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2,600 | 30,944,038 | Education was the most common intervention and the majority of studies targeted parent knowledge or behavior .
Few interventions attempted to change healthcare provider knowledge or behavior .
Assessing barriers to implementation , identifying relevant ED context ual factors , and underst and ing provider and patient attitudes and beliefs about discharge communication were identified as important factors for improving discharge communication practice .
Strengthening discharge communication in a pediatric emergency context presents a significant opportunity for improving parent comprehension and health outcomes for children . | Background The majority of children receiving care in the emergency department ( ED ) are discharged home , making discharge communication a key component of quality emergency care .
Parents must have the knowledge and skills to effectively manage their child ’s ongoing care at home .
Parental fatigue and stress , health literacy , and the fragmented nature of communication in the ED setting may contribute to suboptimal parent comprehension of discharge instructions and inappropriate ED return visits .
The aim of this study was to examine how and why discharge communication works in a pediatric ED context and develop recommendations for practice , policy , and research . | OBJECTIVE To test the hypothesis that educating parents about use of their primary care provider and providing information about common pediatric illnesses will reduce visits to the pediatric emergency department ( PED ) . DESIGN Prospect i ve , r and omized , controlled trial conducted from September 1 , 1993 , to October 31 , 1994 . SETTING Pediatric emergency department of an urban university hospital . PARTICIPANTS Parents of 130 patients seen in the PED for minor illness . INTERVENTIONS Subjects were r and omized to intervention or control groups . Parents in both groups were interviewed about their child 's health and use of health care services . The intervention group received education on pediatric health care issues ; the control group received usual PED discharge instructions . Use of the PED by all subjects was tracked for 6 months by telephone follow-up and medical record review . MAIN OUTCOME MEASURES Differences between the two groups in total number of return visits to the PED and return visits to the PED for minor illness . RESULTS Sixty-seven ( 97 % ) of the 69 patients in the intervention group and 56 ( 92 % ) of the 61 patients in the control group identified a primary care provider . At 6-month follow-up , 21 patients ( 30 % ) from the intervention group and 16 ( 26 % ) from the control group had returned to the PED ( P = .68 , chi 2 ) . Seventeen ( 81 % ) of intervention group returnees to the PED had minor illness , as did 11 ( 69 % ) of control group returnees . CONCLUSIONS A one-time educational intervention in the PED does not alter long-term emergency department utilization habits . More extensive education and greater availability of primary care providers may be needed to decrease use of the PED for minor illness Background Effective communication between physician and patient is essential to optimize care after discharge from the emergency department ( ED ) . Written discharge care instructions ( DCI ) complement verbal instructions and have been shown to improve communication and patient management . In 2012 , Centers for Medicare and Medicaid Services proposed a quality measure ( OP-19 ) that assesses compliance with key elements considered essential for high- quality written DCI . Objective To evaluate the impact of a QI intervention on improving quality of written DCI in a pediatric emergency department ( PED ) . Methods A QI initiative was conducted at a tertiary PED with greater than 60,000 annual visits . Based on Centers for Medicare and Medicaid Services OP-19 measure and group consensus , 8 elements were defined a priori as requisites for good quality DCI . These elements are : Customized noteExplanation of presenting complaint/diagnosisTest(s ) performedTest(s ) results New medication(s)Reason for medication(s ) Reasons to follow-upFollow-up physician's/specialty name Providers review ed a r and om sample of DCI of patients . Proportion of DCI that had each element documented was compared between preintervention phase ( PRE ) and postintervention phase ( POST ) . Results Three hundred twenty-nine DCI ( PRE ) and 1434 DCI ( POST ) were review ed . The POST DCI showed statistically significant improvement for each of the 8 elements . The bundle measure ( proportion containing all 8 elements ) increased from 23 % ( PRE ) to 79 % ( POST ) ( P < 0.001 ) . Conclusions The ED DCI improved in all 8 elements after a QI intervention . A detailed DCI at ED discharge enhances the patient 's ability to comply with postdischarge treatment plan . Further studies are needed to evaluate the impact of improving DCI on ED return rates and other outcomes OBJECTIVE Suicide is the third leading cause of death among adolescents . Many suicidal youths treated in emergency departments do not receive follow-up treatment as advocated by the National Strategy for Suicide Prevention . Two strategies for improving rates of follow-up treatment were compared . METHODS In a r and omized controlled trial , suicidal youths at two emergency departments ( N=181 ; ages ten to 18 ) were individually assigned between April 2003 and August 2005 to one of two conditions : an enhanced mental health intervention involving a family-based cognitive-behavioral therapy session design ed to increase motivation for follow-up treatment and safety , supplemented by care linkage telephone contacts after emergency department discharge , or usual emergency department care enhanced by provider education . Assessment s were conducted at baseline and approximately two months after discharge from the emergency department or hospital . The primary outcome measure was rates of outpatient mental health treatment after discharge . RESULTS Intervention patients were significantly more likely than usual care patients to attend outpatient treatment ( 92 % versus 76 % ; p=.004 ) . The intervention group also had significantly higher rates of psychotherapy ( 76 % versus 49 % ; p=.001 ) , combined psychotherapy and medication ( 58 % versus 37 % ; p=.003 ) , and psychotherapy visits ( mean 5.3 versus 3.1 ; p=.003 ) . Neither the emergency department intervention nor community outpatient treatment ( in exploratory analyses ) was significantly associated with improved clinical or functioning outcomes . CONCLUSIONS Results support efficacy of the enhanced emergency department intervention for improving linkage to outpatient mental health treatment but underscore the need for improved community outpatient treatment to prevent suicide , suicide attempts , and poor clinical and functioning outcomes for suicidal youths treated in emergency departments BACKGROUND Efforts to enroll inner-city asthmatic children into continuity care after a pediatric emergency department ( PED ) visit are frequently unsuccessful . Providing parents with documentation of their child 's allergic status and how this can be used to tailor an asthma management plan may improve adherence to scheduled continuity appointments . OBJECTIVE To determine whether skin testing children during PED visits for wheezing and providing parents with skin test results improves adherence to follow-up visits . METHODS A convenience sample of children aged 2 to 12 years with asthma who presented to the PED with wheezing were eligible . Enrolled children were r and omized to group 1 ( no skin test ) or group 2 ( skin test ) . At discharge , both groups scheduled asthma clinic appointments for within 1 week . Children in group 2 underwent skin testing with st and ard allergens , and parents were given documentation of skin test results . Adherence was assessed by computer confirmation of the patient 's asthma clinic visit . RESULTS Seventy-seven children were enrolled : 39 in group 1 and 38 in group 2 . The mean age was 7 years ; 69 % had mild intermittent asthma . Twenty-four percent of children ( 9 of 38 ) in group 1 vs 46 % ( 17 of 37 ) in group 2 were followed up in the asthma clinic ( P < .05 ) . Children in group 2 were 2.6 ( 95 % confidence interval , 1.02 - 6.65 ) times more likely to keep appointments compared with children in group 1 . CONCLUSIONS Parents who receive evidence in the PED of their child 's allergic status and probable relationship to the child 's asthma are more likely to adhere to scheduled continuity visits Objective : The objective of the study was to compare change in asthma knowledge among parents with low or adequate health literacy after video or written asthma education delivered during their child 's asthma-related emergency department ( ED ) visit . Methods : We recruited a convenience sample of parents presenting to the ED with their asthmatic child 2 to 14 years old . Parents were r and omized to receive video ( intervention ) or written ( active-control ) asthma education material s. Health literacy levels were determined using the Rapid Estimate of Adult Literacy in Medicine tool . Asthma knowledge was evaluated at enrollment and 6-week telephone follow-up . Differences in knowledge scores were analyzed using Wilcoxon signed rank tests ; & khgr;2 tests were used for comparisons of categorical variables . Results : Of 150 eligible parents , 129 participated ( 86 % ) , and 117 were eligible for follow-up . Telephone follow-up was completed with 86 parents ( 74 % ) . Health literacy levels were low in 31 % of the parents . High asthma knowledge scores at enrollment were achieved by 33 % of low-literacy and 59 % of adequate-health-literacy parents ( P = 0.025 ) . Improvement in knowledge was realized for low-literacy parents regardless of the type of education ( P < 0.001 ) . Parents with adequate health literacy showed increased knowledge scores only after viewing the video . Conclusions : Asthma education material s distributed at the time of an ED visit increase parental knowledge about the disease . Video-based asthma education appears promising as a tool for increasing asthma knowledge in both low- and adequate-health-literacy parents Background Mild traumatic brain injury is a frequent cause of presentation to emergency departments . Despite the availability of clinical practice guidelines