroid group ( p < 0.05 ) . These differences were more prominent in the moderate – severe subgroup but not as significant in the mild – moderate subgroup . The prevalence of relative adrenal insufficiency ( RAI ) in both groups was high ( 43 % ) , yet there was no difference in baseline characteristics between patients , with or without RAI . In multiple regression models , RAI seemed to have no influence on clinical courses . Conclusions In moderate – severe CAP , administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy CONTEXT The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress . The relationship between its activation and patient outcome is not known . OBJECTIVE To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock . DESIGN AND SETTING Prospect i ve inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France . PARTICIPANTS A total of 189 consecutive patients who met clinical criteria for septic shock . INTERVENTION A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin ; blood sample s were taken immediately before the test ( T0 ) and 30 ( T30 ) and 60 ( T60 ) minutes afterward . MAIN OUTCOME MEASURES Twenty-eight-day mortality as a function of variables collected at the onset of septic shock , including cortisol levels before the corticotropin test and the cortisol response to corticotropin ( delta max , defined as the difference between T0 and the highest value between T30 and T60 ) . RESULTS The 28-day mortality was 58 % ( 95 % confidence interval [ CI ] , 51%-65 % ) and median time to death was 17 days ( 95 % CI , 14 - 27 days ) . In multivariate analysis , independent predictors of death ( P < or = .001 for all ) were McCabe score greater than 0 , organ system failure score greater than 2 , arterial lactate level greater than 2.8 mmol/L , ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg , cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified : good ( cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL ; 28-day mortality rate , 26 % ) , intermediate ( cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL ; 28-day mortality rate , 67 % ) , and poor ( cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL ; 28-day mortality rate , 82 % ) . CONCLUSION Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death Within the last few years , increasing evidence of relative adrenal insufficiency in septic shock evoked a re assessment of hydrocortisone therapy . To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation , 40 patients with septic shock were r and omized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 ( n = 20 ) or placebo ( n = 20 ) , followed by the opposite medication until Day 6 . Hydrocortisone infusion induced an increase of mean arterial pressure , systemic vascular resistance , and a decline of heart rate , cardiac index , and norepinephrine requirement . A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support . The inflammatory response ( interleukin-6 and interleukin-8 ) , endothelial ( soluble E-selectin ) and neutrophil activation ( expression of CD11b , CD64 ) , and antiinflammatory response ( soluble tumor necrosis factor receptors I and II and interleukin-10 ) were attenuated . In peripheral blood monocytes , human leukocyte antigen-DR expression was only slightly depressed , whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased . Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects . In conclusion , hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock . Forty-six patients entered the study . At study entry , the hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 ) The effects of steroids on the outcome of sepsis are dose dependent . Low doses appear to be beneficial , but high doses do not improve outcome for reasons that are insufficiently understood . The effects of steroids on systemic inflammation as a function of dose have not previously been studied in humans . To determine the effects of increasing doses of prednisolone on inflammation and coagulation in humans exposed to LPS , 32 healthy males received prednisolone orally at doses of 0 , 3 , 10 , or 30 mg ( n = 8 per group ) at 2 h before i.v . injection of Escherichia coli LPS ( 4 ng/kg ) . Prednisolone dose-dependently inhibited the LPS-induced release of cytokines ( TNF-α and IL-6 ) and chemokines ( IL-8 and MCP-1 ) , while enhancing the release of the anti-inflammatory cytokine IL-10 . Prednisolone attenuated neutrophil activation ( plasma elastase levels ) and endothelial cell activation ( von Willebr and factor ) . Most remarkably , prednisolone did not inhibit LPS-induced coagulation activation , measured by plasma concentrations of thrombin-antithrombin complexes , prothrombin fragment F1 + 2 , and soluble tissue factor . In addition , activation of the fibrinolytic pathway ( tissue-type plasminogen activator and plasmin-α2-antiplasmin complexes ) was dose-dependently enhanced by prednisolone . These data indicate that prednisolone dose-dependently and differentially influences the systemic activation of different host response pathways during human endotoxemia RATIONALE Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia ( CAP ) , possibly by diminishing local and systemic antiinflammatory host response . OBJECTIVES To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP . METHODS Hospitalized patients , clinical ly and radiologically diagnosed with CAP using st and ard clinical and radiological criteria , were r and omized to receive 40 mg prednisolone for 7 days or placebo , along with antibiotics . Primary outcome was clinical cure at Day 7 . Secondary outcomes were clinical cure at Day 30 , length of stay , time to clinical stability , defervescence , and C-reactive protein . Disease severity was scored using CURB-65 ( a severity index for community-acquired pneumonia evaluating Confusion , blood Urea nitrogen , Respiratory rate , Blood pressure , and age 65 or older ) and Pneumonia Severity Index . MEASUREMENTS AND MAIN RESULTS We enrolled 213 patients . Fifty-four ( 25.4 % ) patients had a CURB-65 score greater than 2 , and 93 ( 43.7 % ) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 ( 80.8 % ) and 69/104 ( 66.3 % ) in the prednisolone group and 93/109 ( 85.3 % ) and 84/109 ( 77.1 % ) in the placebo group ( P = 0.38 and P = 0.08 ) . Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo . Sub analysis of patients with severe pneumonia did not show differences in clinical outcome . Late failure ( > 72 h after admittance ) was more common in the prednisolone group ( 20 patients , 19.2 % ) than in the placebo group ( 10 patients , 6.4 % ; P = 0.04 ) . Adverse events were few and not different between the two groups . CONCLUSIONS Prednisolone ( at 40 mg ) once daily for a week does not improve outcome in hospitalized patients with CAP . A benefit in more severely ill patients can not be excluded . Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP BACKGROUND Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear . We aim ed to assess effect of addition of dexamethasone on length of stay in this group , which might result in earlier resolution of pneumonia through dampening of systemic inflammation . METHODS In our double-blind , placebo-controlled trial , we r and omly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherl and s to receive intravenous dexamethasone ( 5 mg once a day ) or placebo for 4 days from admission . Patients were ineligible if they were immunocompromised , needed immediate transfer to an intensive-care unit , or were already receiving corticosteroids or immunosuppressive drugs . We r and omly allocated patients on a one-to-one basis to treatment groups with a computerised r and omisation allocation sequence in blocks of 20 . The primary outcome was length of hospital stay in all enrolled patients . This study is registered with Clinical Trials.gov , number NCT00471640 . FINDINGS Between November , 2007 , and September , 2010 , we enrolled 304 patients and r and omly allocated 153 to the placebo group and 151 to the dexamethasone group . 143 ( 47 % ) of 304 enrolled patients had pneumonia of pneumonia severity index class 4 - 5 ( 79 [ 52 % ] patients in the dexamethasone group and 64 [ 42 % ] controls ) . Median length of stay was 6·5 days ( IQR 5·0 - 9·0 ) in the dexamethasone group compared with 7·5 days ( 5·3 - 11·5 ) in the placebo group ( 95 % CI of difference in medians 0 - 2 days ; p=0·0480 ) . In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups , although 67 ( 44 % ) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 ( 23 % ) of 153 controls ( p<0·0001 ) . INTERPRETATION Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia . FUNDING None IMPORTANCE In patients with severe community-acquired pneumonia , treatment failure is associated with excessive inflammatory response and worse outcomes . Corticosteroids may modulate cytokine release in these patients , but the benefit of this adjunctive therapy remains controversial . OBJECTIVE To assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response . DESIGN , SETTING , AND PARTICIPANTS Multicenter , r and omized , double-blind , placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response , which was defined as a level of C-reactive protein greater than 150 mg/L at admission . Patients were recruited and followed up from June 2004 through February 2012 . INTERVENTIONS Patients were r and omized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone ( n = 61 ) or placebo ( n = 59 ) for 5 days started within 36 hours of hospital admission . MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure ( composite outcome of early treatment failure defined as [ 1 ] clinical deterioration indicated by development of shock , [ 2 ] need for invasive mechanical ventilation not present at baseline , or [ 3 ] death within 72 hours of treatment ; or composite outcome of late treatment failure defined as [ 1 ] radiographic progression , [ 2 ] persistence of severe respiratory failure , [ 3 ] development of shock , [ 4 ] need for invasive mechanical ventilation not present at baseline , or [ 5 ] death between 72 hours and 120 hours after treatment initiation ; or both early and late treatment failure ) . In-hospital mortality was a secondary outcome and adverse events were assessed . RESULTS There was less treatment failure among patients from the methylprednisolone group ( 8 patients [ 13 % ] ) compared with the placebo group ( 18 patients [ 31 % ] ) ( P = .02 ) , with a difference between groups of 18 % ( 95 % CI , 3 % to 32 % ) . Corticosteroid treatment reduced the risk of treatment failure ( odds ratio , 0.34 [ 95 % CI , 0.14 to 0.87 ] ; P = .02 ) . In-hospital mortality did not differ between the 2 groups ( 6 patients [ 10 % ] in the methylprednisolone group vs 9 patients [ 15 % ] in the placebo group ; P = .37 ) ; the difference between groups was 5 % ( 95 % CI , -6 % to 17 % ) . Hyperglycemia occurred in 11 patients ( 18 % ) in the methylprednisolone group and in 7 patients ( 12 % ) in the placebo group ( P = .34 ) . CONCLUSIONS AND RELEVANCE Among patients with severe community-acquired pneumonia and high initial inflammatory response , the acute use of methylprednisolone compared with placebo decreased treatment failure . If replicated , these findings would support the use of corticosteroids as adjunctive treatment in this clinical population . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00908713 CONTEXT No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome ( ARDS ) and mortality remains greater than 50 % . OBJECTIVE To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Medical intensive care units of 4 medical centers . PARTICIPANTS Twenty-four patients with severe ARDS who had failed to improve lung injury score ( LIS ) by the seventh day of respiratory failure . INTERVENTIONS Sixteen patients received methylprednisolone and 8 received placebo . Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days . Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment . MAIN OUTCOME MEASURES Primary outcome measures were improvement in lung function and mortality . Secondary outcome measures were improvement in multiple organ dysfunction syndrome ( MODS ) and development of nosocomial infections . RESULTS Physiological characteristics at the onset of ARDS were similar in both groups . At study entry ( day 9 [ SD , 3 ] of ARDS ) , the 2 groups had similar LIS , ratios of PaO2 to fraction of inspired oxygen ( FIO2 ) , and MODS scores . Changes observed by study day 10 for methylprednisolone vs placebo were as follows : reduced LIS ( mean [ SEM ] , 1.7 [ 0.1 ] vs 3.0 [ 0.2 ] ; P<.001 ) ; improved ratio of PaO2 to FIO2 ( mean [ SEM ] , 262 [ 19 ] vs 148 [ 35 ] ; P<.001 ) ; decreased MODS score ( mean [ SEM ] , 0.7 [ 0.2 ] vs 1.8 [ 0.3 ] ; P<.001 ) ; and successful extubation ( 7 vs 0 ; P=.05 ) . For the treatment group vs the placebo group , mortality associated with the intensive care unit was 0 ( 0 % ) of 16 vs 5 ( 62 % ) of 8 ( P=.002 ) and hospital-associated mortality was 2 ( 12 % ) of 16 vs 5 ( 62 % ) of 8 ( P=.03 ) . The rate of infections per day of treatment was similar in both groups , and pneumonia was frequently detected in the absence of fever . CONCLUSIONS In this study , prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality Introduction The aim of this study was to assess the effect of low-dose corticosteroid therapy in reducing shock duration after severe burn . Methods A placebo-controlled , double-blind , r and omized clinical trial ( RCT ) was performed on two parallel groups in the burn intensive care unit ( ICU ) . Patients were r and omized to receive either low-dose corticosteroid therapy or placebo for seven days . A corticotropin test was performed at the time of r and omization , before the administration of the treatment dose . Thirty-two severely burned patients with refractory shock ( > 0.5 μg/kg/min of norepinephrine ) were prospect ively included in the study . Results We included 12 patients in the hydrocortisone-treated group and 15 patients in the placebo group in the final analysis . Among these patients , 21 were nonresponders to the corticotropin test . Median norepinephrine treatment duration ( primary objective ) was significantly lower in the corticosteroid-treated versus the placebo group ( 57 hours versus 120 hours , P = 0.035 ) . The number of patients without norepinephrine 72 hours after inclusion was significantly lower in the treated group ( P = 0.003 , log-rank test analysis ) . The total quantities of norepinephrine administered to patients were lower in the hydrocortisone-treated versus the placebo group ( 1,205 μg/kg ( 1,079 to 2,167 ) versus 1,971 μg/kg ( 1,535 to 3,893 ) , P = 0.067 ) . There was no difference in terms of ICU or hospital length of stay , sepsis incidence , cicatrization or mortality . Conclusions In this placebo-controlled , r and omized , double-blind clinical trial , we show for the first time that the administration of low-dose hydrocortisone in burn patients with severe shock reduces vasopressor administration . Trial registration Clinical trial.gov NCT00149123 . Registered 6 September 2005 Reporting harms may cause more trouble and discredit than the fame and glory associated with successful reporting of benefits ( 1 ) . The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement , a checklist ( Table 1 ) flow diagram first published in 1996 and revised 5 years later ( 2 , 3 ) , is an effort to st and ardize , and thereby improve , published reports of r and omized , controlled trials ( RCTs ) . One of the additions to the 2001 revision was an item about reporting adverse events . This single item did not do full justice to the importance of harms-related issues . The CONSORT Group met in September 2001 to discuss how to correct this deficiency . We aim ed to provide evidence -based guidance on the reporting of harms in RCTs . First , we search ed MEDLINE , EMBASE , Web of Science , and the Cochrane Library using a wide array of terms related to harms and identified pertinent evidence . We also communicated with experts and review ed bibliographies of identified articles to find additional studies . At a meeting in Montebello , Quebec , Canada , in May 2003 , CONSORT Group members , including several journal editors and additional experts in related fields , held a structured discussion of recommendations about reporting of harms-related issues in RCTs . The discussion s led to a written document that we circulated among the team members for comment . The present manuscript describes our recommendations on the appropriate reporting of harms in RCTs . Table 1 . Original CONSORT Checklist The terminology of harms-related issues in RCTs is confusing and often misleading or misused ( see Glossary ) ( 4 , 5 ) . Safety is a reassuring term that may obscure the real and potentially major harms that drugs and other interventions may cause . We encourage authors to use the term harms instead of safety . In addition to misused terminology , reporting of harms in RCTs has received less attention than reporting of efficacy and effectiveness and is often inadequate ( 6 - 14 ) . In short , both scientific evidence and ethical necessity call for action to improve the quality of reporting of harms in RCTs ( 15 , 16 ) . Here , we present a set of recommendations and accompanying explanations for the proper reporting of harms in RCTs . These recommendations should complement the existing CONSORT statement ( Table 2 ) . Examples are presented on the Annals and CONSORT ( www.consort-statement.org ) Web sites . Table 2 . Checklist of Items To Include When Reporting Harms in R and omized , Controlled Trials Recommendations Title and Abstract Recommendation 1 . If the study collected data on harms and benefits , the title or abstract should so state . The title should mention harms if the study of harms was a key trial objective . Many phase I and phase II trials , some phase II/III trials , and most phase IV trials ( 17 , 18 ) target harms as primary outcomes . Yet , the title and abstract seldom contain the word harm . Among 375143 entries in the Cochrane Central Register of Controlled Trials ( Cochrane Library , issue 3 , 2003 ) , search ing titles with the search terms harm or harms yielded 337 references ( compared with 55374 for efficacy and 23415 for safety ) . Of the 337 , excluding several irrelevant articles on self-harm or harm reduction , only 3 trial reports and 2 abstract s contained the word harm in their titles . Authors should present information on harms in the abstract . If no important harms occurred , authors should so state . Explicit reference to the reporting of adverse events in the title or abstract is also important for appropriate data base indexing and information retrieval ( 19 ) . Introduction Background Recommendation 2 . If the trial addresses both harms and benefits , the introduction should so state . The introduction states the scientific background and rationale of an RCT . This requires a balanced presentation whereby the possible benefits of the intervention under investigation are outlined along with the possible harms associated with the treatment . R and omized , controlled trials that focus primarily on harms should clearly state this interest when describing the study objectives in the Introduction and in defining these objectives in the Methods . Methods Outcomes Recommendation 3 . List addressed adverse events with definitions for each ( with attention , when relevant , to grading , expected vs. unexpected events , reference to st and ardized and vali date d definitions , and description of new definitions ) . The Methods section should succinctly define the recorded adverse events ( clinical and laboratory ) . Authors should clarify whether the reported adverse events encompass all the recorded adverse events or a selected sample . They should explain how , why , and who selected adverse events for reporting . In trials that do not mention harms-related data , the Methods section should briefly explain the reason for the omission ( for example , the design did not include the collection of any information on harms ) . Authors should also be explicit about separately reporting anticipated and unexpected adverse events . Expectation may influence the incidence of reported or ascertained adverse events . Making participants aware in the consent form of the possibility of a specific adverse event ( priming ) may increase the reporting rate of the event ( 20 ) . Another example of priming is the finding that the rates of withdrawals due to adverse events and the rates of specific adverse events were significantly higher in trials of aspirin , diclofenac , or indomethacin with comparator drugs compared with placebo-controlled trials ( 21 ) . Presumably , participants were more eager to come forth and report an adverse event or to withdraw from treatment when they knew they could not be receiving inactive placebo . Authors should report whether they used st and ardized and vali date d measurement instruments for adverse events . Several medical fields have developed st and ardized scales ( 22 - 32 ) . Use of nonvali date d scales is common . The source document for well-established definitions and scales should be referenced . New definitions for adverse events should be explicit and clear . Authors should describe how they developed and vali date d new scales . For interventions that target healthy individuals ( for example , many preventive interventions ) , any harm , however minor , may be important to capture and report because the balance of harms and benefits may easily lean toward harms in a low-risk population . For other population s and for interventions that improve major outcomes ( for example , survival ) , severe and life-threatening adverse events may be the only ones that are important in the balance of benefits and harms . Recommendation 4 . Clarify how harms-related information was collected ( mode of data collection , timing , attribution methods , intensity of ascertainment , and harms-related monitoring and stopping rules , if pertinent ) . It is important to describe the question naires , interviews , and tests used to collect information on harms , as well as their timing during follow-up . Passive surveillance of harms leads to fewer recorded adverse events than active surveillance ( 4 ) . Open-ended questions may yield different information , both quantitatively and qualitatively , than structured question naires ( 33 ) . Studies of nonsteroidal , anti-inflammatory drugs ( NSAIDs ) exemplify how data collection methods can affect the detection and reporting of harms . When selective NSAIDs with fewer gastrointestinal adverse events became available , trials reported more than 10 times as many ulcers when comparing these drugs with older NSAIDs as when older NSAIDs were compared with placebo . In the newer trials , more ulcers were detected because participants had regular endoscopy , and the case definition of ulcers was more sensitive ( 34 ) . Authors should specify the time frame of surveillance for adverse events . Some investigators stop recording adverse events at the end of the intervention period or a certain number of days afterward ( for example , 30 days after discontinuation of drug therapy ) and miss events with long latency ( 35 ) . Surgical trials often capture only the adverse events that occur intraoperatively . Several important surgical complications are likely to occur later . Finally , in crossover trials , delayed events might occur while the patient is taking a subsequent assigned treatment . Attribution is the process of deciding whether an adverse event is related to the intervention . Whenever authors filter events through an attribution process , they should state who makes the attribution ( investigators , participants , sponsors , or combinations ) , whether the process is blinded to assigned treatment , and what definitions of adverse events they use ( 4 ) . Discontinuations and withdrawals due to adverse events are especially important because they reflect the ultimate decision of the participant and /or physician to discontinue treatment . Although treatment may occasionally be discontinued for mild or moderate adverse events , attributing discontinuation to a specific reason ( to toxicity , lack of efficacy , other reasons , or combinations of reasons ) may be difficult . For example , in psychopharmacology , dropouts may reflect treatment ineffectiveness as much as toxicity-related intolerance ( 36 ) . Trial reports should specify who gave the reasons for discontinuation ( participants or physicians ) and whether attribution was blinded to the assigned treatment . For example , even in blinded trials , participants and their clinicians are often unblinded before they decide whether to discontinue the intervention . It is important to report participants who are nonadherent or lost to follow-up because their actions may reflect their inability to tolerate the intervention . Moreover , authors should specify how they h and led withdrawals in the analyses of the data . R and omized , controlled trials should report any plan for monitoring for harms and rules for stopping the trial because of harms ( 37 ) . They should clarify whether stopping guidelines examine benefits and harms Objectives : Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock . Retrospective analyses have suggested that there may be an interaction between these drugs , with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids . We aim ed to test for an interaction between vasopressin and corticosteroids in septic shock . Design : Prospect i ve open-label r and omized controlled pilot trial . Setting : Four adult ICUs in London teaching hospitals . Patients : Sixty-one adult patients who had septic shock . Interventions : Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone ( 50 mg 6 hourly ) or placebo . Plasma vasopressin levels were measured at 6–12 and 24–36 hours after hydrocortisone/placebo administration . Measurements and Main Results : Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo . The hydrocortisone group required a shorter duration of vasopressin therapy ( 3.1 d ; 95 % CI , 1.1–5.1 ; shorter in hydrocortisone group ) and required a lower total dose of vasopressin ( ratio , 0.47 ; 95 % CI , 0.32–0.71 ) compared with the placebo group . Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group ( 64 pmol/L difference at 6- to 12-hour time point ; 95 % CI , –32 to 160 pmol/L ) . Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported . There were no differences in mortality rates ( 23 % 28-day mortality in both groups ) or organ failure assessment s between the two treatment groups . Conclusions : Hydrocortisone spared vasopressin requirements , reduced duration , and reduced dose , when used together in the treatment of septic shock , but it did not alter plasma vasopressin levels . Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids Glucocorticoid receptors ( GCRs ) were studied by the radiolig and binding assay in peripheral leukocytes obtained from dogs during intestinal ischemia shock and obtained from patients with septic shock . Sixteen healthy adult mongrel dogs were divided into two groups at r and om . The model of intestinal ischemia shock was made by occluding both superior mesenteric artery and vein in the occlusion group . Leukocytic GCRs and plasma cortisol were measured just at the time when mean arterial pressure ( MAP ) was 13.3 kPa ( 100 mmHg ) , 6.6 kPa ( 50 mmHg ) , and 3.3 kPa ( 25 mmHg ) . Clinical ly leukocytic GCRs were measured in ten patients in septic shock during hypotensive period and in ten normal volunteers used as control subjects . The results showed that in the occlusion group of animals , the levels of GCRs decreased progressively after shock ; there was a significant positive correlation between the extent of reduction of MAP and that of GCRs . Leukocytes from the occlusion group contained significantly lower levels of GCRs than those from controls . The results of clinical observation confirmed the reduction of GCR levels in patients with septic shock . This paper reports for the first time the finding of secondary disorder of GCRs during septic shock , advances a new hypothesis concerning the pathophysiology of shock at the receptor level , and offers the experimental evidence for early use of massive doses of glucocorticoid ( GC ) in dealing with septic shock Naloxone and methylprednisolone sodium succinate ( MPSS ) may act in synergy to improve hemodynamics in patients with septic shock by enhancement of sympathomedullary discharge . This r and omized double-blind study describes the effect of various dosing regimens of naloxone and MPSS upon hemodynamics and plasma catecholamines in patients with septic shock ( n = 57 ) . Consecutive bolus doses of naloxone were given 30 minutes apart ( 10 micrograms/kg;-100 micrograms/kg ) and a single dose of MPSS ( 30 mg/kg ) ; bolus doses of 5 % dextrose in water solution plus single dose of MPSS as above ; bolus dose of naloxone ( 30 micrograms/kg ) followed by continuous infusion ( 30 micrograms/kg/hr for 1 hour ) with single dose of MPSS as above ; a bolus and continuous infusion of naloxone as above without MPSS ; MPSS alone and st and ard therapy alone . In patients treated with bolus doses of naloxone in combination with MPSS , plasma levels of epinephrine and norepinephrine were increased approximately five-to tenfold . In patients treated with bolus plus continuous infusion of naloxone given with or without MPSS , only plasma epinephrine levels were increased . Systolic blood pressure and left ventricular stroke work index were improved within 15 minutes in groups which received naloxone and corticosteroids regardless of dose . In those groups , there were no changes in heart rate or filling pressure . Systemic vascular resistance improved significantly only in the group which received low dose bolus and continuous infusion of naloxone and MPSS . Naloxone and MPSS quickly improved cardiac function in patients with septic shock by enhanced sympathomedullary discharge and may be useful as an adjunct in the therapy of this disorder Objectives : To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release . Design : Prospect i ve study in patients with septic shock treated with low doses of hydrocortisone . Setting : ICUs and general wards . Patients : Over a 2-year period , 170 patients with septic shock treated with low doses of hydrocortisone were enrolled . Blood was sample d from 34 patients for isolation of peripheral blood mononuclear cells and cytokine stimulation before and 24 hours after the start of hydrocortisone . Interventions : None . Measurements and Main Results : After quartile analysis , patients were divided into those with early initiation of hydrocortisone ( < 9 hr after vasopressors , n = 46 ) and those with late initiation of hydrocortisone ( > 9 hr after vasopressors , n = 124 ) . After adjusting for disease severity and type of infection , a protective effect of early hydrocortisone administration against unfavorable outcome was found ( hazard ratio , 0.20 ; p = 0.012 ) . Time of discontinuation of vasopressors was earlier among patients with initiation of hydrocortisone within 9 hours . Production of tumor necrosis factor-&agr ; was lower among patients who had had hydrocortisone early . Conclusions : In patients receiving hydrocortisone for septic shock , early initiation of treatment was associated with improved survival . This treatment was also associated with attenuated stimulation of tumor necrosis Objective To investigate the effects of low-dose hydrocortisone ( HC ) on neutrophil respiratory burst , phagocytosis , and elimination of E. coli from blood and tissue under endotoxemic and non-endotoxemic conditions . Design R and omized , controlled trial . Setting Experimental laboratory , university hospital . SubjectsForty-eight female chinchilla rabbits ( n=8 in six groups A – F ) . Interventions In order to quantify the bacterial clearance process , defined numbers [ 108 colony forming units ( CFU ) ] of Escherichia coli were injected intravenously into all anesthetized rabbits . Group A did not receive further intervention . Group B received bolus administration of HC 1.4 mg/kg and group C 14 mg/kg . Endotoxin ( LPS , 40 μg/kg/h ) was given to groups D , E , and F. Group E received additional bolus administration of HC 1.4 mg/kg and group F 14 mg/kg . All HC groups ( B , C , E , and F ) were continuously infused with HC 0.18 mg/kg/h . Measurements Monitored parameters were neutrophil respiratory burst and phagocytosis activity , rates of bacterial elimination from the blood , arterial blood pressure , serum lactate and LPS concentrations , as well as nitrite and nitrate levels . Tissue sample s of liver , kidney , spleen , and lung were collected for bacterial counts . Main results In controls HC significantly delayed elimination of injected E. coli from the blood ( P<0.01 ) . LPS also prolonged bacterial elimination but additional HC did not further delay removal of E. coli from the blood . Under endotoxemia HC depressed respiratory burst , whereas phagocytosis functions remained unaltered . Moreover , bacterial colonization of organs was reduced after HC in the LPS groups . Significance , however , was reached only in the liver ( P<0.05 ) . Due to HC , clearance from LPS ( P<0.01 ) and lactate ( P<0.05 ) were improved . Levels of nitrite and nitrate did not differ among the groups . Conclusion HC demonstrated immunomodulatory effects even in stress doses . In endotoxemic states use of low-dose HC seems to be favorable , although not in non-septic conditions Objective To investigate the numbers , clinical characteristics , re source use , and outcomes of admissions who met precise clinical and physiologic criteria for severe sepsis ( as defined in the PROWESS trial ) in the first 24 hrs in the intensive care unit . Design Observational cohort study , with retrospective analysis of prospect ively collected data . Setting Ninety-one adult general intensive care units in Engl and , Wales , and Northern Irel and between 1995 and 2000 . Patients Patients were 56,673 adult admissions . Interventions None . Measurements and Main Results We found that 27.1 % of adult intensive care unit admissions met severe sepsis criteria in the first 24 hrs in the intensive care unit . Most were nonsurgical ( 67 % ) , and the most common organ system dysfunctions were seen in the cardiovascular ( 88 % ) and respiratory ( 81 % ) systems . Modeling the data for Engl and and Wales for 1997 suggested that 51 ( 95 % confidence interval , 46–58 ) per 100,000 population per year were admitted to intensive care units and met severe sepsis criteria in the first 24 hrs . Of the intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , 35 % died before intensive care unit discharge and 47 % died during their hospital stay . Hospital mortality rate ranged from 17 % in the 16–19 age group to 64 % in those > 85 yrs . In Engl and and Wales in 1997 , an estimated 24 ( 95 % confidence interval , 21–28 ) per 100,000 population per year died after intensive care unit admissions with severe sepsis in the first 24 hrs . For intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , median intensive care unit length of stay was 3.56 days ( interquartile range , 1.50–9.32 ) and median hospital length of stay was 18 days ( interquartile range , 8–36 days ) . These admissions used 45 % of the intensive care unit and 33 % of the hospital bed days used by all intensive care unit admissions . Conclusions Severe sepsis is common and presents a major challenge for clinicians , managers , and healthcare policymakers . Intensive care unit admissions meeting severe sepsis criteria have a high mortality rate and high re source use CONTEXT When clinicians assess the validity of r and omized controlled trials ( RCTs ) , they commonly evaluate the blinding status of individuals in the RCT . The terminology authors often use to convey blinding status ( single , double , and triple blinding ) may be open to various interpretations . OBJECTIVE To determine physician interpretations and textbook definitions of RCT blinding terms . DESIGN AND SETTING Observational study undertaken at 3 Canadian university tertiary care centers between February and May 1999 . PARTICIPANTS Ninety-one internal medicine physicians who responded to a survey . MAIN OUTCOME MEASURES Respondents identified which of the following groups they thought were blinded in single- , double- , and triple-blinded RCTs : participants , health care providers , data collectors , judicial assessors of outcomes , data analysts , and personnel who write the article . Definitions from 25 systematic ally identified textbooks published since 1990 providing definitions for single , double , or triple blinding . RESULTS Physician respondents identified 10 , 17 , and 15 unique interpretations of single , double , and triple blinding , respectively , and textbooks provided 5 , 9 , and 7 different definitions of each . The frequencies of the most common physician interpretation and textbook definition were 75 % ( 95 % confidence interval [ CI ] , 65%-83 % ) and 74 % ( 95 % CI , 52%-90 % ) for single blinding , 38 % ( 95 % CI , 28%-49 % ) and 43 % ( 95 % CI , 24%-63 % ) for double blinding , and 18 % ( 95 % CI , 10%-28 % ) and 14 % ( 95 % CI , 0%-58 % ) for triple blinding , respectively . CONCLUSIONS Our study suggests that both physicians and textbooks vary greatly in their interpretations and definitions of single , double , and triple blinding . Explicit statements about the blinding status of specific groups involved in RCTs should replace the current ambiguous terminology Objectives : To investigate the effect of low-dose hydrocortisone on time to shock reversal , the cytokine profile , and its relation to adrenal function in patients with early septic shock . Design : Prospect i ve , r and omized , double-blind , single-center study . Setting : Medical intensive care unit of a university hospital . Patients : Forty-one consecutive patients with early hyperdynamic septic shock . Interventions : After inclusion and a short adrenocorticotropic hormone test , all patients were r and omized to receive either low-dose hydrocortisone ( 50-mg bolus followed by a continuous infusion of 0.18 mg/kg body of weight/hr ) or matching placebo . After shock reversal , the dose was reduced to 0.06 mg/kg/hr and afterward slowly tapered . Severity of illness was estimated using Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score . Measurements and Main Results : Time to cessation of vasopressor support ( primary end point ) was significantly shorter in hydrocortisone-treated patients compared with placebo ( 53 hrs vs. 120 hrs , p < .02 ) . This effect was more profound in patients with impaired adrenal reserve . Irrespective of endogenous steroid production , cytokine production was reduced in the treatment group with lower plasma levels of interleukin-6 and a diminished ex vivo lipopolysaccharide-stimulated interleukin-1 and interleukin-6 production . Interleukin-10 levels were unaltered . Adverse events were not more frequent in the treatment group . Conclusions : Treatment with low-dose hydrocortisone accelerates shock reversal in early hyperdynamic septic shock . This was accompanied by reduced production of proinflammatory cytokines , suggesting both hemodynamic and immunomodulatory effects of steroid treatment . Hemodynamic improvement seemed to be related to endogenous cortisol levels , whereas immune effects appeared to be independent of adrenal reserve The effects of massive doses of steroids on septic shock were tested in 48 patients being treated for extensive cellulitis , wet gangrene , or severe peritonitis . From diagnosis until maximum weight gain ( average , 47 hours ) , they received an average of 17.7 L of crystalloid solution and 1.0 L of blood and voided 3.1 L of urine . Of the 48 patients , 23 were selected in r and om fashion to receive dexamethasone sodium phosphate ( 6 mg/kg ) over 48 hours . The average age ( 55 years ) , duration of shock ( 36 minutes ) , and insult were similar for both groups . Each group received similar volumes of fluid and blood . Steroid therapy was associated with a statistically significant rise in diastolic pressure ( 88 v 78 mm Hg ) , mean arterial pressure ( 105 v 95 mm Hg ) , and central venous pressure ( 16 v 10 cm H2O ) . Concomitant blood volume was lower in patients treated with steroids ( 5.2 v 6.1 L ) . All differences between the two groups disappeared after 48 hours when steroid therapy was discontinued . No differences were noted in morbidity and five patients in each group died OBJECTIVE To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING ICUs of five hospitals in Memphis . PARTICIPANTS Ninety-one patients with severe early ARDS ( < /= 72 h ) , 66 % with sepsis . INTERVENTIONS Patients were r and omized ( 2:1 fashion ) to methylprednisolone infusion ( 1 mg/kg/d ) vs placebo . The duration of treatment was up to 28 days . Infection surveillance and avoidance of paralysis were integral components of the protocol . MAIN OUTCOME MEASURE The predefined primary end point was a 1-point reduction in lung injury score ( LIS ) or successful extubation by day 7 . RESULTS In intention-to-treat analysis , the response of the two groups ( 63 treated and 28 control ) clearly diverged by day 7 , with twice the proportion of treated patients achieving a 1-point reduction in LIS ( 69.8 % vs 35.7 % ; p = 0.002 ) and breathing without assistance ( 53.9 % vs 25.0 % ; p = 0.01 ) . Treated patients had significant reduction in C-reactive protein levels , and by day 7 had lower LIS and multiple organ dysfunction syndrome scores . Treatment was associated with a reduction in the duration of mechanical ventilation ( p = 0.002 ) , ICU stay ( p = 0.007 ) , and ICU mortality ( 20.6 % vs 42.9 % ; p = 0.03 ) . Treated patients had a lower rate of infections ( p = 0.0002 ) , and infection surveillance identified 56 % of nosocomial infections in patients without fever . CONCLUSIONS Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay CONTEXT AND OBJECTIVE Systemic inflammatory response syndrome ( SIRS ) is a very common condition among critically ill patients . SIRS , sepsis , septic shock and multiple organ dysfunction syndrome ( MODS ) can lead to death . Our aim was to investigate the efficacy of a single dose of dexamethasone for blocking the progression of systemic inflammatory response syndrome . DESIGN AND SETTING Prospect i ve , r and omized , double-blind , single-center study in a postoperative intensive care unit ( Surgical Support Unit ) at Hospital das Clínicas , Faculdade de Medicina , Universidade de São Paulo . METHODS The study involved 29 patients with SIRS . All eligible patients were prospect ively r and omized to receive either a single dose of 0.2 mg/kg of dexamethasone or placebo , after SIRS was diagnosed . The patients were monitored over a seven-day period using Sequential Organ Failure Assessment score ( SOFA ) . RESULTS The respiratory system showed an improvement on the first day after dexamethasone was administered , demonstrated by the improved PaO2/FiO2 ratio ( p < 0.05 ) . The cardiovascular system of patients requiring vasopressor therapy also improved over the first two days , with a better evolution in the dexamethasone group ( p < 0.05 ) . Non-surviving patients presented higher lactate assays than did survivors ( p < 0.05 ) during this period . CONCLUSIONS Dexamethasone enhanced the effects of vasopressor drugs and evaluation of the respiratory system showed improvements ( better PaO2/FiO2 ratio ) , one day after its administration . Despite these improvements , the single dose of dexamethasone did not block the evolution of SIRS Ten years ago 8.4 % of patients in French intensive care units ( ICUs ) were found to have severe sepsis or shock and 56 % died in the hospital . As novel therapies for severe sepsis are emerging , up date d epidemiological information is required . An inception cohort study conducted in 206 ICUs of r and omly selected hospitals over a 2-week period in 2001 , including all patients meeting criteria for clinical ly or microbiologically documented severe sepsis ( with ≥1 organ dysfunction ) . Among 3738 admissions , 546 ( 14.6 % ) patients experienced severe sepsis or shock , of which 30 % were ICU-acquired . The median age of patients was 65 years , and 54.1 % had at least one chronic organ system dysfunction . The median ( range ) Simplified Acute Physiology Score ( SAPS II ) and Sequential Organ Failure Assessment ( SOFA ) at onset of severe sepsis were 48 ( 2–129 ) and 9 ( 1–24 ) , respectively . Mortality was 35 % at 30 days ; at 2 months the mortality rate was 41.9 % , and 11.4 % of patients remained hospitalized . The median ( range ) hospital stay was 25 ( 0–112 ) days in survivors and 7 ( 0–90 ) days in non-survivors . Chronic liver and heart failure , acute renal failure and shock , SAPS II at onset of severe sepsis and 24-h total SOFA scores were the independent risk factors most strongly associated with death . Although the attack rate of severe sepsis in French ICUs appears to have increased over the past decade , its associated mortality has decreased , suggesting improved management of patients . Severe sepsis incurs considerable re sources use , and implementation of effective management strategies and continued research efforts are needed We conducted a prospect i ve , r and omized , double-blind study to determine whether high-dose methylprednisolone could prevent parenchymal lung injury , including the adult respiratory distress syndrome ( ARDS ) , or improve mortality when administered early in septic shock . All patients already hospitalized in or newly admitted to the medical and surgical intensive care units at San Francisco General Hospital between September 1 , 1983 and August 29 , 1986 were eligible for admission to the study if they had either ( 1 ) an increase in temperature of 1.5 degrees C and a decrease in systolic blood pressure of 20 mm Hg or more from baseline values ( in already hospitalized patients ) , or ( 2 ) a temperature greater than 38.5 degrees C or less than 35.5 degrees C and a systolic blood pressure of less than 90 mm Hg ( in newly admitted patients ) . Patients meeting these criteria were excluded if they ( 1 ) had severe immunodeficiency , ( 2 ) were less than 18 or greater than 76 yr of age , ( 3 ) had multilobar roentgenographic infiltrates , or ( 4 ) were already receiving corticosteroids . Eighty-seven patients enrolled in the study received either methylprednisolone , 30 mg/kg per dose , or mannitol placebo for a total of 4 doses every 6 h , following the presumptive diagnosis of septic shock . Of these patients , 75 ultimately were determined on the basis of culture results to have actually had septic shock at the time of entry . Thirteen of the patients who received methylprednisolone developed ARDS , compared to 14 patients who received placebo . Lesser degrees of parenchymal lung injury did not differ between the 2 groups . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To observe the effect of low-dose hydrocortisone on the requirement of norepinephrine and lactate clearance in patients with refractory septic shock , and to investigate the effect of stress dose corticosteroids in reversing septic shock and improving tissue oxygen supply . METHODS Seventy-seven septic shock patients with hypotension refractory to fluids and administration of norepinephrine were r and omly divided into control and treatment groups . In treatment group intravenous injection of low-dose hydrocortisone was given on top of the treatment given in control group for 14 days . The mean arterial pressure ( MAP ) , lactate clearance and the data of norepinephrine use were compared between two groups during the course of treatment . RESULTS The number of patients requiring norepinephrine was significantly lower and the MAP was significantly higher in 24 hours , 7 days , 14 days than those at the beginning of treatment in both groups ( all P<0.01 ) . Compare to the control group , the course of using norepinephrine was shorter and the number of using norepinephrine was smaller in 7 days in treatment group ( both P<0.05 ) ; the MAP and lactate clearance were higher in 24 hours and 7 days in treatment group ( P<0.05 or P<0.01 ) . But there were no differences in mortality and the length of stay in intensive care unit ( ICU ) . CONCLUSION For the patients with septic shock with refractory hypotension , low-dose hydrocortisone can decrease the time course and dosage of vasopressors , improve tissue oxygen supply , thus can reverse septic shock more rapidly Objective To assess the effects of stress doses of hydrocortisone ( HC ) on clinical parameters and neutrophil functions in patients with septic shock . Design Prospect i ve , double-blind , r and omized , placebo-controlled study . Setting Intensive care units of a university hospital . Patients and participants 30 adult patients with septic shock . Interventions Patients were allocated to receive either HC ( intravenous bolus of 100 mg preceding a continuous infusion 10 mg/h , n = 15 ) or placebo ( n = 15 ) , respectively . The effects of HC were assessed at baseline and after 24 h. Measurements and results As compared with placebo-treated patients , administration of HC significantly decreased norepinephrine requirements ( from 1.5 to 0.8 mg/h ; p < 0.001 ) , interleukin-6 serum concentrations ( from 388.8 to 88.8 pg/ml ; p < 0.02 ) , and the spontaneous release of hydrogen peroxide ( H2O2 ) by neutrophils ( −33.0 % ; p < 0.05 ) . Additionally , HC treatment preserved the autologous plasma-induced amplification of phagocytosis of zymosan particles [ factor of opsonin-induced amplification of phagocytosis of unopsonized particles : 1.80 for placebo vs. 1.75 for HC at baseline ( not significant between groups ) and 0.50 for placebo vs. 1.75 for HC after 24 h of treatment ( p < 0.05 ) ] . These effects were paralleled by respective changes in the phagocytosis-associated H2O2 production . Conclusions In patients with septic shock stress doses of HC exert beneficial effects in terms of improvements in hemodynamics , decrease in pro-inflammatory mediators , and oxidative stress without the compromise of opsonization-dependent phagocytic neutrophil functions ; thus , HC treatment does not aggravate non-specific immunosuppression but instead improves innate immunity in the early stage of septic shock OBJECTIVE To investigate the effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome ( ARDS ) combined with critical illness-related corticosteroid insufficiency ( CIRCI ) . METHODS All early ARDS patients combined with CIRCI were screened by an adrenal corticotrophic hormone ( ACTH ) test and r and omly divided into treatment group ( hydrocortisone 100 mg intravenous , 3 times/day , consecutively for 7 days , n = 12 ) and control group ( equivalent normal saline , n = 14 ) . General clinical data , changes of arterial blood gas , hemodynamics and respiratory mechanics were observed and recorded at admission and at 7 days after treatment . Ventilator-free and shock-free days , ICU stay within 28 days after admission were recorded and 28-day mortality was used as judge prognosis index . RESULTS CIRCI rate in 45 early ARDS patients was 57.8 % ( 26 patients ) , and the shock rate was markedly higher in ARDS patients with CIRCI than patients without CIRCI ( 46.2 % vs 5/19 ) . There were no significant differences in baseline parameters , oxygenation and illness severity between the treatment and control groups , except for markedly lower lactic level in the treatment group [ 2.7(1.2 , 3.9 ) mmol/L vs 4.6(2.5 , 6.3 ) mmol/L , P < 0.05 ] . After 7 days of treatment , PaO2/FiO2 markedly increased , while heart rate obviously decreased in the both groups . Compared with the control group , survival time of patients was significantly longer and shock rate of the patients was markedly lower in treatment group within 28 days ( 5/12 vs 10/14 , P < 0.05 ) . The 28-day mortality , which were adjusted by baseline arterial lactic , was lower in the treatment group ( 2.6/12 ) than in the control group ( 5.8/14 ) while with no significant difference ( P > 0.05 ) . There was no significant difference in complication incidence between the two groups . CONCLUSION Stress dose glucocorticoid could reduce shock incidence and prolong survival time , and has a tendency of lower 28-day mortality in early ARDS patients combined with CIRCI OBJECTIVES Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines . We examined the effect of hydrocortisone on shock reversal , hemodynamics , and survival in this particular setting . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Two intensive care units of a University hospital . PATIENTS Forty-one patients with septic shock requiring catecholamine for > 48 hrs . INTERVENTIONS Patients were r and omly assigned either hydrocortisone ( 100 mg i.v . three times daily for 5 days ) or matching placebo . MEASUREMENTS AND MAIN RESULTS Reversal of shock was defined by a stable systolic arterial pressure ( > 90 mm Hg ) for > or = 24 hrs without catecholamine or fluid infusion . Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients , 15 ( 68 % ) and 4 ( 21 % ) achieved 7-day shock reversal , respectively , a difference of 47 % ( 95 % confidence interval 17 % to 77 % ; p = .007 ) . Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups . At 28-day follow-up , reversal of shock was higher in the hydrocortisone group ( p = .005 ) . Crude 28-day mortality was 7 ( 32 % ) of 22 treated patients and 12 ( 63 % ) of 19 placebo patients , a difference of 31 % ( 95 % confidence interval 1 % to 61 % ; p = .091 ) . Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival . There were no significant differences in outcome in responders and nonresponders to a short corticotropin test . The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups . CONCLUSIONS Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of > 96 hrs result ed in a significant improvement in hemodynamics and a beneficial effect on survival . These beneficial effects do not appear related to adrenocortical insufficiency BACKGROUND Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin . METHODS In this multicenter , r and omized , double-blind , placebo-controlled trial , we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days ; the dose was then tapered during a 6-day period . At 28 days , the primary outcome was death among patients who did not have a response to a corticotropin test . RESULTS Of the 499 patients in the study , 233 ( 46.7 % ) did not have a response to corticotropin ( 125 in the hydrocortisone group and 108 in the placebo group ) . At 28 days , there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin ( 39.2 % in the hydrocortisone group and 36.1 % in the placebo group , P=0.69 ) or between those who had a response to corticotropin ( 28.8 % in the hydrocortisone group and 28.7 % in the placebo group , P=1.00 ) . At 28 days , 86 of 251 patients in the hydrocortisone group ( 34.3 % ) and 78 of 248 patients in the placebo group ( 31.5 % ) had died ( P=0.51 ) . In the hydrocortisone group , shock was reversed more quickly than in the placebo group . However , there were more episodes of superinfection , including new sepsis and septic shock . CONCLUSIONS Hydrocortisone did not improve survival or reversal of shock in patients with septic shock , either overall or in patients who did not have a response to corticotropin , although hydrocortisone hastened reversal of shock in patients in whom shock was reversed . ( Clinical Trials.gov number , NCT00147004 . STEROIDS might be of benefit to the patient with a serious infection.1 In 1961 a Cooperative double-blind study of the effects of administering a dose of 300 mg of hydrocortisone to patients with s Objective : Nitric oxide is an important participant in septic shock . For example , it causes profound vasodilation and hypotension . Despite their potent antiinflammatory properties , glucocorticoids are not routinely used in septic shock . Some studies show that antiinflammatory doses of glucocorticoids can be beneficial , but other studies do not indicate their use in this situation . We have previously shown the inhibitory effect of nitric oxide on glucocorticoid receptor binding in vitro . Nitric oxide donors decreased the binding of immunoprecipitated glucocorticoid receptor obtained from mouse L929 fibroblasts . These in vitro findings prompted us to study whether in vivo manipulations of the nitric oxide system would interfere with the glucocorticoid receptor binding . Design : Prospect i ve , experimental study . Setting : Research laboratory at a university . Subjects : Female Wistar rats . Interventions : Injection of bacterial lipopolysaccharide , anesthesia , cardiovascular perfusion , and organ removal for biochemical assays . Measurements and Main Results : Following lipopolysaccharide injection , plasma nitrate + nitrite increased and inducible nitric oxide synthase activity was stimulated in several organs , the highest rates being in the lung and spleen . If dexamethasone was injected before lipopolysaccharide , it completely blocked inducible nitric oxide synthase induction and the increase in plasma nitrate + nitrite . On the other h and , if dexamethasone was injected after lipopolysaccharide , it failed to affect both inducible nitric oxide synthase induction and increased plasma nitrate + nitrite levels . Lipopolysaccharide also caused an inhibition of glucocorticoid receptor binding in lung and spleen . Previous administration of a nitric oxide synthase inhibitor prevented both lipopolysaccharide-induced decrease in glucocorticoid receptor binding and the increase in plasma nitrate + nitrite . Injection of a nitric oxide donor into naïve animals significantly decreased glucocorticoid receptor binding activity and prevented dexamethasone-induced increase in liver tyrosine aminotransferase activity . Conclusions : The results indicate that the failure of glucocorticoids to exhibit their antiinflammatory effects when administered to endotoxemic rats may be explained , at least in part , by the nitric oxide-induced inhibition of glucocorticoid receptor binding ability , thus precluding the expression of the antiinflammatory effects of both exogenous and endogenous corticosteroids Objective : The aim of this study was to investigate the effect of low-dose hydrocortisone on glomerular permeability measured by the microalbuminuria to creatinine ratio ( MACR ) and on other markers of sepsis in severe septic patients . Design : R and omized prospect i ve study . Setting : University intensive care unit . Patients : The study involved 40 patients with severe sepsis r and omized into the hydrocortisone group ( n = 20 ) and the st and ard therapy group ( n = 20 ) . Interventions : The hydrocortisone group received st and ard therapy plus a continuous infusion of hydrocortisone for 6 days , whereas the st and ard therapy group received only st and ard therapy . Measurements and Main Results : MACR , serum C-reactive protein , and procalcitonin concentrations were recorded every day from the day before the steroid therapy ( T0 ) until the 6 days after ( T1 , T2 , T3 , T4 , T5 , and T6 ) . Concentrations in the hydrocortisone group and the st and ard therapy group were compared using Mann-Whitney test at each time . We also compared with Wilcoxon signed rank test the values determined in each group at T0 with those at each subsequent time . Median MACR decreased from T0 to T6 in both patient groups ; however , values were significantly lower in the hydrocortisone group from T3 through to T6 . Median serum C-reactive protein also decreased from T0 in both patient groups , with significantly lower values in the hydrocortisone group from T3 through to T6 . There were no significant differences in procalcitonin between groups compared with baseline values or at any individual time point . Conclusions : Low-dose hydrocortisone seems to reduce MACR and serum C-reactive protein but not procalcitonin in patients with severe sepsis . Further studies are needed to confirm these results and to underst and the underlying molecular mechanisms A prospect i ve ( Part I ) and a retrospective ( Part II ) study were used to determine the safety and efficacy of corticosteroids in the treatment of septic shock . In Part 1 , 172 consecutive patients in septic shock admitted over an 8-year period were treated with either steroid or saline : 43 received dexamethasone ( DMP ) , 43 received methylprednisolone ( MPS ) , and 86 received saline . The study was double-blind and r and omized , and the three groups were compared for age , severity of shock , presence of underlying disease , and year of study . In the 86 saline-treated patients , the mortality rate was 38.4 % ( 33/86 ) ; in the steroid-treated patients , it was 10.4 % ( 9/86 ) . With MPS the mortality rate was 11.6 % ( 5/43 ) , and with DMP it was 9.3 % ( 4/43 ) . Thus , overall mortality was significantly less in the steroid-treated group than in the control group . Further , there was no significant difference in mortality rate between the DMP- and the MPS-treated patients . In Part II , 328 patients were studied retrospectively . One-hundred sixty were treated without steroid , and 168 were treated with either DMP or MPS . Again , the two groups of patients were compared for severity of shock , underlying disease , age , and year of study . Mortality among patients treated without steroid was 42.5 % ( 68/160 ) and among patients treated with steroid was 14 % ( 24/168 ) ; there was no significant difference in mortality rate between DMP- and MPS-treated patients . In Parts I and II combined , complications occurred in 6 % of steroid-treated patients with no significant difference between DMP- and MPS-treated groups BACKGROUND Results of experimental and clinical studies have shown that septic shock is associated with cardiovascular autonomic failure . Thus , we aim ed to investigate the existence of ischaemia and apoptosis within the cerebral autonomic centres that control the cardiovascular system in patients with septic shock . METHODS In a prospect i ve cohort study , we did post-mortem examinations of supraoptic and paraventricular nuclei , cerebral amygdala , locus coeruleus , and medullary autonomic nuclei in 19 patients with septic shock , seven with non-septic shock and five who died suddenly from extracranial injury . Ischaemic and apoptotic neurons and microglial cells , and expression of tumour necrosis factor alpha ( TNFalpha ) and inducible nitric oxide synthase ( iNOS ) were scored . FINDINGS Ischaemic , neuronal , and microglial apoptosis scores differed between groups ( p=0.0007 , p<0.0001 , and p=0.0037 , respectively ) and were higher in patients with septic shock than in those with non-septic shock ( p=0.0033 , p=0.0005 , and p=0.0235 , respectively ) , and extra-cranial injury related deaths ( p=0.0027 , p=0.0007 , and p=0.0045 , respectively ) . There was little microglial activation and glial expression of TNFalpha . The scores for endothelial iNOS expression were different between the three groups ( p<0.0001 ) , and were higher in septic shock than in non-septic shock ( p=0.0009 ) and than in extracranial injury related deaths ( p=0.0007 ) . Vascular expression of iNOS also correlated ( Spearman tau=0.57 ) with autonomic-centre neuronal apoptosis in the combined septic and non-septic shock group . INTERPRETATION Septic shock is associated with neuronal and glial apoptosis within the autonomic centres , which is strongly associated with endothelial iNOS expression OBJECTIVE To determine the effect of moderate dose dexamethasone administered before antibiotics on the outcome of African children with sepsis . METHODS The design was a r and omized , double blinded , placebo-controlled trial of dexamethasone ( 0.2 mg/kg ) vs. placebo given intravenously before antibiotic therapy . Patients were recruited from the patient population s at two missionary hospitals . Primary outcome variables were determined before analysis of data . RESULTS Seventy-two children with sepsis were enrolled in the study . Treatment with dexamethasone was not associated with improved outcome for any of six outcome variables : survival to discharge ( 83 % , dexamethasone group ; 89 % , placebo group ) ; hemodynamic stability at 48 h ( 33 % , dexamethasone group ; 49 % , placebo group ) ; median length of hospital stay ( 11 days , dexamethasone group ; 11 days , placebo group ) ; normal at discharge ( 90 % , dexamethasone group ; 75 % , placebo group ) ; normal at follow-up ( 90 % , dexamethasone group ; 72 % , placebo group ) ; and afebrile at 48 to 72 h ( 61 % , dexamethasone group ; 44 % , placebo group ) . CONCLUSIONS These data indicate that a moderate dose of dexamethasone given before antibiotic therapy did not improve outcome in the pediatric patients with sepsis whom we studied OBJECTIVE To investigate the effects of stress doses of hydrocortisone on the duration of vasopressor therapy in human septic shock . DESIGN Prospect i ve , r and omized , double-blind , single-center study . SETTING Twenty-bed multidisciplinary intensive care unit in a 1400-bed university hospital . PATIENTS Forty consecutive patients who met the ACCP/SCCM criteria for septic shock . An additional criterion for inclusion in the study was vasopressor support and high-output circulatory failure with a cardiac index of > 4 L/min/m2 after fluid resuscitation ( pulmonary capillary wedge pressure : 12 - 15 mm Hg ) and without the use of positive inotropes such as dobutamine or dopexamine . The primary study end point was the time to cessation of vasopressor support ( norepinephrine or epinephrine in any dose , dopamine > or = 6 microg/kg/min ) . Secondary study end points were the evolution of hemodynamics and the multiple organ dysfunction syndrome ( MODS ) . The severity of illness at recruitment was grade d using the Acute Physiology and Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring systems . MODS was described by the Sepsis-related Organ Failure Assessment score . INTERVENTIONS All eligible patients were prospect ively r and omized to receive either stress doses of hydrocortisone or placebo . Hydrocortisone was started with a loading dose of 100 mg given within 30 mins and followed by a continuous infusion of 0.18 mg/ kg/hr . When septic shock had been reversed , the dose of hydrocortisone was reduced to 0.08 mg/kg/hr . This dose was kept constant for 6 days . As soon as the underlying infection had been treated successfully or sodium serum concentrations had increased to > 155 mmol/L , the hydrocortisone infusion was tapered in steps of 24 mg/day . Physiologic saline solution was the placebo . MEASUREMENTS AND MAIN RESULTS Hemodynamic and oxygen-derived variables were measured at previously defined time points over a study period of 5 days . Relevant clinical and laboratory measurements were registered for a study period of 14 days to assess the evolution of organ dysfunction . Baseline data at recruitment did not differ between the two groups . Shock reversal was achieved in 18 of the 20 patients treated with hydrocortisone vs. 16 of the 20 patients treated with placebo . Hydrocortisone significantly reduced the time to cessation of vasopressor support . The median time of vasopressor support was 2 days ( 1st and 3rd Quartiles , 1 and 6 days ) in the hydrocortisone-treated group and 7 days ( 1st and 3rd Quartiles , 3 and 19 days ) in the placebo group ( p = .005 Breslow test ) . There was a trend to earlier resolution of the organ dysfunction syndrome in the hydrocortisone group . CONCLUSIONS Infusion of stress doses of hydrocortisone reduced the time to cessation of vasopressor therapy in human septic shock . This was associated with a trend to earlier resolution of sepsis-induced organ dysfunctions . Overall shock reversal and mortality were not significantly different between the groups in this low-sized single-center study Objective : To study the efficacy of low-dose intravenous hydrocortisone therapy in the management of pediatric septic shock with respect to the time taken for shock reversal and requirement of inotropes . Design : Open label r and omized pilot study . Setting : Pediatric intensive care unit of a tertiary care pediatric center in a third world country . Patients : Thirty-eight children , 2 months–12 yrs of age , with septic shock unresponsive to fluid therapy alone . Intervention : Intravenous hydrocortisone 5 mg/kg/day in four divided doses followed by half the dose for a total duration of 7 days or normal saline ( similar amount in a similar manner ) for the same duration . Results : There was a trend toward earlier reversal of shock ( median 49.5 vs. 70 hrs , p = 0.65 , Mann-Whitney U test ) and lower inotropes requirement ( median { lsqb;10th–90th centile{rsqb ; inotropes score : 20 { lsqb;15–60{rsqb ; vs. 50 { lsqb;20–80{rsqb ; , p = 0.15 ) in the hydrocortisone-treated patients as compared with controls , although the difference was not statistically significant . Mortality rate was similar in both groups . Conclusions : Our data , although , inconclusive favor the need for a study with a larger sample size to clearly define role of low-dose hydrocortisone in pediatric septic shock in developing countries , while taking in consideration effect of malnutrition , delayed presentations , and their interactions with the hypothalamic-pituitary-adrenocortical axis BACKGROUND There is considerable global uncertainty on the role of low-dose corticosteroids in septic shock , which translates into variations in prescribing practice s. OBJECTIVE To describe the protocol for a large-scale multicentre r and omised controlled trial in critically ill patients with septic shock , comparing the effects of hydrocortisone and placebo ( in addition to st and ard treatment ) on 90-day mortality and other outcomes such as shock reversal , duration of mechanical ventilation and quality of life . METHODS We will recruit 3800 critically ill patients with septic shock treated in an intensive care unit , to concealed , r and omised , parallel assignment of hydrocortisone or placebo . The primary outcome will be all-cause mortality at 90 days postr and omisation . Secondary outcomes will include ICU and hospital mortality , length of ICU stay and quality of life at 6 months . Subgroup analyses will be conducted in two predefined subgroups . All analyses will be conducted on an intention-to-treat basis . RESULTS AND CONCLUSIONS The run-in phase has been completed and the main trial commenced in February 2013 . The trial should generate results that will inform and influence prescribing of corticosteroids in septic shock The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial . Our study was design ed as a prospect i ve , r and omized , double-blind , placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock . Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia ( rectal temperature greater than 38.3 degrees C [ 101 degrees F ] or less than 35.6 degrees C [ 96 degrees F ] ) , tachypnea ( greater than 20 breaths per minute ) , tachycardia ( greater than 90 beats per minute ) , and the presence of one of the following indications of organ dysfunction : a change in mental status , hypoxemia , elevated lactate levels , or oliguria . Three hundred eighty-two patients were enrolled . Treatment -- either methylprednisolone sodium succinate ( 30 mg per kilogram of body weight ) or placebo -- was given in four infusions , starting within two hours of diagnosis . No significant differences were found in the prevention of shock , the reversal of shock , or overall mortality . In the subgroup of patients with elevated serum creatinine levels ( greater than 2 mg per deciliter ) at enrollment , mortality at 14 days was significantly increased among those receiving methylprednisolone ( 46 of 78 [ 59 percent ] vs. 17 of 58 [ 29 percent ] among those receiving placebo ; P less than 0.01 ) . Among patients treated with methylprednisolone , significantly more deaths were related to secondary infection . We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock RATIONALE A decade after drotrecogin alfa ( activated ) ( DAA ) was released on the market worldwide , its benefit-to-risk ratio remains a matter of debate . OBJECTIVES The current investigator-led trial was design ed to evaluate the efficacy and safety of DAA , in combination with low-dose steroids , in adults with persistent septic shock . METHODS This was a multicenter ( 24 intensive care units ) , placebo-controlled , double-blind , 2 × 2 factorial design trial in which adults with persistent septic shock and no contraindication to DAA were r and omly assigned to DAA alone ( 24 μg/kg/h for 96 h ) , hydrocortisone and fludrocortisone alone , their respective combinations , or their respective placebos . Primary outcome was mortality rate on Day 90 . MEASUREMENTS AND MAIN RESULTS On October 25 , 2011 , the trial was suspended after the withdrawal from the market of DAA . The Scientific Committee decided to continue the trial according to a two parallel group design comparing low-dose steroids with their placebos and to analyze the effects of DAA on patients included before trial suspension . At the time trial was suspended , 411 patients had been recruited , 208 had received DAA , and 203 had received its placebo . There was no significant interaction between DAA and low-dose steroids ( P = 0.47 ) . On Day 90 , there were 99 deaths ( 47.6 % ) among the 208 patients receiving DAA and 94 deaths ( 46.3 % ) among the 203 patients receiving placebo ( P = 0.79 ) . There was no evidence of a difference between DAA and its placebo for any secondary outcomes or serious adverse events . CONCLUSIONS In adults with established and severe septic shock , DAA showed no evidence of benefit or harm . Clinical trial registered with www . clinical trials.gov ( NCT00625209 ) |
2,470 | 20,091,569 | There are no proven clinical ly significant short or long-term benefits of PET in polycythemic newborn infants who are clinical ly well or who have minor symptoms related to hyperviscosity .
PET may lead to an increase in the risk of NEC . | BACKGROUND Hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery .
In the neonate , hyperviscosity can cause abnormalities of central nervous system function , hypoglycemia , decreased renal function , cardiorespiratory distress , and coagulation disorders .
Hyperviscosity has been reported to be associated with long-term motor and cognitive neurodevelopmental disorders .
Blood viscosity exponentially increases when an infant has polycythemia ( hematocrit > /= 65 % ) .
Partial exchange transfusion ( PET ) is traditionally used as the method to lower the hematocrit and treat hyperviscosity .
OBJECTIVES To evaluate the effect of PET on mortality and neurodevelopmental outcome in infants with neonatal polycythemia . | The study of the developmental outcome of neonatal polycythemia was performed on 47 polycythemic and 21 controlled infants who were born at the same period of time . It was found that at the age of 1 1/2 to 2 years the number of infants with abnormal DQ was higher in the group of total polycythemic infants ( 47 % ) and in the group of asymptomatic polycythemic infants ( 45 % ) than that of the control groups ( 19 % and 5.6 % of the groups including twin sibs and excluding twin sibs respectively ) . There was no difference in the developmental test between the symptomatic and asymptomatic patients . In asymptomatic infants the benefit of partial plasma exchange transfusion on developmental outcome was not found and only low birthweight and small for gestational age infants are the risk factors for poor developmental outcome To determine the effect of partial plasma exchange transfusion , 20 newborn infants with neonatal hyperviscosity were r and omly assigned to observation or treatment with partial plasma exchange transfusion within the first eight hours after birth . They were studied for organ involvement by roentgenogram , blood count , coagulation studies , and neurologic behavior and were followed up using the Brazelton Neonatal Behavior Assessment scale at 8 , 24 , and 72 hours and 2 weeks of age ; in addition , ten control infants without hyperviscosity of similar birth weights and gestational ages were also studied . Exchange transfusion improved blood viscosity but both hyperviscous groups showed a higher proportion of abnormal results than did the control subjects . Infants receiving exchange transfusions subsequently improved during the period from 8 hours to 2 to 3 weeks of age , until they were indistinguishable from the control subjects . Neurologic improvement in hyperviscous infants who had not received exchange transfusions were significantly slower during this period . At 8 months of age , abnormal neurologic and developmental findings were impressive in both groups ; no significant differences in neurologic abnormalities were noted at that time . Developmental delays , tremors , spastic diplegia , and monoparesis were found in four of six untreated infants and five of ten infants who had received exchange transfusions . A fine tremor was present in one control child A prospect i ve study to evaluate efficacy and safety of partial exchange blood transfusion ( PEBT ) with normal saline or plasma was conducted in 30 symptomatic polycythemic newborns . Babies were r and omly assigned to receive PEBT either with normal saline or plasma . Both groups were comparable in terms of birth weight , gestational age , preexchange hematocrit and viscosity . A significant fall in hematocrit and viscosity was noticed at 6 hours following PEBT which persisted even at 24 hours ( P < 0.001 ) . Hematocrit and viscosity were comparable in the two groups at 6 and 24 hours ( p > 0.05 for both ) . Majority of babies became asymptomatic after 24 hours of PEBT , but one baby in the saline group remained polycythemic and symptomatic requiring repeat PEBT . No complications related to the procedure were encountered in the two groups . Partial exchange with normal saline was as effective and safe as plasma in symptomatic polycythemic newborns The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated . Ninety-three infants with polycythemia and hyperviscosity were r and omly assigned to receive either partial plasma exchange transfusion or symptomatic treatment ; the infants were matched with control infants without polycythemia . Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups . Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants . At 2 years of age , polycythemic infants had more gross motor delays , neurologic diagnoses , fine motor abnormalities , and speech delays than did the control infants . There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care . At 2 years , the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities This r and omized controlled trial was conducted to determine the effect of partial exchange transfusion in polycythemic babies . Forty five asymptomatic polycythemic babies with birth weight < or = 2000 g were included and r and omly assigned to undergo either partial exchange transfusion using isotonic saline within 4 hours of screening or routine medical management . Outcome measures were neonatal morbidity ( especially hypoglycemia and neurological alterations ) and mortality ; developmental delays using DDST-II , neurological deficits , tone and DTR abnormalities over 18 months follow up period . The overall neonatal morbidity in this study was low and comparable in the two groups . Some of the polycythemic babies in the non-exchanged group found initially at 3 months age with " suspected development " grew out of their developmental delay at 18 months of age or later while those who underwent exchange transfusion and with retarded development at 3 months of age remained so even at 18 months of age We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion ( PPET ) would affect hemodynamics as well as outcome . From a routine cord blood hematocrit screening , 71 babies were identified as needing to be tested for polycythemic hyperviscosity . In addition to clinical evaluation , each infant had radial artery hematocrit and viscosity determinations , blood gas determinations , cerebral blood flow velocity studies , cranial ultrasonography , and noninvasive intracranial pressure determination . Babies with symptomatic hyperviscosity ( n = 17 ) were treated by PPET , whereas those with asymptomatic hyperviscosity ( n = 28 ) were r and omly selected to have PPET ( n = 14 ) or to be observed ( n = 14 ) . The remaining babies ( n = 26 ) with normal viscosity served as control subjects . Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed . Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity , whereas those who had no symptoms had normal results on Doppler studies at the outset , and no significant changes occurred with either PPET or observation . There were two deaths in the group with symptoms . A total of 46 babies returned for follow-up evaluation at a mean age of 30 + /- 7.7 months . Outcome of the control group was no better than that of those who had hyperviscosity , and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity , nor between those treated with PPET and those who were only observed . Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET , significantly influenced long-term outcome BACKGROUND Neonatal polycythemia remains a significant clinical problem in Thail and . Partial exchanges transfusion ( PET ) with fresh frozen plasma ( FFP ) has been the mainstay of management for this condition in Thail and . Since FFP is difficult to find in certain areas and can cause concerns of transfusion related diseases , this study was undertaken to investigate the possibility of using plasma substitute and normal saline ( NSS ) for PET in the newborn infant with polycythemia . OBJECTIVE 1 . To compare the rate and duration of decrease of venous hematocrit ( Hct ) before and after PET with FFP , Haemaccel and NSS . 2 . To compare any complications from using FFP , Haemaccel and NSS such as coagulation defect , electrolytes change , etc . in PET . METHODS AND SUBJECTS A r and omized prospect i ve trial was conducted in Neonatal Unit , Department of Pediatrics , Ramathibodi Hospital . The first phase of study : July 1 , 1993 to June 30 , 1994 : r and omized prospect i ve trial using FFP or Haemaccel for PET in 26 newborn infants with polycythemia . The second phase of study : July 1 , 1994 to June 30 , 1995 : consecutive enrollment trial using NSS for PET in 38 consecutive newborn infants with polycythemia . RESULTS There was significant decrease in Hct in both groups after PET but there was no statistically significant difference in the rate of decrease of Hct . There was no significant difference in biochemical profiles in both groups of infants 24 hours after PET . In the NSS group , there was significant decrease of Hct level after PET . There was no significant change of biochemical profiles and coagulation activity in these patients 24 hours after exchange transfusion . There were 2 patients with complications related to umbilical venous catheter and PET . CONCLUSION Haemaccel and NSS can be safely used for PET to treat neonatal polycythemia . However , the attending physician should be aware of possible complications related to umbilical venous catheterization and PET The neurologic outcome of 23 seven-year old children who had cord blood hyperviscosity was compared with that of children with normal cord blood viscosity in a r and omised , controlled and blinded study . Viscosity was measured using a coaxial narrow-gap couette viscometer . Sixteen ( 69.6 % ) of the children with hyperviscous cord blood had a disability ; this incidence being three times greater ( 22.7 % ) than in children whose cord blood was not hyperviscous ( P < 0.01 ) . In three children with cord-blood hyperviscosity , the disability was severe . No child had a severe disability with normal cord blood viscosity . Of the eight children whose cord blood was hyperviscous , but not polycythemic , six ( 75.0 % ) had a disability and in one child the disability was severe . These results demonstrate an association between cord blood hyperviscosity and later neurologic development . Cord studies are non-invasive and result in the rapid diagnosis of the neonatal hyperviscosity syndrome , so allowing earlier treatment . This may be crucial in altering the effects of hyperviscosity on the developing brain in the early neonatal period . Because the neurologic outcome of children was similar whether polycythemia was present or not , the prime factor was the viscosity and not the hematocrit level . We suggest it may be necessary to perform cord blood viscosity studies routinely We tested whether crystalliod solutions could be used instead of colloid solutions for partial exchange transfusions ( PET ) in polycythaemic neonates because crystalloid solutions are cheap , carry no risk of anaphylactic reactions and can be sterilized . We r and omly assigned 20 term neonates with venous haematocrit (Hct)>0.65 l/l to PET with either a serum preparation ( BISEKO ) or Ringer solution . Plasma volume ( PV ) was measured with Evans blue dilution . Blood volume ( BV ) and red cell mass were calculated from PV and venous Hct . Before PET both serum and Ringer groups had the same Hct ( 0.69 ( 0.66–0.76 ) vs 0.69 ( 0.66–0.71 ) l/l ; median ( range ) ) and BV ( 108 ( 81–116 ) versus 96 ( 68–121 ) ml/kg . During PET an equivalent amount of blood was withdrawn stepwise ( 19 ( 14–26 ) versus 17 ( 13–25 ) ml/kg and replaced by either serum or Ringer solution . More of the Ringer solution ( median 77 % ) than of the serum ( median 36 % ) given left the intravascular space within 4 h after PET ( P=0.016 ) ; but there was no signficant difference in Hct after Ringer-PET compared to serum-PET ( median 0.58 vs 0.56 l/l ) . No infant required repeat PET . Ringer-PET reduced BV from high to normal values ( from median 96 to 83 ml/kg;P=0.005 ) , whereas after serum-PET BV remained high ( from median 108 to 98 ml/kg ; not significant ) . Conclusion PET with Ringer solution result ed in a haemodilution comparable to PET with serum and a correction of hypervolaemia AIM To compare the efficacy of using isotonic saline ( crystalloid ) or 5 % albumin ( colloid ) as replacement fluid in partial exchange transfusion ( PET ) for the treatment of neonatal polycythaemia . METHODS One hundred and two polycythaemic full term infants were r and omly allocated to receive PET with either isotonic saline or 5 % albumin . The criteria for PET were : ( a ) venous haematocrit ⩾ 0.7 ; or ( b ) venous haematocrit 0.65 - 0.69 with symptoms or signs attributable to polycythaemia . RESULTS PET with either saline ( n=53 ) or 5 % albumin ( n=50 ) result ed in a significant and sustained decline in haematocrit up to 24 hours after PET . Although the immediate haemodilution effect of isotonic saline was statistically smaller than that of 5 % albumin ( decline in haematocrit 19.3 % vs22.8 % of pre-PET value ) , the difference was too small to be of any clinical significance , and the haematocrit at 4 or 24 hours after PET did not differ significantly between the two groups . PET with either replacement fluid was not associated with any complication . The serum sodium and potassium concentrations were not significantly affected by the PET in either group . CONCLUSIONS Both isotonic saline and 5 % albumin are effective when used as replacement fluid in PET for the treatment of neonatal polycythaemia . Isotonic saline , which is cheaper and free of infection , should be the replacement fluid of choice Necrotizing enterocolitis is uncommon among term infants . In this group , necrotizing enterocolitis has been associated with two risk factors : polycythemia and umbilical catheterization . During a r and omized trial of partial plasma exchange transfusion for treatment of polycythemia , an increased risk of gastrointestinal problems was noted . Eight hyperviscous patients treated with partial plasma exchange transfusion , no symptomatically treated patients , and no control infants developed typical necrotizing enterocolitis ( blood in the stools , pneumatosis , and systemic signs ) . The incidence of necrotizing enterocolitis was significantly greater among patients treated with exchange transfusion compared with patients treated symptomatically or control subjects ( P less than .001 ) The objective of this observational study was to determine the relationship between tobacco smoking during pregnancy and neonatal Polycythaemia , and to assess the dose-response relationship . Thirty two pregnant women who smoked tobacco ( cases ) , and ninety pregnant women who did not smoke ( controls ) , were r and omly selected from the annual obstetrics population in the Erinville hospital in Cork . This study was carried out over eighteen months and the subjects were seen three times , at 28 , 32 , and 36 weeks gestation . At each visit , a smokalyser test was preformed and the results were recorded . The subjects were also given charts to fill in the number of cigarettes they smoked each day for the four week period . Nicotine consumption milligrams per day was calculated depending on the br and they smoked . Finally , at labour , cord blood sample s were obtained and sent for haemoglobin and haematocrit estimation . At the end of the study it was found that both cord blood haemoglobin and haematocrit were statistically significantly higher in smoking mothers , p < 0.01 and p < 0.001 respectively . The dose-response relationship was also statistically significant |
2,471 | 20,238,344 | Treatment outcome was significantly better for patients receiving the combined treatment ( Figures 4 to 6 ) .
The limited number of patients available for analysis , method ological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to st and ard radiotherapy .
However , available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity | BACKGROUND Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells .
It was introduced into clinical oncology practice several decades ago .
Positive clinical results , mostly obtained in single institutions , result ed in clinical implementation albeit in a limited number of cancer centres worldwide .
Because large scale r and omised clinical trials ( RCTs ) are lacking , firm conclusions can not be drawn regarding its definitive role as an adjunct to radiotherapy in the treatment of locally advanced cervix carcinoma ( LACC ) .
OBJECTIVES To assess whether adding hyperthermia to st and ard radiotherapy for LACC has an impact on ( 1 ) local tumour control , ( 2 ) survival and ( 3 ) treatment related morbidity . | From November 1977 to July 1981 , 441 patients with cervical carcinoma were r and omized between pelvic irradiation and pelvic and para-aortic irradiation . Included were patients with stage I and IIB with proximal vaginal and /or parametrial involvement with positive pelvic lymph nodes either on lymphangiogram or at surgery , and stage IIB with distal vaginal and /or parametrial involvement and III regardless of pelvic node status on lymphangiogram . Patients with clinical ly or surgically involved para-aortic nodes were not included . The external beam dose to the para-aortic area was fixed at 45 Gy . There was no statistically significant difference between the two treatment arms in terms of local control , overall distant metastases and survival with no evidence of disease ( NED ) , although the incidence of para-aortic metastases and distant metastases without tumor at pelvic sites was significantly higher in patients receiving pelvic irradiation alone ( pelvic group ) . The 4-year NED survival rate was 51 % . The incidence of severe digestive complications was significantly higher in patients receiving para-aortic irradiation ( para-aortic group ) . Routine para-aortic irradiation for all high risk patients with cervical carcinoma is of limited value , but patients with a high probability of local control can benefit from extended field irradiation , despite an increase in severe digestive complications Experimental evidence suggests that the hypoxic fraction in a solid tumor may increase its malignant potential and reduce its sensitivity towards non-surgical treatment modalities ( e.g. st and ard irradiation , certain anticancer agents ) . However , the clinical importance of tumor hypoxia remains uncertain since valid methods for the routine measurement of intratumoral O2-tensions in patients have so far been lacking . A clinical ly applicable st and ardized procedure has been established which enables the determination of intratumoral oxygen tensions in advanced cervical cancers by use of a computerized polarographic needle electrode histography system . Tumor oxygenation as measured by this method represents a novel tumor feature which can be individually determined for each tumor and which is independent from other known oncological parameters . The results of an interim analysis of an open prospect i ve clinical trial to evaluate the prognostic significance of tumor oxygenation based on the survival data of the first 31 patients are presented . Fifteen patients have been treated by primary radiation , 11 patients received multimodality therapy including irradiation . After a median follow-up of 19 months ( range 5 - 31 months ) , Kaplan-Meier-life table analysis showed significantly lower survival and recurrence-free survival for patients with a median pO2 of < or = 10 mmHg compared to those with better oxygenated tumors ( median pO2 > 10 mmHg ) . The Cox proportional hazards model revealed that the median pO2 and the clinical stage according to the FIGO are independent , highly significant predictors of survival and recurrence-free survival . We conclude from these preliminary results that tumor oxygenation as determined with this st and ardized procedure appears to be a new independent prognostic factor influencing survival in advanced cancer of the uterine cervix PURPOSE To test the hypothesis that cisplatin ( CDDP ) administered concurrently with st and ard radiotherapy ( RT ) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix . PATIENTS AND METHODS A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were r and omized to receive RT ( external-beam RT plus brachytherapy ) plus weekly CDDP chemotherapy ( 40 mg/m(2 ) ) ( arm 1 ) or the same RT without chemotherapy ( arm 2 ) . RESULTS A total of 253 patients were available for analysis . Median follow-up was 82 months . No significant difference was found in progression-free survival ( P = .33 ) . No significant difference in 3- and 5-year survival rates was found ( 69 % v 66 % and 62 % v 58 % , respectively ; P = .42 ) . The hazard ratio for survival ( arm 2 to arm 1 ) was 1.10 ( 95 % confidence interval , 0.75 to 1.62 ) . CONCLUSION This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2 ) to radical RT as given in this trial . Careful attention to RT details is important for achieving optimum outcome for patients with this disease Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin‐containing chemotherapy . It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin . In the current study , the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma PURPOSE To assess the impact of tumor size and extent , and dose of irradiation on pelvic tumor control , incidence of distant metastases , and disease-free survival in carcinoma of the uterine cervix . METHODS AND MATERIAL S Records were review ed of 1499 patients ( Stages IA-IVA ) treated with definitive irradiation ( combination of external beam plus two intracavitary insertions to deliver doses of 65 - 95 Gy to point A , depending on stage and tumor volume ) . Follow-up was obtained in 98 % of patients ( median 11 years , minimum 3 years , maximum 30 years ) . The relationship between outcome and tumor size was analyzed in each stage . Pelvic tumor control was correlated with total doses to point A and to the lateral pelvic wall . RESULTS The 10-year actuarial pelvic failure rate in Stage IB was 5 % for tumors < 2 cm , 15 % for 2.1 - 5 cm , and 35 % for tumors > 5 cm ( p = 0.01 ) ; in Stage IIA , the rates were 0 % , 28 % , and 25 % , respectively ( p = 0.12 ) . Stage IIB unilateral or bilateral nonbulky tumors < 5 cm had a 23 % pelvic failure rate compared with 34 % for unilateral or bilateral bulky tumors > 5 cm ( p = 0.13 ) . In Stage IIB , pelvic failures were 18 % with medial parametrial involvement only , compared with 28 % when tumor extended into the lateral parametrium ( p = 0.05 ) . In Stage III , unilateral parametrial involvement was associated with a 32 % pelvic failure rate versus 50 % for bilateral extension ( p < 0.01 ) . Ten-year disease-free survival rates were 90 % for IB tumors < 2 cm , 76 % for 2.1 - 4 cm , 61 % for 4.1 - 5 cm , and 47 % for > 5 cm ( p = 0.01 ) ; in Stage IIA , the rates were 93 % , 63 % , 39 % , and 59 % , respectively ( p < or = 0.01 ) . Patients with Stage IIB medial parametrial involvement had better 10-year disease-free survival ( 67 % ) than those with lateral parametrial extension ( 56 % ) ( p = 0.02 ) . Stage III patients with unilateral tumor extension had a 48 % 10-year disease-free survival rate compared with 32 % for bilateral parametrial involvement ( p < or = 0.01 ) . The presence of endometrial extension or tumor only in the endometrial curettings had no significant impact on pelvic failure . However , in patients with Stage IB disease , the incidence of distant metastases was 31 % with positive curettings , 15 % with negative curettings , and 22 % with admixture ( p < or = 0.01 ) . In Stage IIA , the corresponding values were 51 % , 33 % , and 18 % ( p = 0.05 ) . The 10-year disease-free survival rates in Stage IB were 67 % with positive curettings , 81 % for negative curettings , and 77 % for admixture ( p = 0.02 ) ; in Stage IIA , the rates were 45 % , 66 % , and 67 % , respectively ( p = 0.14 ) . Because this is not a prospect i ve Phase II dose-escalation study , the correlation of doses of irradiation with pelvic tumor control in the various stages and tumor size groups is not consistent . Nevertheless , with Stage IB and IIA tumors < 2 cm in diameter , the pelvic failure rate was under 10 % with doses of 70 - 80 Gy to point A , whereas for larger lesions even doses of 85 - 90 Gy result ed in 25 % to 37 % pelvic failure rates . In Stage IIB with doses of 70 Gy to point A , the pelvic failure rate was about 50 % compared with about 20 % in nonbulky and 30 % in bulky tumors with doses > 80 Gy . In Stage III unilateral lesions , the pelvic failure rate was about 50 % with < or = 70 Gy to point A versus 35 % with higher doses , and in bilateral or bulky tumors it was 60 % with doses < 70 Gy and 50 % with higher doses . CONCLUSIONS Clinical stage and size of tumor are critical factors in prognosis , therapy efficacy , and evaluation of results in carcinoma of the uterine cervix . The doses to point A suggest that for lesions < 2 cm , doses of 75 Gy result in < or = 10 % pelvic failures , whereas in more extensive lesions , even with doses of 85 Gy , the pelvic failure rate is about 30 % ; and in Stage IIB-III tumors , doses of 85 Gy result in 35 - 50 % pelvic failures . Refinements in brachytherapy techniques and /or use of agents to selectively sensitize the tumors to irradiation will be necessary to improve the present results in invasive carcinoma of Background In the United Kingdom ( UK ) , there is an extensive market for the class ' A ' drug heroin . Many heroin users spend time in prison . People addicted to heroin often require prescribed medication when attempting to cease their drug use . The most commonly used detoxification agents in UK prisons are buprenorphine , dihydrocodeine and methadone . However , national guidelines do not state a detoxification drug of choice . Indeed , there is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons . This study seeks to address the paucity by evaluating routinely used interventions amongst drug using prisoners within UK prisons . Methods / Design The Leeds Evaluation of Efficacy of Detoxification Study ( LEEDS ) Prisons Pilot Study will use r and omised controlled trial methodology to compare the open use of buprenorphine and dihydrocodeine for opiate detoxification , given in the context of routine care , within HMP Leeds . Prisoners who are eligible and give informed consent will be entered into the trial . The primary outcome measure will be abstinence status at five days post detoxification , as determined by a urine test . Secondary outcomes during the detoxification and then at one , three and six months post detoxification will be recorded Summary We investigated the feasibility and the anti-tumour activity of weekly cisplatin and the simultaneous application of local hyperthermia in patients with a pelvic recurrence of cervical cancer in previously irradiated area . Dose levels of cisplatin 60 mg m–2 , 70 mg m–2 and 80 mg m–2 were studied . Treatment objective of hyperthermia was the achievement of a tumour temperature of ≥ 42 ° for 60 min , during cisplatin administration . The protocol advised six weekly cycles of combined treatment . Nineteen patients , median age 47 years ( range 26–71 ) , were treated . A total of 89 cycles of combined treatment were administered . Even at the highest dose level of cisplatin , 80 mg m–2 weekly , no dose-limiting toxicity was observed . Leucocytopenia at scheduled retreatment result ed in 1 or 2 weeks postponement in five cases . Neurotoxicity and renal toxicity were mild or absent . Maximum tumour temperatures achieved ranged 39.7–43.6 ° C , mean 41.6 ± 0.7 ° C . All 19 patients were evaluable for response . One patient achieved a complete response that lasted 20 months , and nine patients achieved a partial response for a median duration of 6 months ( range 4–50 + months ) , for an overall response rate of 53 % . One patient subsequently underwent salvage surgery and currently remains free of disease at 4 years . We found that this combined hyperthermia- dose-intensive cisplatin regimen was well-tolerated . The true impact of the combination of cisplatin and locoregional hyperthermia can only be answered in a r and omized study . Nonetheless , based on existing data on the poor efficacy of cisplatin in pelvic recurrent cervical cancer , we believe that the combined modality approach of weekly hyperthermia plus dose-intensive cisplatin is an attractive regimen , particularly if subsequent salvage surgery is available PURPOSE The local failure rate in patients with locoregionally advanced cervical cancer is 41 - 72 % after radiotherapy ( RT ) alone , whereas local control is a prerequisite for cure . The Dutch Deep Hyperthermia Trial showed that combining RT with hyperthermia ( HT ) improved 3-year local control rates of 41 - 61 % , as we reported earlier . In this study , we evaluate long-term results of the Dutch Deep Hyperthermia Trial after 12 years of follow-up . METHODS AND MATERIAL S From 1990 to 1996 , a total of 114 women with locoregionally advanced cervical carcinoma were r and omly assigned to RT or RT+HT . The RT was applied to a median total dose of 68 Gy . The HT was given once weekly . The primary end point was local control . Secondary end points were overall survival and late toxicity . RESULTS At the 12-year follow-up , local control remained better in the RT+HT group ( 37 % vs. 56 % ; p=0.01 ) . Survival was persistently better after 12 years : 20 % ( RT ) and 37 % ( RT+HT ; p=0.03 ) . World Health Organization ( WHO ) performance status was a significant prognostic factor for local control . The WHO performance status , International Federation of Gynaecology and Obstetrics ( FIGO ) stage , and tumor diameter were significant for survival . The benefit of HT remained significant after correction for these factors . European Organization for Research and Treatment of Cancer Grade 3 or higher radiation-induced late toxicities were similar in both groups . CONCLUSIONS For locoregionally advanced cervical cancer , the addition of HT to RT result ed in long-term major improvement in local control and survival without increasing late toxicity . This combined treatment should be considered for patients who are unfit to receive chemotherapy . For other patients , the optimal treatment strategy is the subject of ongoing research BACKGROUND AND METHODS On behalf of the Gynecologic Oncology Group , we performed a r and omized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone ; cisplatin , fluorouracil , and hydroxyurea ; and hydroxyurea alone -- in patients with locally advanced cervical cancer . Women with primary untreated invasive squamous-cell carcinoma , adenosquamous carcinoma , or adenocarcinoma of the cervix of stage IIB , III , or IVA , without involvement of the para-aortic lymph nodes , were enrolled . The patients had to have a leukocyte count of at least 3000 per cubic millimeter , a platelet count of at least 100,000 per cubic millimeter , a serum creatinine level no higher than 2 mg per deciliter ( 177 micromol per liter ) , and adequate hepatic function . All patients received external-beam radiotherapy according to a strict protocol . Patients were r and omly assigned to receive one of three chemotherapy regimens : 40 mg of cisplatin per square meter of body-surface area per week for six weeks ( group 1 ) ; 50 mg of cisplatin per square meter on days 1 and 29 , followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29 , and 2 g of oral hydroxyurea per square meter twice weekly for six weeks ( group 2 ) ; or 3 g of oral hydroxyurea per square meter twice weekly for six weeks ( group 3 ) . RESULTS The analysis included 526 women . The median duration of follow-up was 35 months . Both groups that received cisplatin had a higher rate of progression-free survival than the group that received hydroxyurea alone ( P<0.001 for both comparisons ) . The relative risks of progression of disease or death were 0.57 ( 95 percent confidence interval , 0.42 to 0.78 ) in group 1 and 0.55 ( 95 percent confidence interval , 0.40 to 0.75 ) in group 2 , as compared with group 3 . The overall survival rate was significantly higher in groups 1 and 2 than in group 3 , with relative risks of death of 0.61 ( 95 percent confidence interval , 0.44 to 0.85 ) and 0.58 ( 95 percent confidence interval , 0.41 to 0.81 ) , respectively . CONCLUSIONS Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer BACKGROUND Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers . For the Gynecologic Oncology Group , we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer . METHODS Women with bulky stage IB cervical cancers ( tumor , > or = 4 cm in diameter ) were r and omly assigned to receive radiotherapy alone or in combination with cisplatin ( 40 mg per square meter of body-surface area once a week for up to six doses ; maximal weekly dose , 70 mg ) , followed in all patients by adjuvant hysterectomy . Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement . The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A ( cervical parametrium ) and 55 Gy to point B ( pelvic wall ) . Cisplatin was given during external radiotherapy , and adjuvant hysterectomy was performed three to six weeks later . RESULTS The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin , as compared with the 186 women assigned to receive radiotherapy alone , were 0.51 ( 95 percent confidence interval , 0.34 to 0.75 ) and 0.54 ( 95 percent confidence interval , 0.34 to 0.86 ) , respectively . The rates of both progression-free survival ( P<0.001 ) and overall survival ( P=0.008 ) were significantly higher in the combined-therapy group at four years . In the combined-therapy group there were higher frequencies of transient grade 3 ( moderate ) and grade 4 ( severe ) adverse hematologic effects ( 21 percent , vs. 2 percent in the radiotherapy group ) and adverse gastrointestinal effects ( 14 percent vs. 5 percent ) . CONCLUSIONS Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers PURPOSE In 1986 , a protocol comparing primary radiation therapy ( RT ) plus hydroxyurea ( HU ) to irradiation plus fluorouracil ( 5-FU ) and cisplatin ( CF ) was activated by the Gynecologic Oncology Group ( GOG ) for the treatment of patients with locally advanced cervical carcinoma . The goals were to determine the superior chemoradiation regimen and to quantitate the relative toxicities . METHODS All patients had biopsy-proven invasive squamous cell carcinoma , adenocarcinoma , or adenosquamous carcinoma of the uterine cervix . Patients underwent st and ard clinical staging studies and their tumors were found to be International Federation of Gynaecology and Obstetrics stages IIB , III , or IVA . Negative cytologic washings and para-aortic lymph nodes were required for entry . Patients were r and omized to receive either st and ard whole pelvic RT with concurrent 5-FU infusion and bolus CF or the same RT plus oral HU . RESULTS Of 388 r and omized patients , 368 were eligible ; 177 were r and omized to CF and 191 to HU . Adverse effects were predominantly hematologic or gastrointestinal in both regimens . Severe or life-threatening leukopenia was more common in the HU group ( 24 % ) than in the CF group ( 4 % ) . The difference in progression-free survival ( PFS ) was statistically significant in favor of the CF group ( P = .033 ) . The sites of progression in the two treatment groups were not substantially different . Survival was significantly better for the patients r and omized to CF ( P = .018 ) . CONCLUSION This study demonstrates that for patients with locally advanced carcinoma of the cervix , the combination of 5-FU and CF with RT offers patients better PFS and overall survival than HU , and with manageable toxicity The results from experimental studies indicate that hyperthermia is both an effective complementary treatment to , and a strong sensitiser of , radiotherapy and many cytotoxic drugs . Since the first international hyperthermia conference in 1975 , Washington DC , techniques to increase tumour temperature have been developed and tested clinical ly . Hyperthermia can be applied by several methods : local hyperthermia by external or internal energy sources , perfusion hyperthermia of organs , limbs , or body cavities , and whole body hyperthermia . The clinical value of hyperthermia in combination with other treatment modalities has been shown by r and omised trials . Significant improvement in clinical outcome has been demonstrated for tumours of the head and neck , breast , brain , bladder , cervix , rectum , lung , oesophagus , for melanoma and sarcoma . The addition of hyperthermia result ed in remarkably higher ( complete ) response rates , accompanied by improved local tumour control rates , better palliative effects , and /or better overall survival rates . Toxicity from hyperthermia can not always be avoided , but is usually of limited clinical relevance . In spite of these good clinical results , hyperthermia has received little attention . Problems with acceptance concern the limited availability of equipment , the lack of awareness concerning clinical results , and the lack of financial re sources . In this paper the most relevant literature describing the clinical effects of hyperthermia is review ed and discussed , and means to overcome the lack of awareness and use of this modality is described PURPOSE Hyperthermia can be used to enhance the effects of radiation , and a combined treatment may , in some circumstances , be an advantage . Uterine cervical cancer is very common in developing countries . The control of locally advanced pelvic tumors is difficult with conventional treatment modalities . Based upon the biologic rationale and in view of the recent advances in heating and thermometry techniques , radiotherapy in combination with hyperthermia was investigated in a multi-institutional prospect i ve r and omized trial sponsored by the International Atomic Energy Agency . The primary purpose was to clarify whether the combination of hyperthermia and radiotherapy improves the rate of local control , compared with radiotherapy alone . METHODS AND MATERIAL S A total of 110 patients with biopsy-proven , locally advanced carcinoma of the uterine cervix were r and omized to treatment by radiotherapy with or without hyperthermia . The patients were stratified by institution , stage , and histologic type . Each patient received external beam radiation therapy and brachytherapy . For the patients r and omized to receive hyperthermia , a minimum of five sessions ( 60 min each , once per week ) were administered , employing a radiofrequency ( RF ) capacitive heating device . Intratumoral temperature was measured at the first hyperthermic treatment , and at least once more during the course of treatment . The equipment and the policies and procedures at each participating institution except one ( Pusan ) were personally inspected at least once by the corresponding author , to ensure that quality assurance procedures were in place and were followed for treatment according to the protocol guidelines . The median follow-up period was 466 days for all the patients and 512 days for the surviving patients . RESULTS The two arms were well balanced with regard to the patient factors , tumor factors , and treatment factors . The overall survival rate at 3 years was 73.2 % , and the local control rate was 68.5 % . There were no significant differences between the patients treated with or without hyperthermia , either with regard to the survival ( p = 0.1893 ) or the rate of local control ( p = 0.58 ) . The survival was significantly worse among the patients with Stage IIb disease who received hyperthermia ( p = 0.0162 ) although there was no difference in their rate of local control ( p = 0.7988 ) . Further analysis is necessary to determine if the difference in survival is due to a greater incidence of distant metastases or some other cause . Acute Grade 2 - 3 toxicity was seen in 10/55 patients ( 18 % ) treated by hyperthermia and in 2/55 of the patients ( 4 % ) treated without hyperthermia ( p = 0.01 ) . There was no significant difference in the late toxicity observed in the two arms . CONCLUSION This prospect i ve r and omized study failed to show any benefit from the addition of hyperthermia to radiotherapy in the treatment of locally advanced carcinoma of the uterine cervix . The acute toxicity was significantly greater among the patients receiving hyperthermia , and the survival was significantly worse among the Stage IIb patients receiving hyperthermia even though there was no difference in the local control rate The biologic rationale for combining cisplatin with locoregional hyperthermia ( HT ) relates to the potentiating effect of HT on cisplatin cytotoxicity BACKGROUND AND METHODS We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer . Between 1990 and 1997 , 403 women with advanced cervical cancer confined to the pelvis ( stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes ) were r and omly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin ( days 1 through 5 and days 22 through 26 of radiation ) . Patients were then to receive one or two applications of low-dose-rate intracavitary radiation , with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group . RESULTS Of the 403 eligible patients , 193 in each group could be evaluated . The median duration of follow-up was 43 months . Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone ( P=0.004 ) . Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group ( P<0.001 ) . The rates of both distant metastases ( P<0.001 ) and locoregional recurrences ( P<0.001 ) were significantly higher among patients treated with radiotherapy alone . The seriousness of side effects was similar in the two groups , with a higher rate of reversible hematologic effects in the combined-therapy group . CONCLUSIONS The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer A clinical trial was performed to investigate the efficacy of hyperthermia in combination with chemotherapy for gynecological malignancies . Sixty-nine patients with vaginal or vulvar malignancies ( 9 primary vulvar , 3 recurrent vulvar , 11 primary vaginal , 4 primary cervical , 40 recurrent cervical , and 2 recurrent ovarian carcinomas ) were treated by thermochemotherapy ( 42 cases ) or chemotherapy alone ( 27 cases ) . After treatment , 7 patients underwent surgery and 46 patients irradiation . The chemotherapeutic schedule was mainly a combination therapy with bleomycin and mitomycin C ( B-M ) . Microwaves of 2.45 GHz were applied to induce local hyperthermia . The side effects of chemotherapy were not increased by hyperthermia . The rate of partial response plus complete response increased to 84 % ( 16/19 ) in primary cancers and 45 % in recurrent cancers by hyperthermia , compared to the respective values of 40 % ( 2/5 ) and 17 % ( 3/17 ) for chemotherapy alone . However , a satisfactory prognosis can not be expected with thermochemotherapy , unless additional treatments are performed . Subsequent surgery or radiation treatment improved the progression-free interval BACKGROUND AND PURPOSE Hypoxia appears to be an important factor in predicting tumor relapse following radiation therapy . This study measured oxygenation prior to treatment in patients with cervix cancer using a polarographic oxygen electrode to determine if oxygenation was an important prognostic factor with regard to tumor control and survival . MATERIAL S AND METHODS Between May 1994 and June 1997 , 74 eligible patients with cervix cancer were entered into an ongoing prospect i ve study of tumor oxygenation prior to primary radiation therapy . All patients were evaluated with an Eppendorf oxygen electrode during examination under anesthesia . Oxygenation data are presented as the hypoxic proportion , defined as the percentage of pO2 readings of < 5 mm Hg ( abbreviated as HP5 ) . RESULTS The HP5 ranged from 2 to 99 % with a median of 52 % . With a median follow-up of 1.2 years , the disease-free survival ( DFS ) rate was 69 % for patients with HP5 of < or = 50 % compared with 34 % for those with HP5 of > 50 % ( log-rank P = 0.02 ) . Tumor size above and below the median of 5 cm was also significantly related to DFS ( P = 0.0003 ) and patients with bulky hypoxic tumors had a significantly lower DFS ( 12 % at 2 years ) than either bulky oxygenated or non-bulky oxygenated or hypoxic tumors ( 65 % , P = 0.0001 ) . CONCLUSIONS Hypoxia and tumor size are significant adverse prognostic factors in a univariate analysis of disease-free survival in patients with cervix cancer . A high risk group of patients with bulky hypoxic tumors have a significantly higher probability of relapse and death To clarify the role of thermoradiotherapy for FIGO Stage IIIB cervical carcinomas , both the clinical response and survival of patients treated with radio- or thermoradiotherapy were investigated . Forty patients with Stage IIIB uterine cervix carcinoma were treated with external beam irradiation to the pelvis , combined with iridium 192 high-dose-rate intracavitary brachytherapy . All patients were divided r and omly into the following two groups : the radiotherapy ( RT ) group of 20 patients , who underwent radiotherapy alone ; and the thermoradiotherapy ( TRT ) group of 20 patients , who underwent three sessions of hyper-thermia in addition to radiotherapy . The primary endpoint of this study was local complete response and survival . A complete response was achieved in 50 % ( 10 of 20 ) in the RT group versus 80 % ( 16 of 20 ) in the TRT group ( p = 0.048 ) . The 3-year overall survival and disease-free survival of the patients who were treated with TRT ( 58.2 and 63.6 % ) were better than those of the patients treated with RT ( 48.1 and 45 % ) , but these differences were not significant . The 3-year local relapse-free survival of the patients who were treated with TRT ( 79.7 % ) was significantly better than that of the patients treated with RT ( 48.5 % ) ( p = 0.048 ) . TRT , as delivered in this trial , was well tolerated and did not significantly add to either the relevant clinical acute or long-term toxicity over radiation alone . TRT result ed in a better treatment response and 3-year local relapse-free survival rate than RT for patients with FIGO Stage IIIB cervical carcinoma OBJECTIVES To investigate whether irradiation to the st and ard pelvic field only improves the response rate and survival in comparison with pelvic plus para-aortic irradiation in patients with high-risk cervical carcinoma , and to investigate patterns of failure and treatment-related toxicity . DESIGN R and omized controlled trial from November 1979 to October 1986 , with stratification by histology , para-aortic nodal status , and International Federation of Gynecology and Obstetrics ( FIGO ) stage . SETTING Radiation Therapy Oncology Group ( RTOG ) multicenter clinical trial . PATIENTS A total of 367 patients with FIGO stage IB or IIA primary cervical cancers measuring 4 cm or greater in lateral diameter or with FIGO stage IIB cervical cancers were r and omized to RTOG protocol 79 - 20 to receive either st and ard pelvic only irradiation or pelvic plus para-aortic irradiation . INTERVENTION Pelvic only irradiation consisted of a midplane pelvic dose of 40 to 50 Gy in 4.5 to 6.5 weeks with daily fractions of 1.6 to 1.8 Gy for 5 d/wk . Pelvic plus para-aortic irradiation delivered 44 to 45 Gy in 4.5 to 6.5 weeks with daily fractions of 1.6 to 1.8 Gy for 5 d/wk . A total dose of 4000 to 5000 mg/h of radium equivalent or 30 to 40 Gy was provided by intracavitary brachytherapy to point A. MAIN OUTCOME MEASURES Response rate , overall and disease-free survival , patterns of failure , and treatment-related toxicities . RESULTS Ten-year overall survival was 44 % for the pelvic only irradiation arm and 55 % for the pelvic plus para-aortic irradiation am ( P = .02 ) . Cumulative incidence of death due to cervical cancer was estimated as significantly higher in the pelvic only arm at 10 years ( P = .01 ) . Disease-free survival was similar in both arms ; 40 % for the pelvic only arm and 42 % for the pelvic plus para-aortic arm . Locoregional failures were similar at 10 years for both arms ( pelvic only , 35 % ; pelvic plus para-aortic , 31 % ; P = .44 ) . In complete responders , the patterns of locoregional failures were the same for both arms , but there was a lower cumulative incidence for first distant failure in the pelvic plus para-aortic irradiation arm ( P = .053 ) . Survival following first failure was significantly higher in the pelvic plus para-aortic arm ( P = .007 ) . A higher percentage of local failures were salvaged long-term on the pelvic plus para-aortic arm compared with the pelvic only arm ( 25 % vs 8 % ) . The cumulative incidence of grade 4 and 5 toxicities at 10 years in the pelvic plus para-aortic arm was 8 % , compared with 4 % in the pelvic only arm ( P = .06 ) . The death rate due to radiotherapy complications was higher in the pelvic plus para-aortic arm ( four [ 2 % ] of 170 ) compared with the pelvic only arm ( one [ 1 % ] of 167 ) ( P = .38 ) . The proportion of deaths due to radiotherapy complications in the pelvic plus para-aortic arm was higher than in the pelvic only arm ( four [ 6 % ] of 67 vs one [ 1 % ] of 85 ; P = .24 ) . If the patient had abdominal surgery prior to para-aortic irradiation , the estimated cumulative incidence of grade 4 and 5 complications was 11 % , compared with 2 % in the pelvic only arm . CONCLUSIONS The statistically significant difference in overall survival at 10 years for the pelvic plus para-aortic irradiation arm , without a difference in disease-free survival , can be explained by the following two factors : ( 1 ) a lower incidence of distant failure in complete responders and ( 2 ) a better salvage in the complete responders who later failed locally Between 1977 and 1985 , the Gynecologic Oncology Group ( GOG ) conducted three clinical trials in locally advanced carcinoma of the cervix , clinical Stages I to IVA as classified by the International Federation of Gynecology and Obstetrics ( FIGO ) . All 626 patients had primary carcinoma of the cervix and underwent operative assessment of the para‐aortic ( PA ) lymph nodes . Patients received st and ardized external radiation therapy to the pelvis or to the pelvis and PA lymph nodes followed by one or two brachytherapy applications . To date , no statistically significant differences in progression‐free interval ( PFI ) or survival time have been identified between the r and omization treatment arms on any of these studies . Basic similarities among these studies led us to pool these data to identify patient characterisitcs and tumor characteristics associated with an increased risk of treatment failure . Multi‐variate analysis showed patient age , performance status ( PS ) , PA lymph node status , tumor size , and pelvic node status to be significantly associated with PFI . When modeling for survival , all these factors and clinical stage and bilateral extension were significant Aim The disappointing results for inoperable , advanced tumors of the uterine cervix after conventional radiotherapy alone necessitates improving of radiation therapy . Simultaneous chemotherapy or altered radiation fractionation , such as accelerated regimen , increase acute toxicity and treatment is often difficult to deliver in the planned manner . The purpose of this phase II study was to investigate the toxicity and effectiveness of a combined approach with radiotherapy and regional hyperthermia . Patients and Methods From January 1994 to October 1995 18 patients with advanced carcinomas of the uterine cervix were treated in combination with radiotherpay and hyperthermia . The patients were treated with 6 to 20 MV photons delivered by a linear accelerator in a 4-field-box technique to a total dose of 50.4 Gy in 28 fractions . In the first and fourth week 2 regional hyperthermia treatments were each applied with the Sigma-60 applicator from a BSD-2000 unit . After this a boost to the primary tumor was given with high-dose-rate iridium-192 brachytherapy by an afterloading technique with 4 × 5 Gy at point A to a total of 20 Gy and for the involved parametrium anterioposterior-posterioanterior to 9 Gy in 5 fractions . Results The acute toxicity was low and similar to an external radiotherapy alone treatment . No Grade III/IV acute toxicity was found . The median age was 47 years ( range 34 to 67 years ) . In 16 of 18 patients a rapid tumor regression was observed during combined thermo-radiotherapy , which allowed the use of intracavitary high-dose-rate brachytherapy in these cases . Complete and partial remission were observed in 13 and 4 cases , respectively . One paitent die not respond to the treatment . The median follow-up was 24 months ( range 17 to 36 months ) . The local tumor control rate was 48 % at 2 years . Median T20 , T50 and T90 values were 41.7 ° C ( range 40.3 to 43.2 ° C ) , 41.1 ° C ( range 39.2 to 42.5 ° C ) and 39.9 ° C ( range 37.7 to 41.9 ° C ) , respectively . Cumulative minutes of T90>40 ° C ( Cum40T90 ) and cumulative minutes , which were isoeffective to 43 ° C , were calculated ( CEM43T90 , CEM43T50 , CEM43T20 ) . CEM43T90 was found to be a significant parameter in terms of local tumor control for the 4 hyperthermia treatments ( p=0.019 ) . Conclusion sThis treatment modality has proved to be feasible and well tolerable . The rapid tumor shrinkage in the combined approach of radiotherapy with hyperthermia before beginning brachytherapy seems to be a good prerequisite for improving of the disappointing results in cure of advanced cancer of the uterine cervix . ZusammenfassungZielDie unbefriedigenden Ergebnisse lokal fortgeschrittener , inoperabler Tumoren der Cervix uteri nach konventioneller Strahlentherapie machen eine Intensivierung der Therapie erforderlich . Simultane Chemotherapie oder akzelerierte Fraktionierungsschemata erhöhen meist die akute Toxizität , so daß die Therapie in der geplanten Form nur schwer durchgeführt werden kann . Das Ziel dieser Phase-II-Studie wares , Toxizität und Effektivität der kombinierten Strahlentherapie und regionalen Hyperthermie zu untersuchen . Patienten und Method enVon Januar 1994 bis Oktober 1995 wurden 18 Patientinnen mit lokal fortgeschrittenen Karzinomen der Cervix uteri mit einer kombinierten Strahlentherapie und regionalen Hyperthermie beh and elt . Die Patientinnen wurden mit 6-bis 20-MV-Photonen eines Linearbeschleunigers in einer 4-Felder-Box-Technik bis zu einer Gesamtdosis von 50,4 Gy in 28 Fraktionen bestrahlt . Während der ersten und vierten Woche erfolgten jeweils zwei regionale Hyperthermiebeh and lungen mit dem Sigma-60-Applikator eines BSD-2000-Gerätes . Nach 50,4 Gy wurde ein Brachytherapie-Boost auf den Primärtumor mit HDR-Iridium 192 in Afterloading technik ( 4 × 5 Gy am Punkt A ) bis zu einer Dosis von 20 Gy gegeben . Die initial befallenen Parametrien erhielten eine perkutane Dosiserhöhung um 9 Gy in fünf Fraktionen über ventrodorsale Gegenfelder . ErgebnisseDie akute Toxizität war gering , Nebenwirkungen Grad 3 oder 4 wurden nicht beobachtet . Das mediane Alter betrug 47 Jahre ( Altersspanne 34 bis 67 Jahre ) . Bei 16 von 18 Patientinnen wurde eine rasche Tumorregression während der kombinierten Hyperthermie und Strahlentherapie beobachtet , wodurch die intrakavitäre Brachytherapie in diesen Fällen ermöglicht wurde . Eine komplette Remission wurde in 13 Fällen erreicht , viermal eine partielle Remission , in einem Fall erfolgte keine Reaktion . Die mediane Nachbeobachtungszeit betrug 24 Monate ( 17 bis 36 Monate ) . Nach zwei Jahren waren 48 % der Tumoren lokal kontrolliert . Die medianen T20- , T50-und T90-Werte lagen bei 41,7 ° C ( 40,3 bis 43,2 ° C ) , 41,1 ° C ( 39,2 bis 42,5 ° C ) und 39,9 ° C ( 37,7 bis 41,9 ° C ) . Zusätzlich wurden die kumulativen Minuten der T90-Werte über 40 ° C ( Cum40T90 ) und die kumulativen Minuten , die isoeffektiv zu 43 ° C waren ( CEM43T90 , CEM43T50 , CEM43T20 ) , kalkuliert . Die CEM43T90-Werte für alle vier Hyperthermiebeh and lungen waren ein signifikanter prognostischer Parameter in bezug auf die lokale Tumorkontrolle (p=0,019).Schlußfolgerung enDie beschreibene Therapie erwies sich als durchführbar und gut verträglich . Die gute Tumorregression während der kombinierten Therapie bis zum Beginn der Brachytherapie stellt eine günstige Voraussetzung zur Verbesserung der Heilungsergebnisse dieser lokal fortgeschrittenen Tumoren dar PURPOSE To assess the prognostic value of the pretreatment potential doubling time ( Tpot ) in carcinoma of the uterine cervix , relative to other established clinical factors . METHODS AND MATERIAL S Fifty-two patients with cervical cancer were studied prospect ively from March 1991 to October 1993 . Pretreatment evaluation included examination under anesthesia and tumor biopsy 6 h following the intravenous administration of bromodeoxyuridine ( 200 mg ) . Tpot was determined by deriving the labeling index ( LI ) and S-phase synthesis time ( Ts ) using flow cytometry . Six patients were not evaluable and excluded . The remaining 46 patients ( average age 55 years ) were treated uniformly with radical radiation therapy . There were 39 squamous carcinomas and 7 adenocarcinomas . Fédération Internationale de Gynécologie et d'Obstétrique ( FIGO ) stages were : Ib and IIa , 12 patients ; IIb , 18 patients ; III and IV , 16 patients . The median external beam dose was 50 Gy ( range , 45 - 52.8 Gy ) delivered in 25 fractions . The median intracavitary dose was 40 Gy ( range . 25.5 - 40 Gy ) delivered with a single line source to a point 2 cm lateral of the midline , with a mean dose rate of 0.71 Gy/h . The median overall treatment time was 45 days ( range , 34 - 73 days ) . As of July 31 , 1994 , 12 patients had died of disease , and the average follow-up for alive patients was 1.4 years ( range , 0.5 - 3.3 years ) . RESULTS There were 27 tumors with diploid deoxyribonucleic acid ( DNA ) content and 19 tumors were aneuploid . The median and mean Tpot for the 46 patients were 5.5 and 6.6 days , respectively [ range , 2.0 - 25.6 days ; coefficient of variation ( CV ) , 74 % ] . For 25 patients where Tpot measurements were performed at two separate laboratories , there was a fair correlation ( r = 0.74 ) , but systematic differences were detected suggesting that the lack of agreement was not simply due to intratumoral variation . To date , 30 patients remained disease free , while 8 patients had pelvic failure and 9 patients developed distant metastases as the first failure site ( 1 patient developed both at the same time ) . In univariate analysis , the only significant prognostic factor for disease-free survival was tumor size ( p = 0.004 ) . A short Tpot ( or high LI ) and long overall treatment time ( OTT ) were weakly associated with poorer disease-free survival , although not statistically significant ( 1/Tpot , p = 0.14 ; LI , p = 0.23 ; OTT , p = 0.04 ) . Age , FIGO stage , hemoglobin level , S-phase fraction , DNA ploidy , and Ts were not associated with disease-free survival . Multiple regression analysis was not performed because of the relatively small number of patients and short follow-up . CONCLUSIONS Tpot values determined with current techniques by different laboratories can not be used interchangeably for the purpose of therapy decisions . Vigorous quality assurance and st and ardization of the laboratory procedures and analysis methods are important to reduce interlaboratory variation . In this uniformly treated group of patients with cancer of the uterine cervix , traditional clinical prognostic factors remain the most important . Preliminary data suggest that the flow cytometry-determined Tpot and labeling index predict for disease-free survival , although a larger number of patients with longer follow-up is required to assess the true prognostic significance of these assays and to determine if their effect is independent of other clinical factors |
2,472 | 24,314,854 | Adding an active intervention to usual continuing care seems to improve treatment outcomes . | BACKGROUND A chronic care perspective should be adopted in the treatment of patients with alcohol use disorders ( AUDs ) .
Initial treatment in a more intense psychiatric care setting should be followed by continuing care .
This systematic review aims to identify effective continuing care interventions for patients with AUDs . | CONTEXT The prevalence of medical disorders is high among substance abuse patients , yet medical services are seldom provided in coordination with substance abuse treatment . OBJECTIVE To examine differences in treatment outcomes and costs between integrated and independent models of medical and substance abuse care as well as the effect of integrated care in a subgroup of patients with substance abuse-related medical conditions ( SAMCs ) . DESIGN R and omized controlled trial conducted between April 1997 and December 1998 . SETTING AND PATIENTS Adult men and women ( n = 592 ) who were admitted to a large health maintenance organization chemical dependency program in Sacramento , Calif. INTERVENTIONS Patients were r and omly assigned to receive treatment through an integrated model , in which primary health care was included within the addiction treatment program ( n = 285 ) , or an independent treatment-as-usual model , in which primary care and substance abuse treatment were provided separately ( n = 307 ) . Both programs were group based and lasted 8 weeks , with 10 months of aftercare available . MAIN OUTCOME MEASURES Abstinence outcomes , treatment utilization , and costs 6 months after r and omization . RESULTS Both groups showed improvement on all drug and alcohol measures . Overall , there were no differences in total abstinence rates between the integrated care and independent care groups ( 68 % vs 63 % , P = .18 ) . For patients without SAMCs , there were also no differences in abstinence rates ( integrated care , 66 % vs independent care , 73 % ; P = .23 ) and there was a slight but nonsignificant trend of higher costs for the integrated care group ( $ 367.96 vs $ 324.09 , P = .19 ) . However , patients with SAMCs ( n = 341 ) were more likely to be abstinent in the integrated care group than the independent care group ( 69 % vs 55 % , P = .006 ; odds ratio [ OR ] , 1.90 ; 95 % confidence interval [ CI ] , 1.22 - 2.97 ) . This was true for both those with medical ( OR , 3.38 ; 95 % CI , 1.68 - 6.80 ) and psychiatric ( OR , 2.10 ; 95 % CI , 1.04 - 4.25 ) SAMCs . Patients with SAMCs had a slight but nonsignificant trend of higher costs in the integrated care group ( $ 470.81 vs $ 427.95 , P = .14 ) . The incremental cost-effectiveness ratio per additional abstinent patient with an SAMC in the integrated care group was $ 1581 . CONCLUSIONS Individuals with SAMCs benefit from integrated medical and substance abuse treatment , and such an approach can be cost-effective . These findings are relevant given the high prevalence and cost of medical conditions among substance abuse patients , new developments in medications for addiction , and recent legislation on parity of substance abuse with other medical benefits OBJECTIVE This article examines client drinking and related psychosocial functioning during the course of alcoholism treatment . It focuses on ( 1 ) the main effects of the three Project MATCH treatments , ( 2 ) the prognostic value of client attributes employed in the matching hypotheses , and ( 3 ) the attribute by treatment interaction effects . METHOD Clients recruited from outpatient setting s ( n = 952 ) or from aftercare setting s ( n = 774 ) were r and omized to one of the following treatments : Motivational Enhancement Therapy ( MET ) , Cognitive Behavioral Therapy ( CBT ) and Twelve-Step Facilitation ( TSF ) . Alcohol consumption and psychosocial functioning during treatment were assessed at the end of the 12-week treatment phase . RESULTS During the treatment phase , small but statistically significant differences among treatments were found only in the outpatient arm on measures of alcohol consumption and alcohol-related negative consequences . Forty-one percent ( 41 % ) of CBT and TSF clients were abstinent or drank moderately without alcohol-related consequences , compared with 28 % of MET clients . Tests of 10 a priori primary client-treatment matching hypotheses failed to find any interaction effects that had an impact on drinking throughout the treatment phase . CONCLUSIONS In the outpatient setting there appears to be a temporary advantage to assigning individuals to CBT or TSF rather than MET . When there is a need to quickly reduce heavy drinking and alcohol-related consequences , it appears that CBT or TSF should be the treatment of choice Objective : Mobile technology has the potential to radically improve addiction treatment and continuing care by offering emotional and instrumental support anywhere and just in time . This is particularly important in addiction because timing is critical to preventing relapse . Although most experts consider alcoholism to be a chronic disease , providers do not typically offer ongoing support for relapse prevention after patients complete treatment , even though a central characteristic of alcoholism and other addictive behaviors is their chronically relapsing nature . A-CHESS is a smartphone-based system for preventing relapse to heavy drinking among people leaving active alcohol dependence treatment . A-CHESS is design ed to improve competence , social relatedness , and motivation , the three tenets of self-determination theory . This paper reports on the relative impact and use of A-CHESS 4 months after patients entered the study and discusses implication s of the results on treating addiction and chronic diseases generally . Methods : A total of 349 individuals with alcohol dependence leaving residential treatment were r and omly assigned to either receive A-CHESS + Treatment as usual or treatment as usual ( st and ard aftercare ) . Patients came from two treatment agencies , one in the Midwest and one in the Northeast . Patients assigned to A-CHESS received a smartphone for 8 months and were followed for 12 . The authors analyzed use patterns during the first 4 months of use by those receiving A-CHESS . Results : Participants used A-CHESS heavily and sustained their use over time . Ninety-four percent of A-CHESS participants used the application during the first week after residential treatment . At week 16 , almost 80 % continued to access A-CHESS . Participants with alcohol and drug dependence showed higher levels of system use than those with alcohol dependence only . Participants with a mental health diagnosis had slightly lower levels of use at the end of the intervention period ( week 16 ) , although more than 70 % still accessed the system . Conclusions : These findings illustrate that patients with alcohol dependence , alcohol and drug dependence , and mental health issues will use smartphone applications such as A-CHESS for ongoing support , re sources , and information , thus extending patient care if given the opportunity . Further analysis is needed to determine whether sustained A-CHESS use improves outcomes . This clinical trial is registered at www . clinical trials.gov as trial # NCT01003119 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 Developed and evaluated a home-based contracting program to determine its effect on the compliance rates of discharged alcohol patients to a disulfiram ( antabuse ) regimen . The three comparison groups included ( a ) no contract/no recording ; ( b ) contract/recording ; and ( c ) contract/recording plus instructions for positive reinforcement . Twenty-five patients who had been treated in a behaviorally oriented inpatient alcohol dependence treatment program and who lived with a significant other ( i.e. , spouse , sibling , parent ) participated in the study . At the end of the 3-month period for which the disulfiram was prescribed , those Ss who were involved in contracting and recording reached criterion more frequently than those who were in the minimal treatment group . Furthermore , 84 % of this S sample were abstinent at the 3-month follow-up according to collateral reports . The discussion centers on the use of home-based contracting as an inexpensive alternative to other , more costly disulfiram programs . Additional methods for obtaining measures of reliability on self-report of disulfiram usage also are discussed Alcoholics from two hospital-based treatment centers participated in an experimental test of the effects of extended aftercare on inpatient recovery rates . At discharge from inpatient treatment , subjects were r and omly assigned either to an experimental group scheduled to be called by a center counselor every 2 weeks for 1 year or to a control group that experienced only the usual treatment . Follow-up interviews conducted approximately 12 months after hospital discharge found that the experimental group had no higher recovery rates than the control group . There was weak evidence that the calls reduced the burden that alcoholics place on community control and service agencies . There was no evidence that either the phone calls were more effective for some patients than for others or that some kinds of phone calls were more effective than others . Although most subjects said they liked the calls , wanted them to continue and perceived them as " good treatment , " only one subject gave the calls credit for helping him maintain sobriety This study evaluated whether alcoholics who received couples relapse prevention ( RP ) sessions in the year after short-term behavioral marital therapy ( BMT ) did better than those who did not receive additional RP . Couples ( n = 59 ) with an alcoholic husb and , after participating in weekly BMT couples sessions for 5 months , were assigned r and omly to receive or not receive 15 additional conjoint couples relapse prevention ( RP ) sessions over the next 12 months . Outcome measures were collected before and after BMT and at quarterly intervals for the year after BMT . Significant improvements in the alcoholics ' drinking and the couple 's marital adjustment occurred from before to after BMT replicating results of our own and other 's earlier studies of BMT with alcoholics , and outcomes remained significantly improved through 12-months follow-up independent of the amount of aftercare received . Given these favorable outcomes overall , the present study provided a stringent test of the hypothesized utility of RP . As predicted , alcoholics who received RP after BMT had more days abstinent and fewer days drinking , maintained their improved marriages better and used behaviors targeted by BMT more than those who received BMT alone . The prediction that greater continued use of behaviors targeted by BMT would be associated with better outcomes irrespective of the amount of aftercare received also was supported . The final prediction that couples with more severe alcohol and marital problems at study entry would show the greatest additional benefit from RP was not supported . The relatively clear-cut findings favoring RP may be due to the fact that RP in this study was an intensive , multifaceted booster maintenance intervention delivered in a couples format over a lengthy period of time . Moreover , the present results occurred during the time that couples were still getting RP . Limitations to the generalizability and interpretation of the results are discussed OBJECTIVE To examine the impact of three common comorbid disorders on a variety of outcomes 3 years after inpatient alcoholism treatment . METHOD Using a prospect i ve cohort design , we examined the frequency and intensity of drinking , the severity of alcohol-related symptoms , global alcohol-related outcome and severity of psychiatric symptoms in a group of 225 ( 74 % male ) alcoholics . At the index admission , patients were categorized as to the lifetime presence of major depression , antisocial personality disorder ( ASP ) and drug abuse/dependence . Multiple linear regression was used hierarchically to step in blocks of predictors in a logical sequence : ( 1 ) gender and age ; ( 2 ) number of comorbid psychiatric diagnoses and the presence or absence of the three individual comorbid psychiatric disorders ; and ( 3 ) the interaction between gender and each of the three diagnostic groups . RESULTS Men showed greater intensity of drinking , more alcohol-related symptoms and poorer global alcohol-related outcome . Younger patients also showed more alcohol-related symptoms . Although the number of comorbid diagnoses was correlated with both the intensity of drinking and the severity of psychopathology , each of the specific comorbid diagnoses accounted for unique variance in outcome . Comorbid drug abuse/dependence was associated with more drinking days and more alcohol-related symptoms . In contrast , the presence of comorbid major depression was associated with lower intensity of drinking . Finally , ASP was associated with poorer global alcohol-related outcome . CONCLUSIONS Outcomes 3 years after alcoholism treatment are related to the presence of specific lifetime comorbid psychiatric diagnoses . Since such disorders may positively influence the course of alcoholism , trials of clinical interventions that target these disorders are warranted AIMS To measure the effect of community nurse follow-up on abstinence and retention rates in the outpatient treatment of alcohol-dependent patients treated with acamprosate . METHODS Recently detoxified alcohol-dependent patients were prescribed acamprosate for 26 weeks and r and omized to either physician-only follow-up , or physician plus regular visits from a community nurse . Drinking behaviour in the next 26 weeks was assessed at monthly visits to non-blind clinicians . RESULTS The cumulative abstinence duration proportion ( CADP ) was significantly longer in ( P=0.03 ) the subjects who had received community nurse support ( 0.57 ) than in those who had not ( 0.39 ) . This might , in part , be an artefact of the higher retention rate among those followed up by the nurse , in that , the method of calculating CADP allocates 100 % days of drinking for the month before a failed attendance . Differences favouring nurse in the follow-up were seen for time to first drink , and clinical global impression . CONCLUSIONS For recently detoxified alcohol-dependent patients treated with acamprosate , follow-up by a community nurse improves patient retention and probably also improves the 6-month drinking outcome Objective : In spite of the increasing interest in out‐patient treatment programmes for alcoholics , there still exist only a few experimental studies on this issue . In this still ongoing study the efficacy of different behaviour therapy strategies is to be examined The effect of an appointment-keeping intervention on attendance at aftercare was examined for 50 male participants in an inpatient alcohol treatment program . Subjects received either a calendar prompt and home-based attendance contract intervention ( Experimental group , N = 25 ) or st and ard aftercare treatment arrangements ( Control group , N = 25 ) . Participants were followed for eight aftercare sessions over a 6-month period . Results showed significant attendance differences between groups for the first seven aftercare sessions , with nearly twice as many experimental subjects as control subjects attending aftercare sessions . Further , significantly fewer experimental than control subjects ( 24 % fewer ) were dropped from the alcohol program for three consecutive nonattendances . The present study provides an effective technology for increasing aftercare attendance and thus potentially increasing the probability of long term maintenance of alcohol treatment effects The major purpose of this study was to provide descriptive data on the first relapse episodes and reasons for terminating relapses of subjects who completed a course of behavioral marital therapy ( BMT ) for alcoholism . Another aim of the study was to compare the relapse episodes and relapse terminations of subjects who received BMT with or without additional relapse prevention ( RP ) treatment for one year . The subjects were selected from a sample of 74 men who began an outpatient Department of Veterans Affairs BMT program . These men were evaluated pre- and post-BMT , and at 3 , 6 , 9 , and 12 months after completing BMT . A total of 31 subjects relapsed at least once after they began BMT . The data showed that these men tended to report more than one situational or personal precipitant of their first relapses . Similarly , they tended to report more than one reason for ending their relapse episodes . Comparison of the subjects assigned to the two RP conditions revealed an equal number ( 12 ) of relapse episodes , but RP subjects ' relapses tended to last fewer days than did no-RP subjects ' . The consistency of these findings with previous research on cognitive-behavioral models of relapse and the implication s of these findings for the concept of high-risk situation , are discussed OBJECTIVE This article provides a complete report of outcome data from a study of behavioral marital therapy ( BMT ) with and without additional couples relapse prevention ( RP ) sessions . ( See J. Stud . Alcohol 54 : 652 - 666 , 1993 , for an earlier partial report . ) METHOD Fifty-nine couples with an alcoholic husb and , after receiving weekly BMT couples sessions for 5 - 6 months , were assigned r and omly to get or not get 15 additional couples relapse prevention ( RP ) sessions over the next 12 months . Outcome measures were collected before and after BMT and at quarterly intervals for the 30 months after BMT . RESULTS BMT-plus-RP produced more days abstinent and greater use of the Antabuse Contract than BMT-only ; and these superior drinking outcomes for BMT-plus-RP lasted through 18-month follow-up ( i.e. , 6 months after the end of RP ) . BMT-plus-RP had better wives ' marital adjustment than BMT-only throughout the 30 months of follow-up , with the superiority of BMT-plus-RP over BMT-only being greatest for wives with poorer pretreatment marital adjustment during the later months of follow-up . BMT-plus-RP also maintained their improved marriages longer ( through 24-month follow-up ) than BMT-only ( through 12-month follow-up ) . Irrespective of treatment condition , more use of BMT-targeted marital behaviors ( e.g. , shared recreational activities , constructive communication ) was associated with better marital and drinking outcomes throughout the 30-month follow-up period whereas more use of the Antabuse contract was associated with better marital and drinking outcomes through 12-month follow-up . Alcoholics with more severe marital problems had more abstinent days and maintained relatively stable levels of abstinence if they received BMT-plus-RP , while their counterparts who received BMT-only had fewer abstinent days and showed a steep decline in abstinent days during the 30 months of follow-up . Furthermore , alcoholics with more severe alcohol problems used the Antabuse contract more and showed a less steep decline in use of the Antabuse contract in the 30 months of follow-up if they received BMT-plus-RP than if they received BMT-only . CONCLUSIONS For the entire sample , BMT-plus-RP produced better marital outcomes throughout the 30 months of follow-up and better drinking outcomes during and for the 6 months following RP sessions , relative to BMT-only outcomes . For alcoholics with more severe marital and drinking problems , BMT-plus-RP produced better drinking outcomes than BMT-only throughout the 30-month follow-up period Substance-abusing patients often relapse soon after undergoing treatment , thus requiring intensive aftercare or re-treatment . More efficient monitoring and follow-up of patients could contribute to better treatment outcomes . This study evaluated the feasibility of a computer-automated interactive voice response ( IVR ) system to reduce relapse following discharge from residential treatment . Sixty participants completing a residential treatment program and meeting DSM-IV criteria for alcohol dependence were r and omized to three groups : ( 1 ) daily IVR reporting with personal follow-up on noncompliant callers ; ( 2 ) daily IVR reporting without follow-up ; or ( 3 ) no IVR reporting ( control group ) . At 30 , 90 , and 180 days after discharge , participants were interviewed to obtain timeline follow-back drinking data and completed the Work and Social Adjustment Scale , Obsessive-Compulsive Drinking Scale , SF-36 , and Drinker Inventory of Consequences . This pilot study suggests that using automated IVR technology to monitor clients after discharge is feasible and warrants further research and development . IVR systems also provide the potential for delivering individualized feedback Although continuing care is strongly related to positive treatment outcomes for substance use disorder ( SUD ) , participation rates are low and few effective interventions are available . In a r and omized clinical trial with 150 participants ( 97 % men ) , 75 graduates of a residential Veterans Affairs Medical Center SUD program who received an aftercare contract , attendance prompts , and reinforcers ( CPR ) were compared to 75 graduates who received st and ard treatment ( STX ) . Among CPR participants , 55 % completed at least 3 months of aftercare , compared to 36 % in STX . Similarly , CPR participants remained in treatment longer than those in STX ( 5.5 vs. 4.4 months ) . Additionally , CPR participants were more likely to be abstinent compared to STX ( 57 % vs. 37 % ) after 1 year . The CPR intervention offers a practical means to improve adherence among individuals in SUD treatment Alcoholic clients were given role-play tests , involving various social and drinking-related scenarios , before and after two types of aftercare treatment . The assessment s were used both to evaluate the effects of treatment and to determine whether any dimensions of pretreatment role-play performance interact with treatment type to predict treatment outcome . Eighty-nine patients were r and omly assigned to aftercare group treatment involving either interactional therapy or coping skills training . Clients in both treatments experienced declines in their urge to drink during the role-play scenes from pre- to posttreatment , and these declines were related to reductions in heavy drinking . Three pretreatment role-play variables interacted with type of treatment to predict outcome : observer-rated skill , observer-rated anxiety , and self-reported urge to drink . In general , those patients who did better in the role plays had better drinking outcomes following interactional therapy . Those who experienced more difficulty in the role plays fared best with coping skills training . The results suggest that role-play measures could be used for patient-treatment matching , although it remains to be determined whether they will be superior to more easily assessed patient characteristics Burtscheidt W , Wölwer W , Schwarz R , Strauss W , Gaebel W. Out‐patient behaviour therapy in alcoholism : treatment outcome after 2 years . Acta Psychiatr Sc and 2002 : 106 : 227–232 . © Blackwell Munksgaard 2002 Introduction : Alcohol consumption and drug use , as well as alcohol- and drug-related problems , vary considerably in different regions in Sweden , and between men and women of different ages . Aim : The aim of the present study was to examine the regional , gender and socioeconomic distribution of risk consumption of alcohol , alcohol dependency and drug use in a r and om sample in Sweden . Material and methods : In both May 2003 and 2004 , 7200 gender-stratified adults ( a total of 14,400 ) , r and omly selected from 12 regions in Sweden , were contacted by mail , and asked to fill out an enclosed question naire . The question naire concerned use of alcohol , alcohol-related problems , and use of illicit drugs . Results : Heavy alcohol consumption and cannabis use were more frequent in the south of Sweden than in the north , and the further north , the lower the frequency . Alcohol and drug use decreased with age , and was higher for men than for women . On average , 11.5 % of all men and 5.0 % of all women consumed alcohol intensively at least weekly , 8.6 % of men and 4.5 % of women had a generally high alcohol consumption , 4.1 % of men and 2.5 % of women were alcohol addicted , and 2.9 % of men and 1.3 % of women had used cannabis during the last 12 months . Conclusions : High alcohol consumption and use of illegal drugs seem to be more prevalent in those parts of Sweden that are closer to the European continent . In our opinion , this might be an effect of the closeness to other European countries with lower prices for alcohol , less strict alcohol control policies , and higher availability of drugs . Consideration of regional , gender and age differences in problems related to alcohol and drugs seem to be important in the planning and development of preventive activities A pragmatic r and omised trial examined the effects of Early Warning Signs Relapse Prevention Training ( EWSRPT ) on drinking in alcohol dependent persons with history of relapse . Participants were 124 abstinent alcohol dependent patients with a history of relapse ( median five relapses ) who entered the trial as they completed a 6-week day treatment programme . They were r and omly allocated to receive either ( 1 ) Aftercare as Usual ( AU ) or ( 2 ) AU plus 15 individual sessions of EWSRPT using Gorski 's protocol . Assessment carried out at entry to the trial , and 4 , 8 , and 12 months later , included self-report of drinking , blood tests ( gamma glutamyl transferase , GGT ; serum alanine aminotransferase , ALT ) and measures of functioning ( Alcohol Problems Question naire , APQ ; SF36 , Brief Symptom Inventory , BSI ; Assessment of Warning-signs of Relapse , AWARE ) . Intention to treat analysis found no significant differences in continuous abstinence during the follow-up year ( 17 % of 58 AU , 31 % of 58 EWSRPT , p=0.08 ) . The EWSRPT participants had a significantly lower probability of drinking heavily ( 74 % of AU , 55 % of EWSRPT , p=0.04 ) , and significantly fewer days drinking ( p=0.05 ) and heavy drinking ( p=0.04 ) . These clinical ly worthwhile effects for a relapse-prone group justify further research into EWSRPT Men inpatient alcoholics ( N = 174 ) from a Veterans Administration medical center who were preselected by employment status were r and omly assigned to one of three outpatient treatment interventions : ( 1 ) medication only , ( 2 ) active support or ( 3 ) untreated medical monitoring . Subjects were followed monthly for 1 year , with an 85 % 12-month follow-up rate . Although the sample as a whole showed reduced alcohol misuse and improved social functioning after 12 months , the specific form of treatment was unrelated to outcome . These findings suggest that the intensity of the outpatient treatment experience is not related to outcome and that time-consuming interventions are not differentially cost-effective Aftercare to prevent relapse following alcohol treatment has not received adequate experimental investigation . The present study monitored alcohol intake of 50 patients following assignment to either an intensive aftercare recruitment procedure or regular clinic aftercare . The results indicated that those who received the intensive aftercare procedure showed delayed relapse . In addition , regardless of group assignment those who attended aftercare had significantly more success as measured by alcohol intake . The implication s of these results for the design of treatment and aftercare programs are discussed |
2,473 | 32,182,549 | Our meta- analysis results indicated that CTCs are significant associated with prognosis of patients with HNSCC . | BACKGROUND The prognostic significance of circulating tumor cells ( CTCs ) in patients with head and neck squamous cell carcinoma ( HNSCC ) is still unclear .
The objective of this study was to estimate its correlation with clinicopathological and prognostic significance in HNSCC . | OBJECTIVES to present and discuss a high-performance negative depletion method for the isolation of circulating tumor cells ( CTCs ) in the blood of patients with head and neck cancer and to determine the correlation between the presence of CTCs and early clinical outcome in these patients . DESIGN prospect i ve clinical follow-up study of patients with squamous cell carcinoma of the head and neck ( SCCHN ) undergoing surgical intervention , who had peripheral blood examined for the presence of CTCs . PATIENTS the study population comprised 48 patients diagnosed as having SCCHN and undergoing surgical intervention . INTERVENTION a negative depletion process to isolate and quantify CTCs from the blood of patients with SCCHN using immunomagnetic separation was developed and vali date d. Immunostaining for cytokeratin was performed on the enriched sample s to determine the number of CTCs extracted from each patient 's blood sample . Correlation of the presence of CTCs , tumor stage , nodal status , clinical characteristics , and outcome was made . MAIN OUTCOME MEASURE disease-free survival . RESULTS our initial data , that have a mean follow-up of 19.0 months , suggest that patients with no detectable CTCs per milliliter of blood had a significantly higher probability of disease-free survival ( P = .01 ) . There was no correlation between the presence of CTCs with regard to age , sex , tumor site , stage , or nodal involvement . CONCLUSIONS our enrichment technology , based on the removal of normal cells , has been used on the peripheral blood of patients with head and neck cancer for which follow-up data were collected . If no CTCs were present , a statistically significant improved disease-free survival was observed in SCCHN . A blood test with such a prognostic capability could have important implication s in the treatment of patients with head and neck cancer Background The prognostic role of circulating tumor cells ( CTCs ) after induction chemotherapy using docetaxel , cisplatin and fluorouracil ( TPF ) prior to surgery and adjuvant (chemo)radiation in locally advanced oral squamous cell cancer ( OSCC ) was evaluated . Methods In this prospect i ve study , peripheral blood sample s from 40 patients of the phase II study TISOC-1 ( NCT01108042 ) with OSCC before , during , and after treatment were taken . CTCs were quantified using laser scanning cytometry of anti– epithelial cell adhesion molecule – stained epithelial cells . Their detection was correlated with clinical risk factors , recurrence-free ( RFS ) and overall survival ( OS ) . Results Before starting the treatment CTCs were detected in 32 of 40 patients ( 80 % ) . The median number at baseline was 3295 CTCs/ml . The median maximal number of CTCs during treatment was 5005 CTCs/ml . There was a significant increase of CTCs before postoperative radiotherapy compared to baseline before 1st cycle of IC ( p = 0.011 ) , 2nd cycle of IC ( p = 0.001 ) , 3rd cycle of IC ( p = 0.004 ) , and before surgery ( p = 0.002 ) , but not compared to end of therapy ( p = 0.118 ) . CTCs at baseline > median was also associated to risk of recurrence ( p = 0.014 ) . Maximal CTCs during therapy > median was more frequently observed in tumors of the oral cavity ( p=0.022 ) and related to higher risk of death during follow-up ( p = 0.028 ) . Patients with CTCs at baseline > median value had significant lower RFS than patients with CTCs at baseline < median value ( p = 0.025 ) . Patients with maximal CTCs values > median during the complete course of therapy had a significantly lower OS than patients with values < median ( p = 0.049 ) . Finally , the multivariate analysis revealed that OS was significantly lower in patients with maximal CTCs during treatment higher than the median value ( HR=6.151 ; CI : 1.244 - 30.420 ) . Conclusions Baseline CTCs and maximal CTCs during therapy both seem to be good prognostic markers for OSCC when treated by TPF induction chemotherapy , surgery , and postoperative (chemo)radiation BACKGROUND The prognostic role of persistence of circulating tumor cells ( CTC ) after upfront tumor surgery for outcome of adjuvant (chemo)radiation in locally advanced squamous cell carcinoma of the head and neck ( LASCCHN ) was evaluated . PATIENTS AND METHODS In this prospect i ve study , peripheral blood sample s from 144 patients with LASCCHN presenting after tumor resection for adjuvant treatment were analyzed for CTC . Their detection was correlated with tumor site , clinical risk factors , disease-free ( DFS ) and overall survival ( OS ) . RESULTS CTC were detected in 42 of 144 patients ( 29 % ) . CTC detection was higher in cases with nodal involvement and in carcinomas located at the tonsil or base of tongue but was not influenced by age , smoking history , T stage , extracapsular lymph node extension , surgical margins or the human papillomavirus status . Overall , the presence of CTC was not predictive for OS or DFS . However , while in oropharyngeal carcinomas ( OPC , n = 63 ) , the detection of CTC was associated per trend with improved DFS [ CTC+ versus CTC- ( % of patients without evidence of disease at 2 years ) : 100 % versus 79 % ; log rank : P = 0.059 ] ; the reverse was observed for carcinomas from other sites ( non-OPC , n = 81 ; CTC+ versus CTC- : 29 % versus 75 % ; P = 0.001 ) . In multivariate analysis , CTC remained an independent prognostic marker for DFS [ hazard ratio ( HR ) 4.3 , 95 % confidence interval ( CI ) 1.7 - 10.9 , P = 0.002 ] and OS ( HR 2.7 , 95 % CI 1.2 - 6.3 , P = 0.016 ) in non-OPC . CONCLUSIONS Assessment of CTC in non-OPC should prove useful for identification of patients who benefit from treatment intensification . The basis for the good prognostic value of CTC in OPC has to be eluci date d in future studies BACKGROUND AND PURPOSE The mechanism of dissemination of locally advanced head and neck cancer ( LAHNC ) is far to be resolved . Circulating tumour cells ( CTC ) have been identified as a prognostic factor in metastatic breast and prostate cancer . This prospect i ve multi-centric analysis studied the possible role of CTC identification in LAHNC . MATERIAL S AND METHODS CTC were search ed in 73 patients with LAHNC ( oropharynx , n=39 ; nasopharynx , n=10 ; larynx , n=10 ; paranasal sinuses , n=6 , of whom 3 with sinonasal undifferentiated carcinoma , SNUC ; hypopharynx , n=5 ; oral cavity , n=3 ) . All of them ( apart from SNUC ) had squamous cell cancers . The relationship between CTC positivity and other clinical prognostic factors has been investigated . Response to treatment and survival has been related with changes in CTC number during the treatment . RESULTS CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC . They were more frequent in stage IV than in stages I-III disease ( 18 % versus 6 % , p = NS ( not significant ) ) . Partial or complete response ( CR ) was related with the absence or disappearance of CTC during treatment ( p=0.017 ) . A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease , after both complete or incomplete remission and with the proportion of patients alive and NED ( no evidence of disease ) ( p=0.009 ) . CONCLUSIONS These preliminary data suggest a possible role of CTC determination in head and neck cancer . Additional and longer follow up data need to be collected to confirm these findings PURPOSE The numbers of circulating tumor cells ( CTCs ) and their expression/activation of epidermal growth factor receptor ( EGFR ) during the course of combined chemo- or bioradiotherapy regimens as potential biomarkers of treatment efficacy in squamous cell carcinoma of the head and neck ( SCCHN ) were determined . METHODS AND MATERIAL S Peripheral blood sample s from SCCHN patients with locally advanced stage IVA/B disease who were treated with concurrent radiochemotherapy or induction chemotherapy followed by bioradiation with cetuximab were included in this study . Using flow cytometry , the absolute number of CTCs per defined blood volume as well as their expression of EGFR and its phosphorylated form ( pEGFR ) during the course of treatment were assessed . RESULTS Before treatment , we detected ≥1 CTC per 3.75 mL blood in 9 of 31 patients ( 29 % ) . Basal expression of EGFR was detected in 100 % and pEGFR in 55 % of the CTC+ cases . The frequency of CTC detection was not influenced by induction chemotherapy . However , the number of CTC+ sample s significantly increased after radiotherapy . This radiation-induced increase in CTC numbers was less pronounced when radiotherapy was combined with cetuximab compared to its combination with cisplatin/5-fluorouracil . The former treatment regimen was also more effective in reducing pEGFR expression in CTCs . CONCLUSIONS Definitive radiotherapy regimens of locally advanced SCCHN can increase the number of CTCs and might thus contribute to a systemic spread of tumor cells . Further studies are needed to evaluate the predictive value of the radiation-induced increase in CTC numbers and the persistent activation of the EGFR signalling pathway in individual CTC+ cases CD133 has been associated with cell properties such as self renewal , migration and vasculogenic mimicry , potentially involved in generation of circulating tumor cells ( CTCs ) . We characterized CD133 expression in CTCs of 98 nometastatic breast cancer ( BC ) patients . CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody ( CK3 - 11D5 ) and CTCs and CD133 detection through immunocytochemical methods . CK(+ ) /CD133(+ ) CTCs were identified in 65 % of patients at baseline and 47.8 % after systemic therapy ( p = 0.53 ) . Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed . Her2 not amplified and low Ki-67 index were positively correlated with presence of CK(+ ) /CD133(+ ) CTCs . Before any treatment , CK(+ ) /CD133(+ ) CTCs were more frequently isolated in patients with luminal BC subtype . No statistically significant differences were found between proportion of CK(+ ) /CD133(+ ) CTCs and BC subtypes after systemic therapy , implying a relative enrichment of CK(+ ) /CD133(+ ) CTCs in triple negative and HER2-amplified tumors . While CK(+ ) /CTCs decreases after chemotherapy when analyzing the whole population , CK(+ ) /CD133(+ ) CTCs were enriched in post-treatment sample s in nonluminal BC subtypes . These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients . Further prospect i ve studies and extensive pre clinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy , and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature Studies in circulating tumor cells ( CTCs ) have proceeded to be accepted as prognostic markers in several types of cancers . But they are still limited because many are mainly from enumeration of CTCs . Here , we tried to evaluate the tumorigenicity of CTCs from advanced gastric cancer patients ( n = 42 ) . Peripheral blood mononuclear cells ( P BMC ) from the patients were separated into CD45 negative and positive fractions and both were subcutaneously injected into immunodeficient mice . Within 5 months nine tumor-like-structures from six patients but not from healthy volunteers were established . They were durable for passages and all had been confirmed human origin . Eight of the nine tumor-like-structures were from nonauthorized CTC containing cells expressing CD45 and B-cell markers . On the contrary , one of them was developed from CD45(- ) P BMC fraction of a patient with bone marrow metastasis reflecting authorized CTCs . Histopathology showed common features with that of original gastric tumor . The cells isolated from the tumor-like-structure expressed EpCAM and CEA further supporting they were from the original tumor . Moreover the cells were CD44 positive to varying degree and a limiting dilution study showed that the CD44(+/high ) fraction had tumorigenicity . The CD44 was dominantly in the form of CD44 variant 8 - 10 . The CD44(+/high ) cells had higher expression of the glutamate/cysteine transporter xCT compared with the CD44(-/low ) cells . Our results showed the existence of tumor-initiating cells in blood of advanced gastric cancer patients and they could be a therapeutic target and prospect i ve tool for further investigations Background Successful application of programmed death 1 ( PD1 ) checkpoint inhibitors in the clinic may ultimately benefit from appropriate patient selection based upon predictive biomarkers . Molecular characterization of circulating tumor cells ( CTC ) is crucial for the investigation of molecular-targeted therapies while predictive biomarkers for response to PD1 checkpoint inhibitors are lacking . We sought to assess whether overexpression of PD-L1 in CTCs could be detected at baseline and at different timepoints during treatment in a prospect i ve cohort of head and neck squamous cell carcinoma ( HNSCC ) patients and used to predict clinical outcome after treatment with curative intent . Patients and methods We developed a highly sensitive , specific and robust RT-qPCR assay for PD-L1 mRNA expression in EpCAM(+ ) CTCs . In a prospect i ve cohort of 113 locally advanced HNSCC patients treated with curative intent we evaluated PD-L1 expression in the EpCAM(+ ) CTC fraction at baseline , after 2 cycles of induction chemotherapy ( week 6 ) and at the end of concurrent chemoradiotherapy ( week 15 ) . Results PD-L1 overexpression was found in 24/94 ( 25.5 % ) patients at baseline , 8/34 ( 23.5 % ) after induction chemotherapy and 12/54 ( 22.2 % ) patients at the end of treatment . Patients with CTCs overexpressing PD-L1 at end of treatment had shorter progression-free survival ( P = 0.001 ) and overall survival ( P < 0.001 ) . Multivariate analysis revealed that PD-L1 overexpression at end of treatment was independent prognostic factor for progression-free survival and overall survival . The absence of PD-L1 overexpression at the end of treatment was strongly associated with complete response with an odds ratio = 16.00 ( 95 % CI = 2.76 - 92.72 , P = 0.002 ) . Conclusions We demonstrate that detection of CTCs overexpressing PD-L1 is feasible and may provide important prognostic information in HNSCC . Our results suggest that adjuvant PD1 inhibitors deserve evaluation in HNSCC patients in whom PD-L1(+ ) CTCs are detected at the end of curative treatment |
2,474 | 15,495,027 | REVIEW ERS ' CONCLUSIONS The findings in this review suggest that antisecretory drugs are effective in the empirical treatment of complaints likely to originate from GORD and in treatment of ENRD and furthermore that PPIs are superior to H2RAs in empirical treatment of typical GORD symptoms | BACKGROUND Heartburn affects 25 % of the adult population on a monthly basis and represents the core symptom of gastro-oesophageal reflux disease ( GORD ) .
Treatment is readily available and puts a large dem and on healthcare budgets .
A majority of GORD patients show no endoscopic abnormalities and in daily practice most patients are treated empirically .
OBJECTIVES Summarise , quantify and compare the efficacy of the short-term use of proton pump inhibitors ( PPI ) , H2-receptor antagonists ( H2RA ) and prokinetics in adults with GORD and endoscopy negative reflux disease ( ENRD ) . | BACKGROUND & AIMS Gastroesophageal reflux is considered a common condition , but detailed population -based data on reflux in the United States are lacking . The aim of this study was to determine the prevalence and clinical spectrum of gastroesophageal reflux in Olmsted County , Minnesota . METHODS A reliable and valid self-report question naire was mailed to an age- and sex-stratified r and om sample of 2200 Olmsted County residents aged 25 - 74 years . RESULTS The prevalence per 100 of heartburn and /or acid regurgitation experienced at least weekly was 19.8 ( 95 % confidence interval [ 95 % CI ] , 17.7 - 21.9 ) . Heartburn and acid regurgitation were associated with noncardiac chest pain ( odds ratio [ OR ] , 4.2 ; 95 % CI , 2.9 - 6.0 ) , dysphagia ( OR , 4.7 ; 95 % CI , 2.9 - 7.4 ) , dyspepsia ( OR , 3.1 ; 95 % CI , 1.9 - 5.0 ) , and globus sensation ( OR , 1.9 ; 95 % CI , 1.0 - 3.6 ) but not with asthma , hoarseness , bronchitis , or a history of pneumonia . Among subjects with reflux symptoms , 1.0 % reported an episode of hematemesis and 1.3 % had a past esophageal dilatation . CONCLUSIONS Symptoms of reflux are common among white men and women who are 25 - 74 years of age . Heartburn and acid regurgitation are significantly associated with chest pain , dysphagia , dyspepsia , and globus sensation . The percentage of patients reporting complications is low , but the absolute number is probably considerable given the high prevalence of the condition in the community OBJECTIVES To evaluate complete symptom resolution , mucosal healing , and tolerability of omeprazole , ranitidine , or ranitidine/metoclopramide in patients with poorly responsive , symptomatic gastroesophageal reflux disease ( GERD ) . METHODS Adults with persistent symptomatic GERD after ranitidine treatment were stratified by esophagitis grade and r and omized to omeprazole 20 mg once daily , ranitidine HCI 150 mg twice daily , or ranitidine HCI 150 mg twice daily plus metoclopramide HCI 10 mg four times daily . Endoscopies were conducted at baseline and at wk 4 and 8 . Patients assessed overall symptom improvement at wk 4 and 8 and evaluated daytime and nighttime heartburn , dysphagia , and acid regurgitation daily . RESULTS After 1 wk , 13 % of patients receiving omeprazole ( N = 100 ) had complete resolution of all GERD symptoms versus 1 % and 3 % of patients receiving ranitidine ( N = 97 ) or ranitidine/metoclopramide ( N = 93 ) , respectively ( p < 0.001 ) . More patients receiving omeprazole had complete symptom resolution at wk 4 ( 33 % ) and at the end of the study ( 64 % ; both p < 0.001 ) than patients receiving ranitidine ( 8 % and 28 % , respectively ) or ranitidine/metoclopramide ( 7 % and 29 % , respectively ) . Regardless of baseline esophagitis grade , more patients receiving omeprazole had complete symptom resolution . At wk 8 , more than 91 % of patients with grade 0 or 1 esophagitis at baseline were still healed irrespective of treatment . At wk 8 , 80 % of patients with esophagitis grade 2 or higher at entry were healed with omeprazole ( p < 0.001 vs ranitidine [ 40 % ] and ranitidine/metoclopramide [ 46 % ] ) . Thirty-four percent of patients reported an adverse event . Significantly more patients receiving combination treatment reported an adverse event than patients treated with single agents . CONCLUSIONS In patients with persistent GERD symptoms after ranitidine , omeprazole ( 20 mg daily for up to 8 wk ) provides faster and more complete resolution of common GERD symptoms than continued ranitidine ( 300 mg daily ) alone or in combination with metoclopramide ( 40 mg daily ) . Omeprazole provides significantly higher rates of endoscopic healing than ranitidine alone or with metoclopramide . Omeprazole and ranitidine are generally well tolerated . The addition of metoclopramide to ranitidine significantly increases adverse events BACKGROUND Up to three quarters of patients with gastroesophageal reflux disease ( GERD ) have symptoms , such as heartburn , but no macroscopic evidence of erosive esophagitis , making symptomatic GERD a common clinical problem in the primary care setting . OBJECTIVE To compare the efficacy and safety of omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; and placebo in the treatment of symptomatic GERD without erosive esophagitis . METHODS Patients with a history of heartburn ( > or = 12 months ) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week , r and omized , double-blind , placebo-controlled trial . The absence of erosive esophagitis was established through endoscopy . Eligible patients were r and omized to 1 of 3 treatment groups : omeprazole , 20 mg once daily ; omeprazole , 10 mg once daily ; or placebo . Patients were assessed at weeks 2 and 4 . The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data : daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment . The efficacy of omeprazole for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea was also assessed . RESULTS Of 359 r and omized patients , 355 were included in the statistical analysis ( intention-to-treat population ) . Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group ( 62 % , day 7 ; 74 % , day 27 ) than in the 10-mg omeprazole group ( 41 % , day 7 ; 49 % , day 27 ) or the placebo group ( 14 % , day 7 ; 23 % ; day 27 ) . Complete resolution of heartburn every day during the last treatment week was significantly ( P < or = .002 ) higher in the 20-mg omeprazole group ( 48 % ) than in the 10-mg omeprazole ( 27 % ) or placebo ( 5 % ) group . Omeprazole was significantly ( P < or = .003 ) more effective than placebo for the treatment of acid regurgitation , dysphagia , epigastric pain , and nausea . CONCLUSIONS Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief . Omeprazole , 20 mg once daily , was superior to omeprazole , 10 mg once daily , and to placebo in providing early and sustained resolution of heartburn , as well as treatment of other troublesome GERD symptoms Symptoms suggestive of gastro-oesophageal reflux disease are very common . The aim of the study was to assess the prevalence of these symptoms and factors influencing them in an unselected adult population . A question naire was mailed to a r and om sample of 2500 people aged > or = 20 years . The questions concerned heartburn , regurgitation , dysphagia , chest and upper abdominal pain , as well as medication and medical consultations for these symptoms . Of the 1700 ( 68 % ) responders , 9 % had experienced heartburn on the day of response and 15 % , 21 % and 27 % during the preceding week , month and year , respectively . The corresponding figures for regurgitation were 5 , 15 , 29 and 45 % . During the past year 43 % of the study group had had no such symptoms . Age , overweight , pregnancy and cigarette smoking significantly influenced the prevalence of symptoms . Using daily heartburn and /or regurgitation as dominant indicators 10.3 % ( 95 % CI 12 - 11.7 ) of the responders had gastro-oesophageal reflux disease . Medication ( most commonly antacids ) was used by only 16 % of the symptomatic people , and only 5.5 % had sought medical advice for symptoms during the past year . Thus , despite commonness of symptoms suggestive of gastro-oesophageal reflux disease only a minority of the individuals suffering from such symptoms use medication or have medical consultation Objective : We evaluated the efficacy and safety of a twice-daily dosage regimen of cisapride 20 mg in relieving the symptoms of mild-moderate gastroesophageal reflux disease ( GERD ) in patients with moderate intensity heartburn and no history of erosive esophagitis . Methods : After a 2-wk , single-blind , placebo run-in period , 398 patients who continued to experience moderate intensity heartburn were r and omized to either placebo ( n = 196 ) or cisapride 20 mg ( n = 202 ) twice daily for 4 wk . Results : Compared with placebo , cisapride significantly reduced scores for daytime and nighttime heartburn ( p < 0.001 ) , total regurgitation ( p < 0.001 ) , eructation ( p= 0.04 ) , and early satiety ( p= 0.04 ) . Cisapride 20 mg b.i.d . was also superior to placebo in reducing total use of rescue antacid medication ( p < 0.001 ) ; reducing , in concordance analyses , daytime and nighttime heartburn with antacid usage ( p < 0.001 ) ; increasing the percentage of heartburn-free days and antacid-free nights ( p < 0.5 ) ; and increasing the percentage of patients self-rated as having minimal or better symptomatic improvement ( p= 0.01 ) . Cisapride 20 mg b.i.d . was well tolerated . The most common adverse event in the cisapride group was diarrhea , reported by 10 % of patients , compared with an incidence of 4 % in the placebo group . Conclusion : Cisapride 20 mg b.i.d . was shown to be effective and safe for the short-term treatment of daytime and nighttime heartburn and for other symptoms associated with mild-moderate GERD Since metoclopramide increases lower-esophageal-sphincter pressure in patients with gastroesophageal reflux , we compared the effects of metoclopramide , 10 mg four times daily , with those of placebo on symptoms in 31 patients with chronic heartburn . Eighteen patients completed a r and om-order , double-blind crossover study of two consecutive eight-week periods . The final 13 patients crossed over only if their symptoms were not substantially improved after the first eight weeks . Response of low-esophageal-sphincter pressure to metoclopramide did not correlate significantly with symptomatic improvement . After the metoclopramide treatment period , mean basal pressure was unchanged from values before study . In both treatment periods , metoclopramide-treated patients had significantly more symptomatic improvement than the control group ( P less than 0.05 ) In a 6 to 12-week double-blind trial , the effect of cisapride ( 10 mg q.i.d . ) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and /or biopsy . In only one patient ( 3 % ) in the cisapride group but in 43 % of the placebo patients ( p = 0.001 ) , symptoms had not improved after 6 weeks . Forty patients continued treatment until week 12 . At that time , control endoscopy showed a significantly ( p = 0.005 ) higher rate of healing ( no erosions , ulcers , or bleeding mucosa ) in the cisapride patients ( 63 % ) than in the placebo patients ( 12 % ) . At week 12 , only three of the 21 cisapride patients still had moderate reflux symptoms , whereas eight of the 19 placebo patients had moderate or severe symptoms ( p less than 0.05 ) . Cisapride patients also took significantly ( p less than 0.001 ) less antacids during the trial . These results show that cisapride , 10 mg q.i.d . , heals esophagitis lesions and greatly reduces associated symptoms . The treatment was well tolerated BACKGROUND : At least 10 - 15 % of patients with reflux symptoms have a normal endoscopy and physiological levels of acid reflux on pH monitoring . Such patients with 50 % or more of symptoms associated with acid reflux episodes have " a positive symptom index " ( SI ) , and it has been proposed that this defines the " sensitive oesophagus " . AIM : To test the response to omeprazole 20 mg twice daily for four weeks of patients with normal levels of acid reflux using a r and omised , placebo controlled , double blind , cross-over design . PATIENTS : Eighteen patients with normal levels of reflux , 12 of whom had a positive SI . METHODS : Response was measured by symptomatic assessment and the SF-36 quality of life ( QOL ) question naire . RESULTS : Patients with a positive SI showed the following improvements on omeprazole compared with placebo : decrease in symptom frequency ( p < 0.01 ) , severity ( p < 0.01 ) and consumption of antacids ( p < 0.01 ) . In the group with a negative SI only one patient clearly improved . The QOL parameters for bodily pain ( 65.6 v 53.4 , p = 0.03 ) and vitality ( 60.6 v 48.8 , p = 0.049 ) were significantly better on omeprazole than placebo for the group overall . CONCLUSION : Omeprazole improves symptoms in 11 of 18 patients with normal endoscopy and pH monitoring , particularly those with a positive SI . This supports the theory that such patients have an oesophagus which is " sensitive " to acid reflux and are part of the GORD spectrum Background : To assess symptom relief in patients with heartburn following treatment with esomeprazole 40 mg daily . Methods : Patients with heartburn ( for ≥6 months ) were assessed in this double-blind , multicenter study . After a 3-day single-blind placebo run-in , 440 patients were r and omized to esomeprazole 40 mg o.d . , esomeprazole 20 mg b.i.d . or placebo for 14 days . Heartburn symptoms were recorded daily ; as insufficient patients had data available from days 13 and 14 , analyses included data up to day 12 . Gastroesophageal reflux disease ( GERD ) was diagnosed by upper GI endoscopy and 24-h pH- monitoring . The primary end-point was total heartburn relief defined as no heartburn symptoms during the preceding 24-h period . Results : 240 patients had erosive esophagitis ( EO ) and 114 patients had GERD defined by pH-monitoring . Proportions of patients with total heartburn relief increased during the first days of treatment and stabilized after Day 4 . Total heartburn relief occurred in 67%-73 % , 62%-70 % , and 21%-32 % of patients in the esomeprazole 40 mg o.d . , esomeprazole 20 mg b.i.d . , and placebo groups , respectively , between days 6 and 12 . Proportions of patients with total heartburn relief were higher in patients with EO ( 71%-80 % of patients from Day 4 onwards ) compared to those without EO ( 52%-67 % of patients from Day 4 onwards ) . Figures for patients diagnosed by pH-monitoring were 65%-73 % of those with a positive diagnosis and 51%-58 % with a negative diagnosis . Conclusion : Esomeprazole 40 mg o.d . treatment produces total heartburn relief in a high proportion of patients with GERD . Once-daily esomeprazole 40 mg dosing is recommended as no advantage was gained by splitting the dose This article presents the relevance of norm values to a battery of Quality of Life question naires for use in upper gastrointestinal disorders . The derivation of reference values offers an important contribution by confirming the ability of the question naires to differentiate patients from healthy controls . Two self-administered question naires , the Psychological General Well-being ( PGWB ) index and the Gastrointestinal Symptom Rating Scale ( GSRS ) were used . The norm values were derived in a r and omly selected sample from a Swedish population consisting of 4624 individuals ( reference group ) . The patients comprised more than 900 patients with gastroesophageal reflux disease ( GORD ) included in clinical trials . In the reference group , males reported significantly higher values on well-being as compared with women , whereas women reported more pronounced gastrointestinal symptoms than men . Generally , the younger persons and the group aged 60 - 70 years reported the highest well-being . Among gastrointestinal patients women scored lower and reported more symptoms than men . With increasing age , well-being improved and symptoms declined . Even though the well-being and symptoms scores differed between patient and the reference group similar patterns in terms of age and gender were observed . In summary , the results show that there are differences with respect to gender and age among normal controls as well as in GORD patients . These aspects have to be considered in clinical studies . The results also support the discriminative ability of the Quality of Life instruments Background / Aim : Gastroesophageal reflux disease ( GERD ) is a prevalent disease associated with a high symptom burden and a reduced quality of life . This multicenter , r and omized , double-blind study compared relief from key GERD symptoms ( heartburn , acid eructation , and pain on swallowing ) and from other gastrointestinal symptoms ( epigastric pain , vomiting , nausea , flatulence , retching , and retrosternal feeling of tightness ) and safety profiles of the proton pump inhibitor pantoprazole and the H2 antagonist ranitidine in patients suffering from symptomatic GERD . Methods : The patients [ 338 intention-to-treat ( ITT ) population ; 284 per- protocol ( PP ) population ] received 20 mg pantoprazole ( once daily in the morning ) plus ranitidine placebo ( once daily in the evening ; ITT n = 167 , PP n = 136 ) or pantoprazole placebo ( once daily in the morning ) plus 300 mg ranitidine ( once daily in the evening ; ITT n = 171 , PP n = 148 ) for 28 days . The primary efficacy criterion ( ITT and PP population s ) was relief from key GERD symptoms ( heartburn , acid eructation , and pain on swallowing ) after 28 days of treatment . Secondary criteria ( PP ) included relief from key GERD symptoms on day 14 , relief from all gastrointestinal symptoms on days 14 and 28 , and relief from key GERD symptoms on days 14 and 28 . Safety evaluations included adverse events and laboratory assessment s. Results : Significantly more pantoprazole-treated patients were free from key GERD symptoms at day 28 ( 68.3 % , n = 114 ) as compared with ranitidine-treated patients ( 43.3 % , n = 74 ; 95 % confidence interval for odds ratio 1.84–4.51 ) . Pantoprazole was also significantly more efficacious in controlling all gastrointestinal symptoms of GERD . By day 28 , 51.5 % ( n = 70 ) of the pantoprazole-treated patients were completely symptom free versus 31.1 % ( n = 46 ) of the ranitidine-treated patients ( 95 % confidence interval for odds ratio1.45–3.83 ) . Both treatments were well tolerated . Conclusion : Pantoprazole is significantly superior to ranitidine in the treatment of key and associated gastrointestinal symptoms of GERD and is well tolerated One hundred and twenty‐five patients with symptoms of heartburn and acid regurgitation but without endoscopic abnormalities were r and omized to receive 200 mg cimetidine suspension four times daily or placebo for two weeks . Daily diary cards were kept to evaluate the frequency and degree of symptoms . At two weeks cimetidine was significantly more effective than placebo . It is concluded that placebo suspension has a considerable effect on gastro‐oesophageal reflux disease symptoms , but cimetidine suspension provides significantly better relief Abstract Objective : To compare the effects and tolerability of omeprazole and cisapride with that of placebo for control of heartburn in primary care patients . Design : R and omised , double blind , placebo controlled study Setting : 65 primary care practice s in Norway Participants : 483 untreated patients with complaints of heartburn ≥3 days a week , with at most grade 1 reflux oesophagitis Interventions : Omeprazole 20 mg once daily , cisapride 20 mg twice daily , or placebo for 8 weeks Main outcome measures : Adequate control of heartburn , defined as ≥1 day of the past 7 days with no more than mild heartburn , after 4 weeks of treatment . Results : In the all patients treated analysis , adequate control of heartburn was achieved in 71 % of patients taking omeprazole , 22 % taking cisapride , and 18 % taking placebo after 4 weeks of treatment ( omeprazole v cisapride and placebo , P<0.0001 ; cisapride v placebo , non-significant ) . Results were comparable in patients with or without reflux oesophagitis . In patients treated with omeprazole only , symptom control was achieved significantly more often in patients positive for Helicobacter pylori . Antacid use was 2 - 3 times greater in patients taking cisapride or placebo than in those taking omeprazole . Relief of non-reflux symptoms did not significantly differ between the three groups . Significantly more patients taking cisapride reported adverse events than those taking omeprazole or placebo . Conclusions : Omeprazole 20 mg once daily was highly effective in relieving heartburn whereas cisapride 20 mg twice daily was not significantly more effective than placebo . Key messages In primary care patients , heartburn is commonly treated empirically Most r and omised clinical trials of treatment for heartburn have been conducted in specialist care , and documentation for empirical treatment is limited Omeprazole was significantly more effective than cisapride or placebo in controlling heartburn and other symptoms of gastro-oesophageal reflux after 2 , 4 and 8 weeks , whereas cisapride did not differ significantly from placebo Omeprazole should be considered as a first choice for empirical treatment of heartburn in primary Gastric acid suppression could improve heartburn by healing oesophagitis or by reduction of oesophageal sensitivity to acid . To independently assess changes in oesophageal sensitivity , it would be necessary to study patients with reflux disease but no oesophagitis . The aim of this study was to investigate the effect of acid suppression on oesophageal sensitivity and to assess the time course of any measured effect . Twenty seven patients were recruited , of whom 25 completed the study ( 14 men and 11 women , mean ( SD ) age 50 ( 15 ) years ) . All had classic symptoms of gastro-oesophageal reflux but normal results of upper gastrointestinal endoscopy and oesophageal mucosal histological tests . Each had abnormal 24 hour pH studies and a positive acid perfusion tests . Subjects were assigned double blind to placebo ( n = 11 ) or famotidine 40 mg twice daily ( n = 14 ) for four weeks . Acid perfusion tests were carried out at 0 , 4 , 5 , and 8 weeks and time to heartburn recorded . Time to heartburn ( mean ( SEM ) ) was 124 ( 78 ) seconds in the famotidine and 187 ( 154 ) in the placebo group at week 0 ( NS ) . Compared with baseline , significant increases in time to heartburn was found with famotidine at weeks 4 ( 383 ( 102 ) , p < 0.01 ) and 5 ( 344 ( 92 ) , p < 0.01 ) but not week 8 ( 336 ( 90 ) seconds ) . No significant effects were found with placebo ( 219 ( 41 ) , 146 ( 23 ) , and 144 ( 25 ) seconds for weeks 4 , 5 , and 8) . Heartburn symptom score decreased significantly with famotidine ( mean scores 3.6 , 1.9 , 2.1 , and 2.6 at weeks 0 , 4 , 5 , and 8 ( p=0.001 ) ) and showed a significant negative correlation with time to heartburn ( r(s)=-0.60 ; p<0.0001 ) . It is concluded that oesophageal sensitivity to acid is reduced by famotidine independent of and effect on oesophagitis ; the effect wanes one to four weeks after the end of treatment and correlates with change in heartburn score Background : There are few data on empiric , stepped therapy for heartburn relief or subsequent relapse in primary care OBJECTIVES To investigate whether pantoprazole ( 20 mg/d ) produces significantly greater symptom control than ranitidine ( 300 mg/d ) in patients with gastro-oesophageal reflux disease ( GORD ) . DESIGN Multicentre , r and omised , double-blind , parallel-group comparison . SETTING 76 general practice s in north-west Sydney and Newcastle , New South Wales ( Australia ) , from 19 January 1999 to 22 September 2000 . PATIENTS 307 patients aged 18 years or over presenting with symptomatic GORD . INTERVENTIONS Pantoprazole ( 20 mg once daily ) or ranitidine ( 150 mg twice daily ) . MAIN OUTCOME MEASURES Patient-assessed frequency and severity of heartburn using the Gastrointestinal Symptom Rating Scale ( GSRS ) and a patient heartburn diary . RESULTS Pantoprazole was associated with significantly higher rates of complete control of GORD symptoms than ranitidine at four weeks ( 40 % v 19 % ; P < 0.001 ) , eight weeks ( 55 % v 33 % ; P < 0.001 ) , six months ( 71 % v 56 % ; P = 0.007 ) and 12 months ( 77 % v 59 % ; P = 0.001 ) . CONCLUSIONS Low-dose pantoprazole is an effective alternative to st and ard-dose ranitidine for initial and maintenance treatment of patients with symptomatic GORD AIMS To investigate quality of life in patients with gastro-oesophageal reflux disease . PATIENTS A series of 704 patients were r and omised to treatment with ranitidine 150 mg bd , omeprazole 10 mg om or omeprazole 20 mg om for 2 weeks . Asymptomatic/mildly symptomatic patients were followed for 12 months . METHODS The Psychological General Well-Being index and the Gastrointestinal Symptom Rating Scale were completed before and during short-term and intermittent treatment . RESULTS The quality of life response rate was > 80 % . The majority of the patients receiving omeprazole 20 mg om ( 55 % ) had symptom relief after 2 weeks despite the fact that more patients on ranitidine required 4 weeks ' treatment and an increased dose . There was no difference in the reflux dimension of Gastrointestinal Symptom Rating Scale between treatments in the initial treatment phase , but the total Gastrointestinal Symptom Rating Scale score improved significantly more on omeprazole 10 mg om than on ranitidine 150 mg bd ( p = 0.006 ) . Both doses of omeprazole improved the total Psychological General Well-Being score more than ranitidine ( omeprazole 10 mg om versus ranitidine 150 mg bd , p = 0.005 , omeprazole 20 mg om versus ranitidine 150 mg bd , p = 0.031 ) . During follow-up , relapsing patients returned to pre-treatment symptom and well-being scores , but these dimensions were restored after treatment . CONCLUSION The quality of life is impaired in patients presenting with reflux symptoms . Irrespective of whether the patients presented with endoscopy positive or endoscopy negative reflux disease , treatment on dem and improved the quality of life OBJECTIVE To determine the diagnostic value of empirical treatment with omeprazole in the diagnosis of gastroesophageal reflux disease ( GERD ) . METHODS Patients with symptoms suggestive of GERD underwent upper gastrointestinal endoscopy and 24-h esophageal pH monitoring . Patients with reflux esophagitis grade 0 or 1 were included in the study and were r and omized to double-blind treatment with either 40 mg omeprazole or placebo o.m . The effect of treatment was evaluated after 1 and 2 wk with a symptom question naire with a four- grade Likert scale , and symptomatic response outcome was compared with the results of 24-h pH-metry . RESULTS Ninety-eight patients were included ; however , 13 were excluded from the final analysis because of protocol violation . Of the remaining 85 patients , 54 had no signs of esophagitis at endoscopy , and 31 had esophagitis grade 1 . The pH registration showed pathological gastroesophageal reflux in 47 patients ( 55 % ) . Forty-one patients were r and omized to treatment with omeprazole and 44 to placebo . There was a significant correlation between the pH registration result and response to omeprazole ( p = 0.04 , chi2 ) , but not to placebo ( p = 0.16 ) . With pH-metry as the gold st and ard , the omeprazole test had positive and negative predictive values of 68 % and 63 % , respectively , for the diagnosis of GERD . When the omeprazole test was used as the gold st and ard , the positive and negative predictive values of pH monitoring were 68 % and 63 % , respectively . Similar sensitivity was found when the pH-metry was compared with presence of esophagitis . CONCLUSION Determination of the symptomatic response to 40 mg of omeprazole for 14 days is a simple and inexpensive tool for the diagnosis of GERD , with a sensitivity and specificity comparable to 24-h pH monitoring BACKGROUND In the absence of highly specific symptoms and without esophageal erosions , long-term pH monitoring is necessary for diagnosing gastroesophageal reflux disease . This method , however , is not generally available . OBJECTIVE To determine whether gastroesophageal reflux disease can be diagnosed empirically by acid suppression in patients with normal results of endoscopy . METHODS We studied 33 consecutive out patients with pathologic findings on pH monitoring who had symptoms compatible with gastroesophageal reflux disease and normal results of esophagogastroduodenoscopy , particularly a normal appearance of the esophageal mucosa . The severity of symptoms was grade d on a visual analog scale from 1 to 10 by the patient . The patients were treated for at least 7 days with either ranitidine , 150 mg twice daily ( patients 1 through 10 ) , omeprazole , 40 mg/d ( patients 11 through 21 ) , or omeprazole , 40 mg twice daily ( patients 22 through 33 ) . A re assessment of symptoms and second pH monitoring were performed during the last day of treatment . RESULTS Omeprazole , 40 mg/d , significantly reduced the severity of symptoms from 7.1 ( range , 4 to 9 ) to 3.7 ( 0 to 8) and the reflux measure mean acidity from 0.98 mmol/L ( 0.21 to 76 mmol/L ) to 0.02 mmol/L ( 0 to 0.47 mmol/L ) . Omeprazole , 40 mg twice daily , significantly reduced the severity of symptoms from 6.8 ( 3 to 10 ) to 0.6 ( 0 to 2 ) and the mean acidity from 0.38 mmol/L ( 0.13 to 8.5 mmol/L ) to 0.01 mmol/L ( 0 to 0.14 mmol/L ) . Both doses of omeprazole were superior to ranitidine , 150 mg twice daily . When a 75 % reduction of symptoms was defined as positive , the " omeprazole test " with 40 mg twice daily had a sensitivity of 83.3 % , whereas the sensitivity with 40 mg/d was only 27.2 % . CONCLUSION In practice , the diagnosis of gastroesophageal reflux disease can be ruled out if symptoms do not improve with a limited course of high-dose proton pump inhibitors The efficacy of cisapride , as compared with cimetidine , in the treatment of erosive esophagitis was studied in a double-blind trial . One hundred and twenty-nine patients were assigned to one of four dosage schedules : cisapride 10 mg b.i.d . ( 20 mg group ) or q.i.d . ( 40 mg group ) , or cimetidine 400 mg b.i.d . ( 800 mg group ) or q.i.d . ( 1600 mg group ) . Treatment lasted 8 to 12 weeks . The degree of esophagitis and the severity of diurnal and nocturnal heartburn and regurgitation were significantly ( p less than 0.01 ) reduced in the four treatment groups . Endoscopy did not show any significant differences among the four groups , although cisapride tended to be more effective in moderate to severe esophagitis , in which cases mucosal healing ( i.e. absence of erosions and ulcers ) was observed in 69 % , 64 % , 55 % and 55 % of the patients treated with cisapride 40 mg , cisapride 20 mg , cimetidine 1600 mg and cimetidine 800 mg . Improvement in reflux symptoms in the two cisapride groups was not significantly different from that in the cimetidine 1600 mg group , but was better ( p less than 0.05 ) than that in the cimetidine 800 mg patients . The severity score for all reflux symptoms had decreased by 79 % , 74 % ( cisapride 40 mg and 20 mg ) , 69 % and 57 % ( cimetidine 1600 mg and 800 mg ) by the end of treatment . These results show that cisapride is at least as effective as acid-suppressing therapy in patients with reflux esophagitis , and is therefore a valuable alternative to it Background : Lacking an objective ‘ gold st and ard ’ for diagnosing dyspepsia , several symptom‐based classifications have been suggested OBJECTIVES : Clinical results to date suggest that antisecretory therapy may be less effective in providing symptom relief for patients with nonerosive gastroesophageal reflux disease ( GERD ) than for patients with erosive disease . This study was carried out to assess the efficacy and rapidity of once-daily rabeprazole ( 10 mg or 20 mg ) in relieving symptoms in endoscopically negative patients with moderately severe GERD symptoms and to evaluate the safety of these doses over 4 wk . METHODS : This placebo-controlled , double blind study enrolled 203 men and women with moderately severe symptoms of GERD . After a 2-wk , single-blind placebo run-in phase , patients were r and omized to receive 10 mg or 20 mg of rabeprazole or placebo once daily for 4 wk . RESULTS : Rabeprazole rapidly and effectively relieved heartburn , with significant improvements on day 1 of dosing . It also improved most other GERD-related symptoms , including regurgitation , belching , bloating , early satiety , and nausea . Both rabeprazole doses were significantly superior to the placebo with respect to time to the first 24-h heartburn-free interval ( 2.5 and 4.5 days for 10 mg and 20 mg of rabeprazole , respectively , vs 21.5 days for the placebo ) and first daytime or nighttime heartburn-free interval ( 1.5–3 days for rabeprazole groups vs 12.5–15 days for the placebo ) , as well as to percentage of time patients were heartburn-free and free of antacid use . Both rabeprazole doses were well tolerated . CONCLUSIONS : Based on these findings and prior studies , rabeprazole reliably relieves GI symptoms equally well in both nonerosive GERD and erosive GERD BACKGROUND : The management of Helicobactor pylori negative patients with dyspepsia in primary care has not been studied in placebo-controlled studies . METHODS : H. pylori negative patients with dyspepsia symptoms of at least moderate severity ( ≥4 on a seven-point Likert scale ) were recruited from 35 centers . Patients were r and omized to a 4-wk treatment of omeprazole 20 mg od , ranitidine 150 mg bid , cisapride 20 mg bid , or placebo , followed by on-dem and therapy for an additional 5 months . Treatment success was defined as no or minimal symptoms ( score ≤ 2 out of 7 ) , and was assessed after 4 wk and at 6 months . RESULTS : Five hundred and twelve patients were r and omized and included in the intention-to-treat ( ITT ) analysis . At 4 wk , success rates ( 95 % CI ) were : omeprazole 51 % ( 69/135 ; 43–60 % ) , ranitidine 36 % ( 50/139 , 28–44 % ) , cisapride 31 % ( 32/105 , 22–39 % ) , and placebo 23 % ( 31/133 , 16–31 % ) . Omeprazole was significantly better than all other treatments ( p < 0.05 ) . The proportion of patients who were responders at 4 wk and at 6 months was significantly greater for those receiving omeprazole 31 % ( 42/135 , 23–39 % ) compared with cisapride 13 % ( 14/105 , 7–20 % ) , and placebo 14 % ( 18/133 , 8–20 % ) ( p= 0.001 ) , but not ranitidine 21 % ( 29/139 , 14–27 % ) ( p= 0.053 ) . The mean number of on-dem and study tablets consumed and rescue antacid used was comparable across groups . Economic analysis showed a trade-off between superior efficacy and increased cost between omeprazole and ranitidine . CONCLUSION : Treatment with omeprazole provides superior symptom relief compared to ranitidine , cisapride , and placebo in the treatment of H. pylori negative primary care dyspepsia patients This article reports quality of life ( QoL ) aspects of a study that investigated the efficacy of three treatment regimens in gastro-oesophageal reflux disease patients . Following a 4-week symptom-control phase ( esomeprazole 40 mg once daily ) , patients were r and omised to 6 months ' esomeprazole 20 mg once daily continuously ( n = 658 ) , on-dem and ( n = 634 ) or ranitidine 150 mg twice daily continuously ( n = 610 ) . Esomeprazole 40 mg once daily improved QoL during the symptom-control phase . At 6 months , both esomeprazole regimens were more effective than ranitidine in all dimensions of the Quality of Life in Reflux and Dyspepsia question naire ( p < 0.0001 ) . Esomeprazole continuous and on-dem and led to a significant improvement in symptoms ( Overall Treatment Evaluation question naire ) compared with ranitidine ( continuous : 80.2 % , on-dem and : 77.8 % , vs. ranitidine 47.0 % ; p < 0.001 ) . Esomeprazole once daily continuously maintained QoL better than esomeprazole on-dem and and was associated with greater patient satisfaction . In conclusion , esomeprazole 20 mg once daily continuously and on-dem and were more effective than ranitidine continuously for maintaining : This r and omized , double‐blind , multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non‐erosive gastro‐oesophageal reflux disease ( GERD ) ABT‐229 , a motilin agonist without antibacterial activity , has been shown to enhance both lower oesophageal sphincter pressure in cats and gastric emptying in humans In an eight-week double-blind trial , the effectiveness of cimetidine ( 1.6 g/day ) was compared to placebo in 34 patients with symptomatic esophagitis confirmed by endoscopy with biopsies and /or by acid infusion test . Patients treated with cimetidine had significantly less symptomatic days during the first six weeks and less symptomatic nights during the first two weeks , and they consumed less antacids during the whole trial period . Endoscopic evaluation of 17 patients on cimetidine and of 15 patients on placebo did not show any significant difference in severity and extent of esophageal lesions after eight weeks , but histological assessment of 16 patients on cimetidine and 13 patients on placebo showed a significant improvement after eight weeks of cimetidine ( P<0.025 ) . These results show that cimetidine has a rapid effect on symptoms of reflux esophagitis and that , in some cases , it may reduce the esophageal lesions after eight weeks The purpose of this study was to assess the rapidity of symptom relief and 4-week efficacy of rabeprazole 20 mg in patients with moderately severe nonerosive gastroesophageal reflux disease . Data were analyzed from 2 similarly design ed , double-blind , placebo-controlled , multicenter , U.S. trials . After a 2-week placebo run-in period , patients ( N = 261 ) were r and omized to 4 weeks of rabeprazole 20 mg once daily or placebo . Patients kept symptom diaries and scored symptom severity . Median time to first 24-hour heartburn-free interval was 3.5 days for the rabeprazole group compared with 19.5 days for the placebo group ( P ≤ .0002 ) . Complete heartburn relief at week 4 was 32 % with rabeprazole and 3.8 % with placebo ( P ≤ .001 ) . Rabeprazole also significantly improved other GERD-associated symptoms ( e.g. , regurgitation , belching , early satiety ) by week 4 compared with placebo ( P ≤ .05 ) . Rabeprazole provides fast and potent relief from heartburn and other symptoms of nonerosive gastroesophageal reflux disease In a multicenter , double-blind trial , 284 patients with gastroesophageal reflux disease were evaluated before , during , and after six weeks of treatment with either placebo or ranitidine ( 150 mg twice daily ) . R and omization result ed in two comparable patient groups . Ranitidine treatment was significantly more effective than placebo treatment in decreasing the frequency and the severity of heartburn during both daytime and nighttime assessment periods . There was a significant correlation between improvement in heartburn symptoms and decrease in antacid consumption ; hence , patients receiving ranitidine consumed significantly fewer antacid tablets . Among patients with endoscopic esophagitis at baseline , the overall change in endoscopic classification after six weeks of therapy was significantly better for the ranitidine-treated patients . The ranitidine-treated group had less evidence of erosions and ulcerations as well as greater healing . There were no differences between the groups with respect to changes in esophageal mucosal sensitivity to acid perfusion or changes in histologic grading of esophageal mucosal biopsy specimens . The ranitidine safety profile was similar to that of previous studies . We conclude that , in patients with gastroesophageal reflux disease , ranitidine therapy , 150 mg twice daily , markedly reduced the heartburn symptoms of reflux disease and significantly improved the endoscopic appearance of the esophageal mucosa Background : Previous studies have demonstrated greater efficacy for omeprazole compared with cimetidine in patients with endoscopically verified oesophagitis , but excluded the substantial group of gastro‐oesophageal reflux disease ( GERD ) patients with reflux symptoms but without endoscopic abnormality . This prospect i ve , r and omized , double‐blind study compared omeprazole and cimetidine in the treatment of GERD‐associated heartburn both in patients with symptomatic non‐ulcerative oesophagitis and in those with heartburn but without oesophagitis BACKGROUND Gastroesophageal reflux disease ( GERD ) , often characterized as heartburn , is a highly common presenting complaint to family physicians . This study is the first large , prospect i ve , nationwide family practice outpatient evaluation of the effectiveness of the histamine (H2)-receptor antagonist ranitidine as medical therapy for this disorder . METHODS This r and omized , double-blind , placebo-controlled , parallel group , 6-week study was design ed to evaluate the effect of ranitidine on clinical outcomes and quality of life in patients with GERD . Eligible patients included those who were at least 18 years old and had at least a 3-month history of heartburn or heartburn therapy and a minimum of 4 days with at least one heart-burn episode in the week preceding the baseline visit . Quality -of-life effects were measured using a general health status instrument and a previously vali date d heartburn-specific question naire . RESULTS Ranitidine treatment conferred clinical ly and statistically significant reductions in mean heartburn pain scores within the first 24 hours ( P < or = .001 ) and mean number of heartburn episodes within the first 48 hours ( P < or = .001 ) . These reductions were maintained throughout the 6-week trial , during both daytime and nighttime . Compared with patients receiving placebo , patients treated with ranitidine also used significantly fewer doses of antacids ( P < or = .003 ) . Further , both ranitidine-treated patients ' and their physicians ' global assessment s of decreases in heartburn severity , as well as clinical improvement on ranitidine , proved superior to those of controls ( P < or = .001 ) . The rate of adverse events associated with ranitidine and placebo was low and similar . Ranitidine-treated patients had more favorable scores on the general health status dimensions of physical functioning , bodily pain , and vitality ( P < .05 ) , and more favorable scores on all dimensions of the heartburn-specific question naire ( P < .05 ) . CONCLUSIONS Twice-daily treatment with ranitidine 150 mg is a valuable therapy for GERD in a typical family practice setting . It reduces the frequency and severity of symptoms within the first 24 to 48 hours of treatment and diminishes the use of nonprescription antacids while improving the quality of life as measured by both a general health status instrument and a disease-specific instrument Background Health-related quality of life ( HRQoL ) is impaired in untreated patients with gastroesophageal reflux disease ( GERD ) . In the absence of an objective marker such as erosions , assessment of treatment efficacy can be based on symptoms and HRQoL. Objective To evaluate changes in HRQoL during treatment with pantoprazole or nizatidine in patients with GERD . Methods This was a prospect i ve , r and omized , double blind Canadian multicenter study . Patients with GERD , characterized by heartburn that had occurred 4 or more times per week for at least 6 months , were treated for 28 days with either pantoprazole 40 mg once daily or nizatidine 150 mg twice daily . HRQoL assessment was performed before endoscopy ( baseline ) and on days 7 and 28 after treatment . HRQoL was assessed using 4 domains of the SF-36 , the SF-12 summary scales and the gastrointestinal system rating scale ( GSRS ) . Results A total of 208 patients ( n = 106 pantoprazole treatment group , n = 102 nizatidine treatment group ) was available for intention-to-treat analysis . Baseline HRQoL scores were comparable between the 2 treatment groups . After 7 days , treatment with pantoprazole led to a statistically significant greater improvement in HRQoL in 2 SF-36 domains : bodily pain ( pantoprazole versus nizatidine , P = 0.0088 ) and vitality ( pantoprazole versus nizatidine , P = 0.0137 ) , and in the GSRS reflux score ( pantoprazole versus nizatidine , P = 0.0078 ) . After 28 days of treatment , the changes in scores relative to baseline were still greater with pantoprazole than with nizatidine . The improvement in the 4 SF-36 domains and the GSRS reflux score achieved by pantoprazole after 7 days were also significantly greater than those achieved by nizatidine after 28 days . Conclusions HRQoL improves more rapidly and to a greater degree following treatment with pantoprazole than nizatidine . Control of heartburn strongly predicts HRQoL improvement during the acute treatment of GERD . Our data support the approach to use pantoprazole instead of nizatidine as the initial therapy for patients with heartburn in a primary care practice setting BACKGROUND Traditionally , proton pump inhibitors are used primarily for patients with esophagitis . However , patients with nonerosive reflux disease may also benefit from these powerful medications . OBJECTIVE To compare the safety and symptom relief efficacy of lansoprazole with ranitidine therapy and with placebo . METHODS In 2 r and omized , double-blind , multicenter trials of 901 patients with symptomatic reflux disease , which was confirmed by endoscopy to be nonerosive , received lansoprazole , 15 or 30 mg once daily ; ranitidine , 150 mg twice daily ; or placebo for 8 weeks . RESULTS Analysis of daily diary data during the first 4 weeks and for the entire 8 weeks of treatment revealed that patients who were treated with either dosage of lansoprazole reported significantly ( P<.05 ) lower percentages of days and nights with heartburn , less pain severity of both day and night heartburn , fewer days of antacid use , and smaller amounts of antacid use compared with patients who were treated with ranitidine or placebo . The incidence of possible or probable treatment-related adverse reactions was comparable among the treatment groups ; abdominal pain and diarrhea were the most commonly reported adverse events . No statistically significant differences were noted between treatment groups in laboratory analyses . CONCLUSION Lansoprazole therapy is more effective than st and ard dosages of ranitidine or placebo in relieving symptoms in patients with endoscopically confirmed non-erosive reflux esophagitis OBJECTIVES : Patients with acid-related symptoms in general practice are often treated empirically with a st and ard dose of proton pump inhibitors ( PPIs ) . The effect of higher doses is not known . The study compared the immediate symptom relieving as well as the long-term effect of st and ard and double dose of omeprazole in such patients . METHODS : Consecutive patients with dyspeptic symptoms , normally treated by the general practitioner with PPIs or H2-blockers were r and omized to treatment with omeprazole 40 mg , 20 mg , or placebo in the morning for 2 wk . Patients with alarm symptoms , IBS , and PPI-treated patients were excluded . Dyspeptic symptoms and Helicobacter pylori status were recorded . The study endpoint was complete relief of the dyspeptic symptoms , which initiated the consultation . Relapse rates and health-care consumption were recorded during 12-month observation . RESULTS : Eight hundred and twenty-nine patients were r and omized . Complete relief of the predominant symptom was obtained by 66 % , 63 % , and 35 % in patients treated with omeprazole 40 mg , 20 mg , and placebo , respectively . No difference was found comparing H. pylori-positive and -negative patients . Relapse rates were high and health-care consumption during 12 months was related to the treatment outcome , but not to the omeprazole dose or the H. pylori status . CONCLUSIONS : Compared to placebo , omeprazole 40 mg and 20 mg were equally and significantly better in relieving acid-related symptoms ; the numbers needed-to-treat ( NNT ) were 3.2 ( 40 mg ) and 3.7 ( 20 mg ) . Relief of the dyspeptic complaint was followed by significantly reduced health-care consumption during 12-month observation Background : Several studies in Western countries showed that proton‐pump inhibitors are superior to histamine2‐receptor antagonists or placebo in the treatment of non‐erosive gastro‐oesophageal reflux disease . The efficacy of acid‐suppressive drugs for non‐erosive gastro‐oesophageal reflux disease in Japan , in which the prevalence of Helicobacter pylori infection is higher compared with Western countries , is unknown BACKGROUND The first step in the management of uncomplicated dyspepsia in primary care often consists of prescribing empirical therapy , but in certain cases prompt endoscopy might be preferred . Any decision is usually based on the patient 's symptoms and the presumed underlying pathology that causes these symptoms . AIM To assess the relationship between symptom subgroups and the effect of management strategies on primary care patients with dyspepsia . DESIGN OF STUDY R and omised controlled trial . SETTING All patients presenting successively with a new episode of dyspepsia between January 1995 and November 1997 . METHOD The results of four management strategies in dyspeptic primary care patients were compared and the value of subgrouping within this trial was estimated . Patients were allocated to one of either ( a ) empirical treatment in which therapy was based on the presented symptoms , or empirical treatment with ( b ) omeprazole or ( c ) cisapride regardless of the presented symptoms , or ( d ) prompt endoscopy followed by the appropriate treatment . Patients were retrospectively classified into the subgroups for each strategy using baseline data . The yield of each strategy was measured by counting the number of strategy failures in the first year . RESULTS Of the 349 included patients , 326 were analysed . No statistically significant difference could be demonstrated between the strategies or between the symptom subgroups . However , patients in the reflux-like subgroup showed a trend towards a better outcome in all empirical strategies . Ulcer-like dyspepsia seemed to benefit from omeprazole . The non-specific subgroup seemed to benefit from cisapride but also had the highest proportion of strategy failure . Prompt endoscopy did not appear especially useful in any subgroup . CONCLUSION Although this study has relatively low power , we conclude that the use of symptom subgroups seems to be a sensible approach when choosing empirical therapy in dyspepsia . Patients with reflux-like symptoms seem to have the best prognosis in the first year in every strategy BACKGROUND Symptoms of gastro-oesophageal reflux are common , and currently available methods for diagnosing reflux disease are expensive and uncomfortable for the patient . The diagnostic value of a treatment test with omeprazole is unclear . METHODS Patients with dyspepsia including heartburn admitted for upper gastrointestinal endoscopy were studied in a prospect i ve , r and omized , double-blind Sc and inavian multicentre study . Before entry 188 patients were enrolled , and 160 were r and omized to 1-week treatment with 20 mg omeprazole twice daily or placebo . Gastro-oesophageal reflux disease ( GERD ) was defined as reflux oesophagitis Savary-Miller grade s II-III at endoscopy or pH < 4 exceeding 4 % of the total time at 24-h oesophageal pH-monitoring and was found in 135 patients . The treatment test was considered positive when the patient 's symptoms improved during the treatment week compared with the pretreatment day . RESULTS The sensitivity in diagnosing reflux disease was 71 - 81 % with omeprazole as a diagnostic test , compared with 36 - 47 % for placebo during treatment days 3 - 7 . The specificity was similar for the two treatment arms during the first days of the study . During the end of the week a larger proportion of the patients with normal endoscopy and pH test responded to omeprazole treatment , giving omeprazole lower specificity than placebo . The investigators ' overall evaluation of whether the patient was a responder to the test had a sensitivity of 75 % and a specificity of 55 % in the omeprazole-treated patients . The corresponding figures in the placebo group were 17 % and 92 % , respectively . CONCLUSION One week of omeprazole treatment is a simple diagnostic test with a fairly high sensitivity . The specificity is poor owing to the placebo effect and to the lack of a gold st and ard in diagnosing reflux disease BACKGROUND Data are limited on the value of effective antisecretory therapy in the relief of heartburn in patients without oesophagitis . METHODS Patients with heartburn , without endoscopic signs of oesophagitis , were r and omized to double-blind treatment with omeprazole , 20 or 10 mg once daily , or placebo , for 4 weeks ( n = 509 ) . Pre-treatment oesophageal acid exposure was assessed using 24-h intra-oesophageal pH monitoring . Heartburn was assessed at 2 and 4 weeks . RESULTS At 4 weeks the proportion of patients with complete absence of heartburn was 46 % ( 95 % confidence interval , 39 - 53 % ) with 20 mg omeprazole , 31 % ( 25 - 38 % ) with 10 mg omeprazole , and 13 % ( 7 - 20 % ) with placebo . Satisfaction with therapy was reported by 66 % , 57 % , and 31 % of the patients , respectively . CONCLUSION Omeprazole , 20 and 10 mg once daily , provides rapid relief of heartburn in patients without endoscopic oesophagitis In a double-blind , r and omized , comparative trial of the prokinetic drug cisapride and the H2-blocker cimetidine , mucosal healing and changes in symptoms of gastroesophageal reflux were evaluated in patients with erosive reflux esophagitis . The patients were treated with either cisapride , 10 mg four times a day ( N=36 ) or cimetidine , 400 mg four times a day ( N=37 ) for six weeks , or for 12 weeks if mucosal healing was not obtained by week 6 . Upon entry , two thirds of the patients in each group had grade I ( Savary-Miller ) esophagitis , and the remainder grade II or III . At the end of treatment , endoscopy showed mucosal healing in 56 % ( 38–72 % ; 95 % confidence interval ) of cisapride and 57 % ( 39–73 % ; 95 % confidence interval ) of cimetidine patients . After six weeks , both drugs significantly ( P<0.01 ) decreased the intensity and frequency of heartburn , regurgitation , and the postural syndrome . No significant inter group differences were found regarding endoscopic parameters or the improvement of heartburn and regurgitation . Concomitant antacid use was also comparable . Adverse effects were reported by four cisapride and nine cimetidine patients . These results indicate that the effects of cisapride compare well with those of cimetidine in terms of both esophageal mucosal healing and symptom relief A postal question naire on heartburn sent to 6760 r and omly selected subjects yielded 3971 replies suitable for analysis . Heartburn had never been experienced by 1665 ( 42 % ) respondents . Significant symptoms of more than three months ' duration that had occurred at least once a month in the preceding 12 months were reported by 1337 ( 34 % ) respondents . Of these , 875 had not consulted their general practitioner and were invited to attend for a structured interview with question naire and upper gastrointestinal endoscopy . A total of 177 were interviewed , and 143 underwent upper gastrointestinal endoscopy . Of those endoscoped , 106 ( 74 % ) experienced symptoms at least once a week . These were relieved by alginate consumption in 97 ( 68 % of ) cases . Just nine ( 6 % ) patients had been taking H2-receptor antagonists . Macroscopic appearances of oesophagitis were seen in 46 cases [ 13 ( 6 % ) grade 1 , 24 ( 11 % ) grade 2 , five ( 2 % ) grade 3 , two ( 1 % ) grade 4 , and two ( 1 % ) grade 5 ] . Three patients had mild strictures and six patients had Barrett 's oesophagus . There were no appearances suggestive of malignancy . Biopsies were taken in 122 cases , including all those in which abnormalities had been seen . Histological evidence of oesophagitis was seen in 47 cases . Gastric metaplasia was found in six cases and dysplasia seen in three . Patients who self-medicate for reflux symptoms have a low prevalence of pre-neoplastic and neoplastic pathology . A substantial proportion , however , have histological evidence of oesophagitis and a small number have metaplasia Gastroesophageal reflux disease ( GERD ) is characterized by heartburn and related symptoms that are distressing to patients and interfere with everyday functioning and well-being . A measure of symptom distress , the GERD Symptom Assessment Scale ( GSAS ) , was included in two r and omized , placebo-controlled trials of rabeprazole among patients with nonerosive GERD . The age ( mean ± SD ) of the 223 patients was 43.5 ± 11.9 years , and most were female ( 67 % ) and Caucasian ( 78 % ) . Significantly greater reductions in symptom distress were observed among patients receiving rabeprazole 20 mg daily for 4 weeks relative to those receiving placebo ( −0.62 vs −0.36 , P < 0.0001 ) . The magnitude of this treatment difference was comparable to the differences observed between levels of overall symptom improvement on the patient global rating ( 0.2 and 0.3 points ; P < 0.0001 ) . In conclusion , reducing symptom distress is an important goal of therapeutic interventions for GERD . Rabeprazole significantly reduced the distress associated with a broad range of GERD symptoms , and the magnitude of this effect was meaningful to patients Twenty-seven patients with symptomatic gastro-oesophageal reflux received cimetidine 1.6 g daily for 6 weeks and matching placebo for 6 weeks in a r and omised double-blind crossover trial . They complained of significantly more episodes of pain on placebo than on cimetidine ( 1186 vs 581 ) and consumed significantly more antacid tablets on placebo than on cimetidine ( 1645 vs. 1011 ) . Cimetidine and placebo had similar effects on mucosal sensitivity to acid and on oesophagitis assessed endoscopically and histologically , suggesting that the symptomatic benefit is the result of a simple antacid effect Background : As many as 50 % of patients with reflux symptoms have no endoscopic evidence of oesophagitis . This multicentre study was design ed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro‐oesophageal reflux disease but without endoscopic evidence of oesophagitis A double-blind crossover study was conducted of two gastric prokinetic drugs in 23 patients with gastroesophageal reflux . Patients were divided into two groups on the basis of a dual-isotope mixed-meal study of their gastric emptying ( GE ) . Group I had normal GE and group II delayed GE . Nine gastrointestinal symptoms were assessed for frequency and severity before treatment . The trial had three 1-month treatment periods using metoclopramide 10 mg q.i.d . , domperidone 20 mg q.i.d . , or placebo on a r and om basis . Symptoms were reassessed at the end of each month . Taken as a whole , the group showed a significant symptomatic response in all three treatment periods ( p less than 0.0001 ) , but patients with delayed or normal GE did not differ significantly in their symptomatic response . Eleven patients complained of side effects with metoclopramide and three stopped therapy before the 1-month course was completed . Two patients described side effects with domperidone , including one woman with galactorrhea after 36 h of treatment . Three patients on placebo also complained of important side effects . We conclude that a significant placebo effect is present in the treatment of gastroesophageal reflux . No significant difference was demonstrated in symptomatic improvement between placebo , domperidone , and metoclopramide in this study The effect of 150 mg ranitidine twice daily was compared with placebo by the double-blind crossover technique ( 8 weeks twice ) in patients with gastro-oesophageal reflux ( paired comparison in 38 patients ) . Ranitidine was superior to placebo with regard to effect on symptoms , improvement of oesophagitis as assessed by endoscopy and biopsy , and decrease of oesophageal acid hypersensitivity . The symptomatic response to ranitidine was , however , unsatisfactory in more than half of the cases . When symptomatic responders taking ranitidine ( R ) were compared with non-responders ( NR ) , there was no difference with regard to the severity of oesophagitis or frequency of positive acid perfusion tests before or after the 8-week treatment . NR were younger and more often had endoscopic signs of incompetence of the cardia and gastric prolapse . Ranitidine is an efficient drug in patients with reflux disease . It can not be expected that mechanical problems in the hiatal region will be influenced by ranitidine , which is probably why half the patients did not respond The healing effect of the prokinetic drug cisapride ( 10 mg q.i.d . ) on esophageal lesions , and its therapeutic control of gastroesophageal reflux symptoms were compared with the effects of the H2-antagonist ranitidine ( 150 mg b.i.d . + placebo b.i.d . ) in a double-blind trial . In each group , 28 patients with Savary-Miller Grade I or II esophagitis were treated for 6 or 12 weeks . At the end of treatment , follow-up endoscopy showed that mucosal lesions were absent in 89 % of the cisapride patients and in 79 % of the ranitidine patients . In addition , 86 % and 82 % of the patients in the cisapride and the ranitidine group , respectively , had no , or only mild , reflux symptoms . Minor side effects were experienced in both groups . From these data , cisapride appears to be as effective as ranitidine in controlling reflux symptoms and in promoting the healing of mucosal lesions in milder forms of reflux esophagitis Previous clinical trials have evaluated a large number of symptomatic individuals with heartburn . Most studies have documented the need for multiple daily dosing with H2‐antagonists to achieve clinical and statistical efficacy for symptom relief . The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens , 40 mg nocte and 20 mg b.d . with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non‐erosive oesophagitis . Famotidine ( 20 mg ) b.d . reduced and eventually completely relieved gastro‐oesophageal reflux disease symptoms in most patients during the 6‐week trial . Global assessment of improvement at 2 and 6 weeks indicated significantly greater improvement with a b.d . treatment regimen than with either a 40 mg nocte or placebo treatment . No statistically significant differences between famotidine and placebo in the number of patients who experienced clinical adverse experiences were noted and no serious adverse events attributable to famotidine occurred . Based upon these findings , patients with gastro‐oesophageal reflux symptoms experience good relief of their complaints with twice daily famotidine in st and ard doses Abstract Objective : To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease . Design : R and omised , multicentre , double blind , controlled study . Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks . Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks . Patients who were symptomatic or mildly symptomatic were followed up for 12 months . Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control . Setting : Hospitals and primary care practice s between 1994 and 1996 . Subjects : 677 patients with gastro-oesophageal reflux disease . Main outcome measures : Total time off active treatment , time to failure of intermittent treatment , and outcomes ranked from best to worst . Results : 704 patients were r and omised , 677 were eligible for analyses ; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs . The median number of days off active treatment during follow up was 142 for the entire study ( 281 for the 526 patients who reached a treatment related end point ) . Thus , about half the patients did not require treatment for at least 6 months , and this was similar in all three treatment groups . According to outcome , 378 ( 72 % ) patients were in the best outcome ranks ( no relapse or one ( or more ) relapse but in remission until 12 months ) ; 630 ( 93 % ) had three or fewer relapses in the intermittent treatment phase . Omeprazole 20 mg provided faster relief of heartburn . The results were similar in patients with erosive and non-erosive disease . Conclusions : Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease . It is simple and applicable in general practice , where most patients are seen OBJECTIVE To investigate the effect of ranitidine in patients with functional dyspepsia according to different subgroups . SETTING University Hospital Utrecht , department of gastroenterology . DESIGN Prospect i ve double blind cross-over study . METHOD Thirty patients with chronic upper abdominal symptoms were included , without somatic cause was found at gastroscopy ( no Helicobacter pylori ) , ultrasonography and blood tests . The mean symptom score of : nausea , vomiting , retrosternal pain , epigastric pain , heartburn , bloating , belching , and early satiety was > or = 2 . The patients recorded severity and frequency of the symptoms in a diary . The same diary was used to score the symptoms during treatment with ranitidine ( 2 dd 150 mg ) or placebo , each for 2 weeks with a wash out period of 3 days . 29 patients scored correctly . RESULTS 13 ( 43 % ) patients had dysmotility-like dyspepsia , 5 ( 17 % ) reflux-like dyspepsia , and 11 ( 40 % ) non-specific dyspepsia ( i.e. a combination of dysmotility-like , reflux-like or ulcer-like symptoms ) . Ranitidine significantly improved the severity of heartburn after two weeks of treatment , as compared to placebo ( p = 0.035 ) , notably in the patients with reflux-like dyspepsia . Because of a carry-over effect analysis of the symptoms ' belching ' and ' early satiety ' was not possible . CONCLUSION Within the group of patients with functional dyspepsia a subgroup of reflux-like dyspepsia patients can be identified that responds well to ranitidine Background : Patients with chronic heartburn but with no endoscopic evidence of erosive oesophagitis require gastric acid suppression to relieve symptoms We compared the effects of cimetidine , metoclopramide , and placebo in the short-term therapy of symptomatic gastroesophageal reflux in a placebo double-blind trial . Of 50 patients , 20 received cimetidine 300 mg , 20 received metoclopramide 10 mg , and 10 received placebo , all four times a day before meals and at bedtime . Patients followed other conventional therapy for gastroesophageal reflux . Before and at the end of the 8-week period , the esophagus was assessed endoscopically , its mucosal sensitivity was tested by a quantitative Bernstein test , and its mean resting lower sphincter pressure ( LESP ) was measured . We made frequent assessment s of symptom severity , frequency of antacid usage , adverse effects , and laboratory studies . After 8 weeks , the percentage of patients with endoscopic improvement was slightly higher for metoclopramide-treated patients than for the others . LESP was not different for cimetidine , metoclopramide , or placebo patients and did not rise from low pretreatment values . Bernstein tests showed mucosai sensitivity had not altered in cimetidine or metoclopramide patients . A significant number of patients who were taking cimetidine or metoclopramide , however , had less pain than before . Although antacid usage decreased in all three groups , it was significantly lower only in patients treated with cimetidine or metoclopramide . There were no laboratory abnormalities . Six of 20 patients taking metoclopramide reported neurologic and psychotropic symptoms such as drowsiness , lethargy and hyperactivity ; three withdrew after 48 hours , one had acute torticollis , and of the remaining three , two became depressed . Cimetidine or metoclopramide is therefore more effective than placebo for the relief of symptoms of gastroesophageal reflux disease , but metoclopramide is attended by significant side effects Background : Few studies have specifically addressed the management of the symptoms of gastro‐oesophageal reflux disease , and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents BACKGROUND The efficacy of omeprazole , 20 mg once daily , in the treatment of reflux oesophagitis and the therapeutic advantages over the histamine H2 receptor antagonists are well documented . This study assessed 20 mg omeprazole daily ( OM20 ) , 10 mg omeprazole daily ( OM10 ) , and 150 mg ranitidine ( RAN ) twice daily for symptom relief in gastro-oesophageal reflux disease ( GORD ) . METHODS Patients ( n = 994 ) presenting with heartburn to their general practitioner underwent endoscopy to exclude peptic ulcer disease and were r and omized into a UK , multicentre , parallel-group , double-blind comparison of the three treatments for 4 weeks . Symptoms were assessed at clinic visits after 2 and 4 weeks . RESULTS Symptom relief after 4 weeks was achieved by 61 % ( OM20 ) , 49 % ( OM10 ) , and 40 % ( RAN ) patients ( OM20 versus OM10 , P < 0.0167 ; OM20 versus RAN , P < 0.0001 ; OM10 versus RAN , P < 0.01 ) . Among the patients ( 32 % ) with erosive reflux oesophagitis , symptom relief was achieved in 79 % ( OM20 ) , 48 % ( OM10 ) , and 33 % ( RAN ) ( OM20 versus OM10 , P < 0.0001 ; OM20 versus RAN , P < 0.0001 ; OM1O versus RAN , NS ) . CONCLUSION Omeprazole , 20 mg , is the most effective initial therapy for relief of GORD symptoms OBJECTIVES : Gastroesophageal reflux disease ( GERD ) in primary care practice presents symptomatically , and re sources to distinguish promptly between erosive esophagitis and endoscopy-negative reflux disease ( ENRD ) are limited . It is therefore important to determine the roles of proton pump inhibitors and histamine-2–receptor antagonists for first-line symptom-based therapy in patients with erosive esophagitis and ENRD . The aim of this study was to compare pantoprazole 40 mg once daily versus nizatidine 150 mg b.i.d . in a mixed GERD patient population with ENRD or erosive esophagitis ( Savary-Miller grade s 1–3 ) . METHODS : A 4-wk r and omized , double-blind , parallel-group , multicenter study conducted in Canada . Eligible patients had experienced GERD symptoms ≥4 times weekly for > 6 months . Patients were r and omized to pantoprazole 40 mg once daily or nizatidine 150 mg b.i.d .. Endoscopy was performed before r and omization and after 4 wk of therapy . RESULTS : Of 220 patients r and omized to therapy , 208 were available for a modified intent-to-treat analysis . Erosive esophagitis was present in 125 patients ; 35 patients were Helicobacter pylori positive . There was complete symptom relief after 7 days of therapy in 14 % of patients on nizatidine and in 40 % of those on pantoprazole ( p < 0.0001 ) , and after 28 days of treatment in 36 % and 63 % of patients , respectively ( p < 0.0001 ) . After 28 days of treatment , adequate heartburn control was reported by 58 % of the nizatidine group and in 88 % of the pantoprazole ( p < 0.0001 ) ; erosive esophagitis healing rates were 44 % for nizatidine and 79 % for pantoprazole ( p < 0.001 ) . Rescue antacid was needed by a greater number of patients using nizatidine than of those using pantoprazole ( p < 0.001 ) . H. pylori infection was associated with an increased probability of erosive esophagitis healing . CONCLUSIONS : Pantoprazole once daily was superior to nizatidine b.i.d . in producing complete heartburn relief in a mixed population of GERD patients and in achieving erosion healing . The proportions of patients with complete symptom relief were greater with pantoprazole after 7 days of therapy than with nizatidine after 28 days . The present study data suggest that pantoprazole is a highly effective first-line therapy for the management of gastroesophageal reflux disease in a primary care practice setting BACKGROUND This study was performed to study the demography , effect of treatment with ranitidine and relapse pattern in patients with reflux symptoms . METHODS Patients with reflux symptoms were examined by endoscopy and included in a double-blind , comparative trial of placebo and ranitidine 150 mg b.i.d . for two weeks . At two weeks satisfied patients continued the same treatment . Non-satisfied patients were r and omised to ranitidine 150 mg b.i.d . or q.i.d for another two weeks . After four weeks medication was stopped and satisfied patients were followed for 24 weeks . No further endoscopy was performed . RESULTS Four hundred and twenty-seven patients were r and omised . At two weeks there was no significant difference between placebo and ranitidine , regarding the proportion of patients with complete relief from symptoms or satisfied with treatment . Ranitidine was superior to placebo in improving symptoms at two weeks . Ranitidine , 150 mg q.i.d . offered no additional advantage in weeks three to four over prolonging treatment with 150 mg b.i.d . after the first two weeks . Patients with oesophagitis at inclusion relapsed more than those with symptoms only , 67 % compared with 52 % , ( p = 0.013 ) . CONCLUSIONS The effect of ranitidine was marginal compared to placebo . The relapse rate was high after treatment stopped As part of a multicenter trial evaluating ranitidine in the treatment of gastroesophageal reflux disease , the therapeutic responses of patients with and without abnormal endoscopic findings were evaluated . All patients were r and omized to either placebo or ranitidine ( 150 mg bid ) treatment groups . The treatment interval was 6 wk . Thirty-seven percent of 283 patients enrolled in the trial had normal baseline endoscopy . Compared to the placebo group , 147 evaluable ranitidine patients with abnormal endoscopy displayed a marked and rapid symptom reduction which was sustained throughout the last 4 wk of therapy . Despite r and omization of endoscopically normal patients , those treated with ranitidine had significantly more heartburn at baseline . However , the 89 evaluable ranitidine-treated patients with normal endoscopy also experienced a marked and rapid reduction in heartburn at the end of 1 wk . The symptomatic improvement in the endoscopically abnormal ranitidine patients was significantly greater ( p less than 0.05 ) than that observed in the endoscopically normal ranitidine group . Since both groups fared better on ranitidine than placebo , the results of this study indicate that ranitidine is an effective treatment for patients with heartburn symptoms and documented esophageal acid sensitivity whether or not endoscopic parameters for esophagitis are present A question naire was constructed and vali date d to improve the accuracy of symptom assessment in diagnosing gastro‐oesophageal reflux disease ( GERD ) . The GERD question naire consisted of four questions describing an upward moving , uncomfortable feeling in the chest frequently accompanied by retrosternal burning that is improved with antacids . It was found that if a patient answered yes to all four questions the likelihood was 85 % that erosive oesophagitis would be detected on endoscopy or that pathological gastro‐oesophageal reflux on 24‐hour pH‐monitoring would be documented , or both |
2,475 | 25,108,904 | On the basis of this systematic review and meta- analysis of 5 r and omized controlled trials , there is no statistically significant difference in outcome between patients undergoing ACL reconstruction with hamstring autograft and those undergoing ACL reconstruction with soft-tissue allograft . | PURPOSE To compare outcomes of anterior cruciate ligament ( ACL ) reconstruction with hamstring autograft versus soft-tissue allograft by systematic review and meta- analysis . | Although allograft use for primary anterior cruciate ligament reconstruction has continued to increase during the last 10 years , concerns remain regarding the long-term function of allografts ( primarily that they may stretch with time ) and clinical efficacy compared with autograft tendons . We attempted to address these issues by prospect ively comparing identical quadrupled hamstring autografts with allograft constructs for primary anterior cruciate ligament reconstruction in patients with a minimum followup of 3 years . Eighty-four patients ( 37 with autografts and 47 with allografts ) were enrolled ; the mean followup was 52 ± 11 months for the autograft group and 48 ± 8 months for the allograft group . Outcome measurements included objective and subjective International Knee Documentation Committee scores , Lysholm scores , Tegner activity scales , and KT-1000 arthrometer measurements . The two cohorts were similar in average age , acute or chronic nature of the anterior cruciate ligament rupture , and incidence of concomitant meniscal surgeries . At final followup , we found no difference in terms of Tegner , Lysholm , KT-1000 , or International Knee Documentation Committee scores . Five anterior cruciate ligament reconstructions failed : three in the autograft group and two in the allograft group . Our data suggest laxity is not increased in allograft tendons compared with autografts and clinical outcome scores 3 to 6 years after surgery are similar . Level of Evidence : Level II , therapeutic study . See the Guidelines for Authors for a complete description of levels of evidence PURPOSE To investigate the influence of harvesting semitendinosus and gracilis tendons on the rotational muscle strength of the limb after anterior cruciate ligament ( ACL ) reconstruction . TYPE OF STUDY Prospect i ve study . METHODS We performed a prospect i ve study of 62 consecutive ( 34 male , 28 female ) patients with ACL reconstructions using the semitendinosus and gracilis tendons . The mean age at surgery was 20.8 years . The semitendinosus tendon was harvested in 32 patients ( ST group ) , and semitendinosus and gracilis tendons in 30 patients ( STG group ) . The peak isokinetic torques for extension , flexion , internal rotation , and external rotation were measured before and 12 months after ACL reconstruction using the Cybex 6000B system ( Cybex Division of Lumex , Ronkonkoma , NY ) . The rotational torque was measured at 30 degrees/sec and 120 degrees/sec . RESULTS Before reconstruction , the mean isokinetic peak torque of the involved limb was decreased in extension and internal rotation . The mean isokinetic peak torque of the involved limb in extension recovered 12 months after ACL reconstruction ; however , the weakness in internal rotation persisted . The preoperative weakness of the involved limb in extension and internal rotation recovered in the male patients , but not in the female patients after postoperative rehabilitation . The peak torque of the involved limb in internal rotation was decreased in the STG group , but not in the ST group . CONCLUSIONS The internal rotational torque was influenced by harvesting the semitendinosus and gracilis tendons after ACL reconstruction , especially in female patients and patients from whom the gracilis tendon was harvested . Semitendinosus and gracilis tendons are important for the internal rotation of the limb and it was difficult to compensate for this function . Thus , we recommend harvesting the semitendinosus tendon only if tendon quality is sufficient to further minimize harvesting morbidity Purpose This study is to compare the clinical and radiographic results of anterior cruciate ligament ( ACL ) reconstruction with four-str and ed autogenous hamstring tendon and two-str and ed free tendon Achilles allograft fixed with EndoButton in the femoral tunnel and Intrafix in the tibial tunnel . Material s and methods 106 patients diagnosed with ACL rupture underwent ACL reconstruction . Autogenous hamstring tendon was used in 33 patients ( group I ) and free tendon Achilles allografts were used in 32 patients ( group II ) . Median age was 23 years old ( 20–51 ) in group I and 22 years old ( 20–55 ) in group II . Range of motion , Lachman test , Pivot shift test , IKDC score , Lysholm score and side-to-side difference ( SSD ) were evaluated preoperatively and at the last follow-up . Tegner activity scale was evaluated before injury and at the last follow-up . Results The mean follow-up periods were 28.1 months in group I and 31.6 months in group II . Range of motion of the knee was not different from that of the unaffected side in most cases except one flexion deficit in group I and three in group II ( n.s . ) . One in group I and three in group II showed grade two or three laxity on Lachman test at the last follow-up . One in group I and three in group II showed clear positive results on Pivot shift test at the last follow-up . Thirty in group I and 26 in group II were classified to IKDC A or B at the last follow-up ( n.s . ) . Median Lysholm scores were 98 ( 85–100 ) in group I and 99 ( 85–100 ) in group II at the last follow-up ( n.s . ) . Median Tegner activity scales were 6 ( 5–9 ) in group I and 6 ( 4–9 ) in group II at the last follow-up ( n.s . ) . The mean SSD at the last follow-up were 1.4 ± 2.0 mm in group I and 1.9 ± 2.4 mm in group II ( n.s . ) . Conclusion Clinical and radiological outcomes of ACL reconstruction with two-str and ed free tendon Achilles allograft were comparable to those of four-str and ed autogenous hamstring tendon . This technique is reasonable to accomplish good results without some weaknesses when using allograft with bone block . Level of evidence Therapeutic r and omized controlled prospect i ve study , Level Background : Most studies of allograft versus autograft for anterior cruciate ligament reconstruction have been of bone – patellar tendon – bone ; outcome reports evaluating anterior cruciate ligament reconstruction with hamstring tendon autograft versus allograft are rare . Purpose : This study was undertaken to compare the clinical outcome of arthroscopic anterior cruciate ligament reconstruction with hamstring tendon autograft versus allograft . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : Between 2000 and 2004 , 208 patients who met the inclusion and exclusion criteria of the study were prospect ively r and omized into autograft ( n = 104 ) or allograft ( n = 104 ) groups . All hamstring tendon allografts were fresh-frozen and obtained from a single certified tissue bank . All the operations were done by the same surgeon with the same surgical technique . Femoral and tibial fixation was by means of an EndoButton and a bioabsorbable interference screw augmented with a staple , respectively . Patients were evaluated preoperatively and postoperatively . Evaluations included detailed history , physical examination , functional knee ligament testing , KT-2000 arthrometer testing , Harner vertical jump and Daniel 1-legged hop tests , Lysholm score , Tegner score , the International Knee Documentation Committee ( IKDC ) st and ard evaluation form , Cincinnati knee score , and radiographs . Results : Of these patients , 186 ( autograft , n = 91 ; allograft , n = 95 ) were available for full evaluation . Demographic data were comparable between groups . The mean follow-up was 7.8 years for both groups . There were no statistically significant differences according to the evaluations of the outcome aforementioned between the 2 groups except that patients in the allograft group had a shorter operation time than the autograft group . Seven patients ( 7.7 % ) in the autograft group and 8 ( 8.4 % ) in the allograft group had a side-to-side difference > 5 mm . Eighty-five patients ( 93.4 % ) in the autograft group and 86 ( 90.5 % ) in the allograft group were normal or nearly normal according to the overall IKDC . According to the subjective IKDC , the average scores were 89 and 90 points , respectively , for the autograft and allograft groups . The mean Lysholm and Tegner scores were 89 points and 7.7 points , respectively , for the autograft group and 90 points and 7.6 points , respectively , for the allograft group . For the Cincinnati knee score , the average scores were 90 and 91 points , respectively , for the autograft and allograft groups . Conclusion : Both groups of patients achieved almost the same satisfactory outcome at an average of 7.8 years of follow-up . Fresh-frozen hamstring tendon allograft is a reasonable alternative choice to autograft for anterior cruciate ligament reconstruction Background : Tearing an anterior cruciate ligament ( ACL ) graft is a devastating occurrence after ACL reconstruction ( ACLR ) . Identifying and underst and ing the independent predictors of ACLR graft failure is important for surgical planning , patient counseling , and efforts to decrease the risk of graft failure . Hypothesis : Patient and surgical variables will predict graft failure after ACLR . Study Design : Prospect i ve cohort study . Methods : A multicenter group initiated a cohort study in 2002 to identify predictors of ACLR outcomes , including graft failure . First , to control for confounders , a single surgeon ’s data ( n = 281 ACLRs ) were used to develop a multivariable regression model for ACLR graft failure . Evaluated variables were graft type ( autograft vs allograft ) , sex , age , body mass index , activity at index injury , presence of a meniscus tear , and primary versus revision reconstruction . Second , the model was vali date d with the rest of the multicenter study ’s data ( n = 645 ACLRs ) to evaluate the generalizability of the model . Results : Patient age and ACL graft type were significant predictors of graft failure for all study surgeons . Patients in the age group of 10 to 19 years had the highest percentage of graft failures . The odds of graft rupture with an allograft reconstruction are 4 times higher than those of autograft reconstructions . For each 10-year decrease in age , the odds of graft rupture increase 2.3 times . Conclusion : There is an increased risk of ACL graft rupture in patients who have undergone allograft reconstruction . Younger patients also have an increased risk of ACL graft failure . Clinical Relevance : Given these risks for ACL graft rupture , allograft ACLRs should be performed with caution in the younger patient population BACKGROUND The Oxford Levels of Evidence are now routinely assigned at many orthopaedic journals . One disadvantage of this approach is that study design s with a higher level of evidence may be given greater weight than the overall quality of the study merits . In other words , there is no guarantee that research is scientifically valid simply because a more sophisticated study design was employed . The aim of this study was to review Level-I and II therapeutic studies on lateral epicondylitis to measure variation in quality among the highest-level study design s. METHODS Fifty-four prospect i ve r and omized therapeutic trials involving patients with lateral epicondylitis were evaluated by two independent review ers according to the Oxford Levels of Evidence , a modification of the Coleman Methodology Score ( a 0 to 100-point scale ) , and the revised CONSORT ( Consoli date d St and ards of Reporting Trials ) score . RESULTS The two review ers were consistent in their use of the Oxford Levels of Evidence ( kappa = 0.73 , p < 0.01 ) , the modified Coleman Methodology Score ( kappa = 0.73 ; p < 0.01 ) , and the CONSORT score ( kappa = 0.53 ; p < 0.01 ) . Both review ers rated the majority of studies as Level II ( 91 % and 94 % ) and as unsatisfactory according to the Coleman Methodology Score ( 87 % and 89 % ) and the CONSORT score ( 62 % and 63 % ) . Areas of deficiency included poor descriptions of recruitment ( > 90 % of the trials ) , power-level calculations ( 73 % ) , r and omization ( 58 % ) , blinding ( 90 % ) , and participant flow ( 50 % ) as well as inadequate follow-up , sample size , and blinding . CONCLUSIONS The use of the gold-st and ard trial design , the prospect i ve r and omized therapeutic study ( Level-I or II evidence ) , does not ensure quality research or reporting . Critical analysis of scientific work is important regardless of the study design . Clinical scientists should be familiar with the CONSORT criteria and adhere to them when reporting clinical trials PURPOSE To compare the clinical outcomes of arthroscopic anterior cruciate ligament ( ACL ) reconstruction with hamstring tendon autograft versus irradiated allograft . METHODS All irradiated hamstring tendon allografts ( gracilis and semitendinosus ) , which were sterilized with 2.5 Mrad of irradiation before distribution , were obtained from a single certified tissue bank . A total of 78 patients undergoing arthroscopic ACL reconstruction were prospect ively r and omized consecutively into 1 of 2 groups : autograft and irradiated allograft . The same surgical technique was used in all operations , which were performed by the same senior surgeon . Before surgery and at a mean of 42.2 months of follow-up , patients were evaluated by the same observer according to objective and subjective clinical evaluations . RESULTS Of the patients , 67 ( 36 in autograft group and 31 in irradiated allograft group ) were available for full evaluation . When the irradiated allograft group was compared with the autograft group at the final follow-up by the Lachman test , anterior drawer test , pivot-shift test , and KT-2000 arthrometer ( MEDmetric , San Diego , CA ) assessment , statistically significant differences were found ( P = .00011 , P = .00016 , P = .008 , and P = .00021 , respectively ) . Most importantly , 86.1 % of patients in the autograft group and only 32.3 % in the irradiated allograft group had a side-to-side difference of less than 3 mm according to KT-2000 assessment . The rate of laxity ( side-to-side difference > 5 mm ) with irradiated allograft ( 32.3 % ) was higher than that with autograft ( 8.3 % ) . The anterior and rotational stabilities decreased significantly in the irradiated allograft group . According to the overall International Knee Documentation Committee rating , functional and subjective evaluations , and activity level testing , no statistically significant differences were found between the 2 groups . However , patients in the irradiated allograft group had a shorter operative time and a longer duration of postoperative fever . When the patients had a fever , the laboratory examination findings of all patients were almost normal ( white blood cell count , normal ; erythrocyte sedimentation rate , 8 to 20 mm/h ; and C-reactive protein level , 4 to 11 mg/L ) . CONCLUSIONS The clinical outcome of ACL reconstruction with hamstring tendon autograft was satisfactory , whereas the difference in instrumented laxity between the 2 groups was significant and the difference in functional test results was not significant . LEVEL OF EVIDENCE Level II , prospect i ve comparative study Objective : The purpose of this study was to evaluate and characterize the agonist-antagonist strength balance ( hamstring/quadriceps [ H/Q ] ratio and dynamic control ratio [ DCR ] ) about the knee specific to velocity , range of motion , and contraction type . We hypothesized that there would be systematic variation in the H/Q ratio and DCR based on knee joint angle , angular velocity , and contraction type . We also hypothesized that these ratios would be altered in the anterior cruciate ligament (ACL)-reconstructed group in favor of protecting the ACL graft ( relative knee flexor strength when strain on the ACL is the greatest ) . Design : Cross-sectional design . Setting : A tertiary care sport medicine clinic . Patients or Participants : Sixteen subjects more than 1 year after hamstring tendon ACL reconstruction were compared with 30 active uninjured control subjects . Interventions : Isokinetic strength testing was performed over 5 ° to 95 ° knee joint range of motion , 5 angular velocities ( 50 , 100 , 150 , 200 , 250 ° /s ) , for concentric and eccentric contractions . Main Outcome Measurements : Angle and velocity-matched H/Q ratio maps and DCR maps were produced for each group . Difference maps allowed quantification of the differences between the groups . Results : Angle and velocity-matched H/Q ratio maps demonstrated systematic variation based on joint angle , velocity , and contraction type for both the control ( H/Q , ~0–1.42 ; DCR , ~0–1.57 ) and the ACL-reconstructed group ( H/Q , ~0–1.33 ; DCR , ~0–1.35 ) . Difference maps demonstrate regional ( angle and velocity-specific ) alteration in the ratio between the ACL-reconstructed and control groups . Conclusions : Specific imbalances were demonstrated in the ACL-reconstructed group compared with control . In high knee flexion angles , the low H/Q ratio may represent a compromised ability of the hamstrings to stabilize the knee joint throughout the full range of motion . Near full knee extension shifts in favor of the knee flexors may represent an attempt to stabilize the knee at the angle of greatest ACL strain . These finding have implication s for graft donor site selection and postoperative rehabilitation as well as provide insight into the neuromuscular control of the knee PURPOSE To compare the results and outcome of anterior cruciate ligament ( ACL ) reconstruction using autogenous hamstring tendon versus fresh-frozen allograft anterior tibialis tendon . METHODS A prospect i ve r and omized study was conducted from September 2002 to October 2006 . We r and omized 147 patients to undergo ACL reconstruction with either autogenous hamstring or fresh-frozen allograft anterior tibialis tendon . Of these patients , 102 ( 69 % ) completed a minimum of 2 years ' follow-up . There were 54 patients in the hamstring group ( 73 % of those originally enrolled in the group ) and 48 patients in the allograft group ( 66 % ) . All patients underwent st and ardized subjective and objective evaluation with functional outcome assessment s ( International Knee Documentation Committee [ IKDC ] ) , and st and ardized radiographs were also obtained . RESULTS The mean age was 32.0 years for the autograft group and 33.3 years for the allograft group . There was no difference in stability between the 2 groups ( P > .05 ) . The mean IKDC subjective score was 91.0 for the autograft group and 90.9 for the allograft group ( P > .05 ) . The functional IKDC scores for the autograft group were normal in 46 patients ( 85 % ) , nearly normal in 7 patients ( 13 % ) , and severely abnormal in 1 patient . For the allograft group , the functional IKDC scores were normal in 43 patients ( 90 % ) and nearly normal in 5 ( 10 % ) ( P > .05 ) . There were 4 reoperations in the allograft group and 3 reoperations in the autograft group . No patient underwent revision ACL surgery or planned to undergo revision surgery because of instability in either group during the study period despite the 1 patient in the autograft group with a pivot shift and a maximum manual KT measurement ( MEDmetric , San Diego , CA ) of 5 mm . CONCLUSIONS The use of fresh-frozen anterior tibialis allograft ( non-treated ) for ACL reconstruction produced similar subjective and functional outcomes at 24 months ' minimal follow-up compared with patients undergoing ACL reconstruction with autograft hamstring tendon . LEVEL OF EVIDENCE Level II , prospect i ve comparative study |
2,476 | 25,963,067 | In conclusion , IFN-based therapy is beneficial and may be recommended in the management of HCV-related HCC patients who are IFN eligible | Hepatitis C virus ( HCV ) is the leading cause of hepatocellular carcinoma ( HCC ) , and several antiviral agents are available for the treatment of chronic HCV infection .
However , the impact of antiviral therapy on the long-term outcomes of HCV-related HCC patients remains inconclusive .
We aim ed to examine the impact of antiviral therapy on the long-term outcomes of HCV-related HCC patients . | Context Hepatocellular carcinoma often follows hepatitis C virus infection . Currently available treatments for hepatocellular carcinoma are unsatisfactory . Percutaneous ethanol injection therapy into tumor nodules shows some promise , but recurrence rates are high . Contribution In a carefully selected group of 74 patients with multicentric hepatocellular carcinoma , mild hepatitis C , and mild cirrhosis , patients r and omly assigned to receive interferon in addition to ethanol injections showed improved survival at 5 and 7 years , particularly among patients with a sustained virologic response . Caution s Combined treatment of multicentric hepatocellular carcinoma offers the possibility of enhanced survival for carefully selected patients ; this study is small , however , and enrolled only patients with low virus levels and mild cirrhosis . The Editors Chronic hepatitis C virus ( HCV ) infection is a common , frequently asymptomatic disease . Despite the clinical ly quiescent course of HCV infection , it may slowly progress to cirrhosis and , eventually , to hepatocellular carcinoma ( 1 , 2 ) . Cirrhosis is a major risk factor for the development of hepatocellular carcinoma ( 3 , 4 ) , and 70 % to 80 % of patients with hepatocellular carcinoma in Japan have HCV infection ( 5 ) . Current strategies for treating hepatocellular carcinoma include surgical resection , transarterial embolization , percutaneous ethanol injection therapy , radiofrequency wave ablation , and chemotherapy ( 6 - 9 ) . Recent studies have shown that percutaneous ethanol injection therapy is effective for hepatocellular carcinoma when the tumors are small ( <3 to 5 cm in diameter ) and limited in number ; survival rates are similar to those obtained with surgery ( 10 - 12 ) . Five-year survival rates , however , are poor ( 30 % to 60 % for both hepatectomy and percutaneous ethanol injection therapy ) . Poor prognosis may be the result of the high incidence of tumor recurrence ; the cumulative recurrence rate at 5 years is 60 % to 100 % ( 10 - 13 ) . Several studies have evaluated the factors that contribute to the recurrence of hepatocellular carcinoma ( 12 , 13 ) . Occasionally , early recurrence develops adjacent to the treated lesion ( local recurrence , 6 % to 33 % depending on tumor size ) ( 14 ) , but most tumors ( 80 % to 90 % ) recur at different sites ( 15 ) . Because hepatocellular carcinoma recurrence and decompensation of underlying liver disease are major problems after medical or surgical treatment , liver transplantation is another option for treating small , unresectable hepatocellular carcinomas in patients with cirrhosis . Studies report 5-year survival rates as high as 75 % with liver transplantation ( 16 - 18 ) . Interferon therapy has beneficial effects in chronic HCV infection ( 19 , 20 ) . In long-term follow-up studies , sustained virologic responders have remained in remission with normal liver function and improved histologic features of inflammation ; in some of these responders , fibrosis even regresses ( 21 , 22 ) . Recently , the frequency of hepatocellular carcinoma in patients receiving interferon therapy has substantially decreased , especially in patients with sustained virologic and biochemical responses ( 23 - 25 ) . This decreased frequency has occurred even in patients with cirrhosis ( 25 , 26 ) . Our study evaluated whether complete ablation of neoplastic nodules and administration of antiviral therapy could increase survival rates . Methods Study Design Our prospect i ve study was design ed by an eight-member committee in December 1992 . The Ethics Committee of the University of Tokyo approved the study . We obtained informed consent from each patient in accordance with the Helsinki declaration . Patients with compensated cirrhosis , three or fewer nodules of hepatocellular carcinoma , and low HCV RNA loads were recruited after complete ablation of the lesions . Eligibility Criteria Inclusion Criteria Hepatitis C virus infection was diagnosed on the basis of identification of anti-HCV antibody using the passive hemagglutination test ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( ELISA ; Ortho Diagnostic Systems , Tokyo , Japan ) . Hepatitis C virus RNA was identified by reverse transcriptase polymerase chain reaction ( RT-PCR ) . The serum HCV RNA level was measured by competitive reverse transcriptase (CRT)-PCR according to the method of Kato and colleagues ( 27 ) ; HCV genotype was determined by the method of Okamoto and colleagues ( 28 ) . Hepatocellular carcinoma was suspected on the basis of several imaging methods , including abdominal ultrasonography , dynamic computed tomography ( CT ) , magnetic resonance imaging ( MRI ) , and arteriography . We confirmed the diagnosis by histologic examination of tumor biopsy specimens obtained from all patients . Evaluation was based on the criteria of the International Working Party ( 29 ) . In addition , we obtained and evaluated biopsy specimens from non-neoplastic lesions according to the methods of Desmet and colleagues ( 30 ) . Hepatocellular carcinoma was treated with percutaneous ethanol injection therapy ( 7 , 8 , 10 ) . Real-time linear-array scanners were used with 3.5-MHz transducers for the sonographic guidance of needles [ 21-gauge with a 15-cm or 20-cm needle ; Hanako , Tokyo , Japan ] into the tumors . Two to 10 mL of 99.5 % ethanol was injected into each lesion . Ethanol injection was repeated several times at different sessions . Complete destruction of the nodules was confirmed on dynamic CT 1 month after ethanol injection according to the following criteria : 1 ) The destructive area was larger than the area of the tumor nodule shown on pretreatment dynamic CT and 2 ) dynamic CT showed no early-phase contrast enhancement of nodules ( 7 , 8 , 10 ) . Inclusion criteria were as follows : 1 ) hepatocellular carcinoma with three or fewer lesions [ verified by histologic examination ] and dynamic CTconfirmed complete ablation of hepatocellular carcinoma lesions by percutaneous ethanol injection therapy , 2 ) detection of HCV RNA by RT-PCR and an HCV RNA load of 2 106 copies/mL or less by CRT-PCR ( the cutoff value was based on unpublished data indicating that interferon treatment was effective in patients with HCV RNA loads of 105 copies/50 L of serum by CRT-PCR [ 27 ] ] , 3 ) platelet count of 50 109 cells/L , 4 ) leukocyte count of 3 109 cells/L or greater , 5 ) compensated cirrhosis in ChildPugh stage A , 6 ) age younger than 70 years , 7 ) no previous treatment with interferon , and 8) su bmi ssion of informed consent . Exclusion Criteria Exclusion criteria were as follows : 1 ) liver diseases due to other causes , such as hepatitis B or primary biliary cirrhosis ; 2 ) HCV RNA load of 2 106 copies/mL or greater by CRT-PCR ; 3 ) severe comorbid diseases , such as heart disease , lung disease , or diabetes mellitus ; 4 ) decompensated cirrhosis in ChildPugh stage B or C ; and 5 ) failure to obtain informed consent . R and omization Patients who enrolled in the study were r and omly assigned in a 2:1 ratio to the interferon group or the control group by the controller . We assigned patients to the treatment group or control group by using a r and omization list . Interferon Therapy and Follow-up of Patients Interferon Therapy We started interferon therapy with natural interferon- ( Sumitomo Pharmaceuticals , Tokyo , Japan ) 2 to 3 months after tumor ablation was confirmed . Patients received 6 million U of interferon by intramuscular injection three times weekly for 48 weeks as out patients . If patients could not tolerate this dose , the interferon dose was reduced to 3 million U. If HCV RNA in serum was still detected by RT-PCR ( detection limit , 102 copies/mL ) after 24 weeks of interferon therapy and serum alanine aminotransferase ( ALT ) levels were higher than pretreatment ALT levels , therapy was discontinued . Criteria for Interferon Response We defined the efficacy of interferon therapy virologically and biochemically . Patients who were negative for HCV RNA ( as determined by RT-PCR ; detection limit , 102 copies/mL ) more than 6 months after the completion of interferon therapy were classified as showing a sustained virologic response . Patients with persistently normal ALT levels after the completion of interferon therapy were classified as showing a sustained biochemical response ; patients with abnormal ALT levels were classified as showing a nonsustained biochemical response . Follow-up Patients attended a monthly medical consultation at the University of Tokyo Hospital outpatient clinic . Blood biochemical measures , including -fetoprotein ( AFP ) tumor markers , were measured every 1 to 2 months ; ultrasonography was performed every 2 to 3 months ; and dynamic CT was performed every 6 months . Recurrence of hepatocellular carcinoma was detected by the finding of abnormal nodules with low or high echogenic appearance on abdominal ultrasonography or by the finding of abnormal density on dynamic CT . The diagnosis was confirmed histologically through ultrasonography-guided fine-needle biopsy of the tumor . Recurrent nodules were divided into two categories [ 14 , 15 ] : 1 ) local recurrence , in which the nodule appeared adjacent to the previously treated nodules , suggesting that residual tumor cells had not been completely ablated by percutaneous ethanol injection therapy , or 2 ) new foci developing at a distant site . New foci of hepatocellular carcinoma , as well as local recurrent nodules at tumor , node , metastasis ( TNM ) stage I , II , and III , were mainly treated by a second course of percutaneous ethanol injection therapy ; local recurrent nodules at TNM stage IV were treated with transarterial chemoembolization or chemotherapy . New development of hepatocellular carcinoma and survival of the patients ( tumor recurrence rate and survival rate ) were analyzed in relation to the time interval after initial treatment . Statistical Analysis When estimating the sample size , we assumed that 5-year survival in the control group would be 40 % according to the data of our previous unpublished study . We predicted that 5-year survival would be increased by 35 % as a result of 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 Interferon therapy decreases the incidence of hepatocellular carcinoma in patients with chronic hepatitis C. OBJECTIVE To evaluate effects of interferon-alpha on recurrence after resection of hepatitis C virus-related hepatocellular carcinoma . DESIGN R and omized , controlled trial . SETTING University hospital , medical center , and affiliated hospital in Osaka , Japan . PATIENTS 30 men were r and omly allocated after resection to the interferon-alpha group ( n = 15 ) or the control group ( n = 15 ) . INTERVENTION Patients in the interferon-alpha group received interferon-alpha , 6 MIU intramuscularly daily for 2 weeks , then three times weekly for 14 weeks , and finally twice weekly for 88 weeks . MEASUREMENTS Recurrence rates after resection . RESULTS Recurrent tumors were detected in 5 patients in the interferon-alpha group and in 12 control patients . The recurrence rate was significantly lower in the interferon-alpha group than in the control group ( P = 0.037 ) . CONCLUSION Postoperative interferon-alpha therapy appears to decrease recurrence after resection of hepatitis C virus-related hepatocellular carcinoma BACKGROUND Patients chronically infected with hepatitis C virus ( HCV ) genotype 2 or 3 for whom treatment with peginterferon is not an option , or who have not had a response to prior interferon treatment , currently have no approved treatment options . In phase 2 trials , regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection . METHODS We conducted two r and omized , phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection . In one trial , patients for whom treatment with peginterferon was not an option received oral sofosbuvir and ribavirin ( 207 patients ) or matching placebo ( 71 ) for 12 weeks . In a second trial , patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks ( 103 patients ) or 16 weeks ( 98 ) . The primary end point was a sustained virologic response at 12 weeks after therapy . RESULTS Among patients for whom treatment with peginterferon was not an option , the rate of a sustained virologic response was 78 % ( 95 % confidence interval [ CI ] , 72 to 83 ) with sofosbuvir and ribavirin , as compared with 0 % with placebo ( P<0.001 ) . Among previously treated patients , the rate of response was 50 % with 12 weeks of treatment , as compared with 73 % with 16 weeks of treatment ( difference , -23 percentage points ; 95 % CI , -35 to -11 ; P<0.001 ) . In both studies , response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and , among patients with genotype 3 infection , lower among those with cirrhosis than among those without cirrhosis . The most common adverse events were headache , fatigue , nausea , and insomnia ; the overall rate of discontinuation of sofosbuvir was low ( 1 to 2 % ) . CONCLUSIONS In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option , 12 or 16 weeks of treatment with sofosbuvir and ribavirin was effective . Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis . In previously treated patients with genotype 3 infection , 16 weeks of therapy was significantly more effective than 12 weeks . ( Funded by Gilead Sciences ; POSITRON and FUSION Clinical Trials.gov numbers , NCT01542788 and NCT01604850 , respectively . ) Background Interferon-based therapy ( IBT ) has been the st and ard of care for hepatitis C virus ( HCV ) infection . However , conflicting results exist regarding the effects of IBT on risk of developing hepatocellular carcinoma ( HCC ) and cirrhosis-associated complications , and most included highly selected patients . Methods This 8-year cohort study was based on the Longitudinal Health Insurance Data base 2000 ( LHID 2000 ) consisting of 1,000,000 beneficiaries r and omly selected from all Taiwan National Health Insurance enrollees in 2000 ( > 23.7 million ) . Patients with newly detected HCV infections ( n = 11,264 ) were classified based on treatment and clinical outcomes . IBTs were defined as regimens that included interferon- alfa , pegylated interferon- alfa -2a , or pegylated interferon- alfa -2b for at least 3 months . The Cox proportional hazards models were used to estimate the hazard ratio ( HR ) and associated confidence interval ( CI ) of HCC and cirrhosis-associated complications for IBT . Results The 8-year incidence rate for HCC was 3.9 % among patients who received IBT and 5.6 % among those who did not . The HCC-free survival rate was significantly higher among patients receiving IBT during the 8-year period than their counterpart ( adjusted HR , 0.50 ; 95 % CI , 0.31–0.81 ; P = .004 ) . Similarly , the event-free survival rates for esophageal variceal bleeding ( adjusted HR , 0.45 ; 95 % CI , 0.22–0.91 ; P = .026 ) , hepatic encephalopathy ( adjusted HR , 0.38 ; 95 % CI , 0.21–0.69 ; P = .001 ) , ascites ( adjusted HR , 0.28 ; 95 % CI , 0.14–0.57 ; P<.001 ) , and cirrhosis ( adjusted HR , 0.63 ; 95 % CI , 0.44–0.91 ; P = .013 ) were significantly higher among patients who received IBT than those who did not , after adjustment for associated factors . Conclusion Treatment with interferon may reduce the 8-year risk of HCC and cirrhosis-associated complications in patients with chronic HCV infection BACKGROUND / AIMS Interferon-alfa is widely used for the treatment of chronic hepatitis C , and has been thought to have a preventive effect on the development of hepatocellular carcinoma . Hepatocellular carcinoma develops from chronic liver diseases such as chronic hepatitis C or liver cirrhosis . We studied the effect of interferon for liver cirrhosis with hepatocellular carcinoma after treating hepatocellular carcinoma itself . METHODOLOGY To evaluate the preventive effect of this drug on local recurrence and /or new development of primary tumor after clearance of hepatitis C virus , 46 patients with hepatocellular carcinoma with low HCV-RNA level were r and omized to receive recombinant interferon-alfa 2b ( n = 22 ) or not ( n = 24 ) after being treated by transcatheter arterial chemoembolization and percutaneous ethanol injection therapy . In the interferon-treated group , patients received 3 million international units of interferon-alfa 2b intramuscularly three times a week for 4 months . In both groups , transcatheter arterial chemoembolization followed by percutaneous ethanol injection therapy was performed as an initial treatment and these therapies were repeated every 4 - 6 months . Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched DNA probe assay . RESULTS In the interferon-treated group , 11 of the 22 ( 50 % ) patients were HCV-RNA negative at the 6 months after completing the course of interferon therapy . HCV-RNA was undetectable during the observation period in 2 of the 24 ( 9.5 % ) patients in the untreated group . The survival rate in the interferon-treated group was significantly higher than that in the untreated group ( P = 0.01 by the log-rank test ) . Though there was no significant difference in the incidence of local recurrence in both groups , the incidence of secondary hepatocellular carcinoma was significantly lower in the interferon-treated group than that in the untreated group . Cox proportional hazards regression analysis vali date d interferon treatment as an independent predictor of hepatocellular carcinoma prognosis . CONCLUSIONS We concluded that , if HCV-RNA level is low , interferon may be a therapy of choice in combination with transcatheter arterial chemoembolization and percutaneous ethanol injection therapy for the treatment of hepatocellular carcinoma Because hepatocellular carcinoma often recurs after surgical resection or ethanol injection therapy , we conducted a prospect i ve r and omized controlled trial of interferon ( IFN ) in patients with chronic liver disease caused by hepatitis C virus ( HCV ) . Twenty eligible patients with cirrhosis were r and omized into two groups : 10 patients treated with 6 million units of natural IFN-beta twice a week for 36 months and 10 patients without IFN therapy . One patient within the treatment group discontinued interferon therapy after 19 months of treatment because of a mild degree of retinopathy . None of the patients in either group lost HCV-RNA until the end of the observation . Although 7 ( 70.0 % ) of 10 patients in the nontreatment group showed tumor recurrence , only 1 ( 10.0 % ) of 10 patients with IFN therapy developed tumor recurrence during a median observation period of 25.0 months . Cumulative recurrence rates of the treated and untreated groups were 0 % and 62.5 % at the end of the first year , and 0 % and 100 % at the second year , respectively ( log-rank test , P = .0004 ) . In conclusion , intermittent administration of IFN suppressed tumor recurrence after treatment with surgery or ethanol injection in patients with HCV-related chronic liver disease BACKGROUND In patients with chronic hepatitis C who do not have a response to antiviral treatment , the disease may progress to cirrhosis , liver failure , hepatocellular carcinoma , and death . Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain . METHODS We conducted a r and omized , controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years , as compared with no treatment , in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin . The patients , who were stratified according to stage of fibrosis ( 622 with noncirrhotic fibrosis and 428 with cirrhosis ) , were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after r and omization . The primary end point was progression of liver disease , as indicated by death , hepatocellular carcinoma , hepatic decompensation , or , for those with bridging fibrosis at baseline , an increase in the Ishak fibrosis score of 2 or more points . RESULTS We r and omly assigned the patients to receive peginterferon ( 517 patients ) or no therapy ( 533 patients ) for 3.5 years . The level of serum aminotransferases , the level of serum hepatitis C virus RNA , and histologic necroinflammatory scores all decreased significantly ( P<0.001 ) with treatment , but there was no significant difference between the groups in the rate of any primary outcome ( 34.1 % in the treatment group and 33.8 % in the control group ; hazard ratio , 1.01 ; 95 % confidence interval , 0.81 to 1.27 ; P=0.90 ) . The percentage of patients with at least one serious adverse event was 38.6 % in the treatment group and 31.8 % in the control group ( P=0.07 ) . CONCLUSIONS Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis , with or without cirrhosis , who had not had a response to initial treatment with peginterferon and ribavirin . ( Clinical Trials.gov number , NCT00006164 . BACKGROUND / AIMS Few data are available concerning the short and long-term effects of beta-IFN in patients with chronic hepatitis C. METHODOLOGY We r and omized 61 consecutive patients with HCV-related cirrhosis to receive : a ) natural beta-IFN with a 6 MU/tiw for 6 months followed by 3 MU/tiw for 6 months schedule or b ) no treatment . Biochemical and virological response was defined by normalization of ALT and negativization of serum HCV-RNA . Patients were followed-up for 5 years . RESULTS A biochemical end-of-therapy response ( ETR ) was observed in 5/38 patients ( 13 % ) who received beta-IFN compared to 2/23 ( 9 % ) of untreated cases , but a virological ETR appeared only in 4/38 ( 11 % ) treated cases . At long-term follow-up , 6 cases ( 16 % ) who received beta-IFN and 4 untreated ( 17 % ) developed a persistent normalization of alanine aminotransferase ( ALT ) but only 2 ( 5 % ) and 1 ( 4 % ) , respectively , were also HCV-RNA negative . The cumulative probability of liver decompensation ( variceal bleeding ascites or hepatic encephalopathy ) at 60 months was 24 % in treated and 35 % in untreated cases . Hepatocellular carcinoma developed in 2 treated and in 1 untreated patients . CONCLUSIONS beta-IFN therapy was not associated with a significant improvement either in biochemical or virological response in cirrhotic patients with chronic hepatitis C. No significant reduction of cirrhosis related clinical events was linked to treatment Objective : This study was aim ed at evaluating the effects of interferon (IFN)-α on survival rate after resection of hepatocellular carcinoma . Methods : In a r and omized , controlled trial by the University Hospital , Medical Center and affiliated hospital in Osaka , Japan , 30 men were after surgery r and omly allocated to an IFN-α group ( 15 patients ) and to a control group . Patients in the IFN group received 6 MIU of IFN-α intramuscularly daily for 2 weeks , then three times a week for 14 weeks , and finally twice a week for 88 weeks . The incidence of recurrence and survival rate were then studied . Results : The response to IFN was sustained viral response ( SVR ) in 2 patients , biochemical response ( BR ) in 6 , partial response ( PR ) in 5 , and no response ( NR ) in 2 . In the control , 8 of the 15 patients demonstrated continuous abnormally high levels of ALT . At the end point of the study , intrahepatic recurrence was detected in 9 of the IFN group and in 13 of the control ( p = 0.065 , log-rank test ) . The cumulative survival rate was higher in the IFN group than in the controls ( p = 0.041 ) . Conclusion : Postoperative IFN therapy improves the outcome after resection of hepatitis C virus-related hepatocellular carcinoma BACKGROUND & AIMS Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma ( HCC ) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program . METHODS Data were analyzed from an open-label r and omized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin . All patients had compensated cirrhosis with no evidence of HCC . Patients received peginterferon alfa-2b ( 0.5 μg/kg/week ; n=311 ) or no treatment ( controls , n=315 ) for a maximum period of 5 years or until 98 patients had a clinical event ( hepatic decompensation , HCC , death , or liver transplantation ) . The primary measure of efficacy was time until the first clinical event . RESULTS There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls ( hazard ratio [ HR ] , 1.452 ; 95 % confidence interval [ CI ] : 0.880 - 2.396 ) . There was no decrease in the development of HCC with therapy . The time to disease progression ( clinical events or new or enlarged varices ) was significantly longer for patients who received peginterferon alfa-2b compared with controls ( HR , 1.564 ; 95 % CI : 1.130 - 2.166 ) . In a prospect ively defined sub analysis of patients with baseline portal hypertension , peginterferon alfa-2b significantly increased the time to first clinical event compared with controls ( P=.016 ) . There were no new safety observations . CONCLUSIONS Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC . However , there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension To examine the effects of interferon ( IFN ) therapy on clinical , biochemical , and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis , we have conducted a r and omized , controlled trial of IFN therapy versus observation . Eight centers included a total of 99 patients with biopsy-proven cirrhosis . IFN-alpha2b , 3 million units three times per week , or no antiviral therapy was given for 48 weeks . Twenty-three patients dropped out . End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients ( P < .02 ) ; sustained biochemical response was obtained in only 2 treated patients . Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin , bilirubin , alpha-fetoprotein , in plasma prothrombin , in histological activity , or liver collagen content . During trial or follow-up ( 160 + /- 57 weeks ) , hepatocellular carcinoma developed in 9 controls and 5 treated patients ( NS ) ; decompensation of cirrhosis occurred in 5 controls and 7 treated patients . Seven controls and 10 treated patients died . In conclusion , in patients with compensated HCV-related cirrhosis , a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients . However , a 48-week course of IFN therapy usually fails to achieve sustained response and , within the limit of this study , did not significantly improve the 3-year outcome . Therefore , a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies BACKGROUND In phase 2 trials , the nucleotide polymerase inhibitor sofosbuvir was effective in previously untreated patients with chronic hepatitis C virus ( HCV ) genotype 1 , 2 , or 3 infection . METHODS We conducted two phase 3 studies in previously untreated patients with HCV infection . In a single-group , open-label study , we administered a 12-week regimen of sofosbuvir plus peginterferon alfa-2a and ribavirin in 327 patients with HCV genotype 1 , 4 , 5 , or 6 ( of whom 98 % had genotype 1 or 4 ) . In a noninferiority trial , 499 patients with HCV genotype 2 or 3 infection were r and omly assigned to receive sofosbuvir plus ribavirin for 12 weeks or peginterferon alfa-2a plus ribavirin for 24 weeks . In the two studies , the primary end point was a sustained virologic response at 12 weeks after the end of therapy . RESULTS In the single-group study , a sustained virologic response was reported in 90 % of patients ( 95 % confidence interval , 87 to 93 ) . In the noninferiority trial , a sustained response was reported in 67 % of patients in both the sofosbuvir-ribavirin group and the peginterferon-ribavirin group . Response rates in the sofosbuvir-ribavirin group were lower among patients with genotype 3 infection than among those with genotype 2 infection ( 56 % vs. 97 % ) . Adverse events ( including fatigue , headache , nausea , and neutropenia ) were less common with sofosbuvir than with peginterferon . CONCLUSIONS In a single-group study of sofosbuvir combined with peginterferon-ribavirin , patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90 % at 12 weeks . In a noninferiority trial , patients with genotype 2 or 3 infection who received either sofosbuvir or peginterferon with ribavirin had nearly identical rates of response ( 67 % ) . Adverse events were less frequent with sofosbuvir than with peginterferon . ( Funded by Gilead Sciences ; FISSION and NEUTRINO Clinical Trials.gov numbers , NCT01497366 and NCT01641640 , respectively . ) Tumor recurrence after resection of hepatocellular carcinoma ( HCC ) can occur early ( < 2 years ) or late ( > 2 years ) as metastases or de novo tumors . Interferon ( IFN ) has the potential for chemoprevention against hepatitis C virus (HCV)‐related cirrhosis . A predetermined group of 150 HCV RNA – positive patients undergoing resection of early‐ to intermediate‐stage HCC was stratified into 80 HCV‐pure ( hepatitis B anticore antibody [anti‐HBc]–negative ) and 70 mixed HCV+hepatitis B virus ( HBV ) ( anti‐HBc – positive ) groups , then r and omized to IFN‐α ( 3 million units 3 times every week for 48 weeks [ n = 76 ] ) versus control ( n = 74 ) . The primary end point was recurrence‐free survival ( RFS ) ; secondary end points were disease‐specific and overall survival . Intention‐to‐treat and subgroup analysis on adherent patients were conducted . Treatment effects on early/late recurrences were assessed using multiple Cox regression analysis . No patient experienced life‐threatening adverse events . There were 28 adherent patients ( 37 % ) . After 45 months of median follow‐up , overall survival was 58.5 % , and no significant difference in RFS was detectable between the two study arms ( 24.3 % vs. 5.8 % ; P = .49 ) . HCC recurred in 100 patients ( 48 IFN‐treated , 52 controls ) , with a 50 % reduction in late recurrence rate in the treatment arm . HCC multiplicity and vascular invasion were significantly related to recurrence ( P = .01 and .0003 ) . After viral status stratification , while no treatment effect was apparent in the mixed HCV+HBV population and on early recurrences ( 72 events ) , there was a significant benefit on late recurrences ( 28 events ) in HCV‐pure patients adherent to treatment ( HR : 0.3 ; 95 % CI : 0.09–0.9 ; P = .04 ) . In conclusion , IFN does not affect overall prevention of HCC recurrence after resection , but it may reduce late recurrence in HCV‐pure patients receiving effective treatment . ( HEPATOLOGY 2006;44:1543–1554 . Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma . Interferon ( IFN ) seems to be effective in some patients but whether it prevents carcinogenesis is unknown . In a prospect i ve r and omised controlled trial , we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma . 90 patients with compensated chronic active hepatitis C with cirrhosis were r and omly allocated to receive IFN-alpha ( 6 MU three times weekly for 12 - 24 weeks ) ( 45 patients ) or symptomatic treatment ( 45 controls ) , and were followed up for 2 - 7 years . In nine controls , alanine aminotransferase ( ALT ) decreased to less than 80 IU/L but did not stay in the normal range . In 19 patients given IFN-alpha , ALT decreased to less than 80 IU/L ( in seven patients , it became and stayed normal ; p = 0.011 , Wilcoxon rank-sum test ) . However , the mean change in ALT was not significantly different between the two groups . The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls ( p = 0.021 ) . The mean change in the serum albumin level was higher in the IFN-alpha group ( p < 0.001 ) . The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved ( p = 0.031 ) . Hepatitis C viral RNA disappeared in seven ( 16 % ) of the 45 IFN-alpha patients ( 95 % CI , 7 - 29 % ) and in none of the 45 controls ( 0 - 8 % ; p = 0.018 ) . Hepatocellular carcinoma was detected in two ( 4 % , 1 - 15 % ) IFN-alpha patients and 17 ( 38 % , 24 - 54 % ) controls ( p = 0.002 , Wilcoxon signed-rank test ) . The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 ( 0.009 - 0.530 ; p = 0.010 Cox 's proportional hazards ) . IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis , and its use was associated with a decreased incidence of hepatocellular carcinoma Interferon therapy seems to decrease the incidence of recurrence after resection of hepatitis C virus (HCV)‐related hepatocellular carcinoma ( HCC ) . Effects of postoperative interferon therapy on the survival rate after resection of such HCC are still unclear BACKGROUND & AIMS Interferon reportedly decreases the incidence of hepatocellular carcinoma ( HCC ) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis ( HALT-C ) Trial showed that 4 years of maintenance therapy with pegylated interferon ( peginterferon ) does not reduce liver disease progression . We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period . METHODS The study included 1048 patients with chronic hepatitis C ( Ishak fibrosis scores ≥ 3 ) who did not have a sustained virologic response ( SVR ) to therapy . They were r and omly assigned to groups given a half-dose of peginterferon or no treatment ( controls ) for 3.5 years and followed up for a median of 6.1 ( maximum , 8.7 ) years . RESULTS Eighty-eight patients developed HCC ( 68 definite , 20 presumed ) : 37 of 515 who were given peginterferon ( 7.2 % ) and 51 of 533 controls ( 9.6 % ; P = .24 ) . There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis , but not fibrosis , based on analysis of baseline biopsy sample s. After 7 years , the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8 % and 24.2 % , respectively ( hazard ratio [ HR ] , 0.45 ; 95 % confidence interval [ CI ] , 0.24 - 0.83 ) ; in treated and control patients with fibrosis , incidences were 8.3 % and 6.8 % , respectively ( HR , 1.44 ; 95 % CI , 0.77 - 2.69 ) . Treated patients with a ≥ 2-point decrease in the histologic activity index , based on a follow-up biopsy , had a lower incidence of HCC than those with unchanged or increased scores ( 2.9 % vs 9.4 % ; P = .03 ) . CONCLUSIONS Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs . Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls |
2,477 | 28,245,559 | In conclusion , daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults | Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function .