in this area , there is variation in practice . One of the aims of the Neurotrauma Evidence Translation program is to develop and evaluate a targeted , theory- and evidence -informed intervention to improve the management of mild traumatic brain injury in Australian emergency departments . This study is the first step in the intervention development process and uses the Theoretical Domains Framework to explore the factors perceived to influence the uptake of four key evidence -based recommended practice s for managing mild traumatic brain injury . Methods Semi-structured interviews were conducted with emergency staff in the Australian state of Victoria . The interview guide was developed using the Theoretical Domains Framework to explore current practice and to identify the factors perceived to influence practice . Two research ers coded the interview transcripts using thematic content analysis . Results A total of 42 participants ( 9 Directors , 20 doctors and 13 nurses ) were interviewed over a seven-month period . The results suggested that ( i ) the prospect i ve assessment of post-traumatic amnesia was influenced by : knowledge ; beliefs about consequences ; environmental context and re sources ; skills ; social/professional role and identity ; and beliefs about capabilities ; ( ii ) the use of guideline -developed criteria or decision rules to inform the appropriate use of a CT scan was influenced by : knowledge ; beliefs about consequences ; environmental context and re sources ; memory , attention and decision processes ; beliefs about capabilities ; social influences ; skills and behavioral regulation ; ( iii ) providing verbal and written patient information on discharge was influenced by : beliefs about consequences ; environmental context and re sources ; memory , attention and decision processes ; social/professional role and identity ; and knowledge ; ( iv ) the practice of providing brief , routine follow-up on discharge was influenced by : environmental context and re sources ; social/professional role and identity ; knowledge ; beliefs about consequences ; and motivation and goals . Conclusions Using the Theoretical Domains Framework , factors thought to influence the management of mild traumatic brain injury in the emergency department were identified . These factors present theoretically based targets for a future intervention OBJECTIVE . Many children are brought to the pediatric emergency department ( ED ) with acute asthma symptoms . Emergency asthma care is costly , and many ED visits may be preventable . Families often do not have written asthma action plans and lack asthma self-managment skills . This study tests a tailored self-managment intervention delivered in the ED for families of children with asthma . The primary hypotheses were that the intervention group would have greater confidence to manage asthma 14 days postintervention and more well-asthma visits and fewer urgent care/ED visits at 9 and 12 months . METHODS . This r and omized intervention/usual-care study was part of a larger ED asthma surveillance project in 4 urban pediatric ED sites . Asthma educators used a computer-based re source to tailor the intervention messages and provide a customized asthma action plan and educational summary . Children with acute asthma were enrolled during an ED visit , and follow-up telephone interviews were conducted during the next 9 months . The ED clinician classified the child ’s acute and chronic severity . RESULTS . To date , 464 subjects aged 1 to 18 years have been enrolled . The ED clinicians reported that 46 % had intermittent and 54 % had persistent chronic severity with 51 % having mild acute severity episodes . The confidence level to prevent asthma episodes and keep them from getting worse was significantly higher in the intervention group at 14 days postintervention . More subjects in the intervention group reported well-asthma visits by 9 months . Return ED visits were significantly lower in the intervention group in those with intermittent asthma . Twelve-month follow-up is in process . CONCLUSIONS . The tailored ED self-management intervention demonstrates significant effects on caregiver self-confidence and well-visit follow-up . Additional evaluation is needed to determine what impact this intervention has long-term Objective The aims of the study were to determine the following : 1 ) if a fever education program ( interactive or written ) reduces parent fever anxiety ; 2 ) if an interactive fever program was more effective as a teaching style than st and ard written material alone ; and 3 ) if a fever program increases parent fever home management and reduces return emergency department ( ED ) visits . Method A quasiexperimental , pretest and post-test pilot study examining parental fever anxiety was conducted at The Children ’s Hospital of Philadelphia . Eligible participants consisted of 87 parents and their children , aged 3 months to 5 years presenting with fever > 38.4 ° C , and without coexisting serious illness . Results Both the interactive fever education program and the st and ard written fever pamphlet were equally effective as teaching methods . Data revealed a 30 % reduction in fever anxiety rated as moderate-severe on arrival to none-low post-fever education , increased parent fever home management skills with correct use of thermometer and antipyretics , and reduced unnecessary return ED visits . Conclusion Parents in the acute and nonacute care setting may benefit from an interactive fever education program that includes the definition and benefit of fever , the correct use of a thermometer , fever home management skills , and appropriate fever telephone follow-up BACKGROUND Lack of underst and ing of diagnosis and disease process remains a major complaint of caregivers who bring their children to the pediatric emergency department ( PED ) . Misunderst and ing of diagnosis and discharge instructions can lead to unnecessary return visits and health disparities . OBJECTIVE We attempted to determine if video discharge instructions when added to st and ard of care written and verbal instruction improved caregivers ' comprehension of their child 's diagnosis , disease process , and discharge instructions . METHODS Caregivers who presented to the PED with a child 's chief complaint of fever or closed head injury ( CHI ) were included and r and omized into a control or intervention group . Each group received st and ard discharge instructions , and the intervention group additionally viewed a video . Participants completed a post-test on knowledge and were followed 2 weeks post-visit to determine follow-up care . RESULTS Sixty-three caregivers participated in the study . Eleven participants had less than a high school ( HS ) education and 52 had more than a HS education . Thirty-one children presented with fever and 32 with CHI . The intervention group had significantly higher percentage of correct answers on postintervention tests ( median [ Mdn ] = 88.89 ) than the control ( Mdn = 75.73 ; p < 0.0001 ) . Participants in the intervention group with less than a HS education ( Mdn = 89.47 ) and more than HS education ( Mdn = 88.89 ) had similar test scores ( p = 0.13 ) , whereas those in the control group with less than a HS education ( Mdn = 66.67 ) had significantly lower test scores than those with more than a HS education ( Mdn = 77.78 ; p = 0.03 ) . CONCLUSION For caregivers with children who presented to the PED with fever and CHI , video discharge instructions improved caregiver comprehension of the child 's diagnosis and disease process when added to verbal and written instructions Abstract Objective Recommended as a ‘ universal pre caution ’ for improving provider – patient communication , teach-back has a limited evidence base . Discharge from the emergency department ( ED ) to home is an important high-risk transition of care with potential for miscommunication of critical information . We examined whether teach-back improves : comprehension and perceived comprehension of discharge instructions and satisfaction among patients with limited health literacy ( LHL ) in the ED . Methods We performed a r and omized , controlled study among adult patients with LHL , r and omized to teach-back or st and ard discharge instructions . Patients completed an audio-recorded structured interview evaluating comprehension and perceived comprehension of ( 1 ) diagnosis , ( 2 ) ED course , ( 3 ) post-ED care , and ( 4 ) reasons to return and satisfaction using four Consumer Assessment of Healthcare Providers and Systems questions . Concordance with the medical record was rated using a five-level scale . We analyzed differences between groups using multivariable ordinal logistic regression . Results Patients r and omized to receive teach-back had higher comprehension of post-ED care areas : post-ED medication ( P < 0.02 ) , self-care ( P < 0.03 ) , and follow-up instructions ( P < 0.0001 ) , but no change in patient satisfaction or perceived comprehension . Conclusion Teach-back appears to improve comprehension of post-ED care instructions but not satisfaction or perceived comprehension . Our data from a r and omized , controlled study support the effectiveness of teach-back in a busy clinical setting . Further research is needed to test the utility and feasibility of teach-back for routine use including its impacts on distal outcomes Objectives The objective was to evaluate the use and utility of a novel set of emergency department discharge instructions ( DIs ) for concussion based on a child 's ongoing symptoms : symptom-guided DIs ( symptom DIs ) . Differences in clinical outcomes were also assessed . Methods A convenience sample of 114 children aged 7 to 17 years presenting to an urban pediatric emergency department with a complaint of concussion was assembled . Children were r and omized to st and ard DIs or symptom DIs . Children completed a grade d symptom checklist ( GSC ) and completed daily the GSC for 1 week . Telephone follow-up was performed at 7 days after enrollment using a st and ardized survey . Results Fifty-eight children received the symptom DIs , and 56 received the st and ard DIs . Rates of use were similar with reported rates of 92 % for symptom DIs and 84 % for st and ard DIs . Caregivers with symptom DIs reported that the DIs were more helpful in determining when their child could return to school and physical activity ( P < 0.05 ) than caregivers