The objective of this work was to determine the efficacy of Bifidobacterium ( B. ) animalis ssp .
lactis HN019 ( HN019 ) supplementation on cellular immune activity in healthy elderly subjects . | BACKGROUND The aging process can lead to a decline in cellular immunity . Therefore , the elderly could benefit from safe and effective interventions that restore cellular immune functions . OBJECTIVE We determined whether dietary supplementation with the known immunostimulating probiotic Bifidobacterium lactis HN019 could enhance aspects of cellular immunity in elderly subjects . DESIGN Thirty healthy elderly volunteers ( age range : 63 - 84 y ; median : 69 y ) participated in a 3-stage dietary supplementation trial lasting 9 wk . During stage 1 ( run-in ) , subjects consumed low-fat milk ( 200 mL twice daily for 3 wk ) as a base-diet control . During stage 2 ( intervention ) , they consumed milk supplemented with B. lactis HN019 in a typical dose ( 5 x 10(10 ) organisms/d ) or a low dose ( 5 x 10(9 ) organisms/d ) for 3 wk . During stage 3 ( washout ) , they consumed low-fat milk for 3 wk . Changes in the relative proportions of leukocyte subsets and ex vivo leukocyte phagocytic and tumor-cell-killing activity were determined longitudinally by assaying peripheral blood sample s. RESULTS Increases in the proportions of total , helper ( CD4(+ ) ) , and activated ( CD25(+ ) ) T lymphocytes and natural killer cells were measured in the subjects ' blood after consumption of B. lactis HN019 . The ex vivo phagocytic capacity of mononuclear and polymorphonuclear phagocytes and the tumoricidal activity of natural killer cells were also elevated after B. lactis HN019 consumption . The greatest changes in immunity were found in subjects who had poor pretreatment immune responses . In general , the 2 doses of B. lactis HN019 had similar effectiveness . CONCLUSION B. lactis HN019 could be an effective probiotic dietary supplement for enhancing some aspects of cellular immunity in the elderly Objective : To define the cellular basis for immune enhancement by a probiotic lactic acid bacteria strain ( Bifidobacterium lactis HN019 ) ; and to determine whether immune enhancement can be optimized by delivery in oligosaccharide-enriched low-fat milk . Design : A double-blind , three-stage before- and -after intervention trial . Setting : Taipei Medical College Hospital , Taipei , Taiwan . Subjects : Fifty healthy Taiwanese citizens ( age range 41–81 ; median 60 ) r and omly allocated to two groups . Interventions : In stage 1 ( run-in control stage ) all subjects consumed reconstituted low-fat milk ( LFM ) for 3 weeks ; in stage 2 ( probiotic intervention ) subjects consumed B. lactis in LFM ( group A ) or B. lactis in lactose-hydrolysed LFM ( group B ) for 3 weeks ; in stage 3 all subjects returned to non-supplemented LFM for a further 3 weeks ( washout stage ) . The innate immune functions of two different leucocyte types ( polymorphonuclear ( PMN ) cells and natural killer ( NK ) cells ) were assessed at four time points via in vitro analyses on peripheral blood sample s. Results : While consumption of LFM alone had no significant effect on immune responses , stage 2 results indicated significantly enhanced PMN cell phagocytosis and NK cell tumour killing activity following consumption of milk containing B. lactis . These increases levelled off following cessation of B. lactis consumption , but remained above the pre-treatment values . Increases in PMN and NK cell activity were greatest among subjects who consumed B. lactis in lactose-hydrolysed LFM . Conclusions : Dietary consumption of the probiotic bacterium B. lactis HN019 enhanced immune function of two different types of leucocytes ; the degree of enhancement was increased by consuming B. lactis in an oligosaccharide-rich substrate . Sponsorship : Financial support was provided by the New Zeal and Dairy Board . European Journal of Clinical Nutrition ( 2000 ) 54 , OBJECTIVE The effectiveness of influenza vaccination in preventing illness is lower in the elderly ; this is why the ability of Lactobacillus plantarum CECT 7315/7316 to stimulate the response to influenza vaccination in elderly was evaluated . RESEARCH METHODS AND PROCEDURES A r and omized , double-blind , placebo-controlled human trial including 60 institutionalized volunteers aged 65 - 85 years was performed . All the volunteers were vaccinated with a trivalent influenza vaccine ( A/Wisconsin/67/2005 NYMC X-161B ( H3N2 ) , A/Solomon Isl and s/3/2006 ( H1N1 ) and B/Malaysia/2506/2004 ) for the Spanish vaccine campaign 2006/2007 . The consumption of the probiotic began between three and four months after the vaccination . Volunteers were r and omly assigned to one of three following groups : group A ( receiving 5 * 10(9 ) cfu/day of L. plantarum CECT 7315/7316 in 20 g powdered skim milk ) , group B ( receiving 5 * 10(8 ) cfu/day of L. plantarum CECT 7315/7316 in 20 g powdered skim milk ) and group C or placebo ( 20 g powered skim milk ) . The participants consumed the probiotic during 3 months . RESULTS The consumption of L. plantarum CECT 7315/7316 during 3 months after influenza vaccination increased the levels of influenza-specific IgA and IgG antibodies . Moreover , a trend towards an increase in influenza-specific IgM antibodies was also observed . CONCLUSION L. plantarum CECT7315/7316 has an immunostimulating effect and could be used to improve the response to influenza vaccination in elderly Elderly adults have alterations in their gut microbiota and immune functions that are associated with higher susceptibility to infections and metabolic disorders . Probiotics and prebiotics , and their synbiotic combinations are food supplements that have been shown to improve both gut and immune function . The objective of this r and omised , double-blind , placebo-controlled , cross-over human clinical trial was to study immune function and the gut microbiota in healthy elderly adults . Volunteers ( n 37 ) consumed prebiotic galacto-oligosaccharides ( GOS ; 8 g/d ) , probiotic Bifidobacterium lactis Bi-07 ( Bi-07 ; 109 colony-forming units/d ) , their combination ( Bi-07 + GOS ) and maltodextrin control ( 8 g/d ) in four 3-week periods separated by 4-week wash-out periods . Immune function was analysed by determining the phagocytic and oxidative burst activity of monocytes and granulocytes , whole-blood response to lipopolysaccharide , plasma chemokine concentrations and salivary IgA levels . Gut microbiota composition and faecal SCFA content were determined using 16S ribosomal RNA fluorescence in situ hybridisation and HPLC , respectively . Primary statistical analyses indicated the presence of carry-over effects and thus measurements from only the first supplementation period were considered valid . Subsequent statistical analysis showed that consumption of Bi-07 improved the phagocytic activity of monocytes ( P < 0·001 ) and granulocytes ( P = 0·02 ) . Other parameters were unchanged . We have for the first time shown that the probiotic Bi-07 may provide health benefits to elderly individuals by improving the phagocytic activity of monocytes and granulocytes . The present results also suggest that in the elderly , the effects of some probiotics and prebiotics may last longer than in adults Purpose There is growing evidence that probiotics confer health benefits to the host by modulating immune function , especially in older people , where immunosenescence is a feature even of healthy ageing . The aim of this study was to investigate the effect of a probiotic drink containing Lactobacillus casei Shirota ( LcS ) on immune function in a healthy non-immunocompromised older population . Methods Thirty healthy old volunteers were recruited into a r and omized placebo-controlled , single-blind crossover study . The volunteers were supplemented with the probiotic drink containing 1.3 × 1010 CFU LcS or skimmed milk per day for 4 weeks , followed by 4 weeks of washout and were crossed over to the other treatment . Peripheral blood and saliva sample s were collected at baseline and end of each treatment . Results Probiotic consumption was associated with a significant increase in natural killer ( NK ) cell activity relative to baseline and a significant decrease in the mean fluorescence intensity of CD25 expression in the resting T cells compared with placebo . Additionally , there was a trend towards an increased ratio of IL-10 to IL-12 relative to baseline after LcS intake . Conclusions Consumption of a probiotic drink containing LcS improved NK cell activity and tended to produce a more anti-inflammatory cytokine profile in an older population Faecal and serum sample s were collected over a period of 6 months from 55 institutionalized elderly subjects , who were enrolled in a double-blind placebo-controlled study . Participants were r and omized in one of the three treatment groups : intervention ( two probiotic Bifidobacterium longum strains : 2C and 46 ) , placebo and commercial control ( Bifidobacterium lactis Bb-12 ) . The faecal Bifidobacterium microbiota was characterized by genus and species-specific PCR . Serum levels of the cytokines IL-10 , tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta1 were determined by enzyme-linked immunosorbent assay . Each participant harboured on average approximately three different bifidobacterial species . The most frequently detected species were B. longum , Bifidobacterium adolescentis and Bifidobacterium bifidum . Depending on the treatment , the intervention result ed in specific changes in the levels of certain Bifidobacterium species , and positive correlations were found between the different species . Negative correlations were observed between the levels of Bifidobacterium species and the pro-inflammatory cytokine TNF-alpha and the regulatory cytokine IL-10 . The presence of faecal B. longum and Bifidobacterium animalis correlated with reduced serum IL-10 . The anti-inflammatory TGF-beta1 levels were increased over time in all three groups , and the presence of Bifidobacterium breve correlated with higher serum TGF-beta1 levels . This indicates that modulation of the faecal Bifidobacterium microbiota may provide a means of influencing inflammatory responses Many elderly subjects are at increased risk of infectious and noninfectious diseases due to an age-related decline in lymphoid cell activity ( immunosenescence ) . Noninvasive means of enhancing cellular immunity are therefore desirable in the elderly . Previous reports have suggested that dietary supplementation could represent an effective means of enhancing the activity of circulating natural killer ( NK ) cells in the elderly . In the present study , we have conducted a pre – post intervention trial to determine the impact of dietary supplementation with probiotic lactic acid bacteria ( LAB ) on peripheral blood NK cell activity in healthy elderly subjects . Twenty-seven volunteers consumed low-fat/low-lactose milk supplemented with known immunostimulatory LAB strains ( Lactobacillus rhamnosus HN001 or Bifidobacterium lactis HN019 ) for a period of 3 weeks . A dietary run-in of milk alone was shown to have no significant effect on NK cells . In contrast , the proportion of CD56-positive lymphocytes in peripheral circulation was higher following consumption of either LAB strain , and ex vivo P BMC tumoricidal activity against K562 cells was also increased . Supplementation with HN001 or HN019 increased tumoricidal activity by an average of 101 and 62 % , respectively ; these increases were significantly correlated with age , with subjects older than 70 years experiencing significantly greater improvements than those under 70 years . These results demonstrate that dietary consumption of probiotic LAB in a milk-based diet may offer benefit to elderly consumers to combat some of the deleterious effects of immunosenescence on cellular immunity BACKGROUND One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer . Although this question has so far remained open , there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer . We began a prospect i ve cohort study among a Japanese general population in 1986 , using various immunological and biochemical markers . METHODS Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age , between 1986 and 1990 . Immunological and biochemical markers were also measured , and participants were given a question naire on lifestyle . We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes , and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up . FINDINGS 154 cancer cases were used in the analysis . When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles , age-adjusted relative risk of cancer incidence ( all sites ) was 0.72 ( 95 % CI 0.45 - 1.16 ) for men with high cytotoxic activity , and 0.62 ( 0.38 - 1.03 ) for men with medium cytotoxic activity , taking the risk of those with low cytotoxic activity as reference . For women with high cytotoxic activity relative risk was 0.52 ( 0.28 - 0.95 ) , and for those with medium cytotoxic activity 0.56 ( 0.31 - 1.01 ) . For both sexes with high and medium cytotoxic activity risk was 0.63 ( 0.43 - 0.92 ) and 0.59 ( 0.40 - 0.87 ) , respectively . INTERPRETATION Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk , whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer Objective : To determine the effects of dietary consumption of Bifidobacterium lactis ( strain HN019 , DR10TM ) on natural immunity . Design : A r and omized , double blind , placebo-controlled clinical trial . Setting : : Janeway Medical Centre , Memorial University , St Johns , Newfoundl and .Subjects : Twenty-five healthy elderly volunteers ( median age 69 y ; range 60–83 y ) . Interventions : Twelve control subjects consumed 180 ml low-fat/low-lactose milk twice daily for a period of 6 weeks ; 13 test subjects consumed milk supplemented with 1.5 × 1011 colony-forming units of B. lactis twice daily . Indices of natural immunity , including interferon production , phagocytic capacity and phagocyte-mediated bactericidal activity , were determined via peripheral blood at 0 , 3 , 6 and 12 weeks post-trial commencement . Results : Subjects who consumed milk containing B. lactis for 6 weeks produced significantly enhanced levels of interferon-alpha , upon stimulation of their peripheral blood mononuclear cells in culture , in comparison to the placebo control group who received milk alone . There were also significant increases in polymorphonuclear cell phagocytic capacity among test group subjects , following consumption of milk supplemented with B. lactis , while individuals who consumed B. lactis-supplemented milk or milk alone showed enhanced phagocyte-mediated bactericidal activity . Conclusions : The results demonstrate that dietary consumption of B. lactis HN019 can enhance natural immunity in healthy elderly subjects , and that a relatively short-term dietary regime ( 6 weeks ) is sufficient to impart measurable improvements in immunity that may offer significant health benefits to consumers . Sponsors : Financial support for this project was provided by the New Zeal and Dairy Board . European Journal of Clinical Nutrition ( 2000 ) 54 , Nine healthy middle-aged and 10 elderly volunteers drank fermented milk containing 4 x 10(10 ) live cells of Lactobacillus casei strain Shirota daily for 3 wk , and their natural killer ( NK ) activity and other immunological functions were examined . In the experiments with middle-aged volunteers , NK activity significantly increased ( P<0.01 ) 3 wk after the start of intake , elevated NK cell activity remained for the next 3 wk , and this effect was particularly prominent in the low-NK-activity individuals . In the experiments with elderly volunteers , NK activity significantly decreased ( P<0.01 ) in the control group 3 wk after the start of intake ; however , the intake of Lactobacillus casei strain Shirota maintained the NK activity . These results suggest that daily intake of Lactobacillus casei strain Shirota provides a positive effect on NK-cell activity BACKGROUND Influenza vaccination is recommended for the elderly in many countries , but immune responses are weaker compared to younger adults . OBJECTIVE To investigate the impact of daily consumption of a probiotic dairy drink on the immune response to influenza vaccination in an elderly population of healthy volunteers over 70 years of age . DESIGN Two r and omised , multicentre , double-blind , controlled studies were conducted during two vaccination seasons in 2005 - 2006 ( pilot ) and 2006 - 2007 ( confirmatory ) . Eighty-six and 222 elderly volunteers consumed either a fermented dairy drink , containing the probiotic strain Lactobacillus casei DN-114 001 and yoghurt ferments ( Actimel , or a non-fermented control dairy product twice daily for a period of 7 weeks ( pilot ) or 13 weeks ( confirmatory ) . Vaccination occurred after 4 weeks of product consumption . Geometric mean antibody titres ( GMT ) against the 3 viral strains composing the vaccine ( H1N1 , H3N2 , and B ) were measured at several time intervals post-vaccination by haemagglutination inhibition test . RESULTS In the pilot study , the influenza-specific antibody titres increased after vaccination , being consistently higher in the probiotic product group compared to the control group under product consumption . Similarly , in the confirmatory study , titres against the B strain increased significantly more in the probiotic group than in the control group at 3 , 6 and 9 weeks post-vaccination under product consumption ( p=0.020 ) . Significant differences in seroconversion between the groups by intended to treat analysis were still found 5 months after vaccination . Similar GMT results were observed for the H3N2 strain and H1N1 strain , confirming the results of the pilot study . CONCLUSION These studies demonstrate that daily consumption of this particular probiotic product increased relevant specific antibody responses to influenza vaccination in individuals of over 70 years of age and may therefore provide a health benefit in this population |
2,478 | 26,751,626 | Physical-exercise-based rehabilitation programs realized 2 - 4 times a week , 60 min each session , for 6 - 12 weeks , and follow-up of 3 months promotes significant positive effects on quality of life in Parkinson 's disease patients at mild to moderate stages and disease duration around 6 years | This study aim ed to determine the effects of physical-exercise-based rehabilitation programs on quality of life of patients with Parkinson 's disease through a systematic review of r and omized clinical trials . | Background People with idiopathic Parkinson ’s disease ( PD ) frequently have low activity levels , poor mobility and reduced quality of life . Although increased physical activity may improve mobility , balance and wellbeing , adherence to exercises and activity programs over the longer term can be challenging , particularly for older people with progressive neurological conditions such as PD . Physical activities that are engaging and enjoyable , such as dancing , might enhance adherence over the long term . The objective of this study was to evaluate the feasibility of a r and omized controlled trial of Irish set dancing compared with routine physiotherapy for people with mild to moderately severe PD . Methods Twenty-four people with idiopathic PD referred for movement rehabilitation were r and omized to receive st and ard physiotherapy exercises or Irish set dancing classes once per week plus a weekly home program for 6 months ( 12 in each group ) . The feasibility and safety of the proposed RCT protocol was the main focus of this evaluation . The primary outcome was motor disability measured by the motor component of the UPDRS , which was assessed prior to and after therapy by trained assessors blinded to group assignment . The Timed Up and Go , the Berg Balance Scale and the modified Freezing of Gait Question naire were secondary measures . Quality of life of the people with PD was evaluated using the PDQ-39 . Results Both the Irish set dancing and physiotherapy exercise program were shown to be feasible and safe . There were no differences between groups in the rate of adverse events such as falls , serious injuries , death or rates of admission to hospital . The physiotherapists who provided usual care remained blind to group allocation , with no change in their st and ard clinical practice . Compliance and adherence to both the exercise and dance programs were very high and attrition rates were low over the 6 months of therapy . Although improvements were made in both groups , the dance group showed superior results to st and ard physiotherapy in relation to freezing of gait , balance and motor disability . Conclusions Irish dancing and physiotherapy were both safe and feasible in this sample from Venice , with good adherence over a comparatively long time period of 6 months . A larger multi-centre trial is now warranted to establish whether Irish set dancing is more effective than routine physiotherapy for enhancing mobility , balance and quality of life in people living with idiopathic PD.Trial registration EudraCT number 2012 - 005769 - A previous r and omized , controlled trial of tai chi showed improvements in objective ly measured balance and other motor-related outcomes in patients with Parkinson 's disease . This study evaluated whether patient-reported outcomes could be improved through exercise interventions and whether improvements were associated with clinical outcomes and exercise adherence . In a secondary analysis of the tai chi trial , patient-reported and clinical outcomes and exercise adherence measures were compared between tai chi and resistance training and between tai chi and stretching exercise . Patient-reported outcome measures were perceptions of health-related benefits result ing from participation , assessed by the Parkinson 's Disease Question naire ( PDQ-8 ) and Vitality Plus Scale ( VPS ) . Clinical outcome measures included motor symptoms , assessed by a modified Unified Parkinson 's Disease Rating Scale – Motor Examination ( UPDRS-ME ) and a 50-foot speed walk . Information on continuing exercise after the structured interventions were terminated was obtained at a 3-month postintervention follow-up . Tai chi participants reported significantly better improvement in the PDQ-8 ( −5.77 points , P = 0.014 ) than did resistance training participants and in PDQ-8 ( −9.56 points , P < 0.001 ) and VPS ( 2.80 points , P = 0.003 ) than did stretching participants . For tai chi , patient-reported improvement in the PDQ-8 and VPS was significantly correlated with their clinical outcomes of UPDRS-ME and a 50-foot walk , but these correlations were not statistically different from those shown for resistance training or stretching . However , patient-reported outcomes from tai chi training were associated with greater probability of continued exercise behavior than were either clinical outcomes or patient-reported outcomes from resistance training or stretching . Tai chi improved patient-reported perceptions of health-related benefits , which were found to be associated with a greater probability of exercise adherence . The findings indicate the potential of patient perceptions to drive exercise behavior after structured exercise programs are completed and the value of strengthening such perceptions in any behavioral intervention AIM The Patient Education Programme for Parkinson 's disease ( PEPP ) was assessed in a recent r and omised controlled trial ( RCT ) . In this study , a trend was identified towards significant improvement of patients ' quality of life ( Qol ) as well as a significant reduction of caregivers ' psychosocial burden and need for help . This study is aim ed at evaluating the effectiveness of the PEPP in clinical practice as compared with the RCT in an academic setting . The second aim is to assess its effectiveness in clinical practice at 6-month follow-up . METHODS Fifty-five patients and 50 caregivers from nine clinical setting s participated in the PEPP consisting of eight weekly sessions of 90 min . Self-report question naires were used to assess patients ' Qol ( PDQ-39 ) and caregivers ' psychosocial burden and need for help ( BELA-A-k ) at baseline , directly after the programme and at 6-month follow-up . To compare the baseline data and short-term effects , data were used from an RCT study which included 64 Parkinson 's disease patients and 46 caregivers . RESULTS Compared with the RCT control group , significant effects , after Bonferoni adjustment , were found for patients ' Qol as well as for caregivers ' psychosocial burden and need for help . No significant changes were found between baseline scores compared with 6-month follow-up . Scores returned to baseline levels at 6-month follow-up . CONCLUSIONS Effects from the RCT study were replicated and the effect on patients ' Qol was now significant . However , at 6-month follow-up , scores returned to baseline levels , indicating the need for some form of a booster session Introduction Physical rehabilitation is commonly used in patients with Parkinson ’s disease ( PD ) to improve their health and alleviate the symptoms . Objective We compared the effects of three programs , strength training ( ST ) , aerobic training ( AT ) , and physiotherapy , on motor symptoms , functional capacity , and electroencephalographic ( EEG ) activity in PD patients . Methods Twenty-two patients were recruited and r and omized into three groups : AT ( 70 % of maximum heart rate ) , ST ( 80 % of one repetition maximum ) , and physiotherapy ( in groups ) . Subjects participated in their respective interventions twice a week for 12 weeks . The assessment s included measures of disease symptoms ( Unified Parkinson ’s Disease Rating Scale [ UPDRS ] ) , functional capacity ( Senior Fitness Test ) , and EEG before and after 12 weeks of intervention . Results The PD motor symptoms ( UPDRS-III ) in the group of patients who performed ST and AT improved by 27.5 % ( effect size [ES]=1.25 , confidence interval [CI]=−0.11 , 2.25 ) and 35 % ( ES=1.34 , CI=−0.16 , 2.58 ) , respectively , in contrast to the physiotherapy group , which showed a 2.9 % improvement ( ES=0.07 , CI=−0.85 , 0.99 ) . Furthermore , the functional capacity of all three groups improved after the intervention . The mean frequency of the EEG analysis mainly showed the effect of the interventions on the groups ( F=11.50 , P=0.0001 ) . Conclusion ST and AT in patients with PD are associated with improved outcomes in disease symptoms and functional capacity Objective : To investigate the feasibility and effectiveness of six weeks of home-based treadmill training in people with mild Parkinson ’s disease . Design : Pilot r and omized controlled trial of a six-week intervention followed by a further six weeks follow-up . Setting : Home-based treadmill training with outcome measures taken at a hospital clinic . Participants : Twenty cognitively intact participants with mild Parkinson ’s disease and gait disturbance . Two participants from the treadmill training group and one from the control group dropped out . Interventions : The treadmill training group undertook a semi-supervised home-based programme of treadmill walking for 20–40 minutes , four times a week for six weeks . The control group received usual care . Main outcome measures : The feasibility of the intervention was assessed by recording exercise adherence and acceptability , exercise intensity , fatigue , muscle soreness and adverse events . The primary outcome measure of efficacy was walking capacity ( 6-minute walk test distance ) . Results : Home-based treadmill training was feasible , acceptable and safe with participants completing 78 % ( SD 36 ) of the prescribed training sessions . The treadmill training group did not improve their walking capacity compared to the control group . The treadmill training group showed a greater improvement than the control group in fatigue at post test ( P = 0.04 ) and in quality of life at six weeks follow-up testing ( P = 0.02 ) . Conclusions : Semi-supervised home-based treadmill training is a feasible and safe form of exercise for cognitively intact people with mild Parkinson ’s disease . Further investigation regarding the effectiveness of home-based treadmill training is warranted This r and omized controlled clinical trial was conducted to compare the effects of movement rehabilitation strategies and exercise therapy in hospitalized patients with idiopathic Parkinson 's disease . Participants were r and omly assigned to a group that received movement strategy training or musculoskeletal exercises during 2 consecutive weeks of hospitalization . The primary outcome was disability as measured by the Unified Parkinson 's Disease Rating Scale , UPDRS ( motor and ADL components ) . Secondary outcomes were balance , walking speed , endurance , and quality of life . Assessment s were carried out by blinded testers at baseline , after the 2 weeks of treatment and 3 months after discharge . The movement strategy group showed improvements on several outcome measures from admission to discharge , including the UPDRS , 10 m walk , 2 minute walk , balance , and PDQ39 . However , from discharge to follow up there was significant regression in performance on the 2 minute walk and PDQ39 . For the exercise group , quality of life improved significantly during inpatient hospitalization and this was retained at follow-up . Inpatient rehabilitation produces short term reductions in disability and improvements in quality of life in people with Parkinson 's disease OBJECTIVES To assess the validity of the Parkinson 's Disease Quality of Life ( PDQL ) question naire , a patient-specific multi-dimensional quality of life measure , in a community-based sample of patients with Parkinson 's disease ( PI ) ) using st and ardized measures of disease severity , depressive symptomatology and cognitive function . DESIGN A group of 194 patients with probable PD were r and omly selected from a community-based register and were invited to self-complete the 37-item PDQL . Disease severity was measured by the disease-specific Webster scale , cognition by the CAMCOG neuropsychological test and depressive symptomatology by the self-report 15-item GDS-15 geriatric depression scale . RESULTS A total of 136 patients returned completed PDQL question naires . Significant differences ( P < 0.05 ) emerged between the pooled PDQL score of patients grouped on the basis of disease severity . Depressive symptoms and cognition were also associated with poorer perceived quality of life as measured by the PDQL . CONCLUSIONS The results of this study are indicative of the validity of the PDQL as an important additional measurement which reflects the impact of PD from the patient perspective . It shows poorer quality of life to be associated with increasing age , disease severity more severe depressive symptomatology and impaired cognitive functioning . However , the responsiveness of this instrument in the evaluation of care in PD remains to be determined Background Exercise confers short-term benefits for individuals with Parkinson disease ( PD ) . Objective The purpose of the study was to compare short- and long-term responses among 2 supervised exercise programs and a home-based control exercise program . Design The 16-month r and omized controlled exercise intervention investigated 3 exercise approaches : flexibility/balance/function exercise ( FBF ) , supervised aerobic exercise ( AE ) , and home-based exercise ( control ) . Setting This study was conducted in outpatient clinics . Patients The participants were 121 individuals with PD ( Hoehn & Yahr stages 1–3 ) . Interventions The FBF program ( individualized spinal and extremity flexibility exercises followed by group balance/functional training ) was supervised by a physical therapist . The AE program ( using a treadmill , bike , or elliptical trainer ) was supervised by an exercise trainer . Supervision was provided 3 days per week for 4 months , and then monthly ( 16 months total ) . The control group participants exercised at home using the National Parkinson Foundation Fitness Counts program , with 1 supervised , clinic-based group session per month . Measurements Outcomes , obtained by blinded assessors , were determined at 4 , 10 , and 16 months . The primary outcome measures were overall physical function ( Continuous Scale — Physical Functional Performance [ CS-PFP ] ) , balance ( Functional Reach Test [ FRT ] ) , and walking economy ( oxygen uptake [ mL/kg/min ] ) . Secondary outcome measures were symptom severity ( Unified Parkinson 's Disease Rating Scale [ UPDRS ] activities of daily living [ ADL ] and motor subscales ) and quality of life ( 39-item Parkinson 's Disease Quality of Life Scale [ PDQ-39 ] ) . Results Of the 121 participants , 86.8 % , 82.6 % , and 79.3 % completed 4 , 10 , and 16 months , respectively , of the intervention . At 4 months , improvement in CS-PFP scores was greater in the FBF group than in the control group ( mean difference=4.3 , 95 % confidence interval [CI]=1.2 to 7.3 ) and the AE group ( mean difference=3.1 , 95 % CI=0.0 to 6.2 ) . Balance was not different among groups at any time point . Walking economy improved in the AE group compared with the FBF group at 4 months ( mean difference=−1.2 , 95 % CI=−1.9 to −0.5 ) , 10 months ( mean difference=−1.2 , 95 % CI=−1.9 to −0.5 ) , and 16 months ( mean difference=−1.7 , 95 % CI=−2.5 to −1.0 ) . The only secondary outcome that showed significant differences was UPDRS ADL subscale scores : the FBF group performed better than the control group at 4 months ( mean difference=−1.47 , 95 % CI=−2.79 to −0.15 ) and 16 months ( mean difference=−1.95 , 95 % CI=−3.84 to −0.08 ) . Limitations Absence of a non-exercise control group was a limitation of the study . Conclusions Findings demonstrated overall functional benefits at 4 months in the FBF group and improved walking economy ( up to 16 months ) in the AE group Background People with Parkinson 's disease are twice as likely to be recurrent fallers compared to other older people . As these falls have devastating consequences , there is an urgent need to identify and test innovative interventions with the potential to reduce falls in people with Parkinson 's disease . The main objective of this r and omised controlled trial is to determine whether fall rates can be reduced in people with Parkinson 's disease using exercise targeting three potentially remediable risk factors for falls ( reduced balance , reduced leg muscle strength and freezing of gait ) . In addition we will establish the cost effectiveness of the exercise program from the health provider 's perspective . Methods / Design 230 community-dwelling participants with idiopathic Parkinson 's disease will be recruited . Eligible participants will also have a history of falls or be identified as being at risk of falls on assessment . Participants will be r and omly allocated to a usual-care control group or an intervention group which will undertake weight-bearing balance and strengthening exercises and use cueing strategies to address freezing of gait . The intervention group will choose between the home-based or support group-based mode of the program . Participants in both groups will receive st and ardized falls prevention advice . The primary outcome measure will be fall rates . Participants will record falls and medical interventions in a diary for the duration of the 6-month intervention period . Secondary measures include the Parkinson 's Disease Falls Risk Score , maximal leg muscle strength , st and ing balance , the Short Physical Performance Battery , freezing of gait , health and well being , habitual physical activity and positive and negative affect schedule . Discussion No adequately powered studies have investigated exercise interventions aim ed at reducing falls in people with Parkinson 's disease . This trial will determine the effectiveness of the exercise intervention in reducing falls and its cost effectiveness . This pragmatic program , if found to be effective , has the potential to be implemented within existing community services . Trial registration The protocol for this study is registered with the Australian New Zeal and Clinical Trials Registry ( ACTRN12608000303347 ) The effects of progressive resistance exercise ( PRE ) on the motor signs of Parkinson 's disease have not been studied in controlled trials . The objective of the current trial was to compare 6- , 12- , 18- , and 24-month outcomes of patients with Parkinson 's disease who received PRE with a stretching , balance , and strengthening exercise program . The authors conducted a r and omized controlled trial between September 2007 and July 2011 . Pairs of patients matched by sex and off-medication scores on the Unified Parkinson 's Disease Rating Scale , motor subscale ( UPDRS-III ) , were r and omly assigned to the interventions with a 1:1 allocation ratio . The PRE group performed a weight-lifting program . The modified fitness counts ( mFC ) group performed a stretching , balance , and strengthening exercise program . Patients exercised 2 days per week for 24 months at a gym . A personal trainer directed both weekly sessions for the first 6 months and 1 weekly session after 6 months . The primary outcome was the off-medication UPDRS-III score . Patients were followed for 24 months at 6-month intervals . Of 51 patients , 20 in the PRE group and 18 in the mFC group completed the trial . At 24 months , the mean off-medication UPDRS-III score decreased more with PRE than with mFC ( mean difference , -7.3 points ; 95 % confidence interval , -11.3 to -3.6 ; P<0.001 ) . The PRE group had 10 adverse events , and the mFC group had 7 adverse events . PRE demonstrated a statistically and clinical ly significant reduction in UPDRS-III scores compared with mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs . © 2013 Movement Disorder Society Objective To evaluate whether a multifaceted behavioural change programme increases physical activities in patients with Parkinson ’s disease . Design Multicentre r and omised controlled trial . Setting 32 community hospitals in the Netherl and s , collaborating in a nationwide network ( ParkinsonNet ) . Participants 586 sedentary patients with idiopathic Parkinson ’s disease aged between 40 and 75 years with mild to moderate disease severity ( Hoehn and Yahr stage ≤3 ) . Intervention Patients were r and omly assigned to the ParkFit programme or a matched general physiotherapy intervention . ParkFit is a multifaceted behavioural change programme , design ed specifically to achieve an enduring increase in the level of physical activity ( coaches using motivational strategies ; ambulatory feedback ) . Main outcome measures The primary endpoint was the level of physical activity , measured every six months with a st and ardised seven day recall ( LASA physical activity question naire — LAPAQ ) . Secondary endpoints included two other measures of physical activity ( activity diary and ambulatory activity monitor ) , quality of life ( Parkinson ’s disease question naire — PDQ-39 ) , and fitness ( six minute walk test ) . Results 540 ( 92.2 % ) patients completed the primary outcome . During follow-up , overall time spent on physical activities ( LAPAQ ) was comparable between the groups ( adjusted group difference 7 % , 95 % confidence interval −3 to 17 % ; P=0.19 ) . Analyses of three secondary outcomes indicated increased physical activity in ParkFit patients , as suggested by the activity diary ( difference 30 % ; P<0.001 ) , the activity monitor ( difference 12 % ; P<0.001 ) , and the six minute walk test ( difference 4.8 m ; P=0.05 ) . PDQ-39 did not differ between ParkFit patients and controls ( difference −0.9 points ; P=0.14 ) . The number of fallers was comparable between ParkFit patients ( 184/299 ; 62 % ) and controls ( 191/287 ; 67 % ) . Conclusions The ParkFit behavioural change programme did not increase overall physical activity , as measured with the LAPAQ . The analysis of the secondary endpoints justifies further work into the possible merits of behavioural change programmes to increase physical activities in daily life in Parkinson ’s disease . Trial registration Clinical trials NCT00748488 Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists This controlled prospect i ve study examined the evolution and predictors of cognitive decline in Parkinson 's disease ( PD ) . Consecutive patients diagnosed at baseline with PD ( n = 89 ) , established PD ( EPD ) patients ( n = 52 ) with a mean disease duration of 6.5 years , and healthy control subjects ( n = 64 ) underwent extensive neuropsychological assessment twice , approximately 3 years apart . A st and ardized regression-based method , normative data , and multivariate normative comparisons were used to assess the cognitive course of PD . Cognitive performance of newly diagnosed patients decreased significantly over time , particularly on measures of psychomotor speed and attention and to a lesser extent on tests of memory , visuospatial skills , and executive functions . About 50 % of the patients showed cognitive decline and 9 % developed dementia . Similar results were observed in EPD patients . None of the baseline features predicted cognitive change in newly diagnosed patients , whereas age at disease onset and axial impairment ( postural and gait disorders ) contributed to decline in established patients . We conclude that within few years after diagnosis , PD patients show faster rate of cognitive decline than matched healthy subjects , particularly in domains of attention and psychomotor speed . Selection bias probably led to underestimation of the true extent of cognitive decline in established patients BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . OBJECTIVE To prospect ively assess the health-related quality of life ( HrQoL ) in Parkinson 's disease ( PD ) during 12 months . METHODS HrQoL was assessed in 145 PD patients using the PD-specific PDQ-39 , PDQL and the generic EQ-5D . In addition , clinical rating-scales were used . RESULTS All scales showed a pronounced effect of PD . In comparison to an age-matched population the EQ-5D was considerably affected . In comparison to baseline , however , there was no significant change in the generic scale but a significant change in the sum-score of disease-specific HrQoL-scales . CONCLUSIONS Only disease-specific scales were sensitive to change . Further studies are necessary to evaluate the time-dependent change in BACKGROUND Parkinson 's disease ( PD ) is a neurodegenerative disease caused by loss of dopaminergic nigrostriatal neurons . Several studies have investigated various physical interventions on PD . The effects of a high intensity exercise program with focus on resistance ; cardio ; equilibrium ; and flexibility training have not been evaluated previously . OBJECTIVE The aim of this study was to investigate the effects of a complex , high intensity physical training program , with a long duration , on motor and non-motor symptoms in patients with PD . METHOD 24 patients with PD Hoehn and Yahr stage 1 - 3 were non-r and omly allocated to an intervention group ( n = 12 ) and a control group ( n = 12 ) . The intervention group underwent 32 weeks of high intensity personalized physical training twice a week , with an optional extra training session once a week . The control group received general recommendations regarding physical activity . The primary outcomes were the change in Unified Parkinson 's Disease Rating Scale Subscores ( UPDRS ) and the Parkinson 's Disease Question naire ( PDQ-39 ) . RESULTS At week 32 , the training significantly improved both UPDRS motor subscores ( p = 0.045 ) , activities of daily living subscores ( ADL ) ( p = 0.006 ) , mentation subscores ( p = 0.004 ) and complication subscores ( p = 0.019 ) . The effect on the PDQ39 total score was not statistically significant . The intervention group however experienced a substantial improvement of the PDQ39 items emotional well-being ( -11.0 ) and bodily discomfort ( -7.14 ) . CONCLUSION The results suggest that a personal high intensity exercise program may favorably influence both motor and non-motor symptoms in patients with mild to moderate PD . More studies with both higher methodology in study design and a follow-up examination are recommended Persons with Parkinson disease ( PD ) often demonstrate bradykinesia during mobility tasks . Bradykinesia combined with other PD-related movement deficits may contribute to self-reported reductions in quality of life . At this time , no studies have examined the effects of resistance exercise as an intervention to reduce bradykinesia and improve self-reported quality of life . Therefore , we examined changes in muscle force production , clinical measures of bradykinesia , and quality of life following 12 weeks of a high intensity eccentric resistance exercise program in persons with mild to moderate PD . Twenty individuals with idiopathic PD were matched into an experimental or an active control group . All participants were tested prior to and following a 12-week intervention period . The experimental group performed high intensity quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks . The active control group participated in an evidence based exercise program of PD . The outcome variables were quadriceps muscle force , clinical bradykinesia measures ( gait speed , timed up and go ) and disease specific quality of life ( Parkinson 's disease question naire-39 [ PDQ-39 ] ) . Data was analyzed using separate 2 ( group ) x 2 ( time period ) ANOVAs . Results demonstrated significant time by group interaction effects for gait speed , timed up and go , and the composite PDQ-39 score ( p < 0.05 ) . Muscle force , bradykinesia , and QOL were improved to a greater degree in those that performed high intensity eccentric resistance training compared to an active control group . Additional research is needed to determine if this type of training has long-term impact and if it results in an alteration of the natural history of mobility and QOL decline in persons with PD The direct costs of care were evaluated prospect ively in a sample of people with Parkinson 's disease ( PD ) in the United Kingdom in 1998 . The subjects were drawn from a r and om sample of general practitioner practice s within a representative sample of 36 Regional Health Authorities and the equivalent . A total of 444 re source use question naires with usable data were returned ( response rate , 59 % ) . The total mean annual cost of care per patient for all patients by age was 5,993 pounds ( 9,554 euro , n = 432 ) . Hoehn and Yahr stage significantly ( P < 0.001 ) influenced expenditure by stage as follows : 0 and I , 2,971 pounds ( 4,736 euro , n = 110 ) ; II , pound 3,065 ( 4,886 euro , n = 89 ) ; III , 6,183 pounds ( 9,857 euro , n = 120 ) ; IV , 10,134 pounds ( euro;16,155 , n = 87 ) ; V , 18,358 pounds ( 29,265 euro , n = 17 ) . National Health Service costs accounted for approximately 38 % and social services for 34 % of the direct costs of care . Drug expenditure accounted for 24 % of overall costs in the < 65 years age group and 10 % in patients aged > 85 years . A move from home to residential care was associated with an approximately 500 % cost increase . In conclusion , PD imposes significant direct costs on public services and on individuals . These costs should be taken into account when allocating public funds The basal ganglia play a role in controlling movement during gait . The aim of the present study was to investigate changes in dopamine transporter ( DAT ) availability in the striatum and extrastriatal region in association with walking exercise in six normal subjects and seven age-matched unmedicated patients with Parkinson 's disease . This was done by comparing DAT radiolig and uptake in the dopaminergic projection areas after gait with that under the resting condition using a DAT probe , 11C-labelled 2-beta-carbomethoxy-3beta-(4-fluorophenyl ) tropane ( [11C]CFT ) and PET . Physiological parameters were stable during and after gait in both groups . The regions of interest method for measuring differences in [11C]CFT uptake level and voxel-based statistical parametric mapping ( SPM96 ) showed that [11C]CFT uptake in the striatum ( specifically the putamen ) was decreased by gait to a greater extent in normal subjects , whereas a significant reduction in [11C]CFT uptake was not found in the putamen but in the cau date and orbitofrontal cortex in Parkinson 's disease patients . These results are the first in vivo evidence that DAT availability is reduced in the nigrostriatal projection area by basic human behaviour , i.e. gait . Alterations in this availability in Parkinson 's disease suggested that shifted activation in the medial striatum and the mesocortical dopaminergic system might reflect the pathophysiology of parkinsonian gait OBJECTIVES To examine the rate and predictors of nursing home placement in patients with Parkinson 's disease . DESIGN Four-year prospect i ve study . SETTING A population -based study in western Norway PARTICIPANTS 178 community-dwelling subjects with Parkinson 's disease . MEASUREMENTS Main outcome measure was the time from baseline to nursing home admission . Baseline evaluation of motor symptoms ( Unified Parkinson 's Disease Rating Scale , UPDRS ) , cognition ( clinical dementia interview , Gottfries , Brane & Steen dementia scale , and Mini-Mental State Examination ) , depression ( clinical interview and the Montgomery & Asberg Depression Rating Scale ) , and psychotic symptoms ( UPDRS Thought Disorder item ) were performed . RESULTS Forty-seven patients ( 26.4 % ) were admitted to a nursing home during the 4-year study period . Institutionalized patients were older , had more advanced Parkinson 's disease with more severe motor symptoms and impairment of activities of daily living , were cognitively more impaired , were more often living alone , and had more hallucinations than those who continued to live at home . Duration of disease , levodopa dose , and gender distribution did not differ between the two groups . A Cox proportional hazards linear regression analysis showed that old age , functional impairment , dementia , and hallucinations were independent predictors of nursing home admission . CONCLUSIONS Both motor and neuropsychiatric symptoms contributed to institutionalization , but the presence of hallucinations was the strongest predictor . This finding indicates it is possible that effective treatment of hallucinations may reduce the need for institutionalization in patients with Parkinson 's disease We evaluated changes in different domains of quality of life ( QL ) for persons with Parkinson 's disease after a program of physical activity . Twenty subjects with a diagnosis of Parkinson 's disease classified as Stages 1 to 3 on the Hoehn and Yahr scale and with a mean age of 61.5 + /- 9.8 years participated in 36 group sessions of a combined group program of aerobic conditioning and muscular strengthening . QL was investigated by the Nottingham Health Profile , a generic question naire composed of six domains . Student 's paired t tests indicated significant gains associated with the program ( P < 0.05 ) on the total score and those related to emotional reactions ( ER ) , social interactions ( SI ) , and physical ability ( PA ) . SI was the domain that showed the greatest program gains ( 41.4 % ) . The program of physical activity performed with persons with Parkinson 's disease at light to moderate stages result ed in improvements in their perception of QL , mainly in the domains of ER , SI , and PA Current management guidelines for the treatment of patients with Parkinson 's disease ( PD ) are limited due to the lack of knowledge of factors that influence health-related quality of life ( HRQL ) . To assess the HRQL of people with PD , and to systematic ally identify and evaluate those factors ( other than disease severity and medication , which could have an impact ) , we undertook a cross-sectional , r and omized selection , multicenter international survey of patients with PD , caregivers , and clinicians . Face-to-face interviews were conducted with subjects in six countries . Disease severity , medication , and other factors hypothesized to influence HRQL were assessed using a combination of specially developed question naires and vali date d instruments including the Parkinson 's Disease Question naire-39 ( HRQL ) , Hoehn and Yahr Stage ( disease severity ) , and Beck 's Depression Inventory ( BDI ; depression ) . Multiple linear regression models were used to demonstrate whether the factors investigated contribute significantly to HRQL . The results obtained indicated that Hoehn and Yahr stage and medication explained only 17.3 % of the variability in HRQL of patients with PD , although both were significant ( R2 = 0.173 , P < 0.05 ) . Other factors increased the explanatory power to adjusted R2 = 0.597 , with BDI being the most significant predictor of variability in HRQL ( adjusted R2 = 0.582 ; P < 0.001 ) , followed by " Satisfaction with the explanation of the condition at diagnosis " and " Current feelings of optimism " ( both P < 0.05 ) . These factors , in addition to disease severity and medication , explain 59.7 % of the variability in HRQL across the population . In conclusion , depression ( as measured by the BDI ) in PD , " satisfaction with the explanation of the condition at diagnosis " and " current feelings of optimism " have a significant impact on HRQL . The completion of this initial analysis is the first step towards developing management guidelines that truly influence the HRQL of patients with PD . © 2001 Movement Disorder Society Cruise KE , Bucks RS , Loftus AM , Newton RU , Pegoraro R , Thomas MG . Exercise and Parkinson ’s : benefits for cognition and quality of life . Acta Neurol Sc and : 2011 : 123 : 13–19 . © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard |
2,479 | 26,947,696 | QoL in the NPWT group was lower in the first week , though no difference in QoL was observed thereafter .
This systematic review observed that QoL improved at the end of therapy independent of which therapy was used .
NPWT led to a lower QoL during the first week of treatment , possible due to aniexty , after which a similar or better QoL was reported when compared with SWC .
It could be suggested that NPWT might be associated with increased anxiety . | OBJECTIVE Negative pressure wound therapy ( NPWT ) is a widely accepted treatment modality for open or infected wounds .
Premature ending of NPWT occasionally occurs due to negative effects on the quality of life ( QoL ) , however , the actual impact on QoL is unknown .
The aim of this review is to analyse the effect of NPWT versus st and ard wound care ( SWC ) on QoL when used for the treatment of open or infected wounds . | Venous leg ulcer pain experienced during compression b and aging is poorly understood . A prospect i ve , pilot cohort study was initiated to determine the feasibility of conducting a large-scale , repeated measures cohort study of venous leg ulcer pain and to document and describe the venous leg ulcer pain experience during the first 5 weeks of treatment with compression b and ages . Eligible individuals admitted to a nurse-led community leg ulcer service in one Canadian community were recruited for the 5-week study . Pain assessment tools ( ie , numerical rating scale and short form McGill Pain Question naire ) were evaluated by 20 venous ulcer patients ( mean age = 73.7 years ) and their nurses for ease of use during one baseline and five weekly follow-up visits . Health-related quality of life ( HRQL ) information was obtained . Nurses reported on ease of integrating pain data collection into regular clinical care . Each pain assessment tool was audited for completion . Most participants found the pain assessment tools easy to use , but nurses reported lengthened visit times with some participants as a result of tool administration difficulties , particularly the visual analogue scale ( VAS ) . Overall completeness of pain assessment tools ranged from 85.0 % ( visual analogue scale ) to 96.3 % ( present pain intensity and word descriptor list ) . The vast majority of patients ( 18 ) reported ulcer pain at baseline . Total mean scores for all pain assessment tools used decreased over time , but most patients reported pain throughout the study . The most common pain descriptors used were " aching , " " stabbing , " " sharp , " " tender , " and " tiring . " Health-related quality of life was low and did not change during the 5-week study . The results of this study suggest that the vast majority of venous ulcer patients experience pain and that it is feasible to examine this pain in individuals receiving care in the community over time Abstract Background : Diabetes Mellitus ( DM ) is the most common endocrine disease worldwide . One of the most important chronic complications of this disease is the development of diabetic foot . The management of diabetic foot wounds is quite important with respect to public health . Aims : To determine the effect of Vacuum Assisted Closure ( VAC ) therapy on the quality of life in the treatment of diabetic foot ulcers and compare it with st and art wound care . Methods : Between May 2007 to December 2008 , 67 consecutive patients with diabetic foot ulcers were r and omly assigned to VAC therapy ( Group1 , n : 30 ) or st and art wound care ( Group 2 , n : 37 ) . The SF-36 question naire was administered the day before and in the month following wound healing . Global analyses of the 8 domains and 2 comprehensive indexes of SF-36 , Physical Component Summary ( PCS ) and Mental Component Summary ( MCS ) were performed . Clinical measures included st and ard antidiabetic treatment , daily wound care including antiseptic bath , debridement , toe removal for gangrene when necessary , and wound care with conventional methods or VAC . Healing time was calculated as the time from hospital admission to the time of re-epithelization . Results : There were no differences in the mean age , ulcer size and pulse status of the patients in both groups . Healing time in the VAC group was significantly reduced ( p < 0.05 ) . All 8 domains of SF-36 and MCS and PCS scores improved remarkably after VAC therapy . Conclusion : Vacuum Assited Closure therapy was found to be effective in the treatment of chronic diabetic ulcers . The improvement of quality of life demonstrates a clear-cut indication in this particular group of patients Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument BACKGROUND Current treatment modalities for chronic leg ulcers are time consuming , expensive , and only moderately successful . Recent data suggest that creating a subatmospheric pressure by vacuum-assisted closure ( V.A.C. , KCI Concepts , San Antonio , Texas ) therapy supports the wound healing process . METHODS The efficacy of vacuum-assisted closure in the treatment of chronic leg ulcers was prospect ively studied in a r and omized controlled trial in which 60 hospitalized patients with chronic leg ulcers were r and omly assigned to either treatment by V.A.C. or therapy with conventional wound care techniques . The primary outcome measure was the time to complete healing ( days ) . Statistical analysis was performed on the intention-to-treat basis . RESULTS The median time to complete healing was 29 days ( 95 % confidence interval [ CI ] , 25.5 to 32.5 ) in the V.A.C. group compared with 45 days ( 95 % CI , 36.2 to 53.8 ) in the control group ( P = .0001 ) . Further , wound bed preparation during V.A.C. therapy was also significantly shorter at 7 days ( 95 % CI 5.7 to 8.3 ) than during conventional wound care at 17 days ( 95 % CI , 10 to 24 , P = .005 ) . The costs of conventional wound care were higher than those of V.A.C. Both groups showed a significant increase in quality of life at the end of therapy and a significant decrease in pain scores at the end of follow-up . CONCLUSIONS V.A.C. therapy should be considered as the treatment of choice for chronic leg ulcers owing to its significant advantages in the time to complete healing and wound bed preparation time compared with conventional wound care . Particularly during the preparation stage , V.A.C. therapy appears to be superior to conventional wound care techniques OBJECTIVE To discover the impact of topical negative pressure ( TNP ) on quality of life . METHOD An exploratory prospect i ve cohort study was conducted on 26 patients undergoing TNP . The Cardiff Wound Impact Schedule ( CWIS ) , a wound-specific tool , was used to investigate quality -of-life scores before therapy and four weeks after therapy or at wound closure . Wound dimensions were measured at both assessment s , and the values for the CWIS domains ( physical symptoms , social functioning , well-being and overall quality of life ) were investigated using parametric and non-parametric tests . RESULTS The mean duration of TNP therapy was 3.3 + /- 1.7 weeks . Topical negative pressure therapy helped to achieve complete wound closure in 14 patients ( 54 % ) , and there was a mean reduction in wound surface area from 52.2 cm2 ( range 4 - 150 ) to 26.8 cm2 ( 0 - 120 ) . While there was no significant change in quality of life in patients whose wounds healed ( 1 + /- 11.9 ) , the physical-functioning domain improved in obese patients ( 20 + /- 21 , p < 0.05 ) and worsened in ambulatory patients ( -3 + /- 13 , p < 0.05 ) . The portableTNP system had no significant impact on quality of life ( -3 + /- 16 ) , while the global quality -of-life score worsened with surgical intervention ( -0.5 + /- 2 , p < 0.05 ) . CONCLUSION Although TNP aids wound closure in patients with complex wounds , in selected cases their quality of life can worsen . This is the first exploratory cohort study of its kind , and has identified an urgent need to vali date the use of patient-based outcome measures in TNP therapy . Such data can be useful in allocating re sources and justifying funding in wound care |
2,480 | 27,833,738 | Conclusions Non-surgical treatment for peri-implant mucositis seems to be effective while modest and not-predictable outcomes are expected for peri-implantitis lesions . | ABSTRACT Objectives The purpose of this paper was to systematic ally evaluate the effectiveness of non-surgical therapy for the treatment of peri-implant diseases including both , mucositis and peri-implantitis lesions . | OBJECTIVE In this radiographic and microbiologic split-mouth clinical trial , efficacy of a diode laser as an adjunct to conventional scaling in the nonsurgical treatment of peri-implantitis was investigated . BACKGROUND DATA Eradication of pathogenic bacteria and infected sulcular epithelium presents a significant challenge in the nonsurgical treatment of peri-implantitis . MATERIAL S AND METHODS Ten patients ( mean age , 55.1 years ; SD , 11.4 ) with 48 two piece , rough-surface implants and diagnosed with peri-implantitis were recruited ( NCT02362854 ) . In addition to conventional scaling and debridement ( control group ) , crevicular sulci and the corresponding surfaces of 24 r and om implants were lased by a diode laser running at 1.0 W power at the pulsed mode ( λ , 810 nm ; energy density , 3 J/cm(2 ) ; time , 1 min ; power density , 400 mW/cm2 ; energy , 1.5 J ; and spot diameter , 1 mm ) ; ( laser group ) . Healing was assessed via periodontal indexes ( baseline and after 1 and 6 months after the intervention ) , microbiologic specimens ( baseline and after 1 month ) , and radiographs ( baseline and after 6 months ) . RESULTS Baseline mean pocket depths ( 4.71 , SD , 0.67 ; and 4.38 , SD 0.42 mm ) and marginal bone loss ( 2.71 , SD 0.11 ; and 2.88 , SD 0.18 mm ) were similar ( p = 0.09 and p = 0.12 ) between the control and laser groups , respectively . After 6 months , the laser group revealed higher marginal bone loss ( 2.79 , SD 0.48 ) than the control groups ( 2.63 , SD 0.53 ) ( p < 0.0001 ) . However , in both groups , the microbiota of the implants was found unchanged after 1 month . CONCLUSIONS In this clinical trial , adjunct use of diode laser did not yield any additional positive influence on the peri-implant healing compared with conventional scaling alone OBJECTIVE The objective of the study is to compare the clinical , microbiological and host-derived effects in the non-surgical treatment of initial peri-implantitis with either adjunctive local drug delivery ( LDD ) or adjunctive photodynamic therapy ( PDT ) after 12 months . MATERIAL S AND METHODS Forty subjects with initial peri-implantitis , that is , pocket probing depths ( PPD ) 4 - 6 mm with bleeding on probing ( BoP ) and radiographic bone loss ≤2 mm , were r and omly assigned to two treatment groups . All implants were mechanically debrided with titanium curettes and with a glycine-based powder airpolishing system . Implants in the test group ( N = 20 ) received adjunctive PDT , whereas minocycline microspheres were locally delivered into the peri-implant pockets of control implants ( N = 20 ) . At sites with residual BoP , treatment was repeated after 3 , 6 , 9 and 12 months . The primary outcome variable was the change in the number of peri-implant sites with BoP. Secondary outcome variables included changes in PPD , clinical attachment level ( CAL ) , mucosal recession ( REC ) and in bacterial counts and crevicular fluid ( CF ) levels of host-derived biomarkers . RESULTS After 12 months , the number of BoP-positive sites decreased statistically significantly ( P < 0.05 ) from baseline in both groups ( PDT : 4.03 ± 1.66 - 1.74 ± 1.37 , LDD : 4.41 ± 1.47 - 1.55 ± 1.26 ) . A statistically significant ( P < 0.05 ) decrease in PPD from baseline was observed at PDT-treated sites up to 9 months ( 4.19 ± 0.55 mm to 3.89 ± 0.68 mm ) and up to 12 months at LDD-treated sites ( 4.39 ± 0.77 mm to 3.83 ± 0.85 mm ) . Counts of Porphyromonas gingivalis and Tannerella forsythia decreased statistically significantly ( P < 0.05 ) from baseline to 6 months in the PDT and to 12 months in the LDD group , respectively . CF levels of IL-1β decreased statistically significantly ( P < 0.05 ) from baseline to 12 months in both groups . No statistically significant differences ( P > 0.05 ) were observed between groups after 12 months with respect to clinical , microbiological and host-derived parameters . CONCLUSIONS Non-surgical mechanical debridement with adjunctive PDT was equally effective in the reduction of mucosal inflammation as with adjunctive delivery of minocycline microspheres up to 12 months . Adjunctive PDT may represent an alternative approach to LDD in the non-surgical treatment of initial peri-implantitis Peri-implantitis is an inflammatory disease affecting soft and hard tissues surrounding dental implants . As the global number of individuals that undergo restorative therapy through dental implants increases , peri-implantitis is considered as a major and growing problem in dentistry . A r and omly selected sample of 588 patients who all had received implant-supported therapy 9 y earlier was clinical ly and radiographically examined . Prevalence of peri-implantitis was assessed and risk indicators were identified by multilevel regression analysis . Forty-five percent of all patients presented with peri-implantitis ( bleeding on probing/suppuration and bone loss > 0.5 mm ) . Moderate/severe peri-implantitis ( bleeding on probing/suppuration and bone loss > 2 mm ) was diagnosed in 14.5 % . Patients with periodontitis and with ≥4 implants , as well as implants of certain br and s and prosthetic therapy delivered by general practitioners , exhibited higher odds ratios for moderate/severe peri-implantitis . Similarly , higher odds ratios were identified for implants installed in the m and ible and with crown restoration margins positioned ≤1.5 mm from the crestal bone at baseline . It is suggested that peri-implantitis is a common condition and that several patient- and implant-related factors influence the risk for moderate/severe peri-implantitis ( Clinical Trials.gov NCT01825772 ) 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 AIM To determine the incidence of peri-implantitis in individuals with mucositis in a 5-year follow-up study . MATERIAL AND METHODS A sample of 212 partially edentulous individuals , rehabilitated with dental implants , underwent periodontal and peri-implant clinical examinations in 2005 ( baseline ) . Five years later , 80 individuals who had been diagnosed with mucositis in the baseline examination were re-examined . These individuals were divided into two groups : one group with preventive maintenance during the study period ( GTP ; n = 39 ) , and another group without preventive maintenance ( GNTP ; n = 41 ) . The following parameters were clinical ly evaluated : plaque index , bleeding on periodontal and peri-implant probing , periodontal and peri-implant probing depth , suppuration and peri-implant bone loss . The influence of biological and behavioural risk variables associated with the occurrence of peri-implantitis was analysed using univariate and multivariate logistic regression analyses . RESULTS The incidence of peri-implantitis in the global sample was 31.2 % ( GNTP = 43.9 % and GTP = 18.0 % ) . CONCLUSION The absence of preventive maintenance in individuals with pre-existing peri-implant mucositis was associated with a high incidence of peri-implantitis . Clinical parameters , such as bleeding on peri-implant probing , periodontal probing depth and the presence of periodontitis were associated with a higher risk of developing peri-implantitis AIM To evaluate the clinical treatment effects of a glycine powder air-polishing or ultrasonic device on peri-implant mucositis . MATERIAL S AND METHODS Thirty-seven patients with one implant diagnosed with peri-implant mucositis ( probing depth ≥4 mm ( 0.2N ) and bleeding on probing ( BOP ) ( primary outcome ) ) were r and omly assigned to treatment with either glycine powder air-polishing ( GPAP ) or ultrasonic ( US ) debridement . Treatment was performed at baseline and at 3 and 6 months . Professional supra gingival cleaning was performed at 9 and 12 months . Oral hygiene instructions were reinforced at each visit . RESULTS At 12 months there was a statistically significant reduction in mean plaque score , bleeding on probing and number of periodontal pockets ≥4 mm within the treatment groups compared to baseline . The percentages of diseased sites were significantly reduced for both groups . CONCLUSIONS Treatment with a glycine powder air-polishing or an ultrasonic device is effective in non-surgical treatment of peri-implant mucositis PURPOSE To evaluate possible benefits of the adjunctive use of light-activated disinfection ( LAD ) in the treatment of peri-implantitis . MATERIAL S AND METHODS A total of 80 patients with at least one implant affected by peri-implantitis defined as at least 3 mm of bone loss on baseline radiographs in the presence of signs of infection ( pus exudation and /or soft tissue swelling and /or soft tissue redness ) were non-surgically or surgically treated for peri-implantitis and 50 % of them were r and omly allocated to receive an additional LAD treatment ( FotoSan ) according to a parallel group design at four different centres . Only one implant per patient was considered . Outcome measures were implant failures , recurrence of peri-implantitis , complications , peri-implant marginal bone level ( RAD ) changes , probing pocket depth ( PPD ) changes and number of re-treatment sessions recorded by blinded assessors . Patients were followed up for 1 year after treatment . RESULTS Five treated patients did not fit the original inclusion criteria : 4 because they were not affected by the present definition of peri-implantitis and 1 due to being treated with antibiotics . However , they were included according to an intention-to-treat- analysis concept . Nine patients of the LAD group were treated surgically versus 10 control patients . After 1 year , 3 patients dropped out , all from the LAD group . One implant treated with the LAD therapy failed versus none of the control group . Four complications occurred : 3 in 3 patients of the LAD group and 1 in the control group . Recurrence of peri-implantitis defined as 2 mm of peri-implant bone loss or more recorded on st and ardised periapical radiographs was observed in 6 patients , 3 from each group . In total , 29 implants were re-treated 1 to 4 times in the LAD group versus 33 implants 1 to 4 times in the control group ; the difference was not statistically significant . Peri-implant marginal bone levels remained stable up to 1 year with no statistically significant differences between groups ( 0.13 mm favouring LAD therapy ; 95 % CI of difference -0.47 to 0.72 ; P = 0.68 ) . PPD significantly reduced in both groups , and at 1 year there were no significant differences between groups ( difference 0.19 mm favouring LAD therapy ; 95 % CI of difference -0.70 to 1.07 ; P = 0.68 ) . There were significant differences between centres for the number of re-treatment sessions delivered , PPD changes , plaque and marginal bleeding 1 year after treatment , but not for implant failures , complications , RAD changes and recurrence of peri-implantitis . The results did not change when removing the 5 patients who did not match the original inclusion criteria . CONCLUSIONS Adjunctive use of LAD therapy ( FotoSan ) with mechanical cleaning of implants affected by peri-implantitis did not improve any clinical outcomes when compared to mechanical cleaning alone up to 1 year after treatment AIM Supportive therapy to maintain dental implants is increasingly important . This study examined the effect of a 0.3 % triclosan/2 % copolymer dentifrice on oral biofilms and gingival inflammation ( GI ) on dental implants and peri-implant tissues . MATERIAL S AND METHODS One hundred and twenty adults with a dental implant and contra-lateral tooth were enrolled in this 6 month , double-blind , two-treatment , parallel group study . Sixty subjects were r and omly assigned to a triclosan/copolymer dentifrice test group and 60 subjects to a fluoride dentifrice control group and instructed to brush twice daily for 6 months . At baseline , 3 , and 6 months , a calibrated dentist assessed dental plaque , GI and collected supragingival dental plaque for microbiological analysis . RESULTS Subjects in the triclosan/copolymer group demonstrated significantly lower levels of dental plaque , gingivitis , and bleeding on probing at 3 and 6 months at both the implant and contra-lateral tooth compared with the fluoride group ( p<0.05 ) . There were significantly fewer Gram-negative anaerobes in the triclosan/copolymer group ( p<0.05 ) including > 90 % reductions in Aggregatibacter actinomycetemcomitans , Campylobacter rectus , Eubacterium saburreum , Fusobacterium nucleatum , Porphyromonas gingivalis , Prevotella melaninogenica , Solobacterium moorei , and Tannerella forsythia . CONCLUSIONS Twice daily use of a triclosan/copolymer dentifrice may enhance dental implant maintenance by reducing dental plaque and GI PURPOSE The aim of the present study was to investigate plaque levels following sonic-powered and manual toothbrushing in subjects with dental implants . MATERIAL S AND METHODS This study included 36 male and 47 female partially edentulous patients ( age range 45 - 78 years , mean age 59.8 years ) that were r and omly assigned to one of two treatment groups : the sonic toothbrush group ( n = 42 ; Philips Sonicare FlexCare ® toothbrush ) or the manual toothbrush group ( n = 41 ; Oral-B P40 ® ) . Clinical , microbiological and immunological examinations were performed blinded at baseline and after 3 , 6 , 9 and 12 months . Microbiological analyses were performed by real-time polymerase chain reaction . Immunological analyses ( prostagl and in E2 ) were performed by chromatography-electrospray spectrometry . RESULTS The plaque index difference between baseline and 12 months at implants showed no significant difference between sonic or manual toothbrushing in a two-sided Mann-Whitney test ( W = 773.5 , P = 0.426 , 95 % CI -0.64 to 0.20 ) . At the end of the study , there were no significant changes in plaque index , bleeding on probing , gingival index , pocket probing depth , gingival recession , clinical attachment level or the microbiological and immunological outcomes at implants or teeth in either group . CONCLUSIONS This study uncovered no significant difference between sonic and manual toothbrushing for plaque reduction at implants and teeth . Both toothbrushes maintain healthy peri-implant soft tissue PURPOSE This double-blind r and omized controlled trial assessed the effect of subgingival ozone ( O3 , gaseous ozone , HealOzone MK II , KaVo ) and /or hydrogen peroxide ( H2O2 ) on the development of peri-implant mucositis . MATERIAL S AND METHODS Twenty subjects ( mean age , 60 ± 7.7 years ) with 80 implants ( 4 implants each ) were recruited . First , a 2-week pretrial phase took place to achieve healthy gingiva . Subsequently , partial gum shields were constructed for the experimental area ( around the 4 implants ) ; subjects were asked to refrain from brushing in that area by wearing the gum shield . The following treatments were r and omly applied ( for 60 seconds ) to implant sites on days 0 , 7 , and 14 : ( 1 ) air ( O2 ) and saline ( 0.9 % NaCl ) ( control group ) , ( 2 ) O2 and H2O2 ( 3 % ) , ( 3 ) O3 and saline , and ( 4 ) O3 and H2O2 . Plaque , gingival , and bleeding indices were recorded on days 0 , 7 , 14 , and 21 . RESULTS Significant differences were seen among the treatments ( P < .01 ) in plaque ( F = 16.68 ) , modified gingival ( F = 7.86 ) , and bleeding ( F = 18.42 ) indices . O3 + saline and O3 + H2O2 produced optimum gingival health scores and were equally effective and the most effective in controlling bleeding ( mean score = 0.05 ) , while O2 + saline was the least effective ( mean score = 0.56 ) . CONCLUSION Ozone showed great potential for management of peri-implant mucositis OBJECTIVE The aim of this prospect i ve study was to assess the outcomes of an implant maintenance protocol for implants supporting a full-arch rehabilitation . MATERIAL S AND METHODS Sixty-one patients ( 28 women and 33 men ) treated with immediately loaded full-arch rehabilitation , both m and ibular and maxillary , supported by a combination of two tilted and two axial implants , were included in the study . Patients were scheduled for follow-up visits every 6 months for + 2 years , then yearly up to 4 years . Each patient received professional oral hygiene treatment and detailed oral hygiene instructions . During each visit , modified plaque index , bleeding index and probing depth were assessed . The presence of peri-implant tissue inflammation was also evaluated . RESULTS Mean observation time , considering both m and ible and maxilla , was 18.3 months ranging from 6 months to 5 years . Both plaque and bleeding indexes frequency decreased over time . Probing depth was stable ( 2.46 ± 0.5 mm at 4 years ) . Only three implants were lost due to peri-implantitis ( 1.4 % at 12 months ) , whereas the incidence of peri-implant mucositis was less than 10 % in each considered period . CONCLUSIONS The adoption of a systematic hygienic protocol is effective in keeping low the incidence of peri-implant mucositis as well as in controlling plaque accumulation and clinical attachment loss OBJECTIVES The aim of this prospect i ve , parallel group design ed , r and omized controlled clinical study was to evaluate the effectiveness of an air-abrasive device ( AAD ) for non-surgical treatment of peri-implantitis . MATERIAL AND METHODS Thirty patients , each of whom displayed at least one implant with initial to moderate peri-implantitis , were enrolled in an oral hygiene program ( OHI ) and r and omly instrumented using either ( 1 ) AAD ( amino acid glycine powder ) or ( 2 ) mechanical debridement using carbon curets and antiseptic therapy with chlorhexidine digluconate ( MDA ) . Clinical parameters were measured at baseline , 3 and 6 months after treatment [ e.g. bleeding on probing ( BOP ) , probing depth ( PD ) , clinical attachment level ( CAL ) ] . RESULTS At 6 months , AAD group revealed significantly higher ( p<0.05 ; unpaired t-test ) changes in mean BOP scores when compared with MDA-treated sites ( 43.5 ± 27.7%versus 11.0 ± 15.7 % ) . Both groups exhibited comparable PD reductions ( AAD : 0.6 ± 0.6 mm versus MDA : 0.5 ± 0.6 mm ) and CAL gains ( AAD : 0.4 ± 0.7 mm versus MDA : 0.5 ± 0.8 mm ) ( p>0.05 ; unpaired t-test , respectively ) . CONCLUSIONS Within its limitations , the present study has indicated that ( i ) both treatment procedures result ed in comparable but limited CAL gains at 6 months , and ( ii ) OHI+AAD was associated with significantly higher BOP reductions than OHI+MDA A prospect i ve clinical study was conducted to explore the possible link between peri-implant bone loss and the widespread habits of tobacco smoking and alcohol consumption . One hundred and eighty-five patients who received 514 implants were followed up for 3 years . Peri-implant marginal bone loss was evaluated by digital panoramic radiography and image analysis techniques . Multivariate analysis showed that peri-implant marginal bone loss was significantly related to a daily consumption of > 10 g of alcohol , tobacco use and increased plaque levels and gingival inflammation . The present results indicate that daily alcohol consumption and tobacco use may have a negative influence on predictable long-term implant treatment outcomes , producing peri-implant bone loss and compromising restorative treatment with implant-supported prostheses AIM To compare the effectiveness of two anti-infective protocol s for the treatment of peri-implant mucositis . MATERIAL S AND METHODS Twenty-nine patients with one implant diagnosed with peri-implant mucositis ( bleeding on probing [ BOP ] with no loss of supporting bone ) were r and omly assigned to a control or test group . Following an assessment of baseline parameters ( probing depth , BOP , suppuration , presence of plaque ) , all patients received non-surgical mechanical debridement at the implant sites and were instructed to brush around the implant twice daily using a gel provided for a period of 4 weeks . The test group ( 15 patients ) received a chlorhexidine gel ( 0.5 % ) , and the control group ( 14 patients ) received a placebo gel . The study was performed double blind . After 4 weeks , patients were instructed to discontinue using the gel and to continue with routine oral hygiene at the implant sites . Baseline parameters were repeated at 1 and 3 months . RESULTS At 1 month , there was a statistically significant reduction in the mean number of sites with BOP and mean probing depth measurements at implants in both groups . There were also some statistically significant changes in these parameters from 1 to 3 months . However , there were no statistically significant differences between test and control groups . One month following treatment , 76 % of implants had a reduction in BOP . Complete resolution of BOP at 3 months was achieved in 38 % of the treated implants . The presence of a submucosal restoration margin result ed in significantly lower reductions in probing depth following treatment . CONCLUSIONS Non-surgical debridement and oral hygiene were effective in reducing peri-implant mucositis , but did not always result in complete resolution of inflammation . Adjunctive chlorhexidine gel application did not enhance the results compared with mechanical cleansing alone . Implants with supramucosal restoration margins showed greater therapeutic improvement compared with those with submucosal restoration margins Objectives The purpose of this prospect i ve , parallel group- design ed , r and omized controlled clinical study was the evaluation of the effectiveness of an air-abrasive device ( AAD ) for nonsurgical treatment of peri-implantitis . Material and methods Twenty five patients , showing at least one implant with initial to moderate peri-implantitis , underwent an oral hygiene programme and were r and omly treated using either ( 1 ) AAD ( amino acid glycine powder ) or ( 2 ) mechanical debridement using carbon curettes and antiseptic therapy with chlorhexidine digluconate ( mechanical debridement ( MDA ) ) . Clinical parameters were measured at baseline and 12 months after treatment ( e.g. bleeding on probing ( BOP ) , probing depth ( PD ) , clinical attachment level ( CAL ) ) . Results At 12 months , the AAD group revealed significantly higher ( p < 0.05 ; unpaired t test ) decrease in mean BOP scores when compared with MDA-treated sites ( 41.2 ± 29.5 vs. 16.6 ± 33.4 % ) . Both groups exhibited comparable PD reductions ( AAD = 0.5 ± 0.9 mm vs. MDA = 0.4 ± 0.9 mm ) and CAL gains ( AAD = 0.6 ± 1.3 mm vs. MDA = 0.5 ± 1.1 mm ) ( p > 0.05 ; Mann-Whitney test , respectively ) . Conclusions Within its limitations , the present study has indicated that both treatment procedures result ed in comparable but limited CAL gains at 12 months . Furthermore , it could be detected that AAD was associated with significantly higher BOP decrease than MDA . Clinical relevance The present results have indicated that nonsurgical therapy of peri-implantitis using both AAD and MDA result ed in comparable PD reductions and CAL gains after 12 months of healing . The BOP reductions were significantly higher in the AAD in comparison to the MDA group . So , AAD may be more effective for nonsurgical therapy of peri-implantitis than MDA OBJECTIVE To compare the adjunctive clinical effects in the non-surgical treatment of peri-implantitis with either local drug delivery ( LDD ) or photodynamic therapy ( PDT ) . MATERIAL AND METHODS Forty subjects with initial peri-implantitis , i.e. pocket probing depths ( PPD ) 4 - 6 mm with concomitant bleeding on probing ( BoP ) and marginal bone loss ranging from 0.5 to 2 mm between delivery of the reconstruction and pre-screening appointment were r and omly assigned to two treatment groups . All implants underwent mechanical debridement with titanium curettes , followed by a glycine-based powder airpolishing . Implants in the test group ( n = 20 ) received adjunctive PDT , whereas minocycline microspheres were locally delivered into the peri-implant pockets of control implants ( n = 20 ) . At sites with residual BoP , treatment was repeated after 3 and 6 months . The primary outcome variable was the change in the number of sites with BoP. Secondary outcome variables were changes in PPD , in clinical attachment level ( CAL ) , and in mucosal recession ( REC ) . RESULTS After 3 months , implants of both groups yielded a statistically significant reduction ( P < 0.0001 ) in the number of BoP-positive sites compared with baseline ( LDD : from 4.41 ± 1.47 to 2.20 ± 1.28 , PDT : from 4.03 ± 1.66 to 2.26 ± 1.28 ) . After 6 months , complete resolution of mucosal inflammation was obtained in 15 % of the implants in the control group and in 30 % of the implants in the test group ( P = 0.16 ) . After 3 months , changes in PPD , REC , and modified Plaque Index ( mPlI ) were statistically significantly different from baseline ( P < 0.05 ) . No statistically significant changes ( P > 0.05 ) occurred between 3 and 6 months . CAL measurements did not yield statistically significant changes ( P > 0.05 ) in both groups during the 6-month observation time . Between-group comparisons revealed no statistically significant differences ( P > 0.05 ) at baseline , 3 and 6 months with the exception of the mPlI after 6 months . CONCLUSIONS In cases of initial peri-implantitis , non-surgical mechanical debridement with adjunctive use of PDT is equally effective in the reduction of mucosal inflammation as with the adjunctive use of minocycline microspheres up to 6 months . Adjunctive PDT may represent an alternative treatment modality in the non-surgical management of initial peri-implantitis . Complete resolution of inflammation , however , was not routinely achieved with either of the adjunctive therapies BACKGROUND Universal strategies for managing peri-implantitis are yet to be adopted . The aim of this study is to examine a protocol of intensive application of chlorhexidine containing chips in sites with peri-implantitis . MATERIAL S AND METHODS This multi-centre , r and omized , double-blind , parallel , two-arm clinical trial included 60 patients ( 77 implants ) with probing depth ( PD ) 6 - 10 mm and bone loss ≥2 mm around 1 - 2 implants . One to two weeks following SRP , baseline measurements were made followed by implants ' debridement . Patients were r and omized to receive matrix chips ( MatrixC ) or chlorhexidine Chips ( PerioC ) . Measurements and chips placement were repeated at weeks 2 , 4 , 6 , 8 , 12 and 18 . At 6 months , patients returned for final examination . RESULTS Probing depth reduction was greater in the PerioC ( 2.19 ± 0.24 mm ) compared with MatrixC ( 1.59 ± 0.23 mm ) , p = 0.07 . Seventy percentage of the implants in the PerioC and 54 % in the MatrixC had PD reduction ≥ 2 mm . Likewise , 40 % of the sites ( PerioC ) and 24 % ( MatrixC ) had PD reduction ≥ 3 mm . Clinical attachment level gains for both groups were significant ; however , the changes in the PerioC group were significantly greater than in MatrixC [ 2.21 ± 0.23 mm . and 1.56 ± 0.25 mm respectively , p = 0.05 ] . Bleeding on probing was reduced by half in both groups . CONCLUSION Frequent placement of PerioC and MatrixC together with implants debridement result ed in a substantial improvement in sites with peri-implantitis . Further studies will be required to fully appreciate the mechanism of this treatment BACKGROUND Non-surgical peri-implantitis therapies appear to be ineffective . Limited data suggest that ER : YAG laser therapy improves clinical conditions . The present study aim ed at comparing the treatment effects between air-abrasive ( AM ) and Er : YAG laser ( LM ) mono-therapy in cases with severe peri-implantitis . MATERIAL S AND METHODS Twenty-one subjects in each group were r and omly assigned to one time intervention by an air-abrasive device or an Er : YAG laser . Clinical data were collected before treatment and at 6 months . Data analysis was performed using repeat univariate analysis of variance controlling for subject factors . RESULTS No baseline subject characteristic differences were found . Bleeding on probing and suppuration decreased in both the groups ( p<0.001 ) . The mean probing depth ( PPD ) reductions in the AM and LM groups were 0.9 mm ( SD 0.8 ) and 0.8 mm ( SD ± 0.5 ) , with mean bone-level changes ( loss ) of -0.1 mm ( SD ± 0.8 ) and -0.3 mm ( SD ± 0.9 ) , respectively ( NS ) . A positive treatment outcome , PPD reduction ≥0.5 mm and gain or no loss of bone were found in 47 % and 44 % in the AM and LM groups , respectively . CONCLUSIONS The clinical treatment results were limited and similar between the two methods compared with those in cases with severe peri-implantitis BACKGROUND Glycine powder air-polishing ( GPAP ) has the potential to effectively erase biofilms and may improve the treatment efficacy of peri-implant mucositis . This pilot clinical trial evaluated the effect of GPAP as an adjunct in treating peri-implant mucositis . MATERIAL S AND METHODS Twenty-four subjects having at least one implant with peri-implant mucositis were r and omly assigned to test ( 12 subjects with 17 implants ) and control ( 12 subjects with 16 implants ) groups . Following baseline assessment , all subjects received oral hygiene instruction and non-surgical debridement . In the test group , the sites with probing depth ( PD ) ≥4 mm were additionally treated by GPAP for 5 sec. Clinical parameters were measured at 1-week , 1-month , and 3-month recall visits . RESULTS At the 3-month visit , the mean reductions in PD at site level were 0.93 ± 0.93 mm and 0.91 ± 0.98 mm in the test and control groups , respectively ( P < 0.05 ) , and no significant difference existed between two groups . Mean bleeding score was also significantly reduced in both groups after the intervention . No complications or discomfort were reported during the study . CONCLUSIONS This pilot clinical trial suggests that non-surgical mechanical debridement may effectively control peri-implant mucositis , and adjunctive GPAP treatment seems to have a limited beneficial effect as compared with mechanical debridement alone . However , further clinical trials with a large sample size are needed to confirm this preliminary observation |
2,481 | 18,641,037 | There was no evidence suggesting a survival benefit by the administration of activated protein C , non-invasive mechanical ventilation , anticoagulants , immunoglobulin , granulocyte-colony-stimulating factor , statins , probiotics , chest physiotherapy , antiplatelet drugs , over-the-counter cough medications , beta(2)-agonists , inhaled nitric oxide and angiotensin-converting enzyme inhibitors in patients with CAP . | BACKGROUND We endeavoured to accumulate and evaluate the available evidence regarding therapies that have been investigated as potential adjuncts to antimicrobials for the treatment of immunocompetent adult patients with bacterial community-acquired pneumonia ( CAP ) . | Background —Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities . We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis . The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently . Methods and Results —In this prospect i ve observational cohort study , consecutive patients admitted with presumed or documented acute bacterial infection were enrolled . The primary outcomes were the rate of severe sepsis and intensive care unit ( ICU ) admission . Of the 361 patients enrolled , 82 ( 22.7 % ) were treated with statins before their admission . Both groups had a similar severity of illness on admission . Severe sepsis developed in 19 % of patients in the no-statin group and in only 2.4 % of the statin group ( P<0.001 ) . Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 ( 95 % CI , 0.03 to 0.52 ) and an absolute risk reduction of 16.6 % . The overall ICU admission rate was 10.2 % ( 37/361 ) : 12.2 % of the no-statin group required ICU admission , whereas in the statin group only 3.7 % were admitted to the ICU ( P=0.025 ) , reflecting a relative risk of ICU admission of 0.30 ( 95 % CI , 0.1 to 0.95 ) . Conclusions —Prior therapy with statins may be associated with a reduced rate of severe sepsis and ICU admission . If supported by prospect i ve controlled trials , statins may have a role in the primary prevention of sepsis Recent studies suggest that statins and angiotensin-converting enzyme ( ACE ) inhibitors may have beneficial effects for some types of infections . The present study aim ed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged > 65 yrs and hospitalised with community-acquired pneumonia . A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged ≥65 yrs hospitalised with community-acquired pneumonia , and having ≥1 yr of prior Veterans Affairs outpatient care . In total , 8,652 subjects were identified with a mean age of 75 yrs , 98.6 % were male , and 9.9 % of subjects died within 30 days of presentation . In this cohort , 18.1 % of subjects were using statins and 33.9 % were using ACE inhibitors . After adjusting for potential confounders , current statin use ( odds ratio ( OR ) 0.54 , 95 % confidence interval ( CI ) 0.42–0.70 ) and ACE inhibitor use ( OR 0.80 , 95 % CI 0.68–0.89 ) were significantly associated with decreased 30-day mortality . Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia . R and omised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial Background Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia . Objectives The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia ( CAP ) requiring hospitalization . Design and Setting An open label , prospect i ve , r and omized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan . Patients Thirty-one adult CAP patients who required hospitalization were enrolled . Measurements and Results Fifteen patients received 40 mg of prednisolone intravenously for 3 days ( steroid group ) . Sixteen patients did not receive prednisolone ( control group ) . Both groups were also evaluated for their adrenal function . The primary endpoint was length of hospital stay . Secondary endpoints were duration of intravenous ( IV ) antibiotics and time required to stabilize vital signs . Both groups demonstrated similar baseline characteristics and length of hospital stay , and yet a shorter duration of IV antibiotics was observed in the steroid group ( p < 0.05 ) . In addition , vital signs were stabilized earlier in the steroid group ( p < 0.05 ) . These differences were more prominent in the moderate – severe subgroup but not as significant in the mild – moderate subgroup . The prevalence of relative adrenal insufficiency ( RAI ) in both groups was high ( 43 % ) , yet there was no difference in baseline characteristics between patients , with or without RAI . In multiple regression models , RAI seemed to have no influence on clinical courses . Conclusions In moderate – severe CAP , administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy A r and omised double-blind trial involving vitamin C/placebo supplementation was conducted on 57 elderly patients admitted to hospital with acute respiratory infections ( bronchitis and bronchopneumonia ) . Patients were assessed clinical ly and biochemically on admission and again at 2 and 4 weeks after admission having received either 200 mg vitamin C per day , or placebo . This relatively modest oral dose led to a significant increase in plasma and white cell vitamin C concentration even in the presence of acute respiratory infection . Using a clinical scoring system based on major symptoms of the respiratory condition , patients supplemented with the vitamin fared significantly better than those on placebo . This was particularly the case for those commencing the trial most severely ill , many of whom had very low plasma and white cell vitamin C concentrations on admission . Various mechanisms by which vitamin C could assist this type of patient are discussed STUDY OBJECTIVE To determine if the use of statins affects pneumonia-related outpatient visits , hospitalizations with survival , and deaths . DESIGN Population -based , retrospective , nested case-control analysis . DATA SOURCE United Kingdom-based General Practice Research Data base . PARTICIPANTS The study population ( 134,262 patients aged > or = 30 yrs ) consisted of 55,118 patients who took statins and /or fibrates , 29,144 patients with hyperlipidemia not taking lipid-lowering agents , and 50,000 r and omly selected patients without hyperlipidemia and without lipid-lowering treatment . MEASUREMENTS AND MAIN RESULTS We identified 1253 patients with pneumonia and matched them with 4838 control subjects based on age , sex , general practice , and index date . After adjusting for comorbidity and frequency of visits to general practitioners , we calculated the risks ( odds ratios with 95 % confidence intervals ) of uncomplicated pneumonia , hospitalization for pneumonia with survival , and fatal pneumonia in participants who used statins compared with those who did not . Current statin users had a significantly reduced risk of fatal pneumonia ( adjusted odds ratio 0.47 , 95 % confidence interval 0.25 - 0.88 ) and slightly but not significantly reduced risks of uncomplicated pneumonia and pneumonia hospitalization with survival . Recent or past statin use and fibrate use at any time were not associated with a reduced risk of pneumonia . CONCLUSION Current use of statins was associated with a reduced risk of pneumonia . The risk reduction was particularly strong in the subgroup of patients with fatal pneumonias Because of the critical role of neutrophils in host defenses , it was hypothesized that stimulation of neutrophil production and function with Filgrastim would improve the outcome of hospitalized patients with community-acquired pneumonia . To test this hypothesis , a r and omized , placebo-controlled , multicenter trial of Filgrastim ( 300 micrograms/day up to 10 days ) as an adjunct to antibiotics was conducted for these patients . Outcome measures included time to resolution of morbidity ( TRM , a composite measure of temperature , respiratory rate , blood oxygenation , and chest radiograph ) , 28-day mortality , length of stay , and adverse events . Filgrastim increased blood neutrophils 3-fold , but TRM , mortality , and length of hospitalization were not affected . Treatment , however , accelerated radiologic improvement and appeared to reduce serious complications ( e.g. , empyema , adult respiratory distress syndrome , and disseminated intravascular coagulation ) . Filgrastim administration was safe and well tolerated in these patients . Additional trials are needed to establish the value of this approach to treatment of infectious diseases A r and omised trial was undertaken in one hundred patients with heart failure and /or chest infection to determine whether low-dose subcutaneous heparin reduced the frequency of deep vein thrombosis ( DVT ) in the legs . Heparin , ( 5000 units 8 hourly ) significantly reduced the frequency of DVT , diagnosed by the125I-fibrinogen scan technique , from 26 to 4 per cent ( p < 0.01 ) . Heparin was started within 12 hours of admission to hospital and continued until the patient was fully mobile . Heparin did not cause bleeding problems except for a 20 per cent incidence of injection site bruising . We therefore recommend prophylaxis with low-dose subcutaneous heparin in patients with heart failure or chest infection who require more than three days bed rest Two hundred and seventy patients over 65 years were included in a placebo-controlled r and omized double-blind trial to determine whether a small dose of a low molecular weight ( LMW ) heparin prevents the occurrence of deep vein leg thrombosis ( DVT ) diagnosed by 125I fibrinogen scanning . LMW heparin ( 60 mg daily ) significantly reduced the frequency of DVT from 9 to 3 percent ( p = 0.03 ) . Adverse drug reactions did not differ significantly between the 2 groups , except for the injection site hematomas that were more frequent in the LMW heparin group . In conclusion , LMW heparin appears of value in preventing the occurrence of DVT in an unselected elderly in-patient population BACKGROUND The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately design ed trials . METHODS In a double-blind study , we r and omly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin , 20 mg of enoxaparin , or placebo subcutaneously once daily for 6 to 14 days . Most patients were not in an intensive care unit . The primary outcome was venous thromboembolism between days 1 and 14 , defined as deep-vein thrombosis detected by bilateral venography ( or duplex ultrasonography ) between days 6 and 14 ( or earlier if clinical ly indicated ) or documented pulmonary embolism . The duration of follow-up was three months . RESULTS The primary outcome could be assessed in 866 patients . The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin ( 5.5 percent [ 16 of 291 patients ] ) than in the group that received placebo ( 14.9 percent [ 43 of 288 patients ] ) ( relative risk , 0.37 ; 97.6 percent confidence interval , 0.22 to 0.63 ; P < 0.001 ) . The benefit observed with 40 mg of enoxaparin was maintained at three months . There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin ( 43 of 287 patients [ 15.0 percent ] ) and the placebo group . The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group . By day 110 , 50 patients had died in the placebo group ( 13.9 percent ) , 51 had died in the 20-mg group ( 14.7 percent ) , and 41 had died in the 40-mg group ( 11.4 percent ) ; the differences were not significant . CONCLUSIONS Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses BACKGROUND Community-acquired pneumonia is a major cause of death in third world countries . Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia . We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha ( TNF-alpha ) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy . AIM To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia . DESIGN R and omized placebo-controlled study . SETTING Multidisciplinary ICU of a tertiary care teaching hospital . PATIENTS AND METHODS Patients with three or more British Thoracic Society criteria of severe pneumonia were studied . Patients were r and omized to receive either a single dose of hydrocortisone ( 10 mg/kg ) or placebo 30 min prior to commencing antibiotic therapy . Patients were treated with cefotaxime and other antibiotics as clinical ly indicated . Blood for TNF-alpha was taken at the time of hospital admission and repeated 2 , 6 , and 12 h after starting antibiotic therapy . RESULTS Thirty patients were studied : 16 received placebo and 14 received hydrocortisone . The patients who received placebo tended to be sicker than the patients who received hydrocortisone . The baseline TNF-alpha value was 989 + /- 374 pg/ml in the placebo group and 827 + /- 394 pg/ml in the hydrocortisone group . In both groups of patients , the TNF-alpha levels did not change significantly with time . There was no correlation between the TNF-alpha levels and the APACHE II score , lung injury score , or outcome . The only variable that predicted outcome was the APACHE II score . CONCLUSION Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia . Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia Objective Antimicrobial effects of nitric oxide ( NO ) have been demonstrated in vitro against a variety of infectious pathogens , yet in vivo evidence of a potential therapeutic role for exogenous NO as an antimicrobial agent is limited . Thus , we assessed the effects of inhaled NO on pulmonary infection , leukocyte infiltration , and NO synthase ( NOS ) activity in a rat model of Pseudomonas aeruginosa pneumonia . Design Controlled animal study . Setting Research laboratory of an academic institution . Subjects Male Sprague-Dawley rats . Interventions After intratracheal instillation of either P. aeruginosa or saline ( sham ) , rats were r and omly exposed to either 40 ppm of inhaled NO or room air ( RA ) for 24 hrs before they were killed . Measurements and Main Results Inhaled NO in pneumonia rats markedly reduced pulmonary bacterial load ( 0.02 ± 0.01 % vs. 0.99 ± 0.59 % of bacterial input in pneumonia with room air , p < .05 ) and pulmonary myeloperoxidase activity , a marker of leukocyte infiltration ( 21.7 ± 3.8 vs. 55.0 ± 8.1 units in pneumonia with room air , p < .05 ) , but had no effect on systemic hemodynamics or gas exchange . Pneumonia was associated with enhanced pulmonary NOS activity ( 8.8 ± 2.4 vs. 0.2 ± 0.1 pmol citrulline/min/mg protein in sham , p < .01 ) and increased plasma levels of nitrites/nitrates ( NOx− ; 45 ± 7 vs. 16 ± 3 & mgr;mol/L in sham , p < .01 ) . Inhaled NO therapy attenuated the pneumonia-induced increase in pulmonary calcium-independent NOS activity ( p < .05 ) and markedly increased plasma NOx− levels . Exposure of P. aeruginosa in culture to 40 ppm of ambient NO confirmed a delayed antibacterial effect of NO in vitro . Conclusions Inhaled NO has an important antibacterial effect both in vitro and in vivo against P. aeruginosa and is associated with reduced pulmonary leukocyte infiltration in vivo . These results in a rat model of P. aeruginosa pneumonia suggest that future studies should address the possible clinical effects of inhaled NO therapy in pneumonia Objective : Alveolar fibrin deposition is a hallmark of pneumonia . It has been proposed that recombinant human activated protein C exerts lung-protective effects via anticoagulant and anti-inflammatory pathways . We investigated the role of the protein C system in pneumonia caused by Pseudomonas aeruginosa , the organism that is predominantly involved in ventilator-associated pneumonia . Design : An observational clinical study and a controlled , in vivo laboratory study . Setting : Multidisciplinary intensive care unit and a research laboratory of a university hospital . Patients and Subjects : Patients with unilateral ventilator-associated pneumonia and male Sprague-Dawley rats . Interventions : Bilateral bronchoalveolar lavage was performed in five patients with unilateral ventilator-associated pneumonia . A total of 62 rats were challenged with intratracheal P. aeruginosa ( 108 colony-forming units ) , inducing pneumonia . Rats were r and omized to treatment with normal saline , recombinant human activated protein C , heparin , or recombinant tissue plasminogen activator . Measurements and Main Results : Patients with pneumonia demonstrated suppressed levels of protein C and activated protein C in bronchoalveolar lavage fluid obtained from the infected site compared with the contralateral uninfected site . Intravenous administration of recombinant human activated protein C in rats with P. aeruginosa pneumonia limited bronchoalveolar generation of thrombin – antithrombin complexes , largely preserving local antithrombin activity . However , recombinant human activated protein C did not have effects on neutrophil influx and activity , expression of pulmonary cytokines , or bacterial clearance . Conclusions : In patients with ventilator-associated pneumonia , the pulmonary protein C pathway is impaired at the site of infection , and local anticoagulant activity may be insufficient . Recombinant human activated protein C prevents procoagulant changes in the lung ; however , it does not seem to alter the pulmonary host defense against P. aeruginosa pneumonia BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic One hundred and seventy one patients with primary pneumonia entered a single blind , placebo controlled trial of physiotherapy . Treatment was allocated at r and om , physiotherapy consisting of postural drainage , external help with breathing , percussion , and vibration and the controls receiving advice on expectoration , deep breathing , and how to exercise to avoid thrombosis . Principles of pharmaceutical management were the same in the two groups . There was no objective evidence that daily physiotherapy helped during the acute phase of the disease . On the contrary , in younger patients , smokers , and patients with interstitial pneumonia physiotherapy appeared to prolong the duration of fever as well as the hospital stay . It is concluded that chest physiotherapy is at best useless in patients with primary infectious pneumonia Objectives To determine whether statins reduce mortality or need for admission to intensive care in patients admitted to hospital with community acquired pneumonia ; and to assess whether previously reported improvements in sepsis related outcomes were a result of the healthy user effect . Design Population based prospect i ve cohort study . Setting Six hospitals in Capital Health , Edmonton , Alberta , Canada . Participants Adults admitted to hospital with pneumonia and categorised according to use of statins for at least one week before admission and during hospital stay . Main outcome measures Composite of in-hospital mortality or admission to an intensive care unit . Results Of 3415 patients with pneumonia admitted to hospital , 624 ( 18 % ) died or were admitted to an intensive care unit . Statin users were less likely to die or be admitted to an intensive care unit than non-users ( 50/325 ( 15 % ) v 574/3090 ( 19 % ) , odds ratio 0.80 , P=0.15 ) . After more complete adjustment for confounding , however , the odds ratios changed from potential benefit ( 0.78 , adjusted for age and sex ) to potential harm ( 1.10 , fully adjusted including propensity scores , 95 % confidence interval 0.76 to1.60 ) . Conclusions Statins are not associated with reduced mortality or need for admission to an intensive care unit in patients with pneumonia ; reports of benefit in the setting of sepsis may be a result of confounding BACKGROUND Granulocyte colony-stimulating factor ( G-CSF ) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils . In septic shock , the immune system can be considered one of the failing organ systems . G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock . AIM To evaluate the introduction of G-CSF as an adjunct to our st and ard treatment for community-acquired septic shock . METHODS We performed a prospect i ve data collection and analysis to determine whether the addition of G-CSF to our st and ard treatment for community-acquired septic shock was associated with improved hospital outcome , compared with an historical cohort of similar patients . We included all patients admitted to the Intensive Care Unit ( ICU ) with community-acquired septic shock between December 1998 and March 2000 . Patients received 300 microg G-CSF intravenously daily for 10 days in addition to our st and ard treatment for community-acquired septic shock . G-CSF was discontinued early if the patient was discharged from ICU before 10 days or if the absolute neutrophil count exceeded 75 x 10(6)/mL. RESULTS A total of 36 patients with community-acquired septic shock , an average Apache 2 score of 26.7 , and a predicted mortality of 0.79 , were treated with G-CSF from December 1998 to March 2000 . Hospital mortality was 31 % compared with an historical cohort of 11 similar patients with a hospital mortality of 73 % ( P = 0.018 ) . In the subgroup of patients with melioidosis septic shock , the hospital survival improved from 5 % to 100 % ( P < 0.0001 ) . No significant adverse events occurred as a result of the administration of G-CSF . CONCLUSION G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome . The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF . The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended BACKGROUND Atherosclerosis and sepsis share several pathophysiological similarities , including immune dysregulation , increased thrombogenesis , and systemic inflammation . The relation between statins and risk of sepsis in patients with atherosclerosis is unknown . METHODS We did a population -based cohort analysis through linked administrative data bases in Ontario , Canada , with accrual from 1997 to 2002 . We identified 141,487 patients older than 65 years who had been hospitalised for an acute coronary syndrome , ischaemic stroke , or revascularisation , who survived for at least 3 months after discharge . 46,662 ( 33 % ) were prescribed a statin within 90 days of discharge , 94,825 ( 67 % ) were not . Propensity-based matching , which accounted for each individual 's likelihood of receiving a statin , yielded a cohort of 69,168 patients , of whom half ( 34,584 ) received a statin and half ( 34,584 ) did not . FINDINGS Incidence of sepsis was lower in patients receiving statins than in controls ( 71.2 vs 88.0 events per 10,000 person-years ; hazard ratio [ HR ] 0.81 ; 95 % CI 0.72 - 0.91 ) . Adjustment for demographic characteristics , sepsis risk factors , comorbidities , and health-care use gave similar results ( HR 0.81 ; 95 % CI 0.72 - 0.90 ) . The protective association between statins and sepsis persisted in high-risk subgroups , including patients with diabetes mellitus , chronic renal failure , or a history of infections . Significant reductions in severe sepsis ( HR 0.83 ; 95 % CI 0.70 - 0.97 ) and fatal sepsis ( 0.75 ; 0.61 - 0.93 ) were also observed . No benefit was noted with non-statin lipid-lowering agents ( 0.95 ; 0.75 - 1.22 ) . IMPLICATION S Use of statins in patients with atherosclerosis is associated with a reduced risk of subsequent sepsis . R and omised trials of statins for prevention of sepsis are warranted The aim of the study was to assess the potential role of glucocorticoids ( GC ) in modulating systemic and pulmonary inflammatory responses in mechanically ventilated patients with severe pneumonia . Twenty mechanically ventilated patients with pneumonia treated at a respiratory intensive care unit ( RICU ) of a 1,000-bed teaching hospital were prospect ively studied . All patients had received prior antimicrobial treatment . Eleven patients received GC ( mean+/-SD dose of i.v . methylprednisolone 677+/-508 mg for 9+/-7 days ) , mainly for bronchial dilatation . Serum and bronchoalveolar lavage fluid ( BALF ) tumour necrosis factor (TNF)-alpha , interleukin (IL)-1beta , IL-6 and C-reactive protein levels were measured in all patients . The inflammatory response was attenuated in patients receiving GC , both systemically ( IL-6 1,089+/-342 versus 630+/-385 pg x mL(-1 ) , p=0.03 ; C-reactive protein 34+/-5 versus 19+/-5 mg x L(-1 ) , p=0.04 ) and locally in BALF ( TNF-alpha 118+/-50 versus 24+/-5 pg x mL(-1 ) , p= 0.05 ; neutrophil count : 2.4+/-1.1 x 10(9 ) cells x L(-1 ) ( 93+/-3 % ) versus 1.9+/-1.8 x 10(9 ) cells x L(-1 ) ( 57+/-16 % ) , p=0.03 ) . Four of the 11 ( 36 % ) patients receiving GC died compared to six ( 67 % ) who were not receiving GC ( p=0.37 ) . The present pilot study suggests that glucocorticoids decrease systemic and lung inflammatory responses in mechanically ventilated patients with severe pneumonia receiving antimicrobial treatment BACKGROUND : For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS : We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For each treatment , the magnitudes of the effects in the various observational studies were combined by the Mantel-Haenszel or weighted analysis -of-variance procedure and then compared with the combined magnitude of the effects in the r and omized , controlled trials that evaluated the same treatment . RESULTS : There were 136 reports about 19 diverse treatments , such as calcium-channel-blocker therapy for coronary artery disease , appendectomy , and interventions for subfertility . In most cases , the estimates of the treatment effects from observational studies and r and omized , controlled trials were similar . In only 2 of the 19 analyses of treatment effects did the combined magnitude of the effect in observational studies lie outside the 95 percent confidence interval for the combined magnitude in the r and omized , controlled trials . CONCLUSIONS : We found little evidence that estimates of treatment effects in observational studies reported after 1984 are either consistently larger than or qualitatively different from those obtained in r and omized , controlled trials Background —Considerable variability exists in the use of pharmacological thromboprophylaxis among acutely ill medical patients , partly because clinical ly relevant end points have not been fully assessed in this population . We undertook an international , multicenter , r and omized , double-blind , placebo-controlled trial using clinical ly important outcomes to assess the efficacy and safety of dalteparin in the prevention of venous thromboembolism in such patients . Methods and Results — Patients ( n=3706 ) were r and omly assigned to receive either subcutaneous dalteparin 5000 IU daily or placebo for 14 days and were followed up for 90 days . The primary end point was venous thromboembolism , defined as the combination of symptomatic deep vein thrombosis , symptomatic pulmonary embolism , and asymptomatic proximal deep vein thrombosis detected by compression ultrasound at day 21 and sudden death by day 21 . The incidence of venous thromboembolism was reduced from 4.96 % ( 73 of 1473 patients ) in the placebo group to 2.77 % ( 42 of 1518 patients ) in the dalteparin group , an absolute risk reduction of 2.19 % or a relative risk reduction of 45 % ( relative risk , 0.55 ; 95 % CI , 0.38 to 0.80 ; P=0.0015 ) . The observed benefit was maintained at 90 days . The overall incidence of major bleeding was low but higher in the dalteparin group ( 9 patients ; 0.49 % ) compared with the placebo group ( 3 patients ; 0.16 % ) . Conclusions —Dalteparin 5000 IU once daily halved the rate of venous thromboembolism with a low risk of bleeding This study assessed the safety and efficacy of filgrastim ( r-metHuG-CSF [ recombinant human methionine granulocyte colony-stimulating factor ] ) , when combined with intravenous ( IV ) antibiotics , in the treatment of hospitalized adult patients with multilobar community-acquired pneumonia ( CAP ) . Four hundred eighty patients were r and omized to receive placebo ( n=243 ) or filgrastim 300 microg/day ( n=237 ) , in addition to st and ard therapy . Treatment with study drug was continued for 10 days , until the peak white blood cell ( WBC ) count reached 75x109/L , until discharge from the hospital , until death , or until IV antibiotics were discontinued . Study -related observations continued through day 29 . Filgrastim increased WBC counts ( baseline median , 13.3x109/L ; median peak , 43 . 8x109/L ) . The 2 treatment groups were not statistically different with respect to the study end points ; however , there was a trend toward reduction of mortality in patients with pneumococcal bacteremia . Although further studies will be required to vali date this observation , filgrastim was safe and well tolerated when administered to patients with multilobar CAP |
2,482 | 24,906,591 | The evidence for the effectiveness of yoga as a treatment of hypertension is encouraging but inconclusive . | OBJECTIVES To critically evaluate the effectiveness of yoga as a treatment of hypertension . | Background : Hypertension is the most prevalent non-communicable disease causing significant morbidity/mortality through cardiovascular , cerebrovascular , and renal complications . Objectives : This community-based study tested the efficacy of non-pharmacological interventions in preventing/controlling hypertension . Material s and Methods : This is a cross-over r and omized controlled trial ( RCT ) of the earlier RCT ( 2007 ) of non-pharmacological interventions in hypertension , conducted in the urban service area of our Institute . The subjects , prehypertensive and hypertensive young adults ( 98 subjects : 25 , 23 , 25 , 25 in four groups ) were r and omly allotted into a group that he/she had not belonged to in the earlier RCT : Control ( New Group I ) , Physical Exercise ( NG II)-brisk walking for 50 to 60 minutes , three to four days/week , Salt Intake Reduction ( NG III ) to at least half of their previous intake , Yoga ( NG IV ) for 30 to 45 minutes/day , five days/week . Blood pressure was measured before and after eight weeks of intervention . Analysis was by ANOVA with a Games-Howell post hoc test . Results : Ninety-four participants ( 25 , 23 , 21 , 25 ) completed the study . All three intervention groups showed significant reduction in BP ( SBP/DBP mmHg : 5.3/6.0 in NG II , 2.5/2.0 in NG III , and 2.3/2.4 in NG IV , respectively ) , while the Control Group showed no significant difference . Persistence of significant reduction in BP in the three intervention groups after cross-over confirmed the biological plausibility of these non-pharmacological interventions . This study reconfirmed that physical exercise was more effective than Salt Reduction or Yoga . Salt Reduction , and Yoga were equally effective . Conclusion : Physical exercise , salt intake reduction , and yoga are effective non-pharmacological methods for reducing blood pressure in young pre-hypertensive and hypertensive adults In this study 258 patients from the Department of Cardiology in Chhatrapati Shahuji Maharaj Medical University , Lucknow were selected to participate . All had been diagnosed with coronary artery disease . They were r and omly divided into 2 groups , the yoga group and the non-yoga group , 129 in each group ; 208 completed the study protocol . The yogic intervention consisted of 35 - 40 min/day , 5 days a week over a period of 18 months in the Department of Physiology . Autonomic function testing was done in both the groups at zero time and after 18 months . We observed a statistically significant reduction in body mass index , waist circumference , systolic and diastolic blood pressure , and heart rate ( P < 0.05 ) , i.e. , a significant positive effect was observed when yoga therapy was used as an adjunct in patients with coronary artery disease Background Previously alternate nostril yoga breathing ( anuloma-viloma pranayama ) was shown to reduce the blood pressure ( BP ) in people with hypertension . An elevated BP has been associated with poor performance in certain tasks requiring attention and co-ordination . The Purdue pegboard task assesses manual dexterity and eye-h and co-ordination . Material / Methods In the present study there were ninety participants with essential hypertension . Their ages ranged from 20 to 59 years ( group average age ±S.D. , 49.7±9.5 years ; sixty males ) . Participants were r and omized as three groups , with thirty participants in each group . One group practice d alternate nostril yoga breathing for 10 minutes , the second group practice d breath awareness for the same duration and the third group was given a control intervention ( i.e. , reading a magazine with neutral content ) . Assessment s were taken before and after the interventions for participants of the three groups . Assessment s included the blood pressure and performance in the Purdue pegboard task . Data were analyzed with a repeated measures ANOVA and post-hoc analyses were Bonferroni adjusted . Results Following alternate nostril breathing ( ANYB ) there was a significant decrease in systolic and diastolic blood pressure ( p<0.001 and p<0.05 ) , and an improvement in Purdue pegboard task scores for both h and s ( p<0.05 ) , and for the right h and ( p<.001 ) . Breath awareness ( the control session ) also showed a significant decrease in systolic blood pressure ( p<0.05 ) . The right h and scores improved in the group reading a magazine ( p<0.05 ) . Conclusions The results suggest that the immediate effect of ANYB is to reduce the BP while improving the performing in a task requiring attention , bimanual dexterity and visuo-motor co-ordination Various modes of physical activity , combined with dieting , have been widely recommended to prevent or delay type 2 diabetes . Among these , yoga holds promise for reducing risk factors for type 2 diabetes by promoting weight loss , improving glucose levels and reducing blood pressure and lipid levels . This pilot study aim ed to assess the feasibility of implementing a 12-week yoga program among adults at high risk for type 2 diabetes . Twenty-three adults ( 19 Whites and 4 non-Whites ) were r and omly assigned to the yoga intervention group or the educational group . The yoga group participated in a 3-month yoga intervention with sessions twice per week and the educational group received general health educational material s every 2 weeks . All participants completed question naires and had blood tests at baseline and at the end of 3 months . Effect sizes were reported to summarize the efficacy of the intervention . All participants assigned to the yoga intervention completed the yoga program without complication and expressed high satisfaction with the program ( 99.2 % ) . Their yoga session attendance ranged from 58.3 to 100 % . Compared with the education group , the yoga group experienced improvements in weight , blood pressure , insulin , triglycerides and exercise self-efficacy indicated by small to large effect sizes . This preliminary study indicates that a yoga program would be a possible risk reduction option for adults at high risk for type 2 diabetes . In addition , yoga holds promise as an approach to reducing cardiometabolic risk factors and increasing exercise self-efficacy for this group The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions . Iyengar yoga ( IY ) has been purported to reduce blood pressure ( BP ) though evidence from r and omized trials is lacking . We conducted a r and omized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care ( EUC ) ( based on individual dietary adjustment ) on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension . In total , 26 and 31 subjects in the IY and EUC arms , respectively , completed the study . There were no differences in BP between the groups at 6 and 12 weeks . In the EUC group , 24-h systolic BP ( SBP ) , diastolic BP ( DBP ) and mean arterial pressure ( MAP ) significantly decreased by 5 , 3 and 3 mmHg , respectively , from baseline at 6 weeks ( P < .05 ) , but were no longer significant at 12 weeks . In the IY group , 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline ( P = .05 ) . 24 h DBP ( P < .01 ) and MAP ( P < .05 ) decreased significantly each by 5 mmHg . No differences were observed in catecholamine or cortisol metabolism to explain the decrease in BP in the IY group at 12 weeks . Twelve weeks of IY produces clinical ly meaningful improvements in 24 h SBP and DBP . Larger studies are needed to establish the long term efficacy , acceptability , utility and potential mechanisms of IY to control BP Context : Hypertension is a major chronic lifestyle disease . Several non-pharmacological interventions are effective in bringing down the blood pressure ( BP ) . This study focuses on the effectiveness of such interventions among young adults . Aims : To measure the efficacy of physical exercise , reduction in salt intake , and yoga , in lowering BP among young ( 20 - 25 ) pre-hypertensives and hypertensives , and to compare their relative efficacies . Setting s and Design : The study was done in the urban service area of JIPMER . Pre-hypertensives and hypertensives , identified from previous studies , constituted the universe . The participants were r and omized into one control and three interventional groups . Material s and Methods : A total of 113 subjects : 30 , 28 , 28 and 27 in four groups respectively participated for eight weeks : control ( I ) , physical exercise ( II ) - brisk walking for 50 - 60 minutes , four days/week , salt intake reduction ( III ) - to at least half of their previous intake , and practice of yoga ( IV ) - for 30 - 45 minutes/day on at least five days/week . Statistical Analysis Used : Efficacy was assessed using paired t test and ANOVA with Games Howell post hoc test . An intention to treat analysis was also performed . Results : A total of 102 participants ( 29 , 27 , 25 and 21 in groups I , II , III and IV ) completed the study . All three intervention groups showed a significant reduction in BP ( SBP/DBP : 5.3/6.0 in group II , 2.6/3.7 in III , and 2.0/2.6 mm Hg in IV respectively ) . There was no significant change ( SBP/DBP : 0.2/0.5 mmHg ) of BP in control group ( I ) . Physical exercise was most effective ( considered individually ) ; salt intake reduction and yoga were also effective . Conclusions : Physical exercise , salt intake reduction , and yoga are effective non-pharmacological interventions in significantly reducing BP among young hypertensives and pre-hypertensives . These can therefore be positively recommended for hypertensives . There is also a case to deploy these interventions in the general population 34 hypertensive patients were assigned at r and om either to six weeks ' treatment by yoga relaxation methods with bio-feedback or to placebo therapy ( general relaxation ) . Both groups showed a reduction in blood-pressure ( from 168/100 to 141/84 mm . Hg in the treated group and from 169/101 to 160/96 mm Hg in the control group ) . The difference was highly significant . The control group was then trained in yoga relaxation , and their blood-pressure fell to that of the other group ( now used as controls ) On the basis of medical officers diagnosis , thirty three ( N = 33 ) hypertensives , aged 35 - 65 years , from Govt . General Hospital , Pondicherry , were examined with four variables viz , systolic and diastolic blood pressure , pulse rate and body weight . The subjects were r and omly assigned into three groups . The exp . group-I underwent selected yoga practice s , exp . group-II received medical treatment by the physician of the said hospital and the control group did not participate in any of the treatment stimuli . Yoga imparted in the morning and in the evening with 1 hr/session . day-1 for a total period of 11-weeks . Medical treatment comprised drug intake every day for the whole experimental period . The result of pre-post test with ANCOVA revealed that both the treatment stimuli ( i.e. , yoga and drug ) were effective in controlling the variables of hypertension Ayurveda is derived from 2 Sanskrit words , namely , " Ayus " and " Veda , " meaning life and knowledge , respectively . It literally means science of life . Ayurveda , of which yoga is an integral part , is widely practice d in India and is gaining acceptance in many countries around the world . It is a comprehensive and a holistic system , the focus of which is on the body , mind , and consciousness . The Ayurvedic treatment consists of the use herbal preparations , diet , yoga , meditation , and other practice s. Based on the review of available studies , the evidence is not convincing that any Ayurvedic herbal treatment is effective in the treatment of heart disease or hypertension . However , the use of certain spices and herbs such as garlic and turmeric in an overall healthy diet is appropriate . Many herbs used by Ayurvedic practitioners show promise and could be appropriate for larger r and omized trials . Yoga , an integral part of Ayurveda , has been shown to be useful to patients with heart disease and hypertension . Yoga reduces anxiety , promotes well-being , and improves quality of life . Its safety profile is excellent . Its use as a complementary therapeutic regimen under medical supervision is appropriate and could be worth considering To determine the effectiveness of a yoga program on blood pressure and stress , a group of hypertensive patients in Thail and were studied , with the experimental group showing significantly decreased mean stress scores and blood pressure , heart rate , and body mass index levels compared with the control group . Further studies are suggested to determine the effects of yoga on hypertension in Thail and OBJECTIVE People living with HIV infection are at increased risk for developing cardiovascular disease ( CVD ) . Safe and effective interventions for lowering CVD risk in HIV infection are high priorities . We conducted a prospect i ve , r and omized , controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors , virological or immunological status , or quality of life ( QOL ) in HIV-infected adults relative to st and ard of care treatment in a matched control group . METHODS Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 weeks of supervised yoga practice or st and ard of care treatment . Baseline and week 20 measures were : 2-h oral glucose tolerance test with insulin monitoring , body composition , fasting serum lipid/lipoprotein profile , resting blood pressures , CD4 T-cell count and plasma HIV RNA , and the Medical Outcomes Study Short Form (SF)-36 health-related QOL inventory . RESULTS Resting systolic and diastolic blood pressures improved more ( P=0.04 ) in the yoga group ( -5 + /- 2 and -3 + /- 1 mmHg , respectively ) than in the st and ard of care group ( + 1 + /- 2 and + 2 + /- 2 mmHg , respectively ) . However , there was no greater reduction in body weight , fat mass or proatherogenic lipids , or improvements in glucose tolerance or overall QOL after yoga . Immune and virological status was not adversely affected . CONCLUSION Among traditional lifestyle modifications , yoga is a low-cost , simple to administer , nonpharmacological , popular behavioural intervention that can lower blood pressure in pre-hypertensive HIV-infected adults with mild-moderate CVD risk factors OBJECTIVE --To determine the long term effects of relaxation therapy on 24 hour ambulatory intra-arterial blood pressure in patients with mild untreated and uncomplicated hypertension . DESIGN --Four week screening period followed by r and omisation to receive either relaxation therapy or non-specific counselling for one year . Ambulatory intra-arterial blood pressure was measured before and after treatment . SETTING --Outpatient clinic in Amsterdam 's university hospital . SUBJECTS--35 Subjects aged 20 - 60 who were being treated by general practitioners for hypertension but were referred to take part in the study . At three consecutive screening visits all subjects had a diastolic blood pressure without treatment of 95 - 110 mm Hg . Subjects were excluded if they had damaged target organs , secondary hypertension , diabetes mellitus , a cholesterol concentration greater than 8 mmol/l , or a history of malignant hypertension . INTERVENTIONS --The group allocated to relaxation therapy was trained for eight weeks ( one hour a week ) in muscle relaxation , yoga exercises , and stress management and continued exercising twice daily for one year with monthly visits to the clinic . The control group had the same attendance schedule but had no training and were requested just to sit and relax twice a day . All subjects were asked not to change their diet or physical activity . MAIN OUTCOME MEASURE -- Changes in ambulatory intra-arterial blood pressure after one year of relaxation therapy or non-specific counselling . RESULTS --Mean urinary sodium excretion , serum concentration of cholesterol , and body weight did not change in either group . Diastolic pressures measured by sphygmomanometry were 2 and 3 mm Hg lower in subjects in the relaxation group and control group respectively at the one year follow up compared with initial readings . The mean diastolic ambulatory intra-arterial pressure during the daytime had not changed after one year in either group , but small treatment effects could not be excluded : the mean change for the relaxation group was -1 mm Hg ( 95 % confidence interval -6 to 3.9 mm Hg ) and for the control group -0.4 mm Hg ( -5.3 to 4.6 mm Hg ) . Mean ambulatory pressure in the evening also had not changed over the year , and in both groups nighttime pressure was 5 mm Hg higher . The variability in blood pressure was the same at both measurements . CONCLUSIONS --Relaxation therapy was an ineffective method of lowering 24 hour blood pressure , being no more beneficial than non-specific advice , support , and reassurance -- themselves ineffective as a treatment for hypertension The purpose of this study was to compare the effects of yoga with an active control ( nonaerobic exercise ) in individuals with prehypertension and stage 1 hypertension . A r and omized clinical trial was performed using two arms : ( 1 ) yoga and ( 2 ) active control . Primary outcomes were 24-hour day and night ambulatory systolic and diastolic blood pressures . Within-group and between-group analyses were performed using paired t tests and repeated- measures analysis of variance ( time × group ) , respectively . Eighty-four participants enrolled , with 68 participants completing the trial . Within-group analyses found 24-hour diastolic , night diastolic , and mean arterial pressure all significantly reduced in the yoga group ( -3.93 , -4.7 , -4.23 mm Hg , respectively ) but no significant within-group changes in the active control group . Direct comparisons of the yoga intervention with the control group found a single blood pressure variable ( diastolic night ) to be significantly different ( P=.038 ) . This study has demonstrated that a yoga intervention can lower blood pressure in patients with mild hypertension . Although this study was not adequately powered to show between-group differences , the size of the yoga-induced blood pressure reduction appears to justify performing a definitive trial of this intervention to test whether it can provide meaningful therapeutic value for the management of hypertension BACKGROUND Preliminary studies investigating yoga and breath work for treating asthma have been promising . Several r and omized controlled trials have shown a benefit from yoga postures and breathing vs control , but the control in these cases involved no intervention other than usual care . This study advances the field by providing an active control . OBJECTIVE To determine the effectiveness and feasibility of a yoga and breath work intervention for improving clinical indices and quality of life in adults with mild-to-moderate asthma . METHODS A r and omized , controlled , double-masked clinical trial was conducted between October 1 , 2001 , and March 31 , 2003 . R and om assignment was made to either a 4-week yoga intervention that included postures and breath work or a stretching control condition . Outcome measures were evaluated at 4 , 8 , 12 , and 16 weeks and included the Mini Asthma Quality of Life Question naire , rescue inhaler use , spirometry , symptom diaries , and health care utilization . RESULTS Sixty-two participants were r and omized to the intervention and control groups , and 45 completed the final follow-up measures . Intention-to-treat analysis was performed . Significant within-group differences in postbronchodilator forced expiratory volume in 1 second and morning symptom scores were apparent in both groups at 4 and 16 weeks ; however , no significant differences between groups were observed on any outcome measures . CONCLUSIONS Iyengar yoga conferred no appreciable benefit in mild-to-moderate asthma . Circumstances under which yoga is of benefit in asthma management , if any , remain to be determined OBJECTIVES Breathing exercises practice d in various forms of meditations such as yoga may influence autonomic functions . This may be the basis of therapeutic benefit to hypertensive patients . DESIGN The study design was a r and omized , prospect i ve , controlled clinical study using three groups . SUBJECTS The subjects comprised 60 male and female patients aged 20 - 60 years with stage 1 essential hypertension . INTERVENTION Patients were r and omly and equally divided into the control and other two intervention groups , who were advised to do 3 months of slow-breathing and fast-breathing exercises , respectively . Baseline and postintervention recording of blood pressure ( BP ) , autonomic function tests such as st and ing-to-lying ratio ( S/L ratio ) , immediate heart rate response to st and ing ( 30:15 ratio ) , Valsalva ratio , heart rate variation with respiration ( E/I ratio ) , h and -grip test , and cold pressor response were done in all subjects . RESULTS Slow breathing had a stronger effect than fast breathing . BP decreased longitudinally over a 3-month period with both interventions . S/L ratio , 30:15 ratio , E/I ratio , and BP response in the h and grip and cold pressor test showed significant change only in patients practicing the slow-breathing exercise . CONCLUSIONS Both types of breathing exercises benefit patients with hypertension . However , improvement in both the sympathetic and parasympathetic reactivity may be the mechanism that is associated in those practicing the slow-breathing exercise |
2,483 | 23,904,176 | tubular or glomerular kidney injury , 2 . | BACKGROUND There is some evidence for the benefits of leukodepletion in patients undergoing coronary artery surgery .
Its effectiveness in higher risk patients , such as those undergoing heart valve surgery , particularly in terms of overall clinical outcomes , is currently unclear .
OBJECTIVES To assess the beneficial and harmful effects of leukodepletion on clinical , patient-reported and economic outcomes in patients undergoing heart valve surgery . | Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response . We examined combined use of heparin coating of the cardiopulmonary bypass circuit and a leukocyte-depleting arterial line filter to reduce this response . Thirty patients were allocated r and omly to equal groups with a conventional circuit and arterial line filter ( C group ) , a heparin-coated circuit with a conventional filter ( H group ) , or a heparin-coated circuit with a leukocyte-depleting arterial line filter ( HF group ) . Cytokines and respiratory function were repeatedly measured perioperatively . Plasma interleukin (IL)-6 concentrations in the HF group were lower than in the C group immediately following bypass and operation , at 4 h , and 12 h ( p < 0.05 ) . Plasma IL-8 was lower in the HF group than in the C group at 4 h ( p < 0.05 ) . The respiratory index was lower immediately after bypass in the HF group than the C group ( 0.61 + /- 0.2 versus 1.05 + /- 0.4 , p < 0.05 ) . Heparin-coated circuits with leukocyte-depleting filters decrease inflammatory responses and improve pulmonary function during operation Leukocyte mediated pulmonary injury may delay recovery after cardiac surgery , and leukocyte depletion during bypass has been suggested . Two groups of patients were r and omly , prospect ively assigned from 50 sequential patients to undergo open heart surgery using cardiopulmonary bypass , either with ( n = 25 ) or without ( n = 25 ) leukocyte filters . The two groups were not significantly different regarding age , gender , race , pre-operative ejection fraction , pump time , or cross-clamp time . Post operative arterial blood gases ( pO2 : 173 + /- 66 vs 192 + /- 107 ; pCO2 : 30.2 + /- 8.2 vs 30.8 + /- 8.0 ) , pulmonary vascular resistance ( PVR 105 + /- 45 vs 112 + /- 50 dyne cm-5 ) , time on ventilator ( 17.8 + /- 6.4 vs 19.7 + /- 8.6 hr ) , and length of hospital stay ( 7.65 + /- 4.57 vs 8.52 + /- 5.87 days ) were not different between groups ( mean + /- SD , with vs without filters , respectively ) . Arterial oxygenation was somewhat poorer , and PVR was somewhat lower in the leukocyte filtered group . However , these trends did not produce significant decreases in total ventilator time or length of hospital stay . In-line filtration did remove leukocytes , but did not reduce circulating leukocyte count . In effect , leukocyte filtration produced an effective leukocyte concentration at the filter site . These data do not support routine incorporation of in-line leukocyte filtration during bypass Each year , 600 000 patients undergo myocardial revascularization with cardiopulmonary bypass and sustain profound physiologic perturbations that precipitate ischemia and infa rct ion in several organ systems [ 1 - 3 ] . Although medical re sources have been redirected to address perioperative cardiac and neurologic illness , the clinical effect of cardiac surgery on renal function has not been studied rigorously . Nonpulsatile blood flow , increases in levels of circulating catecholamines and inflammatory mediators , macroembolic and microembolic insults to the kidney , and release of free hemoglobin from traumatized erythrocytes result in numerous pathophysiologic renal responses [ 4 - 6 ] . Many studies [ 7 - 9 ] have shown that patients who have undergone cardiac surgery developed maldistributed renal blood flow , increases in renal vascular resistance , and substantive decreases ( 25 % to 75 % ) in renal blood flow and glomerular filtration rate . The effect of these phenomena on clinical outcome is not well known but is thought to be considerable . Studies have reported incidences of oliguric renal failure requiring dialysis as high as 5 % and mortality rates as great as 89 % . Previous studies [ 10 - 19 ] have many limitations because of a wide variability ( threefold or more ) in estimates of adverse renal outcomes : All of the studies were conducted at a single center , most were retrospective , and most were done more than a decade ago . No previous study provided adjusted estimates of risk factors ; in addition , the definition chosen for renal dysfunction was arbitrary , or the study sample consisted only of patients requiring dialysis [ 11 , 13 , 15 - 17 ] . Finally , few studies have investigated re source utilization in patients with renal dysfunction or failure . We therefore studied 2400 patients who underwent myocardial revascularization with cardiopulmonary bypass . Our goals were to determine 1 ) the incidence and characteristics of postoperative renal dysfunction and failure , 2 ) the predictors of renal dysfunction [ determined by the use of multivariate modeling techniques ] , and 3 ) the effect of renal dysfunction on in-hospital re source utilization and patient disposition after discharge . Methods Patients The Multicenter Study for Perioperative Ischemia ( McSPI ) Research Group studied 2417 patients undergoing myocardial revascularization between 1991 and 1993 . Twenty-four diverse U.S. health care facilities-small and large academic institutions , private medical centers , health maintenance organization groups , and Veterans Affairs hospitals-participated in this study . Most patients were representative of consecutive patients seen at a given medical center . We enrolled every nth patient on the basis of a proportion of the site-specific expected annual caseload ( n = 2 through 30 in 24 centers ) . Comprehensive data were collected from preoperative cardiac , surgical , and medical histories ; invasive and noninvasive cardiologic testing ; surgical procedures and techniques ; perioperative hemodynamic events ; postoperative in-hospital events ( illness and death ) ; and hospital re source utilization . In addition , serial preoperative and postoperative 12-lead electrocardiograms were obtained and were central ly analyzed by a consensus panel of cardiologists . Serum creatinine values were recorded before and after surgery . Of the 2417 patients enrolled , 195 were excluded from analysis because of preexisting renal failure ( n = 99 ) or dysfunction ( serum creatinine level > 177 mol/L [ n = 81 ] ) or lack of perioperative serum creatinine measurements ( n = 68 ) . The latter group included patients who died before a postoperative sample could be obtained . Definitions of Renal Failure , Renal Dysfunction , and Comorbid Events Postoperative renal failure was defined by the need for dialysis after surgery . Renal dysfunction was defined as a postoperative serum creatinine level of 177 mol/L or greater and an increase in serum creatinine level of 62 mol/L or greater from preoperative to maximum postoperative values . The criteria for dysfunction were derived from the distribution of serum creatinine values in an uncomplicated patient subset . This subset excluded patients with preoperative renal disease ( serum creatinine level > 124 mol/L ) or medical risk factors ( age > 70 years ; history of congestive heart failure or type 1 diabetes mellitus ) , or a complicated postsurgical course ( in-hospital death ; concomitant valvular surgery ; intraaortic balloon pump insertion ; administration of at least three nonroutine inotropic drugs ; measures of hemodynamic instability ; ventricular fibrillation or dysrhythmia requiring a pacemaker ; complications necessitating a return to cardiopulmonary bypass , the intensive care unit , or the operating room ; or chest tube output exceeding 1 L/d ) . Less than 1 % of patients meeting these criteria had a maximum postoperative creatinine level greater than 177 mol/L and a maximum preoperative-to-postoperative change in creatinine level of 62 mol/L. Comorbid events , assessed through the first postoperative day , consisted of postoperative myocardial infa rct ion , congestive heart failure ( hemodynamic or clinical ) , use of an intraaortic balloon pump or other mechanical circulatory assist device , administration of three or more inotropic drugs , and hemorrhage . A myocardial infa rct ion was defined as either a Q-wave or a non-Q-wave infa rct ion . A Q-wave myocardial infa rct ion was diagnosed central ly by the presence of a new Q wave on each of two postoperative 12-lead electrocardiograms , as defined by Minnesota Code criteria , that were scored by a consensus panel of cardiologists . A non-Q-wave myocardial infa rct ion was determined by an elevated creatine kinase-MB level , a new wall-motion abnormality detected by echocardiography , or a new perfusion defect on a scintigraphy scan . Low output state [ an ordered , categorical variable ] was defined as one of the following : 1 ) severe ventricular dysfunction-intraaortic balloon pump counterpulsation required , 2 ) moderate ventricular dysfunction-hemodynamic congestive heart failure or at least three nonroutine inotropic drugs prescribed after surgery , and 3 ) mild ventricular dysfunction- clinical congestive heart failure . We defined hemodynamic congestive heart failure on the basis of a cardiac index less than 1.5 L/min per m2 body surface area for at least 30 minutes , a central venous pressure greater than 12 mm Hg , or a pulmonary artery occlusion pressure/left ventricular end diastolic pressure greater than 18 mm Hg . Clinical congestive heart failure was defined according to the presence of pulmonary rales , S3 gallop , or chest radiographic findings suggestive of heart failure . We defined hemorrhage as 1 ) chest tube output of at least 1 L/d , 2 ) return to the critical care unit or operating room within the first postoperative day because of bleeding , or 3 ) administration of three or more units of blood products in the operating room or critical care unit within 48 hours of surgery . Statistical Analysis Distributions and univariate measures of preoperative , postoperative , and preoperative-to-postoperative changes in serum creatinine values were examined . Unadjusted relative risks and 95 % CIs were calculated for all perioperative factors . Adjusted relative risk estimates were derived from multivariate logistic regression models because an 8 % incidence of renal dysfunction is relatively rare . Models were analyzed in a piece-wise fashion ( separate models were developed for each preoperative , operative , and postoperative period from the significant unadjusted factors in each period ) . A final model with adjusted estimates of relative risk was derived with factors that remained significant ( P 0.05 ) in the three time period models . Operative and postoperative variables were entered into the model in a forward stepwise fashion after adjustment for preoperative variables . No appreciable differences were noted when all perioperative factors were allowed to enter into the model in forward or backward stepwise selection procedures . The best-fitting models were selected from evaluation of the Hosmer-Lemeshow goodness-of-fit test statistic and the smallest values of the Akaike Information Criterion . The predictive ability of the models of preoperative risk factors alone , as well as the final model , were also evaluated with the area under the receiver-operating characteristic curve ( the concordance or c-index ) . The c-index was also derived from a validation process that involved comparison of the c-index derived from a r and om sample of half of the patients from each site and a computed c-index derived from modeling the remaining sample 's predicted probability of renal dysfunction calculated from the variable estimates from the original 50 % r and om sample . In other words , a predicted probability was derived from variable estimates from those obtained from the 50 % within-center sample ; these estimates were applied to the patients ' combination of risk factors in the remaining sample . The c-index was then calculated from modeling the remaining sample 's predicted probabilities as a single predictor . From the final model of preoperative risk factors , both observed and predicted probabilities were described and the sensitivity and specificity of the preoperative model were reported . The sensitivity and specificity were determined by selecting the highest sensitivity and specificity from a classification table of observed and predicted events ( this occurred with a probability of renal dysfunction 6 % ) . Theoretically , each of the 24 medical centers in the study sample may have characteristics that were not measured and could have influenced patients ' outcomes . To address potential within-center correlation , ancillary analyses were conducted . Logistic regression models using generalized estimating equations with an exchangeable correlation matrix were used to account for within-center correlation . Estimates of SEs are considered corrected for potential within-center AIMS To identify the characteristics , treatment , and outcomes of contemporary patients with valvular heart disease ( VHD ) in Europe , and to examine adherence to guidelines . METHODS AND RESULTS The Euro Heart Survey on VHD was conducted from April to July 2001 in 92 centres from 25 countries ; it included prospect ively 5001 adults with moderate to severe native VHD , infective endocarditis , or previous valve intervention . VHD was native in 71.9 % of patients and 28.1 % had had a previous intervention . Mean age was 64+/-14 years . Degenerative aetiologies were the most frequent in aortic VHD and mitral regurgitation while most cases of mitral stenosis were of rheumatic origin . Coronary angiography was used in 85.2 % of patients before intervention . Of the 1269 patients who underwent intervention , prosthetic replacement was performed in 99.0 % of aortic VHD , percutaneous dilatation in 33.9 % of mitral stenosis , and valve repair in 46.5 % of mitral regurgitation ; 31.7 % of patients had > or = 1 associated procedure . Of patients with severe , symptomatic , single VHD , 31.8 % did not undergo intervention , most frequently because of comorbidities . In asymptomatic patients , accordance with guidelines ranged between 66.0 and 78.5 % . Operative mortality was < 5 % for single VHD . CONCLUSIONS This survey provides unique contemporary data on characteristics and management of patients with VHD . Adherence to guidelines is globally satisfying as regards investigations and interventions OBJECTIVE Cardiopulmonary bypass-induced systemic inflammatory reaction involving the expression of neutrophil surface adhesion molecules is the main mechanism leading to myocardial ischemia-reperfusion injury as well as multiorgan dysfunction . Patients undergoing prolonged cardiopulmonary bypass are especially at risk in this regard . The aim of this prospect i ve , r and omized study was to evaluate the impact of continuous leukocyte filtration on the perioperative expression of neutrophil adhesion molecules along with the markers of systemic inflammation during combined coronary artery revascularization and aortic valve surgery due to aortic stenosis . PATIENT AND METHODS Twenty patients scheduled for combined coronary artery revascularization and aortic valve surgery due to aortic stenosis were r and omized to undergo cardiopulmonary bypass with or without a leukocyte filter ( LeukoGuard LG6 ) . The expression of neutrophil adhesion molecules and proinflammatory cytokine response were measured . RESULTS The use of the leukocyte filter significantly increased neutrophil CD11b expression ( Pg = .003 ) compared to the control group , which was followed by a faster rise in interleukin-6 levels 5 minutes ( median , 125 versus 34 pg/mL ) and 2 hours after cardiopulmonary bypass ( median , 158 versus 92 pg/mL , Pt x g < .001 ) , respectively . No marked differences in terms of levels of CD11a , CD62L , cardiac troponin-I , or oxyhemodynamics were observed . CONCLUSIONS The observed increased neutrophil activation and enhanced inflammatory response do not support the use of continuous leukofiltration in patients undergoing prolonged cardiopulmonary bypass BACKGROUND We tested the hypothesis that leukocyte filtration during pulmonary reperfusion preserves pulmonary function and results in improved oxygenation after cardiopulmonary bypass ( CPB ) in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS In a prospect i ve , r and omized study , the treatment group consisted of 20 patients with COPD from consecutive open-heart procedures . A primed leukocyte filter was connected to the arterial line downstream of the st and ard arterial filter but was excluded from circulation . Circulated blood was directed through the leukocyte filter approximately 10 minutes before aortic cross-clamp removal and at early reperfusion for up to 30 minutes . These patients were compared to 20 additional COPD patients ( controls ) on whom systemic leukocyte filtration was not used during open-heart surgery . RESULTS There was no significant difference in gender , age , left ventricular ejection fraction , type of procedure , aortic cross-clamp time , perfusion time , preoperative FEV1 and preoperative respiratory index ( Pao2/FiO2 ratio ) between treatment and control groups . The respiratory index changed in the treatment group by + 9.8 % of baseline after completion of CPB , by -14.2 % upon arrival in the intensive care unit ( ICU ) , and by -19.6 % 12 hours later , whereas in the control group , it changed by -14.5 % ( p < 0.05 ) , -27.7 % , and -24 % , respectively . Leukocyte-depleted patients required shorter intubation time ( 20.4 + /- 16.1 hours ) , ICU stay ( 46.2 + /- 40.1 hours ) and length of hospitalization ( 8.3 + /- 2.8 days ) than controls ( 29.5 + /- 21.9 hours , p < 0.05 ; 75.5 + /- 34.9 hours , p < 0.005 ; and 10.4 + /- 3.5 days , p < 0.05 , respectively ) . Surgical ( 30-day ) mortality was zero in both groups . CONCLUSIONS In COPD patients having CPB , systemic leukocyte depletion at early reperfusion was associated with better oxygenation , shorter intubation time , and shorter ICU and hospital stays . Leukocyte filtration during CPB most likely preserves pulmonary function by ameliorating pulmonary reperfusion injury The results of leucocyte filtration during cardiac surgery are conflicting . This may be due to timing and duration of the filtration procedure , and to flow and pressure conditions in the filter . Therefore , we prospect ively compared three major leucocyte filtration strategies in cardiac surgical patients . Forty patients were r and omly divided into four groups . Group I : leucofiltration of arterial blood throughout cardiopulmonary bypass ( CPB ) ( associated with high-flow and pressure gradients ) , Group II : leucofiltration of a part of the venous return blood in the re-warming phase during CPB ( associated with intermediate flow , but high pressure ) , Group III : leucofiltration of residual heart-lung machine blood during transfusion into the patient after CPB ( associated with low flow and low pressure ) , Group IV : control group without leucofiltration . We measured circulating leucocyte counts , plasma elastase levels and arterial blood oxygenation . Filters were postoperatively examined using scanning electronmicroscopy ( SEM ) . Leucocyte counts increased over time and oxygenation decreased in all groups , without significant differences between the groups . SEM demonstrated extensive protein deposits and damaged leucocytes in the deeper layers of the filters from Group I. This was not observed in the filters from Group III . The postoperative plasma elastase levels increased in Groups II and IV and decreased in Groups I and III . In conclusion , we could not demonstrate a clinical difference among the three leucocyte depletion strategies . However , our laboratory results suggest that leucocyte filtration at low flow and pressure conditions is associated with less leucocyte damage and less release of elastase BACKGROUND We aim ed to show the impact of leukodepletion on renal function in patients undergoing on-pump coronary revascularization . PATIENTS AND METHODS Fifty patients awaiting elective on-pump coronary revascularization with normal preoperative cardiac functions and with plasma creatinine levels ranging between 1.5 and 2.0 mg/dL were prospect ively r and omized into two groups : on-pump CABG with ( group A : n = 25 ) and without leukodepletion ( group B , n = 25 ) . Renal glomerular and tubular injury were assessed by urinary alpha glutathione s-transferase ( GST ) , plasma creatinine , and blood urea nitrogen ( BUN ) levels . RESULTS The patients consisted of 14 females and 36 males with a mean age of 57.6 + /- 5.3 years . In the leukodepletion group , the mean levels of creatinine , BUN and urinary GST were found to be decreased on the first , third and fifth postoperative days compared with the control group . There was no mortality . Three patients in the control group needed postoperative dialysis . CONCLUSION Patients with renal dysfunction undergoing on-pump CABG surgery seem to benefit from leukodepletion as a measure to prevent tubular damage and renal impairment compared with a control group STUDY OBJECTIVE To determine whether inclusion of a leukocyte specific filter into the extracorporeal circuit during aortocoronary bypass surgery alters postoperative cardiopulmonary function . DESIGN R and omized , double-blinded control trial . SETTING Tertiary care hospital . PATIENTS Convenience sampling of patients undergoing elective aortocoronary bypass between October 1992 and June 1993 . INTERVENTIONS A total of 32 patients were r and omized to a leukocyte specific filter ( n = 16 ) or to a st and ard blood filter ( n = 16 ) during the surgical procedure . MEASUREMENTS AND RESULTS White blood cell count in the st and ard filter group ( 12.2 + /- 3.6 10(9)/L ) was higher ( p = 0.047 ) than in the leukocyte filter group ( 9.9 + /- 2.6 10(9)/L ) at 4 h postoperatively but counts were similar ( p = 0.063 ) at 24 h ( 10.8 + /- 2.7 vs 8.9 + /- 2.6 10(9)/L , respectively ) . Leukocyte activation assessed by chemiluminescence was similar between groups at all measurement periods . We noted transient improvements ( p < 0.05 ) in intrapulmonary shunt ( 19 + /- 50 % vs 24 + /- 9 % ) and mean blood pressure ( 85 + /- 8 vs 76 + /- 9 mm Hg , respectively ) in the leukocyte filter group compared with the st and ard filter group , respectively . Otherwise there were no differences noted between groups . CONCLUSIONS Inclusion of a leukocyte filter during cardiopulmonary bypass caused transient cardiorespiratory improvement that was lost within 24 h and did not offer any significant clinical benefits BACKGROUND Valvular heart diseases are not usually regarded as a major public-health problem . Our aim was to assess their prevalence and effect on overall survival in the general population . METHODS We pooled population -based studies to obtain data for 11 911 r and omly selected adults from the general population who had been assessed prospect ively with echocardiography . We also analysed data from a community study of 16 501 adults who had been assessed by clinical ly indicated echocardiography . FINDINGS In the general population group , moderate or severe valve disease was identified in 615 adults . There was no difference in the frequency of such diseases between men and women ( p=0.90 ) . Prevalence increased with age , from 0.7 % ( 95 % CI 0.5 - 1.0 ) in 18 - 44 year olds to 13.3 % ( 11.7 - 15.0 ) in the 75 years and older group ( p<0.0001 ) . The national prevalence of valve disease , corrected for age and sex distribution from the US 2000 population , is 2.5 % ( 2.2 - 2.7 ) . In the community group , valve disease was diagnosed in 1505 ( 1.8 % adjusted ) adults and frequency increased considerably with age , from 0.3 % ( 0.2 - 0.3 ) of the 18 - 44 year olds to 11.7 % ( 11.0 - 12.5 ) of those aged 75 years and older , but was diagnosed less often in women than in men ( odds ratio 0.90 , 0.81 - 1.01 ; p=0.07 ) . The adjusted mortality risk ratio associated with valve disease was 1.36 ( 1.15 - 1.62 ; p=0.0005 ) in the population and 1.75 ( 1.61 - 1.90 ; p<0.0001 ) in the community . INTERPRETATION Moderate or severe valvular diseases are notably common in this population and increase with age . In the community , women are less often diagnosed than are men , which could indicate an important imbalance in view of the associated lower survival . Valve diseases thus represent an important public-health problem BACKGROUND Chronic obstructive pulmonary disease is a risk factor for postoperative lung injury . Contradictory results have been published about leukocyte filtration ( LF ) because of the heterogeneity of patients and interventions , type of LF , and comorbidities . METHODS Sixty patients with mild moderate chronic obstructive pulmonary disease ( forced expiratory volume in 1 second 40 % to 80 % ) undergoing aortic valve surgery were r and omly assigned to receive systemic arterial and cardioplegic LF during cardiopulmonary bypass ( group L , 30 patients ) or st and ard cardiopulmonary bypass ( group S ) . Perioperative interleukin-6 , interleukin-8 , and tumor necrosis factor-alpha were sample d at different time points . The PaO2/inspired oxygen fraction ( FiO2 ) and alveoloarterial oxygen gradient ( AaDO2 ) were measured preoperatively , at intensive care unit arrival , and at 24 , 48 , and 72 hours postoperatively ; lung compliance was measured after intubation , at intensive care unit arrival , and at 4 and 8 hours postoperatively ; and radiographic lung injury score was determined preoperatively and at 24 , 48 and 72 hours . Length of intubation , intensive care unit stay , hospital stay , need for noninvasive positive-pressure ventilation , acute lung injury , and pneumonia were recorded . Repeated- measures analysis of variance assessed group , time , and group by-time interactions . RESULTS Preoperative and intraoperative data were comparable . Proinflammatory cytokine leakage was reduced by LF . Group L showed shorter intubation time ( median 9.5 hours versus group S , 15.0 hours ; p=0.0001 ) , and intensive care unit length of stay ( median 19.0 hours versus group S , 24.5 ; p=0.0001 ) , lower need for noninvasive positive-pressure ventilation ( 5 of 30 , 16.7 % , versus 12 of 30 , 40 % ; p=0.042 ) . The AaDO2 , PaO2/FiO2 , lung compliance , and radiographic lung injury score worsened early postoperatively , followed by progressive improvements ( time p≤0.001 for all ) . Such decline of AaDO2 , PaO2/FiO2 , lung compliance , and radiographic lung injury score was significantly attenuated by LF ( group by-time p=0.0001 for AaDO2 , PaO2/FiO2 , and lung compliance ; p=0.004 for radiographic lung injury score ) . CONCLUSIONS Arterial plus cardioplegic LF significantly reduced proinflammatory cytokine release after cardiopulmonary bypass , thus ameliorating postoperative indexes of lung function and overall respiratory outcome BACKGROUND Leukocyte filtration of systemic blood during cardiopulmonary bypass surgery to reduce post-operative morbidity has not yet been established because of the enormous leukocyte release from the third space . This study was design ed to examine the efficiency and safety of leukocyte filtration by a new prototype large capacity leukocyte filter . PATIENTS AND METHODS Patients undergoing cardiopulmonary bypass surgery were prospect ively divided into two groups : a leukocyte removal group ( n = 11 ) receiving leukocyte filtration during cardiopulmonary bypass and a control group ( n = 20 ) with no filtration . The filtration efficiency was indicated by electronic leukocyte counts before and after filtration and the clinical efficiency to reduce post-operative morbidity was indicated by PaO2 . Safety was indicated by monitoring the filtration pressure and leukocyte release products across the filter , as well as by examining the post-filtration filter by light and electron microscopy . RESULTS On an average , 75 % of all entering leukocytes were removed by the filter . The post-operative PaO2 showed a tendency to improve after filtration . During filtration , the pressure across the filter material increased in five cases , accompanied by an increase in post-filter plasma hemoglobin and beta-glucoronidase . Within these filters accumulations of fibrin network with many trapped leukocytes were discovered microscopically . CONCLUSIONS The filter was efficient in filtering leukocytes , but the filtration efficiency slowed at the end of filtration . Furthermore , the patients ' post-operative parameters showed a tendency to improve after filtration . However , flow obstruction by means of clotting seems to be an important issue of safety involved in the filtration of large numbers of leukocytes for cardiopulmonary surgical patients BACKGROUND The aim of this prospect i ve study , based on the completion of the short form health survey question naire ( SF36 ) before and 1-year after open heart surgery , was threefold : to evaluate the changes in quality of life ( QOL ) after open heart surgery , to determine the factors influencing QOL , and to assess the relation between preoperative QOL and 1-year cardiac functional status . METHODS Logistic regression was used to determine factors that influence patients ' QOL scores and their 1-year cardiac functional status . Different groups were constituted in terms of 1-year cardiac functional status by means of an arborescent classification . RESULTS Comparison of preoperative and postoperative mean scores in the 293 patients included in the study revealed an improvement in all but three dimensions of the SF36 scale . Quality of life improved after operation in an average of 50 % of patients . The most frequently found independent predictors of impairment after surgery were NYHA functional class III or IV and angina class III or IV . At 1 year , 64 % of patients had satisfactory cardiac functional status . Independent predictive factors of 1-year cardiac functional status were : physical functioning , pain , general health problems , and coronary artery bypass graft . The arborescent classification indicated that the probability of having a " satisfactory " 1-year cardiac functional status was greater than 75 % for patients with at least one preoperative QOL dimension above 75 on the scale . CONCLUSIONS Preoperative QOL determined by the SF36 is predictive of 1-year cardiac functional status . Coronary artery bypass patients do not recover as well as patients having undergone heart valve surgery INTRODUCTION Quality of life ( QOL ) in heart failure patients is severely compromised by the symptoms of the disease . Acute administration of levosimendan improves patients ' symptoms for intervals of 7 - 10 days . The aim of this study was to assess the QOL in heart failure patients , after monthly , intermittent administration of levosimendan for a 6-month period , using 3 activity question naires : Specific Activity Question naire ( SAQ ) , Left Ventricular Dysfunction 36 ( LVD 36 ) , and Minnesota Living with Heart Failure Question naire ( LIhFE ) . METHODS We prospect ively studied 20 patients , age 61.0 + /- 15.7 years ( mean + /- SD ) with heart failure ( NYHA III and IV ) . Levosimendan was administered intravenously for 24 hours ( dose 0.1 mg/kg/min ) , 1 day every month for a 6-month period . Patients were asked to answer the questions of the 3 activity question naires SAQ , LVD36 and LIhFE before and after the end of the 6-month period . RESULTS For the LIhFE ( the best score is 0 and the worst 105 ) before levosimendan the score was 35.4 + /- 18.6 and after 6 months 22.2 + /- 13.0 ( p<0.0001 ) . SAQ ( worst score is 0 and the best is 9 ) before levosimendan was 4.2 + /- 1.6 and after 6 months 4.7 + /- 1.3 ( p<0.05 ) . For the LVD36 ( more ; right ' answers , more severe condition ) before levosimendan values were 52.6 + /- 26.2 and after 6 months 27.4 + /- 17.3 ( p<0.0001 ) . Before levosimendan patients had a mean left ventricular ejection fraction ( LVEF ) 30.3 + /- 6.9 , while after 6 months the LVEF was 32.1 + /- 7.4 ( p=0.01 ) . CONCLUSIONS Levosimendan treatment improved both objective echocardiographic measurements and the subjective QOL question naires . LIhFE and LVD36 show a significant improvement in QOL in heart failure patients after a 6-month period of monthly intermittent administration of levosimendan . The SAQ showed a very small improvement , because it describes more strenuous activity , a situation unusual for these patients , who are severely symptom limited BACKGROUND Cardiopulmonary bypass ( CPB ) is an important contributor to renal failure , which is a well-recognized complication after coronary artery bypass grafting ( CABG ) . Leukodepletion reduces CPB-associated inflammation and result ant end-organ injuries . However , its effectiveness in renal protection has not been evaluated in a prospect i ve r and omized clinical setting . METHODS Forty low-risk patients awaiting elective CABG with normal preoperative cardiac and renal function were prospect ively r and omized into those undergoing nonpulsatile CPB without ( group A : n = 20 ) and with leukodepletion ( group B : n = 20 ) . Renal glomerular and tubular injury were assessed by urinary excretion of microalbumin and retinol binding protein ( RBP ) indexed to creatinine ( Cr ) , respectively . Daily measurements were taken from admission to postoperative day 5 . Fluid balance , serum creatinine , and blood urea were also monitored . RESULTS No mortality or renal complication occurred . Both groups had similar demographic makeups , Parsonnet scores , extents of coronary revascularization and , duration s of CPB and aortic cross-clamping . Daily fluid balance , serum creatinine , and blood urea remained comparable in both groups throughout the study period . From equal preoperative values , a significantly higher release of urinary RBP : Cr ( 7,807 + /- 2,227 vs 3,942 + /- 2,528 ; p < 0.001 ) and urinary microalbumin : Cr ( 59.4 + /- 38.0 vs 4.7 + /- 6.7 ; p < 0.0001 ) occurred in group A , peaking on day 1 before returning to approximate baseline levels . CONCLUSIONS Although clinical ly overt renal complications were absent , sensitive indicators revealed significantly more injury to both renal tubules and glomeruli after nonpulsatile CPB without leukodepletion . These data suggest that leukocytes play an important role in post-CPB renal dysfunction , and leukodepletion may offer some renal protection in low-risk patients during CABG Abstract . Objective and design : The beneficial effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass ( CPB ) is probably due to the limitation of pathogenesis mediated by over-stimulated neutrophils . However , the influence of leukocyte filtration on the functional neutrophil activity has not been studied in detail . Therefore , by using different filtration timing strategies we determined neutrophil effector functions before and after the filter passage as well as blood surrogate markers for neutrophil activation.¶ Methods : We r and omly assigned 80 cardiac surgery patients to four groups ( n = 20 each ) without ( I ) and with three different filtration timing strategies ( II – IV ) . As functional end points neutrophil phagocytic activity and oxidative burst upon ex vivo stimulation with E.coli were analyzed from blood of 31 patients whereas polymorphonuclear elastase ( PMNE ) , myeloperoxidase , and malondialdehyde ( MDA ) , a marker for lipid peroxidation was determined in plasma sample s from 80 patients . Blood was harvested immediately before and behind the filter ( Pall LG6 ) at different times during CPB.¶ Results : We found that none of the filtration strategies either reduced the number of neutrophils capable of eliciting phagocytic activity and oxidative burst or the activity per cell . In contrast , PMNE and MPO levels in peripheral venous blood were found to be significantly increased in groups II – IV compared with group I throughout the entire filtration period in all patients . MDA was not enhanced in the filter groups.¶ Conclusions : Our results show that the leukocyte depletion filter in the arterial line of the heart-lung machine failed to limit neutrophil stimulation but rather augmented PMNE plasma levels . We speculate that augmented PMNE and MPO levels mainly stem from neutrophils that are captured within the mesh of the leukocyte filter OBJECTIVE To observe the effect of cytokines absorption on renal and respiratory function in patients with open-heart surgery . METHODS 30 patients undergoing valve replacement with cardiopulmonary bypass ( CPB ) were r and omly divided into two groups . A sulfonated polyacrylonitrile hemofilter ( AN69 ) that has been used to absorb cytokines was connected into the efferent limb of CPB in Group A ( n = 15 ) , and a cellulose triacetate hemofilter ( CT 190 G ) instead of AN69 was used as controls ( Group B , n = 15 ) . The levels of plasma pro-inflammatory ( TNF-alpha , IL-6 , IL-8 ) anti-inflammatory cytokines ( IL-10 , IL-1ra ) , C-reactive protein ( CRP ) levels , and post-operation renal and respiratory function were compared between the two groups . Blood sample s were analysed for TNF-alpha and IL-6 and IL-8 and C-reactive protein ( CRP ) . The changes in renal , respiratory function were also observed . RESULTS ( 1 ) At the end of CPB , TNF-alpha 10 ng/L + /- 3 ng/L and IL-6 115 ng/L + /- 22 ng/L levels in Group A were significantly lower than that in Group B 13 ng/L + /- 3 ng/L , 134 ng/L + /- 29 ng/L ) respectively ( P < 0.05 in all ) . There is no statistical differences in plasma IL-10 and IL-1ra levels between the two groups . ( 2 ) After 24 hours of CPB , the magnitude of increased body temperature , heart rate , white blood cell and plasma CRP in Group A [ 1.6 degrees C + /- 0.2 degrees C , 15/min + /- 4/min , ( 17 + /- 3 ) x 10(9)/L , 56 mg/L + /- 13 mg/L ] , were significantly lower than that in Group B [ 2.1 degrees C + /- 0.2 degrees C , 23/min + /- 6/min , ( 22 + /- 3 ) x 10(9)/L , 69 mg/L + /- 15 mg/L ] respectively ( P < 0.05 in all ) . ( 3 ) After 24 hours of CPB , the levels of 24h urinary protein excretion and urinary N-acetyl-beta-D-glucosaminidase ( NAG ) were significantly lower in Group A when compared to that in Controls ( 0.20 g/d + /- 0.08 g/d vs 0.30 g/d + /- 0.14 g/d , 28 U/L + /- 11 U/L vs 38 U/L + /- 13 U/L respectively ) , P < 0.05 in all . The level of creatinine clearance ( Ccr ) in Group A ( 68 + /- 7 ) ml.min(-1).1.73 m(-2 ) was significantly elevated than that in Group B ( 57 + /- 11 ) ml.min(-1).1.73 m(-2 ) ( P < 0.05 ) . ( 4 ) One hour after the end of CPB , the magnitude of increased plateau airway pressure ( P(Plateau ) ) and peak airway pressure ( P(Peak ) ) in Group A were significantly lower than that in Controls ( P < 0.01 in all ) . The duration that need mechanical ventilation after operation in Group A ( 4.9 h + /- 0.6 h ) was much shorter than that in Group B ( 5.8 h + /- 0.8 h , P < 0.05 ) . CONCLUSIONS Lowering the plasma levels of cytokines by extracorporeal absorption may attenuate systemic inflammatory response and protect lung and kidney function in patients with open-heart surgery We tested the hypothesis that controlled reperfusion with leukocyte-depleted blood could improve myocardial protection by reducing the oxidative stress in patients undergoing myocardial revascularization . Thirty-four patients receiving ante grade /retro grade blood cardioplegia were divided into : group A : 11 patients with ejection fractions ( EF ) less than 35 % , treated with leukocyte-depleted controlled blood reperfusion , group B : 11 patients with EF less than 35 % in whom no leukocyte depletion was performed , group C : 6 patients with EF more than 45 % treated as group A and group D : 6 patients with EF more than 45 % without leukocyte depletion . To asses the oxidative stress , we evaluated total , total oxidized ( GSSX ) , and reduced glutathione ( GSH ) in coronary sinus plasma , immediately before cross-clamping the aorta ( T0 ) , and at 0 ( T1 ) , 15 ( T2 ) and 30 ( T3 ) min after unclamping it . In groups A and B a significant shift towards oxidation of redox status of glutathione ( GSH/GSSX ) at T1 vs T0 was observed . Glutathione redox ratio remained low in group B while in group A it returned to the basal value at T2 with a significant difference from group B at T2 and T3 . No differences were observed between groups C and D. In conclusion , our data show that leukocyte-depleted reperfusion can afford a better myocardial protection in patients with left ventricular dysfunction , while it seems unnecessary in patients with normal EF Cardiopulmonary bypass ( CPB ) induces a whole body inflammatory response leading to postoperative lung dysfunction . Activated leukocytes may play a role in the pathogenesis of pulmonary dysfunction . We evaluated postoperative lung function after the use of leukocyte-depleting filters incorporated in the extracorporeal circuit during CPB . From November 1997 to March 2000 , 40 patients underwent isolated coronary artery bypass grafting . Patients were r and omly allocated to the leukocyte-depletion group ( group F , 20 patients ) or to the control group ( group C , 20 patients ) . There was no significant difference between the two groups with respect to age , sex , weight , height , body surface area , haemoglobin and haematocrit levels , preoperative left ventricular ejection fraction , cooling temperature , aortic crossclamping and CBP duration . Blood sample s were drawn preoperatively , at aortic declamping , 60 min after CPB , after arriving at the intensive care unit ( ICU ) and 24 h after the operation . We analysed blood cell count , elastase , interleukin-8 ( IL-8 ) and tumour necrosis factor ( TNF-α ) levels and continuous monitoring of arterial blood gases in the intensive care unit ( ICU ) . The analysis of total circulating white blood cells ( WBCs ) showed a significant reduction of WBCs in both groups soon after aortic declamping [ from the right atrium : 6.4 109/l ± 1.4 × 109/l in group F vs 10.3 ± 1.8 × 109/l in group C ( p<0.05 ) ; from the left atrium : 5.8 ± 1.3 × 109/l in group F vs 8.4 ± 1.9 × 109/l in group C ( p<0.05 ) ] and after 60 min of CPB [ 7.1 ± 2.2 × 109/l in group F vs 10.4 ± 1.8 × 109/l in group C ( p<0.05 ) ] . The analysis of circulating neutrophils showed similar findings in both groups . Elastase levels increased during CPB in both groups with a peak at the end of CPB without significant difference between the two groups ( group C : 260 ± 148 μg/l vs group F : 371 ± 68 μg/l ) . The decrease of plasmatic elestase levels was observed , for both groups , in the 24 h after CPB . There was no difference in intubation time between the two groups ( 16.4 h for group C vs 11.2 h for group F ) . Pulmonary function tested by pulmonary respiratory index [ RI = partial pressure of oxygen/fraction of inspired oxygen ( PaO2/FiO2 x 100 ) ] did not show significant difference between the two groups , either arriving in the ICU ( group C RI 265 vs group F RI 322 ) , or after 3 h ( group RI 304 vs group F RI 305 ) or after 6 h ( group C RI 292 vs group F RI 319 ) . Leukocyte-depleting filters reduce with blood cells count during CPB , but , in this study , WBC depletion did not significantly improve clinical conditions or laboratory finding BACKGROUND On the basis of scanty information , the effects of a leukocyte filter during cardiac operations in human beings have been examined from the viewpoint of the expression of neutrophil adhesion molecules . This study was therefore design ed to determine whether leukocyte depletion during cardiopulmonary bypass may interfere with neutrophil adhesion properties . METHODS Twenty-four patients undergoing elective heart operations were r and omly allocated to a leukocyte-depletion group or a control group . Blood sample s were collected at 7 points : before sternotomy , at 10 , 30 , and 60 minutes of cardiopulmonary bypass , at termination of cardiopulmonary bypass , 5 minutes after protamine administration , and 2 hours after cardiopulmonary bypass . The expression of the neutrophil surface adhesion molecules L-selectin and beta2-integrins was determined by flow cytometric analysis in whole blood . RESULTS ( 1 ) CD11a expression did not change significantly in either group . There were no significant differences between control and leukocyte-depletion groups ( P = .63 ) . ( 2 ) There was a significantly higher expression of CD11b on the neutrophils during cardiopulmonary bypass in the control group than in the leukocyte-depletion group ( P = .01 ) . ( 3 ) CD11c expression was initially up-regulated from the onset of cardiopulmonary bypass , reaching a peak at 60 minutes after bypass in the control group ( P = .02 ) . The expression of CD11c did not differ significantly between groups ( P = .23 ) . ( 4 ) L-selectin expression was significantly lower in the leukocyte-depletion group than in the control group ( P = .03 ) . CONCLUSIONS The major findings of the present study in human subjects undergoing elective cardiac operations with cardiopulmonary bypass are as follows : ( 1 ) bypass was associated with an up-regulation of the adhesion molecules L-selectin , CD11b , and CD11c but with no significant change in CD11a expression , and ( 2 ) the clinical use of a leukocyte-depleting filter could down-regulate the expression of CD11b and L-selectin BACKGROUND Acute kidney injury ( AKI ) after cardiac surgery is associated with worse outcomes . However , it is not known how adverse long-term consequences vary according to the duration of AKI . We sought to determine the association between duration of AKI and survival . METHODS Medical records of 4,987 cardiac surgery patients from 2002 through 2007 with serum creatinine ( SCr ) collection at a medical center in northern New Engl and were review ed . Acute kidney injury was defined as at least a 0.3 ( mg/dL ) or at least a 50 % increase in SCr from baseline and further classified into AKI Network stages . Duration of AKI was defined by the number of days AKI was present and categorized as no AKI and AKI for 1 to 2 , 3 to 6 , and at least 7 days . RESULTS Thirty-nine percent of patients exhibited AKI . Long-term survival was significantly different by AKI duration ( p < 0.001 ) . The proportion of patients with AKI duration , adjusted hazard ratio , and 95 % confidence interval for mortality ( no AKI as referent ) were as follows : 1 to 2 days ( 18 % ; adjusted hazard ratio , 1.66 ; 95 % confidence interval , 1.32 to 2.09 ) , 3 to 6 days ( 11 % ; adjusted hazard ratio , 1.94 ; 95 % confidence interval , 1.51 to 2.49 ) , ≥7 days ( 9 % ; adjusted hazard ratio , 3.40 ; 95 % confidence interval , 2.73 to 4.25 ) . This grade d relationship of duration of AKI with long-term mortality persisted when patients who died during hospitalization were excluded from analysis ( p < 0.001 ) . Propensity-matched analysis confirmed results . CONCLUSIONS The duration of AKI after cardiac surgery is directly proportional to long-term mortality . This AKI dose-dependent effect on long-term mortality helps to close the gap between association and causation , whereby AKI stages and AKI duration have important implication s for patient care and can aid clinicians in evaluating the risk of in-hospital and postdischarge death Leukocyte depletion during cardiopulmonary bypass has been demonstrated in animal experiments to improve pulmonary function . Conflicting results have been reported , however , with clinical depletion by arterial line filter of leukocytes at the beginning of cardiopulmonary bypass . In this study , we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass would improve lung function and reduce the postoperative inflammatory response . Thirty patients undergoing elective heart operations were r and omly allocated to a leukocyte-depletion group or a control group . In the leukocyte-depletion group ( n = 20 ) , all residual blood ( 1.2 to 2.1 L ) was filtered by leukocyte-removal filters and reinfused after cardiopulmonary bypass , whereas in the control group an identical amount of residual blood after cardiopulmonary bypass was reinfused without filtration ( n = 10 ) . Leukocyte depletion removed more than 97 % of leukocytes from the retransfused blood ( p < 0.01 ) and significantly reduced circulating leukocytes ( p < 0.05 ) and granulocytes ( p < 0.05 ) compared with the control group . Levels of the inflammatory mediator thromboxane B2 determined at the end of operation ( p < 0.05 ) were significantly lower in the depletion group than in the control group , whereas no statistical differences in interleukin-6 levels were found between the two groups . After operation , pulmonary gas exchange function ( arterial oxygen tension at a fraction of inspired oxygen of 0.4 ) was significantly higher in the leukocyte-depletion group 1 hour after arrival to the intensive care unit ( p < 0.05 ) and after extubation ( p < 0.05 ) . There were no statistical differences between the two groups with respect to postoperative circulating platelet levels and blood loss , and no infections were observed during the whole period of hospitalization . These results suggest that leukocyte depletion of the residual heart-lung machine blood improves postoperative lung gas exchange function and is safe for patients who are expected to have a severe inflammatory response after heart operations Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of heart and lung injury after reperfusion and during cardiopulmonary bypass . This study was design ed to determine whether leukocyte depletion prevents injury to the heart and lung during cardiopulmonary bypass . Twenty-eight open heart surgeries were performed in this study . In Group F , leukocyte depletion was performed with an LG-6 arterial line filter after aortic declamp ( n = 14 ) . Leukocyte depletion was not performed during cardiopulmonary bypass in Group C ( n = 14 ) . Thereafter , cardiac and lung function were assessed in the 24 hr after reperfusion . The total catecholamine dose used for 24 hr after reperfusion ( r ) was 61.9 + /- 13.4 in Group C and 43.9 + /- 19.2 in Group F ( p < 0.05 ) . CK-MB at 3 and 6 hr after reperfusion was 65.9 + /- 13.5 and 64.8 + /- 15.8 in Group C and 45 + /- 11.8 and 38 + /- 10.8 in Group F , respectively ( p < 0.05 ) . The pulmonary index after reperfusion at 3 and 6 hr was 1.7 + /- 0.5 and 1.3 + /- 0.4 in Group C and 0.7 + /- 0.3 and 0.6 + /- 0.4 in Group F , respectively ( p < 0.05 ) . There was significantly better preserved lung function in Group F. In conclusion , leukocyte depletion was significantly effective in preserving heart and lung function during cardiopulmonary bypass BACKGROUND Leukocyte depletion recently has been introduced for cardiac surgical patients to attenuate leukocyte-mediated inflammation and organ reperfusion injury . We evaluated the feasibility of a new leukocyte depletion method in which systemic leukocyte depletion is achieved through the venous side of the cardiopulmonary bypass circuit under low blood flow . METHODS Forty cardiac surgical patients undergoing cardiopulmonary bypass were allocated r and omly to a leukocyte depletion group ( n = 20 ) and a control group ( n = 20 ) . In the depletion group , leukocyte filtration was achieved with two filter sets located between the venous drainage and the venous reservoir . Leukocyte filtration was commenced after the start of rewarming but before the release of the aortic cross-clamp , and it was driven by a spare roller pump of the heart-lung machine . RESULTS All the episodes of filtration went smoothly within a period of 10 minutes and with a blood flow rate of 400 mL/min . The mean leukocyte removal rate calculated at the end of filtration was 69 % . Circulating leukocytes were reduced by 38 % in the depletion group compared with the control group at the moment of cross-clamp release ( 4.3x10(9)/L versus 6.8x10(9)/L , p<0.05 ) . The postoperative inflammatory response also was reduced as indicated by less production of interleukin-8 ( p<0.05 ) . Clinical ly , there was no significant difference between the two groups in postoperative PaO2 or pulmonary hemodynamics . CONCLUSIONS It is technically feasible to deplete circulating leukocytes through the venous side of the cardiopulmonary bypass circuit with a low blood flow rate . Future studies should focus on the duration and timing of leukocyte depletion to optimize the methodology of leukocyte depletion for cardiac surgical patients BACKGROUND To evaluate the effects of leukocyte-depleting filtration on myocardial and pulmonary protection and the inflammatory response in patients undergoing valve surgery . METHODS Fifty-two patients who underwent mitral valve or mitral and aortic valve replacement were r and omized into two groups with or without a leukocyte-depleting filter during surgery . The filter was used from 10 minutes before the release of the aortic cross-clamp to the end of cardiopulmonary bypass . RESULTS Total leukocyte and neutrophil counts showed a short-term reduction in patients undergoing leukocyte filtration , but there was no significant difference between the two groups during the study . Serum levels of cardiac troponin I were lower than that of the control group ( p=0.030 ) . Leukocyte depletion result ed in a significantly higher oxygenation index ( p=0.002 ) and a lower respiratory index ( p=0.003 ) compared with the control group . Serum levels of interleukin-8 were significantly elevated in patients undergoing leukocyte filtration compared with patients without leukocyte filtration ( p=0.001 ) . There were no statistically significant differences between the two groups with regards to the concentration of interleukin-6 and TNFα , or the duration of intensive care and hospital stay . CONCLUSIONS Leukocyte depletion is associated with improved myocardial and lung protection but does not appear to attenuate the inflammatory response in valve surgery BACKGROUND Although leukocyte depletion from systemic circulation during cardiopulmonary bypass ( CPB ) has been studied , the effect of leukocyte depletion on the leukocyte-endothelial cascade remains poorly understood . So far , there has been no published work on the effects of leukocyte filters during cardiac operations from the viewpoint of endothelial activation and transendothelial neutrophil migration . METHODS Thirty-two patients undergoing elective heart operations were r and omly allocated to a leukocyte-depletion ( LD ) group or a control group . Blood sample s were collected at seven time points : before sternotomy , at 30 minutes and at 60 minutes of CPB , at 5 minutes after coronary reperfusion , at the end of CPB , and at 2 hours and 24 hours after the cessation of CPB . The plasma concentrations of P-selectin , intercellular adhesion molecule-1 ( ICAM-1 ) , interleukin-8 , and platelet-endothelial cell adhesion molecule-1 ( PECAM-1 ) were measured using enzyme-linked immunosorbent assays . Plasma malondialdehyde ( MDA ) concentration was determined by measurement of thiobarbituric acid-reactive substances in plasma . In addition , blood sample s collected at intervals before and after operation were used for arterial blood gases . RESULTS Our studies show significant increases of plasma levels of P-selectin , ICAM-1 , interleukin-8 , PECAM-1 , and MDA during and after CPB in the control group . Interestingly , a significant decrease of plasma levels of P-selectin , ICAM-1 , interleukin-8 , PECAM-1 , and MDA , and better preservation of lung function could be found in the LD group compared with the control group . CONCLUSIONS Our results demonstrate a rationale for using a leukocyte filter in patients undergoing cardiac surgery to attenuate the endothelial-mediated component of the CPB-induced inflammatory response by reducing endothelial activation and neutrophil transmigration BACKGROUND Activated leukocytes may increase morbidity in cardiac surgery . The objective of this study is to investigate the influence on morbidity of leukocyte-depleting blood filters placed into the arterial line of cardiopulmonary bypass circuits . METHODS Simple , blind , prospect i ve , r and omized and controlled clinical trial carried out in a cardiac surgery ICU at a university center . We included 159 consecutive low-risk patients ( ie , Parsonnet score < 10 ) undergoing cardiac surgery who were initially stratified in three risk levels according to the Parsonnet score at admission into the hospital ( ie , low , < 4 ; middle , 4 to 7 ; and high , 8 to 10 ) . Once stratified , all patients were r and omized to undergo cardiopulmonary bypass either with a conventional blood filter or with a leukocyte filter ( r and omization ratio , 2:1 ) . The outcome variable was morbidity . Patients were considered to have a high morbidity if any of the following clinical situations were present ( ie , pulmonary dysfunction , cardiac dysfunction , perioperative infections , postoperative hyperthermia , and hyperdynamic states ) . RESULTS The leukocyte filter was used in 52 patients and the conventional filter in 107 patients . The morbidity rate was similar in both groups , but patients with leukocyte filter had a lower incidence of perioperative infections , fever , and hyperdynamic states as compared with patients with the conventional filter . CONCLUSIONS Leukocyte filtration in patients undergoing cardiac surgery with extracorporeal perfusion showed no measurable effects on postoperative morbidity . However , although not statistically significant , a decrease was observed in the rates of perioperative infection , fever , and hyperdynamic states BACKGROUND Despite recent rediscovery of beating heart cardiac surgical techniques , extracorporeal circulation remains appropriate for most heart operations . To minimize deleterious effects of cardiopulmonary bypass , antiinflammatory strategies have evolved . METHODS Four state-of-the-art strategies were studied in a prospect i ve , r and omized , preoperatively risk stratified , 400-patient study comprising primary ( n = 358 ) , reoperative ( n = 42 ) , coronary ( n = 307 ) , valve ( n = 27 ) , ascending aortic ( n = 9 ) , and combined operations ( n = 23 ) . Groups were as follows : st and ard , roller pump , membrane oxygenator , methylprednisolone ( n = 112 ) ; aprotinin , st and ard plus aprotinin ( n = 109 ) ; leukocyte depletion , st and ard plus a leukocyte filtration strategy ( n = 112 ) ; and heparin-bonded circuitry , centrifugal pumping with surface modification ( n = 67 ) . RESULTS Analysis of variance , linear and logistic regression , and Pearson correlation were applied . Actual mortality ( 2.3 % ) was less than half the risk stratification predicted mortality ( 5.7 % ) . The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation . Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation ( p = 0.00001 ) , leukocyte filtration blunted postpump leukocytosis ( p = 0.043 ) , and the aprotinin group had less fibrinolysis ( p = 0.011 ) . Primary end points , length of stay , and hospital charges , were positively correlated with operation type , age , pump time , body surface area , stroke , pulmonary sequelae , predicted risk for stroke , predicted risk for mortality , and risk strata/treatment group interaction ( p = 0.0001 ) . In low-risk patients , leukocyte filtration reduced length of stay by 1 day ( p = 0.02 ) and mean charges by $ 2,000 to $ 6,000 ( p = 0.05 ) . For high-risk patients , aprotinin reduced mean length of stay up to 10 fewer days ( p = 0.02 ) and mean charges by $ 6,000 to $ 48,000 ( p = 0.0007 ) . CONCLUSIONS These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation . This translated variably into improved patient outcomes . The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk OBJECTIVES Open heart surgery is associated with a massive systemic inflammatory response . Neutrophils , are the main mediator of this response . We hypothesised that the degree of neutrophil activation and inflammatory response to open heart surgery varies individually and correlates with clinical outcome . The aim of this study was to determine if individual clinical outcome can be predicted preoperatively through assessment of in-vitro stimulated neutrophil responses . Following that , the effects of neutrophil depletion through leukocyte filters are examined . METHODS Neutrophil responses were assessed preoperatively ( n=40 ) through change in neutrophil adhesion molecule [ CD11b , CD62L and P Selectin Glycoprotein-1 ( PSGL-1 ) ] expression before and after in-vitro stimulation with Phorbol 12-myristate 13-acetate , PMA ( 1 ng/ml ) , lipopolysaccharide , LPS ( 1 μg/ml ) and N-Formyl-Met-Leu-Phe , fMLP ( 1 ng/ml ) . Stimulated neutrophil responses were then correlated with postoperative clinical outcome . Patients were then r and omised to leukocyte filtration ( n=20 ) and a control group ( n=20 ) and the effect of leukocyte filtration on neutrophil response and clinical outcome were investigated . RESULTS An individual variation in in-vitro stimulated neutrophil responses was demonstrated . Significant correlations were shown between neutrophil responses and maximum serum creatinine change , CKMB-fraction , adrenaline requirement , noradrenaline requirement , duration of adrenaline required and time to extubation . White cell count and percentage neutrophils were lower in the LD group ( P=0.05 ) . CD11b expression ( P=0.005 ) and PSGL-1 expression ( P=0.043 ) across leukocyte filters were also increased . However , no significant difference was detected in clinical outcome between the LD and control groups . CONCLUSION Preoperative neutrophil responses to in-vitro stimuli can predict clinical outcome following open heart surgery . However , leukocyte filtration did not offer significant benefit in clinical outcome in our study OBJECTIVE The purpose of this study was to examine the influence of patients ' presurgery illness beliefs and cardiac risk factors on health-related outcomes 3 months following cardiac surgery . METHODS In a prospect i ve design , 56 patients undergoing elective cardiac surgery ( coronary artery bypass grafting ( CABG ) , heart valve surgery , or a combined procedure ) were approached on admission to hospital and reassessed 3 months after surgery . Presurgery assessment included cardiac risk factors and measures of illness severity . Illness beliefs were assessed using the Illness Perception Question naire-Revised ( IPQ-R ) . Outcome measures included levels of illness-related disability , physical functioning , psychological well-being , and depressive symptoms . RESULTS Physical functioning of patients improved 3 months after surgery , while disability and psychological well-being did not change significantly . Cardiac risk factors prior to surgery were unrelated to the outcomes 3 months later . With the use of hierarchical multiple regression analyses , after controlling for demographic variables and baseline scores of outcome variables , patients ' beliefs about their illness predicted disability ( adjusted R(2)=.350 , P<.01 ) , physical functioning ( adjusted R(2)=.283 , P<.01 ) , and depressive symptoms ( adjusted R(2)=.302 , P<.01 ) . Illness severity measures did not mediate the association between illness beliefs and outcomes . CONCLUSION Patients ' beliefs about their illness before surgery strongly influence recovery from cardiac surgery . The results suggest that patients could benefit from presurgery cognitive interventions aim ed at changing maladaptive illness beliefs to improve physical functioning and disability following cardiac surgery Most cardiac operations involve the use of extracorporeal circulation with its attendant systemic inflammatory response syndrome . Many anti-inflammatory strategies hold promise for reducing the associated morbidity of cardiopulmonary bypass . The application of pharmacological and mechanical strategies to control this inflammatory response now has demonstrable clinical benefit . The additional costs of these successful strategies are offset by the economic savings and improved quality of care OBJECTIVES --Measurement of changes in patients ' perceptions of how differing states of health affect their lives and determination of the ability of preoperative variables to predict outcome after coronary artery bypass grafting . DESIGN -- Prospect i ve study with completion of question naires before coronary artery bypass grafting and at three months , one year , and five years afterwards . SETTING --Regional cardiothoracic centre . PATIENTS --100 Male patients all aged below 60 at the time of operation , who were patients of two cardiothoracic surgeons . MAIN OUTCOME MEASURES -- Patients ' assessment of their health state in terms of functional capacity and aspects of distress , according to the Nottingham health profile and outcome of operation in terms of changes in symptoms , working life , and daily activities determined by self completed study question naires before operation and at three and six months afterwards . RESULTS --Intermediate one year results are reported . The differences between the Nottingham health profile scores before operation and at three months afterwards were significantly different ( p less than 0.01 ) , indicating an appreciable improvement in general health state , and at one year compared favourably with those from a normal male population . Analysis of responses to the study question naire showed that 65 of 89 patients ( 73 % ) were working at one year after operation with a further seven ( 8 % ) maintaining that they were fit to work but unable to find employment . The proportion of patients complaining of chest pain fell from 90 % ( 88/98 ) before grafting to 19 % ( 17/89 ) at one year after coronary artery bypass grafting , when 91 % ( 81/89 ) patients maintained that their condition was either completely better or definitely improved . The significant positive factors affecting return to work and home activities were working before operation , short wait for operation , absence of breathlessness , and low physical mobility score in the Nottingham health profile ( all p less than 0.001 ) . CONCLUSIONS --Improvements were evident in general health state , symptoms , and activity at three months and one year after coronary artery bypass graft surgery . Interventions likely to influence outcomes included reduction in waiting times for operation ; rehabilitation initiatives ; and more attention to the quality of information given to patients , their relatives , and the community Purpose To determine whether inclusion of a neutrophil-specific filter into the extracorporeal circuit during open heart valve surgery alters postoperative outcomes . Methods Convenience sampling of 24 patients undergoing elective open heart valve surgery between July 1993 and June 1994 . Patients were r and omized to a neutrophil-specific filter ( n= 11 ) or to a st and ard blood filter ( n= 13 ) during cardiopulmonary bypass . Results Neutrophil-specific filter diminished ( P < 0.02 ) the expression of CD 18 , a neutrophil surface adhesion molecule , at 1 ( 84.5 ± 4.2 vs 94.8 ± 3.8 % ) . 4 ( 80.0 ± 4.2 vs 95.1 ± 3.9 % ) and 24 hr ( 75.2 ± 4.2 vs 98.2 ±3.9 % ) post-operatively compared with st and ard filter . Total white blood cell count , neutrophil count , and proinflammatory cytokmes ( IL-6 , IL-8 ) were similar between groups at all times . Measured outcomes including : PaO2 , cardiac index , ejection fraction , haemodynamic variables , use of motropes , spirometry ( FEV FVC ) . and hospitalization duration were similar between groups . Conclusions Inclusion of the neutrophil filter during open heart valve surgery selectively depletes activated neutrophils . There were no other detectable differences between the two groups and the use of a neutrophilspecific filter in routine clinical practice for patients undergoing open heart valve surgery is not supported . RésuméObjectifDéterminer si l’ajout au circuit extracorporel d’un filtre spécifique aux neutrophiles pendant une chirurgie valvulaire modifiait les résultats de l’interventionMéthodesUn échantillonnage de 24 patients subissant une intervention valvulaire à coeur ouvert entre juillet 1993 et juin 1994 . Les patients ont été répartis aléatoirement à un circuit extracorporel incluant un filtre spécifique aux neutrophiles ( n= 11 ) ou un filtre st and ard ( n= 13).RésultatsLe filtre spécifique aux neutrophiles a diminué l’expression de CD 18 . une molécule adhésive de sur face , une heure ( 84.5 ± 4.2 vs 98.8 ± 3.8 % ) , quatre heures ( 80 ± 4,2 vs 95.1 ± 3,9 % ) et 24 heures ( 75.2 ± 4,2 vs 98.2 ± 3.9 % ) après l’opération comparativement au filtre st and ard . Le décompte total des globules blancs , des neutrophiles et des cytokines pro-inflammatoires ( IL-6 . IL8 ) étaient à tous les moments identiques entre les groupes . Les mesures de résultats incluant la PaO2 , l’index cardiaque , la fraction d’éjection , les données hémodynamiques , l’utilisation d’inotropes , la spirométne ( VEMS , CVF ) et la durée du séjour hospitalier étaient identiques entre les groupes . Conclusion L’ajout d’un filtre spécifique aux neutrophiles pendant la chirurgie à coeur ouvert épuise sélectivement les neutrophiles activés . Aucune autre différence n’est discernable entre les groupes . L’utilisation courante de filtres spécifiques aux neutrophiles en clinique chez des patients soumis à une chirurgie valvulaire à coeur ouvert n’est pas justifiée AIM We examined the impact of leukocyte filtration during the entire bypass time on postoperative leukocytosis , perioperative hemorrhage and overall clinical outcome in patients undergoing elective cardiac surgery . METHODS Eighty patients who electively underwent cardiac surgery were r and omly allocated to a leukocyte depletion group ( n=40 ) or a control group ( n=40 ) . In patients of the leukocyte depletion group an arterial line filter with leukocyte depleting capacity ( Pall LG6 ) was applied instead of a st and ard arterial line filter . White blood cells and platelet count were estimated preoperatively and at various times postoperatively . Postoperative clinical outcomes were also recorded . RESULTS Repeated measure analysis of variance between groups showed that leukocyte counts were significantly lower in the depletion group postoperatively ( p=0.005 ) whereas no difference was found in the platelet counts ( p=0.37 ) . The catecholamine dose required at the time of weaning from cardiopulmonary bypass and during the first 12 postoperative hours was found to be lower in the leukodepletion group ( p=0.027 and p=0.021 , respectively ) . Furthermore leukodepleted patients showed a transient improvement in the oxygenation index ( p=0.029 ) and a shorter period of mechanical ventilation ( p<0.001 ) . The incidences of postoperative complications were similar between the groups . No difference was observed in regard to postoperative blood loss ( p=0.821 ) and amount of packed red blood cells required for transfusion during the first 24 hours ( p=0.846 ) . The duration of intensive care unit stay and of hospitalization were similar between the groups . CONCLUSION Leukocyte depletion contributes to early postoperative improvement in heart and lung function but does not influence significantly the overall clinical outcome of patients undergoing elective cardiac surgery Leukocyte depletion at reperfusion may have a role in myocardial protection when combined with terminal cardioplegia . We applied this method in a selected group of 68 patients with coronary artery bypass grafting either for elective surgical procedures ( n = 38 ) or emergency surgical procedures with the use of a preoperative intraaortic balloon pump ( n = 30 ) because of developing acute myocardial infa rct ion . Basic cold potassium crystalloid cardioplegic solution was used . During delivery of leukocyte-depleted terminal cardioplegic solution , warm arterial blood delivered from cardiopulmonary bypass was passed through a leukocyte removal filter , mixed with potassium crystalloid cardioplegic solution , and administered to the aortic root for the first 10 minutes of reperfusion . Patients were r and omized into three groups for reperfusion : whole blood , terminal cardioplegic solution , and leukocyte-depleted terminal cardioplegic solution reperfusion groups . In elective coronary artery bypass grafting , no significant difference was found in the clinical data . However , in emergency coronary artery bypass grafting , the leukocyte-depleted terminal cardioplegic solution group ( n = 10 ) showed significantly lower peak creatine kinase MB levels ( leukocyte-depleted terminal cardioplegic solution versus terminal cardioplegic solution versus whole blood : 27 + /- 11 , 56 + /- 13 , 74 + /- 18 , respectively ; p < 0.05 ) and maximum dopamine doses required at the weaning of cardiopulmonary bypass ( 6.3 + /- 1.1 versus 11.2 + /- 3.3 versus 9.2 + /- 2.2 ; p < 0.05 ) than did the terminal cardioplegic solution ( n = 10 ) and whole blood groups ( n = 10 ) . Moreover , the leukocyte-depleted terminal cardioplegic solution group showed significantly lower difference of malondialdehyde between arterial and coronary sinus blood ( 0.15 + /- 0.09 versus 0.36 + /- 0.06 versus 0.06 + /- 0.12 nmol/ml , p < 0.05 ) than did the terminal cardioplegic solution or whole blood groups . These results showed that leukocyte-depleted terminal blood cardioplegic solution may have a role in attenuating reperfusion injury in patients with critical conditions such as preoperative myocardial ischemic injury |
2,484 | 23,291,340 | In conclusion , patients receiving SU treatment had increased all-cause and CV mortality risks . | null | null |
2,485 | 18,975,366 | Primary studies of interventions for rheumatoid arthritis generally reported few variables necessary to answer questions about health inequalities .
Most CMSG systematic review s failed to assess those variables even when described in the primary studies . | OBJECTIVE To determine whether Cochrane Musculoskeletal Group ( CMSG ) systematic review s and corresponding primary studies of rheumatoid arthritis interventions report and analyze the data needed to assess the effectiveness of interventions in reducing socioeconomic differences in health and /or improving the health of the poor . | OBJECTIVE To investigate the immediate and short-term effects of 3 commercial wrist orthoses on grip strength and function . METHODS Thirty-six patients with definite rheumatoid arthritis participated in the r and omized , controlled , cross-over design study of 3 commercial wrist extensor orthoses . Dominant-h and dynamometric grip strength was assessed at both initial and followup sessions while splinted and nonsplinted . Functional impact was assessed using a written question naire . RESULTS All 3 commercial orthoses reduced grip strength when first donned . After a 1-week adjustment period , one orthosis , the Smith and Nephew Roylan D-Ring ( Roylan ) , afforded splinted grip strength equal to that of the nonsplinted grip strength . The other 2 orthoses continued to reduce grip strength , and afforded splinted grip strength significantly below that of the Roylan . The Roylan was deemed comfortable by more subjects than the other orthoses . CONCLUSIONS The belief that commercial orthotic use increases grip strength , either immediately or after 1 week , is not supported by this study 's data . Different styles of commercial wrist orthoses appear to have differing influence on splinted grip strength OBJECTIVE In rheumatoid arthritis , education programmes successfully impart knowledge but , notwithst and ing issues of empowerment , this knowledge has to be translated into behavioural change to have a chance of improving disease outcome . Arguably , behavioural change must also occur early if outcomes are to be improved . For these reasons , we planned a study of patient education in early disease , with radiological damage and quality of life as the main outcome variables . METHODS We performed a r and omized controlled trial in people with rheumatoid arthritis of < 5 yr duration . The main intervention was a 4 week education programme , each weekly session lasting 2 h. Assessment s were made at entry , at 4 weeks and at 12 months . The main outcome variables were the modified Larsen radiological score for the h and s and the SF-36 quality of life question naire . Secondary outcome variables were the Health Assessment Question naire ( HAQ ) , Ritchie Articular Index ( RAI ) , Patient Knowledge Question naire ( PKQ ) , Compliance Question naire ( CQ ) , plasma viscosity ( PV ) , pharmaceutical changes and consulting behaviour . RESULTS The patient numbers were 34 ( 10 male , 24 female ) for the control group and 43 ( 16 male , 27 female ) for the education group . The groups were matched for age ( 56.5 yr for control , 55 yr for education ) , disease duration ( 3.5 yr vs 3.0 yr ) and duration of second-line drug therapy ( 14 months vs 12 months ) . We found no significant difference between the groups for Larsen scores at 12 months , although scores for the education group were lower ( 39.5 vs 43.0 , P = 0.13 ) . The ' social functioning ' and ' general health perception ' subscales of the SF-36 showed a significant improvement in the education group , but no significant differences between groups were seen . No significant differences were found for the HAQ , RAI , PV and CQ , but the education group had more disease-specific knowledge than the control group at 12 months ( PKQ scores : 17 vs 21 , P = 0.0002 ) . No differences were found for out-patient visits and in-patient admissions , but the education group had slightly more changes in second-line drugs during the study ( 0.43 changes/person in the control group , 0.51 changes/person in the education group ) . CONCLUSIONS We found no significant difference between the groups in our primary outcome measures , but a trend in favour of the education group was found in radiological progression . Further studies of this kind , using larger patient numbers , are required since the difference may result from improved self-care , better compliance with joint protection strategies and , possibly , improved drug compliance Group counseling and education were studied in patients with rheumatoid arthritis ( RA ) . Patients were matched and r and omly assigned to a control ( CG ) or experimental ( EG ) group . Each group attended an educational session but only the EG participated in 12 weekly group counseling sessions . A test of knowledge about RA and psychological tests were administered before and after these sessions . The EG improved their scores in 2 areas of self-concept and in factual knowledge . There was no increase in depression level . These results provide evidence that formal educational sessions and group counseling may be important in the management of patients with RA To examine the effectiveness of a cognitive-behavioral pain management program for patients with rheumatoid arthritis , three patient groups were studied : a cognitive-behavioral group ( CB ) , an attention-placebo group , and a control group . The CB group received a comprehensive , 12-month pain management program that taught coping strategies such as problem-solving techniques , relaxation training , strategies for attention diversion , and training in family dynamics and communication . Dependent measures included pain , coping strategies , psychological status , functional status , and disease status . Data analysis at 12 months revealed benefits for the CB group in the area of enhanced coping strategies . Specifically , the CB subjects showed significantly greater use of coping strategies and significantly more confidence in their ability to manage pain . The findings are discussed in terms of the importance of enhanced self-efficacy and personal control for patients with rheumatoid arthritis We examined the effectiveness of 2 models of arthritis self-care intervention , the home study model and the small group model . The effects of disease diagnosis and duration , self-care behavior , perceived helplessness , social support , treatment choice , and formal education level on outcomes among persons with arthritis who participated in these programs were evaluated . A pretest-posttest control group design was utilized in the initial experimental study ; comparison group design s were used in the longitudinal studies . Three hundred seventy-four subjects completed the interventions and 12 months of research followup . We found that the intervention models had a statistically significant positive impact on arthritis knowledge , self-care behavior , perceived helplessness , and pain . These findings did not vary when the effects of education level , disease diagnosis and duration , informal social support , and treatment choice were controlled . The small group intervention was more effective in bringing about initial improvements in pain and depression , whereas the home study intervention was more effective in maintaining improvements in perceived helplessness . Changes in perceived helplessness and self-care behavior appear to explain in part the observed improvement in pain OBJECTIVE The aim of this study was to evaluate the therapeutic effects of hydrotherapy which combines elements of warm water immersion and exercise . It was predicted that hydrotherapy would result in a greater therapeutic benefit than either of these components separately . METHODS One hundred thirty-nine patients with chronic rheumatoid arthritis were r and omly assigned to hydrotherapy , seated immersion , l and exercise , or progressive relaxation . Patients attended 30-minute sessions twice weekly for 4 weeks . Physical and psychological measures were completed before and after intervention , and at a 3-month followup . RESULTS All patients improved physically and emotionally , as assessed by the Arthritis Impact Measurement Scales 2 question naire . Belief that pain was controlled by chance happenings decreased , signifying improvement . In addition , hydrotherapy patients showed significantly greater improvement in joint tenderness and in knee range of movement ( women only ) . At followup , hydrotherapy patients maintained the improvement in emotional and psychological state . CONCLUSIONS Although all patients experienced some benefit , hydrotherapy produced the greatest improvements . This study , therefore , provides some justification for the continued use of hydrotherapy OBJECTIVE To test the effects ( on coping , social interactions , loneliness , functional health status , and life satisfaction ) of an intervention aim ed at teaching people with rheumatic diseases to cope actively with their problems . METHODS A total of 168 patients with chronic rheumatic disorders affecting the joints were r and omly assigned to a coping intervention group , a mutual support control group , or a waiting list control group . Measurements were by self-report question naires . RESULTS Post-intervention measurements showed that the coping intervention increased action-directed coping and functional health status , but these effects did not persist up to 6-months followup . In patients who attended at least half of the 10 sessions , the coping intervention contributed to decreased loneliness at post-intervention and to improvements in social interactions and life satisfaction at 6-months followup . CONCLUSION Teaching patients with rheumatic diseases to cope actively with their problems had positive impacts . Consequently it is recommended that the coping intervention be incorporated into regular care . Maintenance sessions are advisable OBJECTIVE To determine whether a patient education programme ( PE ) would improve rates of adherence to a slow acting antirheumatic drug and to assess any subsequent effect on patient outcome . METHODS A r and omly controlled study comprising 100 patients with rheumatoid arthritis ( 49 control CG ; 51 experimental EG ) requiring D-penicillamine ( DPA ) . The same practitioner saw patients on seven occasions , for the same length of time . The EG received 7 x 30 minute one to one sessions of PE , while the CG received st and ard management . The primary measure of adherence was a pharmacological marker ( phenobarbitone ) encapsulated with the DPA assayed at monthly intervals for six months . Plasma viscosity ( PV ) , C reactive protein , articular index , morning stiffness , and pain score were used to assess outcome . RESULTS 454 blood sample s were collected and assayed and the pharmacological marker showed the EG to be significantly more adherent on more occasions than the CG ( p<0.05 ) . Patterns of adherence over time showed that at 12 weeks 86 % ( 38/44 ) of those in the EG compared with 64 % ( 29/45 ) of the CG remained adherent ( p=0.01 ) . These trends continued and by the end of the study 85 % ( 29/34 ) of the EG compared with 55 % ( 23/42 ) of the CG were taking their DPA as prescribed . Fifteen patients ( 12 from the EG ) experienced side effects requiring study withdrawal and 14 patients requested study withdrawal ( two from the EG ) . On study entry patients in the CG had significantly higher levels of PV than the EG and this remained so throughout the research . However , on completion , the health status of patients in both groups had improved significantly ( p<0.01 ) . CONCLUSIONS PE significantly increased adherence to DPA and its effects persisted over a period of six months . No additional clinical benefit was detected in the EG in comparison with the CG Twenty-two men with rheumatoid arthritis were r and omly assigned to either a patient education group , receiving st and ard inpatient medical care in addition to a formal education program , or a control group receiving only the inpatient medical care . Members of the groups were not significantly different in terms of age , degree of life stress , socioeconomic status , educational level , or years since onset of rheumatoid arthritis . Dependent measures included the Arthritis Knowledge Inventory ( AKI ) , the Arthritis Impact Measurement Scales ( AIMS ) , and the Beck Depression Inventory ( BDI ) , and they were collected preeducation , posteducation , and at a three-month followup . Results from the AIMS revealed improvement in dexterity , social role , depression , and overall health status for both groups . The BDI also revealed significantly less depression for both groups , reflecting a general improvement following medical intervention . Although the patient education group revealed significantly higher scores on the knowledge measure , they also revealed significantly more impairment of activity levels and significantly higher pain scores . Education was effective for increasing rheumatoid arthritis knowledge , but such topics as joint protection and disease process may adversely affect how patients view their physical capacities and interpret their pain |
2,486 | 31,364,475 | Conclusion : Overall evidence was weak in suggesting that effects on outcomes were due to the sole influences of shape capture .
However , studies suggest that h and s-on methods are dependent on a prosthetist ’s skill .
H and s-off methods , although repeatable , might still require experience to attain a good fit .
The relation between socket fit and comfort is still unclear .
Clinical relevance A good fitting prosthetic socket is crucial for efficient and comfortable use of a prosthesis . | Introduction : In trans-tibial prosthetics , shape-capture methods are employed to create a representation of the residuum .
Shape-capture methods can be grouped into the categories of ‘ h and s-on ’ , ‘ h and s-off ’ and computer-aided design .
Objective : This review examines the influences and trends of shape-capture methods on the outcomes of quality , comfort of user and clinical efficiency , in the population of trans-tibial prosthesis users .
To attain the best chances of a good fit , it is important that the characteristics of the residuum are captured as accurately as possible during the initial “ shape capture ” stage .
This paper attempts to categorize and evaluate the existing shape capture methods on their influence and trends on various outcomes - Quality of shape capture , comfort of user and clinical efficiency | The aim of this study was to evaluate the validity and reliability of volume determinations using the commercially available Seattle ShapeMaker CAD/CAM system for production of prosthetic sockets and to compare it with the commercially available CAPOD system . We used three types of reference objects for volumetric determinations : steel tubes , plaster of Paris casts , and residual limb models . Three different sizes were examined for each type of object . Volume measurements with the two CAD/CAM systems were compared with measurements obtained by water filling , water immersion , or mathematical calculation ( tubes only ) . We found an inconsistent systematic error of less than 3.1 % for ShapeMaker and no systematic error for CAPOD . R and om errors , represented by the coefficient of variation , were below 1.3 % for the ShapeMaker and , in most cases , below 0.4 % for the CAPOD . Theoretical changes in volume of 2.6 % and 0.8 % are possible to detect with these CAD/CAM systems . In our opinion , both systems have sufficient precision for routine clinical use in prosthetics and orthotics . However , in our study , the ShapeMaker committed larger r and om and systematic errors than CAPOD . This means that , according to our study , CAPOD offers the best possibility to determine and detect small changes in residual limb volume as a function of time The purpose of this study was to evaluate the application of CAD CAM in the production of temporary trans-tibial prostheses . The CAD CAM system was assessed based on the number of socket attempts , number of prosthetic appointments , and temporary prosthesis rehabilitation time . These parameters were considered to be related to the quality of socket fit and were influenced by the entire interdisciplinary team including the patient . A concurrent prospect i ve comparison between the CAD CAM system and an established fibreglass/pelite liner technique was also performed . Patients ( n=30 ) , were fitted with either a conventional or a CAD CAM socket . Records were kept before and after discharge until the interdisciplinary team considered the patient ready for definitive prosthesis casting . After approximately 90 postoperative days , patients were deemed fit to proceed from their initial plaster cast prostheses to their temporary prostheses . The group fitted with conventional sockets had an in-patient rehabilitation phase of 10.5+/−60 days and required 2.9+/−1.1 prosthetic appointments . In- patients fitted with CAD CAM sockets required 5.1+/−1.8 appointments and were hospitalised for 23.6+/−15.0 days . The significantly increased rehabilitation duration and number of appointments ( p=0.01 ) , were generally due to incorrect socket volume and /or inadequately modified relief/loading areas . In this study 67 % of the patients fitted with CAD CAM sockets required at least one additional attempt . The clinical evaluation and modification of the temporary prostheses , including the decision to remake a particular socket , were camed out by the same prosthetist who cast the patients . During the out-patient phase , the type of socket design was not observed to influence either duration of out- patient rehabilitation or frequency of appointments . Out-patient rehabilitation included on average 4 appointments and ended after 90 days . Multidisciplinary discharge criteria and st and ardised follow-up procedures rendered the measured parameters less relevant to this study 's purpose in the out-patient phase This study is an evaluation , from the patient 's point of view , of CAD CAM prosthesis sockets compared with conventional sockets . Twenty-two trans-tibial amputees were divided into two groups . One group was provided with a CAD CAM ( CAPOD ) socket , the other with a conventionally made one . After one month the groups were evaluated with regard to subjective experience , the judgement of a prosthetist and a physiotherapist , social variables and objective gait parameters . Then the groups switched over to the other type of socket , and after another month a new evaluation was performed . The study design was a single-blind study . In total 175 variables were evaluated . No difference was found between the two types of socket , except for a lower number of terry cloth stockings used in the CAD CAM socket . As the st and ard of conventional prosthetics in Sweden is considered to be high , the results were considered as satisfactory . The quality of the CAD CAM sockets was at least at the same level as conventionally made ones During the next decade CAD/CAM technique will probably become routine in prosthetics and orthotics , not only as a complement to manual techniques , but also introducing new possibilities . However , even complex and sophisticated techniques have errors of measurement that must be considered . Such errors are of two principal kinds : systematic errors and r and om errors . In this study we have evaluated the Swedish CAPOD system with respect to volumetric determinations . We used two types of reference objects for volume determinations : cylinders and amputation residual limb models . Three different sizes were examined of each type of object . Volume measurements with CAPOD were compared with volumes obtained by water immersion or mathematical calculation ( cylinders only ) . We found a constant , linear systematic error of + 2.5 % . Such an error can easily be corrected for . The r and om error , represented by the coefficient of variation , was 0.5 % , which means that there is a theoretical possibility to detect volume changes exceeding 1 % . We consider the precision sufficient for clinical practice in prosthetics and orthotics . Biological variations due to soft tissue deformation must be added on top of these errors . Such deformations were not evaluated in this study For this r and omized crossover trial , we compared two common transtibial socket suspension systems : the Alpha liner with distal locking pin and the Pe-Lite liner with neoprene suspension sleeve . Our original hypotheses asserted that increased ambulatory activity , wear time , comfort , and satisfaction would be found with the elastomeric suspension system . Thirteen subjects completed the study . Following 2.5-month accommodation to each condition , ambulatory activity was recorded ( steps/minute for 2 weeks ) , and subjects completed three question naires specific to prosthesis use and pain : the Prosthesis Evaluation Question naire ( PEQ ) , a Brief Pain Inventory ( BPI ) excerpt , and the Socket Comfort Score ( SCS ) . Upon completion , subjects selected their favored system for continued use . Ten subjects preferred the Pe-Lite and three the Alpha . Subjects spent 82 % more time wearing the Pe-Lite and took 83 % more steps per day . Ambulatory intensity distribution did not differ between systems . No statistically significant differences were found in question naire results . Subject feedback for each system was both positive and negative In prosthetic practice , the question often arises as to whether the h and cast should be made from a contracted or from a non-contracted amputation stump . To eluci date this question , the authors have performed a study to quantify the volume difference between these 2 conditions , and to relate the differences to prosthetic fitting . Sixteen ( 16 ) trans-tibial amputees participated in the study . All of them were fitted with an ICEROSS silicone socket . Electromyographic studies , with electrodes attached to the anterior tibial and medial gastrocnemius muscles , were carried out to determine muscle contraction levels . Volume determinations were made with the CAPOD laser scanning system . Measurements were performed with and without the silicone liner on the stump . Without a silicone liner , the volume of the stump increased by 5.8 % ( SD=5.3 ) as the muscles contracted . This increase was statistically significant . With the liner donned the volume increased 3.5 % ( SD=3.3 ) . This increase was also statistically significant . The volume of the prosthetic socket was also compared with the stump volume with a silicone liner on . For the relaxed stump , the difference was 1.8 % ( SD=10.1 ) , and for the contracted stump −1.7 % ( SD=11.3 ) . Neither difference was statistically significant . The importance of these volume changes and how they influence stiffness of the coupling between the stump and the socket are discussed . It is concluded , that the observed difference in volume between a contracted and a non-contracted stump are large enough to be considered by the prosthetist in his decision on how to make a h and cast PURPOSE To perform quantitative evaluation of lower-extremity prosthesis fit by using spiral computed tomography ( CT ) . MATERIAL S AND METHODS Two spiral CT scans were obtained at each of two different sessions in seven adult patients who had undergone amputation below the knee . A rigid-body transformation of the tibia was computed and used to align paired ( intra- and intersession ) spiral CT data sets for each individual in a common coordinate system . Paired scans in each individual were compared to assess registration and precision of soft-tissue change measurement . Clinical prosthesis fit evaluation was demonstrated in an adult amputee volunteer who underwent CT evaluation while wearing two different prostheses . RESULTS In the seven patients examined , more than 90 % of the measured soft-tissue volume displacements between sessions could be explained as true differences . Precision error of soft-tissue volume change was approximately 13 cm3 , or approximately 1 % error relative to the mean volume . Volumetric changes due to different prostheses were substantially larger than the r and om error . CONCLUSION Registration of CT volumetric data sets to quantify residual-limb soft-tissue envelope change in lower-limb prosthetics is precise and can be used to detect the effect of prosthesis shape alterations OBJECTIVE To analyze the reliability of 4 methods ( water immersion , computer-aided design [ CAD ] photometric method , CAD h and scanner , and circumferential measurements ) for stump volume measurement in transtibial amputees . DESIGN Repeated measurements . SETTING General community , ambulatory care . PARTICIPANTS Transtibial amputees ( N=26 ; mean age ± SD , 58.7±11.0y ) . INTERVENTIONS Stump volume of patients with an amputation was measured on 2 occasions , each consisting of 2 sessions . In each session , stump volume was measured by 2 observers using each of the 4 methods . Sequence of observers and measurement methods was determined r and omly . MAIN OUTCOME MEASURE Repeatability coefficients , as a measure for reliability , for each method were calculated , as well as variance components to estimate the influence of measurement conditions on stump volumes measured . RESULTS Repeatability coefficients varied from 129mL CAD h and scanner to 158mL CAD photometric method . Error variance contributed 12 % to the total variance . Methods contributed 36 % , method -amputee and occasion-amputee interactions contributed both 25 % to the error variance . CONCLUSIONS Repeatability coefficient was lowest for the CAD h and scanner , which indicates the best reliability . Substantial differences existed in stump volumes measured between the 4 methods OBJECTIVE The aim was to evaluate stump/socket interface pressure in amputees wearing a socket developed by a pressure casting system . Design . Five unilateral transtibial amputees wore a pressure cast socket and walked at a self-selected speed . BACKGROUND The socket produces equally distributed pressure at the stump/socket interface , deviating from the conventional belief that pressure varies in proportion to the pain threshold of different tissues in the stump . METHODS The socket was fabricated while the subject placed his stump in a pressure chamber . Pressure was applied while he adopted a normal st and ing position . A specially built strain gauged type pressure transducer was used for measuring pressure distribution . Pressure and gait parameters were measured simultaneously while the subjects were st and ing and walking . RESULTS AND CONCLUSION The pressure cast technique was able to provide comfortable fitting sockets . A hydrostatic pressure profile was not evident during st and ing or gait . Results also showed that no st and ard pressure profile for the pressure cast socket was observed . This was expected as no rectifications were done on the pressure cast socket . Pressure profiles at 10 % , 25 % and 50 % of gait cycle did not correlate with the pressure profiles previously proposed . RELEVANCE The hydrostatic theory is an attractive concept in socket design as it produces a stump/socket pressure profile that is evenly distributed . Furthermore , it is a method that is easily implemented , independent of a prosthetist 's skill and experience and reduces manufacturing time . However , there is still controversy surrounding the efficacy of this hydrostatic theory The current method for fabricating prosthetic sockets is to modify a positive mold to account for the nonhomogeneity of the residual limb to tolerate load ( i.e. , rectified socket ) . We tested unrectified sockets by retaining the shape of the residual limb , except for a distal end pad , using an alginate gel process instead of casting . This investigation compared rectified and unrectified sockets . Forty-three adults with unilateral transtibial amputations were tested after r and omly wearing both rectified and unrectified sockets for at least 4 weeks . Testing included a gait analysis , energy expenditure , and the Prosthesis Evaluation Question naire ( PEQ ) . Results indicated no differences between sockets for gait speed and timing , gait kinematics and kinetics , and gait energy expenditure . There were also no differences in the PEQ , and 16 subjects selected the rectified socket , 25 selected the unrectified socket , and 2 subjects selected to use both sockets as their exit socket . Results seemed to indicate that more than one paradigm exists for shaping prosthetic sockets , and this paradigm may be helpful in underst and ing the mechanisms of socket fit . The alginate gel fabrication method was simpler than the traditional method . The method could be helpful in other countries where prosthetic care is lacking , may be helpful with new amputees , and may be helpful in typical clinics to reduce costs and free the prosthetist to focus more time on patient needs |
2,487 | 25,032,820 | The primary outcomes of quality of life and exacerbations leading to use of steroids were not reported by these studies .
The overall quality of the studies was very low , and no clear differences were noted between water-based exercise and comparator treatments .
Therefore , we remain very uncertain about the effects of water-based exercise for adults with asthma .
AUTHORS ' CONCLUSIONS The small number of participants in the three included studies , the clinical and method ological heterogeneity observed and the high risk of bias assessed mean that we are unable to assess the place of water-based exercise in asthma . | BACKGROUND Asthma is a common condition characterised by airway inflammation and airway narrowing , which can result in intermittent symptoms of wheezing , coughing and chest tightness , possibly limiting activities of daily life .
Water-based exercise is believed to offer benefits for people with asthma through pollen-free air , humidity and effects of exercise on physical function .
OBJECTIVES To evaluate the effectiveness and safety of water-based exercise for adults with asthma . | Ventilatory function after three types of exercise — running , cycling , and swimming — was studied in 10 control subjects and 40 asthmatic patients . All performed eight minutes of submaximal aerobic exercise during each of the programmes , which were conducted in a r and omly selected order . Biotelemetric monitoring of heart rates was used to equate the intensity of the exertion undertaken during the three systems of exercise . No control subject showed any significant variation in ventilatory capacity after exercise , and the responses after the three forms of exercise did not differ . In asthmatics exercise-induced asthma was observed after 72·5 % of running tests , 65 % of cycling tests , and 35 % of swimming tests . In addition , those patients who developed exercise-induced asthma after swimming were noted to have significantly smaller falls in FEV1 levels than were recorded after running and cycling . These results were statistically significant ( P < 0·01 ) . The unexplained aetiology of increased airways resistance after exercise in asthmatics is discussed . This study indicates that swimming should be recommended in preference to running or cycling as an exercise programme for adults and children with asthma BACKGROUND Aging compromises the ability of the central nervous system to maintain body balance and reduces the capacity for adaptive reactions . To prevent falls , the reception conditions for sensory information need to be improved . OBJECTIVES To evaluate the impact of a structured aquatic and a non-aquatic exercise program for lower-limb muscle endurance on the static and dynamic balance of elderly people . METHODS This was a prospect i ve r and omized clinical study in which the variables were assessed before and after the training program . Thirty-six elderly people were evaluated using four tests : the Berg Balance Scale , Dynamic Gait Index , gait speed and t and em gait . The participants were r and omized into three groups : aquatic exercise group , non-aquatic exercise group and control group . The exercise groups underwent a program for lower-limb muscle endurance that consisted of 40-minute sessions twice a week for six weeks . The participants were reevaluated after six weeks . The data were analyzed statistically using the univariate ANOVA test for comparisons between the groups before and after the intervention . RESULTS The program for lower-limb muscle endurance significantly increased balance ( p<0.05 ) in the evaluation tests after the training program . CONCLUSION The muscle endurance program provided a significant improvement in static and dynamic balance among community-dwelling elderly people . It was also possible to infer that this improvement occurred regardless of the environment , i.e. aquatic or non-aquatic . Article registered in the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) under the number ACTRN 12609000780257 PURPOSE There is an increased prevalence of asthma and airway hyperresponsiveness in elite athletes , particularly in swimmers . High intensity exercise may induce airway inflammation and subsequent remodelling in these subjects . Our aim was to evaluate the effects of high-intensity training on induced-sputum cell population s in elite athletes . METHODS Swimmers and runners with hyperresponsive airways ( SH and RH ) , defined by a provocative concentration of methacholine inducing a 20 % decrease in FEV1 ( PC20 ) < 16 mg/ml or with normoresponsive airways ( PC20 > 16 mg/ml ; SN , RN ) to methacholine were enrolled . The mean PC20 was 2.27 mg/ml in SH ( n=12 ) , 32.2 in SN ( n=10 ) , 3.25 in RH ( n=10 ) and 41.5 in RN ( n=13 ) . All athletes had two induced sputum analyses at one- to two-week intervals in r and om order : after a period of 72 hours without training , 24 hours after a training session . RESULTS PC20 was unchanged after training . The median % neutrophils and eosinophils in groups SH , SN , RH , and RN , respectively , were 26.5 - 1.6 , 8.6 - 0.3 , 28.0 - 0.03 and 25.5 - 0.1 before and 45.0 - 0.5 , 31.1 - 0.4 , 54.0 - 0.6 and 48.3 - 0.3 after training . While the magnitude of the increase in neutrophils was similar for all groups , it reached statistical significance ( pre-post-training ) only in the SH group ( P = 0.039 ) . CONCLUSION A one-hour session of high-intensity training was associated with an increase in airway neutrophils among hyperresponsive swimmer athletes , while airway responsiveness remained unchanged in all groups Swimming pool attendance and exposure to chlorination by-products showed adverse health effects on children . We assessed whether early swimming pool attendance , especially baby swimming , is related to higher rates of early infections and to the development of allergic diseases . In 2003 - 2005 , 2192 children were analysed for the 6-year follow-up of a prospect i ve birth cohort study . Data on early swimming pool attendance , other lifestyle factors and medical history were collected by parental-administered question naire . Bivariate and multivariate logistic regression analyses were used to evaluate associations . Babies who did not participate in baby swimming had lower rates of infection in the 1st year of life ( i ) diarrhoea : OR 0.68 CI 95 % 0.54 - 0.85 ; ( ii ) otitis media : OR 0.81 CI 95 % 0.62 - 1.05 ; ( iii ) airway infections : OR 0.85 CI 95 % 0.67 - 1.09 . No clear association could be found between late or non-swimmers and atopic dermatitis or hay fever until the age of 6 years , while higher rates of asthma were found ( OR 2.15 95 % CI 1.16 - 3.99 ) , however , potentially due to reverse causation . The study indicates that , in terms of infections , baby swimming might not be as harmless as commonly thought . Further evidence is needed to make conclusions if the current regulations on chlorine in Germany might not protect swimming pool attendees from an increased risk of gastrointestinal infections . In terms of developing atopic diseases there is no verifiable detrimental effect of early swimming RATIONALE Cross-sectional studies have reported inconsistent findings for the association between recreational swimming pool attendance and asthma and allergic diseases in childhood . OBJECTIVES To examine whether swimming in infancy and childhood was associated with asthma and allergic symptoms at age 7 and 10 years in a UK longitudinal population -based birth cohort , the Avon Longitudinal Study of Parents and Children . METHODS Data on swimming were collected by question naire at 6 , 18 , 38 , 42 , 57 , 65 , and 81 months . Data on rhinitis , wheezing , asthma , eczema , hay fever , asthma medication , and potential confounders were collected through question naires at 7 and 10 years . Spirometry and skin prick testing were performed at 7 to 8 years . Data for analysis were available for 5,738 children . MEASUREMENTS AND MAIN RESULTS At age 7 years , more than 50 % of the children swam once per week or more . Swimming frequency did not increase the risk of any evaluated symptom , either overall or in atopic children . Children with a high versus low cumulative swimming pool attendance from birth to 7 years had an odds ratio of 0.88 ( 95 % confidence interval , 0.56 - 1.38 ) and 0.50 ( 0.28 - 0.87 ) , respectively , for ever and current asthma at 7 years , and a 0.20 ( 0.02 - 0.39 ) st and ard deviation increase in the forced midexpiratory flow . Children with asthma with a high versus low cumulative swimming had an odds ratio for current asthma at 10 years of 0.34 ( 0.14 - 0.80 ) . CONCLUSIONS This first prospect i ve longitudinal study suggests that swimming did not increase the risk of asthma or allergic symptoms in British children . Swimming was associated with increased lung function and lower risk of asthma symptoms , especially among children with preexisting respiratory conditions The purpose of this study was to determine whether inactive asthmatic patients could perform high-intensity physical training equally well on l and as in water , and to compare the effects of these training forms . Thirty-two adults with asthma , r and omized into two groups , underwent a 10-week supervised rehabilitation program with emphasis on physical training . All patients , irrespective of training form , were able to exercise to maximal intensity ( 80 - 90 % of estimated maximal heart rate ) . No asthmatic attacks occurred in connection with the training sessions . Respiratory variables remained almost unchanged in both groups . The asthma symptoms declined during the rehabilitation period , and the subjects needed less acute asthma care after the rehabilitation . The cardiovascular condition improved significantly and similarly in the two groups . Ten patients , 5 in each group , had exercise-induced asthma at the start of the rehabilitation . Only 3 patients , 2 from the water group and 1 from the l and group , had exercise-induced asthma after 10 weeks . We conclude that indoor training , either on l and or in water , is beneficial . The effects of these two training forms are almost equivalent |
2,488 | 28,812,109 | In spite of the heterogeneity of the protocol s , all the studies had the goal of assessing the effects of vibration on the PFM , and the stimulation was found to be effective in reducing urinary leakage , improving muscle strength and consequently the patients ’ quality of life . | Introduction and hypothesisThe pelvic floor muscles ( PFM ) play an important part in the urinary continence mechanism .
Changes in their structure and functionality may lead to a predisposition to pelvic floor dysfunction such as urinary incontinence ( UI ) , which is the involuntary loss of urine .
Some techniques for conservative treatment of UI are already well documented .
However , new approaches have been found that require scientific proof of their effectiveness , such as vibratory stimulation ( VS ) .
Thus , we performed a systematic review of studies that investigated the use of perineal VS ( PVS ) for the treatment of stress UI . | Objective : To determine whether Whole Body Vibration Training ( WBVT ) is effective at improving pelvic floor muscles strength in women with Stress Urinary Incontinence ( SUI ) . Material s and methods : The study was design ed as a r and omized clinical trial . 43 women with SUI were r and omly assigned in two groups ; WBVT and Pelvic Floor Muscle Training ( PFMT ) and received interventions for four weeks . Pelvic floor muscle ( PFM ) strength , quality of life and incontinence intensity were evaluated . All measurements were conducted pre and post intervention and also after 3 months in all participants . The ANOVA and the independent sample t test were applied respectively to determine the differences in each group and between the groups . Results : This study showed the WBVT protocol in this study was effective in pelvic floor muscles strength similar to PFMT , and also in reducing the severity of incontinence and increasing I-QOL question naire score . We found significant differences in each group pre and post intervention ( p = 0.0001 ) ; but no significant difference in comparison of two groups ' outcomes . Also after three-month follow up , there was no significant difference between groups . Conclusion : The findings of this study showed the beneficial effects of WBVT in improving pelvic floor muscles strength and quality of life in patients with urinary incontinence in four-week treatment period and after three months follow up PURPOSE to compare the effects of functional electrostimulation of the pelvic floor and therapy with cones in women with stress urinary incontinence ( SUI ) . METHODS r and omized clinical study for which 45 patients with SUI were selected . The effects of functional electrostimulation of the pelvic floor were evaluated in the SUI treatment of 24 women , with the use of clinical data ( micturition diary , pad test and a question naire about quality of life - I-QoL ) . The patients were su bmi tted to two 20 ' weekly sessions for four consecutive months , under the supervision of a physiotherapist . The electrode used had 10 cm length and 3.5 cm width with a double metallic ring and a cylindrical shape , positioned in the medium third of the vagina . The electric parameters used were : intensity varying from 10 to 100 mA and 50 Hz of fixed frequency , with pulse duration of 1 ms . Also , we evaluated 21 patients who were su bmi tted to vaginal cone treatment . The cone therapy was done with two 45 minute sessions per week . The cones ' weight varied from 20 to 100 gr . RESULTS there was no difference between the outcomes of electrostimulation of the pelvic floor and the vaginal cones for the treatment of SUI ( p>0.05 ) . After four months , there was a significant improvement in the I-QoL index of the patients treated both with electrostimulation ( 40.3 versus 82.9 ) or with the cones ( 47.7 versus 84.1 ) . There was a significant decrease in pad weight in both groups , measured before and after the treatment ( 28.5 and 32 g versus 2.0 and 3.0 g for the electrostimulation and cone group , respectively ) . Finally , there was a significant decrease in the number of urinary leakage evaluated by the micturition diary in both groups ( p<0.0001 ) . CONCLUSIONS both electrostimulation and vaginal cones were effective in the treatment of women with SUI OBJECTIVE To evaluate the effectiveness of pelvic floor muscle exercises ( PFMEs ) performed with the new biofeedback Vibrance Kegel Device ( VKD ) , compared to PFMEs alone , in treating stress urinary incontinence ( SUI ) . MATERIAL S AND METHODS This was a pilot prospect i ve , r and omized trial of women aged ≥18 years with SUI symptoms who underwent PFMEs at University Malaya Medical Centre from October 2011 to October 2013 . The patients were r and omly divided into two groups : control ( PFMEs alone ) and VKD ( PFMEs with VKD biofeedback ) . The patients underwent 16 weeks of pelvic floor training , during which they were assessed using Australian pelvic floor question naires and modified Oxford scales for pelvic floor muscle strength at week 0 , 4 , and 16 . RESULTS Forty patients were recruited ( control 19 , VKD 21 ) . Three patients in the control group dropped out during week 16 training , whereas the VKD group had no dropouts . The VKD group reported significantly earlier improvement in SUI scores , as assessed by the Australian pelvic floor question naires ( P = .035 ) at week 4 . However , there was no significant difference between the groups ' SUI scores at week 16 . Pelvic floor muscle strength was significantly better in the VKD group at week 4 ( P = .025 ) and week 16 ( P = 0.001 ) . The subjective cure rate was similar in both groups at week 16 ( 62.5 % for control and 61.9 % for VKD ) ( P = 0.742 ) . CONCLUSION Using the VKD result ed in significant early improvement in SUI scores , and pelvic muscle strength had improved significantly by the end of the study . The VKD proved useful as an adjunct for pelvic floor training OBJECTIVE To evaluate the effects of surface electrical stimulation ( SES ) and to compare them with the effects of the intravaginal electrical stimulation ( IVES ) in women with stress urinary incontinence ( SUI ) . STUDY DESIGN This r and omized controlled study included 48 women aged over 50 years , who complained of SUI evaluated according to two structured questions of King 's Health Question naire ( KHQ ) and who had not previously undergone physical therapy for SUI . The calculation of the sample size estimated a sample of 45 volunteers with a significance level of 5 % and statistical power of 90 % . The women were r and omized to : Surface Electrical Stimulation Group ( SESG ) ( n=15 ) , Intravaginal Electrical Stimulation Group ( IVESG ) ( n=15 ) and Control Group ( CG ) ( n=15 ) . Subjects in the intervention groups were treated with the same parameters of electrical stimulation for 12 sessions . The SESG had four silicone electrodes fixed in the suprapubic and ischial tuberosity regions . The IVES group used an intravaginal electrode . The CG did not receive any treatment during the corresponding time . They were evaluated before and after treatment by a physical therapist who was blind to group allocation . The primary outcomes were urinary leakage , pressure and strength of pelvic floor muscle ( PFM ) contraction . The secondary outcome was quality of life ( QOL ) evaluated by KHQ . Forty-five women completed the study and were included in the analysis . Statistical analysis was performed using the Wilcoxon test for intragroup analysis and Kruskal-Wallis and Mann-Whitney tests for intergroup analysis ( p<0.05 ) . RESULTS There was significant improvement in urinary loss and pressure of contraction in the SESG and IVESG . PFM strength increased only in the IVESG . Intergroup analysis found differences after the treatment in : urinary leakage between the SESG and CG ( p<0.001 ) and the IVESG and CG ( p<0.001 ) . Regarding QOL , there was significant reduction in the incontinence impact , limitations of daily activities , physical limitation , emotion , sleep and disposition and severity domains in the SESG ( all p<0.02 ) and IVESG ( all p<0.04 ) after the treatments . CONCLUSION SES and IVES are important treatments to improve the SUI . Both improved the QOL , urinary leakage , and strength and pressure of PFM contraction OBJECTIVE The aim of this study was to determine if two different whole body vibration , sinusoidal vibration ( SV ) and stochastic resonance vibration ( SRV ) , using various intensities lead to a reactive activation of pelvic floor muscles . STUDY DESIGN We compared the pelvic floor muscle response of a healthy control group with that of a post partum group with weakened pelvic floor contraction . Activation effects of stochastic resonance vibration and sinusoidal vibration with six increasing vibration intensities were investigated using pelvic floor EMG and compared to activity during rest and maximum voluntary contraction . RESULTS Both whole body vibration systems were able to activate pelvic floor muscles significantly depending on vibration intensity . Generally , the SRV achieved a significantly higher activation than maximum voluntary contraction , especially in women post partum and using a frequency of 6 - 12 Hz . CONCLUSION SRV , compared to SV , leads to higher pelvic floor muscle activation in subjects with weakened pelvic floor muscles and achieves higher pelvic floor activation than maximum voluntary contraction alone . Neurourol . Urodynam . 28:405 - 410 , 2009 . ( c ) 2009 Wiley-Liss , Background More and more frequently stress urinary incontinence affects young healthy women . Hence , early implementation of effective preventive strategies in nulliparous continent women is essential , including pelvic floor muscle training . An initial evaluation based on the bioelectrical activity of the pelvic floor muscles ( PFM ) during whole-body vibration ( WBV ) would help to devise the best individualized training for prevention of stress urinary incontinence in woman . We hypothesized that synchronous WBV enhances bioelectrical activity of the PFM which depends on vibration frequency and peak-to-peak vibration displacement . Methods The sample consisted of 36 nulliparous continent women r and omly allocated to three comparative groups . Group I and II subjects participated in synchronous whole-body vibrations on a vibration platform ; the frequency and peak-to-peak displacement of vibration were set individually for each group . Control participants performed exercises similar to those used in the study groups but without the concurrent application of vibrations . Pelvic floor surface electromyography ( sEMG ) activity was recorded using a vaginal probe during three experimental trials limited to 30s , 60s and 90s . The mean amplitude and variability of the signal were normalized to the Maximal Voluntary Contraction – MVC . Results Friedman ’s two-way ANOVA revealed a statistically significant difference in the mean normalized amplitudes ( % MVC ) of the sEMG signal from the PFM during 60s- and 90s-trials between the group exposed to high-intensity WBV and control participants ( p < 0.05 ) . Longer trial duration was associated with a statistically significant decrease in the variability of sEMG signal amplitude in the study and control groups ( p < 0.05 ) . Conclusions Synchronous high-intensity WBV ( 40 Hz , 4 mm ) of long duration ( 60s , 90s ) significantly enhances the activation of the PFM in young continent women . Prolonged maintenance of a static position significantly decreases the variability of sEMG signal amplitude independent of whole-body vibrations . Single whole-body vibrations in nulliparous continent women does not cause pelvic floor muscle fatigue . Trial registration The trial was registered in the Australian and New Zeal and Clinical Trials Registry ( no. ACTRN12615000966594 ) ; registration date : 15/09/2015 BACKGROUND Neuromuscular electrical stimulation ( NMES ) is widely treatment for stress urinary incontinence ( SUI ) but there is no consensus in literature regarding the most effective treatment parameters . OBJECTIVE To compare two NMESintra-vaginal protocol s for the treatment of SUI in women . METHODS The study included 20 volunteers with an average age of 55.55±6.51 years and with the clinical diagnosis of SUI . Volunteers were r and omly divided into two groups : group 1 ( G1 ) received NMES with medium-frequency current and group 2 ( G2 ) received NMES with low-frequency current . Functional assessment s of pelvic floor muscles ( PFM ) were performed by perineometry . The severity of signs and symptoms were objective ly evaluated using the 1 hour pad test and subjectively evaluated using a visual analog scale that measured the discomfort caused by the SUI . Shapiro-Wilk test was used to analyze data normality , and the Friedman test was used to analyze nonparametric data . For analysis of symptoms related to SUI the Fisher exact test and the Mann-Whitney test were used . Significance level of 5 % was set for all data analysis . RESULTS No significant differences ( p>0.05 ) were found between groups for any of the variable assessed . The within group analysis of initial and final evaluations ( after NMES ) demonstrated significant differences ( p<0.05 ) in amount of urine lost , the discomfort caused by urinary incontinence and perineal pressure for both treatment groups . CONCLUSION The two NMES protocol s applied were equally effective in the treatment of SUI 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 |
2,489 | 28,292,696 | Within the limitation of this review , a possible improvement in bone density can be found when LLLT is applied postoperatively in maxillofacial bony defects .
LLLT also seems to promote anti-inflammatory and analgesic effects and accelerate healing , as well as enhance quality of life related to oral health . | PURPOSE This systematic review evaluates the effectiveness of low-level laser therapy ( LLLT ) to enhance maxillofacial area bone repair . | Little is known about the benefits of low-level laser therapy ( LLLT ) on improvement of stability of dental implants . The aim of this r and omized clinical study was to assess the LLLT effect on implants stability by means of resonance frequency analysis ( RFA ) . Thirty implants were distributed bilaterally in the posterior m and ible of eight patients . At the experimental side , the implants were su bmi tted to LLLT ( 830 nm , 86 mW , 92.1 J/cm2 , 0.25 J , 3 s/point , at 20 points ) , and on the control side , the irradiation was simulated ( placebo ) . The first irradiation was performed in the immediate postoperative period , and it was repeated every 48 h in the first 14 days . The initial implant stability quotient ( ISQ ) of the implants was measured by means of RFA . New ISQ measurements were made after 10 days , 3 , 6 , 9 , and 12 weeks . The initial ISQ values ranged from 65–84 , with a mean of 76 , undergoing a significant drop in stability from the 10th day to the 6th week in the irradiated group , and presenting a gradual increase from the 6th to the 12th week . The highest ISQ values were observed on the 10th day in the irradiated group , and the lowest in the 6th week in both groups . Under the conditions of this study , no evidence was found of any effect of LLLT on the stability of the implants when measured by RFA . Since high primary stability and good bone quality are of major relevancy for a rigid bone – implant interface , additional LLLT may have little impact macroscopically In our previous studies , we confirmed that low-level laser therapy ( LLLT ) with a 980-nm gallium – aluminum – arsenide diode laser was beneficial for the healing of the alveolar bone in rats with systemic disease . However , many factors can affect the biostimulatory effects of LLLT . Thus , we attempted to investigate the effects of irradiation time on the healing of extraction sockets by evaluating the expressions of genes and proteins related to bone healing . The left and right first maxillary molars of 24 rats were extracted . Rats were r and omly divided into four groups in which extraction sockets were irradiated for 0 , 1 , 2 , or 5 min each day for 3 or 7 days . Specimens containing the sockets were examined using quantitative real-time reverse transcription polymerase chain reaction and western blotting . LLLT increased the expressions of all tested genes , Runx2 , collagen type 1 , osteocalcin , platelet-derived growth factor-B , and vascular endothelial growth factor , in a time-dependent manner . The highest levels of gene expressions were in the 5-min group after 7 days . Five minutes of irradiation caused prominent increases of the expression of all tested proteins after both 3 and 7 days . The expression level of each protein in group 4 was higher by almost twofold compared with group 1 after 7 days . Laser irradiation for 5 min caused the highest expressions of genes and proteins related to bone healing . In conclusion , LLLT had positive effects on the early stages of bone healing of extraction sockets in rats , which were irradiation time-dependent Bisphosphonates ( BSPs ) are used for the treatment of multiple myeloma , metastatic breast and lung cancer , Paget 's disease , osteoporosis , hypercalcemia due to malignancy , and many other skeletal diseases . BSPs reduce osteoclastic functions , which result in bone resorption . Bisphosphonates-related osteonecrosis of jaws ( BRONJ ) is a newly developed term that is used to describe the significant complication in patients receiving bisphosphonates . BSPs are known to exhibit an anti-angiogenetic effect that initiates tissue necrosis of the hard tissue . There is currently no consensus on the correct approach to this issue . The aim of this retrospective study is to compare the effects of laser surgery with biostimulation to conventional surgery in the treatment of BSP-induced avascular bone necrosis on 20 patients who have been treated in our clinic . BRONJ was evaluated in patients with lung , prostate , and breast cancer under intravenous BSP treatment . Twenty patients in this study developed m and ibular or maxillary avascular necrosis after a minor tooth extraction surgery or spontaneously . Bone turnover rates were evaluated by serum terminal C-telopeptide levels ( CTX ) using the electrochemiluminescence immunoassay technique and patients were treated with laser or conventional surgical treatments and medical therapy . Ten patients were treated with laser surgery and biostimulation . An Er : YAG laser ( Fotona Fidelis Plus II ® Combine laser equipment , Slovenia ) very long pulse ( VLP ) mode ( 200 mJ , 20 Hz ) using a fiber tip 1.3 mm in diameter and 12 mm in length was used to remove the necrotic and granulation tissues from the area of avascular necrosis . Biostimulation was applied postoperatively using an Nd : YAG laser . Low-level laser therapy ( LLLT ) was applied to the tissues for 1 min from 4 cm distance using an Nd : YAG laser ( Fotona-Slovenia ) with a R24 950-µm fiber h and piece long-pulse ( LP ) mode , 0.25-W , 10 Hz power/cm2 from the mentioned distance the spot size was 0.4 cm2 , and power output was 2.5 J. Energy density from the mentioned distance was calculated to be 6.25 J/cm2 . The other ten patients were treated with conventional surgery . Treatment outcomes were noted as either complete healing or incomplete healing . There were no statistically significant differences between laser surgery and conventional surgery ( p > 0.05 ) . CTX values also did not affect the prognosis of the patients . Treatment outcomes were significantly better in patients with stage II osteonecrosis than in patients with stage I osteonecrosis . Our findings suggest that dental evaluation of the patients prior to medication is an important factor in the prevention of BRONJ . Laser surgery is a beneficial alternative in the treatment of patients with this situation . Further r and omized studies with larger patient numbers may also improve our underst and ing of treatment protocol s for this situation A r and omised , double blind comparative study was undertaken to assess the efficacy of low level laser therapy in the reduction of postoperative pain and swelling in patients undergoing the extraction of bilaterally impacted m and ibular third molar teeth . Healing of the sockets was also compared after 1 week . A group of 64 patients had one r and omly-selected operation side treated with a semi-conductor laser and the other side with an apparently identical but non-operating model . Complete data were obtained from 52 of the 64 patients . The results showed that there was no evidence of a difference in pain and swelling on the third day after operation between laser and placebo sides . There was no difference between the two sides when they were assessed for healing 7 days after surgery Recent pre clinical and clinical data have suggested the potential benefit of photodynamic therapy ( PDT ) in the treatment of periodontitis . However , currently , there are very limited data from controlled clinical trials evaluating the effect of PDT in the treatment of periodontitis . The aim of the present study was to evaluate the clinical and microbiological effects of the adjunctive use of PDT in non-surgical periodontal treatment in patients receiving supportive periodontal therapy . Twenty-four patients receiving regularly supportive periodontal therapy were r and omly treated with either subgingival scaling and root planing followed by a single episode of PDT ( test ) or subgingival scaling and root planing alone ( control ) . The following parameters were evaluated at baseline and at 3 months and 6 months after therapy : full mouth plaque score ( FMPS ) , full mouth bleeding score ( FMBS ) , bleeding on probing ( BOP ) at experimental sites , probing pocket depth ( PPD ) , gingival recession ( REC ) , and clinical attachment level ( CAL ) . Primary outcome variables were changes in PPD and CAL . Microbiological evaluation of Aggregatibacter actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , Prevotella intermedia ( P.i . ) , Tannerella forsythensis ( T.f . ) , Treponema denticola ( T.d . ) , Peptostreptococcus micros ( P.m . ) , Fusobacterium nucleatum ( F.n . ) , Campylobacter rectus ( C.r . ) , Eubacterium nodatum ( E.n . ) , Eikenella corrodens ( E.c . ) , and Capnocytophaga species ( C.s . ) was also performed at baseline and at 3 months and 6 months after therapy , using a commercially available polymerase chain reaction test . No differences in any of the investigated parameters were observed at baseline between the two groups . At 3 months and 6 months after treatment , there were no statistically significant differences between the groups in terms of PPD , CAL and FMPS . At 3 months and 6 months , a statistically significantly higher improvement of BOP was found in the test group . At 3 months after therapy , the microbiological analysis showed a statistically significant reduction of F.n . and E.n . in the test group . At 6 months , statistically significantly higher numbers of E.c . and C.s . were detected in the test group . The additional application of a single episode of PDT to scaling and root planing failed to result in an additional improvement in terms of PPD reduction and CAL gain , but it result ed in significantly higher reduction of bleeding scores than following scaling and root planing alone BACKGROUND AND OBJECTIVE The goal of this study was to investigate the effects of low level laser therapy ( LLLT ) in osteoporotic rats by means of subjective histopathological analysis , deposition of collagen at the site of fracture , biomechanical properties and immunohistochemistry for COX-2 , Cbfa-1 and VEGF . MATERIAL AND METHODS A total of 30 female Wistar rats ( 12weeks-old , ±250 g ) were su bmi tted to ovariectomy ( OVX ) . Eight weeks after the OVX , a tibial bone defect was created in all animals and they were r and omly divided into 3 groups ( n=10 ) : control bone defect group ( CG ) : bone defects without any treatment ; laser 60J/cm(2 ) group ( L60 ) : animals irradiated with LLLT , at 60J/cm(2 ) and laser 120J/cm(2 ) group ( L120 ) : animals irradiated with LLLT , at 120J/cm(2 ) . RESULTS In the laser treated groups , at both fluences , a higher amount of newly formed bone was evidence d as well as granulation tissue compared to control . Picrosirius analysis demonstrated that irradiated animals presented a higher deposition of collagen fibers and a better organization of these fibers when compared to other groups , mainly at 120J/cm(2 ) . COX-2 , Cbfa-1 or VEGF immunoreactivity was detected in a similar manner either 60J/cm(2 ) or 120J/cm(2 ) fluences . However , no differences were shown in the biomechanical analysis . CONCLUSION Taken together , our results support the notion that LLLT improves bone repair in the tibia of osteoporotic rats as a result of stimulation of the newly formed bone , fibrovascularization and angiogenesis This study evaluated the effect of low-level laser therapy ( LLLT ) on bone regeneration at the midpalatal suture ( MPS ) after rapid maxillary expansion ( RME ) , using cone beam computed tomography . Fourteen 8–14-year-old patients with transverse maxillary deficiency underwent RME with a Hyrax-type exp and er activated with one full turn after installation and two half turn daily activations until achieving overcorrection . Patients were r and omly assigned to either a control group ( RME alone , n = 4 ) or an experimental group ( n = 10 ) in which RME was followed by 12 LLLT sessions ( GaAlAs , p = 70 mW , λ = 780 nm , Ø = 0.04 cm2 ) . Two tomographic images of the MPS were obtained — T0 , after disjunction and T1 , after 4 months . Bone regeneration was evaluated by measuring the optical density ( OD ) on the tomographic images using InVivo Dental 5.0 software . Data were analyzed by the paired Student ’s t test ( α = 0.05 % ) . A statistically significant difference between T0 and T1 OD values was observed in the laser-treated group ( p = 0.00 ) , but this difference was not significant in the control group ( p = 0.20 ) . Intergroup comparison of OD values at T1 revealed higher OD in the laser-treated group ( p = 0.05 ) . In conclusion , LLLT had a positive influence on bone regeneration of the midpalatal suture by accelerating the repair process OBJECTIVE The aim of the study was to evaluate effect of the different frequencies of low-level laser radiation ( diode 670 nm and Helium-Neon 632.8 nm ) on the healing process after human molar extraction s. Frequencies of 5 Hz , 292 Hz , and 9,000 Hz were used in experiments . Monitoring of secretory IgA and albumin level in saliva and changes in bone density were used as objective markers of biostimulatory effect . SUMMARY BACKGROUND DATA From the literature , it is known that if the alveolus is irradiated after extraction along with the lingual and buccal bony wall , faster coagulation , less postoperative discomfort , and quicker healing can be expected . METHODS Subjective evaluation of therapy was observed using a scale ( from - , negative therapeutic effect , to + + + + , excellent treatment effect ) . Changes of secretory immunoglobulin A ( sIgA ) , albumin levels , and bone density were compared in a group of 150 patients ( nonlaser therapy , 30 patients ) . RESULTS Differences in levels of the saliva markers ( sIgA and albumin ) were found to be significant when comparing irradiated and nonirradiated groups , and in comparison with those groups irradiated by various modulatory frequencies . Significant differences were observed between the increase of sIgA res . albumin and subjective feelings during treatment . Bone density after extraction and 6 months after surgical treatment was examined using dental digital radiovisiography . No significant differences were detected between bone density in irradiated and nonirradiated groups , perhaps due to our therapy protocol . CONCLUSIONS The low-level laser has no influence on the process of osseointegration . This effect was observed on fracture healing in rats using He-Ne laser radiation . We found no differences in the bone density when compared to the control group To evaluate the effectiveness low-level laser therapy ( LLLT ) on the repair of the mid palatal suture , after rapid maxillary expansion ( RME ) . A single-operator , r and omized single-blind placebo-controlled study was performed at the Orthodontic Department at the Dental Hospital of Bellvitge . Barcelona University , Hospitalet de Llobregat , Spain . Thirty-nine children ( range 6–12 years old ) , completed RME and were r and omized to receive active LLLT ( n = 20 ) or placebo ( n = 19 ) . The laser parameters and dose were 660 nm , 100 mW , CW , InGaAlP laser , illuminated area 0.26 cm2 , 332 mW/cm2 , 60 s to four points along midpalatal suture , and 30 s to a point each side of the suture . A total of seven applications were made on days 1 , 7 , 14 , 28 , 42 , 56 , and 70 of the retention phase RME . A cone beam computed tomography ( CBCT ) scan was carried out on the day of the first laser treatment , and at day 75 , a second CBCT scan was performed . Two radiologists synchronized the slices of two scans to be assessed . P = 0.05 was considered to be statistically significant . At day 75 of the suture , the irradiated patients presented a greater percentage of approximate zones in the anterior ( p = 0.008 ) and posterior ( p = 0.001 ) superior suture— and less approximation in the posterior superior suture ( p = 0.040)—than the placebo group . LLLT appears to stimulate the repair process during retention phase after RME AIM The aim of this study was to evaluate the immediate post-operative pain , wound healing and clinical results after the application of an enamel matrix protein derivative ( EMD ) alone or combined with a low-level laser therapy ( LLLT ) for the treatment of deep intra-bony defects . MATERIAL AND METHODS This study was an intra-individual longitudinal test of 12 months ' duration conducted using a blinded , split-mouth , placebo-controlled and r and omized design . In 22 periodontitis patients , one intra-bony defect was r and omly treated with EMD+LLLT , while EMD alone was applied to the contra-lateral defect site . LLLT was used both intra- and post-operatively . Clinical measurements were performed by a blinded periodontist at the time of surgery , in the first week and in the first , second , sixth and 12th month . Visual analogue scale ( VAS ) scores were recorded for pain assessment . RESULTS The results have shown that the treatment of intra-bony defects with EMD alone or EMD+LLLT leads to probing depth reduction and attachment-level gain . In addition , EMD+LLLT had result ed in less gingival recession ( p<0.05 ) , less swelling ( p<0.001 ) and less VAS scores ( p<0.02 ) compared with EMD alone . CONCLUSION This study shows that EMD is an effective , safe and predictable bio material for periodontal regeneration and LLLT may improve the effects of EMD by reducing post-operative complications BACKGROUND Many studies have examined laser treatment of scars , but cosmetic results have been variable . Although no studies have examined the effect of purpura on scar improvement using the pulsed dye laser ( PDL ) , many clinicians believe inducing purpura results in better and quicker improvement . OBJECTIVE To determine whether PDL treatment of fresh surgical scars with purpura‐inducing setting s improves clinical appearance more than non‐purpura‐inducing setting s or no treatment . METHODS Twenty‐six subjects with surgical scars enrolled in this prospect i ve study . Scars were divided into three equal segments ; treatment was r and omized : 595‐nm PDL with purpuric ( 1.5 ms ) or nonpurpuric ( 10 ms ) setting s or no treatment . Fluences were adjusted to Fitzpatrick skin type . Scars were treated three times , 1 month apart , beginning at suture removal . Outcome measures included Vancouver Scar Scale ( VSS ) and blind clinical ratings . RESULTS The nonpurpuric condition showed significant improvement on the VSS total score , vascularity , and pliability ratings . The purpuric condition demonstrated a trend for improvement on the VSS total . According to blind observer ratings , all conditions improved , without differences between groups . CONCLUSION Nonpurpuric setting s on the PDL result ed in significant improvements in the appearance of fresh surgical scars for vascularity , pliability , and VSS total scores , although all scar segments improved over time OBJECTIVE The aim of this study was to evaluate the effects of laser therapy on bone regeneration in the midpalatal anterior suture ( MPAS ) after surgically assisted rapid maxillary expansion ( SARME ) . METHODS Thirteen patients aged between 18 and 33 years old with maxillary transverse deficiency ( > or = 7.0 mm ) were evaluated . All patients underwent subtotal Le Fort I osteotomy with separation of the pterygomaxillary suture with the use of Hyrax exp and er , and were divided into 2 groups : control group ( n = 6 ) and laser group ( n = 7 ) . A GaAlAs laser ( P = 100 mW , lambda = 830 nm , Ø = 0.06 cm(2 ) ) was used . The laser was applied in 8 treatment sessions with intervals of 48 hours . Each treatment session consisted of laser applications , per point ( E = 8.4J , ED = 140J/cm(2 ) ) , at 3 points on the MPAS , and total dose of E = 25.2 J , ED = 420 J/cm(2 ) . Digital radiographs were taken before the surgical procedure and at 1- , 2- , 3- , 4- , and 7-month follow-up visits . Optical density analysis of the regenerated bone was performed using Adobe Photoshop 8.0 software . RESULTS Bone regeneration associated with the use of laser after SARME showed a statistically significant difference . A higher mineralization rate was found in the laser group ( 26.3 % , P < .001 ) than the control group . CONCLUSION Low-level laser irradiation ( GaAlAs ) accelerates bone regeneration in MPAS after SARME . However , the optical density measurements after 7 months of follow-up were lower in comparison with the preoperative measurements The purpose of this study was to assess the effect of 810-nm ( DMC Equipamentos , Sao Carlos , Brazil ) continuous wave low-level laser therapy ( LLLT ) on the pain caused by orthodontic elastomeric separators . Thirty-seven orthodontic patients ( 12 male and 25 female , aged 11–32 years , mean age = 24.97 years ) participated in the study , including 20 subjects aged 18 years or more , and 17 under 18 years of age . Four elastomeric separators ( Dentarum , Springen , Germany ) were placed for the first permanent molars ( distal and mesial ) , either for maxillary ( 22 patients ) or m and ibular ( 15 patients ) arches ; one quadrant was r and omly selected and used as a placebo group ( received no laser irradiation ) . After separator placement for each quadrant , patients received 10 doses ( 2 J/cm2 , 100 mW , 20 s ) of laser irradiation on the buccal side ( at the cervical third of the roots ) , for distal and mesial of the second premolars and first permanent molars , as well as distal of second permanent molars ( five doses ) . The same procedure was repeated for the lingual or palatal side ( five doses ) . After 24 h , patients returned to the clinic and received another 10 doses of laser irradiation on the same quadrant . Postseparation pain level recorded on a 10-cm visual analog scale for both jaws immediately ( hour 0 ) , and after 6 , 24 , 30 h , as well as on days 3 , 4 , 5 , 6 , and 7 . Significant differences in the pain perception ( PP ) were found between the laser and placebo groups at 6 , 24 , 30 h , and day 3 of the experiment ( P < 0.05 ) . Friedman ’s test of multiple comparisons revealed significant differences in the PP among various time intervals for laser ( chi-square = 173.407 , P = 0.000 ) and placebo ( chi-square = 184.712 , P = 0.000 ) groups . In both groups , pain was highest at 6 and 30 h after placing elastomeric separators . No gender differences were observed in both groups . More pain was recorded in the m and ible ( P < 0.05 ) at 24 ( laser group ) and 30 h ( both groups ) after starting the experiment . The PP was significantly higher ( P < 0.05 ) for the group aged 18 years or more , only at days 3 [ both groups ] and 4 [ laser group only ] of the experiment . The 810-nm continuous wave LLLT significantly reduced the PP in the first 3 days after orthodontic separation . However , the mean postseparation PP in both groups was low and wide ranges of PP scores were observed Among the available techniques to treat gingival recession , connective tissue graft ( CTG ) presents more foreseeability and better results in the long term . However , this technique causes morbidity and discomfort in the palatine region due to graft removal at that site . The aim of this clinical trial was to evaluate the influence of low-level laser therapy ( LLLT ) on the healing of the donor palatine area after CTG . Thirty-two patients presenting buccal gingival recession were selected and r and omly assigned to receive LLLT irradiation ( test group ) or LLLT sham ( control group ) in the palatine area after connective graft removal . A diode laser ( AsGaAl , 660 nm ) was applied to test the sites immediately after surgery and every other day for 7 days . The evaluated parameters were wound remaining area ( WRA ) , scar and tissue colorimetry ( TC ) , tissue thickness ( TT ) , and postoperative discomfort ( D ) . These parameters were evaluated at baseline and 7 , 14 , 45 , 60 , and 90 days after surgery . Two-way repeated measures ANOVA was used for analysis . The test group presented statistically significant smaller wounds at days 14 and 45 . None of the patients presented a scar at the operated area , and colorimetry analysis revealed that there was no statistically significant difference between groups ( p > 0.05 ) . Patients reported mild to moderate discomfort , with low consumption of analgesic pills . We concluded that LLLT irradiation can accelerate wound healing on palatine mucosa after connective tissue removal for root coverage techniques ( Clinical Trial.org NCT02239042 ) This study assessed the effects of low-level laser treatment in combination with scaling and root planing ( SRP ) in patients with periodontitis . Sixty subjects with chronic advanced periodontitis were assigned r and omly to three treatment groups ( n = 20 ) after collecting gingival clinical parameters . Group A received SRP on a single quadrant per day for four consecutive days ; on the fifth day , all quadrants were rescaled . Group B received the same treatment as Group A , followed by laser application for five days . Group C received the same treatment as Group B but the laser treatment was administered for a total of 10 days . For Groups B and C , a low-level diode laser ( 630 to 670 nm ) was used . The plaque index , gingival index , and sulcular bleeding index were recorded for all groups . For all clinical parameters , all three groups reported statistically significant differences ( p < 0.005 ) compared to baseline data . Compared to Group A , Groups B and C showed statistically significant improvement for all clinical parameters . These findings suggest that a low-level diode laser can have a beneficial effect for treating inflammatory chronic advanced periodontitis BACKGROUND The pulsed dye laser ( PDL ) has long been used for treatment of erythematous and hypertrophic scars . Its effectiveness has been attributed in large part to its vascular-specificity . The vascular-specific potassium titanyl phosphate ( KTP ) laser has also been reported to be clinical ly effective for scars , but has not been compared to the PDL . OBJECTIVE To compare the safety and clinical efficacy of a 532-nm KTP laser versus a 595-nm PDL in improving the appearance of erythematous surgical scars . METHODS Twenty patients with matched bilateral erythematous surgical scars or a single linear erythematous scar measuring longer than 5 cm were enrolled in the study . Single scars were divided into equal halves with each half r and omized to receive 3 successive treatments at 6-week intervals with either a 532-nm KTP laser ( Excel V ; Brisbane , CA ) or a 595-nm PDL ( Cynergy ; Cynosure Inc. , Chelmsford , MA ) at equivalent laser parameters . Bilateral matched scars were similarly r and omized to receive three 532-nm KTP or 595-nm PDL treatments . Clinical efficacy was evaluated 12 weeks after the third ( final ) laser treatment by independent , blinded photographic scar assessment s. Secondary evaluations included final investigator and subject treatment/satisfaction assessment s , Vancouver scar scale ( VSS ) scores , subject scar symptoms , intraoperative pain scores , and incidence of side effects . RESULTS Clinical improvement of erythematous surgical scars was observed with both 532-nm KTP and 595-nm PDL systems . No statistically significant differences between the 2 treatment arms were noted in the independent , blinded photographic scar assessment s , investigator and subject treatment/satisfaction assessment s , subject scar symptoms , and intraoperative pain scores . The KTP arm produced statistically significant improvement for the vascularity component of the VSS only . Side effects were limited to mild treatment discomfort and minimal transient post-treatment erythema and purpura . No vesiculation , infection , scarring or other adverse events were experienced . Subject satisfaction surveys mirrored the observed clinical effects . CONCLUSION The-532 nm KTP laser is comparable in efficacy and safety to the 595-nm PDL laser in the treatment of erythematous surgical scars OBJECTIVE The therapeutic outcomes of low-level laser therapy ( LLLT ) on closed bone fractures ( CBFs ) in the wrist and h and were investigated in this controlled study . BACKGROUND DATA Animal research has confirmed that LLLT increases osteocyte quantity ; however , little research has been conducted to determine the effect of LLLT on the treatment of human bone fractures . METHODS In this study , the therapeutic outcomes of administering 830 nm LLLT to treat CBFs in the wrist or h and were examined . Fifty patients with CBFs in the wrist and h and , who had not received surgical treatment , were recruited and r and omly assigned to two groups . The laser group underwent a treatment program in which 830 nm LLLT ( average power 60 mW , peak power 8 W , 10 Hz , 600 sec , and 9.7 J/cm(2 ) per fracture site ) was administered five times per week for 2 weeks . Participants in a placebo group received sham laser treatment . The pain , functional disability , grip strength , and radiographic parameters of the participants were evaluated before and after treatment and at a 2-week follow-up . RESULTS After treatment and at the follow-up , the laser group exhibited significant changes in all of the parameters compared with the baseline ( p<0.05 ) . The results of comparing the two groups after treatment and at the follow-up indicated significant between-group differences among all of the parameters ( p<0.05 ) . CONCLUSIONS LLLT can relieve pain and improve the healing process of CBFs in the human wrist and h and |
2,490 | 24,402,059 | Rehabilitations with 2 implants showed more complications and required more maintenance according to the connection type .
Given the limitations of this review , m and ibular overdentures with 4 implants showed better results with respect to survival and success rates , especially those with a bar connection . | This systematic review evaluated the influence played by the number of implants on the results of rehabilitation treatment with m and ibular overdentures on 2 or 4 implants . | PURPOSE The present study evaluated implant and peri-implant outcomes as well as prosthodontic maintenance efforts for implant/bar-supported m and ibular prostheses with different prosthesis anchorage systems . MATERIAL S AND METHODS Seventy-six patients who received two or four interforaminal implants were assigned to one of three different bar design s and subsequently to different prosthesis supporting systems . Forty-nine patients received implants and a mucosa-supported implant-retained overdenture ( OD ) with an ovoid bar ( two implants ; design 1 ) or multiple ovoid bars ( four implants ; design 2 ) . Twenty-seven patients received four implants and a rigid implant-supported prosthesis ( ISP ) with a milled bar ( design 3 ) . Implant survival , peri-implant parameters ( marginal bone resorption , pocket depth , and plaque , bleeding , gingival , and calculus indices ) , and postinsertion prosthodontic maintenance were followed over a 5-year period and compared among the different retention modalities . At the most recent follow-up examination , subjective patient satisfaction was additionally evaluated using a simplified scoring system ( ranging from 1 = not satisfactory to 5 = excellent ) . RESULTS Implant survival rates ( 100 % ) and all peri-implant parameters evaluated showed no differences among the three design s used for implant prosthesis anchorage . Prosthodontic maintenance did not differ between the different ODs ( OD design 1 : average of 1.04 maintenance visits/year/patient ; OD design 2 : 1.2 maintenance visits/year/patient ) , but it was significantly lower for the dentures that were rigidly stabilized with milled bars ( ISP : 0.37 maintenance visits/year/patient ) . A high subjective satisfaction rate ( range : 4.5 to 5.0 ) was registered at the final examination , without any differences among the design s used . CONCLUSIONS Rigid anchorage with milled bars on four-implant prostheses combined with a metal-reinforced framework showed a lower extent of prosthodontic maintenance issues than round bars on two- or four-implant overdentures with resilient denture stabilization . Nevertheless , implants and peri-implant structures were not negatively affected by either resilient or rigid anchorage mechanisms This study is a two-center clinical trial with the aim to assess the treatment effects of implant-retained m and ibular overdentures versus conventional complete dentures . Treatment had been assigned according to a balanced allocation method . The following criteria were used to enhance the comparability of the treatment groups : age , gender , the edentulous period of the m and ible , the number of previously made m and ibular dentures , the number of years having worn the present m and ibular denture and the symphyseal bone height . 151 patients with severely resorbed m and ibles participated in the study , they were treated at two centers . Ninety-one patients received an implant-retained m and ibular overdenture ( IRO ) and 60 patients a conventional complete denture ( CD ) . Since some patients refused the allocated treatment the " Intention To Treat " principle was applied . This implies that patients are evaluated in the originally allocated treatment group regardless of the actual treatment they received . Patient 's experiences were evaluated before treatment and 1 yr after insertion of the new dentures . Results before treatment showed that both treatment groups were comparable : they were dissatisfied with their m and ibular denture and they could hardly chew tough or hard foods . One year after insertion of the new dentures the IRO-group was satisfied with their m and ibular denture , whereas only one third of the CD-group was satisfied . With respect to the chewing ability the IRO-group scored significantly better than the CD-group(P<0.0001 ) PURPOSE The aim of this research was to determine the long-term prosthodontic maintenance requirements of m and ibular two-implant overdentures using different loading protocol s and attachment systems . MATERIAL S AND METHODS A total of 106 participants were allocated r and omly to one of four different implant systems ( Steri-Oss , Southern , Straumann , or Branemark ) . Three different loading protocol s ( 2 , 6 , and 12 weeks ) were used with six different ball abutment patrices and their respective matrices ( Steri-Oss rubber , Straumann gold , Straumann titanium , Branemark gold , Southern plastic , and Southern gold/platinum ) . Prosthodontic maintenance events were documented prospect ively from baseline until the 8-year recall according to predefined categories . RESULTS After 6 years , 90 participants attended recall and , thereafter , 68 participants were followed for 8 years . No significant differences were found between the number of prosthodontic maintenance events and the loading protocol used . Steri-Oss rubber matrices had the highest mean number of maintenance events at 32.2 ± 14.5 events , followed by the Branemark gold matrices at 28.8 ± 12.6 events . The Southern plastic matrices had a significantly lower mean number of maintenance events ( 8.7 ± 4.2 ) when compared with all other groups . Over a 6-year period , the matrices with the best longevity were Straumann gold at 3.9 ± 2.1 years . Straumann gold matrices also lasted significantly longer than all other matrices ( P < .05 ) . Southern gold/platinum , Branemark gold , and Southern plastic matrices all lasted significantly longer than the Straumann titanium and Steri-Oss matrices ( P < .05 ) . The mean time to reline for overdentures was 3.37 ± 2.06 years ; remaking of overdentures peaked by year 7 , with a mean time to remake of 5.81 ± 2.04 years . CONCLUSION Early loading protocol s do not influence long-term prosthodontic maintenance requirements of unsplinted m and ibular two-implant overdentures . By contrast , attachment systems do influence prosthodontic maintenance , particularly with regard to the type of matrices used PURPOSE This prospect i ve study evaluated the prosthodontic maintenance requirements during the first year of service of m and ibular overdentures supported by two unsplinted implants using three different implant systems . MATERIAL S AND METHODS Seventy-two patients r and omly allocated to three equal groups were each provided with a conventional complete maxillary denture and a m and ibular overdenture supported by two unsplinted implants . A different implant system was used for each group ( Steri-Oss , ITI , or Southern Implants ) , and their prosthodontic maintenance requirements were compared , primarily for the patrix and matrix . Additional maintenance categories recorded included any type of overdenture fracture , reline or remake of the overdenture , and maintenance of the maxillary denture . RESULTS Sixty-eight percent of the patients , regardless of implant system , required prosthodontic maintenance in the first year , most commonly for the matrices . The Southern Implants matrices required less maintenance than those of Steri-Oss or ITI ( P < .05 ) . Additional overdenture maintenance was required by 28 % of patients , irrespective of implant system . When all categories of prosthodontic maintenance were combined , there were no differences between implant groups . Evaluation of overall prosthodontic success using six-field tables revealed statistically significant differences between the three implant systems , with more ITI and Steri-Oss patients than Southern Implants patients requiring overdenture retreatment ( repair ) . CONCLUSION During the first year of service , the matrix maintenance requirements of Southern Implants were significantly lower than those of the ITI or Steri-Oss groups ; this was reflected in the number of retreatment ( repair ) categories recorded . Although the three systems did not differ significantly for overall prosthodontic maintenance , both the Steri-Oss and the ITI titanium matrices showed problems of clinical significance PURPOSE Implant success , peri-implant conditions , and prosthodontic maintenance requirements were evaluated and compared for m and ibular overdentures supported by two implants and retained with ball or resilient telescopic crown attachments during a 5-year period . MATERIAL S AND METHODS Twenty-five patients with an edentulous m and ible each received two root-form dental implants in the m and ibular interforaminal ( canine ) region . The type of denture attachment was chosen r and omly ; 13 patients received ball attachments and 12 patients received resilient telescopic crowns . Implant success and peri-implant conditions ( bone resorption , pocket depth , Plaque Index , Gingival Index , Bleeding Index ) as well as prosthodontic maintenance and patient satisfaction were evaluated annually during a 5-year follow-up period and compared with respect to the two retention modalities used . RESULTS Implant success , peri-implant conditions , and subjective patient satisfaction scores did not differ between the two retention modalities used . However , during the 5-year observation period , significantly more postinsertion complications/ interventions for maintenance purpose s were registered in the ball group ( 87 interventions , 61.1 % ) than in the telescopic crown group ( 53 interventions , 37.9 % ; P < .01 ) . Differences in prosthodontic maintenance efforts were most significant in the second and third years ( P < .05 ) of the follow-up period but were similar at the end of the study for both anchorage systems . CONCLUSION Both ball attachments and resilient telescopic crowns on isolated implants in the atrophic m and ible are viable treatment options for implant-supported overdentures . No implant losses , good peri-implant conditions , and general patient satisfaction were noted . Although the frequency of technical complications was initially higher with ball attachments than with resilient telescopic crowns over a 5-year period , similar frequencies of maintenance efforts may be anticipated for both retention modalities In this prospect i ve multicenter study , non-submerged ITI implants were followed in order to evaluate their long-term prognosis in fully edentulous jaws . A total of 1286 implants were inserted in 233 consecutive patients and , after a healing period of three to six months , the successfully integrated implants were restored with 163 overdentures and 95 fixed full-arch bridges . This prospect i ve study not only calculated the 10-year cumulative survival and success rates for the 1286 implants by life table analysis , but also evaluated the actual survival and success rates for 498 implants after at least five years of functional loading . In addition , cumulative success rates were calculated for implant subgroups according to implant length and location . Additional analyses were performed to evaluate the estimated and actual survival and success rates of the implants in relation to various prosthetic rehabilitation techniques . The 10-year cumulative survival and success rates were 95.9 % and 92.7 % , respectively . The actual 5-year survival and success rates of the first 498 implants that were inserted were 97.7 % and 95.0 % , respectively . The analysis of implant subgroups showed slightly more favourable cumulative success rates for 12 mm long implants ( 93 % ) , in comparison to 10 mm and 8 mm long implants ( 91.6 % and 89.6 % , respectively ) . The cumulative success rate for m and ibular implants ( approximately 94 % ) was also more favourable than that for maxillary implants ( approximately 91 % ) . Patients who were loaded with both maxillary and m and ibular prostheses maintained success rates well above 90 % ; while only implants that were inserted to support maxillary overdentures that were retained by Dolder bars showed a success rate below 90 % 86 patients , in 2 Sc and inavian centers , participated in a prospect i ve study of m and ibular edentulism , treated with overdentures supported by Bioceram sapphire implants . Implant success and prosthesis stability as well as parameters for peri-implant health were evaluated . Masticatory function and complications were also documented . The study began in 1991 and clinical treatment of the last patients was completed in 1991 . The patients have been followed for at least 3 years , and up to 12 years . 4 patients were lost to follow-up . Of the initial 324 implants , 7 implants failed before prosthetic treatment . 3 patients lost 1 implant each within the 1st year , and 4 patients lost all 4 implants . 16 implants were lost between 36 and 42 months in function , due to lack of osseointegration and pain . The loss of implants could be attributable to an association , not statistically verified , between bone quality and anatomy , with heavy smoking as a risk factor . Based on the remaining implants , the cumulative implant success rates were 95.2 % , 91.3 % , 91.3 % , 91.3 % at 3 , 5 , 10 and 12 year follow-up respectively . The cumulative success rates for overdentures were 96.4 % , 92.8 % and 92.8 % respectively , for the same follow-up periods . Indices for the health of the peri-implant mucosa disclosed no serious inflammatory reactions in the surrounding soft tissues . Patient satisfaction with this form of oral rehabilitation was high in all but 2 patients who experienced discomfort This prospect i ve study has been design ed to compare the results of immediate and delayed loading of implant-retained m and ibular overdentures after a 2-year follow-up . Twenty patients have been r and omly divided into two groups . Group 1 patients ( test group ) received four ITI implants in the intraforaminal area of the m and ible . Octa abutments were immediately screwed on implants ; 2 days after surgery , the implants were rigidly connected with a U-shaped Dolder gold bar and loaded with an overdenture . Group 2 patients ( control group ) received , in the same area , the same type and number of implants , which were left to heal according to the st and ard protocol . At 3 - 4 months , Octa abutments were screwed on the implants and the same prosthetic procedure of the test group was applied . The minimum follow-up period lasted 2 years , with recall appointments at 2 weeks , 1 , 3 , 6 months , 1 year and every following year postoperatively , evaluating : MPI , MBI , PD , Periotest and radiographic peri-implant bone resorption . Success criteria according to Albrektsson et al. were used . Only one implant out of the 40 of group 2 failed , whereas none failed in group 1 . No statistical difference of the clinical parameters evaluated was noticed in the two groups . Therefore , immediate loading of implants , if connected with a U-shaped bar , can provide the same results of the ' traditional ' technique as far as osseointegration and short-term survival rates of implants are concerned . Moreover , this method significantly shortens the treatment period , thus increasing patient satisfaction PURPOSE This prospect i ve study was performed to evaluate the outcomes of XiVE ® S plus implants ( Dentsply Friadent , Mannheim , Germany ) following conventional restoration with bar structures and overdentures in the edentulous m and ible . MATERIAL S AND METHODS A total of 39 patients were treated with four interforaminal implants ( n = 156 ) splinted by a Dolder bar . Overdentures were attached to the bars after 3 months of healing . As primary outcome measures , clinical and radiological parameters were evaluated at the time of implant placement ( baseline ) and once a year ( 1 , 2 , 3 , 4 , 5 years ) after functional loading . Secondary outcome measures included ( i ) primary stability and surgical complications , as well as ( ii ) Periotest ® ( Medizintechnik Gulden , Modautal , Germany ) values , implant survival , and prosthetic complications at baseline and follow-up . RESULTS A total of 156 implants were placed . The vast majority ( n = 149 ) were tightened to > 30 Ncm , while torques in the range of 20 - 30 Ncm were obtained in the remaining cases ( n = 7 ) . Mean crestal bone levels around the implants were 0.41 mm at baseline and 1.04/1.20/1.34/1.45/1.44 mm after 1/2/3/4/5 years respectively . The mean values of the plaque , calculus , bleeding , and mucosal indices remained low throughout this period . The reported follow-up periods involved one implant loss after 3 months ( survival rate : 99.4 % ) and one implant failure after 4 years ( success rate : 98.4 % ) . Prosthetic complications included factures of bars ( n = 3 ) and denture teeth ( n = 7 ) . Prosthetic survival was 100 % . CONCLUSIONS Dolder bars to restore oral implants in the edentulous m and ible appear to offer a high rate of implant survival , good stability of the peri-implant tissue , and a low rate of prosthetic complications This report presents the results of a 5-year prospect i ve multicenter study including nine centers worldwide . A total of 30 patients received 117 Brånemark implants in the maxillae , and 103 patients received 393 implants in the m and ibles . According to the protocol , all integrated maxillary implants were to be loaded ; however , only two of four m and ibular implants were planned for support of the overdentures , leaving the remaining implants covered by mucosa as backup for possible implant failures . Thirty-five patients ( 26.3 % ) who were provided with 127 implants ( 24.9 % ) were withdrawn from the study . Six patients treated in the maxilla lost all their implants and resumed wearing complete dentures . The cumulative success rates for implants and for overdentures supported by two implants in the edentulous m and ible were 94.5 % and 100 % , respectively . The corresponding cumulative success rates for implants and for overdentures supported by an optimal number of implants in the maxilla were 72.4 % and 77.9 % , respectively . Significantly better jawbone characteristics at the time of implant surgery were considered to contribute to the better cumulative success rates in the m and ibles . Mean marginal bone loss was 0.8 mm ( SD 0.8 ) and 0.5 mm ( SD 0.8 ) for loaded implants during a 5-year period of time in the maxillae and m and ibles , respectively . Measurements of the clinical height of the abutment cylinders indicated a mean recession ( 0.2 mm ) of peri-implant mucosa during the follow-up period in the m and ibles . Conversely , hyperplasia was observed in the maxillae Nine clinical centers participated in a prospect i ve study of overdentures supported by Brånemark implants in the maxilla or m and ible . The study initially comprised 133 patients provided with 117 implants placed in the maxilla and 393 implants placed in the m and ible . The preliminary results indicate a success rate in the m and ible comparable with the reports on fixed prostheses . Conversely , overdenture treatment in the maxilla seems to be less favorable than previous reports of fixed restorations . The differences between the fixed and the present overdentures in the maxilla were mainly based on differences in patient selection and bone quality . A total of 32 implants was mobile and removed and another 29 implants were lost to follow-up because of patient dropout up to the first annual checkup after denture placement . A higher implant failure rate occurred in the maxilla . Mucosal reactions were also more unfavorable around implants placed in the maxilla In a 5-year prospect i ve clinical study , 155 endosseous implants were installed in the m and ible anterior to the mental foramina in 33 edentulous patients ( 13 males and 20 females ) . Usually 6 implants were installed for fixed prostheses ( FP ) , 13 patients with 77 implants , and 4 implants for overdentures ( OD ) with a Dolder bar , 20 patients with 78 implants . At the time of abutment connection 1 implant in 2 patients was found to be loose and removed . However , in both these patients overdentures were successfully placed on the remaining 3 implants . Narrow-beam radiography was used for radiological evaluation . The mean ( SD ) total marginal bone loss in 5 years was 0.48 ( 0.38 ) mm ( 0.36 ( 0.22 ) mm in the FP group and 0.56 ( 0.45 ) mm in the OD group ) . Very few complications were reported during the 5 years , most of them being related to the superstructures . The overall cumulative implant survival rate was 98.7 % ( 100 % in the FP group and 97.4 % in the OD group ) . The survival rate of the superstructures was 100 % . The present study has demonstrated that Astra Tech implants offer reliable and predictable medium-term support for fixed prostheses and overdentures in the edentulous m and ible An international prospect i ve study of Brånemark implants retaining overdentures was conducted at nine clinical centers . One hundred thirty-three subjects were recruited in a 12-month period and provided with 510 implants , 117 of which were in maxillae and 393 were in m and ibles . This study reports the 3-year follow-up status of 120 overdentures and 444 implants . There were 11 overdenture failures ( 9.2 % ) . Maxillary overdenture failure rates ( 27.6 % ) were nearly nine times greater than m and ibular overdenture failure rates ( 3.3 % ) . Maxillary overdenture treatment was less successful than previously reported fixed implant-supported restorations . However , their m and ibular counterparts had success rates slightly higher than those reported for fixed implant-supported restorations . At 3 years , 150 implants remained submerged and 66 implants had been withdrawn because the subjects discontinued study participation . Eleven m and ibular and 29 maxillary implants had failed and had been removed from 21 subjects . Logistic regression with forward model selection indicated that one two-way interaction was significantly related to implant failure . At highest risk were the subjects who possessed dental arches with bone quantity E and bone quality 4 . Subjects with one implant failure were likely to have more than one failure . The Generalized Estimating Equation was used to adjust for the cluster effect in this population because multiple implants ( 2 to 6 ) were placed and evaluated in each of the 133 subjects |
2,491 | 27,904,549 | In addition , N. sativa reduced levels of glycosylated hemoglobin ( HbA1c ) .