with st and ard DIs . Children continued to have postconcussive symptoms days and weeks after their injury with 44 % of children with symptom DIs and 51 % of children with st and ard DIs reporting symptoms on the GSC at 1 week . Conclusions Both study groups reported frequent use of the DIs . Caregivers with symptom DIs found them particularly helpful in determining when their child could return to school and physical activity . Larger-scale investigations are needed to further develop instructions that are easy to use and that may decrease the postconcussive period To determine whether st and ardized instructions enhance communication of discharge information , we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department : ( 1 ) instruction by individual housestaff and medical students after consultation with an attending physician ( control group ) ; ( 2 ) st and ardized verbal instructions given by housestaff and students trained in their use ( verbal group ) ; or ( 3 ) the same instructions given to the verbal group , together with a type-written copy of the information to take home ( verbal + written group ) . Prior to leaving the emergency department and , again , by phone , 1 and 3 days later , parents were question ed concerning the prescribed medication 's name , dose , frequency , and duration of administration ( medication data ) , three signs of improvement , and eight signs indicating the need for medical advice ( worrisome signs ) . The mean percentage of correct responses per parent in each group was computed for each information category . Both at exit interview and at follow-up , parents receiving either form of st and ardized instructions showed significantly greater knowledge of information related to their child 's illness than did controls . Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs . The addition of written instructions to st and ardized verbal instructions did not improve parental recall of discharge information RATIONALE An acute-care visit for asthma often signals a management failure . Although a written action plan is effective when combined with self-management education and regular medical review , its independent value remains controversial . OBJECTIVES We examined the efficacy of providing a written action plan coupled with a prescription ( WAP-P ) to improve adherence to medications and other recommendations in a busy emergency department . METHODS We r and omized 219 children aged 1 - 17 years to receive WAP-P ( n = 109 ) or unformatted prescription ( UP ) ( n = 110 ) . All received fluticasone and albuterol inhalers , fitted with dose counters , to use at the discretion of the emergency physician . The main outcome was adherence to fluticasone ( use/prescribed × 100 % ) over 28 days . Secondary outcomes included pharmacy dispensation of oral corticosteroids , β(2)-agonist use , medical follow-up , asthma education , acute-care visits , and control . MEASUREMENTS AND MAIN RESULTS Although both groups showed a similar drop in adherence in the initial 14 days , adherence to fluticasone was significantly higher over Days 15 - 28 in children receiving WAP-P ( mean group difference , 16.13 % [ 2.09 , 29.91 ] ) . More WAP-P than UP patients filled their oral corticosteroid prescription ( relative risk , 1.31 [ 1.07 , 1.60 ] ) and were well-controlled at 28 days ( 1.39 [ 1.04 , 1.86 ] ) . Compared with UP , use of WAP-P increased physicians ' prescription of maintenance fluticasone ( 2.47 [ 1.53 , 3.99 ] ) and recommendation for medical follow-up ( 1.87 [ 1.48 , 2.35 ] ) , without group differences in other outcomes . CONCLUSIONS Provision of a written action plan significantly increased patient adherence to inhaled and oral corticosteroids and asthma control and physicians ' recommendation for maintenance fluticasone and medical follow-up , supporting its independent value in the acute-care setting . Clinical trial registered with www . clinical trials.gov ( NCT 00381355 ) OBJECTIVE . We sought to study the impact of emergency department (ED)–based intensive primary care linkage and initiation of asthma case management on long-term , patient-oriented outcomes for children with an asthma exacerbation . METHODS . Our study was a r and omized , 3-arm , parallel-group , single-blind clinical trial . Children aged 2 through 17 years treated in a pediatric ED for acute asthma were r and omly assigned to st and ard care ( group 1 ) , including patient education , a written care plan , and instructions to follow up with the primary care provider within 7 days , or 1 of 2 interventions . Group 2 received st and ard care plus assistance with scheduling follow-up , while group 3 received the above interventions , plus enrollment in a case management program . OUTCOMES . The primary outcome was the proportion of children having an ED visit for asthma within 6 months . Other outcomes included change in quality -of-life score and controller-medication use . RESULTS . Three hundred fifty-two children were enrolled ; 78 % completed follow-up , 69 % were black , and 70 % had persistent asthma . Of the children , 37.8 % had a subsequent ED visit for asthma , with no difference among the treatment groups ( group 1 : 38.4 % ; group 2 , 39.2 % ; group 3 , 35.8 % ) . Children in all groups had a substantial , but similar , increase in their quality -of-life score . Controller-medication use increased from 69.4 % to 81.4 % , with no difference among the groups . CONCLUSION . ED-based attempts to improve primary care linkage or initiate case management are no more effective than our st and ard ED care in improving subsequent asthma outcomes over a 6-month period OBJECTIVES While physicians provide discharge instructions to patients and families following emergency department ( ED ) visits , injury prevention information may not be routinely included in these instructions . This study assessed emergency physicians ' knowledge and provision of child passenger safety ( CPS ) information to patients following motor vehicle crashes ( MVCs ) . METHODS This study was both a survey of emergency physician knowledge and provision of CPS information and an examination of frequency of CPS information in discharge instructions at a single institution . Members of the American Academy of Pediatrics ( AAP ) Section on Emergency Medicine were invited to participate in the survey . Respondents were asked about their provision of CPS information to patients and knowledge of national AAP CPS recommendations . The institutional ED medical record chart review assessed the frequency of written CPS information for patients of MVC-related visits who were discharged home . RESULTS There were 317 survey respondents from 1,024 eligible physicians , of whom 43 began but did not complete the survey . The data analyzed are from the 274 who completed the survey . While 85 % ( 95 % confidence interval [ CI ] = 81 % to 89 % ) of physicians believed that CPS information should be included in discharge instructions , only 36 % ( 95 % CI = 31 % to 42 % ) correctly answered all knowledge questions . Of the 51 self-identified division/department chiefs , 15 ( 29.4 % ; 95 % CI = 16.9 % to 41.9 % ) reported that their EDs routinely provide CPS information in discharge instructions for pediatric passengers in MVCs . For the medical record review , of the 152 r and omly selected MVC visits , 13 ( 8.6 % ; 95 % CI = 4.1 % to 13.0 % ) had documented CPS information in the discharge instructions . Patients with documented CPS information were younger , but there were no significant differences in race , sex , or maximum abbreviated injury scale score between patients with versus without CPS information . CONCLUSIONS While emergency physicians value the use of CPS information in discharge instructions following MVCs , they do not have adequate knowledge of , nor do they regularly disseminate , this information INTRODUCTION Most patients presenting to the emergency department ( ED ) with minor head injury ( HI ) can be discharged , provided a caregiver is present and careful discharge instructions are given . The study ED uses an advice leaflet with verbal reinforcement to patients and caregivers detailing post-discharge instructions and warning symptoms of worsening HI . We aim to evaluate local patients ' and caregivers ' compliance to discharge instructions and their ability to recall HI advice . METHODS A prospect i ve study was conducted in an adult ED between April 10 , 2006 and May 1 , 2006 . All patients with minor HI discharged from the ED or its 24-hour observation ward were included in the study . A telephone survey was conducted within 48 hours of discharge using a st and ardised question naire . RESULTS During the study period , 292 patients had HI , of which 182 were eligible for the study . 71 were uncontactable and one refused to participate , leaving 110 patients in the study . Patients ' age ranged between 7 and 109 years ( median 41 years ) . 100 confirmed receiving HI advice ( 57 percent received by patients , 26 percent caregivers , 16 percent both patients and caregivers ) . 29 percent of respondents reported non-compliance to discharge advice . Mean HI-symptom recall score was 1.9 ( SD 1.6 ) ( total 9 symptoms ) . 