Our systematic review revealed that N. sativa supplementation might be effective in glycemic control in humans | BACKGROUND Nigella sativa ( N. sativa ) has been used in traditional medicine and several studies have been performed in the last decades to reveal the effects of it on different medical disorders such as diabetes , dyslipidemia , hypertension , and obesity .
We evaluated the effects of N. sativa supplementation on lipid profiles , glycemic control , blood pressure ( BP ) , and some anthropometric indices in humans . | AIM : The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries , especially in the Middle East and in Southeast Asia . This plant has been a focus of much research . This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome . MATERIAL S AND METHODS : This prospect i ve study was conducted at a tertiary health care center in North India . After confirmation of diagnosis , 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study . Written informed consent was taken from all the patients enrolled . Approval from the institutional ethical committee was also obtained . The patients were divided into two groups of 30 each . In group I ( the st and ard group ) , patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks . In group II ( the N. sativa group ) , the patients were advised tablet atorvastatin 10 mg once a day , tablet metformin 500 mg twice a day , and N. sativa oil 2.5 ml twice daily for a period of 6 weeks . Fasting and postpr and ial blood glucose , fasting lipid profile , and waist circumference were recorded before therapy and after completion of therapy . RESULT : The treatment group showed significant ( P < 0.05 ) improvement with reference to total cholesterol , low density lipoprotein cholesterol ( LDL-C ) , and fasting blood glucose ( P < 0.05 ) . CONCLUSION : N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome . N. sativa oil has a significant activity in diabetic and dyslipidemic patients Hypertension ( HT ) is a lifestyle‐related disease and dietary modifications are effective for its management and prevention . We conducted a r and omized , double‐blind , placebo‐controlled trial to evaluate the efficacy of treatment with an oral Nigella sativa ( NS ) seed extract supplement in patients with mild HT . Subjects were r and omized into three groups : a placebo and two test groups that received 100 and 200 mg of NS extract twice a day . After 8 weeks , systolic blood pressure ( SBP ) values in both case groups were found to be significantly reduced when compared with the baseline values for each group . In addition , the decrease in SBP in the two case groups was statistically significant relative to the placebo group ( P < 0.05–0.01 ) . Meanwhile , diastolic blood pressure ( DBP ) values in the case groups were found to be significantly reduced from the baseline and a significant reduction was also observed in these groups ( P < 0.01 ) when compared with the placebo group . In addition , extract administration reduced both SBP and DBP in a dose‐dependent manner . Meanwhile , NS extract caused a significant decline in the level of total and low‐density‐lipoprotein (LDL)‐cholesterol relative to baseline data . No complications caused by NS were observed . The results suggest that the daily use of NS seed extract for 2 months may have a blood pressure‐lowering effect in patients with mild HT Background The risk of cardiovascular diseases ( CVD ) is increased tremendously among menopausal women , and there is an increasing dem and for alternative therapies for managing factors like dyslipidemia that contribute to CVD development . Methods In this study , Nigella sativa was evaluated for its hypolipidemic effects among menopausal women . In a r and omised trial , hyperlipidemic menopausal women were assigned to treatment ( n = 19 ) or placebo groups ( n = 18 ) , and given N. sativa or placebo for two months after their informed consents were sought . At baseline , blood sample s were taken and at one month intervals thereafter until one month after the end of the study . Results The results showed that N. sativa significantly improved lipid profiles of menopausal women ( decreased total cholesterol , low density lipoprotein cholesterol and triglyceride , and increased high density lipoprotein cholesterol ) more than the placebo treatment over 2 months of intervention . One month after cessation of treatment , the lipid profiles in the N. sativa-treated group tended to change towards the pretreatment levels . Conclusions N. sativa is thought to have multiple mechanisms of action and is cost-effective . Therefore , it could be used by menopausal women to remedy hypercholesterolemia , with likely more benefits than with single pharmacological agents that may cause side effects . The use of N. sativa as an alternative therapy for hypercholesterolemia could have profound impact on the management of CVD among menopausal women especially in countries where it is readily available BACKGROUND Natural products are proved to play a good role as an alternative to synthetic chemicals in many clinical conditions . Hypercholesterolemia is the most important risk factor for atherosclerosis . Previous studies showed that Nigella sativa L. has both antioxidant and lipid lowering potentials . THE AIM OF THIS STUDY To evaluate the efficacy of the seeds of Nigella sativa on the treatment of hyperlipidemia . METHODS In this r and omized , placebo controlled clinical trial which was conducted in Isfahan city ( Iran ) , 88 subjects aged > or = 18 years with a total cholesterol concentration > 200 mg/dl were included . According to the patients " profiles number , they were r and omized to receive either N. sativa capsules or the matching placebo . Each N sativa capsule contained 500 + /- 10 mg N. sativa crushed seeds , and patients had to take 2 g N. sativa per day for 4 weeks . Fasting baseline laboratory values ( fasting blood sugar , total cholesterol , low density lipoprotein , high density lipoprotein and triglyceride ) were obtained for all parameters on each subject prior to the start of the study and at the end of 4 weeks . RESULTS In our study a significant decrease was observed in the concentration of total cholesterol ( 4.78 % ) , Low density lipoprotein ( 7.6 % ) and Triglyceride ( 16.65 % ) , and this decrease was more significant for TG concentration . N. sativa had not any beneficial effects on Fasting blood sugar and High density lipoprotein . CONCLUSION According to the results of our present study it seems that N. sativa may have some beneficial therapeutic effects in the treatment of hyperlipidemia . However , further investigations with a larger sample size are necessary OBJECTIVES Evaluation of therapeutic potentials of α-lipoic acid ( α-LA ) , L-carnitine , Nigella sativa ( N. sativa ) or combination of them in carbohydrate and lipid metabolism of DM type I. METHODS Rat model of diabetes was induced by single i.p injection of Streptozocin ( STZ ) 65 mg/kg . The rats were r and omly assigned to 6 groups ( G ) : healthy reference ( HR ) , diabetic ( DM ) , DM treated with α-lipoic acid , DM treated with L-carnitine , DM treated with N. sativa , and DM treated with combination of the 3 compounds . After 30 days from onset of diabetes , serum and tissue homogenate were obtained for evaluation of glucose metabolism as fasting blood glucose , insulin , insulin sensitivity , HOMA , C-peptide , and pyruvate dehydrogenase ( PDH ) activity . For lipid metabolism evaluation , total cholesterol and triacylglycerol ( TG ) were determined . Markers of antioxidants and oxidative status as total antioxidant capacity ( TAC ) , glutathione-S-transeferase ( GST ) , 8-hydroxy-2-deoxyguanosine ( 8-OH-dG ) were measured . RESULTS Either α-LA or N. sativa significantly reduced the elevated blood glucose level . The combination of 3 compounds significantly increased the level of insulin and C-peptide . Also , increased the antioxidant activity measured by TAC and decreased the oxidative damage of DNA as measured by 8-OH-dG. HOMA- β increased in G3 and G6 compared to G2 . However , the decrease in TG , and total cholesterol levels were non-significant in all groups . CONCLUSION Combination of α-LA , L-carnitine and N. sativa will contribute significantly in improvement of the carbohydrate metabolism and to less extent lipid metabolism in diabetic rats , thus increasing the rate of success in management of DM . Also , this combination will have implication s in clinical studies and clinical applications 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 This experiment was carried out to investigate the effect of N. sativa L. on histopathology of pancreatic beta-cells , and blood insulin and glucose concentrations in streptozotocin-induced diabetic rats . Fifty male Wistar rats ( 200 - 250 g ) were divided into two experimental groups ( diabetics with no treatment and diabetics with N. sativa L. treatment ) , each containing twenty-five rats . Diabetes was induced in both groups by a single intraperitoneal injection of streptozotocin ( STZ ) ( 50 mg/kg ) . The experimental animals in both groups became diabetic within 24 hours after the administration of STZ . The rats in N. sativa L.-treated group were given the daily intraperitoneal injection of 0.20 ml/kg of N. sativa L. volatile oil for 30 days starting the day after STZ injection . Control rats received only the same amount of normal saline solution . The rats in both groups received the last injection 24 hours before the sacrification and 5 r and omly-selected rats in each group were sacrificed before , and the 1 , 10 , 20 and 30 days after the STZ injection to collect blood and pancreatic tissue sample s. The N. sativa L. treatment caused a decrease in the elevated serum glucose , an increase in the lowered serum insulin concentrations and partial regeneration/ proliferation of pancreatic beta-cells in STZ-induced diabetic rats with the elapse of the experiment . It is concluded that the hypoglycaemic action of N. sativa L. could be partly due to amelioration in the beta-cells of pancreatic islets causing an increase in insulin secretion . More studies are needed to demonstrate the exact mechanism of action of N. sativa L. on ameliorated blood glucose concentration in STZ-induced diabetes Nigella sativa L. seeds ( N. sativa ) have been used as a traditional remedy for a wide range of diseases including hypertension . The present study was performed to explore the effects of N. sativa oil on blood pressure ( BP ) in healthy volunteers . In a double-blind , r and omized study , 70 healthy volunteers aged 34 to 63 years with systolic BP from 110 to 140 mmHg and diastolic BP from 60 to 90 mmHg were r and omly allocated to receive 2.5 mL N. sativa oil or placebo two times a day for 8 weeks . The systolic and diastolic BPs , body mass index and blood levels of aspartate transaminase , alanine transaminase , alkaline phosphatase , creatinine and blood urea nitrogen were determined at baseline and endpoint . Results showed that in N. sativa oil treated group the systolic and diastolic BPs decreased significantly compared with baseline and placebo group at the endpoint . Other parameters did not significantly change in both groups at the endpoint . No adverse effects were reported . In conclusion , oral daily administration of 5 mL N. sativa oil to healthy volunteers for 8 weeks lowers systolic and diastolic BPs without any adverse effects UNLABELLED Diabetes mellitus is a common chronic disease affecting millions of people world wide . St and ard treatment is failing to achieve required correction of blood glucose in many patients . Therefore , there is a need for investigating potential hypoglycemic drugs or herbs to improve glycemic control in diabetic patients . Nigella sativa seeds were used as an adjuvant therapy in patients with diabetes mellitus type 2 added to their anti-diabetic medications . A total of 94 patient were recruited and divided r and omly into three dose groups . Capsules containing Nigella sativa were administered orally in a dose of 1 , 2 and 3 gm/day for three months . The effect of Nigella sativa on the glycemic control was assessed through measurement of fasting blood glucose ( FBG ) , blood glucose level 2 hours postpr and ially ( 2 hPG ) , and glycosylated hemoglobin ( HbA1c ) . Serum C-peptide and changes in body weight were also measured . Insulin resistance and beta-cell function were calculated usin the homeostatic model assessment ( HOMA2 ) . Nigella sativa at a dose of 2 gm/day caused significant reductions in FBG , 2hPG , and HbA1 without significant change in body weight . Fasting blood glucose was reduced by an average of 45 , 62 and 56 mg/dl at 4 , 8 and 12 weeks respectively . HbAlC was reduced by 1.52 % at the end of the 12 weeks of treatment ( P<0.0001 ) . Insulin resistance calculated by HOMA2 was reduced significantly ( P<0.01 ) , while B-cell function was increased ( P<0.02 ) at 12 weeks of treatment . The use of Nigella sativa in a dose of 1 gm/day also showed trends in improvement in all the measured parameters but it was not statistically significant from the baseline . However , no further increment in the beneficial response was observed with the 3 gm/day dose . The three doses of Nigella sativa used in the study did not adversely affect either renal functions or hepatic functions of the diabetic patients throughout the study period . IN CONCLUSION the results of this study indicate that a dose of 2 gm/ day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic agents in type 2 diabetic patients The influence of an increase in the polyunsaturated fat linoleic acid on blood pressure and erythrocyte membrane sodium transport was investigated in normotensive first degree relatives of hypertensive patients and controls by the double blind administration of safflower oil or paraffin oil ( placebo ) capsules for four weeks separated by a four week washout period . Systolic blood pressure fell in the controls with linoleic acid supplementation but there was no significant change in total sodium efflux rate constant . When the pattern of response was compared the changes in supine systolic blood pressure , plasma renin activity , total and ouabain-sensitive sodium efflux rate constant were significantly different in the controls compared to the relatives . These results show that dietary linoleic acid supplementation may have effects on ionic fluxes across cell membranes and cause a modest fall in blood pressure . In addition , since the response to the change in fat intake was different in the relatives and the controls , this provides further evidence of differences in the physicochemical structure of the plasma membrane in hypertensive subjects and their offspring The present study was undertaken to evaluate the protective effect of thymoquinone ( TQ ) , the main constituent of the volatile oil from Nigella sativa seeds , in rats after chronic inhibition of nitric oxide synthesis with N(omega)-nitro-l-arginine methyl esters ( l-NAME ) . Rats were divided r and omly into different treatment groups : control , l-NAME , TQ and l-NAME + TQ . Hypertension was induced by 4 weeks administration of l-NAME ( 50 mg/kg/day p.o . ) . TQ was administered alone or in combination with l-NAME and continued for 4 weeks . The animals were killed , and the serum and kidney tissues were isolated for the determination of creatinine and glutathione ( GSH ) , respectively . Rats receiving l-NAME showed a progressive increase in systolic blood pressure compared with control rats . Concomitant treatment with TQ ( 0.5 and 1 mg/kg/day p.o . ) reduced the increase in systolic blood pressure induced by l-NAME in a dose dependent manner . Kidney injury was demonstrated by a significant increase in serum creatinine and a decrease in GSH in kidney tissue from l-NAME treated rats . Treatment of rats with TQ decreased the elevated creatinine and increased GSH to normal levels . TQ inhibited the in vitro production of superoxide radical in enzymatic and non-enzymatic systems . In conclusion , TQ is effective in protecting rats against l-NAME-induced hypertension and renal damage possibly via antioxidant activity OBJECTIVE The seed extracts from Nigella sativa is used by Unani physicians of traditional medicine ( Hakims or Tabibs ) and Ayurvedic practitioners ( Vaids ) in the treatment of several medical disorders including dyslipidemia , obesity , and hypertension . It is , therefore , important to prove or disprove the effectiveness , safety , and tolerability of powdered N. sativa ( Kalonji ) seed in capsules on serum lipid levels , blood sugar , blood pressure , and body weight in adults . DESIGN The study design was a r and omized , double-blind trial . SETTING S/LOCATION Conducted at Aga Khan University Hospital , Karachi , from February 2006 to January 2007 . SUBJECTS Half of the respondents received powdered N. sativa ( Kalonji ) seed in capsule and the rest received a placebo . INTERVENTION/ OUTCOME Baseline and after-intervention variables recorded were the following : body-mass index , waist-hip ratio , blood pressure , fasting blood sugar , serum lipids , serum alanine aminotransferase , and serum creatinine . RESULTS One hundred and twenty-three ( 123 ) patients were recruited . Sixty-four ( 64 ) and 59 patients were r and omized to the intervention and the control arms , respectively . Thirty-nine ( 39 ) patients in the intervention group and 34 in the control group completed the study . Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant because of small sample size . CONCLUSIONS Favorable impact of powdered N. sativa ( Kalonji ) seed in capsule was noted on almost all variables , but results were not statistically significant . A larger study with adequate sample size is recommended |
2,492 | 15,353,012 | Probiotics are remarkably safe .
This was true no matter what probiotic was used .
Lactobacillus GG was the most extensively studied probiotic for this condition .
In conclusion , probiotics are safe and effective in the prevention and treatment of watery diarrhea .
They are especially effective in children under the age of 5 with Rotavirus infection .
Lactobacillus GG is the most extensively studied probiotic . | Dear Editor : Humans are born without any microorganisms inhabiting their gastrointestinal tract .
Soon thereafter , strains of bacteria colonize the lining of the digestive system and become an integral part of helping to maintain a person ’s health .
There are several strains of bacteria that can be found in an average human ’s body .
Some of the better known strains are Lactobacillus , Bifidobacterium , Streptococcus , and Escherichia coli .
Some bacteria have been found to be useful in treating specific diseases .
These particular microorganisms are known as probiotics , also known as “ good gut ” bacteria .
They have been used in the treatment of diarrhea ( Arvola et al. , 1999 ; Saavedra , 2000 ; V and erhoof et al. , 1999 ) , allergic symptoms ( Majamaa and Isolauri , 1997 ) , and eczema ( Malin et al. , 1996 ; Pelto et al. , 1998 ; Ruseler-van Embden et al. , 1995 ) .
Some preliminary work has also been done with cancer ( Goldin et al. , 1996 ; Gorbach , 2000 ) .
We performed a systematic review of the literature looking at the question of whether probiotics were effective in the prevention and treatment of diarrhea . | BACKGROUND The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier . We have previously shown that a human intestinal floral strain , Lactobacillus GG ( ATCC 53103 ) , promotes local antigen-specific immune responses ( particularly in the IgA class ) , prevents permeability defects , and confers controlled antigen absorption . OBJECTIVE The aim of this study was to evaluate the clinical and immunologic effects of cow 's milk elimination without ( n = 14 ) and with ( n = 13 ) the addition of Lactobacillus GG ( 5 x 10(8 ) colony-forming units/gm formula ) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow 's milk allergy . The second part of the study involved 10 breast-fed infants who had atopic eczema and cow 's milk allergy . In this group Lactobacillus GG was given to nursing mothers . METHODS The severity of atopic eczema was assessed by clinical scoring . The concentrations of fecal alpha 1- antitrypsin , tumor necrosis factor-alpha , and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention . RESULTS The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG . The concentration of alpha 1-antitrypsin decreased significantly in this group ( p = 0.03 ) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68 ) . In parallel , the median ( lower quartile to upper quartile ) concentration of fecal tumor necrosis factor-alpha decreased significantly in this group , from 709 pg/gm ( 91 to 1131 pg/gm ) to 34 pg/gm ( 19 to 103 pg/gm ) ( p = 0.003 ) , but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38 ) . The concentration of fecal eosinophil cationic protein remained unaltered during therapy . CONCLUSION These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy , and by alleviating intestinal inflammation , may act as a useful tool in the treatment of food allergy BACKGROUND Oral administration of live Lactobacillus casei strain GG is associated with the reduction of duration of diarrhea in children admitted to the hospital because of diarrhea . The purpose s of this work were to investigate the clinical efficacy of oral administration of Lactobacillus in children with mild diarrhea who were observed as out patients , and to see whether Lactobacillus GG can reduce the duration of rotavirus excretion . METHODS Duration of diarrhea was recorded in 100 children seen by family pediatricians and r and omly assigned to receive oral rehydration or oral rehydration followed by the administration of lyophilized Lactobacillus casei , strain GG . Rotavirus was looked for in the stools of all children and in those in whom results were positive , stools were examined again 6 days after the onset of diarrhea . RESULTS In 61 children results were positive for rotavirus and in 39 results were negative . Duration of diarrhea was reduced from 6 to 3 days in children receiving Lactobacillus GG , with a similar pattern in rotavirus-positive and -negative children . Six days after the onset of diarrhea , stools in only 4 out of 31 children that received Lactobacillus GG were positive for rotavirus compared with positive findings in 25 out of 30 control subjects . CONCLUSIONS Oral administration of Lactobacillus GG is effective in rotavirus-positive and rotavirus-negative ambulatory children with diarrhea . Furthermore , it reduces the duration of rotavirus excretion A prospect i ve , placebo controlled , triple blind clinical trial was undertaken in Thail and to determine the effect of Lactobacillus GG on recovery from acute diarrhoea in children . Thirty-nine children ( mean age = 8 months ) were enrolled and following rehydration received either oral Lactobacillus GG ( n = 20 ) as a freeze-dried preparation or placebo ( n = 19 ) twice daily for 2 days . The clinical characteristics of the study groups were similar . There was no significant difference overall in clinical response detected between the study groups . When only those with acute non-bloody diarrhoea ( n = 26 ) were considered , the mean duration of diarrhoea was significantly shorter in the lactobacillus group ( 1.9 days ) than in the placebo group ( 3.3 days ) ( P < 0.055 ) . Stool frequency was less on the second day in the lactobacillus group ( P < 0.05 ) . The results suggest that Lactobacillus GG accelerates recovery from acute watery diarrhoea in young children in a tropical setting A placebo-controlled double-blind study was conducted on the efficacy of Lactobacillus GG in preventing travellers ' diarrhoea . Altogether 820 persons travelling on holiday to southern Turkey to two destinations were r and omized into two groups receiving either Lactobacillus GG or placebo in identical sachets . On the return flight each participant completed a question naire indicating the incidence of diarrhoea and related symptoms during the trip . Of the original group 756 ( 92 % ) subjects completed the study acceptably . The overall incidence of diarrhoea was 43.8 % ( 331 cases ) . The total incidence of diarrhoea in the placebo group was 46.5 % and in the Lactobacillus GG 41.0 % indicating an overall protection of 11.8 % . Protection rates varied between two different destinations with the maximum protection rate reported as 39.5 % . Among older age groups there was significantly less diarrhoea when compared to younger travellers . Lactobacillus GG appeared to be effective in reducing the occurrence of travellers ' diarrhoea in one of the two destinations with no side effects OBJECTIVE Nosocomial diarrhea is a major problem in pediatric hospitals worldwide . We evaluated the efficacy of orally administered Lactobacillus GG ( LGG ) in the prevention of this disease in young children . STUDY DESIGN Eighty-one children aged 1 to 36 months who were hospitalized for reasons other than diarrhea were enrolled in a double-blind trial and r and omly assigned at admission to receive LGG ( n = 45 ) at a dose of 6 x 10(9 ) colony-forming units or a comparable placebo ( n = 36 ) twice daily orally for the duration of their hospital stay . RESULTS LGG reduced the risk of nosocomial diarrhea ( > or =3 loose or watery stools/24 h ) in comparison with placebo ( 6.7 % vs 33.3 % ; relative risk : 0.2 ; [ 95 % CI : 0.06 - 0.6 ] ; number needed to treat : 4 [ 95 % CI : 2 - 10 ] ) . The prevalence of rotavirus infection was similar in LGG and placebo groups ( 20 % vs 27.8 % , respectively ; relative risk : 0.72 ; 95 % CI : 0.33 - 1.56 ) . However , the use of LGG compared with placebo significantly reduced the risk of rotavirus gastroenteritis ( 1/45 [ 2.2 % ] vs 6/36 [ 16.7 % ] , respectively ; relative risk : 0.13 ; 95 % CI : 0.02 - 0.79 ; number needed to treat : 7 ; 95 % CI : 3 - 40 ) . CONCLUSIONS Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in infants , particularly nosocomial rotavirus gastroenteritis BACKGROUND Addition of a medication to the World Health Organization protocol for treatment of acute diarrhea in children is controversial . In this trial , the clinical efficacy of a medication ( Lactéol Fort sachets ; Laboratoire du Lactéol du Docteur Boucard , Houdan France ) containing lyophilized heat-killed Lactobacillus acidophilus LB was assessed as an adjunct to oral rehydration therapy . METHODS Children aged 3 to 24 months with acute diarrhea and mild or moderate dehydration were enrolled in the study . Children received oral rehydration therapy for the first 4 hours . After this first rehydration phase , undiluted milk formula or breast milk was fed alternately with oral rehydration solution . Children were fed rice gruel as tolerated . They received either one sachet containing 10 billion of lyophilized heat-killed L. acidophilus LB or placebo at admission and at 12-hour intervals for five doses . RESULTS Seventy-three children ( 37 L. acidophilus LB , 36 placebo ) were enrolled , of whom 40 ( 17 L. acidophilus LB , 23 placebo ) received an antibiotic before inclusion . Rotavirus was identified in approximately 50 % of the children in each group . After 24 hours of treatment , the number of rotavirus-positive children with watery stools was significantly lower ( p = 0.012 ) in the L. acidophilus LB group . Mean duration of diarrhea was decreased ( p = 0.034 ) with L. acidophilus LB ( 43.4 hours ) versus placebo ( 57.0 hours ) . This decreased duration was particularly marked in children with no antibiotic therapy before inclusion ( 31.1 hours ) : 42.9 hours for the L. acidophilus LB group versus 74.0 hours for the placebo group ( p = 0.016 ) . CONCLUSIONS Addition of L. acidophilus LB to oral rehydration therapy was effective in the treatment of children with acute diarrhea by decreasing the duration of diarrhea OBJECTIVE Lactobacillus GG ( L-GG ) , an acid- and bile-resistant strain that colonizes the intestinal mucosa , has been used to manage diarrhea in children . Our objective was to evaluate the prophylactic use of L-GG to prevent diarrhea in children at high risk from a developing country in a r and omized , placebo-controlled trial . STUDY DESIGN Two hundred four undernourished children 6 to 24 months old from an indigent peri-urban Peruvian town received either L-GG or placebo in flavored gelatin once daily , 6 days a week , for 15 months . Episodes of diarrhea were documented by daily home visits , and diagnostic studies were done in a subset of cases . Recovery of L-GG in stool from subjects and from family contacts was examined . RESULTS Subjects in the L-GG group had significantly fewer episodes of diarrhea ( 5.21 episodes diarrhea/child/year [ ' ecy ' ] L-GG group , 6 . 02 ecy placebo group ; P = .028 ) . The decreased incidence of diarrhea in the L-GG group was greatest in the 18- to 29-month age group ( P = . 004 ) and was largely limited to nonbreastfed children ( Breastfed : 6 . 59 ecy L-GG , 6.32 ecy placebo , P = .7 ; Nonbreastfed : 4.69 ecy L-GG , 5 . 86 ecy placebo , P = .005 ) . The duration of diarrhea episodes and the causes of diarrhea were similar in both groups , except adenovirus was more common in the placebo group . CONCLUSION L-GG supplementation may be useful as a prophylactic measure to control diarrhea in undernourished children at increased risk , especially nonbreastfed children in the toddler age group Background . Oral bacteriotherapy promotes recovery from acute childhood diarrhea , but few strains have been shown to have therapeutic potentials . We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea . Methods . Sixty-nine children were r and omized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070 - 2 and Lactobacillus reuteri DSM 12246 , 1010 colony-forming units of each strain or placebo twice daily for 5 days . Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers . Results . In patients receiving probiotics , the diarrheal phase was reduced by 20 % . The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group ( not significant , P = 0.07 ) . However , 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period ( P = 0.03 ) . In patients with diarrhea for < 60 h before start of treatment ( early intervention ) , a clear effect of the probiotics was demonstrated ( 80 h in the treatment group vs. 130 h in the control group , P = 0.003 ) . After early intervention , the length of hospitalization was reduced by 48 % ( 3.5 vs. 1.7 days , P = 0.03 ) . At the end of the intervention , rotavirus antigen was found in 12 % of patients from the treatment group vs. 46 % from the control group ( P = 0.02 ) . Conclusions . The two probiotics , L. rhamnosus 19070 - 2 and L. reuteri DSM 12246 , ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion . Oral bacteriotherapy was associated with a reduced length of hospital stay . The beneficial effects were most prominent in children treated early in the diarrheal phase Background . Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children . Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea . Methods . We studied in a r and omized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070 - 2 and Lactobacillus reuteri DSM 12246 , 1010 colony-forming units of each strain twice daily for 5 days , on acute diarrhea in children in a cohort of children recruited from local day-care centers . The duration of diarrhea and assessment of stool consistency were recorded by the parents . Results . In patients treated with the selected Lactobacillus strains , the mean duration of diarrhea after intervention was reduced ( 76 h in patients treated with probiotics vs. 116 h in the placebo group;P = 0.05 ) . In patients with diarrhea for < 60 h before start of treatment ( early intervention ) , a more pronounced effect of probiotics was found . The time to recovery after early treatment was 79 h vs. 139 h in the placebo group ( P = 0.02 ) ; 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment ( P = 0.03 ) . Conclusions . In children from day-care centers with mild gastroenteritis , the combination of L. rhamnosus 19070 - 2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea Background and aims Gastrointestinal toxicity is frequently observed during radiotherapy for malignancies in the abdomen and pelvis . This study was performed to determine the efficacy and tolerability of Lactobacillus rhamnosus ( Antibiophilus ® ) in comparison to placebo in a double-blind trial design . Its aim was to determine any clinical ly relevant difference between Antibiophilus ® and placebo in terms of efficacy in patients suffering from mild to moderate diarrhoea induced by radiation therapy . Methods The study was performed in two radiotherapy units in Hungary ; the results are based on the data for 206 recruited patients . Results Based on statistical analysis , Antibiophilus ® patients showed superiority with respect to the number of bowel movements ( P < 0.10 ) and faeces consistency ratings by the investigators ( P < 0.05 ) at the study end . Statistical analysis of the patients ’ self-ratings with regard to diarrhoea grade and faeces consistency showed a statistically highly significant treatment-by-time interaction ( P < 0.001 ) which was supported by the evidence of tendencies or P values below the nominal 5 % level in the second half of this study . Conclusions Overall , there was a highly favourable benefit/risk ratio in favour of Antibiophilus ® Lactobacilli in the intestines play an important role in developing natural defenses against both intestinal bacterial and viral infections . So a prospect i ve clinical study was carried out at Cathay General Hospital to determine the effect of Lactobacillus acidophilus and Bifidobacterium infantis on the course of acute diarrhea in hospitalized children . Altogether 100 children between 6 and 60 months of age were collected and r and omly allocated into 2 groups . Study group ( n = 50 ) was given Infloran Berna , which contains 10(9 ) viable Lactobacillus acidophilus and 10(9 ) Bifidobacterium infantis , one capsule tid for 4 days and control group ( n = 50 ) received parenteral rehydration only without any medication . Only 20 stool cultures in study group had positive culture results for Lactobacillus or Bifidobacterium . All children were evaluated for the degree of dehydration before rehydration . The clinical course of diarrhea was followed during the treatment period . Features on admission were similar between the study group and control group in age , duration of diarrhea at home , serum sodium & potassium and dehydration degree . The duration of diarrhea was defined as the time until the last appearance of watery stool . There was no difference between the study group and control group in the frequency of diarrhea stools on the day before admission ( p > 0.05 ) . However , the frequency of diarrhea for study group improved on the first and second day of hospitalization with statistical difference ( p < 0.01 ) . The duration of diarrhea during hospitalization in study group also decreased ( 3.1 vs. 3.6 days , p < 0.01 ) . Oral bacterial therapy is an effective adjuvant therapy in rotavirus positive and negative children with diarrhea and can safely be administered during an episode of acute diarrhea BACKGROUND Certain strains of lactobacilli may promote recovery from acute diarrhea . Lactobacillus reuteri is of human origin and is a natural colonizer of gastrointestinal tract . In this trial , exogenously administered L. reuteri was studied as a therapeutic agent in acute diarrhea . METHODS Forty patients between 6 and 36 months of age hospitalized with acute diarrhea ( 75 % rotavirus ) were studied . After parental consent , the patients were r and omized to one of two treatment groups to receive either 10(10 ) to 10(11 ) colony-forming units of L. reuteri or a matching placebo daily for the length of hospitalization or up to 5 days . The clinical outcome of diarrhea and colonization of L. reuteri were evaluated . RESULTS The mean ( SD ) duration of watery diarrhea after treatment was 1.7 ( 1.6 ) days in the L. reuteri group and 2.9 ( 2.3 ) days in the placebo group ( p = 0.07 ) . On the second day of treatment only 26 % of patients receiving L. reuteri had watery diarrhea , compared with 81 % of those receiving placebo ( p = 0.0005 ) . Cultures of lactobacilli from stool sample s demonstrated that administration of L. reuteri result ed in colonization of the gastrointestinal tract . Lactobacillus reuteri accounted for > 75 % of the total lactobacilli found in children fed with this product . CONCLUSIONS Lactobacillus reuteri is effective as a therapeutic agent in acute rotavirus diarrhea in children . Further studies are warranted to confirm the present finding and to explore the full therapeutic potential of L. reuteri in acute viral diarrhea Probiotic bacteria can influence immune responses both specifically by stimulating antibody production and nonspecifically by enhancing phagocytosis of pathogens and modifying cytokine production . A prospect i ve , placebo-controlled , triple blind clinical trial was carried out in Pakistan to determine the effect of Lactobacillus GG on the course of acute diarrhea in hospitalized children . Forty children ( mean age , 13 months ) were enrolled and after rehydration received either oral Lactobacillus GG ( n = 21 ) or placebo ( n = 19 ) twice daily for 2 days , in addition to the usual diet . The clinical course of diarrhea was followed during the treatment period . Features on admission into the study groups were similar and were characterized by severe diarrhea , malnutrition and inappropriate management before presentation . Response was evident on Day 2 when the frequency of both vomiting and diarrhea was less in the Lactobacillus group . In those who had presented with acute nonbloody diarrhea ( n = 32 ) , the percentage of children with persistent watery diarrhea at 48 hours was significantly less in the Lactobacillus group : 31 % vs. 75 % ( P < 0.01 ) . No significant difference was observed by 48 hours in those presenting with bloody diarrhea . The relevance of this finding to the management of diarrhea in the tropics is discussed The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied . Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week . The volunteers were r and omly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment . Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt . Other side effects of erythromycin , such as abdominal distress , stomach pain and flatulence , were less common in the GG yoghurt group than in the placebo yoghurt group . The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG . No Lactobacillus GG was found in the faecal sample s of volunteers in the group taking pasteurized yoghurt Acute diarrhoea is a serious cause of infant morbidity and mortality , and the development of preventive measures remains an important goal . Bifidobacteria ( which constitute the predominant intestinal flora of breastfed infants ) , as well as other lactic-acid-producing organisms such as Streptococcus thermophilus , are thought to have a protective effect against acute diarrhoeal disease . However , their efficacy has not been assessed in controlled trials . In a double-blind , placebo-controlled trial , infants aged 5 - 24 months who were admitted to a chronic medical care hospital were r and omised to receive a st and ard infant formula or the same formula supplemented with Bifidobacterium bifidum and S thermophilus . Patients were evaluated daily for occurrence of diarrhoea , and faecal sample s , obtained weekly , were analysed for rotavirus antigen by enzyme immunoassay . Faecal sample s were also obtained during an episode of diarrhoea for virological and bacteriological analyses . 55 subjects were evaluated for a total of 4447 patient-days during 17 months . 8 ( 31 % ) of the 26 patients who received the control formula and 2 ( 7 % ) of 29 who received the supplemented formula developed diarrhoea during the course of the study ( p = 0.035 , Fisher 's exact test , two-tailed ) . 10 ( 39 % ) of the subjects who received the control formula and 3 ( 10 % ) of those who received the supplemented formula shed rotavirus at some time during the study ( p = 0.025 ) . The supplementation of infant formula with B bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding in infants admitted to hospital |
2,493 | 24,793,264 | Overall , we did not see an effect of amantadine on failure to achieve a sustained virological response .
Subgroup analyses demonstrated that the combination of amantadine plus interferon-alpha and ribavirin seems to increase the number of patients achieving a sustained virological response .
Based on the results of the overall evidence , it appears less likely that future trials assessing amantadine for patients with chronic hepatitis C will show strong benefits .
We found a lack of evidence on other aminoadamantanes than amantadine | BACKGROUND Around 3 % of the world 's population ( approximately 160 million people ) are chronically infected with hepatitis C virus .
The proportion of infected people who develop clinical symptoms varies between 5 % and 40 % .
Combination therapy with pegylated interferon-alpha plus ribavirin eradicates the virus from the blood six months after treatment ( sustained virological response ) in approximately 40 % to 80 % of infected patients , depending on the viral genotype .
New antiviral agents , such as boceprevir and telaprevir , in combination with st and ard therapy , can increase sustained virological response in genotype 1 infected patients to at least 70 % .
There is therefore an unmet need for drugs that can achieve a higher proportion of sustained virological response .
Aminoadamantanes are antiviral drugs used for treatment of patients with chronic hepatitis C. OBJECTIVES To assess the beneficial and harmful effects of aminoadamantanes for patients with chronic hepatitis C infection by conducting a systematic review with meta-analyses of r and omised clinical trials , as well as trial sequential analyses . | OBJECTIVES : Amantadine reduces liver transaminase levels in some patients with chronic hepatitis C at doses of 200 mg daily and may improve the sustained virological response ( SVR ) when given with interferon and ribavirin . The primary purpose of the present investigation was to study the safety and toxicity of higher doses of amantadine in subjects who previously failed or were intolerant to interferon . The secondary aim was to test the efficacy of higher dose of amantadine against hepatitis C. METHODS : An open-labeled prospect i ve study was conducted starting with amantadine 200 mg daily and increasing to 500 mg daily while monitoring for safety , toxicity , and efficacy . An amantadine blood level exceeding 1,600 ng/ml was considered toxic requiring dose reduction . The patient 's symptoms , laboratory tests , and quality of life were monitored . RESULTS : One hundred patients enrolled in the study . Normalization of alanine aminotransferase ( ALT ) for each dose was as follows : 200 mg ( 35 % ) , 300 mg ( 49 % ) , 400 mg ( 53 % ) , and 500 mg ( 56 % ) . The incidence of toxic amantadine plasma levels increased with dose , i.e. , 200 mg ( 0 % ) , 300 mg ( 6 % ) , 400 mg ( 27 % ) , and 500 mg ( 49 % ) . The frequency and severity of arthralgias and fatigue improved at all dosages administered . No changes in the occurrence or severity of headache , insomnia , or depression were reported . Serious adverse events included myocardial infa rct ion and suicide attempt . Other side effects included impotence , confusion , alopecia , and hoarseness . CONCLUSIONS : Amantadine given at a dose of 300 mg daily is safe , and significantly lowers ALT blood levels more than 200 mg daily . The enzyme response rate does not significantly improve above 300 mg , but toxicity increases Abstract Background : Concurrent potent therapy of hepatitis C ( HCV ) and HIV includes at least five antiviral drugs . Drug interactions , toxicity , tolerance and acceptance by patients of such treatment regimens are unknown . Study design : A prospect i ve open r and omized pilot trial was conducted to test interferon-α ( 6 million units/day for the 1st month followed by 6 million thrice weekly ) and amantadine versus interferon-α monotherapy for tolerability and feasibility among HIV and HCV co-infected patients on stable antiretroviral combination therapy . Results : 1,013 HIV-infected patients were consecutively evaluated . 314 were anti-HCV antibody positive ; only eight ( 2.4 % ) were eligible . Major reasons for exclusion were : normal transaminase levels ( 34 % ) , ongoing intravenous drug use ( 33 % ) , or recent change in antiretroviral therapy ( 31 % ) . Study drugs were stopped in all of the seven patients enrolled because of side effects and /or failure of anti-HCV-therapy . CD4 lymphocyte counts and HIV-1 RNA remained stable . Conclusion : Among patients on highly active antiretroviral therapy , the addition of interferon-α with or without amantadine was inefficient and poorly tolerated , but had no negative influence on HIV infection . Eligibility for the study was unexpectedly low A r and om-primed complementary DNA library was constructed from plasma containing the uncharacterized non-A , non-B hepatitis ( NANBH ) agent and screened with serum from a patient diagnosed with NANBH . A complementary DNA clone was isolated that was shown to encode an antigen associated specifically with NANBH infections . This clone is not derived from host DNA but from an RNA molecule present in NANBH infections that consists of at least 10,000 nucleotides and that is positive-str and ed with respect to the encoded NANBH antigen . These data indicate that this clone is derived from the genome of the NANBH agent and are consistent with the agent being similar to the togaviridae or flaviviridae . This molecular approach should be of great value in the isolation and characterization of other unidentified infectious agents Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment‐naive patients with chronic hepatitis C yielded contradictory results . We therefore conducted a large , double‐blind , placebo‐controlled , multicenter trial in naive patients with chronic hepatitis C : 246 patients were r and omized to receive interferon alfa‐2a ( 6 MIU sc thrice weekly for 20 weeks , then 3 MIU sc thrice weekly ) and either amantadine sulphate ( 2 × 100 mg po QD ) or placebo . Treatment continued for a total of 52 weeks , if HCV‐RNA in serum polymerase chain reaction ( PCR ) had fallen below detection limit ( 1,000 copies/mL ) at treatment week 10 , and stopped otherwise . All patients were followed for 24 weeks off therapy . After 10 weeks of treatment , 66/121 patients treated with amantadine ( 55 % ) and 78/125 treated with placebo ( 62 % ) had lost HCV‐RNA ( n.s . ) . After 24 weeks of follow‐up , 25 patients in the amantadine ( 21 % ) and 17 ( 14 % ) in the placebo group remained HCV‐RNA negative ( n.s . ) . During therapy , virologic breakthroughs occurred less often in the amantadine than in the placebo group [ 14 ( 12 % ) vs. 27 ( 22 % ) patients ; P = .04 ] . Multivariate logistic regression analysis revealed genotype , viremia level , age , and amantadine therapy [ risk ratio 0.4 ( 95%CI 0.2‐1.0 ) , P = .05 ] as predictors of sustained virologic response . Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients . Compared with current st and ard treatment ( interferon/ribavirin ) , the interferon/amantadine combination was not cost‐effective . In conclusion , amantadine does not add to a clinical ly relevant extent to the treatment of naive patients with chronic hepatitis BACKGROUND / AIMS The effect of interferon treatment for chronic hepatitis C patients with genotype 1b virus has been suboptimal . We studied the effect of the combination therapy of interferon and amantadine on patients with a high serum viral load of genotype 1b virus . METHODOLOGY We studied the virological response of naive chronic hepatitis C patients with a high viral load of genotype 1b virus ( 4.5 log copies/50 microL or 100 kcopies/mL and higher ) during interferon and amantadine administration for 6 months and 6 months after the end of treatment . Twenty patients were treated with interferon alone ( natural interferon-beta 6 MU daily for 6 weeks and thrice-a-week for 20 weeks ) for 26 weeks . Eleven patients were treated with the combination therapy of interferon and amantadine hydrochloride ( 100 mg orally daily ) for 26 weeks . RESULTS After daily administration of interferon-beta intravenously once a day for 6 weeks , all patients showed the negative tests of serum HCV-RNA by polymerase-chain-reaction methods by the combination therapy , while 13 patients ( 65.0 % ) showed the negative tests by interferon alone ( p = 0.0257 ) . At the end of treatment , serum HCV-RNA were not detected in 54.5 % of patients treated with interferon and amantadine , while it was detected in 50.0 % of patients treated with interferon alone . At 6 months follow-up , only one patient ( 9.1 % ) could eradicate HCV-RNA in patients with interferon and amantadine , while no patient could with interferon monotherapy ( not significantly ) . CONCLUSIONS Amantadine hydrochloride has the additive effects to interferon treatment on the virological responses of serum HCV-RNA during a co-administration , although the combination therapy has not shown a significantly promising effect on the eradication of HCV-RNA in the patients with chronic hepatitis C with a high viral load of genotype 1b virus Background Efficacy and safety of interferon induction therapy alone or in combination with ribavirin or ribavirin plus amantadine were evaluated in chronic hepatitis C patients who were nonresponders to primary antiviral treatment . Methods The study was design ed to have 225 HCV nonresponder patients , but at an interim analysis the response rate difference between groups was lower than expected and the enrollment was stopped when 75 patients had been r and omized to receive interferon-α2a ( group A , n = 26 ) , interferon-α2a plus 15 mg/kg per day of ribavirin ( group B , n = 24 ) , or interferon-α2a plus ribavirin plus 200 mg/day of amantadine hydrochloride ( group C , n = 25 ) . Treatment duration was 48 weeks . The dose of interferon was 6 MU/day for 4 weeks followed by 3 MU/day for the remaining 44 weeks . Results On intention-to-treat , the sustained virological response at 24 weeks of follow-up was 11.5 % in group A , 12.5 % in group B , and 12 % in group C. Therapy was discontinued because of adverse effects in three patients in group A ( 11.5 % ) , three in group B ( 12.5 % ) , and two in group C ( 8 % ) . Conclusions Nonresponders with chronic hepatitis C may achieve a sustained virological response rate of approximately 12 % if retreated with interferon induction treatment followed by administration of a daily dose . The addition of ribavirin or amantadine did not seem to improve the response rates OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials BACKGROUND : Retreatment for 6 months with the association ribavirin-interferon of HCV-related chronic active hepatitis relapser patients has high probability of failure , mostly in those with genotype 1b . We evaluated the efficacy of extending the therapy from 6 to 12 months without or with the addition of amantadine . METHODS : Forty-nine genotype 1b relapser patients were treated with 3 MU of IFN-alpha2b three times per week and ribavirin 1000 - 1200 mg daily ( double therapy ) . Twenty-four patients , who did not respond after 6 months of treatment , were r and omized to continue for further 6 months either with the same schedule or with also the addition of amantadine 200 mg daily ( triple therapy ) . RESULTS : A sustained virological response was observed in 15/37 subjects ( 41 % ) treated for 12 months of double therapy . In the arm of the study evaluating amantadine , end of treatment virologic response was observed in 0/12 patients of double therapy group and in 4/12 of triple therapy ( P=0.09 ) . After 6 months of follow-up , a sustained virologic response ( SVR ) was observed in two patients treated with the triple therapy . CONCLUSIONS : This study confirms poor results of retreatment ( even if 12 months double or triple therapy ) in relapser patients with HCV hepatitis , genotype 1b . No gain was obtained in prolonging from 6 to 12 months the st and ard double therapy , while triple therapy with amantadine as an additional regimen for this difficult subgroup of patients showed some cases of SVRs : amantadine addition deserves to be evaluated in larger trials BACKGROUND / AIMS To determine whether addition of amantadine to pegylated interferon/ribavirin improved response rates among chronic hepatitis C patients , non-responders to interferon/ribavirin and study the dynamic of response . METHODS In a double blind , multicenter , r and omized trial , 200 non-responder patients received pegylated interferon 1.5 microg/kg per week and ribavirin 800 - 1200 mg/day , plus either amantadine 200 mg/day or placebo for 48 weeks . Endpoints were virological responses , ALT normalization , and histological benefit overtime . RESULTS Twenty percent of all patients achieved a sustained virological response ( SVR ) . This rate was 8 % higher in the triple therapy group ( 24 % ) compared with the double therapy group ( 16 % ) ( P = 0.22 ) . A better virological response rate at week 24 was observed in the triple regimen group ( 43 vs 29 % ; P = 0.06 ) , which was lost at week 48 suggesting viral escape . The biochemical response rate was also significantly higher with triple therapy at week 12 ( 63 vs 49 % ; P = 0.05 ) and week 24 ( 64 vs 49 % ; P = 0.03 ) . Fibrosis stabilized or improved in 77 % of all patients . CONCLUSIONS Re-treatment of interferon/ribavirin non-responder patients should be encouraged since a substantial proportion benefits from re-treatment with pegylated interferon/ribavirin + /- amantadine . In triple therapy involving amantadine , a time wise response and an increased SVR rate in subgroups less prone to viral breakthrough suggest clues for existing controversies BACKGROUND Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy . We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 912 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin ( 1000 or 1200 mg orally per day , depending on body weight ) for 24 or 48 weeks . Efficacy was assessed by measurements of serum hepatitis C virus ( HCV ) RNA and serum aminotransferases and by liver biopsy . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed ) was higher among patients who received combination therapy for either 24 weeks ( 70 of 228 patients , 31 percent ) or 48 weeks ( 87 of 228 patients , 38 percent ) than among patients who received interferon alone for either 24 weeks ( 13 of 231 patients , 6 percent ) or 48 weeks ( 29 of 225 patients , 13 percent ) ( P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment ) . Among patients with HCV genotype 1 infection , the best response occurred in those who were treated for 48 weeks with interferon and ribavirin . Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks ( 57 percent ) or 48 weeks ( 61 percent ) than in those who were treated with interferon alone for either 24 weeks ( 44 percent ) or 48 weeks ( 41 percent ) . The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy . CONCLUSIONS In patients with chronic hepatitis C , initial therapy with interferon and ribavirin was more effective than treatment with interferon alone BACKGROUND Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial . AIMS We aim ed to examine whether such policy enhances sustained viral response in treatment-naïve patients . METHODS 297 naïve hepatitis C patients were r and omized for treatment with amantadine 200 mg or placebo , combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy , followed by PEG-interferon alpha-2b ( 1.5 microg/kg/week up to 26 weeks and thereafter , 1.0 microg/kg/week until week 52 ) . Treatment was discontinued if hepatitis C virus ( HCV ) RNA was positive at week 24 . RESULTS 49 % of patients were ( former ) drug users . Genotype 1 occurred in 45 % , high viral load in 70 % and severe fibrosis/cirrhosis in 32 % , without differences between amantadine or placebo groups . 90 patients prematurely discontinued treatment , mainly because of grade 3 or 4 toxicity . Intention-to-treat analysis revealed sustained viral response in 47 % and 51 % of amantadine and placebo groups ( p=0.49 ) . Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response , breakthrough or relapse rates . Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response . CONCLUSION Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects BACKGROUND In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin , outcomes after retreatment are suboptimal . Boceprevir , a protease inhibitor that binds to the HCV nonstructural 3 ( NS3 ) active site , has been suggested as an additional treatment . METHODS To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection , we r and omly assigned patients ( in a 1:2:2 ratio ) to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks , and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . RESULTS A total of 403 patients were treated . The rate of sustained virologic response was significantly higher in the two boceprevir groups ( group 2 , 59 % ; group 3 , 66 % ) than in the control group ( 21 % , P<0.001 ) . Among patients with an undetectable HCV RNA level at week 8 , the rate of sustained virologic response was 86 % after 32 weeks of triple therapy and 88 % after 44 weeks of triple therapy . Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10 ) IU per milliliter at treatment week 4 , the rates of sustained virologic response were 0 % , 33 % , and 34 % in groups 1 , 2 , and 3 , respectively . Anemia was significantly more common in the boceprevir groups than in the control group , and erythropoietin was administered in 41 to 46 % of boceprevir-treated patients and 21 % of controls . CONCLUSIONS The addition of boceprevir to peginterferon-ribavirin result ed in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection , as compared with peginterferon-ribavirin alone . ( Funded by Schering-Plough [ now Merck ] ; HCV RESPOND-2 Clinical Trials.gov number , NCT00708500 . ) INTRODUCTION A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy . Therefore , we evaluated the efficacy of amantadine combined with the st and ard of care(pegylated interferon plus ribavirin ) in patients who had not responded to or had relapsed after ≥ 24 weeks of treatment with conventional interferon plus ribavirin . MATERIAL AND METHODS Patients stratified by previous response ( i.e. , non-response or relapse ) were r and omized to 48 weeks of open-label treatment with peginterferon alfa-2a ( 40KD ) 180 µg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day ( triple therapy ) , or the st and ard of care ( peginterferon alfa-2a [ 40KD ] plus ribavirin ) . RESULTS The primary outcome was sustained virological response ( SVR ) , defined as undetectable hepatitis C virus RNA in serum ( < 50 IU/mL ) at end of follow-up ( week 72 ) . Among patients with a previous non-response , 12/53 ( 22.6 % ; 95 % confidence interval [ CI ] 12.3 - 36.2 % ) r and omized to triple therapy achieved an SVR compared with 16/52 ( 30.8 % ; 95 % CI 18.7 - 45.1 % ) r and omized to the st and ard of care . Among patients with a previous relapse 22/39 ( 56.4 % ; 95 % CI 39.6 - 72.2 % ) r and omized to triple therapy achieved an SVR compared with 23/38 ( 60.5 % ; 95 % CI 43.4 - 76.0 % ) r and omized to the st and ard of care . Undetectable HCV RNA ( < 50 IU/mL ) at week 12 had a high positive predictive value for SVR . A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a ( 40KD ) plus ribavirin . CONCLUSION Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and can not be recommended in this setting Aim The aim of this study was to investigate whether amantadine reduces deterioration of quality of life in patients with chronic hepatitis C during and after treatment with interferon-&agr ; ( IFN-&agr ; ) and ribavirin . Patients and methods In this r and omized , prospect i ve , placebo-controlled , multicenter trial , previously untreated patients with chronic hepatitis C were treated with IFN-&agr ; plus ribavirin [ 17 ] and r and omized for treatment with amantadine ( 200 mg/day , orally , n=136 ) or placebo ( n=131 ) . Quality of life was assessed with the ‘ Profile of Mood States ’ scale and the ‘ Everyday Life ’ question naire at baseline , treatment week ( TW ) 8 , TW24 , TW48 , and at follow-up . Results Early during treatment at TW8 , quality of life was not different between patients in the control and the amantadine group . At TW24 , the control group but not the amantadine group , however , showed significant deterioration of the modalities depression , fatigue , and vigor compared with baseline . Especially , nonresponders in the amantadine group showed significantly lower deterioration of depression , anger , mind function , everyday life , and zest for life than those in the placebo group . After treatment , the beneficial effects of amantadine disappeared . Conclusion The addition of amantadine to IFN-&agr ; plus ribavirin combination therapy may reduce deterioration of depression , fatigue , and vigor during treatment but does not affect quality of life after treatment BACKGROUND Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy , but most subsequently relapse . We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment . A total of 173 patients were r and omly assigned to receive st and ard-dose recombinant interferon alfa-2b concurrently with ribavirin ( 1000 to 1200 mg orally per day , depending on body weight ) for six months , and 172 patients were assigned to receive interferon and placebo . RESULTS At the completion of treatment , serum levels of hepatitis C virus ( HCV ) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone ( 82 percent vs. 47 percent , P<0.001 ) . Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients ( 49 percent ) in the combination-therapy group , but in only 8 patients ( 5 percent ) in the interferon group ( P<0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response . Base-line serum HCV RNA levels of 2 x 10(6 ) copies per milliliter or less were associated with higher rates of response in both treatment groups . Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group . Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone . CONCLUSIONS In patients with chronic hepatitis C who relapse after treatment with interferon , therapy with interferon and oral ribavirin results in higher rates of sustained virologic , biochemical , and histologic response than treatment with interferon alone The aim of the study was to evaluate the efficacy of triple antiviral therapy with interferon , ribavirin , and amantadine in comparison with interferon and ribavirin combination treatment in patients with interferon‐nonresponsive chronic hepatitis C. We performed an open‐label , prospect i ve r and omized controlled trial at a secondary referral center . We used a 2:1 ratio , patients received interferon , ribavirin , and amantadine , or interferon and ribavirin for 12 months , and were followed up for an additional 6 months . Ninety‐four consecutive adult interferon nonresponders with chronic hepatitis C were screened . Sixty consecutive elected patients entered the study . No patients withdrew because of adverse effects . Forty patients received interferon alfa ( 5 megaunits on alternate days ) , ribavirin ( 800‐1,000 mg daily ) , and amantadine ( 200 mg daily ) for 12 months , and 20 patients received the same treatment without amantadine . At the end of follow‐up , alanine transaminase ( ALT ) level normalization was maintained in 23 of 40 patients ( 57 % ) after triple therapy , but in 2 of 20 patients ( 10 % ) after double therapy ( P < .001 , RR = 2.11 , 95 % CI , 1.43‐3.12 ) , whereas disappearance of serum HCV RNA persisted in 19 of 40 patients ( 48 % ) and in 1 of 20 patients ( 5 % ) , respectively ( P < .001 , RR = 1.81 , 95 % CI , 1.32‐2.47 ) . The safety profile was similar in the 2 groups . In conclusion , in patients with interferon‐nonresponsive chronic hepatitis C , triple antiviral therapy for 1 year results in a high rate of sustained biochemical and virologic responses BACKGROUND : Combination of the antiviral drug amantadine with interferon ( IFN ) may be more effective than IFN monotherapy for treatment of chronic hepatitis C. METHODS : We r and omised 93 patients with chronic hepatitis C to IFNIFN 6 MU 3 times/week for 24 weeks , followed by IFN 3 MU 3 times/week for further 24 weeks given in combination with amantadine 100 mg t.i.d . ( regimen A , n=48 ) or as monotherapy ( regimen B , n=45 ) . Control liver biopsies were obtained 6 months post treatment . RESULTS : At the end of the trial a similar proportion of patients had normal serum ALT levels ( 35 % for regimen A , and 44 % for regimen B ) as measured by intention to treat criteria . Sustained biochemical response at 6 months post treatment was 15 and 20 % , and sustained virological response was 10 and 20 % for regimen A and B , respectively . The effect on liver histology was also similar : the inflammatory components of the Knodell score decreased by 1.3+/-0.6 points for regimen A and by 1.6+/-0.6 for regimen B , and score for fibrosis remained unchanged with both regimens . CONCLUSIONS : Combination of IFN therapy with amantadine does not enhance the effect of IFN as shown by biochemical , virological and histological criteria BACKGROUND / AIMS Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients . Using a novel design , amantadine was studied in naïve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin . METHODS Patients enrolled in this r and omized , placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity ( stratum I , 24-h HCV-RNA decline > 1.4-log10 ; II , 0.8 - 1.39-log10 ; III , < 0.8-log10 ; a reliable means of identifying nonresponders to interferon/ribavirin ) and fibrosis grade ( F0/1/2 vs. F3/4 ) at baseline . All patients received peginterferon alfa-2a ( 40KD ) 180 microg/week plus ribavirin 1000 - 1200 mg/day and were r and omized to receive amantadine 100 mg twice daily ( N = 114 ) or placebo ( N = 95 ) for 48 weeks . RESULTS Week-24 virological response rates in strata II and III , the primary outcome , were similar in patients treated with amantadine ( 63.7 % ) or placebo ( 65.7 % ) , as were sustained virological response rates at week 72 ( 46.5 and 51.6 % , respectively ) . Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo . Interferon sensitivity was the only significant predictor of treatment outcome . CONCLUSIONS Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients . Virological response was almost exclusively determined by interferon sensitivity at baseline BACKGROUND Therapy options for patients with chronic hepatitis C who failed prior treatment are needed . In recent studies triple antiviral therapy with Interferon-alpha , ribavirin , and amantadine seemed to increase sustained virological response rates in this group . METHOD To evaluate efficacy , side effects and safety of a triple re-therapy in an open labeled prospect i ve study , we compared 23 nonresponders to interferon monotherapy ( 9 nonresponders , 3 relapsers , 11 with breakthrough ) with 23 nonresponders to st and ard combination therapy ( interferon plus ribavirin ) ( 16 nonresponders , 7 breakthroughs ) . All out patients enrolled for re-therapy received interferon-alpha 2a ( 6 mega units [ MU ] three times in week ) , ribavirin ( 1000 - 1200 mg daily in divided doses ) and amantadine ( 200 mg daily ) for six months . In case of virological re-therapy response ( negative qualitative HCV RNA ) study medication was continued with interferon monotherapy for another six months . RESULTS Sustained virological response was achieved in 16 ( 35 % ) out of 46 prior therapy nonresponders . Response rates were dependent on pretreatment outcome . In the st and ard combination therapy group only 1 ( 6 % ) primary nonresponder achieved sustained response , but none of the 9 monotherapy nonresponders did . After primary breakthrough sustained response was seen in 8 of 11 ( 73 % ) patients in the interferon monotherapy and in 5 of 7 ( 71 % ) in the combination therapy group . Of 3 monotherapy relapsers 2 ( 66 % ) did also clear the virus sustained . Safety profile under triple therapy was similar to the previous therapy . Compliance was higher and side effects lower in those patients already experienced in combination therapy . CONCLUSION In patients with a breakthrough or relapse after interferon monotherapy or st and ard combination therapy with interferon and ribavirin a re-therapy with a triple combination of interferon , ribavirin , and amantadine results in a high rate of sustained virological response The aim of this study was to compare , in an open‐label study , the efficacy and safety of a combination of interferon ( IFN ) and amantadine ( AMA ) with that of IFN alone in previously untreated patients with chronic hepatitis C. A total of 200 patients were r and omized to 6 MU of IFN‐α2a 3 times per week , with 200 mg of AMA daily ( n = 99 ) or to an identical dose of interferon α2a ( n = 101 ) . Patients were treated for 12 months and observed for 6 months ' posttreatment . At the completion of treatment , 28.7 % of patients in the monotherapy group and 45.5 % in the combination group had a virologic response ( P = .014 ) . At 6 months ' posttreatment , a sustained virologic response was observed in 16.8 % ( 95 % CI : 9‐23 ) of patients with IFN alone versus 29.3 % ( 95 % CI : 19‐37 ) of patients who were treated with combination therapy ( P = .036 ) . In each of the 2 treatments , genotype was the only predictive parameter for a sustained response . At the logistic regression analysis , therapy and genotype were the only 2 parameters with an independent predictive value . In the combination group , at examination of month 3 , hepatitis C virus (HCV)‐RNA status had a 97.6 % ( 95 % CI : 93‐102 ) positive predictive value and a 50 % ( 95 % CI : 37‐63 ) negative predictive value for a sustained virologic clearance . A substantial proportion of naïve patients with chronic hepatitis C have an end‐of‐treatment and end‐of‐follow‐up virologic and biochemical response to a combination of IFN and AMA . This new treatment appears safe and well tolerated . ( HEPATOLOGY 2001;33:989‐993 . Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Background : Fifty per cent of chronic hepatitis C patients are non-responders to interferon . At present , there are no recommended therapeutic options for non-responders . Aims : The safety and long term effect of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non-responsive chronic hepatitis C was evaluated . Patients and methods : A total of 114 consecutive patients were r and omly divided into three groups with a final 2:2:1 ratio : group A ( 44 patients ) received interferon alfa 2b , 3 million units ( MU ) , three times a week , and oral ribavirin ( 1000 mg/day ) ; group B ( 46 patients ) received interferon 3 MU daily for the first four weeks and subsequently 3 MU three times a week , and ribavirin as in regimen A ; and group C ( 24 patients ) received interferon and ribavirin as in regimen B , plus oral amantadine hydrochloride ( 200 mg/day ) . The duration of treatment was 12 months . Results : The end of treatment response for groups A and B was 25 % and 29 % , respectively , and for group C , 68 % ( p<0.005 ) . At the end of one year of follow up , a sustained response was observed for six ( 25 % ) patients in group C , one ( 2 % ) patient in group A , and two ( 4 % ) patients in group B ( p<0.002 ) . The triple regimen was well tolerated and did not increase the frequency or severity of side effects . Conclusions : The study demonstrates that for the treatment of interferon non-responder hepatitis C patients , the association of interferon-ribavirin has a negligible long term effect whereas a triple regimen including interferon , ribavirin , and amantadine can be an effective and safe treatment Although the antiviral effects of amantadine sulphate ( 1‐aminoadamantan sulphate ) have not been characterized for the hepatitis C virus ( HCV ) , previous pilot studies have suggested promising results in patients with chronic hepatitis C. The aim of the present study was to compare the efficacy , safety , and health‐related quality of life ( HRQOL ) of interferon alfa ( IFN‐α ) alone or in combination with oral amantadine for treatment of chronic hepatitis C. One hundred nineteen previously untreated patients with chronic hepatitis C were r and omly allocated to treatment with IFN‐α2a at a dose of 6 megaunits 3 times a week subcutaneously for 24 weeks , followed by 3 megaunits thrice weekly for an additional 24 weeks plus amantadine sulphate administered orally 100 mg twice a day for 48 weeks or the same IFN regimen plus a matched placebo . The primary endpoint was undectable serum HCV RNA ( < 1,000 copies/mL ) at week 24 after treatment . At the end of treatment and the 24‐week follow‐up period serum HCV RNA was undetectable in 20 ( 34 % ) and 6 ( 10 % ) of the 59 patients treated with the combination IFN‐α plus amantadine and in 20 ( 33 % ) and 13 ( 22 % ) of the 60 patients treated with IFN‐α alone , respectively ( P = n.s . ) . Discontinuation of therapy for adverse events was similar in both treatment groups . Although treatment with IFN‐α worsened HRQOL , combination with amantadine showed a substantial trend to improve fatigue and vigor . In conclusion , combination therapy IFN‐α plus amantadine is as effective as IFN‐α monotherapy in previously untreated patients with chronic hepatitis BACKGROUND / AIMS Treatment options for interferon-non-responders ( INF-NR ) with chronic hepatitis C are limited . Our aim was to compare efficacy and tolerability of an interferon-alfa-2a ( INF ) , ribavirin ( RIBA ) and amantadine ( AMA ) combination with those of an INF and RIBA combination . METHODS 30 patients with biopsy proven chronic hepatitis C were r and omised to INFRIBA-AMA or INF-RIBA , stratified according to genotype ( 1/4 versus 2/3 ) and presence or absence of cirrhosis . They were treated with INF 6 million units subcutaneously daily for the first four weeks , RIBA ( > or=75 kg 1200 mg , < 75 kg 1000 mg ) with or without AMA 200 mg daily . If serum hepatitis C RNA was undetectable after 28 days , therapy was continued for a total of 48 weeks and INF was reduced to 6 million units thrice weekly ( tiw ) . After stopping therapy all patients were followed up for six months . RESULTS The end of treatment response was 25 % ( 4/16 ) after INF-RIBA-AMA and 29 % ( 4/14 ) after INF-RIBA , and a sustained virologic response ( SVR ) was observed in 19 % ( 3/16 ) in the triple therapy group compared to 14 % ( 2/14 ) in the double therapy group , with a similar safety and tolerability profile . CONCLUSION Although similarly tolerated triple combination with INF , RIBA and AMA does not seem to offer relevant efficacy advantages over double combination with INF and RIBA in INF non-responders with chronic hepatitis Background With only a third of Latinos achieving sustained virologic response ( SVR ) , there is a need for enhanced HCV treatment . Amantadine has been proposed to improve response rates in addition to st and ard therapy with peginterferon α and ribavirin . Our objective is to evaluate whether triple therapy with amantadine improves SVR rates in this special population . Method Treatment-naïve Latino subjects with HCV genotype 1 infection were r and omized to receive peginterferon α-2a plus weight-based ribavirin for 48 weeks ( double therapy ) or the same regimen plus amantadine 200 mg daily ( triple therapy ) . The primary endpoint was SVR . Predictors of liver fibrosis using APRI and Forns indices were also evaluated . Results We enrolled 124 patients with chronic hepatitis C genotype 1 . Sixty-three received conventional therapy and 61 patients had triple therapy with amantadine . SVR at week 72 was achieved in 25 patients ( 39.7 % ) vs. 26 patients ( 42.6 % ) in the double and triple regimen , respectively ( p = 0.561 ) . After multivariate analysis , advanced fibrosis , obesity , and low pretreatment ALT levels were associated with non-response in both groups ( p = 0.0234 , p = 0.0012 , p = 0.0249 , respectively ) . APRI values delimited an area under the ROC curve ( AUROC ) of 0.724 and Forns index with AUROC of 0.733 . There was no difference between both indices in predicting significant fibrosis ( Knodell index : F3–F4 ) . Conclusion Our study demonstrates that the addition of amantadine to st and ard treatment of chronic HCV does not improve SVR rates in Latino patients with genotype 1 . Further research to improve response rates in this special population is needed BACKGROUND In phase 2 trials , telaprevir , a hepatitis C virus ( HCV ) genotype 1 protease inhibitor , in combination with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , has shown improved efficacy , with potential for shortening the duration of treatment in a majority of patients . METHODS In this international , phase 3 , r and omized , double-blind , placebo-controlled trial , we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups : a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks ( T12PR group ) , followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point ; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks ( T8PR group ) , followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria ; or a group receiving placebo with peginterferon-ribavirin for 12 weeks , followed by 36 weeks of peginterferon-ribavirin ( PR group ) . The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment ( sustained virologic response ) . RESULTS Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response ( 75 % and 69 % , respectively , vs. 44 % ; P<0.001 for the comparison of the T12PR or T8PR group with the PR group ) . A total of 58 % of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment . Anemia , gastrointestinal side effects , and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone . The overall rate of discontinuation of the treatment regimen owing to adverse events was 10 % in the T12PR and T8PR groups and 7 % in the PR group . CONCLUSIONS Telaprevir with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment , with only 24 weeks of therapy administered in the majority of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ADVANCE Clinical Trials.gov number , NCT00627926 . ) OBJECTIVE : Although treatment of hepatitis C has improved , up to 50 % do not respond to st and ard therapy with interferon regimes or can not tolerate the treatment due to side effects . The purpose of the present investigation was to evaluate the safety and effectiveness of the antiviral drug amantadine for the treatment of hepatitis C in those who had either previously failed interferon therapy or were not c and i date s for interferon . DESIGN : A prospect i ve double-blind r and omized placebocontrolled trial . SETTING : Outpatient research clinic of a teaching hospital . PATIENTS / PARTICIPANTS : One hundred fifty-two patients with confirmed hepatitis C with abnormal liver enzymes , detectable hepatitis C RNA in the blood , and abnormal liver histology by biopsy were r and omized to receive treatment or placebo . MEASUREMENTS AND MAIN RESULTS : Patients received either amantadine 100 mg twice daily by mouth or placebo for 6 months . After 6 months , placebo-treated patients were crossed over and treated with amantadine for 6 months and amantadine-treated subjects received 6 additional months of therapy . Amantadine therapy result ed in a significant decline in serum alanine aminotransferase compared to placebo ( P=.03 ) . Nine percent cleared the virus at the end of therapy and 6.8 % had a sustained virologic response 6 months after discontinuation of amantadine , but this was not statistically significant . Side effects were minimal , and the social quality of life survey improved with 12 months of amantadine ( P=.02 ) . CONCLUSIONS : Oral amantadine may provide a safe alternative treatment for those patients who are intolerant or unresponsive to interferon BACKGROUND / AIMS Electronic search es on data bases for r and omised clinical trials and controlled clinical trials do not identify as many trials as h and search es , and trial reporting may be flawed . The aims were to identify all fully reported r and omised clinical trials in the Journal of Hepatology and to make a qualitative assessment of the reporting . METHODS The publications were identified by systematic ally h and search ing the full text of the journal and search ing MEDLINE . Central dimensions of trial quality were used to assess the reporting quality of the trials . RESULTS R and omised clinical trials represented 8.4 % of the original articles ( 171/2028 ) . Ten original articles ( 0.5 % ) could not be classified . A search on MEDLINE identified 81.3 % of the r and omised clinical trials , i.e. , 139 out of the 171 identified by the h and search . A total of 166 r and omised clinical trials could be quality assessed . Forty-seven ( 28.3 % ) of them reported adequate generation of allocation sequence ; 22 ( 13.3 % ) adequate allocation concealment ; 95 ( 57.2 % ) allowed intention-to-treat analysis with only a few losses to follow-up ; 50 ( 30.1 % ) were double-blind ; 33 ( 19.9 % ) reported sample -size calculations ; 13 trials ( 7.8 % ) employed the crossover design ; and the median number of subjects per intervention arm in parallel group trials was 19 subjects ( interquartile range : 11 - 31 ; range : 5 - 519 ) . The quality of reporting was significantly better in regular issue articles than in supplement articles . CONCLUSIONS Many important r and omised clinical trials are published in the Journal of Hepatology , but there seems to be ample room for improvement of quality of reporting Background : An early virological response to interferon‐α treatment is a strong predictor of sustained response , but it has never been exploited to stratify patients in clinical trials UNLABELLED The impact of amantadine on virologic response rates of interferon-based treatment of chronic hepatitis C is controversial . The aim of this study was to compare virological response rates in patients with chronic hepatitis C virus (HCV)-1 infection treated with 400 mg amantadine or placebo in combination with peginterferon alfa-2a ( 40 kD ) and ribavirin for 48 weeks . Seven hundred four previously untreated chronically HCV-1-infected patients ( mean age , 46 + /- 12 years ) were r and omized to ( A ) amantadine-sulphate ( 400 mg/day ) ( n = 352 ) or ( B ) placebo ( n = 352 ) , both in combination with 180 microg peginterferon alfa-2a once weekly and ribavirin ( 1000 - 1200 mg/day ) for 48 weeks . End of treatment and sustained virological response after a 24-week follow-up period were assessed by qualitative reverse transcription polymerase chain reaction ( RT-PCR ) ( sensitivity , 50 IU/mL ) . Demographic and baseline virological parameters were similar in both treatment groups . In groups A and B , 231 of 352 patients ( 66 % ) and 256 of 352 patients ( 72 % ) achieved an end of treatment response , and 171 of 352 patients ( 49 % ) and 186 of 352 patients ( 53 % ) a sustained virological response , respectively . On-treatment dropout rate in the amantadine group was significantly higher than in the placebo group ( 32 % versus 23 % ; P = 0.01 ) . However , adverse events and laboratory abnormalities were similar between both groups . Per- protocol analysis revealed similar sustained virological response rates in both treatment groups ( 53 % versus 55 % ) . CONCLUSION In this large placebo-controlled multicenter study , amantadine even at a dose of 400 mg/day did not improve virological response rates of peginterferon alfa-2a and ribavirin in patients with chronic genotype HCV-1 infection Evidence shows that the quality of r and omized clinical trials ( RCTs ) affects estimates of intervention efficacy , which is significantly exaggerated in low- quality trials . The present study examines the quality of all 235 RCTs published in HEPATOLOGY from the initiation in 1981 through August 1998 . Quality was assessed by means of a vali date d 5-point scale and separate quality components associated with empirical evidence of bias . Only 26 % of all RCTs reported sample size calculations , 52 % adequate generation of the allocation sequence , 34 % adequate allocation concealment and 34 % double-blinding . The median quality score of all trials was 3 points ( range , 1 - 5 points ) . Multiple logistic regression analysis explored the association between quality and therapeutic areas , number of centers , external funding , year of publication , and country of origin . High- quality trials were most likely to investigate portal hypertension ( odds ratio [ OR ] : 2.4 ; 95 % CI : 1.1 - 5.5 ; P = .03 ) , be multicentered ( OR : 3.4 ; 95 % CI : 1.3 - 8.9 ; P = .01 ) , sponsored by public organizations ( OR : 4.2 ; 95 % CI : 2.1 - 8.6 ; P = .0001 ) , or the drug and device industry ( OR : 4.7 ; 95 % CI : 2.2 - 10.2 ; P = .0001 ) compared with other therapeutic areas , single-center trials , and trials with no external funding . Quality did not improve with time and was not associated with country of origin . The main conclusions are that the quality of RCTs in HEPATOLOGY needs improvement and that the probability of high quality increased with the number of centers involved and external funding BACKGROUND Patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 often need 48 weeks of peginterferon-ribavirin treatment for a sustained virologic response . We design ed a noninferiority trial ( noninferiority margin , -10.5 % ) to compare rates of sustained virologic response among patients receiving two treatment duration s. METHODS We enrolled patients with chronic infection with HCV genotype 1 who had not previously received treatment . All patients received telaprevir at a dose of 750 mg every 8 hours , peginterferon alfa-2a at a dose of 180 μg per week , and ribavirin at a dose of 1000 to 1200 mg per day , for 12 weeks ( T12PR12 ) , followed by peginterferon-ribavirin . Patients who had an extended rapid virologic response ( undetectable HCV RNA levels at weeks 4 and 12 ) were r and omly assigned after week 20 to receive the dual therapy for 4 more weeks ( T12PR24 ) or 28 more weeks ( T12PR48 ) . Patients without an extended rapid virologic response were assigned to T12PR48 . RESULTS Of the 540 patients , a total of 352 ( 65 % ) had an extended rapid virologic response . The overall rate of sustained virologic response was 72 % . Among the 322 patients with an extended rapid virologic response who were r and omly assigned to a study group , 149 ( 92 % ) in the T12PR24 group and 140 ( 88 % ) in the T12PR48 group had a sustained virologic response ( absolute difference , 4 percentage points ; 95 % confidence interval , -2 to 11 ) , establishing noninferiority . Adverse events included rash ( in 37 % of patients , severe in 5 % ) and anemia ( in 39 % , severe in 6 % ) . Discontinuation of all the study drugs was based on adverse events in 18 % of patients overall , as well as in 1 % of patients ( all of whom were r and omly assigned ) in the T12PR24 group and 12 % of the patients r and omly assigned to the T12PR48 group ( P<0.001 ) . CONCLUSIONS In this study , among patients with chronic HCV infection who had not received treatment previously , a regimen of peginterferon-ribavirin for 24 weeks , with telaprevir for the first 12 weeks , was noninferior to the same regimen for 48 weeks in patients with undetectable HCV RNA at weeks 4 and 12 , with an extended rapid virologic response achieved in nearly two thirds of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ILLUMINATE Clinical Trials.gov number , NCT00758043 . ) From August 1978 until March 1979 , 14 batches of anti-D immune globulin contaminated with hepatitis C virus ( HCV ) genotype 1b ( 20 , 000 - 480,000 copies/dose ) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany . All 2,867 women involved had been recalled after January 12 , 1979 for repeated screening of alanine transaminase ( ALT ) . They were prospect ively followed in regional centers . We have reexamined a cohort of 1,018 women ( median age 24 , range 16 - 38 years at infection ) on follow-up for 20 years in 9 representative centers . Within 6 months after anti-D administration , 10 % of these women had no evidence of disease and 90 % had acute hepatitis C ( n = 917 ) including 49 % with symptomatic and 22 % with icteric course . After 20 years , 85 % of the 917 affected women still tested positive for HCV antibodies ( among them 3 % responded to interferon treatment ) and 55 % were positive for HCV RNA ( among them 7 % were nonresponders to interferon and 3 % were apparent HCV carriers ) . Only 4 ( 0.4 % ) had overt cirrhosis . Two ( 0.2 % ) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis , respectively . Histology obtained in 44 % of the viremic women showed hepatitis of minimal to moderate grade in 96 % , portal fibrosis in 47 % , and septal fibrosis in 3 % of the cases . In conclusion , formerly healthy young women , without hepatic comorbidity , may clear HCV ( 1b ) infection in half of the cases or develop mild chronic hepatitis C with low risk of progression to cirrhosis within 20 years BACKGROUND A significant proportion of hepatitis C patients treated with unmodified interferon plus ribavirin fail to respond . The optimal therapy for these patients has not been established yet . The objective of this study was to assess the efficacy and safety of peginterferon plus ribavirin with or without amantidine in such patients . METHODS In this open-label , prospect i ve controlled trial , a total of 63 patients were r and omly divided into groups A and B with a ratio of 1:2 . Group A ( 21 patients ) received weekly peginterferon alpha-2b , 1.5 microg/kg concomitantly with ribavirin 1000 - 1200 mg per day . Group B ( 42 patients ) received peginterferon and ribavirin as in group A , plus amantadine [ corrected ] 200 mg per day . RESULTS At the completion of treatment , serum levels of hepatitis C virus RNA were undetectable in 14 % and 12 % of patients in groups A and B , respectively ( P = NS ) . Hepatitis C virus RNA remained undetectable 24 weeks after the end of treatment in one patient ( 5 % ) in group A and three patients ( 7 % ) in group B ( P = NS ) . Sustained viral clearance was associated with sustained normalization of serum alanine aminotransferase level . Both drug regimens had similar side effect profiles . CONCLUSION Peginterferon plus ribavirin therapy with or without amantadine [ corrected ] is associated with a low sustained virological response in patients who failed interferon and ribavirin combination therapy BACKGROUND / AIMS A recent pilot study suggested that 18 % of patients with hepatitis C viral infection achieved a sustained response to a 6-month course of 200 mg of oral amantadine alone with disappearance of serum hepatitis C virus ribonucleic acid . We prospect ively studied 30 naive patients with chronic hepatitis C viral infection for the possible role of amantadine in improving the efficiency of interferon for the treatment of chronic hepatitis C. METHODOLOGY Patients were assigned into two groups on a double-blind and r and omized controlled basis . Placebo group received 4.5 MU of interferon alfa-2a thrice weekly and oral placebo daily for 24 weeks . Amantadine group received a combination of the interferon and 200 mg of oral amantadine daily for 24 weeks . Patients were observed and tested for blood chemistry every week for the initial 4 weeks and every 2 weeks thereafter during the treatment until 24 weeks . After the end of treatment , patients were followed up at 4-week intervals for an additional 12 months . RESULTS At the end of treatment , 5 ( 33.3 % ) patients responded to the combination therapy , and 7 ( 46.7 % ) patients responded to interferon therapy alone . Twelve months after cessation of the treatment , 3 ( 21.4 % ) patients had a sustained complete response to the combination therapy , and 3 ( 20.0 % ) patients had a sustained complete response to interferon alone ( P = 0.64 ) . CONCLUSION Amantadine does not increase the efficacy of interferon in the treatment of chronic hepatitis BACKGROUND Peginterferon-ribavirin therapy is the current st and ard of care for chronic infection with hepatitis C virus ( HCV ) . The rate of sustained virologic response has been below 50 % in cases of HCV genotype 1 infection . Boceprevir , a potent oral HCV-protease inhibitor , has been evaluated as an additional treatment in phase 1 and phase 2 studies . METHODS We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were r and omly assigned to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( the control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks , and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . Nonblack patients and black patients were enrolled and analyzed separately . RESULTS A total of 938 nonblack and 159 black patients were treated . In the nonblack cohort , a sustained virologic response was achieved in 125 of the 311 patients ( 40 % ) in group 1 , in 211 of the 316 patients ( 67 % ) in group 2 ( P<0.001 ) , and in 213 of the 311 patients ( 68 % ) in group 3 ( P<0.001 ) . In the black cohort , a sustained virologic response was achieved in 12 of the 52 patients ( 23 % ) in group 1 , in 22 of the 52 patients ( 42 % ) in group 2 ( P=0.04 ) , and in 29 of the 55 patients ( 53 % ) in group 3 ( P=0.004 ) . In group 2 , a total of 44 % of patients received peginterferon-ribavirin for 28 weeks . Anemia led to dose reductions in 13 % of controls and 21 % of boceprevir recipients , with discontinuations in 1 % and 2 % , respectively . CONCLUSIONS The addition of boceprevir to st and ard therapy with peginterferon-ribavirin , as compared with st and ard therapy alone , significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection . The rates were similar with 24 weeks and 44 weeks of boceprevir . ( Funded by Schering-Plough [ now Merck ] ; SPRINT-2 Clinical Trials.gov number , NCT00705432 . ) BACKGROUND No effective therapy exists for interferon non-responding chronic hepatitis C patients . AIMS Pilot study evaluating the potential efficacy and safety of triple antiviral therapy in interferon-alpha non-responders . PATIENTS AND METHODS Twenty consecutive adult patients with chronic hepatitis C who had failed to respond to a 6-month course of interferon alpha were r and omly assigned to receive a combination of interferon alpha + oral ribavirin ( double therapy ) , or the same combination + oral amantadine ( triple therapy ) , for 6 months . RESULTS By the end of therapy , normal alanine transaminase ( biochemical response ) was obtained in 2 out of 10 patients on double therapy but in 7 out of 10 on triple therapy ( p < 0.05 ) , and negative serum hepatitis C virus ( HCV ) RNA ( virological response ) occurred in 1 out of 10 patients on double therapy but in 7 out of 10 patients on triple therapy ( p < 0.01 ) . Six months after therapy , biochemical response was sustained in 1 ( double therapy ) and 4 patients ( triple therapy ) , respectively , and the virological response was sustained in no patient on double therapy but in 3 patients on triple therapy . CONCLUSIONS Triple antiviral therapy seems to be able to induce biochemical and virological responses in interferon alpha non-responders with chronic hepatitis BACKGROUND Up to 60 % of patients with hepatitis C virus ( HCV ) genotype 1 infection do not have a sustained virologic response to therapy with peginterferon alfa plus ribavirin . METHODS In this r and omized , phase 3 trial , we evaluated the addition of telaprevir to peginterferon alfa-2a plus ribavirin in patients with HCV genotype 1 infection who had no response or a partial response to previous therapy or who had a relapse after an initial response . A total of 663 patients were assigned to one of three groups : the T12PR48 group , which received telaprevir for 12 weeks and peginterferon plus ribavirin for a total of 48 weeks ; the lead-in T12PR48 group , which received 4 weeks of peginterferon plus ribavirin followed by 12 weeks of telaprevir and peginterferon plus ribavirin for a total of 48 weeks ; and the control group ( PR48 ) , which received peginterferon plus ribavirin for 48 weeks . The primary end point was the rate of sustained virologic response , which was defined as undetectable HCV RNA 24 weeks after the last planned dose of a study drug . RESULTS Rates of sustained virologic response were significantly higher in the two telaprevir groups than in the control group among patients who had a previous relapse ( 83 % in the T12PR48 group , 88 % in the lead-in T12PR48 group , and 24 % in the PR48 group ) , a partial response ( 59 % , 54 % , and 15 % , respectively ) , and no response ( 29 % , 33 % , and 5 % , respectively ) ( P<0.001 for all comparisons ) . Grade 3 adverse events ( mainly anemia , neutropenia , and leukopenia ) were more frequent in the telaprevir groups than in the control group ( 37 % vs. 22 % ) . CONCLUSIONS Telaprevir combined with peginterferon plus ribavirin significantly improved rates of sustained virologic response in patients with previously treated HCV infection , regardless of whether there was a lead-in phase . ( Funded by Tibotec and Vertex Pharmaceuticals ; REALIZE Clinical Trials.gov number , NCT00703118 . ) Background : Treatment of hepatitis C virus ( HCV ) infection with interferon ( IFN ) in older patients may not be feasible on account of side effects : we , therefore , attempted combined treatment with amantadine hydrochloride ( AH ) in order to improve not only the flu-like symptoms associated with IFN but also the anti-viral effect . Methods : Patients over 65 years of age , ( n=165 ) , who had failed to eradicate HCV infection after previous treatment with IFN were r and omized into three groups and treated for 12 months , group A received AH 100 mg twice per day ; group B received IFNalpha-n(3 ) 6 M units every other day for 3 months followed by 3 MU and group C the same dose of IFNalpha-n(3 ) , as in B , and AH 200 mg per day . Results : Group A , 42 patients agreed to undergo treatment ( genotype 1b n=39 ) ; at the end of treatment 21 patients ( 50 % ) had normal ALT and seven ( 17 % ) negative polymerase chain reaction ( PCR ) . HCV-RNA was not detectable in seven patients at the sixth month follow-up and in six ( 14 % ) after 23plus minus2 months . Group B , 39 patients accepted the treatment ( genotype 1b n=31 ) ; at the end of treatment , 17 patients ( 44 % ) had normal ALT and 13 negative PCR ( 13 % ) . HCV-RNA was not detectable in nine patients ( 23 % ) at the sixth month of follow-up and in eight ( 21 % ) after 22plus minus4 months . Group C , 38 patients accepted the treatment ( genotype 1b n=32 ) ; at the end of treatment , 20 ( 53 % ) patients had normal ALT and 15 negative PCR ( 39 % ) . HCV-RNA was not detectable in 15 patients at the sixth month follow-up and in 11 after 21plus minus4 months ( 29 % ) . Forty-six patients did not accept the scheme of treatment and 26 of them had a follow-up of 20plus minus3 months . HCV-RNA copies and prevalence of genotype 1b were comparable to the treated groups : HCV-RNA was fluctuating or unchanged during the entire follow-up . Conclusions : AH associated with IFN was able to improve the negativization of HCV-RNA and sustained response to IFN and decreased the malaise associated with IFN ; an increase in viral copies was observed under AH in about 40 % Chronic hepatitis C ( non-A , non-B hepatitis ) is a common and often progressive viral liver disease . To assess the efficacy of therapy with the antiviral agent interferon alfa , we r and omly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks , or to no treatment . The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon ( P less than 0.001 ) and 28 percent in those treated with 1 million units ( P less than 0.02 ) , but only 8 percent in untreated patients . The serum alanine aminotransferase level became completely normal in 22 of the 26 patients ( 85 percent ) who responded to treatment with 3 million units of interferon and 9 of the 16 patients ( 56 percent ) who responded to treatment with 1 million units . The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation . Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units . We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C , although relapse after the cessation of treatment is common The benefit of the triple therapy ( interferon + amantadine + ribavirim ) is still unknown . The efficacy of induction doses of interferon-alpha-2a monotherapy or in combination with ribavirin and /or amantadine was evaluated in interferon non-responders with chronic hepatitis C. A total of 378 patients were r and omized . All the groups received the same doses and duration of interferon-alpha-2a : ( i ) interferon 9 MUI/day for 4 weeks and then 3 MUI/3 t.i.w . for 44 weeks ( n = 53 ) ; ( ii ) interferon in combination with amantadine 100 mg twice daily for 48 weeks ( n = 111 ) ; ( iii ) interferon in combination with ribavirin 1000 - 1200 mg ( n = 106 ) ; ( iv ) interferon in combination with amantadine and ribavirin ( n = 108 ) . Baseline parameters were similar in the four groups . Sustained virological and biochemical responses were 13 % , 6 % , 18 % and 22 % respectively . No significant differences were found between double ribavirin arm vs triple therapy , but the difference was significant between interferon-amantadine ( P = 0.008 ) and triple therapy ( P = 0.0005 ) . Hence , the induction doses of interferon in combination with ribavirin or ribavirin plus amantadine showed encouraging results in patients with chronic hepatitis C who were resistant to interferon . However , triple therapy is not superior to double We evaluated oral ribavirin as therapy for chronic hepatitis C infection in a pilot study including 10 patients . Patients ( 7 men , 3 women ; mean age 40 years , range 23 - 54 ) all had biopsy-proven chronic non-A , non-B hepatitis and were repeatedly positive for antibodies to hepatitis C virus . Treatment was with oral ribavirin 1000 - 1200 mg per day in two divided doses for 12 weeks . The median serum alanine aminotransferase concentration for all patients at enrollment was 3.15 mu kat/l ( range 1.22 - 7.79 ) and decreased significantly ( p less than 0.005 ) to 1.25 mu kat/l ( 0.78 - 2.04 ) after 12 weeks of treatment . Within 6 weeks of the end of treatment the median serum alanine aminotransferase concentration was not significantly different from that before treatment . Side-effects were mild and fully reversible after cessation of therapy . We conclude that ribavirin is the first drug to offer a potentially effective oral treatment for chronic hepatitis C. It should be further evaluated in controlled trials , possibly in combination with interferon alpha BACKGROUND / AIMS The antiviral agent amantadine may have activity against the hepatitis C virus . To determine whether the combination of interferon-alpha plus amantadine was more effective than interferon monotherapy we conducted a multicentre clinical trial in untreated patients with chronic hepatitis C infection . METHODS We performed a pilot study in two centres ( 36 patients ) to determine the number needed for a statistically significant clinical trial and then conducted a multicentre , r and omized controlled clinical trial involving 14 centres and 143 patients . RESULTS There was no significant difference in sustained response rates in patients receiving interferon and amantadine compared to those receiving interferon alone . The on treatment response rate at 3 months was 65 % on combination vs. 49 % on interferon alone ( P = 0.05 ) while the sustained response was 18 and 15 % , respectively . CONCLUSIONS Combination therapy with interferon plus amantadine does not lead to a significant increase in sustained response rates when compared to interferon monotherapy Interferon alpha and ribavirin ( RBV ) combination therapy is associated with decreases in haemoglobin ( Hb ) concentrations and anaemia . The aim of this analysis was to better characterize the magnitude and frequency of Hb changes and risk factors . This retrospective analysis evaluated treatment-related changes in Hb in 677 patients who participated in either of two interferon alpha-2b plus RBV studies for chronic hepatitis C virus ( HCV ) infection . Study 1 included 192 interferon alpha-naïve patients r and omized to receive RBV 1000 - 1200 mg/day plus interferon alpha-2b 3 million IU daily or three times weekly for 48 weeks . Study 2 included 485 interferon alpha-experienced patients r and omized to receive RBV 1000 - 1200 mg daily plus interferon alpha-2b 3 million IU daily or three times weekly for 4 weeks , followed by three times weekly dosing for 44 weeks . More than 50 % of all patients experienced a decrease in Hb > or = 30 g/L. Women were 4.4 times as likely as men to experience a Hb level of < 100 g/L ; however , men were at a 40 % higher risk to experience a Hb decline of > 30 g/L from baseline . Daily use of interferon alpha-2b did not impact the magnitude of Hb decrease . In this pooled analysis , RBV dose reduction result ed in increases in Hb concentration of approximately 10 g/L. Lower baseline creatinine clearance , higher baseline Hb levels and increased age were independently associated with increased risk of Hb decreases of > 27.7 % . Lower baseline weight was not associated with increased risk of Hb decrease . Substantial Hb decreases occur frequently with interferon alpha/RBV combination therapy . Sex , the magnitude of the Hb decline and renal function are potentially important factors to consider in patients receiving RBV . Further research is needed to determine the impact on virological response and to develop strategies to manage the medical consequences The antiviral efficacy of amantadine in patients with chronic hepatitis C is controversial . In this r and omized , prospect i ve , placebo-controlled , multicenter trial , triple therapy with interferon alfa (IFN-alpha)-2a plus ribavirin and amantadine ( amantadine group ) was compared with combination therapy IFN-alpha plus ribavirin ( control group ) . Four hundred previously untreated patients with histologically proven chronic hepatitis C were r and omly allocated to treatment with amantadine sulphate ( 100 mg twice daily orally ) or a matched placebo together with IFN-alpha induction plus ribavirin ( 1,000 - 1,200 mg/day orally ) for 48 weeks . The primary end point was sustained virologic response ( SVR ) defined as undetectable serum hepatitis C virus ( HCV ) RNA ( < 100 copies/mL ) 24 weeks after the end of treatment . SVR was observed in 52 % of the amantadine group and in 43.5 % of the control group ( P = .11 ) . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 39 % and 31 % , respectively . The virologic on-treatment response rate in week 24 was significantly higher in the amantadine group as compared with the control group ( 70 % vs. 59 % , respectively , P = .016 ) . This beneficial effect was mainly related to HCV type 1-infected patients ( 63 % vs. 47 % , respectively , P = .012 ) . Independent factors associated with SVR , according to multiple logistic regression analysis , were amantadine treatment , low baseline HCV RNA , platelet counts ( > /=250/nL ) , pretreatment ALT quotient > /=3 , and GGT level ( < 28 U/L ) as well as HCV genotypes other than 1 . In conclusion , although we could not demonstrate a significant advantage of the triple regimen in univariate analysis , multivariate analysis offers arguments that amantadine should be considered as a potential anti-HCV drug in future studies The optimal therapy for patients with chronic hepatitis C who have not responded to interferon ( IFN ) is still an unsolved issue . The aim of this study was to evaluate the efficacy and tolerability of a high dose of IFN-alpha2a plus amantadine for chronic hepatitis C patients who were non-responders to a previous course of IFN . Forty consecutive patients with chronic hepatitis C , genotype 1b , who had not responded to IFN-alpha , were r and omized to receive : ( i ) IFN 4.5 MU daily plus amantadine 200 mg/day for 4 weeks and then IFN 6 MU thrice weekly plus amantadine 200 mg/day for an additional 5 months ( group A ) or ( ii ) IFN alone at the same dosage and duration ( group B ) . After 1 month of therapy , normal alanine aminotransferase ( ALT ) values were observed in three of 21 ( 14.3 % ) patients in group A and in three of 19 ( 15.8 % ) in group B ; serum hepatitis C virus (HCV)-RNA clearance was observed in one patient ( 4.8 % ) in group A and in six ( 31.6 % ) in group B. At the end of treatment , six patients ( 28.6 % ) in group A and three ( 15.8 % ) in group B had normal ALT levels ; however , HCV-RNA in serum was detectable in all of them at levels comparable to the basal values ; an ALT relapse occurred within 3 months of stopping therapy . The combination of daily IFN plus amantadine was ineffective in this setting BACKGROUND / AIMS To evaluate the efficacy and tolerance of amantadine in combination with interferon in the treatment of chronic hepatitis C. METHODS Multi-centre trial including 180 chronic hepatitis C patients without cirrhosis , r and omly enrolled to receive interferon 6 MU every other day for 6 months followed by 3 MU for further 6 months ( group A , 90 patients ) , or the same schedule plus amantadine 200 mg/day ( group B , 90 patients ) . Primary end-point was a sustained virological and biochemical response , secondary end-points were on-treatment ( third month ) and end-of-treatment response rates . RESULTS The two groups had similar demographic , biochemical and virological characteristics . A sustained response after 6 months follow-up was observed in 17 % of group A and 24 % of group B patients ( P not significant ) , an end-of-treatment response was observed in 37 % in group A and 47 % in group B ( P not significant ) , an on-treatment response was observed in 46 % in group A and 61 % in group B patients ( P < 0.05 ) . No major side effects due to amantadine administration were observed . CONCLUSIONS Adding amantadine to interferon did not improve the sustained treatment efficacy . However , the rate of early response at the third month of therapy was significantly higher in the combination therapy group Background and aim : In this study , we compared the efficacy of triple therapy ( interferon alfa , ribavirin , and amantadine ) with st and ard therapy ( interferon alfa and ribavirin ) in treatment naïve patients with chronic hepatitis C virus ( HCV ) . Methods : In this prospect i ve , r and omised , double blind , placebo controlled , multicentre study , 85 patients ( amantadine group ) received a three drug regimen of interferon alfa-2b 3 million units three times per week , ribavirin 1000–1200 mg daily in divided doses , and amantadine 100 mg twice daily , and 86 patients ( placebo group ) received interferon alfa-2b , ribavirin , and identical placebo . Treatment was discontinued at 24 weeks if patients had detectable HCV RNA by polymerase chain reaction ( PCR ) . All patients were followed for 24 weeks after completion of treatment . The primary end point was undetectable HCV-RNA by PCR at 24 weeks ( sustained viral clearance ) after completion of treatment . Results : At the end of treatment , HCV RNA clearance was seen in 32.9 % of the amantadine group and 38.4 % of the placebo group ( p = 0.3 ) . Sustained virological response was seen in 24.7 % of the amantadine group and in 27.9 % of the placebo group by intention to treat analysis ; response rate was 30.4 % and 34.8 % , respectively , in those who completed 24 weeks of treatment . Poor response was seen in both groups among cirrhotics , African-Americans , genotype 1 , and those with a higher viral load . By multivariate analysis , genotype 1 , high viral load , and low serum albumin were the only predictors of poor response . Addition of amantadine to the st and ard regimen did not result in any unexpected side effects . Conclusion : Response to triple therapy of interferon alfa , ribavirin , and amantadine was similar to st and ard therapy of interferon alfa and ribavirin . Our results suggest that amantadine has no role in the management of HCV In primary interferon‐α ( IFN‐α ) nonresponders with chronic hepatitis C , retreatment with IFN‐α has only limited efficacy with sustained response rates below 10 % . Therefore , the aims of the present study were to compare the efficacy and safety of IFN‐α alone or in combination with amantadine sulphate in nonresponders to previous IFN‐α monotherapy . Fifty‐five IFN‐α nonresponders with chronic hepatitis C ( mean age : 46.6 years ) received IFN‐α 6 MIU thrice weekly for 24 weeks followed by 3 MIU thrice weekly for additional 24 weeks . Amantadine sulphate ( n=26 ) or a matched placebo ( n=29 ) was given orally twice daily for 48 weeks . Because of a low initial response rate at week 12 ( 13/55 patients ) and a high breakthrough rate ( 8/13 patients ) after IFN‐α dose reduction in week 24 , a virological end‐of‐treatment response with undetectable serum HCV‐RNA ( < 1000 copies/mL ) was achieved in only five patients ( IFN‐α/amantadine sulphate , one patient ; IFN‐α/placebo , four patients ) . After 24 weeks follow‐up a sustained virological response was observed in only two patients receiving IFN‐α and placebo . Health‐related quality ‐of‐life analysis showed a substantial improvement of the Profile of Mood States ( POMS ) scale concerning the subscales fatigue ( P < 0.05 ) and vigor ( P < 0.05 ) in patients receiving combined IFN‐α/amantadine sulphate treatment compared with those treated with IFN‐α alone . IFN‐α/amantadine sulphate combination therapy was well tolerated without any serious adverse events . In conclusion , retreatment with IFN‐α and amantadine sulphate does not increase the low sustained virological response rates of IFN‐α therapy in primary IFN‐α nonresponders with chronic hepatitis C , but may lead to a sustained improvement of health‐related quality ‐of‐life Non-A , non-B post-transfusion hepatitis is a sequela commonly associated with the receipt of blood products . In most prospect i ve series conducted before the introduction of surrogate and acquired immunodeficiency syndrome ( AIDS ) screening , otherwise unexplained abnormalities in serum alanine aminotransferase ( ALT ) levels developed in about 10 % of transfused patients during the 6 months after transfusion [ 1 - 3 ] . Usually , no concomitant serologic evidence of exposure to hepatitis A or B virus could be identified , suggesting that one or more non-A , non-B agents were responsible [ 4 ] . The abnormal ALT values persisted for more than 6 months in about 50 % of patients [ 5 , 6 ] . The magnitude of this disease was not appreciated before these prospect i ve studies because of the difficulty in recognizing these patients on the basis of symptoms . During the early phase of the illness , only a minority of patients experience severe fatigue , nausea , and vomiting , and even fewer manifest full-blown clinical symptoms including jaundice [ 1 ] . Those who have mild fatigue often blame it , perhaps correctly , on the disease for which they received the transfusion . Very few in whom prolonged abnormalities in serum aminotransferase levels develop complain of any symptoms , although some describe varying degrees of fatigue [ 7 ] . Rapidly progressive liver disease and acute symptomatic exacerbations are both uncommon in this form of chronic hepatitis , although the aminotransferase levels may remain abnormal or fluctuate for years . Several diagnostic tools , such as blood tests or biopsies , can detect signs of disease . These signs may exist in the absence of symptoms and may become the focus of attention or of therapy [ 8 ] . Disease is perceived by patients , however , if they have symptoms . Signs such as an abnormal ALT level or histologic evidence of inflammation do not themselves interfere with the quality of a person 's life . As long as liver function is compensated , a person may remain unaware of the presence of cirrhosis . Thus , the important concern for the patient with non-A , non-B post-transfusion hepatitis is the development of liver failure ( or liver cancer ) secondary to cirrhosis . Between 1972 and 1980 , we identified patients with non-A , non-B post-transfusion hepatitis . We recently evaluated this cohort , focusing on the presence or absence of clinical evidence of liver failure . Methods Between 1972 and 1980 , two prospect i ve studies of post-transfusion hepatitis were conducted at the University of California at Los Angeles ( UCLA ) . These studies have been previously described [ 9 ] . All patients had normal ALT levels before transfusion and were prospect ively identified as having developed non-A , non-B post-transfusion hepatitis when they met the following criteria : 1 ) the development of at least two consecutive abnormal ALT levels , at least one being twice the upper limit of normal or greater [ five times the upper limit of normal or greater in the first study ] , occurring within 6 months of transfusion ; 2 ) the absence of serologic evidence for recent hepatitis A ( negative IgM-specific antibody to hepatitis A ) or hepatitis B ( negative hepatitis B surface antigen [ HBsAg ] and negative IgM-specific antibody to hepatitis B core antigen [ anti-HBc ] ) ; and 3 ) the absence of any explanation for the abnormalities in the ALT levels other than the presence of presumed viral infection . Patients who developed post-transfusion hepatitis were asked to continue in the prospect i ve evaluation . Those whose ALT values became normal within 6 months of disease onset were considered to have had acute hepatitis and no additional follow-up was sought at that time . Those whose ALT values remained abnormal for longer than 6 months were considered to have developed chronic hepatitis and were asked to continue in an open-ended follow-up . Over the years , many study patients in whom chronic hepatitis developed were lost to follow-up for various reasons ( death , move from the area , loss of interest , or lack of desire for continued blood tests ) . In the fall of 1988 , a formal attempt was begun to locate all study patients in whom non-A , non-B post-transfusion hepatitis developed and to evaluate each for the presence or absence of symptoms or signs of hepatitis and evidence of clinical hepatic failure . Symptomatic hepatitis was defined as the presence of one or more of the following : jaundice , loss of appetite , weight loss , or fatigue . ( For fatigue to be considered to be significant , it had to interfere with the patient 's daily lifestyle . ) No symptom could be reasonably attributed to a coexistent disease process . Clinical hepatic failure was considered to exist if one or more of the following was found or had occurred : 1 ) Gastrointestinal bleeding of variceal origin ; 2 ) ascites [ not due to noncirrhotic causes ] ; 3 ) hepatic encephalopathy ; 4 ) hepatic coagulopathy [ abnormal prothrombin time not correctable by the parenteral administration of vitamin K ] ; 5 ) hypersplenism ( leukopenia or thrombocytopenia not due to noncirrhotic causes ; or 6 ) hypoalbuminemia ( a serum albumin level less than the normal range not due to noncirrhotic causes ) . A telephone interview was conducted to assess current and past health status of all surviving patients who could be located . Questions were design ed to identify problems related to hepatic failure . Where pertinent , requests were made to obtain outside medical records . Patients were also asked to su bmi t to a formal history and physical examination and to have blood obtained for the following tests : complete blood count , serum chemistry panel , prothrombin time , and partial thromboplastin time ( PT ) . If the patient agreed to come to UCLA , the examination was conducted by one of the investigators . In a few circumstances , the investigator went to the patient 's home . If the patient did not agree to these arrangements , medical records or examinations were sought from his or her personal physician . To be considered evaluable between 1989 and 1992 , patients had to have completed at least the telephone interview and the laboratory tests . If a patient was dead , a telephone interview was conducted with a family member ( or some other knowledgeable contact ) to ascertain the state of the patient 's previous health and the cause of death . In addition , requests were made to obtain pertinent medical records ( for example , death certificates or records of terminal hospitalization ) . Because of the variability in the duration of follow-up , the probability of clinical hepatic failure developing was calculated using life-table analysis [ 10 ] . The end point was the appearance of clinical hepatic failure . The time at risk began with the onset of post-transfusion hepatitis and extended until the end point was achieved , until the last medical evaluation , or until death without evidence of clinical hepatic failure . Other statistical comparisons were made by the chi-square test with the Yates correction or by the Student t-test [ 11 ] . Between 1972 and 1980 , 95 patients with non-A , non-B post-transfusion hepatitis were identified , including the 69 patients previously described [ 7 ] . In addition , 20 patients originally classified as having had hepatitis B have since been reclassified . Eighteen had evidence of anti-HBc in the early post-transfusion serum . None of these 18 patients tested positive for IgM-anti-HBc , and the anti-HBc disappeared shortly afterward in all cases . It was presumed that this finding represented passive transfusion of anti-HBc , and the patients were reclassified as having had non-A , non-B disease . Two patients had had post-transfusion increases in the titer of antibody to HBsAg ( anti-HBs ) ; the increases in both cases were low- grade and may have represented passive administration of anti-HBs . In retrospect , these patients were also not thought to have had hepatitis B viral infection , and they were also reclassified as having had non-A , non-B-induced disease . Finally , six patients were identified from the last part of the second prospect i ve study ; these patients have not been previously described . Of these 95 patients , 5 were excluded from this analysis . In one case , the abnormal ALT level did not reach the biochemical criterion of twice the upper limit of normal until after 6 months of disease . The other four patients had concomitant liver diseases ( sclerosing cholangitis [ one patient ] , biopsy-proven cirrhosis before transfusion ( one patient ) , and other potential causes of chronic hepatitis [ two patients ] ) , which made it difficult to determine the natural history of the transfusion-associated disease . We therefore evaluated the remaining 90 patients . Serologic tests for antibodies against hepatitis C ( anti-HCV ) have become available [ 12 ] . The stored sera of these patients were tested by a commercial assay that detects antibody to the C-100 HCV antigen ( Ortho HCV Enzyme-Linked Immunosorbent Assay [ ELISA ] Test System , Ortho Diagnostic Systems , Raritan , New Jersey ) , and those patients who failed to show seroconversion by this assay were tested by a second-generation test ( Ortho HCV 2.0 ELISA Test System ) [ 13 ] . Patients who were anti-HCV negative before transfusion ( or , in some cases , before the onset of disease ) and who developed anti-HCV in the first year after the hepatitis began were considered to have hepatitis C. ( These seroconversions were not considered to be a consequence of passive transfusion of antibody , because the anti-HCV was shown to persist for more than 6 months or because the titer , as reflected by the optical density , increased over time . ) In addition , patients who no longer had pretransfusion or predisease sera available were defined as having hepatitis C if anti-HCV was present for at least 6 months in their postdisease sera . The study was conducted in accordance with guidelines established by the Human Subject Protection Committee at UCLA . All potential study participants received an oral explanation of the study as well as an informed consent The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Objective The objective of this study was to compare the efficacy of anti-hepatitis C virus ( anti-HCV ) treatment schedules on the basis of an early virological response ( EVR ) , defined as undetectable serum HCV-RNA ( < 50 IU/ml ) after a 12-week induction course of peginterferon & agr;-2a ( PEG-IFN ) 180 mcg/week . Methods A total of 210 interferon-naïve patients ( 69 % male ; median age , 42 years ) with histologically proven chronic hepatitis C infection ( genotype 1 : 62 % ) received PEG-IFN 180 mcg/week for 12 weeks . Patients with EVR ( 58 % ) were r and omized to continue PEG-IFN monotherapy ( n=64 ) or to add ribavirin ( RBV ) , 800 mg/day ( n=57 ) , for 36 additional weeks . Patients without EVR ( 42 % ) were r and omized to add RBV ( n=42 ) , or RBV plus amantadine , 200 mg/day ( n=47 ) , for 36 additional weeks . Sustained virological response ( SVR , undetectable HCV-RNA 24 weeks after treatment completion ) was compared among treatment groups . Results Patients with EVR : SVR rate was 60.3 % in the PEG-IFN group versus 67.2 % in the PEG-IFN+RBV group ( NS ) . In genotypes 2/3 , SVR rates were 66.7 versus 73.1 % ( NS ) ; in genotypes 1/4 , SVR rates were 51.6 versus 61.3 % , respectively ( NS ) . Patients without EVR : SVR was 16.7 % in the PEG-IFN+RBV group versus 31.9 % in the triple therapy group ( P=0.07 ) . In patients with genotypes 1/4 , SVR rates were 9.4 versus 29.7 % ( P=0.041 ) . Conclusion In genotypes 1/4 patients without EVR , triple therapy results in higher SVR rates than st and ard dual therapy . This study confirms that addition of amantadine is beneficial in early-recognized ‘ difficult-to-treat ’ patients Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
2,494 | 17,986,667 | Even small financial incentives were found to be effective in improving physician response .
Token nonmonetary incentives were much less effective .
In terms of design strategies , postal and telephone strategies have generally been more successful than have fax or Web-based approaches , with evidence also supporting use of mixed-mode surveys in this population .