30 percent cited other symptoms not part of the HI advice , which they believed necessitated a return to the ED . Recall scores were not statistically different , regardless of mode of instruction ( verbal or printed ) or the recipient ( patient , caregiver or both ) . CONCLUSION Our study raises concerns about the reliability of discharge advice for minor HI patients OBJECTIVES . The Hawaii Child Asthma Research to Elevate St and ards ( CARES ) Program implemented an emergency department (ED)-based education and management program to facilitate National Asthma Education and Prevention Program ( NAEPP ) guideline underst and ing among asthmatic children and their families , ED staff , and health care providers . METHODS . The multipronged approach used : ( 1 ) 2-phased prospect i ve tracking system of ED asthma patients ; ( 2 ) ED-based educational intervention for patients /families ; and ( 3 ) asthma education for ED staff and community-based health care providers . Data were collected across 4 EDs during phase I ( October 8 , 2002 , to October 1 , 2003 ) and phase II ( October 1 , 2003 , to July 8 , 2004 ) . Follow-up data were collected by telephone 3 weeks ( phase I ) , and 3 weeks and 3 months ( phase II ) after the ED encounter . The patient/family intervention was delivered throughout phase II . During phase I , ED and community-based health care professionals developed strategies for building an integrated asthma care system . ED staff training was delivered before phase II . Continuing medical education for health care providers was delivered before and during the first month of phase II . RESULTS . Tracking data on 706 phase I and 353 phase II patient encounters revealed that the majority of patients with persistent asthma did not use long-term controller medications and did not possess a written asthma action plan . From preintervention to postintervention , the number of patients possessing a written asthma action plan increased from 48 to 322 . Of 186 persistent asthmatics , 34 were using controller medications daily , 34 as needed , and 118 not at all . Daily use increased to 80 3 weeks postintervention and to 68 3 months postintervention . CONCLUSION . An ED-based childhood asthma tracking system can serve as a basis for design ing and implementing an ED-based educational intervention . ED staff , primary care providers , and others can work together to promote asthma care BACKGROUND : Studies in urban emergency departments ( EDs ) have found poor quality of chronic asthma care and identified beliefs and barriers associated with low rates of follow-up with a primary care provider ( PCP ) . OBJECTIVES : To develop an ED-based intervention including asthma symptom screening , a video addressing beliefs and a mailed reminder ; and measure the effect on PCP follow-up and asthma-related outcomes . METHODS : This r and omized , controlled trial enrolled children aged 1 to 18 years who were discharged after asthma treatment in an urban pediatric ED . Control subjects received instructions to follow-up with a PCP within 3 to 5 days . In addition , intervention subjects ( 1 ) received a letter to take to their PCP if they screened positive for persistent asthma symptoms , ( 2 ) viewed a video featuring families and providers discussing the importance of asthma control , and ( 3 ) received a mailed reminder to follow-up with a PCP . All subjects were contacted by telephone 1 , 3 , and 6 months after the ED visit , and follow-up was confirmed by PCP record review . Asthma-related quality of life ( AQoL ) , symptoms , and beliefs about asthma care were assessed by using vali date d surveys . RESULTS : A total of 433 subjects were r and omly assigned , and baseline measures were similar between study groups . After the intervention and before ED discharge , intervention subjects were more likely to endorse beliefs about the benefits of follow-up than controls . However , rates of PCP follow-up during the month after the ED visit ( 44.5 % ) were similar to control subjects ( 43.8 % ) as were AQoL , medication use , and ED visits . CONCLUSIONS : An ED-based intervention influenced beliefs but did not increase PCP follow-up or asthma-related outcomes Background The National Health Service Plan ( July 2000 ) aim ed to empower patients with more influence upon their own treatment . Provision of additional educational health information ( AEHI ) serves to inform families about health conditions and to allow them to manage their own health after discharge . However , to date , it is unknown how parents or carers perceive this information . Objectives To identify parents ' and carers ' views towards the current provision of AEHI following discharge of their child from an emergency care service , to assess their needs concerning AEHI and to provide recommendations for subsequent research . Methods Between 11 April and 19 June 2007 , a piloted question naire was h and ed out at r and om times to each family attending the children 's emergency department while they were waiting to be clinical ly assessed . 1046 families chose to participate and answered questions about their ethnicity , language preference and ability , media access and their sources of health information . The data were analysed using descriptive methods . Results A majority of families wish to receive hospital AEHI as leaflets . Additionally , families frequently use a variety of other re sources such as extended family and friends and the Internet to address their information needs . Poor literacy is a barrier to underst and ing in 15.6 % of the study population . 73 % of carers with children aged between 10 and 16 years wish their children to receive AEHI . Conclusions The authors identified a gap in the provision of health information with respect to appropriate educational material for children and young persons , for families with poor literacy skills and those with language barriers OBJECTIVES Coaching and monetary incentives have been used to modify medical behavior of individuals with several chronic diseases , including asthma . The authors performed a r and omized , controlled trial of an intervention combining asthma coaching during an emergency department ( ED ) visit for asthma , and monetary incentive to improve follow-up with primary care providers ( PCP ) . METHODS Subjects were parents of children 2 - 12 years of age , with Medicaid or no medical insurance , receiving treatment for asthma in the ED . The primary outcome was a verified PCP visit for asthma within two weeks of the index ED visit . All parents received 15 dollars for their time in the ED . Parents in the intervention group were told that they would receive an additional 15 dollars monetary incentive if a PCP visit was completed . The coach engaged in a dialogue with the parent during the ED visit , and discussed the importance and advantages of seeking follow-up care with the child 's PCP . All parents received the usual discharge instructions , including advice to see the PCP within three days . RESULTS The authors enrolled 92 parents ; outcome data were available for 86 ( 42 controls , 50 intervention ) . Demographic characteristics were similar in both groups . There was no significant difference in the proportion of patients who had follow-up PCP visits between the intervention ( 22.0 % ; 95 % confidence interval [ 95 % CI ] = 11.5 % to 36.0 % ) and control ( 23.8 % ; 95 % CI = 12.0 % to 39.4 % ) groups ( p = 0.99 ) . CONCLUSIONS An intervention combining asthma coaching during acute ED visits and a monetary incentive to return for a PCP visit does not appear to increase follow-up with the PCP Objective : To determine whether the use of a bilingual discharge facilitator ( DF ) improves parental recall of discharge instructions in acute gastroenteritis in a pediatric emergency department ( ED ) . Methods : A nonr and omized educational intervention study with a historical control was conducted in a tertiary children 's hospital between January 2004 and November 2004 . English- or Spanish- speaking parents of patients aged 3 months to 18 years with conditions diagnosed as acute gastroenteritis were eligible . The st and ard discharge group received written discharge instructions and st and ard ED discharge protocol s. The intervention group received the written discharge instructions reinforced verbally by the DF in the parent 's language of choice . Recall of 7 warning signs and symptoms was assessed 24 to 48 hours after the ED visit for both groups . Results : For the English-speaking subgroup , a mean of 3.5 ( 95 % confidence interval [ CI ] , 3.26 - 3.78 ) signs or symptoms was identified correctly by 71 subjects in the st and ard discharge group , and a mean of 4.1 ( 95 % CI , 3.83 - 4.43 ) signs or symptoms was identified correctly by 94 subjects in the DF group . For the Spanish-speaking subgroup , a mean of 3.0 ( 95 % CI , 2.67 - 3.36 ) signs or symptoms was identified correctly by 62 subjects in the st and ard discharge group , and a mean of 4.5 ( 95 % CI 4.18 - 4.88 ) signs or symptoms was identified correctly by 64 subjects in the DF group . The differences remained significant after adjusting for patient age and the highest level of education attained by the parent . Conclusions : Verbal reinforcement of written discharge instructions by a bilingual DF improves parental recall of discharge instructions for gastroenteritis OBJECTIVES Follow-up compliance is critical in febrile children because they may harbor unrecognized life-threatening illnesses . This study compares follow-up rates between 2 systems : Wilford Hall Medical Center ( WHMC ) , with preset appointments after ED release , and free medical care ; and Fairfax Hospital ( FFX ) , where parents must arrange follow-up appointments after ED release , and are responsible for payment for their follow-up visits . The study also investigated factors associated with follow-up compliance . METHODS This was a prospect i ve , observational study of febrile children seen in 2 EDs with different systems for patient follow-up . From ED records and parental phone calls , diagnosis , follow-up compliance , and demographics were collected . Data were analyzed using logistic regression and chi2 . RESULTS 423 children met entrance criteria , and 330 parents were successfully contacted after the child 's ED release ( 146 from WHMC ; 184 from FFX ) . The WHMC children were more likely to comply with follow-up than were the children in the FFX system ( 92 % vs 67 % follow-up , odds ratio 2.5 , 95 % CI 1.1 - 5.3 ) . Other factors associated with noncompliance with recommended follow-up were : Hispanic ethnicity , non-English-speaking parents , and follow-up suggested for > 24 hours after ED release . For FFX , self-pay , lack of a follow-up physician , parents ' dissatisfaction with the ED medical care , and diagnosis of otitis media were also significant factors found associated with noncompliance . CONCLUSION Febrile children evaluated in a medical system with prearranged follow-up appointments and free medical care are more likely to comply with recommended follow-up than are those evaluated in a system where payment and appointments are the responsibility of the parents . Efforts should be made to improve follow-up compliance by modeling the WHMC system A r and omized prospect i ve study was made to compare two interventions to improve compliance with follow-up appointments ( FA ) after a pediatric emergency department ( ED ) visit . The study population was 253 patients and families seen during daytime hours at a large pediatric ED and who required follow-up for their diagnosed condition . A control group of patients were told to call the clinic for FA , an appointment group of patients were given a FA in the ED prior to discharge and written reminder , and an intense group of patients were given a FA in the ED prior to discharge , a written reminder ; they were offered a work excuse , child care , and transportation assistance ; they were sent mailed reminders and had attempts at telephone reminders . More patients in the appointment group ( 47 % , P<0.001 ) and intense group ( 52 % , P<0.001 ) kept FA than the control group ( 24 % ) . Attempted telephone contact was unsuccessful in 39 % of the intense group . When telephone contact was successful , patients were more likely to keep FA ( 62 vs 38 % , P<0.04 ) . Families left to make their own FA did so only 32 % of the time . Medical record review of ED and clinic visits for one year after intervention indicated no long-term behavior change in appointment-making behavior or ED use in any group . It was concluded that providing a convenient FA prior to ED discharge improves compliance with clinic follow-up . If telephone contact is successful , telephone reminders also improve compliance . If follow-up is recommended , the majority of patients do not make their own appointments . A one-time intervention does not result in a long-term behavioral change in use of clinics or the ED Our objectives were 1 ) to determine the education attainment level ( EAL ) of parents attending the pediatric emergency department ( PED ) ; 2 ) to assess the readability level ( RL ) of the written instructions available to these parents ; and 3 ) to revise these instruction forms at a level of comprehension based on the EAL of parents . We used a question naire survey of EAL and RL assessment using the SMOG and FOG readability formulas . We then revised the written instructions and used parents in the PED to pretest them . The setting was a PED in a tertiary care hospital ( Children 's Hospital of Western Ontario ) . The participants were 1034 parents of children in the PED between 8 AM and 11 PM over a six-month period . Parents were chosen at 30-minute intervals on r and omly selected weekdays and weekends . A total of 1022 completed the study . Seven forms commonly used in the PED were assessed for RL . Seven forms were rewritten at grade 6 to 7 RL , and each was pretested in 21 to 24 parents or guardians in the PED using a st and ardized question naire with open-ended questions . Ninety percent of respondents spoke English , and 85 % had English as their first language . Forty-nine percent of parents had a grade 13 or lower EAL . This included the following EALs : < grade 12EAL , 23 % ; < grade 10 EAL , 15 % ; and < grade 8 EAL , 4 % . Of the seven forms tested , five were written at a college RL . Pretesting of revised forms elicited the following responses from parents : easy to underst and ( 100 % ) , understood everything ( 96 - 100 % ) , worth remembering ( 77- 96 % ) , liked the form ( 67 - 100 % ) , found it informative ( 52- 85 % ) , and thought it was applicable to all people ( 82 - 100 % ) . They most frequently commented that the forms were easy to read and easy to underst and . Our study showed that discharge instructions are written at a RL at which approximately 50 % of the population served may not underst and . This is supported by available data suggesting that forms should be written at a grade 6 or lower RL . Properly design ed forms that are written at the grade 6 to 7 level were easy to underst and and were associated with parental satisfaction . Design of these forms should not only involve medical personnel but also readability consultants and parents or caregivers Objectives More can be done to eliminate preventable motor vehicle collision (MVC)–related injuries through correct and consistent use of child passenger restraints . This study sought to determine emergency physician awareness of and referral patterns to child passenger safety re sources and to compare awareness and referrals by practice setting . Methods This was a cross-sectional mailed survey of a national r and om sample of 1200 emergency physicians drawn from the American Medical Association Physician Masterfile . Results Responses were returned by 638 ( 64 % ) of 1000 of physicians with a valid mailing address . Fifty-two percent reported working in an emergency department ( ED ) within a pediatric trauma center , 23 % in an adult trauma center , and 25 % in a nontrauma center . Police or fire department car seat installation programs were most frequently available ( 65 % pediatric , 56 % adult , 48 % nontrauma center ) , and free/reduced-price booster seat programs least frequently available ( 46 % pediatric , 30 % adult , 23 % nontrauma center ) ( P < 0.001 ) . Half of pediatric trauma center physicians would always recommend replacement of a 3-year-old ’s car seat following a roll-over MVC compared with one third of adult and nontrauma center physicians ( P < 0.001 ) . There were no significant differences by practice setting for distribution of discharge instructions containing child passenger safety information or referrals to available re sources . Conclusions Availability of child passenger safety re sources for children discharged from EDs following an MVC varies by practice setting . Pediatric injury prevention outreach to general EDs is needed to increase the number of children who are benefiting from existing community child passenger re sources STUDY OBJECTIVE Emergency department patients have been shown to have difficulty underst and ing written discharge instructions . We attempted to determine whether improvements in comprehension can be achieved by simplification of available material s. DESIGN We have previously tested patient underst and ing of st and ard discharge instructions . For this study , we simplified the st and ard instructions . Patients were given one of two simplified instruction sets . After reading the instructions , each patient was asked to answer five specific written questions about them . Results were compared with those from the original study . SETTING ED of a large inner-city university hospital . PARTICIPANTS Four hundred twenty-three adult ED patients who presented on r and omly selected days . RESULTS The current and original groups were well matched for demographic variables . Each subject 's responses were analyzed for overall success and for success with individual questions . The mean score for the current group was significantly improved over that of the original group . A trend toward improvement was demonstrated in all demographic groups with use of the simplified instructions . CONCLUSION Simplified written material s may help patients who do not underst and current st and ard material s. Health care providers should simplify written material s to make them underst and able to the greatest number of patients AIM This paper is a report of the efficacy of a parental educational intervention on children 's pain intensity and experience of pain-related unpleasantness at 24 hours post-discharge from the emergency department , and on parents ' beliefs about pain . BACKGROUND Parents ' misbeliefs about pain management may inhibit them from managing their child 's pain appropriately . Educating parents about pain management may increase their knowledge , dispel myths and help decrease children 's pain intensity and unpleasantness related to pain following a visit to an emergency department . METHOD A r and omized design was adopted with sample s of parent/child dyads . The experimental group received a bookmark , booklet on pain management and pain scale . The control group only received a pain scale . Pain intensity and unpleasantness were measured at triage and 24 hours after discharge from the emergency department . Parents ' beliefs were measured with the Pain Belief Question naire . Data were collected from November 2005 to May 2006 . RESULTS Sample s of 98 ( experimental ) and 97 ( control ) children/parents were recruited . No statistically significant differences were found between both groups regarding pain intensity and unpleasantness , at triage and 24 hours post-discharge . Results for the Pain Belief Question naire were similar between the groups ( t = 1·751 , P = 0·082 ) . CONCLUSION The interventions were not effective to reduce pain and unpleasantness related to pain , as well as to improve pain beliefs of parents . Other interventions , such as having parents participate actively in their child 's pain management , might be more effective than a passive educational intervention Objective : This study was design ed to assess the impact of a brief educational video shown to parents during an emergency department visit for minor febrile illnesses . We hypothesized that a video about home management of fever would reduce medically unnecessary return emergency department visits for future febrile episodes . Methods : A convenience sample of 280 caregivers presenting to one urban pediatric emergency department was enrolled in this prospect i ve , r and omized cohort study . All the caregivers presented with a child aged 3 to 36 months with complaint of fever and were independently triaged as nonemergent . A pretest and posttest were administered to assess baseline knowledge and attitudes about fever . One hundred forty subjects were r and omized to view either an 11-minute video about home management of fever or a control video about child safety . Subjects were tracked prospect ively , and all return visits for fever complaints were independently review ed by 3 pediatric emergency physicians to determine medical necessity . Results : There were no differences between the fever video and the control groups in baseline demographics ( eg , demographically comparable ) . The fever video group had a significant improvement in several measures relating to knowledge and attitudes about childhood fever . There was no statistical difference between the intervention and control groups in subsequent return visits or in the determination of medical necessity . Conclusions : A brief st and ardized video about home management of fever improved caregiver knowledge of fever but did not decrease emergency department use or increase medical necessity for subsequent febrile episodes Aim : To assess MDIS usage in patients discharged from a children ’s hospital emergency department following a mild to moderate asthma attack . Methods : Prospect i ve observational study of 