In addition , use of first-class stamps on return envelopes and question naires design ed to be brief , personalized , and endorsed by legitimizing professional associations were also more likely to be successful . | Although physician surveys are an important tool in health services and policy research , they are often characterized by low response rates . | Background —Few data have evaluated physician adherence to cardiovascular disease ( CVD ) prevention guidelines according to physician specialty or patient characteristics , particularly gender . Methods and Results —An online study of 500 r and omly selected physicians ( 300 primary care physicians , 100 obstetricians/gynecologists , and 100 cardiologists ) used a st and ardized question naire to assess awareness of , adoption of , and barriers to national CVD prevention guidelines by specialty . An experimental case study design tested physician accuracy and determinants of CVD risk level assignment and application of guidelines among high- , intermediate- , or low-risk patients . Intermediate-risk women , as assessed by the Framingham risk score , were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles ( P<0.0001 ) , and trends were similar for obstetricians/gynecologists and cardiologists . Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy . After adjustment for risk assignment , the impact of patient gender on preventive care was not significant except for less aspirin ( P<0.01 ) and more weight management recommended ( P<0.04 ) for intermediate-risk women . Physicians did not rate themselves as very effective in their ability to help patients prevent CVD . Fewer than 1 in 5 physicians knew that more women than men die each year from CVD . Conclusions —Perception of risk was the primary factor associated with CVD preventive recommendations . Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men . Educational interventions for physicians are needed to improve the quality of CVD preventive care and lower morbidity and mortality from CVD for men and women PURPOSE This study compared the response time , response rate , and cost of two types of survey administration techniques : e-mail/web-based versus conventional postal mail . The main aim of the survey was to collect descriptive information on the existence of Acute Care for Elders units and their characteristics by surveying geriatric division chiefs . DESIGN AND METHODS Two r and omized cohorts of geriatric division chiefs were formed to receive a survey either by electronic mail ( n = 57 ) or by conventional postal mail ( n = 57 ) . If there was no response to the initial mailing , two follow-up mailings were sent to both groups using the original modality ; a third follow-up was performed using the alternative modality . For each group , response rate and response time were calculated . The average total cost was computed and compared across two groups . RESULTS The aggregate response rate was 58 % ( n = 31 ) for the e-mail group versus 77 % ( n = 44 ) for the postal mail group . The overall average response time was shorter in the e-mail group , 18 days compared with 33 days for the conventional postal mailing group . The cost comparison showed that average cost was $ 7.70 for the e-mail group , compared to $ 10.50 per response for the conventional mail group . IMPLICATION S It appears that although the web-based technology is gaining popularity and leads to lower cost per response , the conventional postal method of surveying continues to deliver a better response rate among the geriatric medicine division chiefs . The web-based approach holds promise given its lower costs and acceptable response rate combined with the shorter response time The objective of this study was to compare the impact of closed- versus open-ended question formats on the completeness and accuracy of demographic data collected in a mailed survey question naire . We surveyed general internists in five Canadian provinces to determine their career satisfaction . We r and omized respondents to receive versions of the question naire in which 16 demographic questions were presented in a closed-ended or open-ended format . Two questions required respondents to make a relatively simple computation ( ensuring that three or four categories of response added to 100 % ) . The response rate was 1007/1192 physicians ( 80.0 % ) . The proportion of respondents with no missing data for all 16 questions was 44.7 % for open-ended and 67.0 % for closed-ended formats ( P < 0.001 ) . The odds of having missing items remained higher for open-ended response options after adjusting for a number of respondent characteristics ( 2.67 , 95 % confidence interval 2.01 to 3.55 ) . For the two questions requiring computations focused on professional activity and income , there were more missing data ( P = 0.02 , 0.02 , respectively ) but fewer inaccurate responses ( P = 0.009 , 0.20 , respectively ) for the open-ended compared to the closed-ended format . Investigators can achieve higher response rates for demographic items using closed format response options , but at the risk of increasing inaccuracy in response to questions requiring computation OBJECTIVES The effects of incentive size on physicians ' response rates to a mail survey were determined . METHODS One thous and US primary care physicians were assigned r and omly to receive a survey with either a $ 5 bill or a $ 2 bill as an incentive . For each of the two incentive groups , the overall response rate for three mailing waves , the total cost , and the total cost per usable response were measured . RESULTS The response rate among those receiving the $ 5 bill ( 61 % ) was 32 % higher than the response rate among those receiving the $ 2 bill ( 46 % ) ; overall costs were slightly higher in the $ 5 group , but the cost per response for each group was similar ( $ 15.46 versus $ 14.93 ) . For the same cost , a higher response rate could have been achieved in the $ 2 group if costs saved from foregoing the third mailing were instead used to increase the incentive for a portion of the subjects . CONCLUSIONS A $ 5 bill incentive yielded a higher response rate among the physicians in this study than did a $ 2 bill incentive . Moreover , the powerful effect of the incentive size , combined with the consequent decline in the costs of subsequent mailing waves , suggests that re sources in a fixed survey budget are allocated more efficiently to increasing the initial incentive rather than to providing a third wave to nonresponders BACKGROUND Historically , achieving a high response rate on physician surveys has been a challenging task . Given such concerns , underst and ing research strategies that facilitate adequate response rates is important . Primary care physician responses to a mail survey on smoking cessation are summarized by physician specialty and timing of incentive . METHODS A stratified r and om- sample design , stratified by patient population s-adults , adolescents , and pregnant women-was used . The sampling frame included New Jersey internists , general practitioners , family physicians , pediatricians , and obstetrician-gynecologists . A total of 2100 physicians , 700 physicians from each patient strata , were sample d and mailed a smoking-cessation survey in summer 2002 . The sample was r and omized by incentive timing : Half received the incentive ( i.e. , 25 dollars gift card ) with the first survey mailing , and half received the incentive on receipt of their completed survey . RESULTS The promised-incentive group achieved a significantly lower response rate ( 56 % ) compared with the up-front-incentive group ( 71.5 % ) . Response rates by medical specialty varied overall and within incentive groups . The difference between the incentive groups was greatest among obstetrician-gynecologists ( i.e. , 20.2 percentage points ) and was least among pediatricians ( i.e. , 5.8 percentage points ) . CONCLUSIONS Physician response rates to mail surveys are greatly improved , especially among certain medical specialties , by using up-front incentives Background Low response rates among surgeons can threaten the validity of surveys . Internet technologies may reduce the time , effort , and financial re sources needed to conduct surveys . Objective We investigated whether using Web-based technology could increase the response rates to an international survey . Methods We solicited opinions from the 442 surgeon – members of the Orthopaedic Trauma Association regarding the treatment of femoral neck fractures . We developed a self-administered question naire after conducting a literature review , focus groups , and key informant interviews , for which we used sampling to redundancy techniques . We administered an Internet version of the question naire on a Web site , as well as a paper version , which looked similar to the Internet version and which had identical content . Only those in our sample could access the Web site . We alternately assigned the participants to receive the survey by mail ( n=221 ) or an email invitation to participate on the Internet ( n=221 ) . Non-respondents in the mail arm received up to three additional copies of the survey , while non-respondents in the Internet arm received up to three additional requests , including a final mailed copy . All participants in the Internet arm had an opportunity to request an emailed Portable Document Format ( PDF ) version . Results The Internet arm demonstrated a lower response rate ( 99/221 , 45 % ) than the mail question naire arm ( 128/221 , 58 % ) ( absolute difference 13 % , 95 % confidence interval 4%-22 % , P<0.01 ) . Conclusions Our Internet-based survey to surgeons result ed in a significantly lower response rate than a traditional mailed survey . Research ers should not assume that the widespread availability and potential ease of Internet-based surveys will translate into higher response rates In 1989 , the authors tested the effectiveness of two response-enhancing techniques , a postage stamped or franked return envelope and a prenotification letter , in a survey of pregnancy among 10,047 resident physicians in the United States . The techniques were r and omly assigned using a factorial design . No significant interactions were observed between the techniques . After two mailings , those who received a stamped return envelope had a response of 71.2 % , compared with 68.2 % for those who received a franked return envelope ( 95 % confidence interval 1.3 - 4.9 % ) . Men who received the stamped envelope had a 5.9 % greater response than those who received the franked envelope ( p less than 0.001 ) , but the type of postage did not influence response among women ( p = 0.84 ) ; this interaction was statistically significant ( p = 0.006 ) . Physicians who received a prenotification letter had a response of 69.0 % , compared with 70.5 % for those who did not receive the letter ( 95 % confidence interval -3.3 to 0.2 % ) . The authors conclude that seemingly minor changes in survey design could have saved from 12 % to 19 % of the total cost of the study OBJECTIVES To compare 3 communication modes ( postal , fax , and e-mail ) in a rotavirus vaccine physician survey . METHODS We used 3 communication modes to distribute a survey to physicians listed in the membership directory of the Georgia Chapter of the American Academy of Pediatrics . The directory listed 1391 members ; however , 404 were deemed ineligible on the basis of their listing as a specialist , retiree , resident in training , or government public health employee . Of the 987 members expected to administer vaccines , 150 were selected r and omly to receive the postal survey ( postal group ) . Of the remaining listings , 488 ( 58 % ) of 837 listed a fax number ; 150 members were selected r and omly and faxed a survey ( fax group ) . Of the remaining members , 266 ( 39 % ) of 687 had e-mail addresses listed ; 150 members were selected r and omly for the e-mail survey ( e-mail group ) . A follow-up survey was sent by the same mode at 2 weeks . A final survey was sent via another mode ( mixed mode ) at 1 month : by fax to e-mail and postal nonresponders and by post to fax nonresponders and those without fax . RESULTS Eligible respondents in the 3 survey groups were similar in their practice setting and location . Although the e-mail group had fewer median years ( 8 years ) since medical school graduation than the fax group ( 19 years ) and postal group ( 17 years ) , a similar percentage of responders in all groups had computers ( > 85 % ) and Internet access ( > or = 70 % ) at work . However , only 39 % of members listed an e-mail address in the directory . In the 2 weeks after the first mailing , 39 surveys were completed via postal mail , 50 via fax , and 16 via e-mail . In the 2 weeks after the second contact ( sent at 2 weeks ) , 20 surveys were completed via postal mail , 15 via fax , and 17 via e-mail . The response rate after the first 2 mailings was 41 % ( 59 of 143 ) for postal , 47 % ( 65 of 137 ) for fax , and 26 % ( 33 of 125 ) for e-mail surveys . The third and final survey ( sent 1 month after the first mailing ) was sent by a different ( ie , mixed ) mode and elicited an additional 73 responses : 19 responses ( 15 postal , 4 fax ) from the postal group , 19 responses ( 18 postal , 1 fax ) from the fax group , and 35 responses ( 15 postal , 13 fax , 7 e-mail ) from the e-mail group . Twenty-three percent ( 9 of 40 ) of the e-mail and 18 % ( 15 of 83 ) of the fax surveys completed were returned on the same or subsequent day they were sent , compared with none of the postal surveys . There were significant differences among the 3 groups for invalid addresses/numbers ( 4 % postal , 8 % fax , and 16 % e-mail ) listed in the directory . Using mixed modes as the third contact , the overall response rate increased from 39 % before mixed mode to a final of 53 % . On the basis of the 3 initial groups , responses to 1 of 12 rotavirus questions differed significantly . CONCLUSIONS Future use of e-mail surveys in selected circumstances is promising , because the majority of providers have Internet access and acknowledged interest in participating in e-mail surveys . E-mail surveys could be especially useful if rapid response time is necessary . There were fewer incomplete questions by participants who completed the e-mail survey compared with postal or fax participants . Updating membership e-mail addresses and routinely using e-mail as a communication tool should improve the ability to use e-mail surveys . There may need to be ongoing evaluations that critically evaluate providers ' responses to e-mail surveys compared with other survey modes before e-mail surveys can become a st and ard survey tool . In the meantime , mixed-mode surveys may be an option To evaluate response‐aiding strategies feasible in large surveys , we r and omly allocated general practitioners ( GPs ) to one of four intervention groups : Group 1 received ‘ exhaustive ’ telephone prompts by a medical peer in advance of a question naire ; Group 2 , inclusion of an embossed pen with the question naire ; Group 3 , an advance letter prompt ; and Group 4 , a ‘ single attempt ’ advance telephone prompt by a non‐medical research assistant . Follow‐up procedures were identical . Response rates by group were not significantly different overall ( χ24.59 , df=3 , p=0.20 ) although advance prompts by a medical peer were significantly more effective than other strategies for male GPs . The difference in overall response rates between males ( 63 % ) and females ( 74 % ) was significant ( χ2=15.40 , df=1 , p<0.01 ) . No other response bias was evident . Our demonstration of a significant interaction between respondent sex and response‐aiding strategy invites further research BACKGROUND Low response rates are acknowledged as a potential source of bias in survey results . Response rates are a particular problem in surveys of GPs . Thus , the methods used to encourage response to mailed surveys and the influence of inducements in maximizing response rates are fundamental issues to be examined when addressing the problem of response bias . AIM To increase the overall response rate to a national study of GPs and to explore the effects of financial and non-financial inducements on response rates . METHODS Two mailing waves of a postal question naire to a 20 % r and om sample of all GPs in Engl and and Wales had achieved a 33 % response rate . For the third mailing wave , the non-responding GPs were then divided into a control group , a group who were offered a donation to charity to complete the question naire and a group who were offered cash . The charity and cash groups were further subdivided into 5 pounds and 10 pounds groups to assess the effect of the size of the inducement offered . For the control group , a fourth wave was sent the offer of a 5 pounds or 10 pounds incentive . RESULTS Response was positively affected by the offer of an inducement . Cash , however , had a more substantial effect than the offer of a donation to charity . Older GPs were less likely to participate overall , whereas male GPs were more likely to respond to a cash inducement . Doctors who had seen more patients were less likely to reply earlier and were more likely to respond to the offer of cash . CONCLUSIONS Primary care is going through many changes , some of which have increased the workload of the GP . It may now be that , to achieve the response rates needed to vali date policy-related research , the offer of inducements will become a necessary part of the research process CONTEXT Health plan utilization review rules are intended to enforce insurance contracts and can alter and constrain the services that physicians provide to their patients . Physicians can manipulate these rules , but how often they do so is unknown . OBJECTIVE To determine the frequency with which physicians manipulate reimbursement rules to obtain coverage for services they perceive as necessary , and the physician attitudes and personal and practice characteristics associated with these manipulations . DESIGN , SETTING , AND PARTICIPANTS A r and om national sample of 1124 practicing physicians was surveyed by mail in 1998 ; the response rate was 64 % ( n = 720 ) . MAIN OUTCOME MEASURE Use of 3 different tactics " sometimes " or more often in the last year : ( 1 ) exaggerating the severity of patients ' conditions ; ( 2 ) changing patients ' billing diagnoses ; and /or ( 3 ) reporting signs or symptoms that patients did not have to help the patients secure coverage for needed care . RESULTS Thirty-nine percent of physicians reported using at least 1 tactic " sometimes " or more often in the last year . In multivariate models comparing these physicians with physicians who " never " or " rarely " used any of these tactics , physicians using these tactics were more likely to ( 1 ) believe that " gaming the system " is necessary to provide high- quality care today ( odds ratio [ OR ] , 3.67 ; 95 % confidence interval [ CI ] , 2.54 - 5.29 ) ; ( 2 ) have received requests from patients to deceive insurers ( OR , 2.44 ; 95 % CI , 1.72 - 3.45 ) ; ( 3 ) feel pressed for time during patient visits ( OR , 1.69 ; 95 % CI , 1.21 - 2.37 ) ; and ( 4 ) have more than 25 % of their patients covered by Medicaid ( OR , 1.60 ; 95 % CI , 1.08 - 2.38 ) . Notably , greater worry about prosecution for fraud did not affect physicians ' use of these tactics ( P = .34 ) . Of those reporting using these tactics , 54 % reported doing so more often now than 5 years ago . CONCLUSIONS A sizable minority of physicians report manipulating reimbursement rules so patients can receive care that physicians perceive is necessary . Unless novel strategies are developed to address this , greater utilization restrictions in the health care system are likely to increase physicians ' use of such manipulative " covert advocacy " tactics BACKGROUND Opinion leaders have been shown to have significant influence on the practice of health professionals and patient outcomes . METHODS Using focus groups , key informants , and sampling to redundancy techniques , we developed a question naire of surgeons ' preferences in the treatment of tibial shaft fractures . Twenty-two well-respected and widely known orthopaedic traumatologists endorsed the question naire . We r and omized 395 surgeon members of the Orthopaedic Trauma Association to receive either a question naire that included a letter informing them of the opinion leaders ' endorsement , or a question naire without the endorsement . RESULTS Surgeons who received the letter of endorsement had a significantly lower response rate at 2 , 4 , and 8 weeks . The absolute difference in response rates was 7.8 % ( 4.6 % versus 12.4 % , P < 0.05 ) at 2 weeks , 13.1 % at 4 weeks ( 28.6 % versus 41.7 % P < 0.02 ) , and 12.3 % at 8 weeks ( 47.5 % versus 59.8 % P = 0.02 ) . CONCLUSIONS The addition of a letter listing expert surgeons who endorse the survey lead to significantly lower primary response rates . Those interested in influencing physician responses can not always assume a positive effect from endorsement by opinion PURPOSE To test the effect of a AU dollars 2 scratch lottery ticket on response rates to a national mailed question naire of Australian general practitioners ( GPs ) and medical specialists . METHODS A r and omized controlled trial was conducted and the incentive sent to half of the participants with the first mailing . A single follow-up mailing without incentive was sent to all non-respondents . Survey respondents were then informed of the research question regarding incentives and allowed to withdraw their study data . Differences in response rates between doctors receiving and not receiving the incentive , and between respondents and non-respondents , were examined . RESULTS The overall response rate was 47 % ( 443 respondents ) . Twenty-two respondents ( 5 % ) withdrew their data after being informed of the research question . Of the remaining 421 respondents , 233 had received the incentive ( response rate 49.7 % ) and 188 had not ( 40.1 % , p=0.0032 ) . The absolute increase in response rate with the incentive ( 9.6 % , 95%CI 3.2 , 15.9 ) was quantitatively similar in effect to the reminder mailing ( 11.8 % ) . The incentive had a larger effect among the GP sample compared with specialists ( 13.4 vs. 5.9 % ) , although the difference was not statistically significant ( p=0.20 ) . There were no systematic differences in demographic characteristics between respondents and non-respondents . CONCLUSIONS Increased response rates associated with a small incentive may reduce the need for a second mailed reminder , but strong views about the use of incentives may negatively influence the participation of some practitioners . While the overall response rate was low , there was no evidence of bias in our sample Background Monetary incentives in survey research may provide important gains from a method ological perspective in the control and reduction of survey error associated with potential nonresponse of participants . However , few studies have systematic ally investigated the use of monetary incentives or other methods to improve the response rates in the nonphysician clinician population . Objective To investigate differences in response rates to a mailed self-administered survey of nonphysician clinicians who were r and omized to receive a prepaid monetary incentive , a postsurvey prize drawing , or no incentive . Methods A r and omized controlled trial of financial incentives was conducted from November 2002 to February 2003 . Nonphysician clinicians ( nurse practitioners [ NPs ] and physician assistants [ PAs ] ; N = 3,900 ) r and omly selected to participate in a national ethics-related study were assigned r and omly in equal allocations ( n = 1,300 [ 650 NPs , 650 PAs ] ) to three incentive groups : ( a ) no incentive ; ( b ) a $ 5 prepaid token incentive in the initial mailing ; or ( c ) a chance to win one of ten $ 100 prize drawings upon completion and return of a self-administered survey . Results A $ 5 cash incentive increased survey response rates to an adjusted 64.2 % : a 19.5 percentage point increase over the lottery group ( 44.7 % response rate ) , and a 22 percentage point increase over the control group ( 42.2 % response rate ) . Discussion A nominal cash incentive of $ 5 yields a significantly higher response rate from nonphysician providers than receiving either a lottery option or no incentive Purpose A r and omized unblinded controlled trial was used to assess the utility of electronic question naires in a survey of Canadian anesthesiologists . Methods Postal or electronic question naires were sent between November 2001 and March 2002 to 1,333 anesthesiologists registered with the Canadian Anesthesiologists ’ Society . The primary outcome measure was the difference in response rates between electronic and postal question naires . Secondary outcome measures included a comparison of demographic characteristics , cost , and knowledge and practice regarding prophylactic perioperative beta blockade . Results The overall response rate was 52 % . E-mail participants were half as likely as postal participants to respond to the question naire ( 35 % vs 69 % , relative risk = 0.51 , 95 % confidence interval 0.45–0.58 ) . Respondents who provided an e-mail address were younger and more likely to be affiliated with an academic institution . There were no significant differences in responses to knowledge and practice questions . The electronic arm was faster than the postal arm and the cost per reply was one-third the cost of the postal arm ( $ 2.50 vs $ 8.02 ) . Conclusions Electronic surveys are a means of acquiring information from a large number of individuals in a rapid , efficient and cost-effective manner . This methodology may be particularly valid and useful in surveys of participants with similar background s and internet access . However the lower response rates achieved as compared with postal surveys indicates a need to use vigilance when generalizing results to a broader population .RésuméObjectifNous avons utilisé une épreuve r and omisée , contrôlée et ouverte pour évaluer l’utilité de question naires électroniques lors d’une enquête auprès des anesthésiologistes canadiens . MéthodeDes question naires postaux et électroniques ont été envoyés entre novembre 2001 et mars 2002 à 1 333 anesthésiologistes membres de la Société canadienne des anesthésiologistes . La principale mesure a été la différence du taux de réponses aux envois postaux et électroniques . La seconde comprenait une comparaison des caractéristiques individuelles , du coût , et des connaissances et de la pratique en regard du bêta blocage périopératoire préventif . RésultatsLe taux de réponse général a été de 52 % . Les participants par courriel ont été deux fois moins nombreux que par la poste à répondre au question naire ( 35 % vs 69 % , le risque relatif a été de 0,51 , l’intervalle de confiance de 95 % 0,45–0,58 ) . Les répondants par courriel étaient plus jeunes et plus souvent affiliés à une institution universitaire . Il n’y a pas eu de différence significative de réponses sur les connaissances et la pratique . Le groupe du courriel a répondu plus rapidement que le groupe de la poste et le coût par réponse a été le tiers du coût postal ( 2,50 $ vs 8,02 $ ) . Conclusion Les enquêtes électroniques permettent d’obtenir de l’information d’un gr and nombre de personnes d’une manière rapide , efficace et économique . Cette méthodologie peut être particulièrement valide et utile auprès de participants do nt les connaissances sont comparables et qui ont accès à Internet . Cependant , les taux de réponses plus bas obtenus en comparaison avec les enquêtes postales indiquent la nécessité d’être vigilant au moment de généraliser les résultats pour une importante population Low response rates , especially among physicians , are a common problem in mailed survey research . We conducted a r and omized trial to examine the effects of cash and lottery incentives on response rates . A total of 4,850 subjects were r and omized to one of three interventions accompanying a mailed survey-no incentive ( n = 1,700 ) , cash payment [ three levels of Hong Kong dollars ( HKD ) $ 10 , $ 20 , and $ 40 ; N = 50 in each subgroup ] , or entry into a lottery ( three levels of HKD$1,000 , $ 2,000 , and $ 4,000 ; N = 1,000 in each subgroup ) on receipt of the completed question naire . The response rates were higher among those offered incentives than those without ( 19.8 % vs. 16.8 % , P = .012 ) . Cash was the more effective incentive compared to lottery ( 27.3 % vs. 19.4 % , P = .017 ) . Response also increased substantially between the first and second mailings ( 14.2 % vs. 18.8 % , P > .001 ) . In addition , those with specialist qualifications were more willing to participate in mailed surveys . We found no significant differences in response outcomes among the various incentive arms . Cash reward at the $ 20 level was the most cost-effective intervention , in terms of cost per responder . Further systematic examination of the effects of different incentive strategies in epidemiologic studies should be encouraged Background Response rates to postal question naires are falling and this threatens the external validity of survey findings . We wanted to establish whether the incentive of being entered into a prize draw to win a personal digital assistant ( PDA ) would increase the response rate for a national survey of consultant obstetricians and gynaecologists . Methods A r and omised controlled trial was conducted . This involved sending a postal question naire to all Consultant Obstetricians and Gynaecologists in the United Kingdom . Recipients were r and omised to receiving a question naire offering a prize draw incentive ( on response ) or no such incentive . Results The response rate for recipients offered the prize incentive was 64 % ( 461/716 ) and 62 % ( 429/694 ) in the no incentive group ( relative rate of response 1.04 , 95 % CI 0.96 – 1.13 ) Conclusion The offer of a prize draw incentive to win a PDA did not significantly increase response rates to a national question naire survey of consultant obstetricians and gynaecologists OBJECTIVE Improving response rates , particularly among physicians , is important to minimize nonresponder bias and increase the effective sample size in epidemiologic research . We conducted a r and omized trial to examine the impact of prepayment vs. postpayment incentives on response rates . STUDY DESIGN AND SETTING Self-completion postal question naires were mailed to 949 physicians who were respondents to an earlier survey and representative of the general physician population in Hong Kong . These physicians were r and omly allocated to receive a HK dollar 20 cash prepayment incentive that accompanied the survey ( n=474 ) or a postpayment reward of the same amount on receipt of the completed question naire ( n=475 ) . RESULTS The final prepayment response rate was 82.9 % , compared with 72.5 % in the postpayment arm ( P < .001 ) . Of the eight alternative incentive and follow-up strategies evaluated , three lie on the efficiency frontier ( i.e. , not dominated ) , including postpayment with three mailings at HK dollar 42.7 , prepayment with three mailings at HK dollar 66.5 and prepayment with three mailings and telephone follow-up at HK dollar 112.1 per responder recruited ( US dollar 1=HK dollar 7.8 ) . CONCLUSION The findings demonstrate that prepayment cash incentives are superior to postpayment of the equivalent amount in improving response rates among a representative sample of Hong Kong physicians . Further research should concentrate on confirming the generalizability of these findings in other health care occupation groups and setting Euthanasia and physician-assisted suicide are highly controversial societal issues ( 1 - 3 ) . In the past decade , there have been numerous surveys of physicians throughout the world on euthanasia and physician-assisted suicide ( 1 , 4- 14 ) . Nevertheless , important deficiencies in information remain . First , most studies have been snapshotssurveys of attitudes or experiences at one point in time ( 15 ) . Second , more than a fourfold variation exists in the reported rate of requests for and performance of euthanasia and physician-assisted suicide among U.S. physicians , making it difficult to draw definitive conclusions about physician practice s ( 10 , 11 , 13 , 14 ) . Most important , almost all surveys of physicians have focused exclusively on euthanasia or physician-assisted suicide as isolated practice s. None of the existing data provide insight into how these practice s relate to optimal end-of-life care . To address some of these deficiencies , the American Society of Clinical Oncology ( ASCO ) surveyed all of its U.S. members about end-of-life care practice s ; we report part of the results of that survey . Our focus on oncologists is appropriate because data from the Netherl and s and Oregon indicate that more than 70 % of patients using euthanasia or physician-assisted suicide have cancer ( 7 , 16 ) . In the United States , where patients with cancer tend to be treated by specialists , oncologists are likely to have to address the issue of euthanasia and physician-assisted suicide more often than other physicians ( 11 , 14 ) . Methods Physician Identification General eligibility requirements for the study were membership in ASCO in 1997 , which included at least 85 % of all oncologists in the United States , and being active in the management of patients at the very end of life . Two groups were identified for participation ; neither was compensated . First , all 8715 oncologists from the United States who were ASCO members were mailed a survey with a postage-paid return envelope . Physicians who did not return the survey after 4 weeks were mailed a reminder letter with another copy of the survey . Of U.S. oncologists , 6642 were eligible ; 2645 of these physicians completed the survey ( response rate , 39.8 % ) . Second , 1550 medical , surgical , radiation , and pediatric oncologists were r and omly selected in a prospect i ve manner to be contacted through personal telephone calls and additional mailings urging them to complete the survey . Of these physicians , 1273 were eligible and 655 completed the survey ( response rate , 51.5 % ) . The responses to all questions about euthanasia and physician-assisted suicide from these cohorts were statistically indistinguishable ; therefore , responses from the two groups were combined , providing a total of 3299 responses . Survey Development In conjunction with the Center for Survey Research , a multidisciplinary task force created a survey instrument . After pretesting among oncologists , the instrument was finalized with 118 questions in eight areas . The precise wording of the questions that we analyzed is provided in the Appendix Table . Because the terms euthanasia and physician-assisted suicide can be both misunderstood and emotionally charged , previously reported descriptions of these activities were used in all questions ( 1 , 13 , 15 ) . Statistical Analysis Comparisons among groups were performed by using the Pearson chi-square test of independence . Predictors of support for and performance of physician-assisted suicide and euthanasia were identified by using stepwise logistic regression analysis . To minimize type I errors and reduce the probability of identifying factors associated with differences that are not clinical ly meaningful , the selection criteria for entry into the model were set at an level of 0.005 . Potential explanatory variables in all analyses were age , sex , religious affiliation , religiosity , importance of religious beliefs , death of a relative within the past 5 years , specialty , rural or urban practice , academic practice , amount of time in patient care , number of new patients in the past 6 months , and number of patients who died in the past year . Additional explanatory variables were barriers to providing optimal care to terminally ill patients , time available to talk to terminally ill patients , perceptions of reimbursement levels , perceived difficulties in getting patients the care that they required , poor pain management decisions , proportion of terminally ill patients who are depressed , and personal responsibility for care of terminally ill patients . Results Table 1 provides basic sociodemographic data on the 3299 U.S. oncologists who participated . Among all ASCO oncologists , 17.3 % are female and 33.4 % work in academic setting s ; these overall values are similar to those among survey respondents . More than 85 % of respondents spent at least half their working time in direct patient care ; 52 % indicated that they devoted more than 90 % of their time to clinical activities . Almost two thirds ( 61.4 % ) of respondents reported that 25 or more of their patients had died during the previous year . Table 1 . Sociodemographic Characteristics of Surveyed U.S. Oncologists Appendix Table . Survey Questions Attitudes toward Euthanasia and Physician-Assisted Suicide Of the 3299 U.S. oncologists who responded , 22.5 % supported physician-assisted suicide for a terminally ill patient with prostate cancer who had unremitting pain despite optimal pain management , and 6.5 % supported euthanasia ( Table 2 ) . Furthermore , 15.6 % of the respondents indicated that they themselves would be willing to provide physician-assisted suicide and 2.0 % would be willing to carry out euthanasia . These responses varied by oncologic subspecialty . Table 2 . Attitudes and Practice s regarding Euthanasia and Physician-Assisted Suicide among Oncologic Specialties In multivariate analysis , four factors were associated with oncologists who were significantly less likely to support euthanasia and physician-assisted suicide : 1 ) reluctance to increase the intravenous morphine dose for a patient with metastatic breast cancer who was experiencing pain and requested relief ( odds ratio [ OR ] , 0.61 [ CI , 0.48 to 0.77 ] ] ; 2 ) reporting that they had sufficient time to talk to dying patients about end-of-life care issues ( OR , 0.79 [ CI , 0.71 to 0.87 ] ] ; 3 ) viewing themselves as religious ( OR , 0.68 [ CI , 0.64 to 0.74 ] ] ; and 4 ) being Catholic ( OR , 0.57 [ CI , 0.45 to 0.72 ] ) . Surgical oncologists were significantly more likely to support euthanasia or physician-assisted suicide ( OR , 2.11 [ CI , 1.52 to 2.92 ] ) . Attitudes toward euthanasia or physician-assisted suicide did not differ by age , sex , geographic region , year of graduation from medical school , number of new patients per year , number of patients who died in the past year , proportion of income from managed care , and clinical practice setting . Practice s regarding Euthanasia and Physician-Assisted Suicide Of the 3299 responding oncologists , 62.9 % had received requests for euthanasia or physician-assisted suicide during their career and 31.1 % had received such requests during the previous 12 months ( Table 2 ) . The majority of requests were not fulfilled . Overall , 10.8 % of responding oncologists had performed physician-assisted suicide in their career and 3.4 % had done so in the preceding 12 months ; 3.7 % of oncologists reported performing euthanasia during their career while 0.8 % had done so in the prior 12 months . Of the 10.8 % of oncologists who had performed physician-assisted suicide , 37 % had done so only once and 18 % had done so five or more times . Of the oncologists who performed euthanasia , the majority ( 57 % ) had done so only once and 12 % had done so five or more times . These practice s varied significantly among oncologic subspecialties ( Table 2 ) . Multivariate logistic regression analysis suggested that oncologists were significantly less likely to have performed euthanasia or physician-assisted suicide if they were unwilling to increase the dose of intravenous morphine for pain control in a patient with breast cancer who had excruciating pain ( OR , 0.58 [ CI , 0.43 to 0.79 ] ) and if they reported that their training in end-of-life care was helpful ( OR , 0.86 [ CI , 0.79 to 0.95 ] ) . Conversely , oncologists who were less spiritual were significantly more likely to have performed euthanasia or physician-assisted suicide ( OR , 1.77 [ CI , 1.40 to 2.26 ] ) . Of note , 1.5 % of oncologists who reported that they could get their dying patients all necessary care had performed euthanasia , whereas 6.2 % of oncologists who reported that administrative , fiscal , and structural barriers allowed them to provide their dying patient with only some of the care they needed had performed euthanasia ( P < 0.001 ) . Discussion Our study of 3299 U.S. oncologists , the largest survey of physicians on the subject of euthanasia and physician-assisted suicide , provides four insights . First , concern among oncologists about performing euthanasia and physician-assisted suicide may limit their willingness to prescribe opioids , thereby leading to inadequate pain management ( 8) . Physicians who neither supported nor performed euthanasia and physician-assisted suicide were significantly less willing to increase the dose of intravenous opioids for patients with unremitting pain . This reticence probably reflects fear that increasing opioid dose increases the risks for respiratory depression and death and might be construed as a form of euthanasia . This view may be encouraged by proponents of euthanasia who have argued that there is no difference between increasing morphine for pain relief and euthanasia ( 2 , 17 , 18 ) . The ASCO and others must educate physicians on the ethical and legal acceptability of increasing narcotics for pain control , even at the risk of respiratory depression and death ( 1 , 3 ) . Second , the data suggest a relationship between the likelihood of performing euthanasia and physician-assisted suicide and the inability of physicians to obtain adequate end-of-life care for OBJECTIVE To examine response rate information from mailed physician question naires reported in published articles . DATA SOURCES / STUDY SETTING Citations for articles published between 1985 and 1995 were obtained using a key word search of the Medline , PsychLit , and Sociofile data bases . STUDY DESIGN A 5 percent r and om sample of relevant citations was selected from each year . DATA COLLECTION / EXTRACTION METHODS Citations found to be other than physician surveys were discarded and replaced with the next r and omly assigned article . Selected articles were abstract ed using a st and ardized variable list . PRINCIPAL FINDINGS The average response rate for mailed physician question naires was 61 percent . The average response rate for large sample surveys ( > 1,000 observations ) was 52 percent . In addition , only 44 percent of the abstract ed articles reported a discussion of response bias , and only 54 percent reported any type of follow-up . CONCLUSIONS ( 1 ) Response rates have remained somewhat constant over time , and ( 2 ) research ers need to document the efforts used to increase response rates to mailed physician question naires Background : Achieving acceptable response rates from health care providers via postal question naires is an ongoing challenge . The use of monetary incentives is one of the most effective strategies for increasing response rates . However , the effect and cost of such an incentive on retail pharmacists ’ response rates has not been well studied . Methods : A sample of 700 pharmacies was selected at r and om from the electronic Yellow Pages in NSW Australia and mailed a brief survey regarding pharmacotherapies and advice for smoking cessation . Half of the sample was r and omly allocated to receive an offer of an US$ 14 gift voucher . Results : The response rates were 65.9 % for the voucher group and 53.5 % for the no-voucher group . The odds of response from the voucher group was 1.68 ( 95%CI = 1.23 , 2.30 ) times greater than for the no-voucher group . The cost per additional respondent was US$ 67.95 . The incentive also reduced follow up costs by 10 % . Conclusions : A moderately sized monetary incentive is able to achieve a significant increase in response rates for retail pharmacists , thereby reducing potential bias in the sample BACKGROUND AND OBJECTIVES To compare general practitioner ( GP ) response to a telephone interview with response to a postal survey with three reminders in a r and omized controlled trial . METHODS GPs were r and omly assigned to either a telephone interview or a postal survey . GPs in the telephone group were mailed a letter of invitation and asked to undertake a telephone interview . GPs in the postal group were mailed a letter of invitation and question naire . Non-responders were sent up to three reminders , the final by registered post . Response rates were calculated for each group . RESULTS 416 GPs were r and omized to the telephone interview and 451 to the postal survey . Eighty-six in the telephone group and 30 in the postal were ineligible . One hundred thirty-four GPs completed the telephone interview with a response rate of 40.6 % ( 95 % confidence interval [ CI ] : 35.3 % , 46.1 % ) . Two hundred fifty-two GPs completed the postal survey with a response rate of 59.9 % ( 95%CI : 55.0 % , 64.6 % ) . The difference in response was 19.3 % ( 95%CI : 12.2 % , 26.3 % ) . CONCLUSIONS These results show that postal surveys with three reminders can have superior response rates compared with a telephone interview Mailed surveys are a popular means of obtaining data on large population s. In July 1999 a mail survey was conducted among 3000 r and omly selected members of the American Society of Hematology to assess their approach to diagnosis and treatment of polycythemia vera . Because the research ers and the study population are members of the same professional organization with a vested interest in the results , we anticipated that the advantages of return stamped postage seen in previous studies would be less significant . The response rate for stamped return envelopes was 38 % versus 32 % for business reply envelopes . This statistically significant difference ( P = .0005 ) of six percentage points is comparable to previous research . Excluding labor , the total cost per returned survey was $ 2.62 for business reply envelopes versus $ 1.82 for stamped return envelopes . We conclude that stamped return envelopes are a more effective and cost-efficient means of procuring data from physician specialists OBJECTIVES To assess the use of new technology by American urologists . METHODS Using the American Urological Association directory , surveys were sent via the U.S. postal service to 1000 r and omly selected American urologists and 3065 urologists who had an Internet address listed in the directory . RESULTS Responses were received from 601 urologists ( 415 postal , 186 Internet ) . Overall , 81 % of survey respondents reported performing fewer or the same number of percutaneous procedures as compared with 3 to 4 years ago and 84 % reported carrying out more or the same number of ureteroscopic procedures in the treatment of patients with stone disease . Open dismembered pyeloplasty ( 43 % ) and Acucise endopyelotomy ( 42 % ) were most frequently reported as the preferred treatment for adult patients with symptomatic ureteropelvic junction obstruction . Although 60 % of respondents reported that they have taken a laparoscopy course , 67 % currently do not perform any laparoscopy in their practice . In addition , only 7 % of urologists stated that laparoscopy comprises more than 5 % of their practice . When stratified by the number of years in practice , those in practice less than 10 years were more likely than those in practice 10 to 20 years and those in practice longer than 20 years to have performed an endopyelotomy ( 77 % , 60 % , and 48 % , respectively , P < 0.001 ) and to be currently performing laparoscopy ( 49 % , 36 % , and 18 % , respectively , P < 0.001 ) . CONCLUSIONS Compared with 3 to 4 years ago , American urologists are performing more ureteroscopy and fewer percutaneous stone procedures . Although most urologists have taken laparoscopy courses , this modality has not been widely incorporated into their practice s at present OBJECTIVES This report describes effects due to form length and /or item formats on respondent cooperation and survey estimates . METHODS Two formats were used for the Patient Record form for the 2001 NAMCS and OPD component of the NHAMCS : a short form with 70 subitems and a long form with 140 subitems . The short form also contained many write-in items and fit on a one-sided page . The long form contained more check boxes and other unique items and required a two-sided page . The NAMCS sample of physicians and NHAMCS sample of hospitals were r and omly divided into two half sample s and r and omly assigned to either the short or long form . Unit and item nonresponse rates , as well as survey estimates from the two forms , were compared using SUDAAN software , which takes into account the complex sample design of the surveys . RESULTS Physician unit response was lower for the long form overall and in certain geographic regions . Overall OPD unit response was not affected by form length , although there were some differences in favor of the long form for some types of hospitals . Despite having twice the number of check boxes on the long form as the short form , there was no difference in the percentage of visits with any diagnostic or screening services ordered or provided . However , visit estimates were usually higher for services collected with long form check-boxes than with ( recoded ) short form write-in entries . Finally , the study confirmed the feasibility of collecting certain items found only on the long form . CONCLUSION Overall , physician cooperation was more sensitive to form length than was OPD cooperation . The quality of the data was not affected by form length . Visit estimates were influenced by both content and item format The authors r and omly selected 400 physicians from a population of 1,545 practicing physicians providing follow-up care to patients who received bone marrow or blood stem cell transplants at the Fred Hutchinson Cancer Research Center to determine interest in receiving Internet-based transplant information . In a two-factor completely r and omized factorial design , the 400 physicians were assigned to receive mailed surveys with either no compensation or a $ 5 check and either no follow-up call or a follow-up call 3 weeks after mailing . Overall , 51.5 % of the physicians returned the mailed surveys . Comparison of logit models showed that inclusion of a $ 5 check in the mailer significantly ( p = .016 ) increased the probability of returning the surveys ( 57.5 % vs. 45.5 % ) . In contrast , the telephone follow-up had no overall effect . The authors concluded a modest financial reward can significantly improve physician response rates to research surveys but a telephone follow-up may be inefficient and even ineffective It is becoming increasingly difficult to obtain high response rates in physicians ' mail surveys . In 1983 - 84 , we tested the effectiveness of two techniques among 604 Quebec physicians who had not responded to an initial letter . A h and written thank you note at the bottom of the letter accompanying the question naire and a more personalized mailout package increased response rates by 40.7 per cent and 53.1 per cent , respectively , compared to control groups OBJECTIVE To compare e-mail with regular mail for conducting surveys of physicians . DESIGN R and omized controlled trial . SETTING Ontario , Canada . PARTICIPANTS A r and om sample of physicians listed in the College of Family Physicians of Canada 's membership data base . INTERVENTIONS Survey delivered by e-mail and by post . MAIN OUTCOME MEASURES Response rates and times , and completeness and characteristics of responses to the survey . RESULTS Overall response rate was 44.7 % ( 33.6 % of e-mail recipients , 52.7 % of post recipients who have e-mail , and 47.8 % of post recipients without e-mail ) . While the e-mail rate was significantly lower than for both post groups , e-mail responses were received much faster . There was no significant difference among groups as to completeness of responses , but e-mail responses had more frequent and longer comments . CONCLUSION E-mail provides faster but fewer responses to surveys . Content of structured-response questions was similar in all groups , but e-mail provided more and longer responses to open-ended questions . Where a quick response to a survey is required , e-mail is superior BACKGROUND Response rates to recent surveys of general practitioners have ranged from 44 - 95 % . The effectiveness of a telephone prompt by a non-medical research assistant in advance of survey mail-out was unknown at the time of this study . OBJECTIVE To determine the effectiveness of a telephone prompt by a non-medical research assistant to enhance response rates to a lengthy survey . SUBJECTS 364 r and omly selected general practitioners r and omised into intervention and control groups . OUTCOME VARIABLE Cumulative response rate at Day 18 and Day 60 . DESIGN Intervention group received a telephone call in advance of the survey . The control group received conventional mail-outs . Non-responders in both groups were telephoned at Day 28 and sent a reminder letter and question naire . RESULTS 77 % of the intervention group responded to the survey compared to 64 % of the control group . Intention-to-treat analysis demonstrated a significantly earlier response by Day 18 ( continuity corrected chi 2 = 18.15 ; df = 1 ; p < 0.001 ) and a significantly higher overall response by Day 60 ( continuity corrected chi 2 = 5.41 , df = 1 , p < 0.009 ) from the intervention group . CONCLUSION A telephone prompt by a non-medical research assistant will accelerate and enhance response rates to a survey of general practitioners although the differential effectiveness of a non-medical research er compared to a medical practitioner conducting such prompts remains unstudied Background It is important that response rates to postal surveys are as high as possible to ensure that the results are representative and to maximise statistical power . Previous research has suggested that any personalisation of approach helps to improve the response rate . This experiment tested whether personalising question naires by h and signing the covering letter improved the response rate compared with a non-personalised group where the investigator 's signature on the covering letter was scanned into the document and printed . Methods R and omised controlled trial . Question naires about surgical techniques of caesarean section were mailed to 3,799 Members and Fellows of the Royal College of Obstetricians and Gynaecologists resident in the UK . Individuals were r and omly allocated to receive a covering letter with either a computer printed signature or a h and written signature . Two reminders were sent to non-respondents . The outcome measures were the proportion of question naires returned and their time to return . Results The response rate was 79.1 % ( 1506/1905 ) in the h and -signed group and 78.4 % ( 1484/1894 ) in the scanned and printed signature group . There was no detectable difference between the groups in response rate or time taken to respond . Conclusion No advantage was detected to h and signing the covering letter accompanying a postal question naire to health professionals This study used a r and omised controlled trial to evaluate the effectiveness of telephone prompts to increase the response rate of gynaecologists to a survey . A nine-page question naire about management of women with abnormal Pap smears was mailed to Fellows of the Royal Australian College of Obstetricians and Gynaecologists . A r and om sample was contacted in advance by telephone , and nonrespondents received a telephone reminder 14 days after the initial mail-out . The control group was mailed question naires and a reminder letter conventionally . On Day 25 , nonresponders in both groups were mailed a second question naire . Of the intervention group , 84 per cent responded to the survey compared to 69 per cent of the control group ( P = 0.005 ) . A telephone call in anticipation of a mailed question naire is highly recommended OBJECTIVE To examine the association between question naire length and response rate in a mailed survey of generalist physicians r and omly selected from the American Medical Association master file . STUDY DESIGN AND SETTING In a pilot study , otherwise similar question naires of 30 different lengths ( 849 to 1,867 words ) were mailed to 192 physicians in April 1999 . In the main study , question naires of 16 different lengths ( 564 to 988 words ) were mailed to 1,700 physicians between June 1999 and January 2000 . RESULTS In the pilot study , response rate decreased from 60 % for question naires 849 words in length to 16.7 % for question naires over 1,800 words in length . Logistic regression revealed an odds ratio of 0.887 ( 95%CI 0.813 , 0.968 ; p=0.006 ) for word count , expressed in units of 100 words . In the main study , response rate varied between 51.5 % and 71.4 % . Logistic regression showed no association between response and word count ( OR 0.988 ; 95%CI 0.896 , 1.090 ; p=0.81 ) . CONCLUSION There appears to have been a threshold in these studies of approximately 1,000 words . Question naires above the threshold had lower response rates than those below it ( 38.0 % vs. 59.4 % ) BACKGROUND Physician noncompliance with screening recommendations has been a major barrier to effective colorectal cancer control . The overall objectives of this study were to assess the current attitudes and screening behavior of primary care physicians in light of new efficacy data , revised guidelines , improved technology , and more widespread insurance coverage . METHODS Question naires inquiring about knowledge , beliefs , and practice patterns related to colorectal cancer screening were mailed in mid-1997 to 700 r and omly selected Massachusetts internists . RESULTS The overall response rate was 63 % . Nearly 60 % of respondents reported an increase in screening behavior during the past 5 years . Most ( 80 % ) were aware of at least one set of screening guidelines and 90 % reported utilizing one or more recommended screening strategies . Fecal occult blood testing ( FOBT ) , alone ( 47 % ) or in combination with flexible sigmoidoscopy ( 50 % ) , was the preferred strategy for most respondents . Colonoscopy was rarely utilized ( 5 % ) despite high perceived effectiveness . Concern about patient compliance was a significant determinant of FOBT utilization , whereas perceived effectiveness , concerns about time or efficacy data , prior procedural training , date of licensure , and use of instructional material s were independent determinants of sigmoidoscopy utilization . CONCLUSION Massachusetts ' internists report high rates of utilization of select colorectal cancer screening strategies . Future studies must vali date self-reported compliance and explore barriers to screening colonoscopy OBJECTIVES This study assessed efforts to increase response rates to a mailed physician survey and examined whether , as a result , nonresponse bias was reduced . METHODS R and omly selected physicians and geneticists were mailed a question naire concerning genetics knowledge and attitudes . In the final but not the pilot survey , a $ 25 incentive and intensive follow-up were used to increase the response rate . RESULTS The response rate from physicians in the final survey was 64.8 % ( n = 1140 ) , compared with 19.6 % in the pilot test ( n = 69 ) . Sample representatives in sociodemographic and practice characteristics was improved by follow-up . Respondents recruited with more difficulty did not differ on the principal outcome variable , genetics knowledge , except on one subscore . Pilot study and final survey respondents did not differ in knowledge . CONCLUSIONS Although the effect of increased response rates on the principal outcome variable in this study was minimal , this may not be the case for other studies . Every effort should be made to attain as high a response rate as is practical and to establish that respondents are representative of the population being sample BACKGROUND High response rates to surveys help to maintain the representativeness of the sample . AIM In the course of a wider investigation into counselling services within general practice it was decided to assess the feasibility of increasing the response rate by telephone follow up of non-respondents to a postal survey . METHOD A postal survey was undertaken of a r and om sample of 1732 general practitioners followed by telephone administration of the question naire to non-respondents . The identical question naire was administered by telephone to a separate r and om sample of 206 general practitioners . RESULTS Of 1732 general practitioners first approached by mail , 1683 were still in post of whom 881 ( 52 % ) completed the postal question naire and a further 494 ( 29 % ) the telephone interview . Of 206 general practitioners first contacted by telephone , 197 were still in post of whom 167 ( 85 % ) completed interviews . Compared with doctors first approached by mail , those first approached by telephone were significantly more likely to report having a partner with a special interest in psychiatry ( P < 0.01 ) ; and a general practitioner , practice nurse or health visitor who worked as a counsellor ( P < 0.01 in each case ) . A comparison of doctors first approached by telephone with those who completed telephone interviews after failing to respond to the postal question naire showed that postal non-respondents were significantly less likely to report having a general practitioner , practice nurse , health visitor or community psychiatric nurse who worked as a counsellor ( P < 0.01 in each case ) . CONCLUSION These findings suggest that non-response to the postal survey was associated with lack of activity in the study area . Telephone administration of question naires to postal non-respondents increased response rates to above 80 % but , as telephone administration enhanced the reporting of counsellors , a social desirability bias may have been introduced BACKGROUND Low response rates to surveys are a problem in general practice . There is evidence that offering GPs incentives improves response rates to postal question naires . However , there is less evidence about the most effective form of incentive . OBJECTIVE Our trial aim ed to maximize response to a postal question naire and to test the most effective form of incentive . METHODS The study involved a r and omized controlled trial of a postal survey RESULTS The incentive of a lottery for six bottles of champagne generated a response rate of 79 % . Furthermore , one chance of six bottles generated 9 % more responses than six chances of one bottle . CONCLUSIONS This study has established that , among incentives for postal question naires , one big prize improves the yield more than many small prizes despite the lower odds of winning . It has also confirmed that offering a modest incentive to GPs generates good response rates for postal question naires OBJECTIVE To describe factors that influence participation by general practitioners ( GPs ) in survey research , and in particular to examine the effectiveness of telephone prompts made by a GP research er compared with non-medical research ers in a survey of GPs on sexually transmissible diseases ( STDs ) . DESIGN AND SETTING A question naire survey of knowledge , attitudes , behaviour and practice ( KABP ) in relation to STDs was distributed to 520 Victorian GPs r and omly selected from the Australian Medical Publishing Company 's ( AMPCo ) data base of Australian medical practitioners . MAIN OUTCOME MEASURES Number of GPs able to be contacted by telephone and cumulative and overall response rates to the question naire . RESULTS The overall response rate was 85 % . Although the GP research er was able to make contact by telephone in a higher proportion of cases ( 80 % ) than the non-GP research ers combined ( 69 % , p < 0.01 ) response rates were not significantly different ( 83 % versus 87 % ) . CONCLUSIONS Telephone prompts to encourage GP response in survey research need not be made by a medical practitioner . Other important factors in relation to response rate that should be considered by research ers are GP involvement in the developing and piloting of the survey instrument , incentives and provision of detailed feedback of the results of the survey In the general population , the use of stamps rather than business reply postage significantly improves response rates in mail surveys . Among physicians , however , a smaller effect might be anticipated due to their greater sophistication . An experiment was conducted to test the hypothesis that stamps would improve response rates and lower costs in a physician survey that included intensive follow up . In 1989 , 380 physicians who reported providing primary care were surveyed . The protocol included two mailings , a postcard reminder , and two telephone reminders . Physicians were r and omly assigned to receive a return envelope with a first-class stamp or an envelope that had been preprinted " business reply mail " in the first and second mailings . Response rates , calculated as completed surveys divided by eligible physicians , were 83.8 and 72.1 % for stamps and business reply respectively , a difference of 11.7 percentage points ( p < 0.01 ) . Moreover , the total cost per completed survey was $ 11.18 for the physicians receiving stamps and $ 14.25 for the physicians receiving business reply . As in mail surveys of the general public , the use of first-class stamps on return envelopes both improves response rates and reduces cost in surveys of physicians To determine whether academic physicians ' response rates to a mail survey depend on the envelope used to mail the survey , we r and omized 901 internists affiliated with a university department of medicine to receive a survey in either a university envelope or a Veterans Affairs envelope . The response rate among those receiving the Veterans Affairs envelope ( 41 % ) was 20 % higher than the response rate among those receiving the university envelope ( 34 % ) . We conclude that the packaging of a mail survey can influence the response rate Abstract This study investigated whether the opportunity to obtain Continuing Medical Education ( CME ) credit together with a five-dollar bill increased response rates and question naire completion rates in a physician survey involving mailed question naires . One thous and , three hundred and fourteen cardiologists , family practitioners , general internists ( non-surgeons ) and 264 vascular surgeons r and omly identified from the American Medical Association data base participated . After two , of up to four , question naire mailings , the opportunity to obtain CME credit and a five-dollar bill were included with question naire mailings . Among non-surgeons , 26.5 % responded to pre-incentive mailings and 30.2 % of those initially unresponsive replied after the interventions . Among surgeons , 39 % responded to pre-incentive mailings and 32.7 % of those initially unresponsive replied after the interventions . In conclusion , the opportunity to receive CME credit combined with a small monetary incentive is an effective motivation for physicians participating in a study involving mailed question naires PURPOSE We determine endourological practice patterns among American urologists for the management of distal ureteral calculi , ureteropelvic junction obstruction , staghorn calculi and the use of ureteral stents with extracorporeal shock wave lithotripsy ( ESWLdagger ) . MATERIAL S AND METHODS Surveys were mailed by the United States postal service to 1,000 American urologists selected r and omly from the American Urological Association membership roster . The same survey was sent via the Internet to 3,065 American urologists with an electronic mail address listed in the roster . RESULTS Responses were received from 1,029 urologists ( postal 601 , Internet 428 ) . Ureteroscopy was the preferred treatment for all distal ureteral calculi less than or equal to 10 mm . Acucisedouble dagger endopyelotomy was the most frequently selected therapy for adults with ureteropelvic junction obstruction ( 50.3 % , 514 of 1,022 ) . Open pyeloplasty was recommended by a significantly greater percentage of urologists in practice longer than 15 years compared with the remaining survey respondents ( 166 of 485 , 34.2 % versus 92 of 427 , 21.5 % ) . For patients with renal pelvic stones 10 , 15 or 20 mm . who are treated with ESWL routine stent placement was preferred by 25.3 % ( 259 of 1,022 ) , 57.1 % ( 584 of 1,022 ) and 87.1 % ( 888 of 1 , 019 ) of urologists , respectively . Percutaneous nephrolithotomy was preferred for patients with staghorn calculi by 80.5 % ( 828 of 1,028 ) of survey respondents . CONCLUSIONS Most urologists follow the American Urological Association practice guidelines for patients with distal ureteral calculi and staghorn stones . There is a significant difference of opinion regarding the use of stents with ESWL . No clear consensus has been reached concerning the management of adults with ureteropelvic junction obstruction . These data may be useful in design ing physician education programs and /or future investigations to help define st and ard treatment practice s for urological diseases OBJECTIVE To compare response rate , time to response , and data quality of electronic and postal surveys in the setting of postgraduate medical education . STUDY DESIGN AND SETTING A r and omized controlled trial in a university-based internal medicine residency program . We r and omized 119 residents and 83 faculty to an electronic versus a postal survey with up to two reminders and measured response rate , time to response , and data quality . RESULTS For residents , the e-survey result ed in a lower response rate than the postal survey ( 63.3 % versus 79.7 % ; difference -16.3 % , 95 % confidence interval ( 95 % CI ) -32.3 % to -0.4%% ; P=.049 ) , but a shorter mean response time , by 3.8 days ( 95 % CI 0.2 - 7.4 ; P=.042 ) . For faculty , the e-survey did not result in a significantly lower response rate than the postal survey ( 85.4 % vs. 81.0 % ; difference 4.4 % , 95 % CI -11.7 to 20.5 % ; P=.591 ) , but result ed in a shorter average response time , by 8.4 days ( 95 % CI 4.4 to 12.4 ; P < 0.001 ) . There were no differences in the quality of data or responses to the survey between the two methods . CONCLUSION E-surveys were not superior to postal surveys in terms of response rate , but result ed in shorter time to response and equivalent data quality Postal surveys are a cost effective method of obtaining information from large numbers of geographically disparate medical professionals about their attributes , behaviours , attitudes and beliefs . The validity of the findings of such surveys is primarily dependent upon an adequate response rate and it is of concern that the rates are declining.1 Inclusion of a pen along with the question naire is often used to counter this trend . In theory , the availability of a pen would enable immediate completion of the question naire . The gift of a pen may also predispose the recipient to look upon the question naire more favourably increasing the likelihood of a response . However , the effectiveness of this strategy has not been established . Therefore as part of a national survey of consultant gynaecologists , we conducted a r and omised controlled trial , to determine if Background .Mail surveys of physicians have been characterized by lower response rates than general population surveys , raising concerns about nonresponse bias . Although monetary incentives have routinely been used to improve survey response among physicians , questions remain regarding how much of an incentive is most cost-effective . The present study seeks to further examine the effects of incentive size on response rates to a national mail survey of physicians . Methods .This study used a r and om sample of 873 physicians practicing in the United States ; the response rate was 65 % ( n = 563 ) . Respondents were r and omly assigned to receive a $ 5 , $ 10 , or $ 20 cash incentive in the initial mailing . Except for the magnitude of the incentive , the procedures for each condition were identical , with each respondent receiving up to 3 follow-up mailings and 2 telephone calls . Results .Overall response rates ranged from 60.3 % for the $ 5 incentive category to 68.0 % for the $ 10 incentive category . Differences in overall response rates across the incentive categories , however , were not significant . Higher levels of incentives also did not significantly reduce the number of mail and /or telephone interventions required to reach the target response rate of 60.0 % . As expected , aggregate costs ( excluding labor ) were lowest for the $ 5 incentive group . Conclusions .Our findings suggest that changes in the magnitude of incentive do not automatically result in increases in survey response among physicians . Possible reasons for this lack of effect as well as alternatives to monetary incentives are addressed Effective strategies to maximize response rates to self-administered surveys of clinicians are crucial to minimize response bias . Offers of charitable donations have been assessed for their potential to promote participation of community sample s but not in the context of medical specialist sample s. We r and omized all Australian colorectal surgeons ( n = 219 ) to whom we mailed a survey about clinical practice guidelines to receive either a st and ard covering letter or one promising a donation to their peak professional organization upon our receipt of their completed survey . Contrary to expectations , surgeons advised that their participation would secure a donation to their college were significantly less likely to return their question naire ( 84.3 % , 95 % CI 76.0 - 90.5 % ) than those receiving a st and ard letter ( 93.7 % , 95 % CI 87.4 - 97.4 % ) . They also were more tardy in their response ( Hazard Ratio = 0.75 , 95 % CI 0.57 - 1.00 ) ( P = 0.047 ) . In this context , offering donations to surgeons was counterproductive in enhancing response rates The barrage of requests family physicians receive to complete mail surveys often results in physicians who are unwilling , or unable due to time constraints , to complete each survey they receive . Thus , to obtain an acceptable response rate , state-of-the-art mail survey techniques must be used . This article reports the results of the use of a modest($1 ) monetary incentive to increase a survey response rate . A r and om sample of 600 American Academy of Family Physicians members were mailed a survey of firearm safety counseling ; half received a $ 1 incentive whereas the remaining half served as a control group . The response rate in the incentive group was 63 % compared to 45 % in the control group [ X2 ( 1 , N = 251 ) = 16.0 , p < .0011 . Further , the use of the incentive appears to be more cost-effective than a thirdfollow-up ( postcard reminder ) mailing This study 's goals were to ( a ) determine whether sending a survey by certified mail results in a higher response rate from physicians compared to sending by first-class mail and ( b ) evaluate the cost-effectiveness of this method . The study sample was 409 physicians who were nonrespondents to two previous mailings of a medical specialty society survey . Eligible physicians were design ated at r and om to receive afinal mailing either by U.S. Postal Service certified mail including a return-receipt postcard or by first-class mail . There was a higher response rate from the certified mail group compared with the first-class mail group ( 41.3 % versus 24.8 % ; relative risk = 1.66 , 95 % Confidence Interval 1.25 , 2.21 ) . A cost-effectiveness analysis showed that the cost per respondent was higher using certified mail versus first-class mail in the third mailing ( $ 2.77 versus $ 2.34 ) . Thus , use of certified mail is effective in increasing survey response but more costly To evaluate the cost-effectiveness of a lottery on physicians ’ responses to a mail survey , a r and omized controlled trial was conducted with a r and om sample of 1,000 members of the Quebec Federation of General Practitioners in 1997 . For the first mailing of this survey , each respondent was r and omly assigned to the control or experimental group , which was offered participation in a lottery upon return of the question naire . Response rate was 41.2 % in the experimental group and 34.8 % in the control group , a 6.4 % difference ( CI95 % : 0.6 % – 12.6 % ) . The additional cost of the lottery was about Can$500 , giving an incremental cost of Can$16 per question naire returned . In conclusion , a lottery result ed in a small but statistically significant increase in the response rate of physicians to a mail survey . This method may be a cost-effective option when applied to large surveys |
2,495 | 27,820,225 | Strength exercises had a positive effect on fracture .
Aerobic exercises had a positive impact on lumbar bone mineral density , fall , and balance .
Soy protein supplementation was effective for improving lumbar bone mineral density while vitamin K supplementation had a positive effect on of femur bone mineral density .
Calcium supplementation had a positive impact on femur and lumbar bone mineral density .
The combination of exercise , calcium , and vitamin D supplementation was effective for improving lumbar bone mineral density , risk of fall , and balance .
Self-management programs for better bone health had a positive effect on balance and quality of life .
CONCLUSION The results indicate that lifestyle interventions including exercise and taking daily calcium and vitamin D supplementation are beneficial for improving bone health in women at high risk of osteoporosis . | BACKGROUND Osteoporosis is a disease characterised by low bone mass and microarchitectural deterioration of bone tissue , leading to increased bone fragility and a consequent increase in fracture risk , especially among postmenopausal women .
Management strategies for osteoporosis focus on reducing modifiable risk factors such as poor nutrition , insufficient physical activity , smoking , and heavy alcohol consumption . | BACKGROUND Studies of weight loss and changes in bone mineral density ( BMD ) have primarily been short-term trials in obese subjects . OBJECTIVE We examined the effects of a 5-yr intervention design ed to prevent menopausal weight gain or promote modest weight loss on BMD in premenopausal women participating in the Women 's Healthy Lifestyle Project . DESIGN We enrolled 373 premenopausal women ( age 44 - 50 yr ) and r and omly assigned them to either lifestyle intervention ( 175 women , low-fat dietary modification , weight loss , and physical activity intervention ) or control group ( 198 women ) . BMD and body weight were measured at baseline , annual follow-up visits ( 18 , 30 , 42 , and 54 months ) , and two postintervention follow-ups ( 66 and 78 months ) . BMD was measured by dual x-ray absorptiometry . RESULTS Over the 54 months of intervention , women in the intervention group lost 0.4 kg , whereas control women gained 2.6 kg ( P = 0.011 ) . The intervention group experienced significantly greater hip bone loss ( -0.20%/yr ) than the control group ( -0.03%/yr ) . During the postintervention , differences in rates of bone loss disappeared . When considering both menopausal status and use of hormone therapy ( HT ) , the annualized BMD changes were lower in women reporting HT use ; nevertheless , among women on HT , those who lost more than 3 % body weight experienced greater total hip BMD loss ( -0.25%/yr ) compared with those who gained weight ( -0.02%/yr ) ( P = 0.025 ) . CONCLUSIONS Women r and omized to a lifestyle intervention aim ed at preventing menopausal weight gain or promoting modest weight loss experienced greater rates of hip bone loss than control women Physical exercise has a favorable impact on bones , but optimum training strategies are still under discussion . In this study , we compared the effect of slow and fast resistance exercises on various osteodensitometric parameters . Fifty-three postmenopausal women were r and omly assigned to a strength training ( ST ) or a power training group ( PT ) . Both groups carried out a progressive resistance training , a gymnastics session , and a home training over a period of 12 mo . During the resistance training , the ST group used slow and the PT group fast movements ; otherwise there were no training differences . All subjects were supplemented with Ca and vitamin D. At baseline and after 12 mo , bone mineral density ( BMD ) was measured at the lumbar spine , proximal femur , and distal forearm by dual-energy X-ray absorptiometry . We also measured anthropometric data and maximum static strength . Frequency and grade of pain were assessed by question naire . After 12 mo , significant between-group differences were observed for BMD at the lumbar spine ( P < 0.05 ) and the total hip ( P < 0.05 ) . Whereas the PT group maintained BMD at the spine ( + 0.7 + /- 2.1 % , not significant ) and the total hip ( 0.0 + /- 1.7 % , not significant ) , the ST group lost significantly at both sites ( spine : -0.9 + /- 1.9 % ; P < 0.05 ; total hip : -1.2 + /- 1.5 % ; P < 0.01 ) . No significant between-group differences were observed for anthropometric data , maximum strength , BMD of the forearm , or frequency and grade of pain . These findings suggest that power training is more effective than strength training in reducing bone loss in postmenopausal women BACKGROUND Race and sex differences in the effect of diet on bone mineral density ( BMD ) at the hip in the elderly are unknown . OBJECTIVES This study related cross-sectional nutrient and dairy product consumption to hip BMD in white and black men and women aged > 60 y and evaluated the influence of nutrient and dairy product consumption on changes in BMD in a white cohort participating in a calcium , vitamin D , or placebo trial . DESIGN The Health Habits and History Question naire was used in 289 white women and 116 white men who participated in the trial and in 265 black women and 75 black men to predict total hip and femoral neck BMD or changes in BMD . RESULTS Blacks had higher calcium intakes than did whites ( 700 and 654 mg/d , respectively ; P = 0.0094 ) , and men had higher calcium intakes than did women ( 735 and 655 mg/d , respectively ; P = 0.0007 ) . For men , the correlation between total hip BMD and dairy calcium intake after adjustment for age , race , and weight was 0.23 ( P < 0.005 ) ; this relation was not significant in women ( r = 0.02 , P = 0.12 ) . Similar results were found for femoral neck BMD . In the longitudinal study , calcium supplementation reduced bone loss from the total hip and femoral neck in those who consumed < 1.5 servings of dairy products/d and were < 72 y old . CONCLUSIONS Cross-sectional results indicated that higher dairy product consumption is associated with greater hip BMD in men , but not in women . Calcium supplementation protected both men and women from bone loss in the longitudinal study of whites BACKGROUND No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women . OBJECTIVE Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones ( 80.4 mg/d ) in attenuating bone loss during the menopausal transition . DESIGN Perimenopausal subjects were r and omly assigned , double blind , to treatment : isoflavone-rich soy ( SPI+ ; n = 24 ) , isoflavone-poor soy ( SPI- ; n = 24 ) , or whey ( control ; n = 21 ) protein . At baseline and posttreatment , lumbar spine bone mineral density ( BMD ) and bone mineral content ( BMC ) were measured by using dual-energy X-ray absorptiometry . At baseline , midtreatment , and posttreatment , urinary N:-telopeptides and serum bone-specific alkaline phosphatase ( BAP ) were measured . RESULTS The percentage change in lumbar spine BMD and BMC , respectively , did not differ from zero in the SPI+ or SPI- groups , but loss occurred in the control group ( -1.28 % , P : = 0.0041 ; -1.73 % , P : = 0.0037 ) . By regression analysis , SPI+ treatment had a positive effect on change in BMD ( 5.6 % ; P : = 0.023 ) and BMC ( 10.1 % ; P : = 0.0032 ) . Baseline BMD and BMC ( P : < or = 0.0001 ) negatively affected the percentage change in their respective models ; baseline body weight ( P : = 0.0036 ) and bone-free lean weight ( P : = 0.016 ) contributed positively to percentage change in BMD and BMC , respectively . Serum BAP posttreatment was negatively related to percentage change in BMD ( P : = 0.0016 ) and BMC ( P : = 0.019 ) . Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones , not soy protein , exerted the effect . CONCLUSION Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women BACKGROUND The positive association between body weight and bone mineral density ( BMD ) is well documented ; in contrast , the effect of changes in body weight on BMD is not well understood , particularly , in normal-weight population s. OBJECTIVE We examined the effect of a lifestyle intervention aim ed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy , premenopausal women aged 44 - 50 y. DESIGN All women were participating in a clinical trial known as The Women 's Healthy Lifestyle Project and were r and omly assigned to intervention or control groups . Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial . RESULTS The intervention group ( n = 115 ) experienced a mean ( + /-SD ) weight loss of 3.2 + /- 4.7 kg over the 18 mo compared with a weight gain of 0.42 + /- 3.6 kg in the control group ( n = 121 ) ( P < 0.001 ) . The annualized rate of hip BMD loss was 2-fold higher ( P < 0.015 ) in the intervention group ( 0.81 + /- 1.3 % ) than in the control group ( 0.42 + /- 1.1 % ) ; a similar , although nonsignificant pattern was observed for the loss in spine BMD : 0.70 + /- 1.4 % and 0.37 + /- 1.5 % ( P = 0.093 ) in the intervention and control groups , respectively . Large increases in physical activity attenuated spine BMD loss , but had no significant effect on BMD loss at the hip . CONCLUSIONS The intervention group , who modified their lifestyle to lose weight , had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group . Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss BACKGROUND Impaired hip structure assessed by dual-energy X-ray absorptiometry ( DXA ) areal bone mineral density ( aBMD ) is an independent predictor for osteoporotic hip fracture . Some studies suggest that tea intake may protect against bone loss . OBJECTIVE Using both cross-sectional and longitudinal study design s , we examined the relation of tea consumption with hip structure . DESIGN R and omly selected women ( n = 1500 ) aged 70 - 85 y participated in a 5-y prospect i ve trial to evaluate whether oral calcium supplements prevent osteoporotic fractures . aBMD at the hip was measured at years 1 and 5 with DXA . A cross-sectional analysis of 1027 of these women at 5 y assessed the relation of usual tea intake , measured by using a question naire , with aBMD . A prospect i ve analysis of 164 women assessed the relation of tea intake at baseline , measured by using a 24-h dietary recall , with change in aBMD from years 1 to 5 . RESULTS In the cross-sectional analysis , total hip aBMD was 2.8 % greater in tea drinkers ( x : 806 ; 95 % CI : 797 , 815 mg/cm(2 ) ) than in non-tea drinkers ( 784 ; 764 , 803 mg/cm(2 ) ) ( P < 0.05 ) . In the prospect i ve analysis over 4 y , tea drinkers lost an average of 1.6 % of their total hip aBMD ( -32 ; -45 , -19 mg/cm(2 ) ) , but non-tea drinkers lost 4.0 % ( -13 ; -20 , -5 mg/cm(2 ) ) ( P < 0.05 ) . Adjustment for covariates did not influence the interpretation of results . CONCLUSION Tea drinking is associated with preservation of hip structure in elderly women . This finding provides further evidence of the beneficial effects of tea consumption on the skeleton BACKGROUND The effects of dietary changes on osteoporosis , low bone density , and frequent falls are unestablished . OBJECTIVE We assessed the effect of the Women 's Health Initiative Dietary Modification low-fat and increased fruit , vegetable , and grain intervention on incident hip , total , and site-specific fractures and self-reported falls , and , in a subset , on bone mineral density ( BMD ) . DESIGN Postmenopausal women ( n = 48,835 ) aged 50 - 79 y ( 18.6 % of minority race-ethnicity ) were r and omly assigned to receive the Dietary Modification intervention ( 40 % , n = 19,541 ) ( daily goal : < or = 20 % of energy as fat , > or = 5 servings of vegetables and fruit , and > or = 6 servings of grains ) or to a comparison group that received no dietary changes ( 60 % ; n = 29,294 ) . RESULTS After a mean 8.1 y of follow-up , 215 women in the intervention group and 285 women in the comparison group ( annualized rate : 0.14 % and 0.12 % , respectively ) experienced a hip fracture ( hazard ratio : 1.12 ; 95 % CI : 0.94 , 1.34 ; P = 0.21 ) . The intervention group ( n = 5423 ; annualized rate : 3.44 % ) had a lower rate of reporting > or = 2 falls than did the comparison group ( n = 8695 ; annualized rate : 3.67 % ) ( HR : 0.92 ; 95 % CI : 0.89 , 0.96 ; P < 0.01 ) . There was a significant interaction according to hormone therapy use ; those in the comparison group receiving hormone therapy had the lowest incidence of hip fracture . In a subset of 3951 women , hip BMD at years 3 , 6 , and 9 was 0.4 - 0.5 % lower in the intervention group than in the comparison group ( P = 0.003 ) . CONCLUSIONS A low-fat and increased fruit , vegetable , and grain diet intervention modestly reduced the risk of multiple falls and slightly lowered hip BMD but did not change the risk of osteoporotic fractures . This trial was registered at clinical trials.gov as NCT00000611 Forty-eight community living women 66–87 years old volunteered to participate in a 12-month prospect i ve , r and omized , controlled , trial . The aim was to determine if a combined weight-bearing training program twice a week would be beneficial to bone mineral density and neuromuscular function . The participants were pairwise age-matched and r and omly assigned to either an exercise group ( n=24 ) or a control group ( n=24 ) . Twenty-one subjects in the intervention group and 19 in the control group completed the study . The exercise program lasted for 50 min and consisted of a combination of strengthening , aerobic , balance and coordination exercises . The mean percentage of scheduled sessions attended for the exercise group was 67 % . At the completion of the study , the intervention group showed significant increments in bone mineral density of the Ward ’s triangle ( 8.4 % , P<0.01 ) as well as improvement in maximum walking speed ( 11.4 % , P<0.001 ) and isometric grip strength ( 9.9 % , P<0.05 ) , as compared to the control group . The conclusion was that a combined weight-bearing training program might reduce fracture risk factors by improving bone density as well as muscle strength and walking ability . This program could be suitable for older community living women in general , and might , therefore , have important implication s for fracture prevention Background Whole-body vibration ( WBV ) is a new type of exercise that has been increasingly tested for the ability to prevent bone fractures and osteoporosis in frail people . There are two currently marketed vibrating plates : a ) the whole plate oscillates up and down ; b ) reciprocating vertical displacements on the left and right side of a fulcrum , increasing the lateral accelerations . A few studies have shown recently the effectiveness of the up- and -down plate for increasing Bone Mineral Density ( BMD ) and balance ; but the effectiveness of the reciprocating plate technique remains mainly unknown . The aim was to compare the effects of WBV using a reciprocating platform at frequencies lower than 20 Hz and a walking-based exercise programme on BMD and balance in post-menopausal women . Methods Twenty-eight physically untrained post-menopausal women were assigned at r and om to a WBV group or a Walking group . Both experimental programmes consisted of 3 sessions per week for 8 months . Each vibratory session included 6 bouts of 1 min ( 12.6 Hz in frequency and 3 cm in amplitude with 60 ° of knee flexion ) with 1 min rest between bouts . Each walking session was 55 minutes of walking and 5 minutes of stretching . Hip and lumbar BMD ( g·cm-2 ) were measured using dual-energy X-ray absorptiometry and balance was assessed by the blind flamingo test . ANOVA for repeated measurements was adjusted by baseline data , weight and age . Results After 8 months , BMD at the femoral neck in the WBV group was increased by 4.3 % ( P = 0.011 ) compared to the Walking group . In contrast , the BMD at the lumbar spine was unaltered in both groups . Balance was improved in the WBV group ( 29 % ) but not in the Walking group . Conclusion The 8-month course of vibratory exercise using a reciprocating plate is feasible and is more effective than walking to improve two major determinants of bone fractures : hip BMD and balance Summary This study showed that combination of strength , balance , agility and jumping training prevented functional decline and bone fragility in home-dwelling elderly women . The finding supports the idea that it is possible to maintain good physical functioning by multi-component exercise program and thus postpone the age-related functional problems . Introduction This 1-year r and omized , controlled exercise intervention trial assessed the effects of two different training programs and their combination on physical functioning and bone in home-dwelling elderly women . Methods One hundred and forty-nine healthy women aged 70–78 years were r and omly assigned into : group 1—resistance training ( RES ) , group 2—balance-jumping training ( BAL ) , group 3—combination of resistance and balance-jumping training ( COMB ) , and group 4—controls ( CON ) . Self-rated physical functioning , leg extensor force , dynamic balance , and bone mass and structure were measured . Results Self-rated physical functioning improved in the COMB group , but was reduced in the CON group ; the mean inter-group difference was 10 % ( 95 % CI : 0–22 % ) . Mean increase in the leg extensor force was higher in the RES ( 14 % ; 4–25 % ) and COMB ( 13 % ; 3–25 % ) compared with the CON groups . Dynamic balance improved in the BAL ( 6 % ; 1–11 % ) and in the COMB ( 8 % ; 3–12 % ) groups . There were no inter-group differences in BMC at the proximal femur . In those COMB women who trained at least twice a week , the tibial shaft structure weakened 2 % ( 0–4 % ) less than those in the CON group . Conclusions Strength , balance , agility , and jumping training ( especially in combination ) prevented functional decline in home-dwelling elderly women . In addition , positive effects seen in the structure of the loaded tibia indicated that exercise may also play a role in preventing bone fragility The purpose of this study was to assess the effect of 18-week Tai Chi training on body balance in dynamic trial among elderly men . The study covered 49 subjects from age 60 to 82.1 years , who had osteopenia or osteoporosis . The subjects were recruited from the community by direct mailings and community efforts to participate in studies . The participants were r and omly assigned to either the exercise intervention ( n = 25 ) or control groups ( n = 24 ) . The Tai Chi group participated in an 18-week exercise class held for 45 min , twice a week . Body balance was assessed using a Computer Posturographic System PE 90 produced by the Military Institute of Aviation Medicine in Warsaw with modified software made in Pro-Med . During the measurement of body balance , the capacity to perform specific tasks was analyzed ( deflections in the set scope and direction ) . In the Tai Chi group , an increase ( p < or = 0.01 ) in effectiveness of balance task performance was noted from 80.95 % to 84.45 % after the training . In the control group , no statistically significant improvement in the level of body balance was found in the same period . Thus , an 18-week period of Tai Chi exercises twice a week for 45 min is beneficial for dynamic balance . It can be important for reducing fall risk factors BACKGROUND Exercise programs improve balance , strength and agility in elderly people and thus may prevent falls . However , specific exercise programs that might be widely used in the community and that might be " prescribed " by physicians , especially for patients with osteoporosis , have not been evaluated . We conducted a r and omized controlled trial of such a program design ed specifically for women with osteoporosis . METHODS We identified women 65 to 75 years of age in whom osteoporosis had been diagnosed by dual-energy X-ray absorptiometry in our hospital between 1996 and 2000 and who were not engaged in regular weekly programs of moderate or hard exercise . Women who agreed to participate were r and omly assigned to participate in a twice-weekly exercise class or to not participate in the class . We measured baseline data and , 20 weeks later , changes in static balance ( by dynamic posturography ) , dynamic balance ( by a timed figure-eight run ) and knee extension strength ( by dynamometry ) . RESULTS Of 93 women who began the trial , 80 completed it . Before adjustment for covariates , the intervention group tended to have greater , although nonsignificant , improvements in static balance ( mean difference 4.8 % , 95 % confidence interval [ CI ] -1.3 % to 11.0 % ) , dynamic balance ( mean difference 3.3 % , 95 % CI -1.7 % to 8.4 % ) and knee extension strength ( mean difference 7.8 % , 95 % CI -5.4 % to 21.0 % ) . Mean crude changes in the static balance score were -0.85 ( 95 % CI -2.91 to 1.21 ) for the control group and 1.40 ( 95 % CI -0.66 to 3.46 ) for the intervention group . Mean crude changes in figure-eight velocity ( dynamic balance ) were 0.08 ( 95 % CI 0.02 to 0.14 ) m/s for the control group and 0.14 ( 95 % CI 0.08 to 0.20 ) m/s for the intervention group . For knee extension strength , mean changes were -0.58 ( 95 % CI -3.02 to 1.81 ) kg/m for the control group and 1.03 ( 95 % CI -1.31 to 3.34 ) kg/m for the intervention group . After adjustment for age , physical activity and years of estrogen use , the improvement in dynamic balance was 4.9 % greater for the intervention group than for the control group ( p = 0.044 ) . After adjustment for physical activity , cognitive status and number of fractures ever , the improvement in knee extension strength was 12.8 % greater for the intervention group than for the control group ( p = 0.047 ) . The intervention group also had a 6.3 % greater improvement in static balance after adjustment for rheumatoid arthritis and osteoarthritis , but this difference was not significant ( p = 0.06 ) . INTERPRETATION Relative to controls , participants in the exercise program experienced improvements in dynamic balance and strength , both important determinants of risk for falls , particularly in older women with osteoporosis The purpose of this study was to assess the effects of a water-based exercise and self-management program on balance , fear of falling , and quality of life in community-dwelling women 65 years of age or older with a diagnosis of osteopenia or osteoporosis . Fifty women with an average age of 73.3 years ( range 65.5 - 82.4 , SD 3.9 ) were r and omised to intervention or control groups . The intervention group received a 10-week water-based exercise and self-management program compiled by Community Physiotherapy Services and conducted by a physiotherapist at an aquatic centre twice a week for one hour . The control group did not receive any instructions and were not encouraged to change their physical activity , activities of daily living or social habits during the study . Change in balance , measured using the step test , from baseline to follow-up differed between intervention and control groups , with mean ( 95 % CI ) between-group differences of 1.7 ( 0.9 to 2.6 ) and 2.1 ( 1.1 to 3.1 ) steps on the left and right sides respectively . Between-group differences in score changes were also significant in four of the eight domains of quality of life measured using the Short Form 36 question naire ( SF36 ; physical function 8.6 ( 0.4 to 16.8 ) , vitality 12.0 ( 2.3 to 21.8 ) , social function , and 14.1 ( 0.6 to 27.7 ) mental health 10.2 ( 2.0 to 18.4 ) ) , but not fear of falling measured using the modified falls efficacy scale ( 0.25 ( -0.3 to 0.81 ) . It is concluded that a water-based exercise and self-management program produced significant changes in balance and quality of life , but not fear of falling , in this group of community-dwelling women 65 years of age or older with a diagnosis of osteopenia or osteoporosis The aim of this study is to evaluate the effect of submaximal aerobic exercise program on postural balance in postmenopausal women with osteoporosis . Twenty-five postmenopausal women without osteoporosis and 28 postmenopausal women with osteoporosis enrolled in this study . Balance ability of all subjects was measured by timed up and go test ( TUG ) , four square step test ( FSS ) , Berg balance scale ( BBS ) and Kinesthetic ability trainer 3000 . After completion of initial measurements of balance , postmenopausal women with osteoporosis attended the submaximal aerobic exercise program on treadmill . At the end of the exercise program , balance tests were repeated . Balance tests of postmenopausal women without osteoporosis were repeated approximately 4-weeks after the initial measurement . There was statistically significant improvement in all balance scores in the postmenopausal women with osteoporosis after exercise training whereas there were no statistically significant differences in the scores of postmenopausal women without osteoporosis who did not exercise . This study showed that a 4-week submaximal aerobic exercise program provided significant improvements in static and dynamic balances in postmenopausal osteoporotic women Background Although soy protein and its isoflavones have been reported to reduce the risk of osteoporosis in peri- and post-menopausal women , most of these studies are of short duration ( i.e. six months ) . The objective of this study was to examine if one year consumption of soy-containing foods ( providing 25 g protein and 60 mg isoflavones ) exerts beneficial effects on bone in postmenopausal women . Methods Eighty-seven eligible postmenopausal women were r and omly assigned to consume soy or control foods daily for one year . Bone mineral density ( BMD ) and bone mineral content ( BMC ) of the whole body , lumbar ( L1-L4 ) , and total hip were measured using dual energy x-ray absorptiometry at baseline and after one year . Blood and urine markers of bone metabolism were also assessed . Results and Discussion Sixty-two subjects completed the one-year long study . Whole body and lumbar BMD and BMC were significantly decreased in both the soy and control groups . However , there were no significant changes in total hip BMD and BMC irrespective of treatment . Both treatments positively affected markers of bone formation as indicated by increased serum bone-specific alkaline phosphatase ( BSAP ) activity , insulin-like growth factor-I ( IGF-I ) , and osteocalcin ( BSAP : 27.8 and 25.8 % , IGF-I : 12.8 and 26.3 % , osteocalcin : 95.2 and 103.4 % for control and soy groups , respectively ) . Neither of the protein supplements had any effect on urinary deoxypyridinoline excretion , a marker of bone resorption . Conclusion Our findings suggest that although one year supplementation of 25 g protein per se positively modulated markers of bone formation , this amount of protein was unable to prevent lumbar and whole body bone loss in postmenopausal women Summary The purpose of this study was to determine the optimal intensity of exercise necessary to prevent the postmenopausal bone loss on the basis of anaerobic threshold ( AT ) . Thirty-three postmenopausal women were r and omized to control ( group C : n=12 ) or two exercise groups ( group H and group M ) . All women performed a treadmill exercise test , and the AT was measured by expired gas analysis . The exercise regimen consisted mainly of walking at a speed that kept the exercise heart rate above the AT ( group H : n=12 ) or below the AT ( group M : n=9 ) . Exercise was performed for 30 minutes , three times a week for 7 months . The bone mineral density ( BMD ) of the lumbar vertebrae was measured using dual energy X-ray absorptiometry . The BMD level in group C decreased by 1.7±2.7 % , but there was a significant increase of 1.1±2.9 % in group H. In group M there was a decrease of 1.0±3.1 % which did not differ from group C. In group C , serum osteocalcin and urinary hydroxyproline excretion were significantly increased , but no changes were seen in either of the exercise groups . Urinary calcium significantly decreased in the exercise groups . We conclude that short-term ( 7 months ) exercise with intensity above the AT is safe and effective in preventing postmenopausal bone loss Low bone mass , functional impairment , low muscle strength , and postural instability are predictors of the risk of fracture in an elderly person . The purpose of this study was to investigate the functional impact of an unvarying long-term exercise program to be carried out at home . The exercises had been shown to delay bone loss in an elderly population . At the Department of Physical Medicine and Rehabilitation , University of Vienna , postmenopausal women who had been stratified into exercise or control groups 5 to 10 yr ago were called in for a follow-up examination . Frequency of training , habits , and pain causing disability in activities of daily living were recorded . Walking velocity , muscle strength , and postural stability were measured . Functional assessment , blood analysis , and x-rays of the spine were performed additionally . One hundred twenty-four women aged 68.3 + /- 6.8 yr ( mean + /- SD ) underwent a follow-up investigation at the outpatient clinic . After 7.7 + /- 1.1 yr the compliance of the training group was still 36 % . Self-chosen gait velocity was slightly higher in the regular exercisers than in the controls . No intergroup differences were found for pain induced disability , muscle strength , body sway , and fracture rate . The pain disability index was significantly associated with corrected self-chosen gait velocity . The results suggest that an unvarying home-based exercise program may support general agility but does not yield enough force to improve muscle strength and postural stability in healthy , nondisabled , postmenopausal women who start exercising at the age of 60 yr . Further studies are needed to define more appropriate exercise programs for a comprehensive improvement of functional outcome in a population at high risk for osteoporosis A r and omized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly . Fifty Chinese women , aged 62–92 years , living in a hostel for the elderly in Hong Kong were r and omized to enter one of four treatment groups : ( I ) calcium supplementation of 800 mg ( as calcium lactate gluconate ) daily ; ( II ) load-bearing exercise four times a week plus a daily placebo tablet ; ( III ) calcium supplementation daily and load-bearing exercise four times a week ; ( IV ) a placebo tablet daily . The interventions went on for 10 months . The bone mineral density ( BMD ) was measured at three sites in the hip ( femoral neck , Ward 's triangle and intertrochanteric area ) and the L2–4 level of the spine . The percentage change in BMD in 10 months was used as the main outcome measurement . The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention . The BMD at Ward 's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement ( p<0.05 ) , but there was no significant change at the spine and femoral neck . Exercise had no effect on bone loss at any site . However , the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck ( p<0.05 ) , but not at the other sites . The parathyroid hormone levels fell significantly in subjects on calcium supplements (p<0.01).Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day . It was effective in reducing bone loss at the hip , and there may be interaction effects with exercise in maintaining bone density This study compared the effects of two exercise training programs , 11 months in duration , on bone mineral density ( BMD ) in older , sedentary women . Thirty-nine women , aged 60 - 74 years , were assigned to the following groups : ( a ) a group that performed exercises that introduced stress to the skeleton through ground-reaction forces ( GRF ) ( i.e. , walking , jogging , stairs ) ; ( b ) a group that performed exercises that introduced stress to the skeleton through joint-reaction forces ( JRF ) ( i.e. , weight lifting , rowing ) ; or ( c ) a no-exercise control group . BMD of the whole body , lumbar spine , proximal femur , and distal forearm was assessed five times at approximately 3-month intervals . The GRF and JRF exercise programs result ed in significant and similar increases in BMD of the whole body ( 2.0 + /- 0.8 % and 1.6 + /- 0.4 % , respectively ) , lumbar spine ( 1.8 + /- 0.7 % and 1.5 + /- 0.5 % , respectively ) , and Ward 's triangle region of the proximal femur ( 6.1 + /- 1.5 % and 5.1 + /- 2.1 % , respectively ) . There was a significant in BMD of the femoral neck only in response to the GRF exercise program ( GRF , 3.5 + /- 0.8 % ; JRF , -0.2 + /- 0.7 % ) . There were no significant changes in BMD in control subjects . Among all exercisers , there was a significant inverse ( r = -0.52 , p < 0.01 ) relationship between increases in whole body BMD and reductions in fat mass , suggesting a dose response effect of exercise on bone mass . Although femoral neck BMD was responsive only to the GRF exercise program , some adaptations ( i.e. , increase in lean body mass and strength ) that were specific to the JRF exercise program may be important in preventing osteoporotic fractures by reducing the risk for falls . It remains to be determined whether all of these benefits can be gained through a training program that combines the different types of exercises employed in this study It is an important aim in the prevention of osteoporosis to stop or decelerate bone loss during the early postmenopausal years . Here we report on results of the 3-year EFOPS exercise trial in osteopenic women . The exercise strategy emphasized low-volume high-resistance strength training and high-impact aerobics . Forty-eight fully compliant women ( 55.1±3.3 years ) with no medication or illness affecting bone metabolism participated in the exercise group ( EG ) ; 30 women ( 55.5±3.0 years ) served as non-training controls ( CG ) . At baseline there were no significant between-group differences with respect to physical fitness , bone mineral density , pain and nutritional status . The training consisted of two group training and two home training sessions per week . The study participants of both groups were individually supplemented with calcium and vitamin D ( cholecalciferol ) . Bone mineral density ( BMD ) was measured by DXA at the lumbar spine , proximal femur and distal forearm and by QCT at the lumbar spine . Speed of sound and broadb and ultrasound attenuation were determined at the calcaneus by quantitative ultrasound ( QUS ) . Pain frequency and intensity at different skeletal sites were assessed via question naire . After 38 months , the following within-group changes were measured : DXA lumbar spine , EG : 0.8 % n.s . ; CG : −3.3 % P < 0.001 ; QCT trabecular ROI , EG : 1.1 % n.s ; CG : −7.7 % P < 0.001 ; QCT cortical ROI , EG : 5.3 % P < 0.001 ; CG : −2.6 % P < 0.001 ; DXA total hip : EG : −0.2 % n.s ; CG −1.9 % , P < 0.001 ; DXA distal forearm , EG : −2.8 % P < 0.001 ; CG : −3.8 % P < 0.001 ; BUA , EG : −0.3 % n.s ; CG −5.4 % P < 0.001 ; SOS , EG : 0.3 % n.s ; CG −1.0 % P < 0.001 . At year 3 between-group differences relative to the exercise group were : DXA lumbar spine : 4.1 % P < 0.001 ; QCT trabecular ROI : 8.8 % P < 0.001 ; QCT cortical ROI : 7.9 % P < 0.001 ; DXA total hip : 2.1 % , P < 0.001 ; DXA distal forearm : 1.0 % n.s . ; BUA : 5.8 % P < 0.05 ; SOS : 1.3 % P < 0.001 . Pain frequency and intensity in the spine significantly decreased in the exercise group and increased in the control group , while no between-group differences were detected in the main joints . In summary , over a period of 3 years our low-volume/high-intensity exercise program was successful to maintain bone mineral density at the spine , hip and calcaneus , but not at the forearm Introduction The purpose of this study was to investigate the effect of a 12-month Balance Training Program on balance , mobility and falling frequency in women with osteoporosis . Methods Sixty-six consecutive elderly women were selected from the Osteometabolic Disease Outpatient Clinic and r and omized into 2 groups : the ‘ Intervention ’ , su bmi tted for balance training ; and the ‘ Control ’ , without intervention . Balance , mobility and falling frequency were evaluated before and at the end of the trial , using the Berg Balance Scale ( BBS ) , the Clinical Test Sensory Interaction Balance ( CTSIB ) and the Timed “ Up & Go ” Test ( TUGT ) . Intervention used techniques to improve balance consisting of a 1-hour session each week and a home-based exercise program . Results Sixty women completed the study and were analyzed . The BBS difference was significant higher in the Intervention group compared to Control ( 5.5 ± 5.67 vs −0.5 ± 4.88 score , p < 0.001 ) . Similarly , the number of patients in the Intervention group presented improvement in two conditions of CTSIB compared to Control ( eyes closed and unstable surface condition : 13 vs one patient , p < 0.001 and eyes open , visual conflict and unstable surface condition : 12 vs one patient , p < 0.001 ) . Additionally , the differences between the TUGT were reduced in the Intervention group compared to Control ( −3.65 ± 3.61 vs 2.27 ± 7.18 seconds , p < 0.001 ) . Notably , this improvement was paralleled by a reduction in the number of falls/patient in the Intervention group compared to Control ( −0.77 ± 1.76 vs 0.33 ± 0.96 , p = 0.018 ) . Conclusion This longitudinal prospect i ve study demonstrated that an intervention using balance training is effective in improving functional and static balance , mobility and falling frequency in elderly women with osteoporosis The effect of two structured exercise programmes on the bone mass of 48 healthy postmenopausal white women aged 50 - 62 was studied after one year . Volunteers were r and omised to group 1 ( control ) , group 2 ( aerobic exercise ) , or group 3 ( aerobic and strengthening exercises ) . Before and after the training programme each subject had evaluations of bone mass ( determined by neutron activation analysis and expressed as calcium bone index ) and maximum oxygen uptake attained on a multistage exercise treadmill test . After one year both exercise groups had higher levels of fitness and greater bone mass than controls . Mean values ( 2 SEM ) for changes in the calcium bone index were -0.011 ( 0.037 ) , 0.039 ( 0.035 ) , and 0.066 ( 0.036 ) for groups 1 , 2 , and 3 , respectively . Analysis of variance on the observed data and analysis of covariance adjusting changes to the initial mean value for the whole group showed significant differences between each exercise group and the controls but no difference between the exercise groups themselves . Both exercise groups showed a significant improvement in maximum oxygen uptake . This study suggests that exercise may modify bone loss in healthy postmenopausal women Background Limited information is available on ways to influence osteoporosis risk in premenopausal women . This study tested four hypotheses regarding the effects of individualized bone density ( BMD ) feedback and different educational interventions on osteoporosis preventive behavior and BMD in pre-menopausal women , namely : that women are more likely to change calcium intake and physical activity if their BMD is low ; that group education will be more efficacious at changing behavior than an information leaflet ; that BMD feedback and group education have independent effects on behavior and BMD ; and , that women who improve their physical activity or calcium intake will have a change in bone mass over 2 years that is better than those who do not alter their behavior . Methods We performed a 2-year r and omized controlled trial of BMD feedback according to T-score and either an osteoporosis information leaflet or small group education in a population -based r and om sample of 470 healthy women aged 25–44 years ( response rate 64 % ) . Main outcome measures were dietary calcium intake , calcium supplement use , smoking behavior , physical activity , endurance fitness , lower limb strength and BMD . We used paired t-tests , one-way ANOVA and linear regression techniques for data analysis . Results Women who had feedback of low BMD had a greater increase in femoral neck BMD than those with normal BMD ( 1.6 % p.a . vs. 0.7 % p.a . , p = 0.0001 ) , but there was no difference in lumbar spine BMD change between these groups ( 0.1 % p.a . vs. 0.08 % p.a . , p = 0.9 ) . Both educational interventions had similar increases in femoral neck BMD ( Leaflet = + 1.0 % p.a . , Osteoporosis self-management course = + 1.3 % p.a . , p = 0.4 ) . Femoral neck BMD change was only significantly associated with starting calcium supplements ( 1.3 % p.a , 95%CI + 0.49 , + 2.17 ) and persistent self-reported change in physical activity levels ( 0.7 % p.a . , 95%CI + 0.22 , + 1.22 ) . Conclusion Individualized BMD feedback combined with a minimal educational intervention is effective at increasing hip but not spine bone density in premenopausal women . The changes in behavior through which this was mediated are potentially important in the prevention of other diseases , thus measuring BMD at a young age may have substantial public health benefits , particularly if these changes are sustained Summary One hundred and twelve postmenopausal women with low bone mineral density ( BMD ) and forearm fractures were r and omized to physical training or control group . After one year the total hip BMD was significantly higher in the women in the physical training group . The results indicate a positive effect of physical training on BMD in postmenopausal women with low BMD . Introduction The fivefold increase in hip fracture incidence since 1950 in Sweden may partially be due to an increasingly sedentary lifestyle . Our hypothesis was that physical training can prevent bone loss in postmenopausal women . Methods One hundred and twelve postmenopausal women 45 to 65 years with forearm fractures and T-scores from −1.0 to −3.0 were r and omized to either a physical training or control group . Training included three fast 30-minute walks and two sessions of one-hour training per week . Bone mineral density ( BMD ) was measured in the hip and the lumbar spine at baseline and after one year . Results A per protocol analysis was performed , including 48 subjects in the training group and 44 subjects in the control group . The total hip BMD increased in the training group + 0.005 g/cm2 ( ±0.018 ) , + 0.58 % , while it decreased −0.003 g/cm2 ( ±0.019 ) , −0.36 % , ( p = 0.041 ) in the control group . No significant effects of physical training were seen in the lumbar spine . A sensitivity intention to treat analysis , including all r and omized subjects , showed no significant effect of physical training on BMD at any site . Conclusions The results indicate a small but positive effect of physical exercise on hip BMD in postmenopausal women with low BMD PURPOSE Despite the decreased gravitational loading that is experienced in an aquatic environment , little research has been conducted on this exercise medium for women with osteoporosis ( OP ) . Aquatic exercise ( AE ) may improve function and balance , thus ultimately decreasing fall risk and the potential for hip fractures in this high-risk population . METHOD A total of 68 women with OP , aged 60 years or older , were recruited into a r and omized clinical trial evaluating the impact of AE , l and exercise ( LE ) , and no exercise ( NE ) on balance , functional mobility , and quality of life ( QOL ) . RESULTS Only one balance measure ( backward t and em walk ) significantly improved with AE compared to LE , but this did not translate into a greater improvement in self-report function . There were no significant differences between the exercise interventions and NE , except for in ratings of global change , where participants in the AE group were three times more likely to report improvement than those in the NE group . CONCLUSION There were no differences in balance , function , or QOL in women with OP who followed an AE or LE programme compared to those in an NE control group . However , the significant differences in backward t and em walk between the AE and LE groups and self-reported global change between the AE and NE groups warrant further investigation . Significant improvements in balance and global change suggest that AE is a viable alternative for older women with OP who have difficulty exercising on l and OBJECTIVE to evaluate the effects of brisk walking on bone mineral density in women who had suffered an upper limb fracture . DESIGN r and omized placebo-controlled trial . Assessment s of bone mineral density were made before and at 1 and 2 years after intervention . St and ardized and vali date d measures of physical capacity , self-rated health status and falls were used . SETTING district general hospital outpatient department . SUBJECTS 165 women drawn from local accident and emergency departments with a history of fracture of an upper limb in the previous 2 years . Women were r and omly allocated to intervention ( self-paced brisk walking ) or placebo ( upper limb exercises ) groups . INTERVENTION both groups were seen at 3-monthly intervals to assess progress , measure physical capacity and maintain enthusiasm . The brisk-walking group were instructed to progressively increase the amount and speed of walking in a manner that suited them . The upper limb exercise placebo group were asked to carry out a series of exercises design ed to improve flexibility and fine h and movements , appropriate for a past history of upper limb fracture . RESULTS drop-outs from both intervention and placebo groups were substantial ( 41 % ) , although there were no significant differences in bone mineral density , physical capacity or health status between drop-outs and participants . At 2 years , among those completing the trial , bone mineral density at the femoral neck had fallen in the placebo group to a greater extent than in the brisk-walking group [ mean net difference between intervention and placebo groups 0.019 g/cm2 , 95 % confidence interval ( CI ) -0.0026 to + 0.041 g/cm2 , P = 0.056 ] . Lumbar spine bone mineral density had increased to a similar extent ( + 0.017 g/cm2 ) in both groups . The cumulative risk of falls was higher in the brisk-walking group ( excess risk of 15 per 100 person-years , 95 % CI 1.4 - 29 per 100 person-years , P < 0.05 ) . There were no significant differences in clinical or spinal x-ray fracture risk or self-rated health status between intervention and placebo groups . CONCLUSION the promotion of exercise through brisk-walking advice given by nursing staff may have a small , but clinical ly important , impact on bone mineral density but is associated with an increased risk of falls . Self-paced brisk walking is difficult to evaluate in r and omized controlled trials because of drop-outs , placebo group exercise , limited compliance and lack of st and ardization of the duration and intensity of walking . Further work is needed to evaluate the best means of safely achieving increased activity levels in different groups , such as older women and those at high risk of fractures Introduction Osteoporosis represents a growing public health concern ; however , current rates of management are sub-optimal . The aim of our study was to assess , in a r and omized controlled trial , the effect of a mailed educational intervention on older adults ’ knowledge , attitudes , and preventive behaviors regarding osteoporosis . The setting was a large publicly funded state pharmacy benefits program . The patients were 31,715 Medicare beneficiaries from Pennsylvania who participated in a drug benefits program for low-to-moderate income elderly people . Methods All women aged over 65 years , and all men and women with a history of fracture or long-term oral use of glucocorticoid , were included . Approximately half of the participants ( intervention group ) were r and omly selected to receive three mailings aim ed at improving knowledge of osteoporosis and enhancing preventive activities , such as using calcium and vitamin D , reducing fall risks in the home , obtaining a bone mineral density ( BMD ) test , and taking medications when necessary . The other participants did not receive the intervention mailings and served as controls . We surveyed a sample of intervention and control subjects to determine the effects of the intervention on knowledge , attitudes , self-efficacy ( confidence in one ’s ability to perform specific activities ) , and behavior regarding osteoporosis prevention and treatment . Six hundred r and omly selected participants in the intervention group and an equal number in the control group were invited to participate . Results Twenty-six had died and 636 of the remaining 1,185 ( 54 % ) completed the survey . Respondents and non-respondents did not differ significantly with respect to measured sociodemographic factors . All scales had good reliability ( all Cronbach ’s alphas > 0.65 ) . Knowledge of osteoporosis was generally very good and did not differ between intervention ( mean = 65 % correct responses ) and control subjects ( mean = 67 % correct ; P=0.4 ) . Perceived susceptibility to osteoporosis was relatively high and similar across groups ( P=0.4 ) . Self-efficacy for participating in osteoporosis prevention and treatment was very strong in both the intervention ( mean = 4.3 on a 0–5 scale ) and control ( mean = 4.2 , P=0.03 ) groups . On average , subjects in the intervention group reported participating in 3.5 of 6 preventive osteoporosis activities compared with 3.4 in the control group ( P=0.5 ) . Conclusions Compared with the controls , a mailed educational intervention for osteoporosis was not associated with better knowledge , higher perceived susceptibility , or performance of preventive measures among the at-risk older adults that we studied . The intervention group demonstrated a small increase in self-efficacy . More intensive patient interventions or intervention aim ed at other aspects of the care process may be required to bring about changes that lead to a reduction in fractures OBJECTIVE To determine how multiple risk factors for osteoporotic fractures could be modified by high-intensity strength training exercises in postmenopausal women . DESIGN R and omized controlled trial of 1-year duration . SETTING Exercise laboratory at Tufts University , Boston , Mass. POPULATION Forty postmenopausal white women , 50 to 70 years of age , participated in the study ; 39 women completed the study . The subjects were sedentary and estrogen-deplete . INTERVENTIONS High-intensity strength training exercises 2 days per week using five different exercises ( n = 20 ) vs untreated controls ( n = 19 ) . MAIN OUTCOME MEASURES Dual energy x-ray absorptiometry for bone status , one repetition maximum for muscle strength , 24-hour urinary creatinine for muscle mass , and backward t and em walk for dynamic balance . RESULTS Femoral neck bone mineral density and lumbar spine bone mineral density increased by 0.005 + /- 0.039 g/cm2 ( 0.9 % + /- 4.5 % ) ( mean + /- SD ) and 0.009 + /- 0.033 g/cm2 ( 1.0 % + /- 3.6 % ) , respectively , in the strength-trained women and decreased by -0.022 + /- 0.035 g/cm2 ( -2.5 % + /- 3.8 % ) and -0.019 + /- 0.035 g/cm2 ( -1.8 % + /- 3.5 % ) , respectively , in the controls ( P = .02 and .04 ) . Total body bone mineral content was preserved in the strength-trained women ( + 2.0 + /- 68 g ; 0.0 % + /- 3.0 % ) and tended to decrease in the controls ( -33 + 77 g ; -1.2 % + /- 3.4 % , P = .12 ) . Muscle mass , muscle strength , and dynamic balance increased in the strength-trained women and decreased in the controls ( P = .03 to < .001 ) . CONCLUSIONS High-intensity strength training exercises are an effective and feasible means to preserve bone density while improving muscle mass , strength , and balance in postmenopausal women Summary On the premise that bone response to exercise is locally controlled [ 1 ] , we conducted a r and omized trial to evaluate the effects of a 1-year training of psoas muscles ( treatment group : TG ) versus a 1-year training of deltoid muscles ( control group : CG ) on the lumbar trabecular bone mineral density ( TBMD ) . TBMD was measured with computed tomography scan . Seventy-eight subjects were included and 67 completed the study . Intention to treat analysis revealed no significant change in TBMD from 0 to 12 months . Data analysis in the 67 remaining women , including both assiduous and nonassiduous subjects , revealed greater bone loss in CG than in TG although the difference was not significant . Similar analysis in a subgroup of subjects who performed the exercises assiduously ( TG : n = 23 , CG : n = 26 ) showed that the mean bone loss of all four vertebrae from 0 to 12 months was significantly greater in the CG ( −8.87 ± 12.75 mg/cm3 , mean ± SD ) than in the TG ( 0.14 ± 11.21 mg/cm3 , mean ± SD , P = 0.01 ) . These results suggest that continuous 1-year psoas training can prevent lumbar bone loss in postmenopausal women and support the hypothesis of local action of physical activity BACKGROUND Osteoporosis among older women is a major public health problem . We studied the effects of three approaches to the prevention of osteoporosis in women with low bone density . METHODS One hundred twenty postmenopausal women ( mean [ + /- SD ] age , 56 + /- 4 ) who were selected because they had low forearm bone density were enrolled in a double-blind , placebo-controlled , r and omized study comparing the effects of an exercise regimen ( exercise group , n = 41 ) , exercise plus dietary calcium supplementation ( exercise-calcium group , n = 39 ) , and exercise plus continuous replacement of estrogen and progesterone ( exercise-estrogen group , n = 40 ) . Periodically during the two-year study period , we measured the women 's bone density at three forearm sites , measured indexes of calcium metabolism , and recorded symptom scores . A comparison group of 42 women ( mean age , 55.5 + /- 3.1 ) with normal bone density was also followed for two years . RESULTS Significant bone loss in the distal forearm occurred in the group with normal bone density ( control group ) and the exercise group ( change , -2.7 percent and -2.6 percent of the base-line value per year , respectively ) . Bone loss at the distal forearm site was significantly lower in the exercise-calcium group ( -0.5 percent of the base-line value per year ) , and bone density increased at this site in the exercise-estrogen group ( + 2.7 percent of the base-line value per year ) . Bone loss at the median forearm site was significantly lower in the exercise-calcium group ( -1.3 percent of the base-line value per year ) than in the exercise group ( -2.4 percent ) , and bone density at this site increased significantly in the exercise-estrogen group ( + 0.8 percent of the base-line value per year ) . Breast tenderness occurred in 47 percent of the women in the exercise-estrogen group but in only 20 percent in the other two treatment groups . Vaginal bleeding occurred at some time in 52 percent of the women who had not had a hysterectomy in the exercise-estrogen group , as compared with 11 percent and 12.5 percent , respectively , in the exercise and exercise-calcium groups . CONCLUSIONS In postmenopausal women with low bone density , bone loss can be slowed or prevented by exercise plus calcium supplementation or estrogen-progesterone replacement . Although the exercise-estrogen regimen was more effective than exercise and calcium supplementation in increasing bone mass , it also caused more side effects Osteoporosis is a major public health concern . The combination of exercise , hormone replacement therapy , and calcium supplementation may have added benefits for improving bone mineral density compared to a single intervention . To test this notion , 320 healthy , non-smoking postmenopausal women , who did or did not use hormone replacement therapy ( HRT ) , were r and omized within groups to exercise or no exercise and followed for 12 months . All women received 800 mg calcium citrate supplements daily . Women who exercised performed supervised aerobic , weight-bearing and weight-lifting exercise , three times per week in community-based exercise facilities . Regional bone mineral density ( BMD ) was assessed by dual energy X-ray absorptiometry . Women who used HRT , calcium , and exercised increased femoral neck , trochanteric and lumbar spine bone mineral density by approximately 1–2 % . Trochanteric BMD was also significantly increased by ~1.0 % in women who exercised and used calcium without HRT compared to a negligible change in women who used HRT and did not exercise . The results demonstrate that regional BMD can be improved with aerobic , weight-bearing activity combined with weight lifting at clinical ly relevant sites in postmenopausal women . The response was significant at more sites in women who used HRT , suggesting a greater benefit with hormone replacement and exercise compared to HRT alone This study tested whether moderate resistance training would improve femoral bone mineral density ( BMD ) in long-term users of hormone therapy with low BMD . The study was a 2-year r and omized , controlled , trial ( RCT ) of moderate resistance training of either the lower extremity or the upper extremity . Eighty-five women participated in a 6-month observation period . The setting was center-based and home-based training . The participants were 189 women aged 59–78 years , with total femur T-scores from −0.8 to −2.8 and on hormone therapy ( HT ) for a minimum of 2 years ( mean 11.8 years ) ; 153 completed the trial . Lower extremity training used weight belts ( mean 7.8 kg ) in step-ups and chair rises ; upper extremity training used elastic b and s and dumbbells . Measurements were BMD and body composition [ dual-energy X-ray absorptiometry ( DXA ) ] , bone turnover markers . Total femoral BMD showed a downward trend during the observation period : 0.35%±0.18 % ( P=0.14 ) . The response to training was similar in the upper and lower groups in the primary outcomes . At 2 years , total femoral BMD increased 1.5 % ( 95 % CI 0.8%–2.2 % ) in the lower group and 1.8 % ( 95 % CI 1.1%–2.5 % ) in the upper group . Trochanter BMD increased 2.4 % ( 95 % CI 1.3%–3.5 % ) in the lower group and 2.5 % ( 95 % CI 1.4%–3.6 % ) in the upper group ( for both analyses time effect P<0.001 ) . At 1 year , a bone resorption marker ( C-telopeptide ) decreased 9 % ( P=0.04 ) . Bone formation markers , bone-specific alkaline phosphatase , decreased 5 % ( P<0.001 ) , and N-terminal type I procollagen peptide decreased 7 % ( P=0.01 ) . Body composition ( percent lean and percent body fat ) was maintained in both groups . We concluded that long-term moderate resistance training reversed bone loss , decreased bone turnover , increased femur BMD , and maintained body composition . The similarity of response in upper and lower groups supports a systemic response rather than a site-specific response to moderate resistance training The separate and combined effects of weight-bearing exercise and hormone replacement therapy ( HRT ) on bone mineral density ( BMD ) were studied in 32 women , 60 to 72 years of age . HRT consisted of continuous conjugated estrogens 0.625 mg/day and trimonthly medroxyprogesterone acetate 5 mg/day for 13 days . Exercise consisted of 2 months of low-intensity exercise followed by 9 months of more vigorous weight-bearing exercise approximately 45 minutes/day , > or = 3 days/week , at 65 - 85 % of maximal heart rate . Lumbar spine and proximal femur BMD were significantly increased in response to exercise and to HRT , and total body BMD was significantly increased in response to HRT ; neither exercise nor HRT had an effect on wrist BMD . The combination of exercise + HRT result ed in increased BMD at all sites except the wrist , with effects being additive for the lumbar spine and Ward 's triangle and synergistic for the total body . Based on reductions in serum osteocalcin levels , it appears that increases in BMD in response to HRT and exercise + HRT were due to decreased bone turnover . The lack of change in serum osteocalcin and IGF-I in response to exercise alone suggests that increases in BMD were due to decreased bone resorption and not increased formation . Results indicate that weight-bearing exercise + HRT may be effective in preventing and /or treating osteoporosis . It is likely that the additive effects of weight-bearing exercise and HRT on bone mineral accretion , coupled with other adaptations to the exercise ( i.e. , increased strength and functional capacity ) , could effectively reduce the incidence of falls and osteoporotic fractures 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 Although several observational studies have demonstrated an association between vitamin K status and bone mineral density ( BMD ) in postmenopausal women , no placebo-controlled intervention trials of the effect of vitamin K1 supplementation on bone loss have been reported thus far . In the trial presented here we have investigated the potential complementary effect of vitamin K1 ( 1 mg/day ) and a mineral + vitamin D supplement ( 8 µg/day ) on postmenopausal bone loss . The design of our study was a r and omized , double-blind , placebo-controlled intervention study ; 181 healthy postmenopausal women between 50 and 60 years old were recruited , 155 of whom completed the study . During the 3-year treatment period , participants received a daily supplement containing either placebo , or calcium , magnesium , zinc , and vitamin D ( MD group ) , or the same formulation with additional vitamin K1 ( MDK group ) . The main outcome was the change in BMD of the femoral neck and lumbar spine after 3 years , as measured by DXA . The group receiving the supplement containing additional vitamin K1 showed reduced bone loss of the femoral neck : after 3 years the difference between the MDK and the placebo group was 1.7 % ( 95 % Cl : 0.35–3.44 ) and that between the MDK and MD group was 1.3 % ( 95 % Cl : 0.10–3.41 ) . No significant differences were observed among the three groups with respect to change of BMD at the site of the lumbar spine . If co-administered with minerals and vitamin D , vitamin K1 may substantially contribute to reducing postmenopausal bone loss at the site of the femoral neck The purpose of this study was to examine the effect of a single- vs. a multiple-set resistance training protocol in well-trained early postmenopausal women . Subjects ( N = 71 ) were r and omly assigned to begin either with 12 weeks of the single-set or 12 weeks of the multiple-set protocol . After another 5 weeks of regenerational resistance training , the subgroup performing the single-set protocol during the first 12 weeks crossed over to the 12-week multiple-set protocol and vice versa . Neither exercise type nor exercise intensity , degree of fatigue , rest periods , speed of movement , training sessions per week , compliance and attendance , or periodization strategy differed between exercise protocol s. Body mass , body composition , and 1 repetition maximum ( 1RM ) values for leg press , bench press , rowing , and leg adduction were measured at baseline and after each period . Multiple-set training result ed in significant increases ( 3.5–5.5 % ) for all 4 strength measurements , whereas single-set training result ed in significant decreases ( 21.1 to 22.0 % ) . Body mass and body composition did not change during the study . The results show that , in pretrained subjects , multiple-set protocol s are superior to single-set protocol s in increasing maximum strength UNLABELLED Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women . The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals . Weight reduction result ed in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day . INTRODUCTION Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium ( Ca ) supplementation . However , because bone loss caused by weight loss may be greater in overweight than obese women , it is not clear whether Ca supplementation is also beneficial in overweight women . MATERIAL S AND METHODS We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women ( age , 61 + /- 6 years ; body mass index , 27.0 + /- 1.8 kg/m2 ) . Subjects completed either a 6-month energy-restricted diet ( WL , n = 47 ) and lost 9.3 + /- 3.9 % weight or maintained weight ( WM ; 1 g Ca/day , n = 19 ) . Participants in the WL group were r and omly assigned to either normal ( 1 g/day ; WL NL-Ca ) or high ( 1.7 g/day ; WL Hi-Ca ) Ca intake . Regional BMD and BMC were measured at baseline and after 6 months . RESULTS During normal Ca intake , trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women ( p < 0.05 ) . The WL NL-Ca group lost more trochanter BMD ( -4.2 + /- 4.1 % ) and BMC ( -4.8 + /- 7.1 % ) than the WL Hi-Ca group ( -1.4 + /- 5.6 % and -1.1 + /- 8.1 % , respectively ; p < 0.05 ) . There were no significant changes in BMD or BMC at the femoral neck in any group . Weight loss correlated with trochanter BMD loss ( r = 0.687 , p < 0.001 ) in the WL NL-Ca group . CONCLUSION Despite an intake of 1 g Ca/day , bone loss occurred at some sites because of weight loss . Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women The etiology of age-related bone loss is unclear but both lack of exercise and dietary calcium deficiency have been implicated in its causation . This 2-year r and omized placebo-controlled study was design ed to examine the effects of increased dietary calcium and exercise in 168 women who were more than 10 years postmenopausal . The subjects were r and omized into one of 4 groups : placebo , milk powder containing 1 g of calcium , calcium tablets 1 g/night , and calcium tablets 1 g/night and an exercise regimen . The exercise group aim ed to undertake 4 h of extra weight-bearing exercise per week and were undertaking 10 % more activity than other groups at 2 years . Bone mineral density at the lumbar spine , three hip sites , and two sites of the tibia close to the ankle joint were measured at 6 month intervals . Dietary intake was evaluated by a weighed food record , exercise was evaluated by an exercise diary , and blood and urine sample s were obtained to examine effects on calcium homeostasis . Individual data points were compared using repeated measures ANOVA and least squares regression . Calcium supplementation by either the calcium tablets or the milk powder result ed in cessation of bone loss at the intertrochanteric hip site ( placebo , calcium tablets , calcium and exercise , milk powder -0.81 , + 0.17 , + 0.23 , and + 0.07 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) with similar results at the trochanteric hip site . The calcium and exercise group had less bone loss at the femoral neck site when compared with calcium supplementation alone ( placebo , calcium tablets , calcium and exercise , milk powder -0.67 , -0.18 , + 0.28 , and -0.18 % per year , respectively ; p < 0.05 for calcium and exercise compared with calcium alone ) . There was a significant reduction in the rate of bone loss at the ultradistal site of the tibia ( placebo , calcium tablets , calcium and exercise , milk powder -2.5 , -1.6 , -1.0 , and -1.5 % per year , respectively ; p < 0.05 for all supplementation groups compared with placebo ) . There was no significant bone loss at the spine site in any group . ( ABSTRACT TRUNCATED AT 250 WORDS Summary A simple , appealing , physical activity program can be prescribed to reduce the risk of falls in sedentary , postmenopausal , independent-living , Caucasian women . Foot stamping , progressively loaded squats , and in-line dancing positively influence proximal femoral bone mineral density , lower extremity strength , and static and dynamic balance . Introduction Foot stamping , squats exercises , and in-line dancing together create a suitable activity program for sedentary , independent-living older women . Methods Forty-five postmenopausal women not taking medications for bone health were r and omly assigned to one of three groups . All groups attended one line dance class per week . Two groups additionally performed progressively loaded squats five times per week . One group also performed four foot stamps , twice daily , five times per week . Broadb and ultrasound attenuation ( BUA ) , proximal femur ( PF ) and lumbar spine ( LS ) bone mineral density ( BMD ) , squats number , and balance variables were measured . Results There were no differences within or between groups in baseline and follow-up BUA , PF or LS BMD ; however , a strong stamp compliance effect was apparent for BUA ( r = 0.73 ) and PF BMD ( r = 0.79 ) . Number of squats ( p < 0.01 ) and single leg stance time ( p < 0.01 ) increased , while timed up and go time decreased ( p < 0.01 ) for all participants . Conclusions Line dancing , particularly in concert with regular squats and foot stamping , is a simple and appealing strategy that may be employed to reduce lower extremity bone loss , and improve lower limb muscle strength and balance , in independent living , otherwise healthy , postmenopausal Caucasian women We studied the response of bone at specific skeletal sites to either lower body exercise alone or complemented with upper body exercise in premenopausal women . Thirty-five exercisers and 24 age-matched controls completed the 12-month study . Exercising women ( N = 35 ) were r and omly assigned to either lower body resistance plus jump exercise ( LOWER ) ( N = 19 ) or to lower and upper body resistance plus jump exercise ( UPPER + LOWER ) ( N = 16 ) . Exercisers trained three times per week completing 100 jumps and 100 repetitions of lower body resistance with or without 100 repetitions of upper body resistance exercise at each session . Intensity for lower body exercise was increased using weighted vests for jump and resistance exercises , respectively . Intensity for upper body exercise was increased using greater levels of tautness in elastic b and s. Bone mineral density ( BMD ) at the total hip , greater trochanter , femoral neck , lumbar spine and whole body were measured by dual energy X-ray absorptiometry ( Hologic QDR-1000/W ) at baseline , 6 and 12 months . Data were analyzed first including all enrolled participants who completed follow-up testing and secondly including only those women whose average attendance was > or = 60 % of prescribed sessions . Group differences in 12-month % change scores for BMD variables were analyzed by univariate ANCOVA adjusted for baseline differences in age . Post hoc tests were performed to determine which groups differed from one another . Initial analysis showed significant differences in greater trochanter BMD between each exercise group and controls , but not between exercise groups ( 2.7%+/-2.5 % and 2.2%+/-2.8 % vs. 0.7%+/-1.7 % , for LOWER and UPPER + LOWER vs. controls , respectively ; p < 0.02 ) and near significant group differences at the spine ( p = 0.06 ) . Excluding exercisers with low compliance , group differences at the greater trochanter remained , while spine BMD in UPPER + LOWER was significantly different from LOWER and controls , who were not significantly different from one another ( 1.4%+/-3.9 % vs. -0.9%+/-1.7 % and -0.6%+/-1.8 % , for UPPER + LOWER vs. LOWER and controls , respectively ; p < 0.05 ) . No significant differences among groups were found for femoral neck , total hip or whole body BMD . Our data support the site-specific response of spine and hip bone density to upper and lower body exercise training , respectively . These data could contribute to a site-specific exercise prescription for bone health Dietary studies often report low calcium intake amongst post-menopausal Malaysian women and calcium deficiency has been implicated as part of the etiology of age-related bone loss leading to osteoporosis . Therefore , the objective of this study was to examine the effectiveness of high calcium skimmed milk ( Anlene Gold ™ , New Zeal and Milk , Wellington , New Zeal and ) to reduce bone loss in Chinese postmenopausal women . Two hundred subjects aged 55–65 years and who were more than 5 years postmenopausal were r and omized to a milk group and control group . The milk group consumed 50 g of high calcium skimmed milk powder daily , which contained 1200 mg calcium ( taken as two glasses of milk a day ) . The control group continued with their usual diet . Using repeated measures ANCOVA , the milk supplement was found to significantly reduce the percentage of bone loss at the total body compared to the control group at 24 months ( control −1.04 % , milk −0.13 % ; P<0.001 ) . At the lumbar spine , the percentage of bone loss in the control group was significantly higher ( −0.90 % ) when compared to the milk ( −0.13 % ) supplemented group at 24 months ( P<0.05 ) . Similarly , milk supplementation reduced the percentage of bone loss at the femoral neck ( control −1.21 % , milk 0.51 % ) ( P<0.01 ) and total hip ( control −2.17 % , milk −0.50 % ) ( P<0.01 ) . The supplemented group did not experience any significant weight gain over the 24 months . The serum 25-hydroxy vitamin D level improved significantly ( P<0.01 ) from 69.1±16.1 nmol/l at baseline to 86.4±22.0 nmol/l at 24 months in the milk group . In conclusion , ingestion of high calcium skimmed milk was effective in reducing the rate of bone loss at clinical ly important lumbar spine and hip sites in postmenopausal Chinese women in Malaysia . Supplementing with milk had additional benefits of improving the serum 25-hydroxy vitamin D status of the subjects Abstract : The aim of the study was to investigate the effects of regular aerobic exercise training on bone mineral density ( BMD ) in middle-aged men . A population based sample of 140 men ( 53–62 years ) was r and omly assigned into the exercise and reference groups . BMD and apparent volumetric BMD ( BMDvol ) of the proximal femur and lumbar spine ( dual-energy X-ray absorptiometry , DXA ) and anthropomorphic measurements were performed at the r and omization and 2 and up to 4 years later . The participation rate was 97 % and 94 % at the second and third BMD measurements , respectively . As another indication of excellent adherence and compliance , the cardiorespiratory fitness ( aerobic threshold ) increased by 13 % in the exercise group . The 2 % decrease in the reference group is regarded as an age-related change in cardiorespiratory fitness . Regardless of the group , there was no association between the increase in aerobic threshold and change in BMD . In the entire group , age-related bone loss was seen in the femoral neck BMD and BMDvol ( p<0.01 ) . BMD and BMDvol values increased with age in L2–L4 ( p<0.004 ) . An increased rate of bone loss at the femoral neck was observed in men with a low energy-adjusted calcium intake ( p = 0.003 ) . Men who increased their alcohol intake during the intervention showed a decrease in the rate of bone loss at the femoral neck ( p = 0.040 ) . A decrease in body height associated with decreased total femoral BMD ( r= 0.19 , p = 0.04 ) and the change in body height was a predictor of bone loss in the femoral neck ( β= 0.201 ) . Long-term regular aerobic physical activity in middle-aged men had no effect on the age-related loss of femoral BMD . On the other h and , possible structural alterations , which are also essential for the mechanical strength of bone , can not be detected by the DXA measurements used in this study . The increase seen in lumbar BMD reflects age-related changes in the spine , thus making it an unreliable site for BMD follow-up in men OBJECTIVES To compare the effectiveness of group resistance and agility-training programs in reducing fall risk in community-dwelling older women with low bone mass . DESIGN A r and omized , controlled , single-blind 25-week prospect i ve study with assessment s at baseline , midpoint , and trial completion . SETTING Community center . PARTICIPANTS Community-dwelling women aged 75 to 85 with low bone mass . INTERVENTION Participants were r and omly assigned to one of three groups : resistance training ( n=32 ) , agility training ( n=34 ) , and stretching ( sham ) exercises ( n=32 ) . The exercise classes for each study arm were held twice weekly . MEASUREMENTS The primary outcome measure was fall risk ( derived from weighted scores from tests of postural sway , reaction time , strength , proprioception , and vision ) , as measured using a Physiological Profile Assessment ( PPA ) . Secondary outcome measures were ankle dorsiflexion strength , foot reaction time , and Community Balance and Mobility Scale score . RESULTS Attendance at the exercise sessions for all three groups was excellent : resistance training ( 85.4 % ) , agility training ( 87.3 % ) , and stretching program ( 78.8 % ) . At the end of the trial , PPA fall-risk scores were reduced by 57.3 % and 47.5 % in the resistance and agility-training groups , respectively , but by only 20.2 % in the stretching group . In the resistance and agility groups , the reduction in fall risk was mediated primarily by improved postural stability , where sway was reduced by 30.6 % and 29.2 % , respectively . There were no significant differences between the groups for the secondary outcomes measures . Within the resistance-training group , reductions in sway were significantly associated with improved strength , as assessed using increased squat load used in the exercise sessions . CONCLUSION These findings support the implementation of community-based resistance and agility-training programs to reduce fall risk in older women with low bone mass . Such programs may have particular public health benefits because it has been shown that this group is at increased risk of falling and sustaining fall-related fractures Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women , and no population -based , long-term interventions have been performed . The purpose of this population -based , r and omized , controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density ( BMD ) at the radius and hip . Participants ( n = 160 ) were r and omly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention . The primary outcome measures were femoral neck , trochanter and total hip BMD , and the secondary outcomes were bone density measures at the radius and calcaneum . Outcomes were assessed at baseline , 12 months and 30 months using blinded operators . The analyses were performed on an intention-to-treat analysis . Mean femoral neck and trochanter BMD decreased in the control group [ −1.1 % , 95 % confidence interval ( CI ) −0.1 % to −2.1 % and −1.6 % , 95 % CI −0.4 % to −2.7 % ] , while no change occurred in the exercise group . Mean trochanter BMC decreased more in the control group ( −7.7 % , 95 % CI −9.7 % to −5.6 % vs. −2.9 % , 95 % CI −5.3 to −0.9 ) . There were six falls that result ed in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P = 0.019 ) . A significant bone loss occurred in both groups at the radius and calcaneum . In multivariate analysis , weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups . In conclusion , impact exercise had no effect on BMD , while there was a positive effect on BMC at the trochanter . Exercise may prevent fall-related fractures in elderly women with low bone mass Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density . However , the relationship between training dosage ( intensity , duration , frequency ) and the effect on bone density still is undergoing discussion . Furthermore , the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible . The aim of this investigation was to determine whether a clearly defined training of muscle strength , under defined safety aspects , performed only twice weekly , can counteract bone density loss in women with postmenopausal osteopenia . Data from 16 women in the training group ( age , 63.6 + /- 6.2 yr ) and 15 women in the control group ( age , 67.4 + /-9.7 yr ) , of comparable height and weight , were evaluated . Strength training was performed for 6 mo as continually adapted strength training , providing an intensity of about 70 % of each test person 's one repetition maximum . Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry . Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort . In addition , metabolic data were assessed . In the lumbar spine and femoral neck , the training group showed no significant changes , whereas the control group demonstrated a significant loss of bone mineral density , especially in the femoral neck ( P<0.05 ) . The strength increase was highly significant in all exercised muscle groups , rising to about 70 % above the pretraining status ( P<0.001 ) . Heart rate and blood pressure data indicated a slight economization , metabolism was not significantly influenced . Based on these findings , we conclude that continually adapted strength training is an effective , safe , reproducible , and adaptable method of therapeutic strength training , following only two exercise sessions per week OBJECTIVE To describe the effect of a supervised physical activity program on the physical and psychological health of osteopenic women . DESIGN A r and omized controlled trial . SETTING Sherbrooke , Quebec , Canada . PARTICIPANTS A total of 124 community-living postmenopausal women , between 50 and 70 years of age , with low bone mass took part in the study . INTERVENTION Subjects allocated to the experimental group performed weight-bearing exercises ( walking , stepping up and down from benches ) , aerobic dancing , and flexibility exercises for 60 minutes , three times a week , over a period of 12 months . All subjects were invited to attend bi-monthly educational seminars covering topics related to osteoporosis . OUTCOME MEASURES Spinal and femoral bone mineral density ( BMD ) , functional fitness ( flexibility , coordination , agility , strength/endurance , cardiorespiratory endurance ) , psychological well-being , back pain intensity , and self-perceived health . RESULTS Spinal BMD stabilized in the exercisers while decreasing significantly in the controls ( P = .031 ) . No change in femoral BMD was observed in either group ( P = .597 ) . Four of the five parameters chosen to evaluate functional fitness , namely flexibility , agility , strength , and endurance , were affected positively by the exercise program ( all P < .01 ) . Adjusting for prescores by means of an analysis of covariance revealed a significant difference between the groups in psychological well-being , which favored the exercisers ( P = .012 ) . After 12 months , back pain reported by exercisers was lower than that reported by controls ( P = .008 ) . Finally , self-perceived health increased in the exercise group , whereas no difference was observed in the control group ( P = .790 ) . CONCLUSION These results suggest that after 12 months , exercising can produce a significant increase above initial levels in the functional fitness , well-being , and self-perceived health of osteopenic women . Intensity of back pain can also be lowered by exercise . The exercise program succeeded in stabilizing spinal BMD but had no effect on femoral BMD Summary R and omized controlled study in 80 postmenopausal women with osteoporosis was conducted to investigate the effect of a home-based , simple , low-intensity exercise . Low-intensity back-strengthening exercise was effective in improving the quality of life and back extensor strength . Introduction and hypothesisBack-strengthening exercise is effective in increasing back extensor strength and decreasing risk of vertebral fractures . We hypothesized that a home-based , simple , low-intensity exercise could enhance back extensor strength and improve the quality of life and /or spinal range of motion in postmenopausal women in a short-term follow-up . Methods Eighty postmenopausal women with osteoporosis were r and omly assigned to a control group ( n = 38 ) or an exercise group ( n = 42 ) . Subjects were instructed to lift their upper trunk from a prone position antigravity and maintain the neutral position . Isometric back extensor strength , spinal range of motion , and scores for quality of life were evaluated at baseline and 4 months . Results Back extensor strength significantly increased both in the exercise group ( 26 % ) and in the control group ( 11 % ) . Scores for quality of life increased in the exercise group ( 7 % ) , whereas it remained unchanged in the control group ( 0 % ) . There was a significant difference in quality of life score between the groups ( p = 0.012 ) . Conclusions Low-intensity back-strengthening exercise was effective in improving the quality of life and back extensor strength in patients with osteoporosis One hundred and seventy-nine women aged 60–85 years ( mean age 71.6 years , SD 5.3 years ) were r and omly recruited from the community to participate in a 12-month r and omized controlled trial to determine whether a program of twice-weekly structured exercise has beneficial effects on three factors associated with osteoporotic fractures : quadriceps strength , postural sway and bone density . At initial testing , there were no significant differences in the strength , sway and bone density measures ( assessed at the hip and lumbar spine ) between the exerciser and control groups . The exercise classes included strengthening , coordination and balance exercises , and approximately 35 min of each class comprised weight-bearing exercise . The mean number of classes attended for the 68 exercisers who completed the program was 59.8 of the 82 classes ( 72.9 % ) . At the completion of the trial , the intervention group showed significant improvements in quadriceps strength and sway but not bone mineral density when compared with the control group . Indices of fracture risk , indicated by ( i ) the sum of st and ard score results and ( ii ) the sum of quartile grade s of the femoral neck bone density , sway and strength measures , decreased significantly in the exercisers at the end of the trial compared with the controls . In conclusion , the program of general aerobic exercise may have reduced overall fracture risk , even though it did not significantly increase bone density . Further long-term studies are required that include acceptable weight-loaded exercises to determine optimal programs for reducing fracture risk factors by improving bone density as well as strength and balance Objective To evaluate the effectiveness of an educational video on osteoporosis at increasing knowledge and preventive health behaviors . Design A total of 195 women between 35 and 80 years of age without documented osteopenia or osteoporosis , who presented for a gynecological examination in an outpatient setting , were enrolled . Of this number , 98 women were r and omly assigned to the intervention group that viewed the video before their office visit , and 97 women were assigned to a control group and saw their physician in a routine manner . After their visit , all participants answered a question naire that assessed their knowledge of osteoporosis and baseline health-related behaviors . Three months later , a follow-up question naire was mailed to participants , eliciting whether preventive behavior had commenced . Frequencies were compared using the Fisher exact test ( 2-tailed ) . Continuous variables were analyzed using the Student 's t test . Results The two groups had no statistically significant differences in demographics . The intervention group scored a mean of 92 % compared with a mean of 80 % in the control group on the initial osteoporosis assessment question naire ( P < 0.001 ) . The 3-month follow-up question naire demonstrated that significantly more women in the intervention group started taking calcium supplements ( 26.5 % v 4.9 % ; P < 0.001 ) , started taking vitamin D supplements ( 20.6 % v 6.6 % ; P = 0.02 ) , started a program of weight-bearing exercise ( 13.3 % v 1.7 % ; P = 0.03 ) , and started hormone therapy ( 8 % v 1 % ; P = 0.04 ) . Conclusion The use of an educational video on osteoporosis seems to improve patient knowledge and may positively impact health-related behaviors Objective : The study was design ed to evaluate the effects of strength training ( ST ) on the bone mineral density ( BMD ) of postmenopausal women without hormone replacement therapy . Method : Subjects were r and omized into untrained ( UN ) or trained ( TR ) groups . The TR group exercised three ST sessions per week for 24 weeks , and body composition , muscular strength , and BMD of the lumbar spine and femur neck were evaluated . Results : Body weight , mass index , and fat percentage were lower after 24 weeks only in the TR group ( p < .05 ) . SR also improved the one repetition maximum test in 46 % and 39 % of upper and lower limbs , respectively . The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck ( p < .05 ) . Discussion : Results indicated that 24 weeks of ST improved body composition parameters , increased muscular strength , and preserved BMD in postmenopausal women Introduction : The purpose of this r and omized controlled study was to assess the effects of high-impact exercise on the bone mineral density ( BMD ) of premenopausal women at the population level . Material s and methods : The study population consisted of a r and om population -based sample of 120 women from a cohort of 5,161 women , aged 35 to 40 years . They were r and omly assigned to either an exercise or control group . The exercise regimen consisted of supervised , progressive high-impact exercises three times per week and an additional home program for 12 months . BMD was measured on the lumbar spine ( L1–L4 ) , proximal femur , and distal forearm , by dual-energy X-ray absorptiometry at baseline and after 12 months . Calcaneal bone was measured using quantitative ultrasound . Results : Thirty-nine women ( 65 % ) in the exercise group and 41 women ( 68 % ) in the control group completed the study . The exercise group demonstrated significant change compared with the control group in femoral neck BMD ( 1.1 % vs −0.4 % ; p=0.003 ) , intertrochanteric BMD ( 0.8 % vs −0.2 % ; p=0.029 ) , and total femoral BMD ( 0.1 % vs −0.3 % ; p=0.006 ) . No exercise-induced effects were found in the total lumbar BMD or in the lumbar vertebrae L2–L4 . Instead , L1 BMD ( 2.2 % vs −0.4 % ; p=0.002 ) increased significantly more in the exercise group than in the control group . Calcaneal broadb and ultrasound attenuation showed also a significant change in the exercise group compared with the control group ( 7.3 % vs −0.6 % ; p=0.015 ) . The changes were also significant within the exercise group , but not within the control group . There were no significant differences between or within the groups in the distal forearm . Conclusions : This study indicates that high-impact exercise is effective in improving bone mineral density in the lumbar spine and upper femur in premenopausal women , and the results of the study may be generalized at the population level . This type of training may be an efficient , safe , and inexpensive way to prevent osteoporosis later in life Objective : To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance . Design : R and omized clinical trial . Setting : University hospital physiotherapy department . Subjects : Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score ( SD ) of —1.8 ( 0.8 ) . Interventions : A three-month programme consisting of exercise/protein including training of muscular strength , co-ordination , balance and endurance . Calcium/ vitamin D was supplemented in all participants for a 12-month period . Outcome measures : Assessment took place prior to and following the months 3 , 6 , 9 and at the end of the study ; primary dependent variables assessed were risk of falling ( Berg Balance Test ) and postural balance ( forceplate ) . Secondary measures included body composition , strength , activity level , number of falls , bone mineral content , biochemical indices , nutritional status and general health . Results : Significant reductions of risk of falling ( repeated measures ANOVA F = 8.90 , P = 0.008 ) , an increase in muscular strength ( ANOVA F = 3.0 , P = 0.03 ) , and an increase in activity level ( ANOVA F = 3.38 , P = 0.02 ) were found in the experimental group as compared to the control group . Further on , there was 89 % reduction of falls reported in the experimental group ( experimental pre/post 8/1 falls ; control group pre/post 5/6 falls ) . Conclusion : This study provides support for our intervention programme aim ed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis . The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger r and omized trial This 1 year study examined the effect of high impact and low impact activities on bone mineral density ( BMD ) at the lumbar vertebrae ( L2-L4 ) in healthy , sedentary , early postmenopausal women . Fifteen subjects whose postmenopausal status was verified by the blood levels of follicle stimulating hormone ( FSH ) and estradiol were chosen . These subjects were tested on the following variables : BMD via dual photon absorptiometry , heart rate response to the Balke treadmill test , percent fat via skinfolds , and a 3-d dietary analysis . Subjects were matched and then assigned r and omly to one of three groups : ( a ) a control nonexercising group , ( b ) a low impact exercise group , and ( c ) a high impact exercise group . The control nonexercising group experienced a significant linear decrease in BMD during the study ( F = 12.63 , P = 0.002 ) . Both the low and high impact exercise groups maintained BMD during the study ( F = 0.04 , P = 0.85 ; F = 1.08 , P = 0.31 , respectively ) . The difference in BMD between the low impact and the high impact exercise groups was not significant ( F = 0.36 , P = 0.55 ) . In conclusion , 20 min of moderate intensity low impact or high impact exercise 3 d.wk-1 for 1 yr is effective in maintaining BMD in early postmenopausal women Summary Exercise may affect osteopenic women at risk of falls and fractures . A workstation approach to exercise was evaluated in a r and omised study of 98 women . The intervention group improved in measures of balance , strength and bone density . This study supports a preventative exercise approach that aims to reduce risk factors for fractures and falls , in women already at risk , through balance training and weight-bearing activity . Introduction The objective of this study was to determine the effects of a workstation balance training and weight-bearing exercise program on balance , strength and bone mineral density ( BMD ) in osteopenic women . A single-blinded r and omised controlled trial ( RCT ) was undertaken for 20 weeks with measurements at baseline and completion . Material s and methods Ninety-eight ( 98 ) community-dwelling osteopenic women aged 41–78 years were recruited through the North Brisbane electoral roll . Subjects were r and omised via computer-generated r and om numbers lists into either a control ( receiving no intervention ) , or exercise group ( two one-hour exercise sessions per week for 20 weeks with a trained physiotherapist ) . Assessment s at baseline and post-intervention included balance testing ( five measures ) , strength testing ( quadriceps , hip adductors / abductors / external rotators and trunk extensors ) , and DXA scans ( proximal femur and lumbar spine ) . Baseline assessment showed no significant differences between groups for all demographics and measures except for subjects taking osteoporosis medication . The percentage differences between pre- and post-intervention measurements were examined for group effect by ANOVA using an intention-to-treat protocol . Results Ninety-eight women ( mean age 62.01 years , SD 8.9 years ) enrolled in the study . The mean number of classes attended for the 42 participants in the exercise group who completed the program was 28.2 of a possible 40 classes ( 71 % ) . At the completion of the trial the intervention group showed markedly significant better performances in balance ( unilateral and bilateral stance sway measures , lateral reach , timed up and go and step test ) ( p < 0.05 ) with strong positive training effects reflecting improvements of between 10 % to 71 % . Similarly there were gains in strength of the hip muscles ( abductors , adductors , and external rotators ) , quadriceps and trunk extensors with training effects between 9 % and 23 % . Conclusions Specific workstation exercises can significantly improve balance and strength in osteopenic women . This type of training may also positively influence bone density although further study is required with intervention over a longer period . A preventative exercise program may reduce the risk of falls and fractures in osteopenic women already at risk Objectives : To investigate whether a 12-week home-based programme of trunk-strengthening exercise could benefit spinal mobility , function and quality of life for osteoporotic and osteopenic postmenopausal women without fracture . Design s : R and omized controlled clinical trial . Setting : Department of Physical Therapy in National Taiwan University Hospital . Subjects : Twenty-eight postmenopausal women ( mean age 60.39=9.3 years ) diagnosed with osteoporosis or osteopenia without fracture history were recruited for this study . Subjects were r and omly assigned into exercise or control groups , each consisting of 14 subjects . Interventions : The 12-week exercise programme included strengthening routines for the trunk extensor and flexor muscles . The subjects performed three sets of 10 repetitions for each of the exercises , with programmes carried out three times per day at home . Main outcome measurements : Muscular strength , spinal range of motion ( ROM ) and motion velocity , Oswestry Disability Question naire ( ODQ ) and quality of life ( QOL ) were measured before the start and after completion of the exercise programme . Results : Statistically significant improvements were demonstrated in spinal ROM and motion velocity in the sagittal and frontal planes for the exercise group ( pB=0.05 ) . Further , the strength of the trunk flexors and extensors increased after exercise training ( pB=0.05 ) . ODQ measure was significantly reduced in the exercise group ( pB=0.05 ) , while the controls showed no significant change . Subjects in the exercise group showed better satisfaction in some domains of the Short-Form-36 Health Survey quality of life question naire ( pB=0.05 ) . Conclusions : This 12-week home-based trunk-strengthening exercise programme could improve trunk mobility and strength , and enhance QOL in osteoporotic and osteopenic postmenopausal women without vertebral fracture . Future study should recruit more cases or more severe subjects to verify the results Abstract . The present study completed a previous r and omized trial that demonstrated the protective effect of 1-year psoas training on lumbar bone loss in postmenopausal women . Computerized tomography had been carried out at the beginning ( CT1 ) and at the end ( CT2 ) of this trial . In the present study , 67 women having completed the first trial were asked to practice psoas exercises ( 60 hip flexions in sitting position with a 5 kg weight on the knee ) for 2 additional years with a third CT control at the end of this period ( CT3 ) . The aim of this complementary study was to assess the compliance rate and long-term effect on bone of daily psoas muscle training over a longer period . Twenty-one women performed this daily psoas training for 3 years from CT1 to CT3 , and 14 acted as controls during the same period . Fourteen women were controls during the first year ( from CT1 to CT2 ) but practice d psoas training during the following 2 years ( from CT2 to CT3 ) . Four women were psoas trained during the first year ( from CT1 to CT2 ) and subsequently crossed over to the control group for the last 2 years . The compliance rate was 42 % , with an attendance rate of 88 % . The lumbar bone loss was lower in the 21 women trained over the 3 years ( −3.26 ± 28.45 mg/cm3 ) than in the 14 untrained women ( −16.79 ± 8.51 mg/cm3 ) ( P= 0.02 ) . The bone loss was not significantly reduced between the two periods of the study in the 12 women having been controls from CT1 to CT2 and having crossed over to the active training group from CT2 to CT3 . Psoas training may be effective against lumbar bone loss . We conclude that specific training may play a contributing role in the preventive strategy to avoid osteoporosis Objective : The aim of this study was to assess the independent and additive effects of soy protein isolate ( SPI ) and moderate-intensity exercise ( EX ) on bone turnover and bone mineral density ( BMD ) . Design : This study used a placebo-controlled , double-blind ( soy ) , r and omized 2 ( SPI vs milk protein isolate [ MPI ] ) × 2 ( EX vs no EX ) design . Sixty-one postmenopausal women were r and omized , and 43 ( 62 ± 5 y ) completed the 9-month intervention ( SPI , n = 10 ; MPI , n = 12 ; SPI + EX , n = 11 ; MPI + EX , n = 10 ) . Serum C-terminal cross-linked telopeptides of type I collagen and serum bone-specific alkaline phosphatase were measured as markers of bone resorption and formation , respectively . BMD was measured by dual-energy x-ray absorptiometry . Results : At 9 months , SPI reduced serum C-terminal cross-linked telopeptides ( −13.3 % ± 15.3 % vs −1.5 % ± 21.0 % ; P = 0.02 ) and serum bone-specific alkaline phosphatase ( −4.7 % ± 14.7 % vs 6.5 % ± 17.7 % ; P = 0.02 ) compared to milk protein isolate . EX attenuated the reduction in serum C-terminal cross-linked telopeptides ( −1.9 % ± 21.6 % vs −12.4 % ± 15.3 % ; P = 0.04 ) ; however , no EX effects were apparent in serum bone-specific alkaline phosphatase at 9 months ( 2.8 % ± 16.1 % vs −1.0 % ± 18.3 % ; P = 0.28 ) . Neither SPI nor EX affected BMD at any site ; however , change in BMD was related to change in fat mass ( r = 0.40 , P < 0.05 ) . Conclusions : In postmenopausal women ( 1 ) SPI reduces bone turnover with no impact on BMD over 9 months ; ( 2 ) moderate-intensity endurance exercise training did not favorably alter bone turnover and had no impact on BMD ; and ( 3 ) there were no additive effects of soy and exercise on bone turnover or BMD AIMS The purpose of this study was to evaluate whether a nurse-initiated education programme on four specific osteoporosis-prevention related behaviours leads to their adoption or positive attitude changes compared with women who did not participate in this programme . RESEARCH METHOD The design was a r and omized controlled design and the setting was a local private beauty clinic . OUTCOME MEASURES Pre- , post- and follow-up education data compared attitudes and consumption frequency before and after the education programme . RESULTS The results showed significant increases in the reported follow-up for each behaviour : consumption of soya foods ( mean = 4.3 , SD = 0.5 ) , milk ( mean = 4.2 , SD = 0.8 ) , more exercise ( mean = 4.3 , SD = 0.5 ) and vitamin D/exposure to sunlight ( mean = 4.2 , SD = 0.9 ) for subjects in the case group compared with control group subjects ( soya foods : mean = 3.3 , SD = 0.9 , P < 0.001 ; milk : mean = 3.0 , SD = 0.9 , P < 0.001 ; more exercise : mean = 3.4 , SD = 1.0 , P = 0.003 ; vitamin D/sunlight : mean = 2.7 , SD = 0.9 , P < 0.00 ) . Most of the participants either disagreed ( n = 11 , 55.0 % ) or strongly disagreed ( n = 9 , 45.0 % ) that there was not enough information provided in the education programme to motivate them to change . On the satisfaction score , they rated the nurse 's performance as either satisfactory ( n = 11 , 55.0 % ) or very satisfactory ( n = 9 , 45.0 % ) on presentation and ability to answer their questions and either satisfactory ( n = 12 , 60.0 % ) or very satisfactory ( n = 8 , 40.0 % ) on ability to describe each behaviour clearly . CONCLUSION A targeted education programme conducted with Hong Kong women result ed in significantly increased consumption of calcium including soya-based foods , milk and vitamin D. According to the reported attitudinal and behavioural intentions , participants ' positive feedback suggests that women who participated in this educational programme were motivated to make changes and benefited from the support of this nurse-initiated education programme . RELEVANCE TO CLINICAL PRACTICE Osteoporosis was a serious health concern that most commonly affected women . As indicated by the results of this study , this educational programme can act as simple but effective nursing intervention to promote women 's attitudinal and behavioural intentions towards osteoporosis-prevention Underst and ing the stress/strain relationship between exercise and bone is critical to underst and ing the potential benefit of exercise in preventing postmenopausal bone loss . This study examined the effect of a 2-year exercise intervention and calcium supplementation ( 600 mg ) on bone mineral density ( BMD ) in 126 postmenopausal women ( mean age , 60 + /- 5 years ) . Assignment was by block r and omization to one of three groups : strength ( S ) , fitness ( F ) , or nonexercise control ( C ) . The two exercise groups completed three sets of the same nine exercises , three times a week . The S group increased the loading , while the F group had additional stationary bicycle riding with minimal increase in loading . Retention at 2 years was 71 % ( 59 % in the S group , 69 % in the F group , and 83 % in the C group ) , while the exercise compliance did not differ between the exercise groups ( S group , 74 + /- 13 % ; F group , 77 + /- 14 % ) . BMD was measured at the hip , lumbar spine , and forearm sites every 6 months using a Hologic 4500 . Whole body BMD also was measured every 6 months on a Hologic 2000 . There was no difference between the groups at the forearm , lumbar spine , or whole body sites . There was a significant effect of the strength program at the total ( 0.9 + /- 2.6 % ; p < 0.05 ) and intertrochanter hip site ( 1.1 + /- 3.0 % ; p < 0.01 ) . There was a significant time and group interaction ( p < 0.05 ) at the intertrochanter site by repeated measures . This study shows the effectiveness of a progressive strength program in increasing bone density at the clinical ly important hip site . We concluded that a strength program could be recommended as an adjunct lifestyle approach to osteoporosis treatment or used in combination with other therapies BACKGROUND Osteoporotic fractures among the elderly are common , and without preventive measures the burden of these fractures on health-care systems will increase further . The purpose of this r and omised controlled study was to evaluate , in premenopausal women , the effects of high-impact loading on several determinants osteoporotic fractures . METHODS 98 healthy , sedentary female volunteers aged 35 - 45 years were r and omly assigned to either a training ( n = 49 ) or a control group ( n = 49 ) . Progressive high-impact exercises were done three times per week for 18 months . We measured bone mineral density ( BMD ) in specific axial and lower-limb sites , by dual-energy X-ray absorptiometry , at baseline and after 12 and 18 months . Maximum isometric strength , muscular and cardiovascular performance , and dynamic balance were also assessed . FINDINGS BMD at the femoral neck , a weightbearing site , increased significantly more in the training group ( mean 1.6 % [ 95 % CI 0.8 - 2.4 ] ) than in the control group ( 0.6 % [ -0.2 to 1.4 ] , p = 0.006 ) . By contrast , at non-weightbearing sites , such as the distal radius , there was no significant difference between the training and control groups ( -1.5 % [ -2.7 to -0.3 ] vs -0.7 % [ -1.9 to -0.5 ] , p = 0.60 ) . In the training group there was a significant improvement in vertical jump and predicted oxygen consumption per min at maximum exercise compared with controls . INTERPRETATION High-impact exercises that load bones with a rapidly rising force profile in versatile movements improve skeletal integrity , muscular performance , and dynamic balance in premenopausal women . If done on a regular basis , this type of exercise may help decrease the risk of osteoporotic fractures in later life . Long-term studies are required to show whether these 18-month results can be translated into long-term benefit This study was design ed to assess the effects of 18 months of resistance exercise on regional and total bone mineral density ( BMD ) and soft tissue lean mass ( STL ) in premenopausal women aged 28 - 39 r and omly assigned to an exercise or control group . Twenty-two exercise and 34 control subjects completed the 18-month training study . All subjects were previously inactive and untrained women . Initial , 5- , 12- and 18-month assessment s were made of total and regional BMD and total and regional STL using dual energy X-ray absorptiometry . All subjects consumed a 500 mg/day elemental calcium supplement throughout the study . Initial Ca intake without supplement averaged 1,023 mg/day in total sample . Serum levels of bone osteocalcin and dietary assessment s using 12 r and omly assigned days of diet records were also completed . Muscular strength was assessed from both 1 repetition maximum ( RM ) testing of 10 weightlifting exercises and by peak torque for hip abduction/adduction and knee extension/flexion . Training increased strength by 58.1 % based on 1 RM testing and by 33.8 % based on isokinetic testing at 18 months versus baseline . BMD increased significantly above baseline at the lumbar spine for the exercise group at 5 months ( 2.8 % ) , 12 months ( 2.3 % ) , and 18 months ( 1.9 % ) as compared with controls . Femur trochanter BMD increased significantly ( p < 0.05 ) in the exercise group at 12 months ( 1.8 % ) and 18 months ( 2.0 % ) but not at 5 months ( 0.7 % ) as compared with controls . No changes in total BMD , arm BMD , or leg BMD were found . There was a 20 % increase in BGP in the exercise group as compared with controls at 5 months and this difference was maintained throughout the study . For STL , significant increases for total , arm , and leg were found at 5 , 12 , and 18 months for the exercise group versus control ranging from 1 - 6 % over baseline . These results support the use of strength training for increasing STL and muscular strength with smaller but significant regional increases in BMD in the premenopausal population Healthy premenopausal women were r and omized into control and test groups ; both exercised weekly in class and daily at home for a year . The test class did intermittent high-impact exercise ; the control class did low-impact exercise . Bone density was assessed blind using dual energy X-ray absorptiometry at the femur ( neck , Ward 's triangle and trochanter ) and at the lumbar spine ( antero-posterior L1–4 ) on entry into the study , and again after 6 months ( n=27 ) and 12 months ( n=19 ) . At 6 months the test group ( n=14 ) showed a significant increase of 3.4 % in trochanteric bone density ( p=0.01 ) and this was significantly different from control ( p=0.05 ) . In the second 6 months the control group was crossed over to high-impact exercise and showed a significant increase of 4.1 % in trochanteric density ( n=7 ) while the original group maintained their improvement relative to baseline In this 2-yr r and omized controlled trial , we examined the effect of bone mineral density feedback and two different educational interventions ( an osteoporosis information leaflet and group-based behavioral education [ OPSMC ] ) on osteoporosis knowledge and self-efficacy in 470 women aged 25 - 44 yr . Osteoporosis knowledge increased across all intervention groups . Women receiving the OPSMC had a greater increase in both short ( beta = + 1.33 , 95 % confidence interval [ CI ] = 0.72 - 1.94 ) and long-term ( beta = + 0.64 , 95 % CI = 0.0034 - 1.25 ) osteoporosis knowledge , compared to those receiving the leaflet . In contrast , a low T-score was associated with a significant increase in long-term ( beta = + 0.66 , 95 % CI = 0.0034 - 1.25 ) but not short-term ( beta = + 0.57 , 95 % CI = -0.036 to 1.17 ) osteoporosis knowledge , compared to a normal T-score . Changes in osteoporosis self-efficacy were not associated with either low bone mineral density or receiving the OPSMC but were negatively associated with number of children ( beta = -0.9 , 95 % CI = - 1.4 to -0.3 ) and working more than 20 h per week ( beta = -2.7 , 95 % CI = -4.6 to -0.8 ) . In conclusion , both the OPSMC and bone density feedback increased osteoporosis knowledge but not self-efficacy over 2 yr . Women with children or who worked full time have decreased osteoporosis self-efficacy , suggesting that this group should be a specific target for future interventional strategies The effects of a supervised 1-y walking program and increased dietary calcium ( milk supplement , 831 mg/d , vs placebo drink , 41 mg/d ) on bones were examined in 36 postmenopausal women ( 60.2 + /- 6.5 y ) . Trabecular bone-mineral density ( BMD ) of the lumbar spine ( L1-L3 ) , measured by computed tomography , increased by 0.5 % in exercising women ( n = 18 ) and decreased by 7.0 % in sedentary women ( n = 18 ; P = 0.02 ) . Femoral-neck BMD measured by dual-photon absorptiometry ( DPA ) increased by 2.0 % in women consuming high dietary calcium ( n = 18 ) and decreased by 1.1 % in those on moderate calcium intake ( n = 18 ; P = 0.001 ) . Neither exercise nor dietary calcium had an effect on lumbar spine ( L2-L4 ) measured by DPA , distal radius measured by single-photon absorptiometry , or total body calcium measured by in vivo neutron activation . The varying proportions and rates of turnover of trabecular and cortical bone from one site to another suggest that exercise and high dietary calcium may preferentially alter bone density at different skeletal sites PURPOSE To assess whether young women who participate in an osteoporosis prevention program based on the Health Belief ( Rosenstock , 1966 ) and Self-Efficacy Models ( B and ura , 1977 ) demonstrate higher levels of knowledge regarding osteoporosis prevention than young women who do not participate in such a program . DESIGN A classic experimental design with one treatment group and one control group was used to test the efficacy of the osteoporosis prevention program . Pretest data on knowledge , health belief attitudes ( 7 subscales ) , and self-efficacy ( 2 subscales ) were collected in the treatment and control groups . SAMPLE A convenience sample of 31 young college women were r and omly assigned to an experimental group or to a control group to receive an osteoporosis prevention program . METHOD Subjects in the experimental and control groups completed the Osteoporosis Knowledge Test , the Osteoporosis Health Belief Scale , and the Osteoporosis Self-Efficacy Scale ( Kim et al. , 1991 ) at two times . The experimental group received an osteoporosis prevention program . MAIN RESEARCH CLASSIFICATIONS Osteoporosis , Health Belief , Self-Efficacy , Women 's Health . FINDINGS Subjects in the experimental group had significantly higher knowledge and health belief scores after receiving the intervention than their pretest scores while subjects in the control group had no change in scores . CONCLUSION The osteoporosis program was effective in increasing awareness of osteoporosis prevention in this group of young women . IMPLICATION S FOR NURSING RESEARCH The results may be useful for developing young women 's awareness and knowledge of osteoporosis prevention . Future research could include developing osteoporosis prevention programs at an earlier age when girls are in grade school and junior high school . Teaching health promotion strategies for bone health is essential to all women across the life span Background : Older patients who experience a fragility fracture are at high risk of future fractures but are rarely tested or treated for osteoporosis . We developed a multifaceted intervention directed at older patients with wrist fractures ( in the form of telephone-based education ) and their physicians ( in the form of guidelines endorsed by opinion leaders , supported by reminders ) to improve the quality of osteoporosis care . Methods : In a r and omized controlled trial with blinded ascertainment of outcomes , we compared our intervention with usual care ( provision of printed educational material s to patients ) . Eligible patients were those older than 50 years of age who had experienced a wrist fracture and were seen in emergency departments and fracture clinics ; we excluded those who were already being treated for osteoporosis . The primary outcome was bisphosphonate treatment within 6 months after the fracture . Secondary outcomes included bone mineral density testing , “ appropriate care ” ( consisting of bone mineral density testing with treatment if bone mass was low ) and quality of life . Results : We screened 795 patients for eligibility and r and omly assigned 272 to the intervention ( 137 patients ) or control ( 135 patients ) group . The median age was 60 years ; 210 ( 77 % ) of the subjects were women , and 130 ( 48 % ) reported a previous fracture as an adult . Six months after the fracture , 30 ( 22 % ) of the intervention patients , as compared with 10 ( 7 % ) of the control patients , were receiving bisphosphonate therapy for osteoporosis ( adjusted relative risk [ RR ] 2.6 , 95 % confidence interval [ CI ] 1.3–5.1 , p = 0.008 ) . Intervention patients were more likely than control patients to undergo bone mineral density testing ( 71/137 [ 52 % ] v. 24/135 [ 18 % ] ; adjusted RR 2.8 , 95 % CI 1.9–4.2 , p < 0.001 ) and to receive appropriate care ( 52/137 [ 38 % ] v. 15/135 [ 11 % ] ; adjusted RR 3.1 , 95 % CI 1.8–5.3 , p < 0.001 ) . There were no differences between the groups in other outcomes . One patient died , and 4 others experienced recurrent fracture . Interpretation : A multifaceted intervention directed at high-risk patients and their physicians substantially increased rates of testing and treatment for osteoporosis . Nevertheless , more than half of the patients in the intervention group were not receiving appropriate care 6 months after their fracture , which suggests that additional strategies should be explored . ( Clinical Trials.gov trial register no. NCT00152321 . OBJECTIVE To evaluate the potential benefits of programmed Tai Chi Chun ( TCC ) exercise on the weight-bearing bones of early postmenopausal women . DESIGN Age-matched and r and omized prospect i ve intervention . SETTING University medical school . PARTICIPANTS One hundred thirty-two healthy postmenopausal women ( mean age , 54.0+/-3.5y ) within 10 years of menopause onset were recruited and r and omized into the TCC exercise group ( n=67 ) or the sedentary control group ( n=65 ) . INTERVENTION Supervised TCC exercise was performed by the TCC group for 45 minutes a day , 5 days a week , for 12 months ; control subjects retained a sedentary life style . Main outcome measures Bone mineral density ( BMD ) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography ( pQCT ) . All BMD measurements were repeated after 12 months in both groups . Fracture rate was also documented . RESULTS Baseline measurements showed homogeneity in age , anthropometric variables , and menstruation status between the TCC and control groups . Exactly 81.6 % of the subjects in the TCC group and 83.1 % of subjects in the control group completed the 12-month follow-up study . BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites , but with a reportedly slower rate in the TCC group . A significant 2.6- to 3.6-fold retardation of bone loss ( P<.01 ) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls , as measured by pQCT . A total of 4 fracture cases were documented during follow-up , including 3 subjects in the control group and 1 in the TCC group . CONCLUSIONS This is the first prospect i ve and r and omized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women . Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture A r and omized , prospect i ve , double-blind test was carried out to compare the effects of heated oyster shell-seaweed calcium ( AAA Ca ) , calcium carbonate , and placebo in 58 elderly , hospitalized women with the mean age of 80 divided into three groups . Group A received 900 mg/day Ca as AAA Ca , Group B 900 mg/day Ca as CaCO3 , and Group C placebo besides regular hospital diet containing approximately 600 mg Ca/day for 24 months . From the 25th to the 30th month , all groups were given AAA Ca . Lumbar spine and radial bone mineral density ( BMD ) were measured at 3-month intervals . Urinary Ca/Cr and serum alkaline phosphatase , intact and midportion serum parathyroid hormone ( PTH ) , and calcitonin were also measured at intervals . From the 6th to the 24th month of the study , the ratio of lumbar spine BMD ( L2–L4 by DPX , Lunar ) to the basal pretest value was consistently and significantly higher in Group A than Group C but not higher in Group B than in Group C. PTH , measured 12 months after the beginning of the study , was lower in Group A than in Group C , but no significant difference was found between Groups B and C. At 3 months after the placebo was switched to AAA Ca in Group C , serum PTH was significantly decreased from the level during placebo supplement . Morning urine Ca/Cr decreased in Groups A after 18 months and in B after 12 months , but not in C. Serum alkaline phosphatase decreased in Group A significantly compared with Group C , but not in Group B. AAA Ca appears to be effective for increasing BMD in elderly subjects Exercise is recommended to enhance bone health but data on the maintenance of the exercise-induced bone benefit is sparse . The purpose of the study was to assess the maintenance of the musculoskeletal benefits obtained in an 18-month intervention of high-impact exercise in premenopausal women ( 34 former trainees and 31 controls ) . Physical performance and areal bone mineral density ( aBMD , g/cm2 ) were measured at baseline , after 18 months , and after 5 years . All significant 18-month improvements relative to controls in the trainees ’ neuromuscular performance ( isometric leg press , and vertical jump with and without additional 10 % weight of the body mass ) had been lost at the 5-year follow-up . However , since the changes in aBMD in both former trainees and controls by time were similar , the exercise-induced aBMD gain ( i.e. the mean statistically significant intergroup differences of 1–3 % in favor of the trainees ) was maintained at the femoral neck , distal femur , patella , proximal tibia , and calcaneus at the 5-year follow-up . At lumbar spine , the difference was 1.7 % at both 18-month and at the 5-year follow-ups but the difference was not statistically significant ( NS ) in the latter follow-up . At the trochanter and unloaded distal radius , the intergroup aBMD differences were NS at both the 18-month and 5-year follow-ups . In conclusion , the bone sites aBMD increased in response to the 18-month intervention , also demonstrated maintenance of this gain 3.5 years after the intervention . In contrast , the exercise-induced improvements in the neuromuscular performance vanished during the post intervention follow-up . These findings suggest the possibility of long-term bone benefits of high-impact training in women The purpose of this study was to determine the effect of a 1-year trunk resistive exercise program on bone mineral density at the lumbar spine and hip in postmenopausal women . Forty-nine subjects were divided into exercise and control groups . Dual photon absorptiometry was used to measure bone mineral density and the Muscle Examination and Exercise Dosimeter 3000 system was used to assess trunk muscle strength . Resistive exercise target levels for the exercise group were based on the results of the trunk muscle strength tests . The exercise group performed 3 sets of 10 repetitions for each of the sit-up , prone trunk extension , and double leg flexion exercises . The subjects were seen once per month and performed the exercises a minimum of three times per week . The bone mineral density and strength tests were done at baseline , at 6 months and at 12 months . The results of the study showed that 1 ) the dual photon absorptiometry method and the Muscle Examination and Exercise Dosimeter 3000 system were highly reliable in measuring bone mineral density and trunk muscle strength , respectively ; and 2 ) no significant differences were found between the exercise and control groups at lumbar vertebrae L2 , L3 , L4 , L2-L4 , and the femoral neck , Ward 's triangle , and trochanteric region of the proximal femur at baseline , 6-month , and 12-month evaluation sessions Abstract We examined the effect of exercise training and detraining on bone mineral density ( BMD ) in postmenopausal women with osteoporosis . Thirty-five postmenopausal women with osteoporosis , aged 53–77 years , were r and omly assigned to three groups : a control group ( n = 20 ) , a 2-year exercise training group ( n = 8) , and an 1-year exercise training plus 1-year detraining group ( n = 7 ) . Exercise training consisted of daily brisk walking and gymnastic training . Calcium lactate , 2.0 g , and 1α-hydroxyvitamin D3 , 1 μg were supplied daily to all subjects . No significant differences in initial lumbar BMD , measured by dual-energy X-ray absorptiometry ( DXA ) were found among the three groups . The mean percent change in BMD compared with the baseline was significantly higher at 1 and 2 years in the exercise training group and at 1 year in the detraining group than in the control group , and did not differ significantly at 2 years between the detraining and control groups . These findings indicate that our exercise training program led to a significant increase in lumbar BMD in postmenopausal women with osteoporosis compared with the control , but that the BMD reverted toward a level that was not significantly different from the control with detraining . Continued exercise training is needed to maintain the bone mass gained through exercise training BACKGROUND A previous study on a r and omized controlled trial in 173 postmenopausal Chinese women in Kuala Lumpur showed that milk supplementation was effective to reduce bone loss at the total body , lumbar spine , femoral neck and total hip compared to the control group on a usual diet ( Chee et al. 2003 ) . OBJECTIVE The objective was to determine whether the results were sustained after the conclusion of the study . DESIGN A follow-up study , 18 months after a r and omized controlled trial of milk supplementation was concluded . A total of 139 participants were followed up 21 months after the study ended . Bone mineral density ( BMD ) was measured at the total body , lumbar spine , femoral neck and total hip by dual energy X-ray absorptiometry , and anthropometric measurements as well as changes in dietary habits were measured . RESULTS At the follow-up , the milk supplement group did not show significant bone loss from baseline at most sites ( mean differences + /- SE ) ( total body 0.42 + /- 0.25 % , femoral neck 0.44 + /- 0.58 % , total hip -0.06 + /- 0.46 % ) , unlike the control group ( total body -1.07 + /- 0.28 % p < 0.005 , femoral neck -1.49 + /- 0.56 % p < 0.05 , total hip -0.89 + /- 0.57 % p < 0.05 ) . However , both the milk and control groups showed bone loss from baseline at the lumbar spine ( milk -2.01 % , control -3.29 % , p superior 0.05 ) . The calcium intake of the milk group remained significantly higher than the control group ( milk 710 mg/day , control 466 mg/day , p < 0.005 ) despite discontinuation of the milk supplement . CONCLUSIONS The results showed that some of the beneficial effects of a milk supplement were still evident at follow-up and it was possible to motivate subjects to adopt a positive change in dietary calcium intake after intervention Purpose . This study examined the effects of brief written educational material s on osteoporosis-related knowledge , beliefs , and behaviors . The study also examined whether observed effects varied as a function of one 's stage in the pre caution adoption process . Design . The study used an experimental research design . Setting . Participants were identified from North Carolina driver 's license records . Subjects . Of the 1476 women in the initial sample , 536 ( 36.3 % ) enrolled in the study and 307 completed all follow-up assessment s. Intervention . Participants were r and omly assigned to one of four groups . One group received an information packet containing general information about osteoporosis . One group received an action plan packet containing instructions on how to increase one 's level of exercise and calcium intake . One group received both packets . The final group received neither packet . Measures . Primary study variables were beliefs related to osteoporosis , calcium , and exercise ; osteoporosis knowledge ; calcium and exercise stage ; calcium intake ; and exercise level . Results . Overall , receipt of the information packet was associated with changes in knowledge and beliefs ( F[18,283 ] = 2.11 , p < .01 ) irrespective of participants ' stage of change . No effects on behavior were observed . Conclusions . These findings suggest that brief written educational material s can facilitate knowledge and belief change but that they do not promote behavior change . The generalizability of these findings is limited by the low study response rate CONTEXT Vitamin K has been implicated in bone health , primarily in observational studies . However , little is known about the role of phylloquinone supplementation on prevention of bone loss in men and women . OBJECTIVE The objective of this study was to determine the effect of 3-yr phylloquinone supplementation on change in bone mineral density ( BMD ) of the femoral neck bone in older men and women who were calcium and vitamin D replete . DESIGN , PARTICIPANTS , AND INTERVENTION In this 3-yr , double-blind , controlled trial , 452 men and women ( 60 - 80 yr ) were r and omized equally to receive a multivitamin that contained either 500 mug/d or no phylloquinone plus a daily calcium ( 600 mg elemental calcium ) and vitamin D ( 400 IU ) supplement . MAIN OUTCOME MEASURES Measurements of the femoral neck , spine ( L2-L4 ) , and total-body BMD , bone turnover , and vitamins K and D status were measured every 6 - 12 months . Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial . RESULTS There were no differences in changes in BMD measurements at any of the anatomical sites measured between the two groups . The group that received the phylloquinone supplement had significantly higher phylloquinone and significantly lower percent undercarboxylated osteocalcin concentrations compared with the group that did not receive phylloquinone . No other biochemical measures differed between the two groups . CONCLUSIONS Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin |
2,496 | 30,137,234 | Areas of agreement Shoulder stiffness could be treated with conservative means including nonsteroidal anti-inflammatory medications , corticosteroid injections , or transcutaneous electrical nerve stimulation , manipulation under anaesthesia , and arthroscopic capsular release .
Growing points The rate of failure after treatment for stiff shoulder is higher in the surgical group than in the conservative group .
Areas timely for developing research There is insufficient evidence to establish whether surgical or conservative management is the best choice to manage shoulder stiffness . | Introduction Currently , no therapeutic intervention is universally accepted , and the most effective management for restoring motion and diminishing pain in patients with shoulder stiffness has yet to be defined .
This systematic review analyses outcomes of conservative and surgical interventions to treat shoulder stiffness . | HYPOTHESIS Adhesive capsulitis is a condition that results in restricted glenohumeral motion . Fibroblasts have been implicated in the disease process ; however , their role as a contractile element in the development of fibrosis and capsular contracture is not well understood . We hypothesized ( 1 ) that myofibroblast prevalence in capsular biopsy specimens from patients with adhesive capsulitis would be increased compared with controls and ( 2 ) that patients treated with an intra-articular injection of corticosteroid would have fewer myofibroblasts . METHODS The study prospect ively enrolled 20 consecutive patients with adhesive capsulitis scheduled for capsular release and matched controls . Tissue sample s were collected from the posterior and anterior capsule for histomorphologic and immunohistologic analyses . Identical sectioning and preparation was performed in 14 additional adhesive capsulitis specimens from patients who had not received corticosteroid injections . RESULTS Patients with adhesive capsulitis not treated with preoperative corticosteroid demonstrated more histologic evidence of fibromatosis , synovial hyperplasia , and an increase in positive staining for α-smooth muscle actin than patients who had received intra-articular injections of steroid . No specimens obtained from control patients demonstrated positive staining for α-smooth muscle actin . DISCUSSION There was a higher prevalence of myofibroblast staining in patients with adhesive capsulitis , implicating activation of the myofibroblast in the pathophysiology of capsular contracture . Intra-articular steroid injection decreases the presence and amount of fibromatosis , vascular hyperplasia , fibrosis , and the presence of fibroblasts staining for α-smooth muscle actin . This supports the use of steroid injections to alter the disease process by decreasing the pathologic changes found in the capsular tissue Background and Purpose : The purpose of this study was to determine whether physical therapy interventions predicted meaningful short-term improvement in 4 measures of physical health , pain , and function for patients diagnosed with adhesive capsulitis . Participants : Data were examined from 2,370 patients ( mean age=55.3 years , SD=12.4 ; 65 % female , 35 % male ) classified into ICD-9 code 726.0 who had completed an episode of outpatient physical therapy . Methods : Principal components factor analysis was used to define intervention categories from specific treatments applied during the episode of care . A nested logistic regression model was used to identify intervention categories that predicted a 50 % or greater change in Physical Component Summary -12 ( PCS-12 ) , physical function ( PF ) , bodily pain ( BP ) , and hybrid function ( HF ) scores . Results : None of the patients achieved a 50 % or greater improvement in PCS-12 scores . Improvement in BP scores was more likely in patients who received joint mobility interventions ( odds ratio=1.35 , 95 % confidence interval=1.10–1.65 ) . Improvement in HF scores was more likely in patients who received exercise interventions ( odds ratio=1.50 , 95 % confidence interval=1.03–2.17 ) . Use of iontophoresis , phonophoresis , ultrasound , or massage reduced the likelihood of improvement in these 3 outcome measures by 19 % to 32 % . Limitations : The authors relied on clinician-identified ICD-9 coding for the diagnosis . Impairment measures were not available to support the diagnosis , and some interventions were excluded because of infrequent use by participating therapists . Discussion and Conclusions : These results are consistent with findings from r and omized clinical trials that demonstrated the effectiveness of joint mobilization and exercise for patients with adhesive capsulitis . Ultrasound , massage , iontophoresis , and phonophoresis reduced the likelihood of a favorable outcome , which suggests that use of these modalities should be discouraged OBJECTIVE To determine whether a short course of prednisolone is superior to placebo for improving pain , function , and range of motion in adhesive capsulitis . DESIGN Double blind , r and omised , placebo controlled trial . SETTING Community based rheumatology practice in Australia . PARTICIPANTS 50 participants ( 24 active , 26 placebo ) ; 46 completed the 12 week protocol . Entry criteria were age > or = 18 years , pain and stiffness in predominantly one shoulder for > or =3 weeks , and restriction of passive motion by > 30 degrees in two or more planes . INTERVENTIONS 30 mg oral prednisolone/day for three weeks or placebo . MAIN OUTCOME MEASURES Overall , night , and activity related pain , SPADI , Croft shoulder disability question naire , DASH , HAQ , SF-36 , participant rated improvement , and range of active motion measured at baseline and at 3 , 6 , and 12 weeks . RESULTS At 3 weeks , there was greater improvement in overall pain in the prednisolone group than in the placebo group ( mean ( SD ) change from baseline , 4.1 ( 2.3 ) v 1.4 ( 2.3 ) ; adjusted difference in mean change between the two groups , 2.4 ( 95 % CI , 1.1 to 3.8 ) ) . There was also greater improvement in disability , range of active motion , and participant rated improvement ( marked or moderate overall improvement in 22/23 v 11/23 ; RR = 2 ( 1.3 to 3.1 ) , p = 0.001 ) . At 6 weeks the analysis favoured the prednisolone group for most outcomes but none of the differences was significant . At 12 weeks , the analysis tended to favour the placebo group . CONCLUSIONS A three week course of 30 mg prednisolone daily is of significant short term benefit in adhesive capsulitis but benefits are not maintained beyond six weeks Background : Frozen shoulder has always been considered important because of the impact on the quality -of-life and long period of illness . Therefore , the use of noninvasive and safe techniques that can speed up the healing process of the disease is important . Methods : This study was a r and omized clinical trial study on patients suffering from frozen shoulder who were referred to Isfahan University of Medical Sciences hospitals in 2011 and 2012 . A total of 36 patients were enrolled in the study . Eligible patients were allocated into two groups . Intervention group received extracorporeal shockwave therapy ( ESWT ) once a week for 4 weeks . The control group received sham shockwave therapy once a week for 4 weeks . On the follow-up period , changes in individual performance and the amount of pain and disability were assessed by the Shoulder Pain and Disability Index ( SPADI ) question naire and the range of motion changes were assessed by a goniometer . Data obtained were analyzed using SPSS software . Results : Variance analysis revealed a difference in the mean pain and disability score of the SPADI question naire , flexion , extension , and abduction , external rotation of involved shoulder between two groups before and after the shockwave therapy ( P < 0.05 ) . Improvement was more satisfactory in the intervention group , but the mean internal rotation did not differ significantly in two groups ( P > 0.05 ) . Conclusions : The use of ESWT seems to have positive effects on treatment , quicker return to daily activities , and quality -of-life improvement on frozen shoulder Seventy seven patients with soft tissue shoulder lesions including adhesive capsulitis and disorders of the rotator cuff and acromioclavicular joint were admitted to a trial comparing two different methods of corticosteroid injection with local anaesthetic in a r and omly allocated double blind study . The method of anatomical injection after diagnosis by the technique of selective tissue tension gave 60 % success compared with the method using tender or trigger point localisation , giving 20 % success ( p less than 0.001 ) BACKGROUND AND PURPOSE In many physical therapy programs for subjects with adhesive capsulitis of the shoulder , mobilization techniques are an important part of the intervention . The purpose of this study was to compare the effectiveness of high- grade mobilization techniques ( HGMT ) with that of low- grade mobilization techniques ( LGMT ) in subjects with adhesive capsulitis of the shoulder . SUBJECTS One hundred subjects with unilateral adhesive capsulitis lasting 3 months or more and a > or = 50 % decrease in passive joint mobility relative to the nonaffected side were enrolled in this study . METHODS Subjects r and omly assigned to the HGMT group were treated with intensive passive mobilization techniques in end-range positions of the glenohumeral joint , and subjects in the LGMT group were treated with passive mobilization techniques within the pain-free zone . The duration of treatment was a maximum of 12 weeks ( 24 sessions ) in both groups . Subjects were assessed at baseline and at 3 , 6 , and 12 months by a masked assessor . Primary outcome measures included active and passive range of motion and shoulder disability ( Shoulder Rating Question naire [ SRQ ] and Shoulder Disability Question naire [ SDQ ] ) . An analysis of covariance with adjustments for baseline values and a general linear mixed-effect model for repeated measurements were used to compare the change scores for the 2 treatment groups at the various time points and over the total period of 1 year , respectively . RESULTS Overall , subjects in both groups improved over 12 months . Statistically significant greater change scores were found in the HGMT group for passive abduction ( at the time points 3 and 12 months ) , and for active and passive external rotation ( at 12 months ) . A statistically significant difference in trend between both groups over the total follow-up period of 12 months was found for passive external rotation , SRQ , and SDQ with greater change scores in the HGMT group . DISCUSSION AND CONCLUSION In subjects with adhesive capsulitis of the shoulder , HGMTs appear to be more effective in improving glenohumeral joint mobility and reducing disability than LGMTs , with the overall differences between the 2 interventions being small PURPOSE The purpose of this study was to examine the effectiveness of an arthroscopically placed intra-articular pain catheter for controlling postoperative pain and also review the results following arthroscopic release of refractor adhesive capsulitis . TYPE OF STUDY Retrospective clinical trial . METHODS Twenty-three consecutive cases ( 20 patients ) of arthroscopic adhesive capsulitis release in which an intra-articular pain catheter was used were review ed . Follow-up ranged from 12 to 37 months ( average , 22.4 months ) . An intra-articular catheter was placed under direct arthroscopic visualization from a superior approach into the glenohumeral joint . Postoperatively , patients were injected with 10 mL of 0.5 % bupivacaine every 6 hours as needed . Preoperatively , all patients had filled out a question naire based on the American Shoulder and Elbow Surgeons ( ASES ) outcome guidelines and examined for range of motion . Postoperatively , patients were asked for their precatheter and postcatheter injection pain level based on the visual analog scale ( 1 to 10 points , 1 = no pain ) . Patients were then examined for range of motion and retested with the outcome question naire . An ASES Shoulder Score Index was calculated for each patient before and after the procedure . RESULTS The average forward elevation preoperatively was 102 degrees and external rotation at the side was 4.5 degrees . At most recent follow-up , average forward elevation was 169 degrees with external rotation at the side 47 degrees . The Shoulder Score Index increased from an average of 37.1 out of 100 to 90.9 ( P < .001 ) . Before being injected with anesthetic through the catheter , patients had an average visual analog scale score of 8.1 . Postinjection average pain level was 1.2 ( P < .001 ) and all patients indicated that the pain catheter significantly reduced postoperative pain . Nineteen of 20 patients were satisfied with the procedure . CONCLUSIONS Placement of an intra-articular pain catheter for delivery of bupivacaine was highly effective in controlling postoperative pain . In all cases , postoperative pain was essentially eliminated and this substantially assisted with range of motion exercises . Near complete restoration of range of motion without pain was achieved in 95 % of the patients PRINCIPLE A r and omised , comparative prospect i ve clinical trial was planned to compare the early response to different rehabilitation methods for adhesive capsulitis taking into consideration the clinical efficacy and the cost effectiveness of the methods . METHODS Forty patients with adhesive capsulitis were r and omised into two treatment groups . The first group ( CYR ) received the Cyriax approach of deep friction massage and mobilisation exercises three times weekly . The second group ( PT ) had daily physical therapy including hot pack and short wave diathermy application . Both groups concluded their treatments with stretching exercises and were also instructed to a daily home exercise program . The primary end point of the study was to reach 80 % of the normal passive range of motion ( ROM ) of the shoulder in all planes within a period of two weeks . Secondary end points were the overall ROM and pain response ( spontaneous pain , night pain and pain with motion ) to each treatment . RESULTS 19 patients in the CYR group ( 95 % ) and 13 patients in the PT group ( 65 % ) reached sufficient ROM at the end of the second week ( p < 0.05 ) . The improvement in shoulder flexion , inner and outer rotation values and the decrease in pain with motion were significantly better in the CYR group after the first week of treatment . CONCLUSION The Cyriax method of rehabilitation provides a faster and better response than the conventional physical therapy methods in the early phase of treatment in adhesive capsulitis . The method is non-invasive , effective and requires fewer hospital visits for a sufficient early response Seventy-seven patients with idiopathic frozen shoulder syndrome were included in a prospect i ve study to compare the effect of intensive physical rehabilitation treatment , including passive stretching and manual mobilization ( stretching group ) versus supportive therapy and exercises within the pain limits ( supervised neglect group ) . There were no significant differences in age , sex , time elapsed since onset , and disease severity at inclusion . All patients were followed up for 24 months after the start of treatment . In the patients treated with supervised neglect , 89 % had normal or near-normal painless shoulder function ( Constant score > or = 80 ) at the end of the observation period . This end result was reached by 64 % within 12 months . In contrast , of the group receiving intensive physical therapy treatment , only 63 % reached a Constant score of 80 or higher after 24 months . Both the level of the Constant score at the end of the study and the moment a Constant score of 80 or higher was reached confirm that supervised neglect yields better outcomes than intensive physical therapy and passive stretching in patients with frozen shoulder INTRODUCTION The aim of this prospect i ve study was to assess the immediate and long-term effectiveness of arthroscopic capsular release in a large cohort of patients with a precise and isolated diagnosis of stage II idiopathic frozen shoulder . METHODS All patients underwent a preoperative evaluation . Patients with secondary frozen shoulder and those with concurrent pathology at arthroscopy were excluded . This left 136 patients with a stage II arthroscopically confirmed idiopathic frozen shoulder . At each postoperative attendance , a record was made of pain , function and range of motion . At 12 months , the Oxford shoulder score was calculated , and pain and range of motion were assessed . RESULTS Fifty per cent achieved good pain relief within a week and eighty per cent within six weeks of arthroscopic capsular release . The mean preoperative visual analogue scale pain score was 6.6 and the mean postoperative score was 1.0 . The mean time to achieving good pain relief was 16 days following surgery . No patient could sleep through the night prior to surgery while 90 % reported having a complete night ’s sleep at a mean of 12 days after surgery . The mean postoperative Oxford shoulder score was 38/48 and the mean improvement was 19.2 . CONCLUSIONS This large series demonstrates that arthroscopic capsular release is a safe procedure , with rapid improvement in pain and a marked improvement in range of motion The intraarticular injection of lidocaine immediately before a physiotherapy session may relieve pain during the stretching and mobilization of the affected joint in patients with a frozen shoulder , thus enhancing the treatment effect . To compare the effects of intraarticular injection of lidocaine plus physiotherapy to that of physiotherapy alone in the treatment of a frozen shoulder , a prospect i ve r and omized controlled trial was conducted in the rehabilitation department of a private teaching hospital . Patients with a frozen shoulder were r and omized into the physiotherapy group or the lidocaine injection plus physiotherapy ( INJPT ) group . The subjects in the INJPT group underwent injection of 3 ml of 1 % lidocaine into the affected shoulder 10 to 20 minutes before each physiotherapy session . In each group , the treatment lasted 3 months . The primary outcome measures were the active and passive range of motion of the affected shoulder . The secondary outcome measures were the results of the Shoulder Disability Question naire , the Shoulder Pain and Disability Index , and the 36-item Short-Form Health Survey ( SF-36 ) . The outcome measures were evaluated before treatment and 1 , 2 , 3 , 4 , and 6 months after the start of treatment . The group comparisons showed significantly greater improvement in the INJPT group , mainly in active and passive shoulder range of motion in flexion and external rotation and improvements in pain and disability ( P < 0.05 ) ; however , no significant group difference was seen in the SF-36 results . The intraarticular injection of lidocaine immediately before a physiotherapy session might be superior to physiotherapy alone in the treatment of a frozen shoulder . Trial Registration Clinical Trials.gov OBJECTIVE To study the effect of manipulating a shoulder with adhesive capsulitis ( frozen shoulder ) under anesthesia with and without corticosteroid injection . DESIGN R and omized trial . SETTING Hospital . PARTICIPANTS Twenty-four patients referred for manipulation of a frozen shoulder . INTERVENTION The patients were r and omized into 2 groups . One group received an injection of corticosteroid and manipulation ; the other was only administered manipulation during anesthesia . MAIN OUTCOME MEASURES The degree of shoulder mobility and pain before and after the manipulation . RESULTS Manipulation under anesthesia increased the mobility of the affected shoulder . Injection with lidocaine and betamethason did not enhance the effect of the manipulation . CONCLUSION Manipulation under anesthesia without intraarticular corticosteroids is recommended as the therapy for frozen shoulder Forty-two patients with frozen shoulder were followed up closely for eight months . They were all taught pendular exercises and r and omly allocated to one of four treatment groups : ( a ) intraarticular steroids , ( b ) mobilisations , ( c ) ice therapy , ( d ) no treatment . This study has shown that there is little long-term advantage in any of the treatment regimens but that steroid injections may benefit pain and range of movement in the early stages of the condition Summary We report a prospect i ve study comparing the results of treatment for frozen shoulder by manipulation and physiotherapy , arthroscopic distension and physiotherapy , and physiotherapy alone in 75 patients . The first two gave better results than physiotherapy alone and we recommend arthroscopic distension as a good alternative to manipulation . It is more controllable and gives valuable information about the pathological lesions in the joint . RésuméLes auteurs présentent une étude prospect i ve comparant les résultats du traitement du syndrome de ≪l'épaule gelée»≫ chez 75 malades , soit par manipulations et physiothérapie , soit par distension arthroscopique et physiothérapie , soit par physiothérapie isolée . Les deux premières méthodes donnent de meilleurs résultats que la physiothérapie isolée et les auteurs considèrent que la distension arthroscopique constitue , aux manipulations , une alternative recomm and able . Elle peut être mieux contrôlée et elle fournit des informations valables quant aux lésions pathologiques intra-articulaires Abstract . Adhesive capsulitis is a common musculoskeletal disorder mainly affecting middle aged adults . It is associated with generalized pain and tenderness in the shoulder joint with severe loss of active and passive ranges of motion in all planes . The aim of this study was to compare the efficacy of local steroid injection and physical therapy measures for treating this disorder . Ten male and 10 female patients were enrolled in the study . The patients were divided r and omly into two groups and treated with either 40 mg methylprednisolone acetate injection with local anesthetic ( group A ) or physical therapy measures plus nonsteroidal anti-inflammatory drugs ( group B ) . The mean ages of the patients were 55.6±12.2 years in group A and 56.4±7.1 years in group B. Clinical assessment was performed on initial visit and at the 2nd and 12th weeks . Active and passive range of motion was recorded and the visual analogue scale was used to evaluate pain intensity . At initial visit , these data in both groups of patients were not statistically different . Although both treatment regimens result ed in significant improvement in range of motion , the differences between mean external rotation at the 2nd and 12th weeks were not statistically significant in either group . The improvement in range of motion at the end of the study was similar in both groups ( P>0.05 ) . All patients reported improvement during the study . The differences between mean VAS scores at the 2nd and 12th weeks were statistically significant in both groups . In conclusion , local steroid injection therapy was found to be as effective as physical therapy for the treatment of adhesive capsulitis PURPOSE To evaluate effects of the extent of surgical release and of postoperative physiotherapy on the outcomes of this procedure . TYPE OF STUDY Case-controlled cohort study . METHODS Pain and range of motion scores were compared preoperatively , operatively , and at 1 , 6 , 12 , 24 , 52 , and 104 weeks postoperatively , in 2 temporal cohorts of patients with adhesive capsulitis . The first cohort ( n = 18 ) underwent a 155 degrees + /- 40 degrees ( mean + /- SEM ) st and ard anteroinferior arthroscopic capsule release of the shoulder ( ACR-S ) and rehabilitation . The second cohort ( n = 22 ) underwent capsular release that was extended an additional 65 degrees + /- 65 degrees posteriorly , a portion of the intra-articular part of the subscapularis tendon was divided , and the patients had a modified earlier , supervised postoperative physical therapy program ( ACR-M ) . RESULTS In both cohorts , there was a significant reduction in pain 1 week after surgery , which was maintained at all time-points ( P < .05 ) . More gains in intraoperative range of forward flexion ( 121 degrees v 150 degrees ) , abduction ( 114 degrees v 146 degrees ) and external rotation ( 55 degrees v 68 degrees ) were obtained in the ACR-M cohort ( P < .001 ) . Six weeks after surgery , external and internal rotation regressed to preoperative levels in the ACR-S cohort ; 2 of them required a re-release . This regression was not observed in the ACR-M cohort . There was no instability or weakness in lift-off power in either cohort . CONCLUSIONS This is a level IV study of 2 nonr and omized cohorts where simultaneous changes in surgical technique and rehabilitation were introduced to the ACR-M cohort . Arthroscopic capsular release for adhesive capsulitis result ed in significant reductions in pain by 1 week in both cohorts . A more extensive capsular release with division of the intra-articular portion of subscapularis improved intraoperative motion . Gains in internal and external rotation were lost postoperatively in the ACR-S cohort , but were preserved when an extended surgical release and an early , supervised postoperative physical therapy program was initiated in the ACR-M cohort . LEVEL OF EVIDENCE Level IV A double-blind controlled , between-patient trial was carried out in 40 patients with painful stiff shoulder to compare the effect of treatment with either 50 mg diclofenac sodium or 400 mg ibuprofen given 3-times daily for 2 weeks . The results of assessment s made before and after treatment showed that although both drugs produced some improvement no statistically significant differences between the two groups in terms of pain relief or the range of movement were evident . The incidence of side-effects was also similar A prospect i ve study has been made of 49 patients with the frozen shoulder syndrome ( as distinct from tendinitis , calcific deposits and frozen shoulders occurring after coronary infa rct ion or with pulmonary tuberculosis ) of whom forty-one have been followed up for 5 - 10 years , always to their greatest recovery . There were three consecutive stages : pain , stiffness , and recovery . The stiffness stage was usually related to the duration of the recovery stage . The total duration was longer than is generally supposed ( an average total of 30.1 months in contrast to about 18 months as often postulated ) . Generally speaking , the longer the stiffness stage is , the longer is the recovery stage . In 4 patients the second shoulder became similarly affected , 6 months to 7 years after the first , and followed a similar chronological sequence to the first . After greatest recovery , slight restriction of movement was found in more than half the cases , but in only 3 , all of long duration , was the restriction a h and icap . Arthrography , carried out on both shoulders in all patients during the recovery stage , showed in the affected shoulder fewer rotator cuff defects than expected at this age and fewer ( four ) than in the contralateral one ( twenty-three ) ; seemingly , the condition leads to the obliteration of some defects Our aim was to compare the outcome of arthroscopic release for frozen shoulder in patients with and without diabetes . We prospect ively compared the outcome in 21 patients with and 21 patients without diabetes , two years post-operatively . The modified Constant score was used as the outcome measure . The mean age of the patients was 54.5 years ( 48 to 65 ; male : female ratio : 18:24 ) , the mean pre-operative duration of symptoms was 8.3 months ( 6 to 13 ) and the mean pre-operative modified Constant scores were 36.6 ( st and ard deviation ( sd ) 4.6 ) and 38.4 ( sd 5.7 ) in the diabetic and non-diabetic groups , respectively . The mean modified Constant scores at six weeks , six months and two years post-operatively in the diabetics were 55 . 6 ( sd 4.7 ) , 67 . 4 ( sd 5.6 ) and 84 . 4 ( sd 6.8 ) , respectively ; and in the non-diabetics 66.8 ( sd 4.5 ) , 79.6 ( sd 3.8 ) and 88.6 ( sd 4.2 ) , respectively . A total of 15 ( 71 % ) of diabetic patients recovered a full range of movement as opposed to 19 ( 90 % ) in the non-diabetics . There was significant improvement ( p < 0.01 ) in the modified Constant scores following arthroscopic release for frozen shoulder in both groups . The results in diabetics were significantly worse than those in non-diabetics six months post-operatively ( p < 0.01 ) with a tendency towards persistent limitation of movement two years after operation . These results may be used when counselling diabetic patients for the outcome after arthroscopic treatment of frozen shoulder This study is a comparison of treatments of idiopathic " Frozen Shoulder " ( adhesive capsulitis ) , distension combined with steroid is compared with steroid alone . Evaluation was based on pain scales , analgesic usage , and range of motion outcome scales . Out of one-hundred twenty patients ( age , mean 51 , range 21 - 70 ) that were referred under the diagnosis FS , twenty-six fulfilled the criteria for inclusion in the study , but four patients did not want to participate in the trial , giving a total of 22 patients ( age , mean 53 , range 40 - 65 ) in the study . Patients were r and omised by the envelope method . Two patients dropped-out , one in each treatment group thus leaving the study with 20 patients for the final statistical analysis . Eight were treated with steroid alone and 12 with distension combined with steroid . Patients received one treatment per week for a six weeks period with a follow-up at 12 weeks . They were evaluated by pain VAS on function and at rest within the study period , the different ranges of motion ( ROM ) were measured at inclusion time and subsequent afterwards at 3 , 6 , and 12 weeks . The VAS outcomes showed no difference between the treatments ( VAS-function p=0,1 ; VAS-rest p=0.1 ) , while in the distension group ROM showed significant improvement in all directions except extension ( external p=0.0007 , flexion p=0.03 , extension p=0,01 ) . The analgesic usage was significantly lower in the group treated with distension at the end of the study ( p=0.008 ) . A blinded clinical assessment of ROM also showed significant improvement ( p=0.002 ) . It is concluded that distension with steroid can seem to help in management of " Frozen Shoulder " . Other studies seems to support the conclusion Background Physiotherapy treatment of frozen shoulder is varied , but most lack specific focus on the underlying disorder , which is the adhered shoulder capsule . Although positive effects were found after physiotherapy , the recurrence and prolonged disability of a frozen shoulder are major factors to focus on to provide the appropriate treatment . Questions / purpose sWe wished to study the effectiveness of a shoulder countertraction apparatus on ROM , pain , and function in patients with a frozen shoulder and compare their results with those of control subjects who received conventional physiotherapy . Methods A total of 100 participants were r and omly assigned to an experimental group and a control group , with each group having 50 participants . The control group received physiotherapy and the experimental group received countertraction and physiotherapy . The total treatment time was 20 minutes a day for 5 days per week for 2 weeks . The outcome measures used were goniometer measurements , VAS , and the Oxford Shoulder Score . Results Improvements were seen in the scores for shoulder flexion ( 94.1 ° ± 19.79 ° at baseline increased to 161.9 ° ± 13.05 ° after intervention ) , abduction ROM ( 90.4 ° ± 21.18 ° at baseline increased to 154.8 ° ± 13.21 ° after intervention ) , and pain ( 8.00 ± 0.78 at baseline decreased to 3.48 ± 0.71 after intervention ) in the experimental group . Sixty percent of the participants ( n = 30 ) were improved to the fourth stage of satisfactory joint function according to the Oxford Shoulder Score in the experimental group compared with 18 % ( n = 9 ) in the control group ( p < 0.001 ) . Conclusions Incorporating shoulder countertraction along with physiotherapy improves shoulder function compared with physiotherapy alone for the treatment of a frozen shoulder . Additional studies are needed focusing on this concept to increase the generalizability of the counter-traction apparatus in various groups . Level of Evidence Level II , prospect i ve comparative study . See the Instructions for Authors for a complete description of levels of evidence BACKGROUND Frozen shoulder is a common problem in general practice , but its treatment is difficult since none of the currently used therapies are proven to be effective . AIM To assess the effectiveness of suprascapular nerve block to relieve pain and improve range of movement , and its suitability for use in primary care . This small study by a single practitioner aims to justify a larger multicentred trial . METHOD A r and omized trial of 30 patients to compare a single suprascapular nerve block with a course of intra-articular injections . Patients ' pain levels and ranges of movement were assessed over a 12-week period . RESULTS Suprascapular nerve block produced a faster and more complete resolution of pain and restoration of range of movement than a series of intra-articular injections . These differences were confirmed by statistical analysis using the Mann-Whitney U-test ( P < 0.01 for pain levels and P < 0.05 for range of abduction and external rotation . ) CONCLUSIONS This study suggests that suprascapular nerve block is a safe and effective treatment for frozen shoulder in primary care , and justifies a larger multicentred trial using independent blinded assessment . Such a study should include a third group treated by suprascapular nerve block without steroid ; a more comprehensive assessment of patient debility Abstract Objective : To compare the effectiveness of corticosteroid injections with physiotherapy for the treatment of painful stiff shoulder . Design : R and omised trial . Setting : 40 general practice s. Subjects : 109 patients consulting general practitioners for shoulder pain were enrolled in the trial . Interventions : Patients were r and omly allocated to 6 weeks of treatment either with corticosteroid injections ( 53 ) or physiotherapy ( 56 ) . Main outcome measures : Outcome assessment s were carried out 3 , 7 , 13 , 26 , and 52 weeks after r and omisation ; some of the assessment s were done by an observer blind to treatment allocation . Primary outcome measures were the success of treatment as measured by scores on scales measuring improvement in the main complaint and pain , and improvement in scores on a scale measuring shoulder disability . Results : At 7 weeks 40 ( 77 % ) out of 52 patients treated with injections were considered to be treatment successes compared with 26 ( 46 % ) out of 56 treated with physiotherapy ( difference between groups 31 % , 95 % confidence interval 14 % to 48 % ) . The difference in improvement favoured those treated with corticosteroids in nearly all outcome measures ; these differences were statistically significant . At 26 and 52 weeks differences between the groups were comparatively small . Adverse reactions were generally mild . However , among women receiving treatment with corticosteroids adverse reactions were more troublesome : facial flushing was reported by 9 women and irregular menstrual bleeding by 6 , 2 of whom were postmenopausal . Conclusions : The beneficial effects of corticosteroid injections administered by general practitioners for treatment of painful stiff shoulder are superior to those of physiotherapy . The differences between the intervention groups were mainly the result of the comparatively faster relief of symptoms that occurred in patients treated with injections . Adverse reactions were generally mild but doctors should be aware of the potential side effects of injections of triamcinolone , particularly in women STUDY DESIGN R and omized clinical trial . OBJECTIVE To compare the effectiveness of anterior versus posterior glide mobilization techniques for improving shoulder external rotation range of motion ( ROM ) in patients with adhesive capsulitis . BACKGROUND Physical therapists use joint mobilization techniques to treat motion impairments in patients with adhesive capsulitis . However , opinions of the value of anterior versus posterior mobilization procedures to improve external rotation ROM differ . METHODS AND MEASURES Twenty consecutive subjects with a primary diagnosis of shoulder adhesive capsulitis and exhibiting a specific external rotation ROM deficit were r and omly assigned to 1 of 2 treatment groups . All subjects received 6 therapy sessions consisting of application of therapeutic ultrasound , joint mobilization , and upper-body ergometer exercise . Treatment differed between groups in the direction of the mobilization technique performed . Shoulder external rotation ROM measured initially and after each treatment session was compared within and between groups and analyzed using a 2-way ANOVA , followed by paired and independent t tests . RESULTS There was no significant difference in shoulder external rotation ROM between groups prior to initiating the treatment program . A significant difference between groups ( P = .001 ) was present by the third treatment . The individuals in the anterior mobilization group had a mean improvement in external rotation ROM of 3.0 degrees ( SD , 10.8 degrees ; P = .40 ) , whereas the individuals in the posterior mobilization group had a mean improvement of 31.3 degrees ( SD , 7.4 degrees ; P < .001 ) . CONCLUSIONS A posteriorly directed joint mobilization technique was more effective than an anteriorly directed mobilization technique for improving external rotation ROM in subjects with adhesive capsulitis . Both groups had a significant decrease in pain To clarify the optimal management of rehabilitative intervention for limited glenohumeral joint mobility ( LGHM ) arising from adhesive capsulitis , particularly focusing on the frequency of sessions for joint mobilization and the self-exercise compliance , the functional results of 120 patients with LGHM were prospect ively investigated as follows : Differences in improved angle of the shoulder joint ( IA ) and the time required to reach the range of motion plateau point ( T ) were compared by ( 1 ) age , ( 2 ) gender , ( 3 ) h and edness , ( 4 ) duration before rehabilitative intervention , ( 5 ) frequency of sessions for joint mobilization by physical therapists in the hospital setting , and ( 6 ) self-exercise compliance in the home setting . The lengths of therapy and follow-up were 4.6 and 5.9 months , respectively . IA significantly decreased in the 71-year-old and above group . There were no significant differences in IA between male and female . IA of the dominant-h and ed group was significantly higher than that of the non-dominant-h and ed group . There were no significant differences in T in each item . IA of the group that had experienced more than 7 months of the condition was significantly low . Although the frequency of joint mobilization by physical therapists in the hospital setting showed no relationship with IA or T , IA was significantly higher and T was significantly shorter in the group that performed self-exercise every day than in the groups that performed less . In conclusion , early intervention and self-exercise in the home setting are more important factors than session frequency of joint mobilization in the hospital setting for the successful management of rehabilitation for LGHM BACKGROUND : The treatment of adhesive capsulitis ( AC ) is a well-known , complicated , and long process . Recent studies have shown that pulsed radiofrequency ( PRF ) lesioning of the suprascapular nerve ( SSN ) using a fluoroscopy- or computed tomography-guided technique can alleviate shoulder pain . However , there are no studies of PRF lesioning of the SSN in patients with AC using ultrasound-guided ( UG ) techniques , except for 2 case reports . In this study , we compared the effect of physical therapy alone with physical therapy and PRF lesioning of the SSN using a UG technique . METHODS : Sixty patients with AC were included in the study . Patients were r and omized into the following 2 groups : the intervention group containing patients who received 12 weeks of physical therapy after 1 treatment of PRF lesioning of the SSN , and the control group containing patients who received 12 weeks of physical therapy alone . All outcome measurements including visual analog scale ( VAS ) , shoulder pain and disability index , and passive range of motion ( PROM ) were performed at 1 , 4 , 8 , and 12 weeks after treatment . RESULTS : Forty-two patients ( 21 patients in each group ) completed the study . The intervention group had a notably shorter time to onset of significant pain relief ( 6.1 ± 3.4 vs 28.1 ± 9.2 days ; P < 0.001 ) and noticeable reduction of VAS score at week 1 ( 40 % vs 4.7 % ) than the control group ( P < 0.001 ) . All measured variables in the intervention group and most variables in the control group showed significant improvement from the baseline ( P < 0.05 ) . A comparison of the 2 groups indicated significantly greater improvement in the intervention group at all times in VAS and shoulder pain and disability index scores ( all P < 0.05 ) , and for most gain of PROM ( P < 0.05 ) . There were no serious adverse effects or complications in either group . CONCLUSIONS : This study indicates that the application of PRF lesioning of the SSN using a UG technique combined with physical therapy provided better and faster relief from pain , reduced disability , and improved PROM when compared with physical therapy alone in patients with AC , an effect that persisted for at least 12 weeks OBJECTIVE To assess the effectiveness of intra-articular triamcinolone injection and physiotherapy singly or combined in the treatment of adhesive capsulitis of the shoulder . METHODS Eighty patients with adhesive capsulitis of less than 6 months duration were r and omized to one of four groups : Group A , injection of triamcinolone 20 mg and eight sessions of st and ardized physiotherapy ; Group B , injection of triamcinolone 20 mg alone ; Group C , placebo injection and eight sessions of st and ardized physiotherapy ; or Group D , placebo injection alone . All subjects were given an identical home exercise programme . Outcome measures were assessed at 6 weeks and 16 weeks . The primary outcome measure was Shoulder Disability Question naire ( SDQ ) score . Secondary outcomes were measurement of pain using a visual analogue scale ( VAS ) , global disability using VAS and range of passive external rotation . A two-way analysis of variance was used to explore the effects of corticosteroid injection and physiotherapy . RESULTS At 6 weeks , the SDQ had improved significantly more in the groups receiving corticosteroid injection ( P = 0.004 ) . Physiotherapy improved passive external rotation at 6 weeks ( P = 0.02 ) and corticosteroid injection improved self- assessment of global disability at 6 weeks ( P = 0.04 ) . There was no interaction effect between injection and physiotherapy . At 16 weeks , all groups had improved to a similar degree with respect to all outcome measures . CONCLUSION Corticosteroid injection is effective in improving shoulder-related disability , and physiotherapy is effective in improving the range of movement in external rotation 6 weeks after treatment OBJECTIVE To compare the efficacy of a single intraarticular corticosteroid injection , a supervised physiotherapy program , a combination of the two , and placebo in the treatment of adhesive capsulitis of the shoulder . METHODS Ninety-three subjects with adhesive capsulitis of < 1 year 's duration were r and omized to 1 of 4 treatment groups : group 1 , corticosteroid injection ( triamcinolone hexacetonide 40 mg ) performed under fluoroscopic guidance followed by 12 sessions of supervised physiotherapy ; group 2 , corticosteroid injection alone ; group 3 , saline injection followed by supervised physiotherapy ; or group 4 , saline injection alone ( placebo group ) . All subjects were taught a simple home exercise program . Subjects were reassessed after 6 weeks , 3 months , 6 months , and 1 year . The primary outcome measure was improvement in the Shoulder Pain and Disability Index ( SPADI ) score . RESULTS At 6 weeks , the total SPADI scores had improved significantly more in groups 1 and 2 compared with groups 3 and 4 ( P = 0.0004 ) . The total range of active and passive motion increased in all groups , with group 1 having significantly greater improvement than the other 3 groups . At 3 months , groups 1 and 2 still showed significantly greater improvement in SPADI scores than group 4 . There was no difference between groups 3 and 4 at any of the followup assessment s except for greater improvement in the range of shoulder flexion in group 3 at 3 months . At 12 months , all groups had improved to a similar degree with respect to all outcome measures . CONCLUSION A single intraarticular injection of corticosteroid administered under fluoroscopy combined with a simple home exercise program is effective in improving shoulder pain and disability in patients with adhesive capsulitis . Adding supervised physiotherapy provides faster improvement in shoulder range of motion . When used alone , supervised physiotherapy is of limited efficacy in the management of adhesive capsulitis PURPOSE The aims of our study were to assess the overall effectiveness of arthroscopic capsular release and to determine if the addition of a posterior capsular release had any benefit , particularly in relation to internal rotation . METHODS Forty-eight consecutive patients with primary or secondary frozen shoulder in whom conservative physiotherapy had failed were included in the study . Arthroscopic capsular release was performed in all cases . Group 1 had an anterior and inferior release only ; group 2 included a posterior release . All data were collected prospect ively . Constant-Murley functional scores were used to assess outcome . Overall satisfaction and patient reported outcomes were also measured . RESULTS The mean patient age was 51 years ( range , 28 to 65 years ) , with no difference between the 2 groups . There were 27 patients in group 1 and 21 patients in group 2 . The mean follow-up was 5 months . Etiology of the frozen shoulder was primary ( 22 ) , diabetic ( 7 ) , post-traumatic ( 7 ) , and postoperative ( 11 ) . Overall across both groups , there was a highly significant improvement in Constant score ( P < .001 ) postoperatively . A similar pattern was noted in the range of motion ( P < .001 ) . The mean satisfaction score was 7 of 10 postoperatively . The patients reported overall outcome as much better ( 24 ) , better ( 15 ) , the same ( 1 ) , and worse ( 4 ) . There was no significant difference in Constant score between the 2 groups , and no significant difference in the improvement of the range of motion , in particular internal rotation . CONCLUSIONS We have shown an overall rapid significant improvement following arthroscopic capsular release for primary and secondary frozen shoulder . There was no significant difference in the overall outcome with the addition of a posterior release . LEVEL OF EVIDENCE Level III , therapeutic , retrospective comparative study A prospect i ve study was undertaken of 73 patients with frozen shoulder syndrome who were treated with an arthroscopic capsulotomy . All of the patients were assessed for pain , function , and range of motion before surgery and were monitored through to 1-year follow up . Improvement in all parameters was achieved , with pain taking an average of 2.24 weeks to diminish and range of motion improving to within 10 % of the other side at an average of 5.5 weeks after surgery . Patients were discharged with a full range of motion and without pain at an average of 8.9 weeks . There was , however , some mild reaggravation of most patients ' pain within the postoperative period ( mean 4.5 weeks ) . This pain usually settled with appropriate massage within a 2-week period . In 37 % of cases , however , an injection of corticosteroid was required as part of the postoperative management . These cases were usually in that subgroup of patients who still had significant night pain and were in stage 2 or 3 of the disease process at the time of surgery . The postoperative results continued to the 12-month follow-up , with 11 % of patients having a recurrence of pain or stiffness . This study has demonstrated that arthroscopic capsulotomy is an effective technique in the management of the frozen shoulder . It also has enabled the authors to document postoperative recovery times , which has given prospect i ve patients realistic time frames of functional expectation in their postoperative recovery The aim of this study was to find intraarticular lesions after manipulation under general anesthesia in patients with primary frozen shoulder . In a prospect i ve trial conducted between 2001 and 2003 in 30 patients with primary frozen shoulder , the affected shoulders were manipulated while the patients were under general anesthetia . Exclusion criteria were secondary stiffness caused by rotator cuff tears and glenohumeral arthritis . After manipulation , each patient was examined by arthroscopy , and any intraarticular lesions were documented . In all patients , during manipulation , a significant improvement in the range of motion was achieved . Under anesthesia , flexion improved on average from 70 degrees + /- 33 degrees to 180 degrees + /- 15 degrees , abduction from 50 degrees + /- 20 degrees to 170 degrees + /- 25 degrees , and external rotation from -5 degrees + /- 10 degrees to + 40 degrees + /- 20 degrees . Arthroscopy revealed hemarthrosis in all patients after manipulation . In 22 patients , localized synovitis was detected in the area of the rotator interval , whereas in 8 patients , disseminated synovitis was observed as a feature of adhesive capsulitis . After manipulation , the capsule was seen to be ruptured superiorly in 11 patients , the anterior capsule was ruptured up to the infraglenoid pole in 24 patients , and 16 patients each had a capsular lesion located posteriorly . In 18 patients no additional joint damage was found after manipulation . In 4 patients , iatrogenic superior labrum anterior-posterior lesions were observed . Further injuries detected were 3 fresh partial tears of the subscapularis tendon , 4 anterior labral detachments ( 1 with a small osteochondral defect ) , and 2 tears of the middle glenohumeral ligament . Even though manipulation under anesthesia is effective in terms of joint mobilization , the method can cause iatrogenic intraarticular damage Frozen shoulder is said to be a self-limiting entity but full recovery often takes more than 2 years . For that , most patients are unwilling to tolerate painful restriction while awaiting resolution . We prospect ively investigated 30 patients ( 16 women , 14 men ) for the outcome of arthroscopic capsular release in idiopathic frozen shoulder . Results were determined by the assessment of subjective and objective parameters to estimate both shoulder function and general health status . Symptoms persisted without improvement for a minimum of 6 months of conservative treatment . Preoperative average American shoulder and elbow surgeons score ( ASES ) was 35 , visual analog scale ( VAS ) to measure pain was 7 , and simple shoulder test ( SST ) was 4 . Mean scores of the physical component of SF-36 were considerably reduced . Mean forward elevation was 85 ° , average abduction was 70 ° , mean internal rotation was 15 ° , and mean external rotation was 10 ° . Patients were followed-up at 6 weeks , 3 , 6 , 12 months and by a mean of 36 months . Range of motion for all planes improved ( P < 0.05 ) . Median VAS reduced to 2 , average ASES increased to 91 , and SST enhanced to a mean of 10 ( P < 0.05 ) . We stated improvement of the physical components in the SF-36 question naire in particular bodily pain and the role-physical score . There were no significant differences between the measurements in the early postoperative phase compared to the mid-term follow-up ( P > 0.05 ) . Our results demonstrate that arthroscopic release of refractory idiopathic frozen shoulder combined with a gentle manipulation provides reliable expectations for improvement in both clinical and general health status for most patients . We recommend the use of a limb-specific and a general-health-status question naire to conclude the benefit of the surgical intervention and contribute the optimization of a therapy concept more effectively HYPOTHESIS Oral and intra-articular injections of cortisone will lead to significant improvement and comparable results in the treatment of adhesive capsulitis of the shoulder . MATERIAL S AND METHODS In a prospect i ve r and omized evaluation , 40 patients with idiopathic adhesive capsulitis of the shoulder were treated with an oral corticoid treatment regimen or 3 intra-articular injections of corticosteroids . Follow-up was after 4 , 8 , and 12 weeks , and 6 and 12 months . For the clinical evaluation , the Constant-Murley ( CM ) score , the Simple Shoulder Test ( SST ) and visual analog scales ( VAS ) for pain , function , and satisfaction were used . RESULTS In the patients treated with oral glucocorticoids , significant improvements were found for the CM score ( P < .0001 ) , SST ( P=.035 ) , VAS ( P < .0001 ) , and range of motion ( P < .05 ) at the 4-week follow-up . The patients treated with an intra-articular glucocorticoid injection series also significantly improved in the CM score ( P < .0001 ) , SST ( P < .0001 ) , the VAS ( P < .0001 ) , and range of motion ( P < .05 ) after 4 weeks . These results were confirmed at all other follow-up visits . Superior results were found for intra-articular injections in range of motion , CM score , SST , and patient satisfaction ( P < .05 ) . Differences in the VAS for pain and function were not significant ( P > .05 ) . DISCUSSION The use of cortisone in the treatment of idiopathic shoulder adhesive capsulitis leads to fast pain relief and improves range of motion . Intra-articular injections of glucocorticoids showed superior results in objective shoulder scores , range of motion , and patient satisfaction compared with a short course of oral corticosteroids BACKGROUND There is little evidence for the optimal form of nonoperative treatment in the management of frozen shoulder . This study assesses the efficacy of current physiotherapy strategies . METHODS All primary care referrals of frozen shoulder to our physiotherapy department were included during a 12-month period . Of these referrals , 17 % met the inclusion criteria for primary idiopathic frozen shoulder . The 75 patients were r and omly assigned to 1 of 3 groups : group exercise class , individual physiotherapy , and home exercises alone . A single independent physiotherapist , who was blinded to the treatment groups , made all assessment s. Range of motion , Constant score , Oxford Shoulder Score , Short Form 36 , and Hospital Anxiety and Disability Scale ( HADS ) outcome measures were performed at baseline , 6 weeks , 6 months , and 1 year . RESULTS The exercise class group improved from a mean Constant score of 39.8 at baseline to 71.4 at 6 weeks and 88.1 at 1 year . There was a significant improvement in shoulder symptoms on Oxford and Constant scores ( P < .001 ) . This improvement was greater than with individual physiotherapy or home exercises alone ( P < .001 ) . The improvement in range of motion was significantly greater in both physiotherapy groups over home exercises ( P < .001 ) . HADS scores significantly improved during the course of treatment ( P < .001 ) . The improvement in HADS anxiety score was significantly greater in both physiotherapy intervention groups than in home exercises alone . CONCLUSIONS A hospital-based exercise class can produce a rapid recovery from a frozen shoulder with a minimum number of visits to the hospital and is more effective than individual physiotherapy or a home exercise program |
2,497 | 22,786,492 | Immediate ART reduces morbidity and mortality among infants and may improve neurodevelopmental outcome .
The available evidence suggests that a LPV/r-based first-line regimen is more potent than NVP , regardless of PMTCT exposure status .
This strategy looked promising in the one trial undertaken , but may be difficult to implement in the absence of VL testing . | BACKGROUND In the absence of antiretroviral therapy ( ART ) , over 50 % of HIV-infected infants progress to AIDS and death by 2 years of age .
However , there are challenges to initiate ART in early life , including the possibility of drug resistance in the context of prevention of mother-to-child transmission ( PMTCT ) programs , a paucity of drug choices , uncertain dosing for some medications and long-term toxicities .
Key management decisions include when to start ART , what regimen to start , and whether and when to switch or interrupt therapy .
This review aims to summarize the currently available evidence on this topic and inform the ART management in HIV-infected children less than 2 years of age .
OBJECTIVES To evaluate 1 ) when to start ART in young children ; 2 ) what ART to start with , comparing first-line non-nucleoside reverse transcriptase inhibitor ( NNRTI ) and PI-based regimens ; and 3 ) whether and when ART should be stopped or switched from a PI-based regimen to an NNRTI-based regimen .
However It remains unclear whether all children diagnosed with HIV infection between 1 - 2 years of age should start ART , as has been recommended by the World Health Organization on practical grounds . | BACKGROUND Recent evidence suggests that decreases in morbidity and mortality in cohorts of adults infected with human immunodeficiency virus ( HIV ) are showing signs of reversal . We describe changes over time in these characteristics and in the response to treatment among children in the United Kingdom and Irel and with perinatally acquired HIV infection , many of whom are now adolescents . METHODS We analyzed prospect i ve cohort data reported to the National Study of HIV in Pregnancy and Childhood ( NSHPC ) and the Collaborative HIV Paediatric Study . RESULTS By mid 2006 , 1441 HIV-infected children were reported to NSHPC ; 40 % were > or = 10 years old at their most recent follow-up visit , and 34 % were receiving care outside London . The proportion of children born abroad increased from 24 % during 1994 - 1996 to 64 % during 2003 - 2006 . The percentage of total child time during which children received highly active antiretroviral therapy ( HAART ) increased from 36 % during 1997 - 1999 to 61 % during 2000 - 2002 and 63 % during 2003 - 2006 . Of children who were naive to antiretroviral therapy at the start of HAART , the percentage with an HIV-1 RNA load of < 400 copies/mL after 12 months increased from 52 % during 1997 - 1999 to 79 % during 2003 - 2006 . In multivariate analysis , only calendar time predicted virological response , whereas both younger age and lower CD4 cell percentage at HAART initiation predicted increases of > 10 % in the CD4 cell percentage . A total of 31 % of children aged 5 - 14 years and 38 % aged > or = 15 years at their most recent follow-up visit had been exposed to drugs from each of the 3 main HAART classes . The rate of AIDS and mortality combined decreased from 13.3 cases per 100 person-years before 1997 to 3.1 and 2.5 cases per 100 person-years , respectively , during 2000 - 2002 and 2003 - 2006 ; rates of hospital admission also declined during this interval . Of 18 children known to have died since 2003 , 9 died within 1 month after presentation . CONCLUSIONS Morbidity and mortality rates among HIV-infected children continue to decrease over time . Because these children are increasingly dispersed outside London , specialist care is now provided in national clinical networks . Transition pathways to adolescent and adult services and long-term observation to monitor the effects of prolonged exposure to both HIV and HAART are required Objective To evaluate the feasibility of a large immediate versus deferred antiretroviral therapy ( ART ) study in children . Methods We conducted an open-label pilot r and omized clinical trial study in 43 Thai children with CD4 15 to 24 % of starting generic AZT/3TC/NVP immediately ( Arm 1 ) or deferring until CD4 < 15 % or CDC C ( Arm 2 ) . Primary endpoints were recruitment rate , adherence to r and omized treatment and retention in trial . Secondary endpoints were % with CDC C or CD4 < 15 % . Children were in the trial until the last child reached 108 weeks . Intention to treat and on treatment analyses were performed . Results Recruitment took 15 months . Twenty-six of 69 ( 37.7 % ) were not eligible due mainly to low CD4 % . Twenty four and 19 were r and omized to arms 1 and 2 respectively . All accepted the r and omized arm ; however , 3 in arm 1 stopped ART and 1 in arm 2 refused to start ART . Ten/19 ( 53 % ) in arm 2 started ART . At baseline , median age was 4.8 yrs , CDC A : B were 36:7 , median CD4 was 19 % and viral load was 4.8 log . All in arm 1 and 17/19 in arm 2 completed the study ( median of 134 weeks ) . No one had AIDS or death . Four in immediate arm had tuberculosis . Once started on ART , deferred arm children achieved similar CD4 and viral load response as the immediate arm . Adverse events were similar between arms . The deferred arm had a 26 % ART saving . Conclusion Almost 40 % of children were not eligible due mainly to low CD4 % but adherence to r and omized treatment and retention in trial were excellent . A larger study to evaluate when to start ART is feasible Objectives : Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly . Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required . This feasibility study addresses efficacy of infant antiretroviral therapy in this setting . Methods : HIV-infected infants in Durban , South Africa , received r and omized immediate or deferred ( when CD4 cell count reached < 20 % ) four-drug antiretroviral therapy ( zidovudine/lamivudine/nelfinavir/nevirapine ) . Genotyping for non-nucleoside reverse transcriptase inhibitor ( NNRTI ) resistance was undertaken pre-antiretroviral therapy . Monthly follow-up to 1-year post-antiretroviral therapy included viral load , CD4 cell count and verbal/measured adherence monitoring . Results : All 63 infants were exposed to single-dose nevirapine . Twenty-one out of 51 ( 39 % ) infants with baseline genotyping results had NNRTI resistance ( most frequently Y181C ; 20 % ) . Forty-three infants were r and omized to immediate antiretroviral therapy ( ART ) : three withdrew pre-antiretroviral therapy ; 36 out of 40 completed 1-year of ART . Twenty infants received deferred ART : 17 reached CD4 cell counts less than 20 % ( median d99 ) and 13 out of 17 started antiretroviral therapy in year 1 . Verbal and measured adherence was 99 % and 95 % , respectively . One-year post-ART , 49 out of 49 ( 100 % ) infants had a viral load less than 400 copies/ml ; 46 out of 49 ( 94 % ) had viral load less than 50 copies/ml . Ten infants ( 20 % ) required second-line ART due to virological failure or tuberculosis treatment , therefore 39 out of 49 ( 80 % ) achieved viral load less than 400 copies/ml by intention-to-treat . Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count ( r = −0.42 ; P = 0.005 ) and infant pre-ART viral load ( r = 0.64 ; P < 0.001 ) . NNRTI mutations had no significant effect on virological suppression . Infants starting immediate compared with deferred ART had fewer illness episodes ( P = 0.003 ) , but no significant difference in virological suppression . Conclusion : Excellent adherence and virological suppression are achievable in infants , despite high-frequency NNRTI mutations and rapid disease progression . Infants remain relatively neglected in roll-out programmes and ART provision must be exp and ed ABSTRACT Studies of potent antiretroviral combination regimens were undertaken in young infants to evaluate the potential for long-term suppression of viral replication and to evaluate the immune consequences of such therapies . Early combination antiretroviral therapy led to a loss of plasma viremia , cultivable virus , and labile extrachromosomal replication intermediates . Despite preservation of immune function , persistent human immunodeficiency type 1 (HIV-1)-specific immune responses were not detected in most infants . The absence of detectable , persisting immune responses in most HIV-1-infected infants treated early contrasts with what is typically seen in adults who are treated early . These results are consistent with the notion that early combination antiretroviral therapy of HIV-1-infected infants allows the long-term suppression of viral replication OBJECTIVE To investigate the outcome in children perinatally infected with HIV-1 whose mothers received zidovudine ( ZDV ) monotherapy in pregnancy . DESIGN Observational retrospective study of a prospect ively recruited cohort . SETTING Italian Register for HIV Infection in Children . PATIENTS A group of 216 children perinatally infected with HIV-1 , born in 1992 - 1997 and derived prospect ively from birth : 38 children had mothers receiving ZDV monotherapy and for 178 children the mothers received no antiretroviral treatment during pregnancy . MAIN OUTCOME MEASURES The estimated probability of developing severe disease or severe immune suppression , survival probability [ 95 % confidence interval ( CI ) ] within 3 years , and the hazard ratio ( 95 % CI ) , adjusted for year of birth , maternal clinical condition at delivery , birthweight and treatments ( Pneumocystis carinii pneumonia chemoprophylaxis and /or antiretroviral therapy before the onset of severe disease , severe immune suppression or death ) were compared . RESULTS Comparison of HIV-1-infected children whose mothers were treated with ZDV with children whose mothers were not treated showed that the former group had a higher probability of developing severe disease [ 57.3 % ( 95 % CI 40.9 - 74.3 ) versus 37.2 % ( 95 % CI 30.0 - 45.4 ) ; log-rank test 7.83 , P = 0.005 ; adjusted hazard ratio 1.8 ( 95 % CI 1.1 - 3.1 ) ] or severe immune suppression [ 53.9 % ( 95 % CI 36.3 - 73.5 ) versus 37.5 % ( 95 % CI 30.0 - 46.2 ) ; log-rank test 5.58 , P = 0.018 ; adjusted hazard ratio 2.4 , ( 95 % CI : 1.3 - 4.3 ) ] and a lower survival [ 72.2 % ( 95 % CI 50.4 - 85.7 ) versus 81.0 % ( 95 % CI 73.7 - 86.5 ) ; log-rank test 4.23 , P = 0.039 ; adjusted hazard ratio of death 1.9 ( 95 % CI 1.1 - 3.6 ) ] . CONCLUSIONS This epidemiological observation could stimulate virologic studies to eluci date whether this rapid progression depends on in utero infection or transmission of resistant virus . Findings may suggest a need to hasten HIV-1 diagnosis in infants of ZDV-treated mothers and undertake an aggressive antiretroviral therapy in those found to be infected BACKGROUND Single-dose nevirapine is the cornerstone of the regimen for prevention of mother-to-child transmission of human immunodeficiency virus ( HIV ) in re source -limited setting s , but nevirapine frequently selects for resistant virus in mothers and children who become infected despite prophylaxis . The optimal antiretroviral treatment strategy for children who have had prior exposure to single-dose nevirapine is unknown . METHODS We conducted a r and omized trial of initial therapy with zidovudine and lamivudine plus either nevirapine or ritonavir-boosted lopinavir in HIV-infected children 6 to 36 months of age , in six African countries , who qualified for treatment according to World Health Organization ( WHO ) criteria . Results are reported for the cohort that included children exposed to single-dose nevirapine prophylaxis . The primary end point was virologic failure or discontinuation of treatment by study week 24 . Enrollment in this cohort was terminated early on the recommendation of the data and safety monitoring board . RESULTS A total of 164 children were enrolled . The median percentage of CD4 + lymphocytes was 19 % ; a total of 56 % of the children had WHO stage 3 or 4 disease . More children in the nevirapine group than in the ritonavir-boosted lopinavir group reached a primary end point ( 39.6 % vs. 21.7 % ; weighted difference , 18.6 percentage-points ; 95 % confidence interval , 3.7 to 33.6 ; nominal P=0.02 ) . Baseline resistance to nevirapine was detected in 18 of 148 children ( 12 % ) and was predictive of treatment failure . No significant between-group differences were seen in the rate of adverse events . CONCLUSIONS Among children with prior exposure to single-dose nevirapine for perinatal prevention of HIV transmission , antiretroviral treatment consisting of zidovudine and lamivudine plus ritonavir-boosted lopinavir result ed in better outcomes than did treatment with zidovudine and lamivudine plus nevirapine . Since nevirapine is used for both treatment and perinatal prevention of HIV infection in re source -limited setting s , alternative strategies for the prevention of HIV transmission from mother to child , as well as for the treatment of HIV infection , are urgently required . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00307151 . ) BACKGROUND In countries with a high seroprevalence of human immunodeficiency virus type 1 ( HIV-1 ) , HIV infection contributes significantly to infant mortality . We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy ( CHER ) trial . METHODS HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage ( the CD4 percentage ) of 25 % or more were r and omly assigned to receive antiretroviral therapy ( lopinavir-ritonavir , zidovudine , and lamivudine ) when the CD4 percentage decreased to less than 20 % ( or 25 % if the child was younger than 1 year ) or clinical criteria were met ( the deferred antiretroviral-therapy group ) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age ( the early antiretroviral-therapy groups ) . We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy . RESULTS At a median age of 7.4 weeks ( interquartile range , 6.6 to 8.9 ) and a CD4 percentage of 35.2 % ( interquartile range , 29.1 to 41.2 ) , 125 infants were r and omly assigned to receive deferred therapy , and 252 infants were r and omly assigned to receive early therapy . After a median follow-up of 40 weeks ( interquartile range , 24 to 58 ) , antiretroviral therapy was initiated in 66 % of infants in the deferred-therapy group . Twenty infants in the deferred-therapy group ( 16 % ) died versus 10 infants in the early-therapy groups ( 4 % ) ( hazard ratio for death , 0.24 ; 95 % confidence interval [ CI ] , 0.11 to 0.51 ; P<0.001 ) . In 32 infants in the deferred-therapy group ( 26 % ) versus 16 infants in the early-therapy groups ( 6 % ) , disease progressed to Centers for Disease Control and Prevention stage C or severe stage B ( hazard ratio for disease progression , 0.25 ; 95 % CI , 0.15 to 0.41 ; P<0.001 ) . Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant ; no drugs were permanently discontinued . After a review by the data and safety monitoring board , the deferred-therapy group was modified , and infants in this group were all reassessed for initiation of antiretroviral therapy . CONCLUSIONS Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76 % and HIV progression by 75 % . ( Clinical Trials.gov number , NCT00102960 . BACKGROUND HIV contributes substantially to child mortality , but factors underlying these deaths are inadequately described . With individual data from seven r and omised mother-to-child transmission ( MTCT ) intervention trials , we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors . METHODS Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age ; and late infection by a negative PCR test at or after 4 weeks of age , followed by a positive test . Mortality rate was expressed per 1000 child-years . We investigated the effect of maternal health , infant HIV infection , feeding practice s , and age at acquisition of infection on mortality assessed with Cox proportional hazards models , and allowed for r and om effects for trials grouped geographically . FINDINGS 378 ( 11 % ) of 3468 children died . By age 1 year , an estimated 35.2 % infected and 4.9 % uninfected children will have died ; by 2 years of age , 52.5 % and 7.6 % will have died , respectively . Mortality varied by geographical region , and was associated with maternal death ( adjusted odds ratio 2.27 , 95 % CI 1.62 - 3.19 ) , CD4 + cell counts < 200 per microL ( 1.91 , 1.39 - 2.62 ) , and infant HIV infection ( 8.16 , 6.43 - 10.33 ) . Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children . In infected children , mortality was significantly lower for those with late infection than those with early infection ( 0.52 , 0.39 - 0.70 ) . This effect was also seen in analyses of survival from the age at infection ( 0.74 , 0.55 - 0.99 ) . INTERPRETATION These findings highlight the necessity for timely antiretroviral care , for support for HIV-infected women and children in developing countries , and for assessment of prophylactic programmes to prevent MTCT , including child mortality and infection averted Introduction : Few combinations of highly active antiretrovirals have been studied in nucleoside reverse transcription inhibitor (NRTI)-experienced , human immunodeficiency virus (HIV)-infected children . We tested the efficacy , tolerability and pharmacokinetics of 2 combination therapies containing an NRTI , protease inhibitors ± a nonnucleoside reverse transcription inhibitor ( NNRTI ) . Methods : This was a phase II , r and omized , multicenter study . Forty-one children and youths between 5 months and 21 years with prior NRTI and no prior NNRTI or protease inhibitor experience received either nelfinavir ( NFV ) 30 mg/kg twice daily ( bid ) , ritonavir ( RTV ) 400 mg/m2 bid and buffered didanosine ( ddI ) 240 mg/m2 daily ( arm A ) or NFV 50–55 mg/kg bid , nevirapine ( NVP ) 120 mg/m2 bid and stavudine ( d4 T ) 1 mg/kg bid ( arm B ) . Patients were evaluated clinical ly for 48 weeks after initiation of therapy . Intensive pharmacokinetic sampling occurred after 4 weeks of therapy . Results : The proportion of children with HIV-1 RNA ≤400 copies/mL and on r and omized treatment at 48 weeks was 65 % among children assigned NFV + RTV + ddI versus 28 % among those assigned NFV + NVP + d4 T ( P = 0.039 ) . No significant difference in median CD4 % change from baseline to week 48 was found ( 3 % versus 1 % ) . No significant differences in safety or tolerability between children r and omized to NFV + RTV + ddI versus NFV + NVP + d4 T were identified . However , a trend toward a higher rate of permanent discontinuation of study treatment was noted among children assigned to NFV + NVP + d4 T compared with NFV + RTV + ddI [ 7 of 20 ( 35 % ) versus 2 of 21 ( 10 % ) ; P = 0.12 ] . NFV pharmacokinetic measurements were not statistically different between the treatment groups , yet exposure to the NFV metabolite , M8 , was significantly higher in subjects receiving RTV . The pharmacokinetics for NVP , RTV and d4 T were similar to those of previously reported data . Conclusion : Combination therapy containing NFV + RTV + ddI appears more efficacious in NRTI-experienced children than a regimen containing NFV + NVP + d4 T . Differences in tolerability between the 2 treatment groups were not identified . Systemic exposure of these drugs was similar to that reported in other HIV-infected children and adults Background : Single-dose nevirapine ( sd-NVP ) is the mainstay of prevention of mother-to-child transmission programs in developing countries . Exposure to sd-NVP selects for resistance mutations , however . We longitudinally assessed these mutations in HIV-1-infected infants from Soweto and Durban , South Africa . Methods : We prospect ively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant . If HIV infected , their virus was genotyped , using the ViroSeq HIV-1 Genotyping System , to detect resistant mutations . Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit . Results : Of 53 HIV-infected infants , 24 ( 45.3 % ) had detectable resistance at their first visit , when the most frequent mutations were Y181C ( 75 % ) , K103N ( 25 % ) , and Y188C ( 12 % ) . Of those whose visit was before 12 weeks of age , 2 of 42 infants shared identical resistance mutations with their mothers . By 18 months of age , 11 of 24 infants with resistance had died and 1 still had the Y181C mutation . Conclusions : Resistant mutations were selected in half of the infants exposed to sd-NVP , but fewer were detected over time and , unlike the case in their mothers , Y181C dominated initially and persists . Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children CONTEXT Protease inhibitor (PI)-based therapy is recommended for infants infected with human immunodeficiency virus ( HIV ) who were exposed to nevirapine for prevention of mother-to-child HIV transmission . However , there are limitations of continuing PI-based therapy indefinitely and reuse of nevirapine has many advantages . OBJECTIVE To test whether nevirapine-exposed infants who initially achieve viral suppression with PI-based therapy can maintain viral suppression when switched to nevirapine-based therapy . DESIGN , SETTING , AND PATIENTS R and omized trial conducted between April 2005 and May 2009 at a hospital in Johannesburg , South Africa , among 195 children who achieved viral suppression less than 400 copies/mL for 3 or more months from a cohort of 323 nevirapine-exposed children who initiated PI-based therapy before 24 months of age . INTERVENTIONS Control group children continued to receive ritonavir-boosted lopinavir , stavudine , and lamivudine ( n = 99 ) . Switch group children substituted nevirapine for ritonavir-boosted lopinavir ( n = 96 ) . MAIN OUTCOME MEASURES Children were followed up for 52 weeks after r and omization . Plasma HIV-1 RNA of greater than 50 copies/mL was the primary end point . Confirmed viremia greater than 1000 copies/mL was used as a criterion to consider regimen changes for children in either group ( safety end point ) . RESULTS Plasma viremia greater than 50 copies/mL occurred less frequently in the switch group ( Kaplan-Meier probability , 0.438 ; 95 % CI , 0.334 - 0.537 ) than in the control group ( 0.576 ; 95 % CI , 0.470 - 0.668 ) ( P = .02 ) . Confirmed viremia greater than 1000 copies/mL occurred more frequently in the switch group ( 0.201 ; 95 % CI , 0.125 - 0.289 ) than in the control group ( 0.022 ; 95 % CI , 0.004 - 0.069 ) ( P < .001 ) . CD4 cell response was better in the switch group ( median CD4 percentage at 52 weeks , 34.7 ) vs the control group ( CD4 percentage , 31.3 ) ( P = .004 ) . Older age ( relative hazard [ RH ] , 1.71 ; 95 % CI , 1.08 - 2.72 ) was associated with viremia greater than 50 copies/mL in the control group . Inadequate adherence ( RH , 4.14 ; 95 % CI , 1.18 - 14.57 ) and drug resistance ( RH , 4.04 ; 95 % CI , 1.40 - 11.65 ) before treatment were associated with confirmed viremia greater than 1000 copies/mL in the switch group . CONCLUSION Among HIV-infected children previously exposed to nevirapine , switching to nevirapine-based therapy after achieving viral suppression with a ritonavir-boosted lopinavir regimen result ed in lower rates of viremia greater than 50 copies/mL than maintaining the primary ritonavir-boosted lopinavir regimen . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00117728 BACKGROUND Fixed-dose combination scored dispersible stavudine , lamivudine , and nevirapine minitablets ( Triomune Baby and Junior ; Cipla Ltd ) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus-infected children . However , they can not be used for dose escalation ( DE ) of nevirapine . METHODS Children were r and omized to initiate antiretroviral therapy with full-dose ( FD ) nevirapine ( Triomune Baby or Junior in the morning and evening ) versus DE ( half-dose nevirapine for 14 days [ Triomune in the morning and stavudine-lamivudine { Lamivir-S } in the evening ] , then FD ) , in accordance with World Health Organization weight-b and dosing tables . The primary end point was nevirapine-related clinical or laboratory grade 3 or 4 adverse events ( AEs ) . RESULTS In total , 211 children ( median [ interquartile range { IQR } ] age , 5 [ 2 - 9 ] years ; median [ IQR ] CD4 cell percentage , 13 % [ 8%-18 % ] ) were enrolled and followed up for a median ( IQR ) of 92 ( 68 - 116 ) weeks . There were 31 grade 3 or 4 AEs that were definitely/probably or uncertainly related to nevirapine in the FD group ( 18.0 per 100 child-years ) , compared with 29 in the DE group ( 16.5 per 100 child-years ) ( incidence rate ratio , 1.09 ; 95 % confidence interval , 0.63–1.87 ; P = .74 ) . All were asymptomatic ; 11 versus 3 were single grade 3 or 4 elevations in alanine aminotransferase ( ALT ) or aspartate aminotransferase ( AST ) levels , all of which resolved without a change in nevirapine dose or interruption . Thirteen ( 12 % ) FD versus 2 ( 2 % ) DE children had grade 1 ( 2 in FD ) or grade 2 ( 11 in FD and 2 in DE ) rashes . Three ( 2 in FD and 1 in DE ) substituted efavirenz , 3 ( FD ) continued FD nevirapine , and 9 ( 8 in FD and 1 in DE ) temporarily interrupted nevirapine , followed by successful DE . Predictors of nevirapine rash were older age ( P = .003 ) and higher CD4 cell count for age ( P = .03 ) . Twenty-two children died ( 12 in FD and 10 in DE ) , 1 FD and 5 DE children at < 4 weeks ; none were considered to be drug related by independent review . CONCLUSIONS Rash was more frequent with FD nevirapine , but 88 % had no clinical toxicity ; elevated AST or ALT levels were transient and resolved spontaneously , suggesting that routine laboratory monitoring has limited value . Dual pediatric stavudine-lamivudine minitablets are preferred for safe and simple DE ; if unavailable , initiating FD Triomune requires timely review for rash , which could be managed by temporary reduction to half-dose Triomune or efavirenz substitution . TRIAL REGISTRATION Current Controlled Trials identifier : IS RCT N31084535 BACKGROUND Depletion of CD4 T-cell counts or progression of human immunodeficiency virus ( HIV ) disease occurs rapidly in children , but few data address the efficacy of aggressive therapy for HIV-infected children . METHODS We evaluated the safety , tolerability , and activity of three regimens of antiretroviral therapy in a multicenter , open-label , phase 1 - 2 trial . Children infected with HIV type 1 ( HIV-1 ) were stratified at entry according to age -- three months or younger ( early therapy ) or older than three months ( delayed therapy)-- and assigned sequentially to one of three regimens . Children continued to receive treatment for up to 200 weeks if the plasma HIV-1 RNA level was less than 1000 copies per milliliter by 16 weeks . RESULTS Plasma HIV-1 RNA levels fell from a median of 5.3 log copies per milliliter ( range , 3.3 to 6.4 log copies per milliliter ) at baseline to less than 1000 copies per milliliter at 16 weeks in 32 of 52 infants ( 62 percent ) . Plasma HIV-1 RNA levels were below 400 copies per milliliter at 48 weeks in 26 infants ( 50 percent ) and at 200 weeks in 23 infants ( 44 percent ) . An intention-to-treat analysis revealed that significantly more children who received stavudine , lamivudine , nevirapine , and nelfinavir had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 48 weeks ( 83 percent ) and 200 weeks ( 72 percent ) than children who received reverse-transcriptase inhibitors alone ( P=0.001 and P=0.01 , respectively ) . Fewer infants in the delayed-therapy group than in the early-therapy group ( 30 percent vs. 60 percent ) had plasma HIV-1 RNA levels of less than 400 copies per milliliter at 200 weeks ( P=0.03 ) . Treatment-associated adverse effects were infrequent . CONCLUSIONS In this phase 1 - 2 trial involving HIV-1-infected children , an age of three months or younger at the initiation of therapy and treatment with stavudine , lamivudine , nevirapine , and nelfinavir were associated with improved long-term viral suppression . Larger , r and omized trials are required to define the optimal time to initiate therapy and the optimal regimen for these infants BACKGROUND Combination therapy including protease inhibitors has been shown to be effective in treating adults infected with human immunodeficiency virus type 1 ( HIV-1 ) , but there are only limited data regarding the treatment of children and adolescents . METHODS A cohort of 1028 HIV-1-infected children and adolescents , from birth through 20 years of age , who were enrolled in research clinics in the United States before 1996 was followed prospect ively through 1999 . We used proportional-hazards regression models to estimate the effect on mortality of combination therapy including protease inhibitors . RESULTS Seven percent of the subjects were receiving combination therapy including protease inhibitors in 1996 ; by 1999 , 73 percent were receiving such therapy . In univariate analyses , a higher base-line percentage of lymphocytes that were CD4-positive , a higher weight for age , a higher height for age , black race , Hispanic ethnic background , younger age , and perinatally acquired infection were associated with a longer median time to the initiation of this type of therapy ( P<0.001 ) . After adjustment for covariates , the differences among racial and ethnic groups in the time to initiation were not statistically significant . Mortality declined from 5.3 percent in 1996 to 2.1 percent in 1997 , 0.9 percent in 1998 , and 0.7 percent in 1999 ( P for trend < 0.001 ) . There were reductions in mortality in all subgroups defined according to age , sex , percentage of CD4 + lymphocytes , educational level of the parent or guardian , and race or ethnic background . In adjusted analyses , the initiation of combination therapy including protease inhibitors was independently associated with reduced mortality ( hazard ratio for death , 0.33 ; 95 percent confidence interval , 0.19 to 0.58 ; P<0.001 ) . CONCLUSIONS The use of combination therapy including protease inhibitors has markedly reduced mortality among children and adolescents infected with HIV-1 The relative potency and tolerability of multidrug regimens used to treat infants and children infected with human immunodeficiency virus type 1 ( HIV-1 ) are largely unknown . In Pediatric AIDS Clinical Trials Group ( PACTG ) Protocol 377 , 181 infants and children were assigned to receive stavudine ( d4 T ) plus nevirapine ( NVP ) and ritonavir ( RTV ) ; d4 T plus lamivudine ( 3TC ) and nelfinavir ( NFV ) ; d4 T plus NVP and NFV ; or d4 T plus 3TC , NVP , and NFV . Eleven additional children received d4 T and NVP plus NFV given twice daily . All subjects had not previously received protease inhibitors or nonnucleoside reverse-transcriptase inhibitors and all had been immunologically stable while receiving reverse-transcriptase inhibitor therapy . After 48 weeks of therapy , 17 ( 41 % ) of 41 subjects receiving d4T-NVP-RTV , 13 ( 30 % ) of 44 receiving d4T-NVP-NFV , 21 ( 42 % ) of 50 receiving d4T-3TC and NFV ( 3 times daily ) , and 22 ( 52 % ) of 42 receiving d4T-3TC-NVP-NFV were still receiving their assigned therapy and had HIV-1 RNA suppression to < /= 400 copies/mL. These regimens were similar in their drug activity , but the 4-drug regimen offered slightly more durable suppression of viremia BACKGROUND The extent to which drug-resistant human immunodeficiency virus type 1 ( HIV-1 ) acquired through mother-to-child transmission ( MTCT ) or failed chemoprophylaxis populates viral reservoirs and limits responses to antiretroviral treatment in infants is unknown . METHODS We evaluated the presence , type , and persistence of drug-resistant HIV-1 in pretreatment plasma and resting CD4(+ ) T cells from US infants enrolled in a multicenter , open-label , phase 1/2 treatment trial of lopinavir/ritonavir ( Pediatric AIDS Clinical Trials Group Protocol 1030 ) in young infants . RESULTS Twenty-two consecutively enrolled infants initiating highly active antiretroviral therapy at a median age of 9.7 weeks and treated for up to 96 weeks were studied . Drug-resistant HIV-1 was present in 5 ( 23.8 % ) of 21 infants analyzed ; 4 ( 80.0 % ) had nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 , only 1 of whom had a history of receiving nevirapine chemoprophylaxis . All 4 infants had NNRTI-resistant variants other than the K103N mutation . The fifth infant had the M184V mutation . Drug-resistant virus was archived in the resting CD4(+ ) T cell latent reservoir in all 5 infants . CONCLUSIONS The high rate , types , and early archiving of drug-resistant HIV-1 suggests that resistance testing be considered for infants , especially when an NNRTI-based regimen is planned . Furthermore , drug-resistance outcomes in infants should be an important secondary end point in MTCT trials Objective : To describe the prevalence of HIV-1 drug resistance mutations at the time of treatment initiation in a large cohort of HIV-infected children previously exposed to single-dose nevirapine ( sdNVP ) for prevention of transmission . Design : Drug resistance mutations were measured pretreatment in 255 infants and young children under 2 years of age in South Africa exposed to sdNVP and initiating ritonavir-boosted lopinavir-based therapy . Those who achieved viral suppression were r and omized to either continue the primary regimen or to switch to a nevirapine-based regimen . Pretreatment sample s were tested using population sequencing and real time allele-specific PCR ( AS-PCR ) to detect Y181C and K103N minority variants . Those with confirmed viremia more than 1000 copies/ml by 52 weeks postr and omization in the switch group were defined as having viral failure . Results : Nonnucleoside reverse transcriptase inhibitor ( NNRTI ) mutations , predominantly Y181C , were detected by either method in 62 % of infants less than 6 months of age , in 39 % of children 6–12 months of age , 22 % 12–18 months , and 16 % 18–24 months ( P = < 0.0001 ) . NNRTI mutations detected by genotyping , but not K103N or Y181C mutations detected only by AS-PCR , were associated with viral failure in the switch group . Conclusion : The prevalence of mutations known to compromise primary NNRTI-based therapy is high in sdNVP-exposed children , supporting current guidelines recommending use of protease inhibitor-based regimens for young children . St and ard genotyping is adequate to identify children who could benefit from switching to NNRTI-based therapy BACKGROUND Children with HIV will be on antiretroviral therapy ( ART ) longer than adults , and therefore the durability of first-line ART and timing of switch to second-line are key questions . We assess the long-term outcome of protease inhibitor and non-nucleoside reverse transcriptase inhibitor ( NNRTI ) first-line ART and viral load switch criteria in children . METHODS In a r and omised open-label factorial trial , we compared effectiveness of two nucleoside reverse transcriptase inhibitors ( NRTIs ) plus a protease inhibitor versus two NRTIs plus an NNRTI and of switch to second-line ART at a viral load of 1000 copies per mL versus 30,000 copies per mL in previously untreated children infected with HIV from Europe and North and South America . R and om assignment was by computer-generated sequentially numbered lists stratified by age , region , and by exposure to perinatal ART . Primary outcome was change in viral load between baseline and 4 years . Analysis was by intention to treat , which we defined as all patients that started treatment . This study is registered with IS RCT N , number IS RCT N73318385 . FINDINGS Between Sept 25 , 2002 , and Sept 7 , 2005 , 266 children ( median age 6.5 years ; IQR 2.8 - 12.9 ) were r and omly assigned treatment regimens : 66 to receive protease inhibitor and switch to second-line at 1000 copies per mL ( PI-low ) , 65 protease inhibitor and switch at 30,000 copies per mL ( PI-higher ) , 68 NNRTI and switch at 1000 copies per mL ( NNRTI-low ) , and 67 NNRTI and switch at 30,000 copies per mL ( NNRTI-higher ) . Median follow-up was 5.0 years ( IQR 4.2 - 6.0 ) and 188 ( 71 % ) children were on first-line ART at trial end . At 4 years , mean reductions in viral load were -3.16 log(10 ) copies per mL for protease inhibitors versus -3.31 log(10 ) copies per mL for NNRTIs ( difference -0.15 log(10 ) copies per mL , 95 % CI -0.41 to 0.11 ; p=0.26 ) , and -3.26 log(10 ) copies per mL for switching at the low versus -3.20 log(10 ) copies per mL for switching at the higher threshold ( difference 0.06 log(10 ) copies per mL , 95 % CI -0.20 to 0.32 ; p=0.56 ) . Protease inhibitor resistance was uncommon and there was no increase in NRTI resistance in the PI-higher compared with the PI-low group . NNRTI resistance was selected early , and about 10 % more children accumulated NRTI mutations in the NNRTI-higher than the NNRTI-low group . Nine children had new CDC stage-C events and 60 had grade 3/4 adverse events ; both were balanced across r and omised groups . INTERPRETATION Good long-term outcomes were achieved with all treatments strategies . Delayed switching of protease-inhibitor-based ART might be reasonable where future drug options are limited , because the risk of selecting for NRTI and protease-inhibitor resistance is low . FUNDING Paediatric European Network for Treatment of AIDS ( PENTA ) and Pediatric AIDS Clinical Trials Group ( PACTG/IMPAACT ) One hundred eighty-one antiretroviral-experienced , protease inhibitor-naive , clinical ly stable HIV-infected children between 4 months and 17 years of age were r and omly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA , safety , and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen . All four regimens contained stavudine ; in addition children received nevirapine plus ritonavir , lamivudine plus nelfinavir , nevirapine plus nelfinavir , or lamivudine plus nevirapine plus nelfinavir . Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir , with nelfinavir given bid , rather than tid as for the main regimens . Overall , 51 % ( 89/176 ; 95 % CI 43 - 58 % ) of the children on the r and omized portion of the study had an HIV RNA response ( < or = 400 copies/ml ) on at least two of the three HIV RNA determinations taken at Weeks 8 , 12 , and 16 . At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47 % ( 83/176 ; 95 % CI 40 - 55 % ) and ranged from 41 to 61 % for the four r and omized treatment arms . Rash was frequently seen ( 27 % ) on the treatment arms containing nevirapine . At Week 24 64 % ( 7/11 , 95 % CI 31 - 89 % ) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46 % ( 23/50 ; 95 % CI 32 - 61 % ) on the corresponding tid nelfinavir combination regimen . A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50 % for this patient population We evaluated the validity of CD4 count against CD4 % criteria of 2008 World Health Organization guideline for initiating antiretroviral therapy using the data of 446 human immunodeficiency virus-infected Asian children aged 1 to 12 years who were screened to the Pediatric R and omized of Early versus Deferred Initiation in Cambodia and Thail and study . The overall sensitivity and specificity were 34 % and 98 % , respectively . Using the current CD4 count criteria would globally result in 66 % missed opportunity to initiate treatment in a timely fashion . Raising CD4 count thresholds should be considered to increase its sensitivity and reduce missed opportunity |
2,498 | 23,450,568 | MAIN RESULTS Six RCTs ( 434 participants ) appraised four types of chest physiotherapy ( conventional chest physiotherapy ; osteopathic manipulative treatment ( which includes paraspinal inhibition , rib raising and myofascial release ) ; active cycle of breathing techniques ( which include active breathing control , thoracic expansion exercises and forced expiration techniques ) ; and positive expiratory pressure).None of the physiotherapies ( versus no physiotherapy or placebo ) improved mortality rates of adults with pneumonia .
Conventional chest physiotherapy ( versus no physiotherapy ) , active cycle of breathing techniques ( versus no physiotherapy ) and osteopathic manipulative treatment ( versus placebo ) did not increase the cure rate or chest X-ray improvement rate .
Based on current limited evidence , chest physiotherapy might not be recommended as routine additional treatment for pneumonia in adults | BACKGROUND Despite conflicting evidence , chest physiotherapy has been widely used as an adjunctive treatment for adults with pneumonia .
OBJECTIVES To assess the effectiveness and safety of chest physiotherapy for pneumonia in adults . | Expectoration of mucus is important in preventing the development of airway inflammation in patients with diffuse panbronchiolitis ( DPB ) . To evaluate the clinical efficacy of the FLUTTER device in clearing mucus from the airways of patients with DPB who have difficulty expectorating , we assessed pulmonary function and symptoms in patients treated with FLUTTER . Eight patients in a stable clinical condition with DPB were included in the study . The study was divided into two consecutive , 1-week periods . The initial week was an observation week . During the following week , patients used FLUTTER four times daily . Expectorated sputum was collected in a container and weighed every day during 2 weeks . Pulmonary function , partial oxygen pressure and partial carbon dioxide pressure in arterial blood were measured in all patients on the last day of the observation week and the FLUTTER treatment week . A symptom score for difficulty of expectoration was determined by question naire . A pneumothorax developed in one patient during using FLUTTER . The mean daily sputum weight and peak expiratory flow rate increased significantly after treatment with FLUTTER ( P < 0.04 and P < 0.02 , respectively ) . Symptom score improved significantly after using FLUTTER ( P < 0.02 ) . We conclude that the use of FLUTTER is effective in clearing mucus from the airways . However , the development of a pneumothorax may complicate use of the procedure in some cases Pneumonia in elderly patients is a major public health concern because of greater morbidity and mortality and longer hospital stays relative to younger population s. Based on the premise that osteopathic manipulative treatment ( OMT ) is beneficial in the management of pulmonary infections , the Multicenter Osteopathic Pneumonia Study in the Elderly ( MOPSE ) was design ed as a prospect i ve r and omized controlled trial to evaluate the efficacy of OMT as an adjunct to the current pharmacologic treatment of elderly patients hospitalized for pneumonia . The protocol developed for MOPSE has its origins in early osteopathic medical literature at a time when effective antibiotic therapy was unavailable and osteopathic physicians relied on physical examination and empiric reasoning to develop treatment strategies and OMT techniques to improve host defenses against pneumonia . The present paper review s the early osteopathic medical literature to identify the reasoning behind the OMT techniques that are the basis for the design of the MOPSE protocol . Likewise , the contemporary medical literature relevant to the protocol is review ed . Finally , a description of the study design and the OMT and light touch ( sham ) protocol s used in MOPSE are provided Ventilator-associated pneumonia results from bacterial colonisation of the aerodigestive tract or aspiration of contaminated secretions into the lower airways . As a consequence of infection of the lung parenchyma and alveolitis , accumulation of inflammatory exu date s and infiltration of airway mucosa can lead to unfavourable respiratory mechanics in ventilator-associated pneumonia . Tracheal suction is often employed by nursing staff in the management of mechanically ventilated patients with ventilator-associated pneumonia but this technique has the potential to increase respiratory resistance . Manual hyperinflation is used by physiotherapists to improve lung volume and mobilise secretions and has been shown to increase lung compliance . The effect of manual hyperinflation on airway resistance has not been studied . This study aims to demonstrate an additional mechanical benefit to the respiratory system when manual hyperinflation and suction techniques are combined , by comparing the application of manual hyperinflation and suction with suction alone on static lung compliance ( C(L ) ) and inspiratory resistance ( R(AW ) ) in mechanically ventilated patients with ventilator-associated pneumonia . Fifteen adult patients with ventilator-associated pneumonia were recruited and acted as their own controls . Manual hyperinflation followed by suction ( manual hyperinflation plus suction ) and suction alone were applied consecutively , in r and om order , on two occasions , four hours apart . Respiratory variables , C(L ) and R(AW ) , were measured five times and the averaged value documented . Data were recorded before , immediately after , and 30 minutes after each intervention protocol . C(L ) increased by 22 % and R(AW ) decreased by 21 % , up to 30 minutes after manual hyperinflation plus suction , but not after suction alone . This study suggests that manual hyperinflation in conjunction with suction induces beneficial changes in respiratory mechanics in mechanically ventilated patients with ventilator-associated pneumonia While osteopathic manipulative treatment ( OMT ) is thought to be beneficial for patients with pneumonia , there have been few clinical trials -- especially in the elderly . The authors ' pilot study suggested that duration of intravenous antibiotic use and length of hospital stay were promising measures of outcome . Therefore , a larger r and omized controlled study was conducted . Elderly patients hospitalized with acute pneumonia were recruited and r and omly placed into two groups : 28 in the treatment group and 30 in the control group . The treatment group received a st and ardized OMT protocol , while the control group received a light touch protocol . There was no statistical difference between groups for age , sex , or simplified acute physiology scores . The treatment group had a significantly shorter duration of intravenous antibiotic treatment and a shorter hospital stay To evaluate the benefit of osteopathic manipulative treatment in the elderly with pneumonia , the authors recruited 21 individuals older than 60 years who were hospitalized with acute pneumonia . Eleven patients were r and omly assigned to the treatment group and ten to the control group . The treatment group received specific osteopathic manipulative treatment for somatic dysfunction and a st and ardized treatment protocol . Both groups received conventional therapy , and the attending physician was blind to group assignments . No significant difference existed between groups for age , sex , or severity of illness . Although the mean duration of leukocytosis , intravenous antibiotic treatment , and length of stay were shorter for the treatment group , these measures did not reach statistical significance . However , the mean duration of oral antibiotic use did reach statistical significance at 3.1 days for the treatment group and 0.8 day for the control group . Osteopathic manipulative treatment may reduce antibiotic use and length of stay ; however , a larger study is needed to clarify this outcome A study was carried out to determine whether bottle-blowing has any positive effects in patients with pneumonia . In a prospect i ve open study 145 adults with untreated community-acquired pneumonia requiring hospitalization were r and omized to early mobilization ( group A ) , to sit up and take 20 deep breaths on 10 occasions daily ( group B ) , or to sit up and to blow bubbles in a bottle containing 10 cm water through a plastic tube 20 times on 10 occasions daily ( group C ) . Peak expiratory flow ( PEF ) , vital capacity ( VC ) , forced expiratory volume in 1 sec ( FEV1 ) and serum concentration of C-reactive protein ( CRP ) were determined on admission , and on days 4 and 42 . Fever duration and hospital stay were recorded . In a subset of 16 patients , single breath diffusion capacity of carbon monoxide was measured on 3 occasions . The patients in group A were hospitalized for a mean of 5.3 days , group B for 4.6 days and group C for 3.9 days . Treatment was a significant factor ( p = 0.037 ) in a Cox regression model , with group C significantly better than group A ( p = 0.01 ) . The number of days with fever was 2.3 , 1.7 and 1.6 in groups A , B and C respectively . These differences were not significant ( p = 0.28 ) . No significant differences were found between the groups regarding CRP , PEF , VC , FEV1 , or diffusion capacity . Intensive bottle-blowing shortens the hospital stay in patients with pneumonia . The underlying mechanism is not clear Abstract Objective : To explore three aspects of non-invasive pressure support ventilation ( NIPSV ) applied by face mask to patients with acute respiratory failure ( ARF ) due to severe community-acquired pneumonia ( CAP ) : ( 1 ) the initial acute effects on respiratory rate , gas exchange and hemodynamics , ( 2 ) the clinical course and outcome during ICU and hospital stay , ( 3 ) the nursing workload as measured by the daily PRN 87 ( Project Research in Nursing ) score . Setting : Medical ICU , University Hospital . Design : Prospect i ve , observational study . Patients : Patients without any prior history of chronic lung disease , consecutively admitted to the ICU to receive NIPSV for ARF due to severe CAP . Measurements and results ( means ± SD ) : Twenty-four patients aged 49±17 years , admission APACHE II 13±5 , were included . Admission PaO2/FIO2 , alveolar-arterial oxygen difference ( DA-aO2 ) and PaCO2 were 104±48 , 447±120 and 40±10 mmHg , respectively . All patients were normotensive . During the initial NIPSV trial respiratory rate decreased from 34±8 to 28±10 breaths/min ( p<0.001 ) and arterial oxygenation improved ( PaO2/FIO2 104±48 vs 153±49 , DA-aO2 447±120 vs 370±180 mmHg , p<0.001 ) while PaCO2 remained unchanged . There were no hemodynamic effects . Subsequently , a total of 133 NIPSV trials were performed ( median duration 55 min , range 30–540 min ) over 1–7 days . No complication occurred during NIPSV . Sixteen patients were intubated ( 66 % ) 1.3±1 days after inclusion . Upon inclusion , the patients who were subsequently intubated were older ( 55±15 vs 37±12 years ) and more severely hypoxemic ( 63±11 vs 80±15 mmHg , p<0.05 ) than those not requiring intubation . Eight patients died ( 33 % ) , all in the intubated group . Median lengths of stay in the ICU and hospital were longer in intubated patients ( ICU 16 days , range 3–64 vs 6 days , range 3–7 , p<0.05 ; hospital 23 days , range 9–77 vs 9.5 days , range 4–42 , p<0.05 ) . Mean daily total PRN points were stable throughout the NIPSV period and were not different between the groups . Only 14 % of PRN points result ed from respiratory therapy interventions . PRN score was higher during the first 24 h following intubation than during the first 24 h of NIPSV ( 278±55 vs 228±24 points , p<0.05 ) . Conclusion : Despite initial improvement in arterial oxygenation with NIPSV in patients with ARF due to severe CAP , the intubation rate is high . However , the more favorable outcome and shorter ICU and hospital stays when intubation is avoided , as well as the short delay required to assess the success or failure of NIPSV warrants a trial of NIPSV in this setting . The nursing workload remains stable during NIPSV and does not result predominantly from respiratory therapy interventions Objective To investigate the effect of respiratory physiotherapy on the prevention and treatment of ventilator-associated pneumonia ( VAP ) for adults in an intensive care unit ( ICU ) with an acquired brain injury ( ABI ) . Design and setting Two-part , prospect i ve , r and omised controlled trial . Patients A total of 144 subjects with ABI admitted with a Glasgow Coma Scale ≤9 , requiring intracranial pressure monitoring , and invasive mechanical ventilation ( MV ) for > 24 h ; 33 subjects were subsequently diagnosed with VAP.InterventionRespiratory physiotherapy comprised six treatments ( positioning , manual hyperinflation and suctioning ) in each 24-h period whilst on MV . The Control Group received st and ard medical/nursing care but no respiratory physiotherapy . Measurements and results There were no significant differences between groups for incidence of VAP , duration of MV , length of ICU stay or clinical variables such as requirement for re-ventilation . Conclusions In adults with ABI , regular respiratory physiotherapy in addition to routine medical/nursing care does not appear to prevent VAP , reduce length of MV or ICU stay . Due to small numbers , it is not possible to draw any conclusions as to whether or not respiratory physiotherapy hastens recovery from VAP Abstract Objective . Pneumonia is an important complication in patients who are intubated and mechanically ventilated , when it is commonly referred to as ventilator-associated pneumonia ( VAP ) . Since VAP may be contributed to by impaired sputum clearance , we studied whether chest physiotherapy design ed to enhance sputum clearance decreases the occurrence of VAP . Design . Prospect i ve controlled systematic allocation trial . Setting . Tertiary teaching hospital ICU . Patients and participants . Sixty adult patients intubated and mechanically ventilated for at least 48 h. Interventions . Chest physiotherapy ( intervention group ) or sham physiotherapy ( control group ) . Measurements and results . Control and intervention groups were well matched for age , sex , and admission PaO2/FiO2 ratio , APACHE II score , and Glasgow Coma Score . There were no differences in the duration of mechanical ventilation , length of stay in ICU or mortality . VAP was assessed daily by combined clinical assessment and the clinical pulmonary infection score ( CPIS ) . VAP occurred in 39 % ( 14/36 ) of the control group and 8 % ( 2/24 ) of the intervention group ( OR=0.14 , 95 % CI 0.03 to 0.56 , P=0.02 ) . After adjustment was made by logistic regression for other important variables ( APACHE II score , duration of mechanical ventilation , presence of tracheostomy , and GCS score ) , chest physiotherapy was independently associated with a reduced occurrence of VAP ( adjusted OR=0.16 , 95 % CI 0.03 to 0.94 , P=0.02 ) . Conclusions . In this small trial , chest physiotherapy in ventilated patients was independently associated with a reduction in VAP . This suggested benefit of physiotherapy in prevention of VAP requires confirmation with a larger r and omised controlled trial We undertook a r and omized clinical trial to evaluate the efficacy of chest physiotherapy and intermittent positive-pressure breathing in the treatment of pneumonia . The diagnosis of pneumonia required a compatible clinical history and x-ray confirmation . A total of 54 patients were assigned to treatment and control groups and were similar in age , smoking history , underlying lung disease and prior antibiotic treatment . Antibiotic therapy , guided by Gram stain and sputum and blood cultures , was similar in both groups . Chest physiotherapy , consisting of postural drainage , percussion and vibration , was given concurrently with intermittent positive-pressure breathing with use of racemic epinephrine every four hours . There was no statistically significant difference in duration of fever , extent of radiographic clearing , duration of hospital stay and mortality between the control and treated groups . Chest physiotherapy and intermittent positive-pressure breathing do not hasten the resolution of pneumonia PURPOSE Our purpose was to determine which clinical features predict short-term mortality in patients with community-acquired pneumonia . PATIENTS AND METHODS We conducted a prospect i ve multicenter study of 347 patients hospitalized in Pittsburgh ( the derivation cohort ) and 253 hospitalized and ambulatory patients in Boston ( the validation cohort ) with clinical and radiographic evidence of pneumonia . Patients in the derivation cohort underwent an extensive microbiologic evaluation including bacteriologic sputum culture , blood cultures , direct fluorescent antibody testing for Legionella species , and serologic testing for Mycoplasma pneumoniae , Legionella species , and Chlamydia TWAR . RESULTS The overall mortality was 18 % in the derivation cohort and 13.2 % in the validation cohort . We identified five independent predictors of mortality in the derivation cohort : pleuritic chest pain ( risk ratio , 0.4 ; 95 % confidence interval [ CI ] , 0.17 to 0.99 ) , mental status changes ( risk ratio , 2.6 ; 95 % CI , 1.4 to 4.6 ) , a severe vital sign abnormality ( risk ratio , 2.1 ; 95 % CI 1.2 to 3.6 ) , neoplastic disease ( risk ratio , 5.0 ; 95 % CI , 2.7 to 9.1 ) , and " high-risk " pneumonia etiology ( risk ratio , 2.8 ; 95 % CI , 1.6 to 5.0 ) . A mortality index based on these factors accurately classified patients into five risk classes of increasing mortality . In the derivation cohort , the 6-week mortality rates were 0 % in class I , 2.9 % in class II , 13.1 % in class III , 32.7 % in class IV , and 89.5 % in class V. There was little deterioration in the predictive accuracy of the model when tested in the validation cohort : mortality was 2.2 % in class I , 0 % in class II , 13.5 % in class III , 33.3 % in class IV , and 55.6 % in class V. CONCLUSIONS This prognostic classification may help direct triage decisions , assess appropriateness of care , and guide the design and analysis of therapeutic trials in patients with community-acquired pneumonia OBJECTIVES To determine the mechanism responsible for the increase in oxygen consumption ( VO2 ) during chest physical therapy . Specifically , to examine the hypothesis that muscular activity is the major contributor to the increase in oxygen dem and . DESIGN Prospect i ve , observational study . SETTING University hospital surgical intensive care unit . PATIENTS Phase one included 13 patients who were mechanically ventilated after coronary artery bypass surgery . Phase two involved seven mechanically ventilated patients who had undergone major vascular or abdominal surgery . INTERVENTIONS Phase one involved turning patients to the lateral decubitus position . During the second phase , patients were given midazolam ( 0.15 microg/kg ) 2 mins before an initial chest physiotherapy session and midazolam plus vecuronium ( 0.7 mg/kg ) before a subsequent session . Physiologic measurements were made during the resting periods before and following each session , as well as at the completion of the intervention . MEASUREMENTS AND MAIN RESULTS Turning patients to the lateral position result ed in significant increases in oxygen uptake and CO2 elimination ( VCO2 ) . VO2 increased from 219 + /- 21 ( SD ) mL/min at rest to 324 + /- 58 mL/min ( p < .05 ) with turning . These increases in oxygen dem and were met by increases in both oxygen delivery ( 852 + /- 238 mL/min at rest to 1116 + /- 430 mL/min , p < .05 ) and extraction ( 0.27 + /- 0.7 at rest to 0.32 + /- 0.09 , p < .05 ) . There were associated increases in hemodynamic and respiratory variables including heart rate and systolic blood pressure . The administration of vecuronium completely suppressed the 50 % increases in VO2 and VCO2 seen without the use of a muscle relaxant . The increases in systolic blood pressure were unaffected by vecuronium . The magnitude of the increase in PaCO2 ( 32 + /- 5 torr [ 4.3 + /- 0.7 kPa ] at rest to 36 + /- 5 torr [ 4.8 + /- 0.7 kPa ] during therapy , p < .05 ) , was not accentuated by vecuronium ( 30 + /- 4 torr [ 4.0 + /- 0.5 kPa ] to 35 + /- 6 torr [ 4.7 + /- 0.8 kPa ] , p < .05 ) despite a lack of any increase in minute ventilation or respiratory rate . This change was due to the parallel suppression of VCO2 . CONCLUSIONS The increase in metabolic dem and during chest physiotherapy is the result of increased muscular activity as evidence d by the suppression of VO2 following the administration of the muscle relaxant and the observation that turning a patient into the lateral decubitus position produces similar increases in VO2 . The increases in blood pressure and cardiac output are due to another mechanism , most likely enhanced sympathetic output . The increase in physiologic activity produced by chest physiotherapy is thus secondary to both exercise-like and stress-like responses One hundred and seventy one patients with primary pneumonia entered a single blind , placebo controlled trial of physiotherapy . Treatment was allocated at r and om , physiotherapy consisting of postural drainage , external help with breathing , percussion , and vibration and the controls receiving advice on expectoration , deep breathing , and how to exercise to avoid thrombosis . Principles of pharmaceutical management were the same in the two groups . There was no objective evidence that daily physiotherapy helped during the acute phase of the disease . On the contrary , in younger patients , smokers , and patients with interstitial pneumonia physiotherapy appeared to prolong the duration of fever as well as the hospital stay . It is concluded that chest physiotherapy is at best useless in patients with primary infectious pneumonia |
2,499 | 23,235,680 | Providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking has a small but important effect .
A subgroup analysis of a small number of trials suggests the benefit could be a little greater when the contrast is between a no contact control and a behavioural intervention that provides at least four sessions of contact .
Subgroup analysis also suggests that there may be a smaller incremental benefit from providing even more intensive support via more or longer sessions over and above some personal contact | BACKGROUND Effective pharmacotherapies are available to help people who are trying to stop smoking , but quitting can still be difficult and providing higher levels of behavioural support may increase success rates further .