73 consecutive patients presenting to a children ’s hospital emergency department with a mild to moderate asthma attack . Demographic data , whether asthma literature /written MDIS instructions were provided , and who provided MDIS instructions ( either a discharge coordinator or other emergency department staff ) were noted . Parents of patients were telephoned after the first week following discharge and question ed about patient improvement , MDIS use/ reasons for not using MDIS , and unscheduled presentations to their local doctor or hospital . Results : Following discharge , 50/73 ( 68.5 % ) patients used MDIS exclusively ( compliers ) , while 23/73 used nebulisers some or all of the time ( non-compliers ) . There was no difference in patient improvement or unscheduled presentations between compliers and non-compliers . Most non-compliers 14/23 ( 60.9 % ) changed because of parental preference ; ease of nocturnal nebuliser use was a possible factor . Compliance was associated with the age of the patient , spacer usage at hospital , the size of device used at hospital , and whether an information fact sheet was given . Conclusions : Most children discharged from the emergency department following a mild to moderate asthma attack continue MDIS use exclusively in the first week . MDIS compliance may be associated with knowledge , experience , and ease of spacer usage . The study shows that education for parents is crucial for MDIS compliance OBJECTIVE To evaluate the efficacy of a pictogram-based health literacy intervention to decrease liquid medication administration errors by caregivers of young children . DESIGN R and omized controlled trial . SETTING Urban public hospital pediatric emergency department . PARTICIPANTS Parents and caregivers ( N = 245 ) of children aged 30 days to 8 years who were prescribed liquid medications ( daily dose or " as needed " ) . INTERVENTION Medication counseling using plain language , pictogram-based medication instruction sheets . Control subjects received st and ard medication counseling . OUTCOME MEASURES Medication knowledge and practice , dosing accuracy , and adherence . RESULTS Of 245 r and omized caregivers , 227 underwent follow-up assessment s ( intervention group , 113 ; control group , 114 ) . Of these , 99 were prescribed a daily dose medication , and 158 were prescribed medication taken as needed . Intervention caregivers had fewer errors in observed dosing accuracy ( > 20 % deviation from prescribed dose ) compared with caregivers who received routine counseling ( daily dose : 5.4 % vs 47.8 % ; absolute risk reduction [ ARR ] , 42.4 % [ 95 % confidence interval , 24.0%-57.0 % ] ; number needed to treat [ NNT ] , 2 [ 2 - 4 ] ; as needed : 15.6 % vs 40.0 % ; ARR , 24.4 % ( 8.7%-38.8 % ) ; NNT , 4 [ 3 - 12 ] ) . Of intervention caregivers , 9.3 % were nonadherent ( ie , did not give within 20 % of the total prescribed doses ) compared with 38.0 % of controls ( ARR , 28.7 % [ 11.4%-43.7 % ] ; NNT , 3 [ 2 - 9 ] ) . Improvements were also seen for knowledge of appropriate preparation for both medication types , as well as knowledge of frequency for those prescribed daily dose medications . CONCLUSION A plain language , pictogram-based intervention used as part of medication counseling result ed in decreased medication dosing errors and improved adherence among multiethnic , low socioeconomic status caregivers whose children were treated at an urban pediatric emergency department . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00537433 OBJECTIVE To determine prospect ively whether parental receipt of injury prevention education is associated with new action limiting access to lethal means and if so , what action was taken for which means . METHOD Prospect i ve follow-up of 103 adults whose children made an emergency department visit for mental health assessment or treatment . Record review assessed whether hospital staff provided injury prevention education . Logistic regression was used to determine the likelihood of new caretaker action limiting access to the following potentially lethal means : firearms , alcohol , prescription medications , and over-the-counter medications . RESULTS Significant associations were found between exposure to injury prevention education and action to limit access ( adjusted odds ratio = 3.6 , 95 % confidence interval = 1.1 - 12.1 , p = .04 ) . Five of 8 adults whose households contained firearms took new action to limit access after injury prevention education , whereas none of the 7 firearm-owning families who did not receive injury prevention education took new action to limit firearm access . Similar patterns were seen for other means . Adults more often chose to lock up rather than dispose of lethal means . CONCLUSIONS Injury prevention education should be provided to parents during child/adolescent emergency department mental health-related visits . Potential for violence prevention is real because parents do take new action to limit access to lethal means when means restriction education is provided To determine whether parents who deliver albuterol treatments in a pediatric emergency department with a metered dose inhaler with a spacer device ( MDIS ) report better adherence to MDIS use at home compared to parents whose children undergo st and ard nebulizer therapy . Children aged 1–5 years were r and omized by day to usual treatment with nebulized albuterol ( 40 children ) or to treatment by the parent with albuterol with an MDIS ( 46 children ) . All caregivers received st and ard discharge instructions , a spacer and an MDI . Two weeks following the visit , a trained research assistant blinded to the child 's group status , administered a brief telephone question naire to each caretaker . At follow-up , children in the MDIS group were 7.5 times more likely to be using the MDIS for their albuterol treatments ( 95%CI 1.6 - 35.6 ) . Involving parents in treatment of asthma exacerbations in the emergency department using an MDIS may improve adherence to MDIS use at home Summary Objective Asthma is the most common chronic disease in children . Previous studies described significant variations in acute asthma management in children . This study was conducted to examine whether asthma management in the pediatric emergency department ( ED ) was improved through the use of an evidence -based acute asthma care guideline reminder card . Methods The Pediatric Acute Asthma Management Guideline ( PAMG ) was introduced to the ED of a pediatric tertiary care hospital in Ontario , Canada . Medical charts of 278 retrospective ED visits ( January – December 2002 ) and 154 prospect i ve visits ( July 2003–June 2004 ) were review ed to assess changes in acute asthma management such as medication treatment , asthma education , and discharge planning . Logistic and linear regressions were used to determine the effect of PAMG on asthma management in the ED . The propensity score method was used to adjust for confounding . Results During the implementation of PAMG , patients who visited the ED were more likely to receive oral corticosteroids ( Adjusted Odds Ratio [ AOR ] = 2.26 , 95 % CI : 1.63–3.14 , p < 0.0001 ) and oxygen saturation re assessment before ED discharge ( AOR = 2.02 , 95 % CI : 1.45–2.82 , p < 0.0001 ) . They also received 0.23 ( 95 % CI : 0.03–0.44 , p = 0.0283 ) more doses of bronchodilator in the first hour of ED stay . Improvements in asthma education and discharge planning were noted , but the changes were not statistically significant . Conclusions After the implementation of an evidence -based guideline reminder card , medication treatment for acute asthma in the ED was significantly improved ; however , asthma education and discharge planning remained unchanged . Future efforts on promoting guideline -based practice in the ED should focus on these components Objectives To investigate the contribution of diagnosis-specific information sheets at discharge from the emergency department on parental underst and ing of the discharge instructions . Methods The study group consisted of a convenience sample of parents of children discharged home from the emergency department of an urban tertiary care pediatric facility ( n=95 ) . At discharge by the physician , all were given a disease-specific information sheet to accompany the physician 's discharge instructions . Thereafter , the parents were asked to complete the same 13-item question naire used in our previous study , covering demographics , level of anxiety , and quality of physician 's explanation , in addition to a description , in their own words , of their child 's diagnosis and treatment instruction and an indication of their preferred auxiliary method of delivery of information . The findings were compared with the study group in the first phase study ( n=287 ) who did not receive the disease-specific information sheet . The BMDP statistical package was used for the analysis . Results No statistically significant differences between the two groups in age , sex , and education , level of anxiety before or after the emergency department visit , or time of day were observed . Full underst and ing of the diagnosis was noted in 73 % of the parents who received the information sheet and 72 % of the parents in our previous study who did not . Corresponding rates of underst and ing of the treatment instructions were 92 % and 82 % . On statistical analysis , the distribution of the diagnosis-specific information sheet significantly improved parental underst and ing of the treatment instructions ( P=0.025 ) , but not of the diagnosis ( P=0.54 ) . Conclusions Although overall parental underst and ing of emergency department discharge instructions is good , underst and ing of the treatment instructions can be further improved with the use of diagnosis-specific information sheets OBJECTIVE To evaluate the effect of cartoon illustrations on patient comprehension of and compliance with ED release instructions . METHODS A prospect i ve , r and omized , controlled study of consecutive patients who presented to the ED of a community teaching hospital with lacerations necessitating wound repair during a three-month study period . At ED release , the patients were r and omly assigned to receive wound care instructions with or without cartoon illustrations . Three days later , the patients were followed up by telephone . A blinded investigator asked a series of questions design ed to test the patient 's recall of , underst and ing of , and compliance with wound care instructions . RESULTS A total of 234 patients were successfully contacted by telephone ; 105 ( 45 % ) had been given ED release instructions with cartoons , 129 ( 55 % ) , without cartoons . There was no significant difference in age , gender , level of education , or satisfaction with the ED visit between the two groups . The patients given cartoon instructions were more likely to have read the instructions ( 98 % vs 79 % , p < 0.001 ) , were more likely to answer all wound care questions correctly ( 46 % vs 6 % , p < 0.001 ) , and were more compliant with daily wound care ( 77 % vs 54 % , p < 0.01 ) . Subset analysis of those patients who had less than a high school education ( n = 57 ) demonstrated even larger differences between the two treatment groups in terms of comprehension of and compliance with ED release instructions . CONCLUSION Cartoon illustrations are an effective strategy for conveying information and may improve patient compliance with ED release instructions Objectives Safe and effective care after discharge requires parental education in the pediatric emergency department ( ED ) . Parent-provider communication may be more difficult with parents who have limited health literacy or English- language fluency . This study examined the relationship between language and discharge comprehension regarding medication dosing . Methods We completed a prospect i ve observational study of the ED discharge process using a convenience sample of English- and Spanish-speaking parents of children 2 to 24 months presenting to a single tertiary care pediatric ED with fever and /or respiratory illness . A bilingual research assistant interviewed parents to ascertain their primary language and health literacy and observed the discharge process . The primary outcome was parental demonstration of an incorrect dose of acetaminophen for the weight of his or her child . Results A total of 259 parent-child dyads were screened . There were 210 potential discharges , and 145 ( 69 % ) of 210 completed the postdischarge interview . Forty-six parents ( 32 % ) had an acetaminophen dosing error . Spanish-speaking parents were significantly more likely to have a dosing error ( odds ratio , 3.7 ; 95 % confidence interval , 1.6–8.1 ) , even after adjustment for language of discharge , income , and parental health literacy ( adjusted odds ratio , 6.7 ; 95 % confidence interval , 1.4–31.7 ) . Conclusions Current ED discharge communication results in a significant disparity between English- and Spanish-speaking parents ’ comprehension of a crucial aspect of medication safety . These differences were not explained purely by interpretation , suggesting that interventions to improve comprehension must address factors beyond language alone OBJECTIVES Follow-up with a primary care provider ( PCP ) is recommended after an emergency department ( ED ) visit for asthma to assess clinical status and develop a management plan to improve future care . However , previous ED-based studies of urban children with asthma have reported low follow-up rates . The objective of this study was to determine whether scheduling an appointment at the time of an ED visit improves PCP follow-up for urban children . A secondary goal was to assess the effect of this intervention on short-term health outcomes and the use of recommended preventive controller medications . METHODS This r and omized trial enrolled a convenience sample of children who were 2 to 18 years old and discharged after treatment for acute asthma in an urban children 's hospital ED . Both intervention and control subjects were instructed to follow up with their PCP within 3 to 5 days . Study staff assisted intervention subjects to call their PCP from the ED and schedule an appointment . When follow-up could not be scheduled , assistance continued after ED discharge by telephone until an appointment date was confirmed . Study outcomes included PCP visits , asthma-related morbidity , and daily use of preventive medication 4 weeks after the ED visit . Outcomes were assessed by telephone interview and confirmed by PCP record review . RESULTS A total of 278 eligible subjects were enrolled over 8 months ; intervention and control groups were similar by demographic variables and PCP type as well as by asthma history , symptoms , and previous medication use . Only 38 % of subjects reported using a daily controller medication , although 70 % described persistent asthma symptoms for which these are recommended . For the intervention group , follow-up appointments were successfully obtained during the ED visit for 24 % of subjects ; when unsuccessful , a median of 3 telephone calls ( range : 1 - 14 ) were needed to confirm that an appointment had been scheduled . During the 4 weeks after the ED visit , intervention subjects were more likely than controls to follow up with their PCP ( 64 % vs 46 % ; relative probability for follow-up : 1.4 ; 95 % confidence interval : 1.1 - 1.7 ) . Study groups did not differ in return ED visits , missed school or work , or the percentage reporting daily use of a controller medication ( 58 % vs 54 % ) 4 weeks after the ED visit . The median time to the next PCP visit was shorter among intervention subjects ( 13 vs 54 days ) . CONCLUSIONS Scheduling an appointment after an ED visit increased the likelihood that urban children with asthma would follow up with a PCP . An appointment could not be obtained during the ED visit for most children . Other interventions are needed to improve linkage between ED and primary care for asthma and to improve the use of controller medications Head injury is the leading cause of serious morbidity and mortality in bicycle accidents . There is good evidence to recommend helmets , yet few children wear them . Following a survey of children presenting to the emergency room with a bicycle injury , helmet promotion was evaluated in a r and omized trial . The intervention consisted of physician counseling and take-home pamphlets . The study involved 334 children : 161 in the intervention group and 173 in the control group . In a follow-up telephone call , 2 to 3 weeks later , only 9.3 % of the intervention group had purchased helmets , compared with 8.0 % of the control group . Families in the intervention group received further counseling during the telephone contact , result ing in one additional purchase at 6-week follow-up . Evidence that a bike injury motivates cyclists to purchase helmets , and the influence of the self-administered question naire most likely account for the high purchase rate in the control group . Surprisingly , the helmet promotion intervention , including follow-up phone counseling , made no further impact . The results probably are best explained by a " double threshold " effect . Certain families were easily encouraged to buy a helmet , whereas others were far from ready to adapt this fairly recent innovation as routine cycling equipment . The findings suggest that physicians interested in helmet promotion would do better to participate in the design and implementation of multidisciplinary community campaigns Pediatric unintentional poisoning is common despite preventative efforts . Children who have had a poison exposure are at increased risk for subsequent exposure . The purpose of our trial was to determine how often poison prevention information is provided to child care providers in health care facilities ( HCF ) . This was a prospect i ve telephone survey of 100 cases of unintentional poisonings of children ages 1 - 5 y referred to a HCF . Excluded were cases of patients that had intentional or chronic exposures . Eighty cases received no prevention material ; 20 cases received Poison Prevention Information . Ninety-three of the patients were discharged from the emergency department , 6 patients were discharged from a pediatric floor , and 1 was discharged from a Pediatric ICU . Follow up calls to home may be difficult after the patient is referred to a HCF and many families did not receive poison prevention material s. This study indicates the need for a poison prevention discharge packet to be distributed to provide uniform and complete poison prevention education Objective Previous studies demonstrate that patients often have difficulty underst and ing their discharge instructions . Video discharge instructions have the potential to mitigate factors such as illiteracy and limited physician time , which may affect comprehension . Our goal is to determine if adding video discharge instructions affects caregivers ’ underst and ing of their child ’s emergency department ( ED ) visit , plan , and follow-up . Methods Caregivers of patients , aged 29 days to 18 years , with a diagnosis of fever , vomiting or diarrhea , and wheezing or asthma were r and omized into written or video discharge instruction groups . In the ED , caregivers read st and ard written discharge instructions or watched a 3-minute video based on their child ’s diagnosis . They were then asked questions regarding information covered in these instructions . After completing the 20-point question naire , st and ard discharge procedure was followed . Caregivers were contacted by phone 2 to 5 days after discharge for a follow-up question naire . Usefulness of the discharge instructions was also assessed . Results Of 436 caregivers enrolled , 220 received written and 216 received video discharge instructions . The follow-up question naire was completed by 341 caregivers . The group receiving video discharge instructions scored significantly higher in the ED ( 12.2 vs 8.9 ) and 2 to 5 days after discharge ( 11.1 vs 7.8 ) . At follow-up , 29 % of the written and 42 % of the video groups rated their discharge instructions as being extremely helpful . Conclusions Brief video discharge instructions improved caregiver knowledge both in the ED and 2 to 5 days after discharge compared with written discharge instructions alone . Caregiver satisfaction with video discharge instructions was also greater than with written discharge instructions |
2,601 | 31,494,865 | Pooled evidence demonstrates greater improvements in VO2max in healthy men compared with women in response to a given dose of ET , suggesting the presence of sexual dimorphism in the trainability of aerobic capacity | Increases in maximal oxygen uptake ( VO2max ) are strongly associated with improved cardiovascular health .