OBJECTIVES To evaluate the effect of increasing the intensity of behavioural support for people using smoking cessation medications , and to assess whether there are different effects depending on the type of pharmacotherapy , or the amount of support in each condition . | Tobacco use is the single most important preventable cause of death in military personnel . The purpose of this r and omized clinical trial was to evaluate the effectiveness of two behavioral interventions when added to nicotine-replacement therapy on smoking cessation . The sample of 512 included 52 % active duty military , 29 % family , 11 % retirees , and 8 % Department of Defense civilians . There was a main effect of compliance at the end of the program ( EOP ) ; 69 % of those who attended 75 % of the classes were abstinent from tobacco ; regression analysis found the more intensive program to be twice as effective at EOP and at 3 months , an outcome not continued at 6 months . The longer , more intensive V and erbilt University Medical Center program was significantly more effective at helping the civilian portion of the population ( 85 % versus 60 % in the American Cancer Society program ) but not the active duty participants Subjects ( N = 139 ) were assigned to intensive behavioral or to low-contact smoking treatment and to 2-mg nicotine gum or to placebo gum in a 2 X 2 factorial design . The 2-mg gum produced higher abstinence rates than did the placebo . Subjects receiving the low-contact condition plus the 2-mg nicotine gum had excellent abstinence rates at both 26 weeks ( 56 % abstainers ) and 52 weeks ( 50 % abstainers ) . Smokers who scored at the median on a measure of physical dependence to nicotine were more likely to benefit by nicotine gum treatment than subjects who scored either higher or lower , but this relation was nonsignificant . The results of this study are compared with an earlier nonblind trial OBJECTIVES To investigate the effects on serum lipids , plasma fibrinogen , plasma insulin , plasma C-peptide and blood glucose , of smoking cessation after 4 months . To develop a group-based smoking intervention programme in primary health care . SETTING Twenty health centres in primary health care in southern Sweden . SUBJECTS Four hundred habitual smokers ( > 10 cigarettes per day-1 , > 10 years ) , recruited by advertisement in local papers . INTERVENTION The smokers were r and omized , after stratification for age and sex , to one intervention group ( n = 200 ) and one control group ( n = 200 ) . The intervention group was offered supportive group sessions and free nicotine supplementation ( patches , chewing gum ) . MAIN OUTCOME MEASURES All participants were investigated at the start and after 4 months ( medical history , physical examination , laboratory evaluation ) . Blood sample s were drawn for determination of glucose , insulin and C-peptide , both in the fasting state and during an oral glucose tolerance test ( OGTT ) , and for measurement of lipoproteins , fibrinogen , nicotine and cotinine . RESULTS In the intervention group 98 of the subjects ( 48 % ) had quit smoking after 4 months . They were compared with the 156 subjects in the control group ( 91 % ) who were still daily smokers during the whole period . There were no significant differences in any variable between the two ( total ) experimental groups at baseline . Plasma nicotine and cotinine decreased ( P < 0.001 ) in the intervention group following smoking cessation , and weight increased by 2.7 kg . In the intervention group HDL-cholesterol increased by 11 % ( P < 0.001 ) , whereas HbA1c increased by 2 % ( P < 0.05 ) only in the control group . No changes occurred in levels of glucose , insulin , C-peptide and fibrinogen . CONCLUSION The smoking cessation programme had a success rate of almost 50 % over 4 months . Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance . A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism AIM The study aim ed to test simultaneously our underst and ing of the effects of bupropion sustained-release ( SR ) treatment on putative mediators and our underst and ing of determinants of post-quit abstinence , including withdrawal distress , cigarette craving , positive affect and subjective reactions to cigarettes smoked during a lapse . The specificity of bupropion SR effects was also tested in exploratory analyses . DESIGN Data from a r and omized , placebo-controlled clinical trial of bupropion SR were su bmi tted to mediation analyses . SETTING Center for Tobacco Research and Intervention , Madison , WI , USA . PARTICIPANTS A total of 403 adult , daily smokers without contraindications to bupropion SR use . INTERVENTION Participants were assigned r and omly to receive a 9-week course of bupropion SR or placebo pill and to receive eight brief individual counseling sessions or no counseling . MEASUREMENTS Ecological momentary assessment ratings of smoking behavior and putative mediators were collected pre- and post-quit . FINDINGS Results of structural equation and hierarchical linear models did not support the hypothesis that bupropion SR treatment improves short-term abstinence by reducing withdrawal distress or affecting the subjective effects of a lapse cigarette , but provided partial support for mediation by cigarette craving reduction and enhanced positive affect . Bupropion SR effects on point-prevalence abstinence at 1 month post-quit were also mediated partially by enhanced motivation to quit and self-efficacy . CONCLUSIONS Results provided some support for models of bupropion SR treatment and relapse and suggested that motivational processes may partially account for bupropion SR efficacy Sustained-release bupropion and nortriptyline have been shown to be effcacious in treating cigarette smoking . Psychological intervention is also recognized as efficacious . The cost and cost-effectiveness of the 2 drug therapies have not been estimated . It was hypothesized that nortriptyline would be more cost-effective than bupropion . Hypotheses were not originally proposed concerning the cost-effectiveness of psychological versus drug treatment , but the 2 were compared using exploratory analyses . This was a 3 ( bupropion versus nortriptyline versus placebo ) by 2 ( medical management alone versus medical management plus psychological intervention ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were cost and cost-effectiveness computed at week 52 . Nortriptyline cost less than bupropion . Nortriptyline was more cost-effective than bupropion ; the difference was not statistically significant . Psychological intervention cost less than the 2 drug treatments , and was more cost-effective , but not significantly so . Prospect i ve investigations of the cost and cost-effectiveness of psychological and pharmacological intervention , using adequate sample sizes , are warranted BACKGROUND Sustained-release bupropion hydrochloride and nortriptyline hydrochloride have been shown to be efficacious in the treatment of cigarette smoking . It is not known whether psychological intervention increases the efficacy of these antidepressants . This study compared both drugs with placebo . It also examined the efficacy of these 2 drugs and placebo with and without psychological intervention . METHODS This was a 2 ( medical management vs psychological intervention ) x 3 ( bupropion vs nortriptyline vs placebo ) r and omized trial . Participants were 220 cigarette smokers . Outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 36 , and 52 . RESULTS Psychological intervention produced higher 7-day point-prevalence rates of biochemically verified abstinence than did medical management alone . With the use of point-prevalence abstinence , both nortriptyline and bupropion were more efficacious than placebo . On rates of 1-year continuous abstinence , the 2 drugs did not differ from each other or from placebo . Psychological intervention did not differ from medical management alone on rates of 1-year continuous abstinence . CONCLUSIONS Both nortriptyline and bupropion are efficacious in producing abstinence in cigarette smokers . Similarly , psychological intervention produces better abstinence rates than simple medical management . Both drugs , and psychological intervention , have limited efficacy in producing sustained abstinence . The data also suggest that combined psychological intervention and antidepressant drug treatment may not be more effective than antidepressant drug treatment alone INTRODUCTION Varenicline , a first-line non-nicotine medication , has not been evaluated in Black smokers , and limited attention has been paid to pharmacotherapy adherence in smoking cessation trials . This pilot study estimated quit rates for Black smokers treated with varenicline and tested a behavioral intervention to aid varenicline adherence . METHODS Seventy-two Black smokers ( > 10 cigarettes per day ; cpd ) were r and omly assigned to adherence support ( AS ; n = 36 ) or st and ard care ( n = 36 ) . All participants received 3 months of varenicline and a single counseling session focused on making a quit plan . AS participants received 5 additional counseling sessions to encourage medication use . Outcome measures included salivary cotinine , and carbon monoxide confirmed smoking abstinence , reductions in self-reported cpd , and pill counts of varenicline adherence at Months 1 , 2 , and 3 . RESULTS Sixty-one participants ( 84.7 % ) completed follow-up at Month 3 . Participants were female ( 62.5 % ) , 46.8 years of age , and smoked 16.3 cpd . No treatment group differences were found on the smoking or adherence outcome measures ( p > .05 ) . Collapsing across treatment , varenicline adherence was adequate ( 86.1 % ) , yet despite a reduction of 12.2 ( 6.5 ) cpd from baseline to Month 3 ( p < 0.001 ) , only 23.6 % were confirmed quit at Month 3 . Participants who were quit at Month 3 had higher varenicline adherence rates ( 95.8 % ) than those who continued to smoke ( 80.8 % , p ≤ .05 ) . CONCLUSIONS Studies are needed to examine the efficacy of varenicline among Black smokers . Interventions to facilitate adherence to pharmacotherapy warrant further attention as adherence is linked to improved tobacco abstinence BACKGROUND This study tested the impact of free nicotine patches plus proactive telephone peer support to help low-income women stop smoking . METHODS A total of 214 Medicaid-eligible women smokers of childbearing age were r and omized to receive free nicotine patches through the mail or free nicotine patches through the mail plus the provision of proactive support by telephone from a woman ex-smoker for up to 3 months . Assessment s were conducted by telephone at baseline , 10 days , and 3 and 6 months after enrollment . RESULTS At the 3-month follow-up , significantly more women in the patch plus proactive telephone support condition were abstinent ( 42 % ) compared to the patch only condition ( 28 % ) ( P = 0.03 ) . Similarly , more women in the experimental condition were abstinent at both the 10-day and 3-month assessment s ( 32 v 19 % , P = 0.02 ) . However , differences were not found at the 6-month follow-up , suggesting that the addition of proactive telephone peer support enhanced short-term , but not long-term cessation . CONCLUSIONS This is the first study to demonstrate a beneficial effect for the addition of proactive telephone support as an adjunct to free nicotine replacement in a low-income population Background Telephone quit lines are accessible to many smokers and are used to engage motivated smokers to make quit attempts . Smoking cessation counselling provided via telephone can either be reactive ( i.e. primarily involving the provision of evidence -based information ) , or proactive ( i.e. primarily involving repeated , sequenced calls from and interaction with trained cessation counsellors ) . Some studies have found proactive telephone counselling more effective and this trial will investigate whether or not proactive telephone support for smoking cessation , delivered through the National Health Service ( NHS ) Smoking Helpline is more effective or cost-effective than reactive support . It will also investigate whether or not providing nicotine replacement therapy ( NRT ) , in addition to telephone counselling , has an adjunctive impact on smoking cessation rates and whether or not this is cost effective . Methods This will be a parallel group , factorial design RCT , conducted through the English national NHS Smoking Helpline which is run from headquarters in Glasgow . Participants will be smokers who call the helpline from any location in Engl and and who wish to stop smoking . If 644 participants are recruited to four equally-sized trial groups ( total sample size = 2576 ) , the trial will have 90 % power for detecting a treatment effect ( Odds Ratio ) of 1.5 for each of the two interventions : i ) proactive versus reactive support and ii ) the offer of NRT versus no offer . The primary outcome measure for the study is self-reported , prolonged abstinence from smoking for at least six months following an agreed quit date . A concurrent health economic evaluation will investigate the cost effectiveness of the two interventions when delivered via a telephone helpline . Discussion The PORTSSS trial will provide high quality evidence to determine the most appropriate kind of counselling which should be provided via the NHS Smoking Helpline and also whether or not an additional offer of cost-free NRT is effective and cost effective for smoking cessation . Trial Registration ( clinical trials.gov ) : Purpose . This study describes the design , recruitment , and baseline data of the first smoking-cessation clinical trial for African-American light smokers , Kick It at Swope II ( KIS-II ) . Design . KIS-II was a r and omized trial testing the efficacy of nicotine gum ( vs. placebo gum ) in combination with counseling ( motivational interviewing or health education ) . Setting . This study was conducted at an urban community-based clinic serving predominantly lower-income African-Americans . Subjects . African-Americans who smoked 1 to 10 cigarettes per day were eligible . Of 1933 individuals screened , 1012 ( 52 % ) were eligible and 755 ( 75 % ) were enrolled in the study . Measures . Baseline assessment included smoking history and psychometric measures . Analysis . The majority of participants were women ( 67 % ) with a mean age of 45.1 years ( SD = 10.7 ) . Participants smoked on average 7.6 cigarettes ( SD = 3.21 ) per day , had a mean exhaled carbon monoxide level of 13.9 ppm ( SD = 8.9 ) and a mean serum cotinine level of 244.2 ng/mL ( SD = 154.4 ) , and reported high levels of motivation and confidence to quit smoking . Conclusion . African-American light smokers were motivated to stop smoking and to enroll in a smoking-cessation program . Characteristics of our sample suggest African-American light smokers are an appropriate group for inclusion in smoking-cessation interventions Background : Previously , we have linked theoretically based cognitive and emotional variables to the ability of cancer patients to quit smoking . Purpose : In this study , we evaluated the impact of cognitive-behavioral therapy ( CBT ) , which addressed these theoretically derived cognitive and emotional variables linked to tobacco use in this population , for promoting smoking cessation in a sample of cancer patients and assessed longitudinal predictors of smoking cessation . Methods : Cancer patients ( N=109 ) were r and omized to either the theoretically based CBT intervention or to a general health education ( GHE ) condition , and all patients received nicotine replacement therapy . Results : Contrary to our expectation , no significant difference in 30-day point-prevalence abstinence between the CBT and GHE conditions was detected at either a 1-month ( 44.9 % vs. 47.3 % , respectively ) or 3-month ( 43.2 % vs. 39.2 % , respectively ) follow-up evaluation . Higher quit motivation and lower cons of quitting were related to smoking cessation . Conclusions : Implication s for the implementation of smoking cessation behavioral treatments in the oncologic context are discussed , as are directions for future research in this area This study is a r and omized , double-blind , placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment ( CBTD ) and of bupropion , both singularly and in combination , on smoking cessation in adult smokers . As an extension of our previous work , we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors . Participants were 524 smokers ( 47.5 % female , M ( age ) = 44.27 years ) who were r and omized to one of four 12-week treatments : ( a ) st and ard , cognitive-behavioral smoking cessation treatment ( ST ) plus bupropion ( BUP ) , ( b ) ST plus placebo ( PLAC ) , ( c ) st and ard cessation treatment combined with cognitive-behavioral treatment for depression ( CBTD ) plus BUP , and ( d ) CBTD plus PLAC . Follow-up assessment s were conducted 2 , 6 , and 12 months after treatment , and self-reported abstinence was verified biochemically . Consistent with previous studies , bupropion , in comparison with placebo , result ed in better smoking outcomes in both intensive group treatments . Adding CBTD to st and ard intensive group treatment did not result in improved smoking cessation outcomes . In addition , neither CBTD nor bupropion , either alone or in combination , was differentially effective for smokers with single-past-episode major depressive disorder ( MDD ) , recurrent MDD , or elevated depressive symptoms . However , findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample . An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials OBJECTIVE This study evaluated changes in smoking-related beliefs and behavior following a brief , culturally adapted smoking cessation intervention for Chinese and Korean smokers . METHOD From May 2002 to March 2003 , 66 smokers residing in or around southeastern Pennsylvania were r and omly assigned to a theory-based smoking cessation intervention or general health counseling . Participants completed assessment s of perceived risks of smoking , pros and cons of quitting , quitting self-efficacy , and distress at baseline and follow-up time points . Sessions were conducted in the participant 's native language ( Korean , Cantonese , or M and arin ) . Both groups received nicotine replacement therapy . RESULTS Overall , 38 % of participants reported quitting smoking at 3-month follow-up . Quit rates were higher ( 52.6 % among Chinese , 60.0 % among Korean ) in the intervention condition compared to the control condition ( 23.5 % among Chinese , 40.0 % among Korean ) at 1-month , but not 3-month , follow-up . There was a main effect of treatment condition for self-efficacy with intervention participants reporting significantly higher levels of self-efficacy compared to control participants . Further , a treatment x time interaction was observed for cons of quitting , reflecting fewer cons in the intervention group than the control group at 1-month and 3-month follow-up . CONCLUSION A culturally adapted intervention for Chinese and Korean Americans can be effective in changing specific smoking-related cognitions and behavior . This study represents a promising first step toward advancing our underst and ing of the associations between smoking-related cognitions and behavior among Asian American smokers This article describes the test of the hypothesis that a cognitive-behavioral mood management intervention would be effective for smokers with a history of major depressive disorder ( MDD ) . The method was r and omized trial ; the assessment s occurred at Weeks 0 , 8 , 12 , 26 , and 52 . Ss were 149 smokers ; 31 % had a history of MDD . All received 2 mg of nicotine gum . Mood management was provided in 10 group sessions over 8 weeks . St and ard treatment was provided in 5 group sessions over 8 weeks . Outcome was continuous abstinence . History-positive Ss were more likely to be abstinent when treated with mood management . Treatment condition differences were not significant for history-negative Ss . For history-positive Ss , less anger at baseline predicted abstinence . For history-negative Ss , more years smoked and higher baseline carbon monoxide ( CO ) predicted abstinence . Cognitive-behavioral therapy did not affect mood after quitting . Abstinence predictors differed as a function of baseline diagnosis 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 INTRODUCTION Approximately 60%-70 % of cigarette smokers who try to quit relapse by 2 weeks postcessation . We tested the efficacy of a front-loaded ( FL ) counseling intervention whose goal was to increase the likelihood of successful early abstinence and subsequent long-term abstinence . METHODS We r and omized 278 adult smokers to an FL or weekly behavioral smoking cessation counseling schedule . The total number of sessions across treatment was the same for both groups . However , those assigned to the FL schedule received 6 counseling sessions in the first 2 weeks postcessation , while those in the weekly condition received 2 sessions . Participants in both groups also received st and ard nicotine patch treatment . RESULTS At 1 year postcessation , FL participants were significantly less likely to have relapsed when continuous abstinence was used as the definition of abstinence/relapse ( 11.7 % abstinent vs. 6.3 % , hazard ratio [ HR ] = 0.69 , p = .007 ) ; and there were nonsignificant trends for FL subjects to have better outcomes when abstinence was defined as never smoking for 7 or more consecutive days nor for 7 or more consecutive episodes ( 18.4 % abstinent vs. 14.8 % , HR = 0.83 , p = .20 ) and as point prevalence abstinence ( 15.6 % abstinent vs. 12.9 % , p = .11 ) . The relationship between FL counseling treatment and continuous abstinence was partially mediated by higher postcessation levels of social support perceived from counseling and greater use of cessation-related coping strategies . CONCLUSIONS We conclude that FL counseling is a promising treatment model that should be evaluated further , perhaps using modifications of the FL schedule used in this study The A1 allele of the dopamine D2 receptor gene ( DRD2 ) is associated with a reduced number of dopamine binding sites in the brain and with the increased likelihood of substance abuse and addictive behavior . In a study of smokers enrolled in an open-label , r and omized effectiveness trial , we investigated whether variants in the DRD2 receptor gene are associated with smoking cessation outcomes following treatment with a combination of bupropion SR and behavioral counseling . Adherence to treatment and point-prevalent smoking status were assessed at 3 and 12 months , respectively , following a target quit date . Compared to women who carry both A2 alleles , women with at least one A1 allele were more likely to report having stopped taking bupropion due to medication side effects ( odds ratio (OR)=1.91 , 95 % confidence interval (CI)=1.01–3.60 ; P<0.04 ) and at 12 months were somewhat more likely to report smoking ( OR=0.76 , 95 % CI=0.56–1.03 ; P<0.076 ) . Significant associations or trends were not observed in men . In women , individual variability in responsiveness to bupropion-based treatment may be partially due to differences in genetic variants influencing dopamine receptor function Internet interventions for smoking cessation are ubiquitous . Yet , to date , there are few r and omized clinical trials that gauge their efficacy . This study is a r and omized clinical trial ( N= 284 , n= 140 in the treatment group , n= 144 in the control group ) of an Internet smoking cessation intervention . Smokers were r and omly assigned to receive either bupropion plus counseling alone , or bupropion and counseling in addition to 12 weeks of access to the Comprehensive Health Enhancement Support System for Smoking Cessation and Relapse Prevention ( CHESS SCRP ; a Web site which provided information on smoking cessation as well as support ) . We found that access to CHESS SCRP was not significantly related to abstinence at the end of the treatment period ( OR= 1.13 , 95 % CI 0.66 - 2.62 ) or at 6 months postquit ( OR= 1.48 , 95 % CI 0.66 - 2.62 ) . However , the number of times participants used CHESS SCRP per week was related to abstinence at both end of treatment ( OR= 1.79 , 95 % CI 1.25 - 2.56 ) and at the 6-month follow-up ( OR= 1.59 , 95 % CI 1.06 - 2.38 ) . Participants with access to CHESS SCRP logged in an average of 33.64 times ( SD=30.76 ) over the 90-day period of access . Rates of CHESS SCRP use did not differ by ethnicity , level of education or gender ( all p>.05 ) . In sum , results suggest that participants used CHESS SCRP frequently , CHESS SCRP use was related to success , but the effects in general did not yield intergroup effects ABSTRACT BACKGROUND Varenicline may be associated with greater mood disturbance and side-effects among smokers with psychiatric history , but empirical evidence is limited . Differential treatment effectiveness by psychiatric history may also exist . OBJECTIVE To compare mood , prevalence and intensity of treatment side-effects , and abstinence among people with a probable history of major depression ( DH+ ) or not ( DH− ) who took varenicline and received behavioral smoking cessation treatment . DESIGN Smokers participated in a r and omized behavioral intervention effectiveness trial . Treatment side-effects and outcomes were compared between DH+ and DH− participants ( n = 1,117 ) at 2 days and 3 months after the target quit date . PARTICIPANTS Smokers recruited from a large regional health plan . MEASUREMENTS Change in stress and depression scores , prevalence and intensity of treatment side-effects , and abstinence rates . RESULTS All side-effects averaged moderate intensity or less and were similar across DH groups , except DH+ ’s endorsed slightly worse confusion , nausea ( adjusted P = 0.04 ) and trouble sleeping ( adjusted P = 0.008 ) at 21 days . Depression and stress scores declined in both DH groups and an equal proportion of each evidence d new/worsening depressive symptoms . Despite few differences in symptom intensity , more DH+ participants reported recent tension/agitation , irritability/anger , confusion , and depression at 21 days ( adjusted P < 0.05 ) , and depression and anxiety ( adjusted P < 0.01 ) at three months . Nonsmoking rates did not differ by DH group at follow-up . CONCLUSION While some group differences were noted , DH+ smokers did not report qualitatively worse neuropsychiatric symptoms , more new/worsening mood disturbance , or differential abstinence rates compared to DH- smokers The benefits of smoking cessation on patients ' medical conditions are well documented . Cardiovascular patients who quit smoking significantly reduce their risk of a new event compared with those who continue smoking . Several studies have found that smoking is related to poor quality of life ( QoL ) . In cardiovascular patients , however , less attention has been given to the effect of smoking cessation on patients ' QoL. The present study examined the extent to which smoking cessation leads to changes in QoL in these patients within the first year of follow-up . Data were collected in the context of a r and omized clinical trial . Smoking out patients ( N = 346 ) with atherosclerotic disease were included and received medical treatment . They were r and omized to receive either nicotine replacement therapy ( NRT ) or NRT plus a behavioral intervention meant to promote smoking cessation . At baseline , sociodemographic and clinical characteristics were established . Generic and disease-specific QoL as well as smoking status were assessed at baseline and with three follow-up measurements . Multilevel modeling showed that generic and disease-specific QoL in atherosclerotic patients improved significantly within the first year of follow-up . No main differences were found between quitters and smokers in terms of improvement in QoL. In fact , some subgroups reported a poorer QoL after smoking cessation : More highly educated patients reported lower general QoL ( p < .05 ) , and patients suffering from coronary artery disease who had a low level of education ( p < .01 ) and patients suffering from peripheral arterial disease who had low nicotine dependency ( p < .01 ) reported lower disease-specific QoL. Atherosclerotic patients ' QoL improved significantly but was not enhanced by smoking cessation activities Efficacy of bupropion SR and individual counseling as smoking cessation treatments was assessed in a r and omized , placebo-controlled clinical trial among adult daily smokers . Bupropion SR treatment and counseling were fully crossed in this factorial design so that the efficacy of each treatment and the combination could be estimated , relative to a placebo medication and assessment control condition . Intent-to-treat analyses indicated that bupropion SR increased abstinence rates at the end of treatment , relative to the placebo medication conditions , for both biochemically confirmed 7-day point-prevalence abstinence ( OR = 1.97 , 95 % CI 1.04 - 3.72 ) and self-reported prolonged abstinence ( OR = 2.90 , 95 % CI 1.66 - 5.06 ) . Bupropion SR treatment also improved latency to lapse and relapse and improved the latency between lapse and relapse in survival analyses . Medication effects were more modest for both 12-month point-prevalence abstinence ( OR = 1.47 , 95 % CI 0.74 - 2.92 ) and prolonged abstinence ( OR = 1.34 , 95 % CI 0.66 - 2.72 ) . Counseling was not associated with increases in the likelihood of abstinence at any time point ( odds ratios ranged from 0.80 to 1.16 across abstinence outcomes in the full intent-to-treat sample ) . Counseling and medication did not significantly interact at any time point , and adding counseling did not improve end-of-treatment point-prevalence abstinence ( OR = 1.17 , 95 % CI 0.68 - 2.03 ) or prolonged abstinence ( OR = 1.26 , 95 % CI 0.75 - 2.12 ) substantially when offered in conjunction with active medication Background Smoking is an important risk factor for recurrent events in cardiovascular patients . Evidence exists that nicotine replacement therapy ( NRT ) approximately doubles smoking cessation rates . The minimal intervention strategy ( MIS ) has been used successfully to assist patients to quit smoking in general practice , and was recently adapted for cardiology in patients ( C-MIS ) . It is hypothesized that in cardiovascular out patients the combination of C-MIS and NRT significantly increases the number of quitters compared to NRT alone . Methods A r and omized clinical trial in 385 smoking patients who attended the cardiovascular outpatient departments in the Academic Medical Centre , Amsterdam for the treatment of atherosclerotic disease . Patients were allocated to either NRT + C-MIS or NRT alone . Self-reported and biochemically vali date d abstinence rates were measured at 12 months ' follow-up . Results Including patients with incomplete follow-up as smokers , abstinence was reported by 19 % of the NRT + C-MIS group and 14 % of the NRT group [ absolute risk reduction ( ARR ) = 0.05 ; 95 % confidence interval ( CI ) = −0.02 ; 0.12 ] . According to biochemical markers , abstinence rates were 28 and 24 % , respectively ( ARR = 0.04 , 95 % CI = −0.06 ; 0.14 ) . Hence , no significant differences between groups were found . The number of cigarettes smoked a day decreased significantly at 12 months : from 21 to 15 a day in the experimental group , and from 21 to 14 in the control group ( P<0.001 ) , but did not differ between groups ( P=0.32 ) . Conclusions The effectiveness of a minimal contact intervention was investigated in order to reach as many cardiovascular patients as possible in the setting of outpatient departments . This intervention was not found to be effective This correlational study examined the adherence rates of transdermal nicotine ( TN ) use among a population of males and females 18 years of age and older ( N = 619 ) who received varying levels of behavioral intervention . Rates of patch adherence were assessed for demographic ( e.g. , gender , ethnicity , and age ) , income- , smoking- [ e.g. , baseline carbon monoxide ( CO ) , nicotine dependence , and follow-up quit status ] , and treatment-related ( e.g. , condition , and drop status ) variables . Loglinear and logistic regression analyses were performed to assess adherence rates . Results indicated that male gender [ chi2(2 , n = 485 ) = 20.39 , P = .038 ] , not dropping out of the study [ chi2(2 , n = 485 ) = 13.94 , P < .001 ] , and intensive treatment ( compared to the st and ard care ) [ chi2(4 , n = 485 ) = 14.96 , P = .005 ] were associated with greater adherence to TN . Furthermore , patch adherence was associated with quit status at 6 months ( OR = 2.47 , CI = 1.56 - 3.91 , P < .001 ) and 12 months ( OR = 2.12 , CI = 1.34 - 3.37 , P = .001 ) . Complete and partial patch adherence ( compared to minimal/no adherence ) were associated with a greater number of telephone intervention contacts completed ( OR = 2.621 , CI = 1.421 - 4.832 , P = .002 ) . Noteworthy however , was the lack of association between level of income and patch adherence . These findings suggest characteristics of those more and less likely to adhere to TN in research and clinical setting BACKGROUND AND OBJECTIVE GPs are an important source of smoking cessation advice . This research examined whether a model encouraging GP referral of patients who smoke to a specialist service would be acceptable and effective for increased smoking cessation when compared with a model of in- practice management . METHODS The study design was cluster r and omized controlled trial . Practice s were r and omized to one of two interventions , at a rate of 1:2 : ( i ) st and ard in- practice GP management or ( ii ) referral to a quitline service . The main outcome measures were sustained abstinence of > or=1 month duration at 3-month follow-up and > or=10 months duration at 12 months , using intention to treat analysis . RESULTS At 3-month follow-up , patients in the referral condition were twice as likely to report sustained abstinence than those in the in- practice condition [ 12.3 % compared with 6.9 % ; odds ratio ( OR ) = 1.92 ( 95 % confidence interval ( CI ) 1.17 - 3.13 ] . At 12-month follow-up , patients in the referral condition had nearly three times the odds of sustained abstinence [ 6.5 % compared with 2.6 % ; OR = 2.86 ( 95 % CI 0.94 - 8.71 ) ] . The intervention effect was mediated by the amount of help received outside the practice . CONCLUSIONS This research provided evidence that GPs referring smokers to an evidence -based quitline service results in increased cessation . The benefit is largely due to patients in the referral condition receiving more external help than patients in the in- practice condition , as they received equivalent practice -based help . Where suitable services exist , we recommend that referral become the normative strategy for management of smoking cessation in general practice to complement any practice -based help provided Pharmacological interventions for smoking cessation are typically evaluated using volunteer sample s ( efficacy trials ) but should also be evaluated in population -based trials ( effectiveness trials ) . Nicotine replacement therapy ( NRT ) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New Engl and Veterans Affairs Medical Center . Telephone interviews were completed with 3,239 smokers , and 2,054 agreed to participate ( 64 % ) . Participants were r and omly assigned to one of four conditions : stage-matched manuals ( MAN ) ; NRT plus manuals ( NRT + MAN ) ; expert system plus NRT and manuals ( EXP + NRT + MAN ) ; and automated counseling plus NRT , manuals , and expert system ( TEL + EXP + NRT + MAN ) . Assessment s were completed at baseline , 10 , 20 , and 30 months . The point prevalence cessation rates at final follow-up ( 30 months ) were MAN , 20.3 % ; NRT + MAN , 19.3 % ; EXP + NRT + MAN , 17.6 % ; and TEL + EXP + NRT + MAN , 19.9 % . Stage-matched manuals provided cessation rates comparable with previous studies . The addition of NRT , expert system interventions , and automated telephone counseling failed to produce a further increase in intervention effectiveness Background The use of spirometry for early detection of chronic obstructive pulmonary disease ( COPD ) is still an issue of debate , particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation . We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed " confrontational counselling " ; a patient-centred approach which involves specific communication skills and elements of cognitive therapy . An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions . The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation . Methods / Design The study design is a r and omized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( experimental group ) , health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation ( control group 1 ) , and " care as usual " delivered by the GP ( control group 2 ) . Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry . Due to a comparable baseline risk of airflow limitation and motivation to quit smoking , and because of the st and ardization of number , duration , and scheduling of counselling sessions between the experimental group and control group 1 , the study enables to assess the " net " effect of confrontational counselling . The study has been ethically approved and registered . Discussion Ethical as well as method ological considerations of the study are discussed in this protocol . A significant and relevant effect of confrontational counselling would provide an argument in favour of early detection of current smokers with airflow limitation . Successful treatment of tobacco dependence in respiratory patients requires repeated intensive interventions . The results of this study may also show that respiratory nurses are able to deliver this treatment and that intensive smoking cessation counselling is more feasible . Trial registration : Netherl and s Trial Register ( IS RCT N 64481813 ) Objectives : State and national tobacco quitlines have exp and ed rapidly and offer a range of services . We examined the effectiveness and cost effectiveness of offering callers single session versus multisession counselling , with or without free nicotine patches . Methods : This 3 × 2 r and omised trial included 4614 Oregon tobacco quitline callers and compared brief ( one 15-minute call ) , moderate ( one 30-minute call and a follow-up call ) and intensive ( five proactive calls ) intervention protocol s , with or without offers of free nicotine patches ( nicotine replacement therapy , NRT ) . Blinded staff assessed tobacco use by phone at 12 months . Results : Abstinence odds ratios were significant for moderate ( OR = 1.22 , CI = 1.01 to 1.48 ) and intensive ( OR = 1.29 , CI = 1.07 to 1.56 ) intervention , and for NRT ( OR = 1.58 , CI = 1.35 to 1.85 ) . Intent to treat quit rates were as follows : brief no NRT ( 12 % ) ; brief NRT ( 17 % ) ; moderate no NRT ( 14 % ) ; moderate NRT ( 20 % ) ; intensive no NRT ( 14 % ) ; and intensive NRT ( 21 % ) . Relative to brief no NRT , the added costs for each additional quit was $ 2467 for brief NRT , $ 1912 for moderate no NRT , $ 2109 for moderate NRT , $ 2641 for intensive no NRT , and $ 2112 for intensive NRT . Conclusion : Offering free NRT and multisession telephone support within a state tobacco quitline led to higher quit rates , and similar costs per incremental quit , than less intensive protocol OBJECTIVES To investigate the effectiveness of telephone counselling as an adjunct to nicotine replacement therapy ( NRT ) by transdermal patch in smoking cessation . DESIGN R and omised controlled trial . PARTICIPANTS AND SETTING 854 smokers from New South Wales , aged 18 years and older , who had smoked at least 10 cigarettes per day for the past year and responded to newspaper advertisements between October 2001 and January 2002 ; the trial was conducted between October 2001 and August 2002 . INTERVENTIONS R and om allocation to either NRT alone or NRT plus telephone counselling ( 5 sessions spaced according to a relapse-sensitive call schedule ) . MAIN OUTCOME MEASURES Self-reported abstinence assessed by telephone question naires at 1 , 2 , 3 and 6 months : 28-day continuous abstinence at 3 and 6 months , and 90-day continuous abstinence at 6 months . RESULTS 28-day continuous abstinence rates among participants receiving telephone counselling were significantly greater than among those not receiving telephone counselling at both 3 and 6 months ( 31.6 % v 25.1 % ; P = 0.04 at 3 months ; and 30.1 % v 22.4 % ; P = 0.01 at 6 months ) . Similarly , 90-day continuous abstinence rates at 6 months were significantly greater for participants receiving counselling ( 26.7 % v 18.6 % ; P = 0.004 ) . CONCLUSION Telephone counselling as an adjunct to NRT increases abstinence rates beyond the use of NRT alone Background Smoking is an important risk factor for cardiovascular disease ( CVD ) , and quitting is highly beneficial . Yet , less than 30 % of CVD patients stop smoking . Relapse-prevention strategies seem most effective when initiated during the exacerbation of the disease . Objective A nurse-delivered inpatient smoking cessation program based on the Transtheoretical Model with telephone follow-up tailored to levels of readiness to quit smoking was evaluated on smoking abstinence and progress to ulterior stages of change . Method Participants ( N = 168 ) were r and omly assigned by cohorts to inpatient counseling with telephone follow-up , inpatient counseling , and usual care . The inpatient intervention consisted of a 1-hr counseling session , and the telephone follow-up included 6 calls during the first 2 months after discharge . The nursing intervention was tailored to the individual 's stage of change . End points at 2 and 6 months included actual and continuous smoking cessation rates ( biochemical markers ) and increased motivation ( progress to ulterior stages of change ) . Results Assuming that surviving patients lost to follow-up were smokers , the 6-month smoking abstinence rate was 41.5 % in the inpatient counseling with telephone follow-up group , compared with 30.2 % and 20 % in the inpatient counseling and usual care groups , respectively ( p = .05 ) . Progress to ulterior stages of change was 43.3 % , 32.1 % , and 18.2 % , respectively ( p = .02 ) . Stage of change at baseline and intervention predicted smoking status at 6 months . Discussion This tailored smoking cessation program with telephone follow-up significantly increased smoking cessation at 6 months , and progression to ulterior stages of change . The telephone follow-up was an important adjunct . It is , therefore , recommended to include such comprehensive smoking cessation programs within hospital setting s for individuals with CVD Objective To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to st and ard smoking cessation support offered through a telephone quitline . Design Parallel group , 2 × 2 factorial , r and omised controlled trial . Setting National quitline , Engl and . Participants 2591 non-pregnant smokers aged 16 or more residing in Engl and who called the quitline between February 2009 and February 2010 and agreed to set a quit date : 648 were each r and omised to st and ard support , proactive support , or proactive support with nicotine replacement therapy , and 647 were r and omised to st and ard support with nicotine replacement therapy . Interventions Two interventions were offered in addition to st and ard support : six weeks ’ nicotine replacement therapy , provided free , and proactive counselling sessions ( repeat telephone calls from , and interaction with , cessation advisors ) . Main outcome measures The primary outcome was self reported smoking cessation for six or more months after the quit date . The secondary outcome was cessation vali date d by exhaled carbon monoxide measured at six or more months . Results At six months , 17.7 % ( n=229 ) of those offered nicotine replacement therapy reported smoking cessation compared with 20.1 % ( n=261 ) not offered such therapy ( odds ratio 0.85 , 95 % confidence interval 0.70 to 1.04 ) , and 18.2 % ( n=236 ) offered proactive counselling reported smoking cessation compared with 19.6 % ( n=254 ) offered st and ard support ( 0.91 , 0.75 to 1.11 ) . Data vali date d by carbon monoxide readings changed the findings for nicotine replacement therapy only , with smoking cessation vali date d in 6.6 % ( 85/1295 ) of those offered nicotine replacement therapy compared with 9.4 % ( 122/1296 ) not offered such therapy ( 0.67 , 0.50 to 0.90 ) . Conclusions Offering free nicotine replacement therapy or additional ( proactive ) counselling to st and ard helpline support had no additional effect on smoking cessation . Trial registration Clinical Trials.gov NCT00775944 We assessed the efficacy of a comprehensive programme for stopping smoking in 210 smokers scheduled for surgery , before admission and 3 months after attending a pre‐operative clinic . Participants were r and omly allocated to receive an intervention incorporating nicotine replacement therapy for patients smoking more than 10 cigarettes per day ( ‘ dependent smokers ’ ) , or to a control group to receive usual care . Dependent smokers allocated to the intervention group were more likely to report abstinence before surgery than those allocated to receive usual‐care ( 63 ( 73 % ) vs. 29 ( 56 % ) , respectively ; OR 2.2 ( 95 % CI 1.0–4.8 ) ) , and 3 months after attendance ( 16 ( 18 % ) vs. 3 ( 5 % ) , respectively ; OR = 3.9 ( 95 % CI 1.0–21.7 ) Background : There is insufficient and conflicting evidence about whether more intensive behavioural support is more effective than basic behavioural support for smoking cessation and whether primary care nurses can deliver effective behavioural support . Methods : A r and omised controlled trial was performed in 26 UK general practice s. 925 smokers of ⩾10 cigarettes per day were r and omly allocated to basic or weekly support . All participants were seen before quitting , telephoned around quit day , and seen 1 and 4 weeks after the initial appointment ( basic support ) . Participants receiving weekly support had an additional telephone call at 10 days and 3 weeks after the initial appointment and an additional visit at 2 weeks to motivate adherence to nicotine replacement and renew quit attempts . 15 mg/16 h nicotine patches were given to all participants . The outcome was assessed by intention to treat analyses of the percentage confirmed sustained abstinence at 4 , 12 , 26 and 52 weeks after quit day . Results : Of the 469 and 456 participants in the basic and weekly arms , the numbers ( % ) who quit and the percentage difference were 105 ( 22.4 % ) vs 102 ( 22.4 % ) , 0.1 % ( 95 % CI −5.3 % to 5.5 % ) at 4 weeks , 66 ( 14.1 % ) vs 52 ( 11.4 % ) , −2.6 % ( 95 % CI −6.9 % to 1.7 % ) at 12 weeks , 50 ( 10.7 % ) vs 40 ( 8.8 % ) , −1.9 % ( 95 % CI −5.7 % to 2.0 % ) at 26 weeks and 36 ( 7.7 % ) vs 30 ( 6.6 % ) , −1.1 % ( 95 % CI −4.4 % to 2.3 % ) at 52 weeks . Conclusions : The absolute quit rates achieved are those expected from nicotine replacement alone , implying that neither basic nor weekly support were effective . Primary care smoking cessation treatment should provide pharmacotherapy with sufficient support only to ensure it is used appropriately , and those in need of support should be referred to specialists AIM To assess the efficacy of World Wide Web-based tailored behavioral smoking cessation material s among nicotine patch users . DESIGN Two-group r and omized controlled trial . SETTING World Wide Web in Engl and and Republic of Irel and . PARTICIPANTS A total of 3971 subjects who purchased a particular br and of nicotine patch and logged-on to use a free web-based behavioral support program . INTERVENTION Web-based tailored behavioral smoking cessation material s or web-based non-tailored material s. MEASUREMENTS Twenty-eight-day continuous abstinence rates were assessed by internet-based survey at 6-week follow-up and 10-week continuous rates at 12-week follow-up . FINDINGS Using three approaches to the analyses of 6- and 12-week outcomes , participants in the tailored condition reported clinical ly and statistically significantly higher continuous abstinence rates than participants in the non-tailored condition . In our primary analyses using as a denominator all subjects who logged-on to the treatment site at least once , continuous abstinence rates at 6 weeks were 29.0 % in the tailored condition versus 23.9 % in the non-tailored condition ( OR = 1.30 ; P = 0.0006 ) ; at 12 weeks continuous abstinence rates were 22.8 % versus 18.1 % , respectively ( OR = 1.34 ; P = 0.0006 ) . Moreover , satisfaction with the program was significantly higher in the tailored than in the non-tailored condition . CONCLUSIONS The results of this study demonstrate a benefit of the web-based tailored behavioral support material s used in conjunction with nicotine replacement therapy . A web-based program that collects relevant information from users and tailors the intervention to their specific needs had significant advantages over a web-based non-tailored cessation program The aim of this study was to examine moderating and mediating factors of the efficacy of World Wide Web-based tailored behavioral smoking cessation material s. The design was a two-group r and omized controlled trial in Engl and and the Republic of Irel and . Participants were 3971 subjects who purchased a particular br and of nicotine patch and logged on to use a free Web-based behavioral support program . The intervention was Web-based tailored behavioral smoking cessation material s or Web-based nontailored material s. The 10-week continuous abstinence rate was assessed by Internet-based survey at 12-week follow-up . Potential treatment moderators were examined using subgroups of established or possible predictors of smoking cessation . Treatment mediators examined included 6-week follow-up measures of program relevance and amount of the Web-based material s read . Within all subgroups examined , subjects in the Web-based tailored intervention were more likely to report 10-week continuous abstinence at 12-week follow-up . Significant moderators , indicating a significant difference in program efficacy between subgroups , included presence of a tobacco-related illness ( larger treatment-control differences among subjects with a tobacco-related illness ) , presence of nonsmoking children in the household ( larger treatment-control differences among subjects with nonsmoking children in the household ) , and frequent alcohol consumption ( larger treatment-control differences among subjects with higher alcohol consumption ) . Perceived program relevance at 6-week follow-up was a mediator of cessation at 12-week follow-up . Robust results of the tailored program may be explained by the tailoring strategies utilized in the treatment conditions . Moderating variables may be particularly useful to address in tailored messaging . The mediating factor of perceived message relevance may provide a partial mechanism of effective program tailoring BACKGROUND We previously documented that cognitive behavioral therapy for smoking-related weight concerns ( CONCERNS ) improves cessation rates . However , the efficacy of combining CONCERNS with cessation medication is unknown . We sought to determine if the combination of CONCERNS and bupropion therapy would enhance abstinence for weight-concerned women smokers . METHODS In a r and omized , double-blind , placebo-controlled trial , weight-concerned women ( n = 349 ; 86 % white ) received smoking cessation counseling and were r and omized to 1 of 2 adjunctive counseling components : CONCERNS or ST AND ARD ( st and ard cessation treatment with added discussion of smoking topics but no specific weight focus ) , and 1 of 2 medication conditions : bupropion hydrochloride sustained release ( B ) or placebo ( P ) for 6 months . Rates and duration of biochemically verified prolonged abstinence were the primary outcomes . Point-prevalent abstinence , postcessation weight gain , and changes in nicotine withdrawal , depressive symptoms , and weight concerns were evaluated . RESULTS Women in the CONCERNS + B group had higher rates of abstinence ( 34.0 % ) and longer time to relapse than did those in the ST AND ARD + B ( 21 % ; P = .05 ) or CONCERNS + P ( 11.5 % ; P = .005 ) groups at 6 months , although rates of prolonged abstinence in the CONCERNS + B and ST AND ARD + B groups did not differ significantly at 12 months . Abstinence rates and duration did not differ in the ST AND ARD + B group ( 21 % and 19 % ) compared with the ST AND ARD + P group ( 10 % and 7 % ) at 6 and 12 months , respectively . There were no differences among abstinent women in postcessation weight gain or weight concerns , although ST AND ARD + B produced greater decreases in nicotine withdrawal and depressive symptoms than did ST AND ARD + P. CONCLUSIONS Weight-concerned women smokers receiving the combination of CONCERNS + B were most likely to sustain abstinence . This effect was not related to differences in postcessation weight gain or changes in weight concerns . Trial Registration clinical trials.gov Identifier : NCT00006170 AIMS To determine whether African American light smokers who smoked menthol cigarettes had lower cessation when treated with nicotine replacement therapy and counseling . DESIGN Data were derived from a clinical trial that assessed the efficacy of 2 mg nicotine gum ( versus placebo ) and counseling ( motivational interviewing counseling versus Health Education ) for smoking cessation among African American light smokers ( smoked < or = 10 cigarettes per day ) . PARTICIPANTS The sample consisted of 755 African American light smokers . MEASUREMENTS The primary outcome variable was verified 7-day point-prevalence smoking cessation at 26 weeks follow-up . Verification was by salivary cotinine . FINDINGS Compared to non-menthol smokers , menthol smokers were younger and less confident to quit smoking ( P = 0.023 ) . At 26 weeks post-r and omization , 7-day verified abstinence rate was significantly lower for menthol smokers ( 11.2 % versus 18.8 % for non-menthol , P = 0.015 ) . CONCLUSIONS Among African American light smokers , use of menthol cigarettes is associated with lower smoking cessation rates . Because the majority of African American smokers use menthol cigarettes , a better underst and ing of the mechanism for this lower quit rate is needed We assessed the impact of three conditions on one-year smoking cessation rates . Physicians in 70 community general practice s were r and omly allocated by practice to one of three groups : In the usual care group , smoking patients were to receive the care they normally would receive . In the gum only group , physicians were asked to speak to patients about smoking cessation and offer nicotine gum . In the gum plus group , physicians were trained in the experimental intervention . This intervention involved advice to stop smoking , the setting of a quit date , the offer of nicotine gum , and four follow-up visits . Smoking cessation was measured by self-report after one year and vali date d using saliva cotinine measures . Using a criterion of at least three months of abstinence , 8.8 % of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4 % and 6.1 % of the patients in the usual care and gum only groups , respectively This article examines reported symptoms , nonsmoking rates , and medication use among 1,018 smokers using varenicline in a r and omized trial comparing three forms of behavioral support for smoking cessation ( phone , Web , or phone + Web ) . One month after beginning varenicline , 168 people ( 17 % ) had discontinued the medication . Most ( 53 % ) quit due to side effects and other symptoms . The most common side effect among all users was nausea ( reported by 57 % of users ) . At 1 month post medication initiation , those not taking varenicline were more likely to report smoking than those who continued the medication ( 57 % vs. 16 % , p < .001 ) . Women reported more symptoms but did not discontinue medication at higher rates . Participants who received any telephone counseling ( n = 681 ) were less likely to discontinue their medication than those with Web support only ( 15 % vs. 21 % , p < .01 ) . Counseling may improve tolerance of this medication and reduce the rate of discontinuation due to side effects AIMS Tobacco dependence treatments achieve abstinence rates of 25 - 30 % at 1 year . Low rates may reflect failure to conceptualize tobacco dependence as a chronic disorder . The aims of the present study were to determine the efficacy of extended cognitive behavioral and pharmacological interventions in smokers > or = 50 years of age , and to determine if gender differences in efficacy existed . DESIGN Open r and omized clinical trial . SETTING A free-st and ing , smoking treatment research clinic . PARTICIPANTS A total of 402 smokers of > or = 10 cigarettes per day , all 50 years of age or older . INTERVENTION Participants completed a 12-week treatment that included group counseling , nicotine replacement therapy ( NRT ) and bupropion . Participants , independent of smoking status , were then assigned r and omly to follow-up conditions : ( i ) st and ard treatment ( ST ; no further treatment ) ; ( ii ) extended NRT ( E-NRT ; 40 weeks of nicotine gum availability ) ; ( iii ) extended cognitive behavioral therapy ( E-CBT ; 11 cognitive behavioral sessions over a 40-week period ) ; or ( iv ) E-CBT plus E-NRT ( E-combined ; 11 cognitive behavioral sessions plus 40 weeks nicotine gum availability ) . MEASUREMENTS Primary outcome variable was 7-day point prevalence cigarette abstinence verified biochemically at weeks 24 , 52 , 64 and 104 . FINDINGS The most clinical ly important findings were significant main effects for treatment condition , time and the treatment x time interaction . The E-CBT condition produced high cigarette abstinence rates that were maintained throughout the 2-year study period [ ( week 24 ( 58 % ) , 52 ( 55 % ) , 64 ( 55 % ) and 104 ( 55 % ) ] , and was significantly more effective than E-NRT and ST across that period . No other treatment condition was significantly different to ST . No effects for gender were found . CONCLUSIONS Extended cognitive behavioral treatments can produce high and stable cigarette abstinence rates for both men and women . NRT does not add to the efficacy of extended CBT , and may hamper its efficacy . Research is needed to determine if these results can be replicated in a sample with a greater range of ages , and improved upon with the addition of medications other than NRT Objective : To assess the relative impacts of three physician-delivered smoking interventions in combination with follow-up contact from behavioral counselors . Design : R and omized controlled trial with pre-post measures of smoking rates . This paper reports six-month outcome data . Setting : Participants were recruited from among patients seen by 196 medical and family practice residents in five primary care clinics . Participants : Participants were 1,286 patients out of 1,946 eligible smokers approached . The patient group was 57 % female and 91 % white , had an average age of 35 years , and smoked , on average , slightly over one pack per day . Intervention : Physicians were trained to provide each of three interventions : advice only , brief patient-centered counseling , and counseling plus prescription of nicotine-containing gum ( Nicorette ™ ) . Half the patients received follow-up in the form of telephone counseling at three-monthly intervals from behavioral counselors . Measurements and main results : Changes in smoking behaviors were assessed by telephone interview six months after physician intervention . The differences in one-week point prevalence cessation rates among the physician interventions were significant ( p<0.01 ) : advice only , 9.1 % ; counseling , 11.9 % ; counseling plus gum , 17.4 % ; with no effect for telephone counseling . The time elapsed from physician encounter to initial quitting and the length of that period of abstinence also showed significant benefit of the counseling interventions . Patients receiving physician counseling were much more likely than those not receiving counseling to rate their physician as very helpful ( p<0.001 ) . Multiple regression analyses are also reported . Conclusion : Smoking intervention counseling provided by physicians is well received by patients and significantly increases the likelihood of cessation at six months , an effect that is augmented by the prescription of nicotine-containing gum , when compared with physician-delivered advice . Follow-up telephone counseling does not contribute significantly to smoking behavior changes OBJECTIVES We evaluated smoking-cessation efficacy of an extended course of sustained-release bupropion ( bupropion SR ) and cognitive-behavioral treatment ( CBT ) . METHODS Participants who smoked at least 10 cigarettes per day and who smoked within 30 minutes of arising ( n = 406 ) completed a 12-week smoking-cessation treatment including group counseling , nicotine-replacement therapy , and bupropion SR . Participants were then r and omly assigned to 1 of 5 conditions : ( 1 ) no further treatment , ( 2 ) active bupropion SR for 40 weeks , ( 3 ) placebo for 40 weeks , ( 4 ) active bupropion SR and 11 sessions of CBT for 40 weeks ( A-CBT ) , or ( 5 ) placebo and 11 sessions of CBT for 40 weeks . Participants were assessed at baseline and at weeks 12 , 24 , 52 , 64 , and 104 . RESULTS A-CBT was not superior to the other 3 extended treatments . From weeks 12 through 104 , all extended treatment conditions were superior to st and ard treatment . At weeks 64 and 104 , the 2 CBT conditions produced significantly higher abstinence rates than did the other 3 conditions . CONCLUSIONS Brief contact with providers can increase abstinence during treatment . CBT may increase long-term abstinence after extended treatment is terminated The study was conducted to examine the relative effectiveness of cognitive behavior therapy with a cultural tailoring intervention compared to brief medication management . The study used a two-arm r and omized controlled trial in which participant assignment was stratified by gender . The intervention condition received eight weekly 40-min individualized counseling sessions of culturally tailored cognitive behavior therapy , while the control condition received eight weekly 10-min individualized counseling sessions of medication management . Both conditions received nicotine patches for 8 weeks . Data were collected at baseline and at four follow-up points ( one and 4 weeks , and three and 6 months post-quit ) . Treatment outcomes were presented as an intention-to-treat analysis . Thirty Korean immigrants participated in the study . At 6-month follow-up , 57.1 % of participants in the intervention and 18.8 % of participants in the control had 7-day point prevalence abstinence ( odds ratio = 5.8 , 95 % confidence interval = 1.12–26.04 , P = 0.04 ) . Participants ’ self-reported abstinence was biochemically verified with exhaled carbon monoxide and salivary cotinine levels . A combination of the culturally tailored cognitive behavior therapy and nicotine replacement therapy had a better treatment outcome compared to brief medication management . The promising result suggests a need to further test the intervention in larger sample s and longer follow-up assessment s before it can be adapted in clinical setting Alcohol dependent smokers ( N=118 ) enrolled in an intensive outpatient substance abuse treatment program were r and omized to a concurrent brief or intensive smoking cessation intervention . Brief treatment consisted of a 15-min counseling session with 5 min of follow-up . Intensive intervention consisted of three 1-hr counseling sessions plus 8 weeks of nicotine patch therapy . The cigarette abstinence rate , verified by breath carbon monoxide , was significantly higher for the intensive treatment group ( 27.5 % ) versus the rate for the brief treatment group ( 6.6 % ) at 1 month after the quit date but not at 6 months , when abstinence rates fell to 9.1 % for the intensive treatment group and 2.1 % for the brief treatment group . Smoking treatment assignment did not significantly impact alcohol outcomes . Although intensive smoking treatment was associated with higher rates of short-term tobacco abstinence , other , perhaps more intensive , smoking interventions are needed to produce lasting smoking cessation in alcohol dependent smokers Abstract OBJECTIVE : To examine the predictors of quitting among African American ( AA ) light smokers ( < 10 cigarettes per day ) enrolled in a smoking cessation trial . METHODS : Baseline variables were analyzed as potential predictors from a 2 × 2 cessation trial in which participants were r and omly assigned to 1 of 4 treatment groups : nicotine gum plus health education ( HE ) counseling , nicotine gum plus motivational interviewing ( MI ) counseling , placebo gum plus HE counseling , or placebo gum plus MI counseling . Chi-square tests , 2 sample t-tests , and multiple logistic regression analyses were used to identify predictors of cotinine ( COT ) verified abstinence at month 6 . RESULTS : In the final regression model , HE rather than MI counseling ( odds ratio [OR]=2.26 % , 95 % confidence interval [CI]=1.36 to 3.74 ) , older age ( OR=1.03 % , 95 % CI=1.01 to 1.06 ) , and higher body mass index ( OR=1.04 % , 95 % CI=1.01 to 1.07 ) significantly increased the likelihood of quitting , while female gender ( OR=0.46 % , 95 % CI=0.28 to 0.76 ) , ≤$1,800/month income ( OR=0.60 % , 95 % CI=0.37 to 0.97 ) , higher baseline COT ( OR=0.948 % , 95 % CI=0.946 to 0.950 ) , and not completing all counseling sessions ( OR=0.48 % , 95 % CI=0.27 to 0.84 ) reduced the odds of quitting . CONCLUSIONS : Individual characteristics may decrease the likelihood of quitting ; however , the provision of directive , advice-oriented counseling focused on the addictive nature of nicotine , health consequences of smoking , benefits of quitting , and development of a concrete quit plan may be an important and effective facilitator of quitting among AA light smokers OBJECTIVE To compare the efficacy and safety of 22-mg and 44-mg doses of transdermal nicotine therapy when it is paired with minimal , individual , or group counseling to improve smoking cessation rates . DESIGN An 8-week clinical trial ( 4 weeks double-blind followed by 4 weeks open label ) using r and om assignment of participants to both dose ( 22 or 44 mg ) and counseling ( minimal , individual , or group ) conditions . PARTICIPANTS Daily cigarette smokers ( > or = 15 cigarettes per day for at least 1 year ) who volunteered to participate in a study of smoking cessation treatment . A total of 504 participants were enrolled at two sites . INTERVENTION Four weeks of 22- or 44-mg transdermal nicotine therapy followed by 4 weeks of dosage reduction ( 2 weeks of 22 mg followed by 2 weeks of 11 mg ) . Counseling consisted of a self-help pamphlet ( minimal ) ; a self-help pamphlet , a brief physician motivational message , and three brief ( < 15 minutes ) follow-up visits with a nurse ( individual ) ; or the pamphlet , the motivational message , and eight weekly 1-hour group smoking cessation counseling visits ( group ) . All participants returned weekly to turn in question naires and for assessment of their smoking status . MAIN OUTCOME MEASURES Abstinence from smoking was based on self-report , confirmed by an expired carbon monoxide concentration lower than 10 ppm . Withdrawal severity was assessed by means of an eight-item self-report question naire completed daily . RESULTS Smoking cessation rates for the two nicotine patch doses and three levels of counseling did not differ significantly at either 8 weeks or 26 weeks following the quit date . Among those receiving minimal contact , the 44-mg dose produced greater abstinence at 4 weeks than did the 22-mg dose ( 68 % vs 45 % ; P < .01 ) . Participants receiving minimal-contact adjuvant treatment were less likely to be abstinent at the end of 4 weeks than those receiving individual or group counseling ( 56 % vs 67 % ; P < .05 ) . The 44-mg dose decreased desire to smoke more than the 22-mg dose , but this effect was not related to success in quitting smoking . Transdermal nicotine therapy at doses of 44 mg produced a significantly greater frequency of nausea ( 28 % ) , vomiting ( 10 % ) , and erythema with edema at the patch site ( 30 % ) than did a 22-mg dose ( 10 % , 2 % , and 13 % , respectively ; P < .01 for each adverse effect ) . Three serious adverse events occurred during use of the 44-mg patch dose . CONCLUSIONS There does not appear to be any general , sustained benefit of initiating transdermal nicotine therapy with a 44-mg patch dose or of providing intense adjuvant smoking cessation treatment . The two doses and all adjuvant treatments produced equivalent effects at the 26-week follow-up , and the higher patch dose produced more adverse effects . Higher-dose ( 44-mg ) nicotine replacement does not appear to be indicated for general clinical population s , although it may provide short-term benefit to some smokers attempting to quit with minimal adjuvant treatment Whereas telephone-based counseling has been found to be effective in supporting smokers interested in quitting smoking , it is not known whether proactive efforts to reach smokers receiving cessation medications will enhance their likelihood of successful quitting . We had an opportunity to test , in a health plan setting , an offer of telephone-based counseling with smokers identified from health plan records as recently filling a prescription for nicotine replacement therapy or bupropion . After we removed 31 members determined to be ineligible , 1,329 were r and omly allocated to receive an invitation either to telephone-based counseling ( n = 663 ) or to a control group ( n = 666 ) . On average , 7 days ( range = 3 - 15 days ) elapsed from the day of the prescription fill until the Center for Health Promotion began calling to invite members to participate in telephone counseling . The Center for Health Promotion was able to reach 49 % of those in the intervention group ( 323/663 ) . Of these members , 118 ( 37 % ) declined any participation . Therefore , in response to the proactive contact , 63 % ( 205/323 ) of those reached and 31 % ( 205/663 ) of those eligible participated in some smoking cessation counseling . At the 3-month follow-up , we observed an increased quit rate ( 33.1 % vs. 27.4 % ) among health plan members r and omized to telephone-based smoking cessation counseling . The results varied by gender and amount smoked . In addition , the variables associated with quitting in a multivariate logistic regression model included older age and using more than 30 days of medication BACKGROUND Smoking remains the primary preventable cause of death and illness in the U.S. Effective , convenient treatment programs are needed to reduce smoking prevalence . PURPOSE This study compared the effectiveness of three modalities of a behavioral smoking-cessation program in smokers using varenicline . METHODS Current treatment-seeking smokers ( n=1202 ) were recruited from a large healthcare organization between October 2006 and October 2007 . Eligible participants were r and omized to one of three smoking-cessation interventions : web-based counseling ( n=401 ) ; proactive telephone-based counseling ( PTC ; n=402 ) ; or combined PTC and web counseling ( n=399 ) . All participants received a st and ard 12-week FDA -approved course of varenicline . Self-report determined the primary outcomes ( 7-day point prevalent abstinence at 3- and 6-month follow-ups ) ; the number of days varenicline was taken ; and treatment-related symptoms . Behavioral measures determined utilization of both the web- and Phone-based counseling . RESULTS Intent-to-treat analyses revealed relatively high percentages of abstinence at 3 months ( 38.9 % , 48.5 % , 43.4 % ) and at 6 months ( 30.7 % , 34.3 % , 33.8 % ) for the web , PTC , and PTC-web groups , respectively . The PTC group had a significantly higher percentage of abstinence than the web group at 3 months ( OR=1.48 , 95 % CI=1.12 , 1.96 ) , but no between-group differences in abstinence outcomes were seen at 6 months . CONCLUSIONS Phone counseling had greater treatment advantage for early cessation and appeared to increase medication adherence , but the absence of differences at 6 months suggests that any of the interventions hold promise when used in conjunction with varenicline AIM Approximately 50 % of African American smokers are light smokers ( smoke < or = 10 cigarettes a day ) . The prevalence of light smoking in the United States is increasing , yet there has not been a single smoking cessation clinical trial targeting light smokers . The purpose of this 2 x 2 factorial , r and omized clinical trial was to evaluate the efficacy of nicotine gum ( 2 mg versus placebo ) and counseling ( motivational interviewing versus health education ) for African American light smokers . DESIGN Participants were assigned r and omly to one of four study arms : 2 mg nicotine gum plus health education ( HE ) ; 2 mg nicotine gum plus motivational interviewing ( MI ) ; placebo gum plus HE ; and placebo gum plus MI . PARTICIPANTS AND SETTING A total of 755 African American light smokers ( 66 % female , mean age = 45 ) were enrolled at a community health center over a 16-month period . INTERVENTION AND MEASUREMENTS Participants received an 8-week supply of nicotine gum and six counseling sessions during the course of the 26-week study . Biochemical measures included expired carbon monoxide ( CO ) and serum and salivary cotinine . FINDINGS Seven-day quit rates for nicotine gum were no better than for the placebo group ( 14.2 % versus 11.1 % , P = 0.232 ) at 6 months . However , a counseling effect emerged , with HE performing significantly better than MI ( 16.7 % versus 8.5 % , P < 0.001 ) . These results were consistent across outcome time-points ( weeks 1 , 8 , and 26 ) . CONCLUSIONS Results highlight the potential positive impact of directive information and advice-oriented counseling on smoking cessation . Studies are needed to assess other interventions that may further improve quit rates among African American light smokers who are motivated to quit 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 OBJECTIVE Accepted treatments for cigarette smoking rarely achieve abstinence rates of > 35 % at 1 year . Low rates may reflect failure to provide extended and multifocal treatment for this complex and chronic addiction . Using a chronic disease model of smoking , the authors undertook a study to determine the effects of long-term antidepressant and psychological treatment . METHOD One hundred sixty smokers of > or = 10 cigarettes/day were r and omly assigned to one of four treatment conditions in a two-by-two ( nortriptyline versus placebo by brief versus extended treatment ) design . All subjects received 8 weeks of a transdermal nicotine patch , five group counseling sessions , and active or placebo treatment . Interventions for subjects in brief treatment ended at this point . Subjects in extended treatment continued taking drug or placebo to week 52 and received an additional 9 monthly counseling sessions , with checkup telephone calls midway through each session . Subjects were assessed at baseline and weeks 12 , 24 , 36 , and 52 . The principal outcome variables were repeated abstinence at each assessment after the first over a 1-year period and a point prevalence of 7 days of abstinence . RESULTS At week 52 , point-prevalence abstinence rates with missing subjects imputed as smokers were 30 % for placebo brief treatment , 42 % for placebo extended treatment , 18 % for active brief treatment , and 50 % for active extended treatment . With missing subjects omitted , these rates were 32 % , 57 % , 21 % , and 56 % , respectively . CONCLUSIONS Comprehensive extended treatments that combine drug and psychological interventions can produce consistent abstinence rates that are substantially higher than those in the literature This was the first r and omized , controlled smoking cessation trial assessing the efficacy of an exercise intervention as an adjunct to nicotine gum therapy in comparison with both equal contact control and st and ard care control conditions . Sedentary female smokers aged 18 - 55 years were provided with nicotine gum treatment along with brief behavioral counseling and were r and omized into one of these three behavioral adjunct conditions . In the " intent-to-treat " sample ( N = 182 ) , at end of treatment and at 1-year follow-up , there were clear , but nonsignificant , trends in univariate analyses in which the exercise and equal contact control conditions both had higher rates of abstinence than the st and ard care control . However , when adjusting for other predictors of relapse in a multiple logistic regression , both exercise and equal contact control showed an advantage over st and ard care control in avoiding early relapse ( i.e. , after 1 week ) . In a multivariate survival model adjusting for other predictors , the equal contact condition had a significantly lower likelihood of relapse compared with the st and ard care condition and there was a near significant trend in which exercise offered an advantage over st and ard care as well . While these findings suggest a slightly improved likelihood of abstinence with exercise compared with st and ard care , exercise did not differ from equal contact control in its efficacy . Potential explanations for these equivalent levels of efficacy and implication s for the findings are discussed Abstract INTRODUCTION : Many smokers reduce their cigarette consumption during failed attempts to quit . We report the impact of changes in consumption on smoking-related respiratory symptom severity ( SRRSS ) . METHODS : Between February 2002 and May 2004 we recruited 383 smokers from 5 methadone maintenance programs for a r and omized trial of nicotine replacement plus behavioral treatment versus nicotine replacement alone for smoking cessation . Cigarette use in the 28 days prior to the interview , and severity of SRRSS using a 7-item respiratory index , were assessed at baseline and at 3-month follow-up . OUTCOME : Baseline minus 3-month assessment difference in SRRSS score . RESULTS : Follow-up of 319 participants ( 83.3 % ) , mean age 40.4 years , 51.4 % male , who smoked 26.4 cigarettes per day , demonstrated a mean reduction of 16.7 cigarettes per day . A reduction in cigarette use was positively and significantly ( b=0.29 , t=5.16 , P<.001 ) associated with a reduction in smoking-related symptom severity after adjusting for age , gender , race , years of regular smoking , baseline nicotine dependence , and history of treatment for asthma or emphysema . A 1 st and ard deviation reduction in average daily smoking ( about 14.1 cigarettes ) was associated with a 0.28 st and ard deviation decrease in smoking-related symptom severity . CONCLUSION : Reduction in symptom severity increases as absolute reduction in daily smoking increases . This is the first study to demonstrate an association between subjective short-term health changes and reduction in smoking UNLABELLED PRIMARY AIM : Examine the effectiveness of extended cognitive behavior therapy ( CBT ) in promoting longer-term smoking abstinence . DESIGN Open-label treatment phase followed by extended treatment phase . R and omization conducted prior to entry into open-label treatment phase ; analysis based on intention-to-treat to avoid threat of selection bias . SETTING Community smoking cessation clinic . PARTICIPANTS A total of 304 adult smokers ( > or = 18 years of age ; > or = 10 cigarettes/day ) . INTERVENTION Open-label ( 8 weeks ) : all participants received bupropion SR , nicotine patch , CBT . Extended treatment ( 12 weeks ) : participants received either CBT + voicemail monitoring and telephone counseling or telephone-based general support . MEASUREMENTS Seven-day point prevalence abstinence , expired-air carbon monoxide . RESULTS At week 20 follow-up , CBT produced a higher 7-day point prevalence abstinence rate : 45 % versus 29 % , P = 0.006 ; at 52 weeks the difference in abstinence rates ( 31 % versus 27 % ) was not significant . History of depression was a moderator of treatment . Those with a positive history had a better treatment response at 20 weeks when assigned to the less intensive telephone support therapy ( P < 0.05 ) . CONCLUSION The superiority of CBT to 20 weeks suggests that continued emphasis on the development of cognitive and behavioral strategies for maintaining non-smoking during an extended treatment phase may help smokers to maintain abstinence in the longer term . At present , the minimum duration of therapy is unknown AIM To test , in combination with the nicotine patch , the incremental efficacy of a maximal , tailored behavioral treatment over a minimal treatment for smoking cessation . DESIGN R and omized clinical trial with 6-month follow-up . SETTING Five methadone maintenance treatment centers in Rhode Isl and . PARTICIPANTS Three hundred and eighty-three methadone-maintained smokers . INTERVENTION Participants were assigned r and omly to nicotine patch ( 8 - 12 weeks ) plus either ( 1 ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session and a relapse prevention follow-up session ( Max ) or ( 2 ) brief advice using the National Cancer Institute 's 4 As model ( Min ) . An intent-to-treat analysis with those lost to follow-up assumed to smoke was used . MEASUREMENTS Carbon monoxide (CO)-confirmed 7-day point smoking cessation prevalence at 3 and 6 months , and self-reported numbers of cigarettes smoked per day . FINDINGS Participants had a mean age of 40 years , were 53 % male , 78 % Caucasian , smoked 26.7 ( + /- 12.2 ) cigarettes/day and had a mean methadone dose of 95.5 mg . At 3 months , 317 ( 83 % ) were re-interviewed ; at 6 months , 312 ( 82 % ) were re-interviewed . The intent-to-treat , 7-day point prevalence estimate of cessation was 5.2 % in the Max group and 4.7 % in the Min group ( P=0.81 ) at 6 months . In logistic models with treatment condition , age , gender , race , Fagerström Test for Nicotine Dependence and cigarettes per day as covariates , males were more likely to be abstinent at 3 months ( OR 4.67 ; P=0.003 ) and 6 months ( OR 4.01 ; P=0.015 ) . CONCLUSION A tailored behavioral intervention did not increase quit rates over patch and minimal treatment . Smoking cessation rates in methadone-maintained smokers are low , with men having greater success Introduction . Effective smoking cessation treatment requires active patient engagement . This may be particularly important for rural smokers who have less access to smoking cessation re sources than others . This study describes long-term engagement in counseling for smoking cessation and factors associated with engagement . Methods . As part of a r and omized trial , 231 rural smokers received up to 6 telephone-based counseling sessions at 6-month intervals over 24 months . Engagement in treatment was categorized according to the number of counseling calls each interval . During the final 6-month interval , more than 60 % of continuing smokers remained engaged in treatment . Call completion varied over time ; while levels of engagement dropped after the first interval , many continuing smokers remained engaged throughout the study . Education , age , motivation , income , diabetes , and health insurance status were predictors of treatment engagement . Conclusion . This study demonstrates that smokers will remain engaged in long-term counseling design ed to address the chronic nature of nicotine dependence Gender data for bupropion suggest that it may be a particularly effective smoking cessation medication for women . It is not known whether the efficacy of this pharmacotherapy differs as a function of the psychotherapy with which it is administered . This study used a two level factorial design to examine the independent and interactive effects of medication ( bupropion 300 mg/day vs. placebo ) and psychotherapy ( cognitive-behavioral therapy [ CBT ] vs. supportive therapy [ ST ] ) . In addition to testing the hypothesis that bupropion with CBT would be most effective of all the treatments , we examined medication compliance and its role in the efficacy of bupropion . Participants were 154 women , aged at least 30 years and smoking more than 10 cigarettes/day . Compliance with study medication was assessed using Medication Event Monitoring Systems ( MEMS ) over 7 weeks of treatment . Psychological interventions were delivered in 60-min weekly group sessions . Longitudinal analysis of abstinence outcomes from end of treatment ( EOT ) through 12 months after treatment revealed a significant interaction of medication and therapy . Higher abstinence rates at EOT and 3- , 6- , 9- , and 12-month follow-ups were observed when bupropion was delivered concurrently with CBT ( 44 % , 24 % , 30 % , 23 % , 17 % ) rather than with ST ( 18 % , 1 % , 8 % , 5 % , 2 % ) . The bupropion-CBT combination , however , was not clearly superior to placebo , regardless of therapy assignment . Higher rates of medication compliance were positively predictive of abstinence , and this effect was most evident in the placebo condition . Findings provide only modest support for CBT as the preferred type of intensive therapy in conjunction with bupropion in women We evaluated gender differences in demographic , smoking history , nicotine dependence , transtheoretical , and perceived stress variables as predictors of smoking cessation . Participants ( n = 381 ) smoked at least 15 cigarettes per day and were motivated to quit . The outcome variable was 7-day abstinence at 1-year follow-up . Predictor variables included : age , education level , number of years smoking , cigarettes per day , quit attempts , nicotine dependence , stage of change , decisional balance , processes of change , self-efficacy , and perceived stress . Logistic regression analysis was used to derive predictive models for women and men . In women , lower scores for pre- and mid-treatment perceived stress significantly increased the likelihood of being abstinent at follow-up . For men , a higher level of education or number of quit attempts lasting > 24 hours in the past year , along with less frequent use of behavioural processes of change at baseline increased the probability of being abstinent at follow-up Background Smokers have a higher risk of complicated tissue and wound healing after surgery than nonsmokers . We tested the hypothesis that short‐term pre‐operative cessation of smoking in colorectal surgery decreases the incidence of postoperative tissue and wound complications BACKGROUND A history of major depressive disorder ( MDD ) predicts failure to quit smoking . We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD . The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence . METHODS This was a 2 ( nortriptyline vs placebo ) x 2 ( cognitive-behavioral therapy vs control ) x 2 ( history of MDD vs no history ) r and omized trial . The participants were 199 cigarette smokers . The outcome measures were biologically verified abstinence from cigarettes at weeks 12 , 24 , 38 , and 64 . Mood , withdrawal , and depression were measured at 3 , 5 , and 8 days after the smoking quit date . RESULTS Nortriptyline produced higher abstinence rates than placebo , independent of depression history . Cognitive-behavioral therapy was more effective for participants with a history of depression . Nortriptyline alleviated a negative affect occurring after smoking cessation . Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessment s for MDD history-negative smokers . There was also a sex-by-depression history interaction ; MDD history-positive women were less likely to be abstinent than MDD history-negative women , but depression history did not predict abstinence for men . CONCLUSIONS Nortriptyline is a promising adjunct for smoking cessation . Smokers with a history of depression are aided by more intensive psychosocial treatments . Mood and diagnosis interact to predict relapse . Increases in negative affect after quitting smoking are attenuated by nortriptyline Earlier research indicated that a 10-session mood management ( MM ) intervention was more effective than a 5-session st and ard intervention for smokers with a history of major depressive disorder ( MDD ) . In a 2 x 2 factorial design , the present study compared MM intervention to a contact-equivalent health education intervention ( HE ) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD . Participants were 201 smokers , 22 % with a history of MDD . Contrary to the earlier findings , the MM and HE interventions produced similar abstinence rates : 2 mg gum was no more effective than placebo . History-positive participants had a greater increase in mood disturbance after the quit attempt . Independent of depression diagnosis , increases in negative mood immediately after quitting predicted smoking . No treatment differences were found in trends over time for measures of mood , withdrawal symptoms , pleasant activities and events , self-efficacy , and optimism and pessimism . History-positive smokers may be best treated by interventions providing additional support and contact , independent of therapeutic content OBJECTIVES The aims of this study were to identify prospect i ve determinants of smoking cessation in COPD patients , and to assess whether prospect i ve determinants vary between two different cessation interventions . METHODS Two hundred and twenty-five moderate to severe COPD patients were r and omly allocated to two smoking cessation interventions . One-year cotinine-vali date d continuous abstinence rates were 9 % for the minimal intervention strategy for lung patients ( LMIS ) and 19 % for the SmokeStopTherapy ( SST ) . The baseline characteristics that showed a significant univariate relationship with 1-year continuous abstinence ( p<.20 ) were included in the logistic regression model . This procedure was performed for each intervention separately . Variables that did not remain independent predictors were removed . RESULTS For the SST separately , no independent significant predictor remained . For the LMIS , attitude towards smoking cessation ( OR : 11.8 ; 95 % CI : 1.7 - 81.5 ; p=.013 ) and cotinine level ( OR : 2.1 ; 95 % CI : 1.08 - 3.93 ; p=.028 ) remained significant predictors . Within the LMIS , 31 % of the variance in continuous abstinence was explained by these variables ( p=.003 ) . CONCLUSION This study suggests that a moderately intensive intervention ( LMIS ) is primarily suitable for COPD patients with a positive attitude regarding smoking cessation . The more intensive SST can be an alternative for patients without such baseline characteristic . PRACTICE IMPLICATION S This stepped-care approach in smoking cessation counseling may be useful in clinical practice and will enable health care providers to match interventions to individual needs and increase efficiency OBJECTIVE To examine patient response to a smoking cessation program that combined a nicotine replacement system ( patch ) with telephone support . DESIGN R and omized trial . SETTING A large Midwestern HMO . PARTICIPANTS . Five hundred and nine smokers who attended orientation sessions where an overview of the study and the use of the nicotine patch was presented . INTERVENTION All subjects received a prescription for a nicotine replacement patch ( Prostep , Lederle Laboratories , Wayne , NJ ) . Participants were r and omly assigned to one of three intervention groups . Group I participants ( n = 166 ) received no additional support . Group II participants ( n = 167 ) were registered with a 24-hour telephone hotline . Group III participants ( n = 167 ) were registered with the 24-hour telephone hotline and received four follow-up telephone calls from health educators . OUTCOME MEASURE The primary outcome measure was smoking cessation . Subject satisfaction with study components was also evaluated . RESULTS Overall , there was no significant difference by group in smoking cessation rates : 20 % of patients in all three groups were smoke-free after 12 months . Few patients ( 1 % ) used the telephone hotline . The telephone follow-up did not have an impact on cessation rates , and most patients ( 92 % ) reported that the orientation session was useful . CONCLUSIONS The study experience has helped the HMO evaluate various study components and has had an impact on currently used telephone intervention strategies and educational material The objective of the present study was to test whether confronting smokers with previously undetected chronic obstructive pulmonary disease ( COPD ) increases the rate of smoking cessation . In total , 296 smokers with no prior diagnosis of COPD were detected with mild-to-moderate airflow limitation by means of spirometry and r and omly allocated to : confrontational counselling by a nurse with nortriptyline for smoking cessation ( experimental group ) ; regular counselling by a nurse with nortriptyline ( control group 1 ) ; or “ care as usual ” for smoking cessation by the general practitioner ( control group 2 ) . Only the experimental group was confronted with their abnormal spirometry ( mean forced expiratory volume in one second ( FEV1 ) post-bronchodilator 80.5 % predicted , mean FEV1/forced vital capacity post-bronchodilator 62.5 % ) . There was no difference in cotinine-vali date d prolonged abstinence rate between the experimental group ( 11.2 % ) and control group 1 ( 11.6 % ) from week 5–52 ( odds ratio ( OR ) 0.96 , 95 % confidence interval ( CI ) 0.43–2.18 ) . The abstinence rate was approximately twice as high in the experimental group compared with control group 2 ( 5.9 % ) , but this difference was not statistically significant ( OR 2.02 , 95 % CI 0.63–6.46 ) . The present study did not provide evidence that the confrontational approach increases the rate of long-term abstinence from smoking compared with an equally intensive treatment in which smokers were not confronted with spirometry . The high failure rates ( ≥88 % ) highlight the need for treating tobacco addiction as a chronic relapsing disorder The purpose of this study was to test two combination motivational plus pharmacological interventions for smoking cessation among HIV positive smokers . Participants were 40 adults receiving HIV care who smoked daily reporting interest in smoking reduction . Measures were administered at baseline , 1-month , and 3-month follow-ups . Participants were r and omly assigned to self-guided reading plus nicotine patch ( n = 18 ) or motivational interviewing plus nicotine patch ( n = 22 ) . Groups did not differ at 3 months on biochemically-verified abstinence . The sample reduced cigarettes per day by half a pack and the percent of smoking days by 41 % , and 22 % were abstinent at 3-month follow-up . Compliance with the nicotine patch was poor and declined over time , but patch use was unrelated to carbon monoxide level at 3-month follow-up . Smoking cessation interventions for people with HIV can be helpful and should include components that encourage some smoke-free days , increase self-efficacy , and attend to adherence to nicotine replacement treatment BACKGROUND Little is known about the effectiveness of bupropion SR for smoking cessation outside the context of clinical efficacy trials , where in-person screening and treatment occur at a higher level than provided in a typical health care system . This article describes the methods for recruitment , screening for exclusions , and result ing sample in a field trial of bupropion SR undertaken in a managed-care setting . METHODS A total of 2979 telephone interviews were conducted to screen and identify eligible volunteers using a detailed protocol that allowed for consultation with study physicians when necessary . The volunteers ' primary care physicians were given the option to override their eligibility , and pharmacy data bases were used to verify medication reporting . RESULTS A total of 1909 ( 64 % ) volunteers were considered eligible for the study . The most common reason for exclusion was use of contraindicated medications ( 32 % ) , followed by recent use of one of the behavioral cessation programs ( 14 % ) , brain injury that reduced seizure threshold ( 14 % ) , current depression ( 14 % ) , and high levels of alcohol use ( 13 % ) . CONCLUSIONS The methods used in this field trial show that it is possible to enroll subjects in an effectiveness trial that is successful from the st and point of the consumer , provider , and health care system Compared to the general population , smokers with schizophrenia ( SCZ ) have reduced success in quitting smoking with usual approaches . This study tested two manualized behavioral counseling approaches-Treatment of Addiction to Nicotine in Schizophrenia ( TANS ) or Medication Management (MM)-for smokers who were motivated to quit . Individual counseling sessions were provided by mental health clinicians in mental health setting s , along with nicotine patch . The two treatments varied in intensity and frequency of sessions . Eighty-seven subjects were r and omized and attended at least one treatment session . Twenty-one percent ( n = 18 ) of participants had continuous abstinence at 12 weeks after the target quit date , which was not significantly different between conditions ( 15.6 % TANS vs. 26.2 % MM , chi(2 ) = 1.50 , p = .221 ) . Smokers in both groups significantly reduced smoking as measured by cigarettes per day and expired carbon monoxide . Findings support that mental health clinicians can be trained to effectively help smokers with SCZ maintain tobacco abstinence Objectives : This study evaluated the effectiveness of behavioral interventions ( brief counseling , nonspecific psychological support in groups — NSGS and cognitive behavioral group therapy — CBGT ) in combination with bupropion SR for smoking cessation in the field , through a smoking cessation clinic . Methods : Two-hundred- and -five smokers were enrolled in a 19-week course during 2007/ 2008 , and were r and omly assigned to : bupropion SR combined with brief counseling ( group A ) , bupropion SR combined with NSGS ( group B ) , bupropion SR combined with CBGT ( group C ) , or CBGT as the only approach ( group D ) . Results : Continuous abstinence rates at the end of therapy were 53.2 % for group A , 62.9 % for group B , 50.0 % for group C , and 22.2 % ( p < 0.05 ) for group D. Sustained abstinence rates in 12 months were 29.6 % , 28.1 % , 34.3 % and 19.4 % ( p > 0.05 ) , respectively . Conclusions : Bupropion SR is an effective aid for smoking cessation in clinical practice . NSGT increased the chances for success at the end of therapy when combined with bupropion SR , while CBGT as monotherapy was less effective compared with the approaches including pharmacotherapy . It is suggested that smoking cessation interventions in real-life healthcare setting s should be implemented through comprehensive programs using pharmacotherapy where applicable , combined with NSGT , and integrated by specialized healthcare professionals This study examines the efficacy of a smoking cessation intervention on abstinence rates and motivation to quit smoking . Participants were adult smokers ( N = 543 ) who presented to the emergency department with chest pain and who were admitted to an observation unit for 24-hour observation to rule out myocardial infa rct ion . Participants were r and omly assigned to either usual care or a tailored intervention employing motivational interviewing and telephone follow-up . All individuals choosing to quit were offered nicotine patch therapy . Follow-up assessment s were conducted at 1 , 3 and 6 months . Abstinence ( 7-day point prevalence ) rates were significantly greater among participants receiving the tailored intervention compared with those given usual care ( OR = 1.62 , 95 % CI [ 1.05 - 2.50 ] ) . The largest difference occurred at 1 month : 16.8 % of usual care and 27.3 % of the tailored intervention group were abstinent , with differences decreasing over time . One-third of participants who were quit at month 6 were late quitters whose initial abstinence began after the 1-month follow up . In addition to treatment assignment , psychosocial variables including motivation to quit , confidence , reduced temptation to smoke in response to negative affect , and the perception that their chest pain was related to their smoking , were significant predictors of cessation . Tailored interventions are effective in promoting initial quit attempts for emergency chest pain patients admitted to an observation unit . Additional intervention may be needed to assist late quitters and to prevent relapse Background . The aim was to study the effect of a multimodal smoking cessation intervention regimen on a number of pregnant smokers Two hundred smokers who were judged by their general practitioner to be motivated to stop smoking were allocated to one of two groups . All were offered an initial appointment at which they were advised to stop smoking and offered nicotine gum . One group then received no further appointments . The other was offered four further appointments over three months . Both groups were followed up at six and 12 months . At one year follow up 15.5 % overall had stopped smoking , 14 % in the low and 17 % in the high contact group . This is better than most results so far reported for nicotine chewing gum in general practice , suggesting that general practitioners can use it to good effect . We compare this result with others achieved in general practice INTRODUCTION Patient adherence to smoking cessation medications can impact their effectiveness . It is important to underst and the extent to which prescribed medications are actually taken by smokers , how this influences smoking cessation outcomes , and what factors may influence adherence . METHODS Smokers recruited from a large health plan were r and omized to receive different modes of cessation counseling in combination with varenicline ( Swan , G. E. , McClure , J. B. , Jack , L. M. , Zbikowski , S. M. , Javitz , H. S. , Catz , S. L. , et al. 2010.Behavioral counseling and varenicline treatment for smoking cessation . American Journal of Preventive Medicine , 38 , 482 - 490 ) . One thous and one hundred and sixty-one participants were mailed a 28-day varenicline supply when they set a quit date and were able to request up to two refills from the health plan pharmacy at no cost . Pharmacy fill records were obtained and telephone surveys completed at baseline , 21 days , 12 weeks , and 6 months post target quit date . RESULTS Good adherence to varenicline ( ≥80 % of days taken ) was associated with a twofold increase in 6-month quit rates compared with poor adherence ( 52 % vs. 25 % ) . Smokers were more likely than nonsmokers to stop varenicline early . Purpose ful nonadherence was associated with smoking at 12 weeks and was predicted in multivariate analyses by age , gender , adherence self-efficacy , and initial medication side effect severity . CONCLUSIONS Innovative methods for increasing adherence to smoking cessation medications are needed , particularly early in the quit process . Simple metrics of adherence such as number of days cessation medication is taken can and should be routinely incorporated in effectiveness trials and reported to advance future attempts to underst and and reduce nonadherence A. Batra , S.E. Collins , I. Torchalla , M. Schröter , and G. Buchkremer ( 2008 ) showed that smokers reporting higher levels of nicotine dependence , novelty seeking/hyperactivity , and depressivity ( i.e. , at-risk smokers ) evinced higher rates of posttreatment smoking than smokers reporting lower scores on self-report psychological symptom measures ( i.e. , lower risk smokers ) . This study aim ed to replicate the smoker subgroups and test the comparative effectiveness of st and ard pharmacobehavioral smoking cessation versus modified smoking cessation matched to at-risk smokers ' needs . On the basis of their self-report responses , adult regular smokers ( N = 268 ) were classified into smoker subgroups . At-risk smokers were r and omly assigned to receive the st and ard or modified treatments ; lower risk smokers received st and ard treatment . Modified treatment produced higher abstinence rates than the st and ard treatment for depressive smokers but not for other at-risk smokers . Overall , abstinence rates among at-risk smokers receiving modified treatment were not significantly different from those of lower risk smokers ; however , abstinence among higher dependence smokers receiving modified treatment decreased at higher rates than among lower risk smokers The authors evaluated whether completing a multi-item assessment of smoking craving ( the Question naire of Smoking Urges [ QSU ] ) promoted increases in smoking craving . A sample of 39 regular smokers was r and omly assigned to 1 of 3 manipulations ( each of 3 min duration ): ( a ) complete the QSU-Brief ( 10 items ) , ( b ) complete a noncraving question naire that was structurally identical to the QSU-Brief ( scale-based control ) , and ( c ) a time-based control . Participants responded to an oral question assessing their degree of craving immediately before and after the manipulations . Results indicated that the QSU did not promote increases in craving compared to the 2 control conditions . Despite continuing debate over the most appropriate self-report measure of craving , investigators who use the QSU-Brief can be reasonably sure that the scores that result are not biased due to reactivity effects The authors compared 9- , 16- , 26- , and 52-week outcomes for two r and omly assigned groups of nicotine-dependent subjects : 1 ) nicotine patch plus four smoking cessation sessions with a nurse-practitioner giving advice and instruction ( n = 36 ; moderate-intensity condition , MI ) ; or 2 ) the foregoing treatments plus 16 weekly individual cognitive/ behavioral relapse-prevention therapy sessions ( n = 33 ; high-intensity condition , HI ) . Patch completion rates were 69.7 % in the HI group and 55.6 % in the MI group ( NS ) . Self-reported abstinence rates at the four follow-up points were comparable for the two treatment groups ; HI : 39 % , 36 % , 36 % , and 36 % ; MI : 44 % , 28 % , 25 % , and 28 % , respectively . There was some indication that MI patients with high nicotine dependence had lower abstinence rates than highly dependent HI patients To determine predictors of smoking cessation duration in a r and omized clinical trial , we assigned participants to nicotine patch ( 8 - 12 weeks ) plus either ( a ) a baseline tailored brief motivational intervention , a quit date behavioral skills counseling session , and a relapse prevention follow-up session , or ( b ) brief advice using the National Cancer Institute 's 4A 's model . A total of 383 smokers from five methadone maintenance treatment centers in Rhode Isl and were enrolled , of whom 312 ( 82 % ) completed 6-month follow-up assessment s. The primary outcome was longest period of self-reported abstinence during follow-up . Participants were on average 40.5 years of age ; 51.9 % were male , and 77.6 % were White . In multivariate analysis controlling for demographics , nicotine dependence , depressive symptoms , and smoking-related symptoms , we found longer periods of abstinence in persons reporting at least one 24-hr quit attempt in the year prior to baseline ( OR = 1.97 , p = .003 ) , in those anticipating success in cessation ( OR = 1.33 , p = .024 ) , and in those with a greater percentage of nicotine patch use days ( OR = 2.78 , p<.001 ) . Past quit attempts , self-efficacy , and constant nicotine replacement were associated with duration of abstinence among methadone-maintained smokers . Attention to these domains in future intervention studies may improve treatment success PURPOSE To determine whether an intensive cognitive-behavioral intervention begun during hospitalization when combined with transdermal nicotine replacement therapy is more effective than a minimal counseling intervention combined with transdermal nicotine replacement therapy in helping in patients to quit smoking . METHODS A total of 223 patients who smoked were enrolled in a hospital-based r and omized smoking cessation trial at the San Francisco Veterans Affairs Medical Center . One hundred and seven participants ( 48 % ) received intensive counseling and outpatient telephone follow-up ; 116 participants ( 52 % ) received minimal counseling . All study participants received 2 months of transdermal nicotine replacement therapy . We determined 6-month quit rates by self-report and measured saliva cotinine levels or obtained proxy reports to confirm self-reported smoking cessation at 12 months . Analyses adjusted for baseline differences in the distribution of coronary disease . RESULTS At 6 months , 35 % ( 36/103 ) of the intensive intervention group reported quitting , compared with 21 % ( 23/109 ) of the comparison group ( relative risk [ RR ] = 1.7 ; 95 % confidence interval [ CI ] : 1.1 to 2.7 ) . At 12 months , the self-reported quit rate was 33 % ( 33/99 ) in the intensive intervention group versus 20 % ( 21/103 ) in the comparison group ( RR = 1.7 ; 95 % CI : 1.1 to 2.7 ) . Based on biochemical or proxy confirmation , 29 % ( 30/102 ) in the intensive intervention group versus 20 % ( 21/107 ) in the comparison group quit smoking at 12 months ( RR = 1.6 ; 95 % CI : 0.96 to 2.5 ) . CONCLUSION Hospital-initiated smoking cessation interventions that include transdermal nicotine replacement therapy can improve long-term quit rates PURPOSE To conduct an exploratory study of two interventions to help smokers abstain over a period of 3 months . The specific aims were to describe the outcomes , test feasibility of the study design , and evaluate effect size . DESIGN AND METHODS A r and omized experimental design was used in a sample of 42 patients who received multicomponent treatment intervention ( MTI ) or st and ard care ( SC ) in a midwestern city in the United States . Variables were behavioral ( quit rate , self-efficacy , motivation ) , psychosocial ( depression , partner interaction ) , and symptom management ( use of nicotine replacement therapy [ NRT ] ) . Data analysis included descriptive statistics and repeated measures ANOVA . RESULTS The typical participant was Caucasian , middle aged , nicotine dependent , married or partnered , and employed , and had a high school education . Participants in the MTI group were more likely to use NRT and to have higher self-reported quit rates at follow-up . Statistically significant differences were found between groups over time for self-efficacy and positive to negative behavior ratio . Barriers to quitting were relapse , stress , weight gain , lack of support , and depression that were more frequent in the SC group . For effect size ( 0.25 ) , probability level ( .05 ) , and power ( .80 ) , a sample size of 140 patients was calculated . CONCLUSIONS The MTI group had higher quit rates , more NRT , higher self-efficacy , and more positive behavioral interactions . Limitations of the study included self-report of tobacco use , small sample , and attrition . The investigators suggest a future study with a larger sample to test whether multicomponent interventions with telephone calls after discharge are more effective than is st and ard care in helping patients to quit and continue to abstain from smoking Smokers ( N = 99 ) were r and omly assigned to one of three conditions : nicotine gum ( NG ) , nicotine gum plus psychological treatment ( NG-PT ) , and nicotine gum plus psychological treatment and partner support ( NG-PT-PS ) . Data were collected at Weeks 0 , 4 , 12 , 26 , and 52 from study start . Contrary to expectations , NG-PT-PS and NG-PT failed to increase abstinence rates . Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions , although not significantly at Weeks 26 and 52 . Treatments without partner participation ( NG-PT and NG ) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks . The role of social support in smoking treatment is discussed The patch adherence behavior of 101 smokers receiving 8 weeks of the nicodermal patch was examined while undergoing one of three levels of adjunctive psychosocial treatment . Additionally , regression analyses were undertaken to : ( 1 ) identify subject variables predictive of patch adherence and ( 2 ) to determine the predictive validity of patch treatment dropout , smoking and patch adherence during patch treatment to smoking 9 and 26 weeks post-treatment entry . Fifty-five percent of the patients wore the patch as prescribed for at least 50 of 56 treatment days . A multiple regression model including the Fagerström severity of dependence score , psychosocial treatment group , and the URICA commitment score predicted 18 % of the variance in days of patch use . All treatment dropouts were found to be smoking at followup . Although both smoking and low patch compliance during treatment were significant predictors subjects of week 9 and 26 smoking for the remaining subjects , at the individual variable level of analysis , only smoking during treatment predicted week 9 and 26 outcomes in a two-variable predictor model We tested whether a 3-month beneficial effect of telephone counseling as an adjunct to the use of medications for smoking cessation was maintained through 12 months . Health plan members filling a prescription for cessation medications were r and omized either to a no-contact control group or to proactive recruitment into telephone counseling . An increased point-prevalence quit rate at 3 months ( 33.1 % vs. 27.4 % , p<.05 ) among smokers r and omized to proactive recruitment for telephone counseling was not maintained . Although at 12 months smokers in the proactive recruitment arm were more likely to report a 24-hr quit attempt , compared with control group smokers ( 86.7 % vs. 80.8 % , p = .027 ) , we found no differences between the groups in repeated ( 3-month and 12-month ) 7-day point-prevalence quit rates . In an analysis of predictors of quitting , age , marital status , making a lifestyle change , and the presence of household smokers were associated with repeated 3-month and 12-month point-prevalence abstinence . Offering telephone counseling to insured smokers who have filled prescriptions for cessation medications did not increase long-term quit rates . Although other variations of this approach might be tested , we suspect that it might be more useful to test innovative ways to influence the factors we identified as being most strongly predictive of lack of successful quitting INTRODUCTION Bupropion and cognitive-behavioral treatment ( CBT ) for depression have been used as components of treatments design ed to alleviate affective disturbance during smoking cessation . Studies of treatment-related changes in precessation affect or urges to smoke are needed to evaluate the proposed mechanisms of these treatments . METHODS The present report examines affective trajectories and urges to smoke prior to , on quit day , and after quitting in a sample of 524 smokers r and omized to receive bupropion versus placebo and CBT versus st and ard smoking cessation CBT . RESULTS Bupropion and /or CBT did not affect the observed decreases in positive affect and increases in negative affect prior to cessation . However , on quit day , observed levels of negative affect and urges to smoke were diminished significantly among individuals receiving bupropion . Decreases in positive affect prior to quitting , lower levels of positive affect , and increased levels of negative affect and urges to smoke on quit day were each related to higher risk of smoking lapse . Depression proneness was an independent predictor of lower positive affect and higher negative affect but did not moderate the effects of bupropion on outcomes . In mediational analyses , the effect of bupropion was accounted for in part by lower negative affect and urges to smoke on quit day . DISCUSSION Results support the efficacy of bupropion in reducing relapse risk associated with urges to smoke and negative affect and suggest the need to better underst and the role of low positive affect as a risk factor for early lapse OBJECTIVE To describe the design , implementation , baseline data , and feasibility of establishing a disease management program for smoking cessation in rural primary care . METHOD The study is a r and omized clinical trial evaluating a disease management program for smoking cessation . The intervention combined pharmacotherapy , telephone counseling , and physician feedback , and repeated intervention over two years . The program began in 2004 and was implemented in 50 primary care clinics across the State of Kansas . RESULTS Of eligible patients , 73 % were interested in study participation . 750 enrolled participants were predominantly Caucasian , female , employed , and averaged 47.2 years of age ( SD=13.1 ) . In addition to smoking , 427 ( 57 % ) had at least one additional major risk factor for cardiovascular disease ( diabetes , hypertension , high cholesterol , heart disease or stroke ) . Participants smoked on average 23.7 ( SD=10.4 ) cigarettes per day , were contemplating ( 61 % ) or preparing to quit ( 30 % ) , were highly motivated and confident of their ability to quit smoking , and reported seeing their physicians multiple times in the past twelve months ( Median=3.50 ; Mean=5.48 ; SD=6.58 ) . CONCLUSION Initial findings demonstrate the willingness of patients to enroll in a two-year disease management program to address nicotine dependence , even among patients not ready to make a quit attempt . These findings support the feasibility of identifying and enrolling rural smokers within the primary care setting Patterns of smoking cessation using 6- and 12-month follow-up data are reported for 1,261 primary care patients r and omized to 3 physician-delivered smoking interventions : advice only ( AO ) , counseling ( CI ) , and counseling plus availability of nicotine-containing gum ( CI + NCG ) . One-week-point-prevalence cessation rates at 12 months did not differ among the interventions : AO ( 15.2 % ) , CI ( 12.9 % ) and CI + NCG ( 16.7 % ) . However , maintained cessation rates ( abstinent at both 6 and 12 months ) increased with intervention intensity : AO ( 6.0 % ) , CI ( 7.8 % ) and CI + NCG ( 10.0 % ) : Test of trend chi 2 = 5.06 , p = .02 . CI + NCG was significantly higher than AO ( p = .02 ) . The findings support the following conclusions : Brief physician-delivered intervention with availability of nicotine-containing gum can have a beneficial long-term effect on smoking cessation , and cohort data as well as point-prevalence rates are important when assessing the long-term impact of lifestyle interventions This study , which tested two motivational interviewing treatment approaches , assessed the feasibility of conducting a community-based smoking cessation intervention among homeless smokers . Participants ( N = 46 ) were recruited from multiple facilities in the Kansas City area and were r and omized to two counseling conditions in which they received five individual motivational interviewing sessions , six group meetings , and their choice of 8 weeks of 21-mg nicotine patch or 4-mg nicotine lozenge . The two counseling conditions consisted of motivational interviewing targeted either to smoking behaviors exclusively ( smoking only ) or to smoking and other addictions or life events that could affect ability to quit ( smoking plus ) . Group meetings were design ed to provide educational information and social support . Measures of feasibility assessed included the proportion of participants who returned for r and omization among those eligible , adherence to prescribed nicotine replacement therapies , retention rates at the week 26 final study visit , and biochemically verified 7-day abstinence at week 26 . Most participants ( 69.6 % ) chose nicotine patches , and 32 % of those participants reported using at least four patches per week . Carbon monoxide verified 7-day abstinence rates in the smoking-only and smoking-plus groups were 13.04 % and 17.39 % ( ns ) , respectively , at week 8 and 8.70 % and 17.39 % ( ns ) , respectively , at week 26 . Participants who used at least four patches per week were more likely to have quit at 8 weeks than were those who used fewer patches ( 33.3 % vs. 10.5 % , p = .30 ) . Results support the feasibility of conducting a smoking cessation intervention among homeless smokers . Findings also show promising effects for nicotine replacement therapy and counseling in this population . Developing programs to improve smoking cessation outcomes in underserved population s is an essential step toward achieving national health objectives and for ultimately reducing tobacco-related health disparities OBJECTIVES Transdermal nicotine patches have shown considerable promise in improving smoking cessation outcomes . The present study assessed telephone support as an adjunct to a managed care-based , single-session group orientation smoking cessation program with nicotine patch therapy . METHODS The unit of r and omization was the orientation session ( n = 35 ) . Subjects ( n = 509 ) were r and omly assigned to a group session without telephone support , the session plus access to a toll-free help line , or the session with telephone help line plus active telephone outreach . RESULTS Contrary to hypothesis , there were no differences between treatment conditions . Overall abstinence rates were 22 % at 6 months and 21 % at 1 year . Fewer than 1 % of eligible subjects called the toll-free help line . An average of 3.8 of a possible 4 calls were completed in the telephone outreach condition . CONCLUSIONS Abstinence results obtained in this program were comparable to those obtained with more extensive counseling . However , there was no evidence of benefit from telephone support beyond the initial physician-led group orientation session OBJECTIVES To determine the differential cost effectiveness of 2 dosing regimens of bupropion sustained release ( SR ) in combination with behavioral interventions of minimal intensity ( tailored mailings [ TM ] ) or moderate intensity ( proactive telephone calls [ PTC ] ) for smoking cessation in an actual practice setting . STUDY DESIGN Open-label , r and omized trial , with 1-year follow-up , conducted in a large health system based in Seattle , Washington . METHODS A total of 1524 adult smokers interested in quitting smoking were r and omly assigned to receive 150 mg bupropion SR daily and PTC ( n = 382 ) , 150 mg bupropion SR daily and TM ( n = 381 ) , 300 mg bupropion SR daily and PTC ( n = 383 ) , or 300 mg bupropion SR daily and TM ( n = 378 ) . Sufficient medication for 8 weeks of dosing was provided to patients . The primary outcome measure was self-reported point-prevalence 7-day nonsmoking status at 12 months after the target quit date . RESULTS Although the 300-mg dose was associated with a higher 12-month nonsmoking rate relative to the 150-mg dose with both PTC and TM , the additional cost result ed in lower cost effectiveness . The PTC behavioral intervention was more expensive than TM , but the additional effectiveness result ed in almost equivalent cost effectiveness at the 150-mg dose . Costs per additional 12-month nonsmoker ( above that expected for placebo ) for the 150-mg dose groups averaged 950 dollars and per additional lifetime quitter averaged 1508 dollars ; for the 300-mg groups these costs were 1342 dollars and 2129 dollars , respectively . Cost per life-year and quality -adjusted life-years ( QALYs ) saved varied substantially by age and treatment , but were no greater than 1100 dollars for all treatment groups when averaged across the age and sex distribution for the study population . CONCLUSIONS Although the cost per life-year and QALYs saved were sufficiently low for all doses to rate these smoking cessation interventions as among the most cost effective of life-saving medical treatments , within the regimens tested 150 mg bupropion combined with either PTC or TM was the most cost effective AIMS To examine heterogeneity in outcome following treatment for smoking cessation with combined bupropion SR and behavioral counseling in women and men . DESIGN , SETTING , PARTICIPANTS This study included 875 women and 649 men recruited from a large health-care system and r and omized to one of four combinations of treatment [ two dosage levels of bupropion SR ( Zyban , 150 mg and 300 mg ) were crossed with two counseling programs of lower and higher intensity to create a four-cell design ] . MEASUREMENTS AND FINDINGS A comprehensive set of relevant individual characteristics prior to treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified six subgroups in women that ranged in proportion of non-smokers from 9.8 % to 42.9 % and six subgroups in men that ranged in proportion of non-smokers from 17.3 % to 50.0 % . CONCLUSIONS These results indicate the presence of a substantial amount of variation in treatment outcome among women and men receiving combined bupropion SR and counseling . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following cessation OBJECTIVE Fear of jeopardizing drinking outcomes has result ed in a reluctance to treat tobacco dependence concurrently with alcohol dependence , in spite of the high prevalence of smoking among patients with alcohol dependence . The objective of this study was to compare the effects of smoking treatment and intensive treatment for alcohol dependence , delivered concurrently , with delayed smoking treatment on smoking and alcohol use . METHOD For the study , 1,943 patients in intensive treatment for alcohol dependence or abuse were screened for participation . Of these , 499 smokers were enrolled and r and omized to concurrent ( during alcohol treatment ) or delayed ( 6 months later ) smoking intervention . The smoking intervention included individual behavioral counseling and nicotine replacement . The main smoking outcome measure was 7-day point prevalent tobacco abstinence , and the main drinking outcome was 6-month prolonged abstinence from alcohol ; both measured 18 months after study enrollment . RESULTS Participants in the concurrent group were more likely to participate in smoking treatment than those in the delayed group ( 78.5 % vs 64.5 % , p = .005 ) , but there was no significant difference in cessation rates at 18 months ( 12.4 % vs 13.7 % ) . Prolonged , 6-month abstinence from alcohol was worse in the concurrent group than in the delayed group at 6 , 12 and 18 months ( 41 % vs 56 % , p = .001 ; 33 % vs 42%,p = .06 ; 41 % vs 48 % , p = .14 , respectively ) , and 30-day prolonged alcohol abstinence was also worse in the concurrent treatment group ( 51 % vs 64 % , p = .004 ; 46 % vs 53 % , p = .11 ; 48 % vs 60 % , p = .01 , respectively ) . CONCLUSIONS These data show that patients in alcohol treatment are interested in smoking cessation , participate in treatment and demonstrate success ; but there was no benefit of concurrent treatment . Drinking outcomes were worse with concurrent tobacco treatment . These findings suggest that smoking cessation intervention should be provided to patients after intensive alcohol treatment ; however , the data require confirmation because they are not consistent with the existing literature BACKGROUND Previous studies have found that offering additional callback counseling support to smokers calling a telephone quit line increases quit rates . However , what is less certain is the most cost-efficient protocol for offering such a service . OBJECTIVE This study compares the efficacy of offering 2 versus 4 counseling callbacks after an initial call from Medicaid/uninsured adult smokers contacting the New York State Smokers ' Quit Line ( NYSSQL ) . Outcomes compared are the 7- and 30-day nonsmoker prevalence rates measured at 3-month follow-up and the cost per quit . DESIGN A 2-group r and omized trial was conducted . SETTING AND PARTICIPANTS The study population included 1923 adult ( 18 + years ) Medicaid/uninsured current smokers ( 10 + cigarettes per day ) who called the NYSSQL between February and March 2009 seeking help to stop smoking . At the time of the study , the NYSSQL provided Medicaid/uninsured callers with up to 6 weeks of free nicotine medications and up to 4 counseling callbacks . Half the subjects were r and omized to st and ard care with up to 4 counseling callbacks with the remaining subjects offered only 2 counseling callbacks . All participants were sent a minimum of a 2-week supply of nicotine replacement therapy , with some receiving up to 6 weeks . Participants were recontacted 3 months after enrollment in the study to assess smoking status . MAIN OUTCOME MEASURES Quit rates , total counseling callbacks completed , reductions in cigarette consumption , and cost per quit measures . RESULTS There was not a significant difference between study groups in the number of callbacks completed . There was also no difference in 7- or 30-day nonsmoker prevalence rates measured after 3 months ' follow-up or reported use of the free nicotine replacement therapy between those assigned to either the 2- or 4-callback protocol s. The cost per quit was essentially the same in both groups ( 2 callbacks--$442 per quit vs 4 callbacks--$445 per quit ) . CONCLUSION There was no advantage in terms of quit success or cost to offering up to 4 callbacks instead of 2 callbacks INTRODUCTION Tobacco use is a serious public health problem among low-income Chinese Americans with limited English proficiency . Chinese men are at high risk for smoking-related morbidity and mortality . We tested the feasibility of a culturally and linguistically sensitive smoking intervention program with combined counseling and pharmacological components for Chinese smokers in New York City ; identified factors and techniques that enhance the administration and appropriateness of the intervention program ; and examined the overall impact of this program on quit attempts , quit rates , and overall smoking reduction . METHODS We were guided by the transtheoretical model and used an adapted motivational interviewing ( MI ) approach . The study involved a r and omized sample with pretreatment assessment and multiple follow-up measures . Eligible participants ( N = 122 ) were r and omly assigned to intervention ( 4 individualized counselor-led MI sessions and nicotine replacement therapy [ NRT ] ) or control groups ( 4 general health education sessions , self-help material s , and NRT ) . RESULTS Quit rate at 6 months in the intervention group was 67 % versus 32 % for the control group , indicating minimal relapse and a highly successful intervention program . Increase in self-efficacy and decease in pros of smoking from baseline to 6-month follow-up were positively associated with smoking cessation . The number of cigarette smoked at baseline was inversely related to smoking cessation . Results indicate that a combined intensive behavioral counseling and pharmacological intervention can reduce smoking substantially . CONCLUSION The results of this pilot will be used as a basis for a large-scale r and omized trial of an intervention with combined culturally and linguistically sensitive MI and NRT components for Chinese and other Asian ethnic groups OBJECTIVE A pilot study was conducted to determine the feasibility and potential efficacy of an interactive voice response ( IVR ) follow-up system for smokers recently hospitalized with coronary heart disease ( CHD ) . METHODS Ninety-nine smokers hospitalized with CHD completed a baseline question naire , were provided with bedside counseling , and offered nicotine replacement therapy . They were r and omly assigned to a usual care ( UC ) or an IVR group . The IVR group received automated telephone follow-up calls 3 , 14 and 30 days after discharge inquiring about their smoking status and confidence in remaining smoke-free . When deemed necessary , they were offered additional counseling . Smoking status was determined 52 weeks after hospital discharge . RESULTS The 52-week point prevalence abstinence rate in the IVR group was 46.0 % compared to 34.7 % in the UC group ( OR=1.60 , 95 % CI : 0.71 - 3.60 ; P=.25 ) . After adjustment for education , age , reason for hospitalization , length of hospitalization , and quit attempts in the past year , the odds of quitting in the IVR group compared to the UC group were 2.34 ( 95 % CI : 0.92 - 5.92 ; P=.07 ) . CONCLUSIONS IVR is a promising technology for following CHD patients attempting to quit smoking following discharge from hospital , however , a larger trial is required to confirm its efficacy . PRACTICE IMPLICATION S IVR may enhance the timely provision of follow-up counseling for smoking cessation in patients with CHD To date , only one study has been published on individual characteristics associated with outcome following st and ard treatment with bupropion SR for smoking cessation . To investigate treatment outcome beyond the 6-week end-of-treatment point , the present study examined characteristics associated with more clinical ly relevant smoking endpoints following treatment with bupropion SR in a large health care system . A total of 1,524 smokers ( 649 men and 875 women ) of average age 45.1 years were r and omized to receive one of four combinations of bupropion SR ( 150 or 300 mg ) and behavioral counseling ( tailored mailings or proactive telephone counseling ) and assessed for point-prevalent smoking status at 3 and 12 months . Multiple logistic regression analyses of potential risk factors for 12-month point-prevalent smoking and for persistent smoking ( point-prevalent smoking at both follow-ups ) following treatment were conducted for men and women combined and separately . Risk factors for smoking at both endpoints in the combined sample included treatment with tailored mailings , female gender , younger age , higher levels of tobacco dependence , shorter previous quit attempts , previous use of nicotine replacement therapy , and report of current depressive symptoms or lifetime depression . Risk factors for smoking following treatment identified in women only included treatment with the lower dose of bupropion SR , younger age , and higher perceived stress , whereas those that were unique to men included the presence of lifetime depression . The results are discussed in terms of their implication s for the need for more effective treatments in general , and the role of individual differences in the likelihood of returning to smoking following treatment for quitting BACKGROUND The authors evaluated the incremental efficacy of telephone counselling by a nurse in addition to physician advice and nicotine replacement therapy in helping patients to stop smoking . METHODS The trial was conducted at the University of Ottawa Heart Institute . A total of 396 volunteers who smoked 15 or more cigarettes daily were r and omly assigned to either of 2 groups : usual care ( control group ) and usual care plus telephone counselling ( intervention group ) ; the groups were stratified by sex and degree of nicotine dependence . Usual care involved the receipt of physician advice on 3 occasions , self-help material s and 12 weeks of nicotine replacement therapy . Telephone counselling was provided by a nurse at 2 , 6 and 13 weeks after the target quit date . Point-prevalent quit rates were determined at 52 weeks after the target quit date . RESULTS The point-prevalent quit rates at 52 weeks did not differ significantly between the control and intervention groups ( 24.1 % v. 23.4 % respectively ) . The quit rates did not differ significantly at the secondary measurement points of 4 , 12 and 26 weeks . INTERPRETATION Brief physician assistance , along with nicotine replacement therapy , can help well-motivated smokers to quit . Three additional sessions of telephone counselling by a nurse were ineffective in increasing quit rates . This form of assistance may be useful in the absence of physician advice or when self-selected by patients The study evaluated the efficacy of the Committed Quitters Program ( CQP ) , a computer-tailored set of printed behavioral support material s offered free to purchasers of NicoDerm CQ patches , as a supplement to the nicotine patch and the st and ard brief User 's Guide ( UG ) and audiotape . Callers to the CQP enrollment were r and omized to either CQP ( n=1854 ) or just the UG ( n=1829 ) . Abstinence and use of program material s were assessed by telephone interview at 6 and 12 weeks ( the latter falling 2 weeks after patch use was to be discontinued ) . Considering all respondents , abstinence rates did not differ significantly between the UG and CQP groups . As expected , among those who reported they used their assigned material s ( 80.1 % of the sample ) smokers who received CQP demonstrated higher quit rates at both 6 weeks ( 38.8 % v. 30.7 % ) and 12 weeks ( 18.2 % v. 11.1 % ) , compared to the UG group . Among those who used it , the Committed Quitters Program proved to be an effective behavioral treatment , improving quit rates over nicotine replacement therapy and a brief untailored written guide and audiotape Context Smoking cessation is difficult and may require repeated or intensive interventions . Contribution In this multicenter trial , 750 primary care patients who smoked at least 10 cigarettes per day were r and omly assigned to pharmacotherapy ( nicotine patch or bupropion ) , pharmacotherapy supplemented with up to 2 calls from trained counselors , or pharmacotherapy supplemented with up to 6 counseling calls . Utilization of the interventions , which were offered every 6 months for 2 years , declined over time . Smoking abstinence rates at 2 years were 23 % , 24 % , and 28 % in the 3 groups . Caution Pharmacotherapy was free . Smoking abstinence was self-reported . The Editors Cigarette smoking is a chronic illness characterized by repeated cycles of quit attempts and relapse . Most models for addressing smoking cessation are based on single , short-term interventions lasting only a few weeks or months ( 1 ) . Although most smokers will not quit after a single intervention , few studies have addressed the chronic nature of nicotine dependence by providing systematic , repetitive treatment opportunities ( 1 ) . Providing treatment only to smokers who are already prepared to quit further limits the reach of current smoking cessation interventions ( 2 ) . New models of chronic disease care might provide an alternative approach for exp and ing the reach and effectiveness of smoking cessation efforts ( 3 ) . Physicians are in direct contact with approximately 70 % of smokers each year ( 4 , 5 ) . Their potential role in promoting smoking cessation has been well delineated and incorporated into current clinical practice guidelines ( 1 ) . With the development of new , more effective prescription pharmacotherapy for smoking cessation , the role of primary care practice s in promoting smoking cessation is now more important than ever . Unfortunately , only half of the smokers who see their physicians are asked about their smoking ( 6 ) , and even fewer receive advice from their health care provider to quit or receive pharmacotherapy or follow-up ( 4 , 7 ) . Smoking cessation counseling competes with other pressing clinical tasks , and beyond brief advice , many physicians feel they are too busy to routinely and repeatedly counsel participants who smoke ( 810 ) . To assist primary care physicians in the treatment of rural smokers , we developed KanQuit , a smoking cessation program based on the chronic care model ( 4 ) , which integrates principles of disease management into the treatment of smokers seen in rural primary care . Our objective was to enroll smokers , regardless of their willingness to quit , into a disease registry and compare cessation rates among smokers who received pharmacotherapy alone or combined with either moderate-intensity or high-intensity disease management that includes counseling and provider feedback . Methods Design Overview We did a r and omized , single-blind trial of varying levels of disease management for smoking cessation . We recruited participants who smoked more than 10 cigarettes per day from rural primary care clinics across Kansas and r and omly assigned them to receive pharmacotherapy alone , pharmacotherapy supplemented by 1 to 2 counseling calls every 6 months ( moderate-intensity disease management ) , or pharmacotherapy supplemented by up to 6 counseling calls every 6 months ( high-intensity disease management ) . For recipients of moderate-intensity and high-intensity disease management , we faxed periodic progress reports to their physician . We offered all participants free pharmacotherapy ( either bupropion or transdermal nicotine patch ) every 6 months . We enrolled participants from June 2004 to October 2005 and followed them for 24 months , completing follow-up in December 2007 . All participants provided written informed consent . The University of Kansas Medical Center 's Human Subjects Committee approved the study . Setting and Participants We conducted our study in 50 rural primary care practice s in the Kansas Physicians Engaged in Prevention Research network ( 11 ) . As part of a rural primary care research experience , trained medical students systematic ally screened participants , identified smokers , and recruited them for this study , regardless of their interest in quitting ( 12 ) . We considered smokers eligible if they had a primary care physician who participated in this study ; were older than 18 years ; smoked more than 10 cigarettes per day for at least 1 year and for at least 25 of the past 30 days ; spoke English ; and had a telephone . We excluded smokers if they were pregnant or planned to become pregnant , planned to move out of the study area , had signs of dementia or mental illness that would preclude participation , or lived with a smoker already enrolled in the study . Of the 1827 smokers we screened , 61 % met criteria for study entry ( Figure 1 ) . Of these , we enrolled 67 % . Figure 1 . Study flow diagram . HDM = high-intensity disease management ; MDM = moderate-intensity disease management ; PM = pharmacotherapy management . R and omization and Interventions Participant R and omization R and omization occurred at the participant level . A computer-generated r and om-number table was used to generate allocation cards in blocks of 24 , with allocation equally distributed across treatment groups . To conceal allocation , we placed these cards in sequentially numbered , opaque , sealed envelopes . After research assistants verified participant eligibility and completed the baseline assessment , the project director opened the next sequential sealed envelope and determined the participant 's treatment allocation . One of 9 counselors trained in smoking cessation and motivational interviewing ( 12 ) conducted all interventions from a single central site . We assigned participants to counselors without regard to practice site . Pharmacotherapy At baseline , all smokers received a health education mailing that consisted of a welcome letter , information about the use of bupropion and the nicotine patch for smoking cessation , and copies of You Can Quit Smoking : Consumer Guide ( 13 ) and When Smokers QuitThe Health Benefits Over Time ( 14 ) . At baseline and at 6 , 12 , and 18 months , participants received a mailed offer for free pharmacotherapy that consisted of either a 6-week course of a nicotine patch ( 21 mg/d ) or a 7-week course of sustained-release bupropion ( 150 mg twice daily ) . Participants interested in using either medication could return a postage-paid postcard or call a toll-free number . We screened all participants who requested pharmacotherapy for potential contraindications ( 15 ) . Participants with absolute contraindications for a given drug were ineligible to receive that drug but were offered the option of receiving the other drug . Participants with contraindications to both drugs were not eligible to receive medication from the study but could participate in all other aspects of the intervention . For participants who requested bupropion and those with relative contraindications to the nicotine patch , research staff faxed a prescription request to their primary care physicians . This prescription request delineated any relative contraindications or potential drug interactions . For these participants , their physicians made the final assessment of the appropriateness of the bupropion or the patch . For participants without contraindications to the nicotine patch or on receipt of a faxed , signed prescription , the bupropion or patches were mailed to the participant along with instructions for use . Disease Management In addition to pharmacotherapy , the moderate-intensity and high-intensity disease management groups received educational support , telephone counseling , and periodic progress reports with counseling suggestions faxed to their physician . Every 6 months , they received a KanQuit newsletter that addressed tips on quitting smoking , talking with their physician about smoking , and using pharmacotherapy for cessation . The newsletters were personalized to include study up date s , counselor photographs , physician feature stories , and testimonials of participants who had quit smoking . We offered participants assigned to moderate-intensity disease management up to 2 telephone-based counseling sessions every 6 months ( 1 session to promote a quit attempt and 1 additional follow-up session for those who made a quit attempt ) . We offered participants assigned to high-intensity disease management up to 6 counseling calls every 6 months to either promote quitting or prevent relapse . We scheduled calls at the participant 's convenience , and they varied according to the participant 's quit plan but followed a rough schedule of calls at 1 , 3 , 6 , 9 , and 16 weeks after the onset of each 6-month treatment cycle . Counselors used motivational interviewing techniques and followed a semistructured protocol to promote a cessation attempt or , for abstinent smokers , to encourage relapse prevention . During counseling calls , case managers reminded participants about the availability of pharmacotherapy and , for interested participants , provided immediate support for acquiring either the nicotine patch or bupropion , as described previously . We faxed personalized progress reports with suggestions for interventions to the participant 's physician after the first counseling call ( both moderate-intensity and high-intensity disease management participants ) and after the last counseling call ( high-intensity disease management participants only ) during each 6-month cycle . We faxed additional progress reports to the participant 's physician whenever the moderate-intensity or high-intensity disease management participant set a quit date . Outcomes , Measurements , and Follow-up Research assistants who were blinded to treatment group assignment conducted assessment s by telephone at baseline and at 6 , 12 , 18 , and 24 months . Primary Outcome The primary outcome measure was self-reported 7-day abstinence at 24 months , defined as not having smoked a cigarette during the previous 7 days . Although self-reported abstinence has been Abstract Aim : To examine heterogeneity in outcome at 12 months following 8 weeks of treatment for smoking cessation with bupropion sustained-release ( SR ) 150 or 300 mg/day combined with behavioural counselling . Design , setting , participants : Smokers were recruited from a large healthcare system and then r and omized to receive either bupropion SR 150 mg/day ( n = 763 ) or 300 mg/day ( n = 761 ) taken for 8 weeks in combination with either proactive telephone counselling or a tailored mail approach . Measurements and findings : A comprehensive set of relevant individual pre-treatment and treatment characteristics was included in the analysis . Smoking outcome at 12 months was defined as point-prevalence of any regular self-reported smoking within the 7 days prior to follow-up contact . Classification and regression tree analysis identified subgroups that varied with respect to likelihood of being nonsmokers at 12 months . Seven subgroups were identified among those receiving bupropion SR 150 mg/day ( proportion of nonsmokers at 12 months ranged from 13.7 % to 43.5 % ) and eight subgroups among those receiving bupropion SR 300 mg/day ( proportion of nonsmokers at 12 months ranged from 9.6 % to 51.7 % ) . In the 150-mg/day group , those with the lowest rate reported no previous quit attempt of 1 month or more in duration while those with the highest rate all reported previous quit attempts of 1 month or longer . In the 300 mg/day group , those with the lowest rate had very high levels of dependence while those with the highest rate were more highly educated and smoked at a lower level . Across all subgroups , cost per 12-month quitter ranged from a low of $ US302 to a high of $ US2502 . Conclusions : These results indicate the presence of a substantial amount of variation in outcome following treatment with both dosages of bupropion SR , with substantial cost consequences . Variation in outcome could be reduced by providing treatments tailored to subgroups of individuals who are at exceptionally high risk for smoking following a quit attempt AIMS This paper sets out to evaluate the possibility that smoking cessation interventions which make use of current psychological theories and constructs can be more successful than programmes based largely on nicotine replacement therapy and will be more satisfying to participants . RATIONALE Nicotine replacement therapy is currently the most widely used method for helping smokers give up the habit . Numerous studies have shown this to be a successful approach for many smokers , but the majority still fail to benefit . Typically three quarters of smokers given nicotine replacement are smoking again one year later . This study investigates whether nicotine replacement can be enhanced by the addition of psychological techniques . DESIGN Smokers recruited via publicity in the local media were r and omly assigned to one of two treatment conditions . The first condition consisted of a series of group sessions in which volunteers were instructed in nicotine replacement , and a number of psychological techniques , the most important being cognitive counter conditioning . The second condition was identical to the first but without the cognitive counter conditioning . Finally background quit rate was determined using waiting list controls . RESULTS Both interventions were successful in helping smokers quit the habit , based upon an analysis at 6 months , compared with waiting list controls . The experimental condition incorporating cognitive counter conditioning produced a much higher quit rate than the condition based largely upon nicotine replacement , although the difference was not significant . CONCLUSIONS This study is highly suggestive that nicotine replacement therapy can be enhanced by the inclusion of psychological techniques in group work , result ing in abstention rates higher than nicotine replacement alone and increasing participant satisfaction . Further work is needed with larger numbers to verify that this is indeed a significant gain and to investigate whether psychological techniques can give longer term benefits Abstract Tobacco dependence is prevalent among alcohol dependent patients , and causes increased morbidity and mortality . Concurrent treatment for these disorders may be advantageous , but there are concerns about adverse effects on alcohol treatment outcomes . The Timing of Alcohol and Smoking Cessation ( TASC ) Study is a r and omized controlled clinical trial to compare the effectiveness of smoking cessationtreatment offered concurrently or six months following intensive rehabilitation for alcohol dependence . This paper describes the study design and baseline characteristics of the study population . Participants were current smokers in intensive alcohol dependence treatment , with willingness to consider quitting smoking . Smoking intervention offered behavioral and pharmacological treatment . One thous and nine hundred forty — three patients were screened for enrollment ; 499 were eligible and participated ( 26 % ) . We describe demographic characteristics , smoking behavior and attitudes among participants and non participants toward smoking cessation and drinking . We conclude that there is considerable interest in smoking cessation in alcohol dependent treatment population s , and recruitment to research studies is feasible AIM To evaluate potential mediators of an extended cognitive behavioral smoking cessation intervention . DESIGN Analysis of data from a r and omized clinical trial of smoking cessation . SETTING The Habit Abatement Clinic , University of California , San Francisco . PARTICIPANTS Participants were older cigarette smokers ( > /=50 years old ) . Those receiving St and ard Treatment ( N=100 ) were compared to those receiving extended cognitive behavioral treatment ( N=99 ) . MEASUREMENTS Negative affect was measured with the Profile of Mood States ( POMS ) , the Medical Outcome Studies 36-item Short-Form Health Survey ( SF-36 ) , and the Perceived Stress Scale ( PSS ) . Abstinence-specific social support was measured with the Partner Interaction Question naire ( PIQ ) . Motivation to quit and abstinence self-efficacy were measured on 1 - 10 scales with the Thoughts about Abstinence Question naire . All were measured at the beginning of treatment and week 52 . RESULTS Analyses revealed that extended CBT increased abstinence self-efficacy over the first 52 weeks postcessation . This effect , in turn , was positively associated with 7-day point prevalence abstinence at week 64 while controlling for treatment condition , and eliminated the independent effect of treatment condition on abstinence . The test of mediation indicated a significant effect , and abstinence self-efficacy accounted for 61 % to 83 % of the total effect of treatment condition on smoking abstinence . Results failed to support a mediational role of negative affect , abstinence-specific social support , or motivation to quit . CONCLUSIONS The results of the present study are consistent with theories of relapse and studies of more time-limited interventions , and underscore the importance of abstinence self-efficacy in achieving long-term abstinence from cigarettes BACKGROUND Action aim ed at changing smoking behavior to prevent cardiovascular patients from further impairing their health is advisable . Cognitive behavioral interventions can be effective in this regard since they attempt to influence cognitive determinants that presumably lead to smoking cessation . The Minimal Intervention Strategy for Cardiology patients ( C-MIS ) is such an intervention , tailored to the patients ' readiness to change . Our aim is to investigate whether the C-MIS is successful in changing patients ' cognitions such as attitudes , social influence , self-efficacy and intention to quit during a 1-year period . METHODS Smoking out patients ( N = 315 ) with cardiovascular disease were included . They were r and omized and received either Nicotine Replacement Therapy ( NRT ) or NRT + C-MIS . At baseline ( T1 ) , sociodemographic and clinical characteristics were measured . Cognitions and quitting behavior were assessed at baseline and at four follow-up measurements . RESULTS Comparing treatments , the C-MIS did not affect pros of quitting , pros of smoking and social influence . We did find small effects of the C-MIS on intention to quit and self-efficacy , although only for higher-educated patients . CONCLUSION The C-MIS appears successful in affecting intention to quit and self-efficacy abilities , but only for patients with higher education levels . Initial positive changes in cognitions may also emerge in a medical intervention , such as the provision of NRT BACKGROUND Lack of interest has been cited as a reason not to offer cessation assistance to smokers , but research suggests that smokers accept treatments offered proactively . This study assessed acceptability , utilization , and effectiveness of free smoking cessation treatment among diverse primary care patients . METHOD Medical assistants invited 4174 adult smokers to participate . Enrollees ( 1869 ) self-selected or were assigned to receive free nicotine patch therapy alone or in combination with the Committed Quitters(R ) program , and for some , individual counseling . RESULTS In nearly 68 % of cases , patients accepted a treatment invitation ; 77 % of eligible smokers enrolled ; 85 % of these picked up free patches . Given a choice of treatments , 75 % of participants elected a psychosocial treatment in addition to patch therapy . Thirteen percent of treatment initiators achieved biochemically confirmed 7-day point-prevalence abstinence at 1 year , with no significant treatment effects . Minority patients showed greater initial interest but less utilization did than White patients . CONCLUSIONS Free , readily accessible smoking cessation treatment offered in primary care setting s was accepted and used by the majority of unselected smokers of diverse racial/ethnic origins . Psychosocial treatment components did not significantly increase abstinence rates . Barriers , rather than lack of interest , may keep minority smokers from using cessation treatments AIMS To test the efficacy of two smoking cessation interventions in a HIV positive ( HIV+ ) sample : st and ard care ( SC ) treatment plus nicotine replacement therapy ( NRT ) versus more intensive motivationally enhanced ( ME ) treatment plus NRT . DESIGN R and omized controlled trial . SETTING HIV+ smoker referrals from eight immunology clinics in the northeastern United States . PARTICIPANTS A total of 444 participants enrolled in the study ( mean age = 42.07 years ; 63.28 % male ; 51.80 % European American ; mean cigarettes/day = 18.27 ) . INTERVENTIONS SC participants received two brief sessions with a health educator . Those setting a quit date received self-help quitting material s and NRT . ME participants received four sessions of motivational counseling and a quit-day counseling call . All ME intervention material s were tailored to the needs of HIV+ individuals . MEASUREMENTS Biochemically verified 7-day abstinence rates at 2-month , 4-month and 6-month follow-ups . FINDINGS Intent-to-treat ( ITT ) abstinence rates at 2-month , 4-month and 6-month follow-ups were 12 % , 9 % and 9 % , respectively , in the ME condition , and 13 % , 10 % and 10 % , respectively , in the SC condition , indicating no between-group differences . Among 412 participants with treatment utilization data , 6-month ITT abstinence rates were associated positively with low nicotine dependence ( P = 0.02 ) , high motivation to quit ( P = 0.04 ) and Hispanic American race/ethnicity ( P = 0.02 ) . Adjusting for these variables , each additional NRT contact improved the odds of smoking abstinence by a third ( odds ratio = 1.32 , 95 % confidence interval = 0.99 - 1.75 ) . CONCLUSIONS Motivationally enhanced treatment plus NRT did not improve cessation rates over and above st and ard care treatment plus NRT in this HIV+ sample of smokers . Providers offering brief support and encouraging use of nicotine replacement may be able to help HIV+ patients to quit smoking INTRODUCTION Phone counseling has become st and ard for behavioral smoking cessation treatment . Newer options include Web and integrated phone-Web treatment . No prior research , to our knowledge , has systematic ally compared the effectiveness of these three treatment modalities in a r and omized trial . Underst and ing how utilization varies by mode , the impact of utilization on outcomes , and predictors of utilization across each mode could lead to improved treatments . METHODS One thous and two hundred and two participants were r and omized to phone , Web , or combined phone-Web cessation treatment . Services varied by modality and were tracked using automated systems . All participants received 12 weeks of varenicline , printed guides , an orientation call , and access to a phone supportline . Self-report data were collected at baseline and 6-month follow-up . RESULTS Overall , participants utilized phone services more often than the Web-based services . Among treatment groups with Web access , a significant proportion logged in only once ( 37 % phone-Web , 41 % Web ) , and those in the phone-Web group logged in less often than those in the Web group ( mean = 2.4 vs. 3.7 , p = .0001 ) . Use of the phone also was correlated with increased use of the Web . In multivariate analyses , greater use of the phone- or Web-based services was associated with higher cessation rates . Finally , older age and the belief that certain treatments could improve success were consistent predictors of greater utilization across groups . Other predictors varied by treatment group . CONCLUSIONS Opportunities for enhancing treatment utilization exist , particularly for Web-based programs . Increasing utilization more broadly could result in better overall treatment effectiveness for all intervention modalities OBJECTIVE To examine whether reimbursement for Provider Counseling , Pharmacotherapies , and a telephone Quitline increase smoking cessation relative to Usual Care . STUDY DESIGN R and omized comparison trial testing the effectiveness of four smoking cessation benefits . SETTING Seven states that best represented the national population in terms of the proportion of those > or = 65 years of age and smoking rate . PARTICIPANTS There were 7,354 seniors voluntarily enrolled in the Medicare Stop Smoking Program and they were followed-up for 12 months . INTERVENTION(S ) ( 1 ) Usual Care , ( 2 ) reimbursement for Provider Counseling , ( 3 ) reimbursement for Provider Counseling with Pharmacotherapy , and ( 4 ) telephone counseling Quitline with nicotine patch . MAIN OUTCOME MEASURE Seven-day self-reported cessation at 6- and 12-month follow-ups . PRINCIPAL FINDINGS Unadjusted quit rates assuming missing data = smoking were 10.2 percent ( 9.0 - 11.5 ) , 14.1 percent ( 11.7 - 16.5 ) , 15.8 percent ( 14.4 - 17.2 ) , and 19.3 percent ( 17.4 - 21.2 ) at 12 months for the Usual Care , Provider Counseling , Provider Counseling + Pharmacotherapy , and Quitline arms , respectively . Results were robust to sociodemographics , smoking history , motivation , health status , and survey nonresponse . The additional cost per quitter ( relative to Usual Care ) ranged from several hundred dollars to $ 6,450 . CONCLUSIONS A telephone Quitline in conjunction with low-cost Pharmacotherapy was the most effective means of reducing smoking in the elderly Cigarette smoking is highly prevalent among people living with HIV/AIDS and poses unique health risks . Smoking cessation programs tailored to this population have documented improved smoking outcomes with nicotine replacement therapy ( NRT ) . The current study examined 6-month abstinence rates from a r and omized clinical trial targeting 412 HIV-positive adult current smokers ( 51 % European American , 19 % African American , and 17 % Hispanic American ) and tested whether psychosocial variables , such as self-efficacy and decisional balance , mediated the relationship between NRT and long-term abstinence . Meeting criteria for complete mediation , 6-month smoking abstinence rates improved significantly with increases in these mediators , and the association of NRT and smoking abstinence was no longer significant once changes in self-efficacy and decisional balance were taken into account . Failure to translate gains in self-efficacy among African Americans into improved abstinence rates accounted for racial/ethnic differences among participants . Specific psychosocial factors , such as self-efficacy , may be particularly amenable to change in cessation interventions and should be addressed with greater awareness of how cultural and social context ual factors impact treatment response among people living with HIV/AIDS |
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