The aim was to perform a systematic review and meta- analysis to determine whether VO2max responses to endurance training ( ET ) , the most effective intervention to improve VO2max , are influenced by sex . | Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies With this study we tested the hypothesis that 6 wk of endurance training increases maximal cardiac output ( Qmax ) relatively more by elevating blood volume ( BV ) than by inducing structural and functional changes within the heart . Nine healthy but untrained volunteers ( Vo2max 47 ± 5 ml·min(-1)·kg(-1 ) ) underwent supervised training ( 60 min ; 4 times weekly at 65 % Vo2max for 6 wk ) , and Qmax was determined by inert gas rebreathing during cycle ergometer exercise before and after the training period . After the training period , blood volume ( determined in duplicates by CO rebreathing ) was reestablished to pretraining values by phlebotomy and Qmax was quantified again . Resting echography revealed no structural heart adaptations as a consequence of the training intervention . After the training period , plasma volume ( PV ) , red blood cell volume ( RBCV ) , and BV increased ( P < 0.05 ) by 147 ± 168 ( 5 ± 5 % ) , 235 ± 64 ( 10 ± 3 % ) , and 382 ± 204 ml ( 7 ± 4 % ) , respectively . Vo2max was augmented ( P < 0.05 ) by 10 ± 7 % after the training period and decreased ( P < 0.05 ) by 8 ± 7 % with phlebotomy . Concomitantly , Qmax was increased ( P < 0.05 ) from 18.9 ± 2.1 to 20.4 ± 2.3 l/min ( 9 ± 6 % ) as a consequence of the training intervention , and after normalization of BV by phlebotomy Qmax returned to pretraining values ( 18.1 ± 2.5 l/min ; 12 ± 5 % reversal ) . Thus the exercise training-induced increase in BV is the main mechanism increasing Qmax after 6 wk of endurance training in previously untrained subjects Gender differences in maximal accumulated oxygen deficit ( MAOD ) were examined before and after 4 and 8 wk of high-intensity interval training . Untrained men ( n = 7 ) and women ( n = 7 ) cycled at 120 % of pretraining peak oxygen uptake ( VO2 peak ) to exhaustion ( MAOD test ) pre- , mid- , and posttraining . A posttraining timed test was also completed at the MAOD test power output , but this test was stopped at the time to exhaustion achieved during the pretraining MAOD test . The 14.3 + /- 5.2 % increase in MAOD observed in men after 4 wk of training was not different from the 14.0 + /- 3.0 % increase seen in women ( P > 0.05 ) . MAOD increased by a further 6.6 + /- 1.9 % in men , and this change was not different from the additional 5.1 + /- 2.3 % increase observed in women after the final 4 wk of training . VO2 peak measured during incremental cycling increased significantly ( P < 0.01 ) in male but not in female subjects after 8 wk of training . Moreover , the accumulated oxygen ( AO2 ) uptake was higher in men during the posttraining timed test compared with the pretraining MAOD test ( P < 0.01 ) . In contrast , the AO2 uptake was unchanged from pre- to posttraining in female subjects . The increase in MAOD with training was not different between men and women , suggesting an enhanced ability to produce ATP anaerobically in both groups . However , the increase in VO2 peak and AO2 uptake obtained in male subjects after training indicates improved oxidative metabolism in men but not in women . We conclude that there are basic gender differences that may predispose men and women to specific metabolic adaptations after a period of intense interval training We investigated the effect of endurance training on whole body substrate , glucose , and glycerol utilization during 90 min of exercise at 60 % peak O2 consumption ( VO2(peak ) ) in males and females . Substrate oxidation was determined before and after 7 wk of endurance training on a cycle ergometer , with posttesting performed at the same absolute ( ABS , W ) and relative ( REL , VO2(peak ) ) intensities . [6,6 - 2H]glucose and [1,1,2,3,3 - 2H]glycerol tracers were used to calculate the respective substrate tracee flux . Endurance training result ed in an increase in VO2(peak ) for both males and females of 17 and 22 % , respectively ( P < 0.001 ) . Females demonstrated a lower respiratory exchange ratio ( RER ) both pretraining and posttraining compared with males during exercise ( P < 0.001 ) . Glucose rate of appearance ( R(a ) ) and rate of disappearance ( R(d ) ) were not different between males and females . Glucose metabolic clearance rate ( MCR ) was lower at 75 and 90 min of exercise for females compared with males ( P < 0.05 ) . Glucose R(a ) and R(d ) were lower during exercise at both ABS and REL posttraining exercise intensities compared with pretraining ( P < 0.001 ) . Females had a higher exercise glycerol R(a ) and R(d ) compared with males both pre- and posttraining ( P < 0.001 ) . Glycerol R(a ) was not different at either the ABS or REL posttraining exercise intensities compared with pretraining . We concluded that females oxidize proportionately more lipid and less carbohydrate during exercise compared with males both pre- and posttraining , which was cotemporal with a higher glycerol R(a ) in females . Furthermore , endurance training result ed in a decrease in glucose flux at both ABS and REL exercise intensities after endurance exercise training In perinatal psychiatry , r and omized controlled trials are often not feasible on ethical grounds . Many studies are observational in nature , while others employ large data bases not design ed primarily for research purpose s. Quality assessment of the result ing research is complicated by a lack of st and ardized tools specifically for this purpose . The aim of this paper is to describe the Systematic Assessment of Quality in Observational Research ( SAQOR ) , a quality assessment tool our team devised for a series of systematic review s and meta‐analyses of evidence ‐based literature regarding risks and benefits of antidepressant medication during pregnancy . Copyright © 2011 John Wiley & Sons , We studied the effects of a 38-day endurance exercise training program on leucine turnover and substrate metabolism during a 90-min exercise bout at 60 % peak O(2 ) consumption ( VO(2 peak ) ) in 6 males and 6 females . Subjects were studied at both the same absolute ( ABS ) and relative ( REL ) exercise intensities posttraining . Training result ed in a significant increase in whole body VO(2 peak ) and skeletal muscle citrate synthase ( CS ; P < 0.001 ) , complex I-III ( P < 0.05 ) , and total branched-chain 2-oxoacid dehydrogenase ( BCOAD ; P < 0.001 ) activities . Leucine oxidation increased during exercise for the pretraining trial ( PRE , P < 0.001 ) ; however , there was no increase for either the ABS or REL posttraining trial . Leucine oxidation was significantly lower for females at all time points during rest and exercise ( P < 0.01 ) . The percentage of BCOAD in the activated state was significantly increased after exercise for both the PRE and REL exercise trials , with the increase in PRE being greater ( P < 0.001 ) compared with REL ( P < 0.05 ) . Females oxidized proportionately more lipid and less carbohydrate during exercise compared with males . In conclusion , we found that 38 days of endurance exercise training significantly attenuated both leucine oxidation and BCOAD activation during 90 min of endurance exercise at 60 % VO(2 peak ) for both ABS and REL exercise intensities . Furthermore , females oxidize proportionately more lipid and less carbohydrate compared with males during endurance exercise UNLABELLED There is a wide individual heterogeneity in the maximal aerobic fitness ( V x O 2max ) response to exercise training . PURPOSE To examine predictors of V x O 2max nonresponse after aerobic exercise training in postmenopausal women . METHODS The Dose Response to Exercise in Women ( DREW ) study was a r and omized , controlled trial examining the effects of incremental training doses on sedentary postmenopausal women ( 45 - 75 yr ) . Participants were r and omized to one of three exercise treatment groups ( 4 , 8 , or 12 kcal x kg(-1 ) x wk(-1 ) ) for 6 months . Participants exercised 3 - 4 d x wk(-1 ) at 50 % V x O 2max . Predictors of baseline V x O 2max were determined by ANOVA . We used a logistic regression analyses with categorical ( ethnicity and treatment group ) and st and ardized continuous variables ( age , body mass index [ BMI ] , and baseline V x O 2max ) to determine predictors of nonresponse ( Delta < or= 0 L x min(-1 ) ) . Our analysis included 310 women because the control group was excluded . RESULTS A total of 44.9 % , 23.8 % , and 19.3 % of the 4- , the 8- , and the 12-kcal x kg(-1 ) x wk(-1 ) treatment groups ( P < 0.0001 ) , respectively , were nonresponders . Maximal effort , BMI , age , and race significantly predicted baseline V x O 2max . Treatment group ( 8 and 12 kcal x kg(-1 ) x wk(-1 ) vs 4 kcal x kg(-1 ) x wk(-1 ) ; P = 0.0003 ) , baseline V x O 2max ( P < 0.0001 ) , and age ( P < 0.05 ) were significant predictors of nonresponse . Odds ratios and 95 % confidence intervals were 2.13 ( 1.53 - 2.95 ) for baseline V x O 2max ; 1.35 ( 1.00 - 1.83 ) for age ; 0.45 ( 0.24 - 0.85 ) for the 8- versus the 4-kcal x kg(-1 ) x wk(-1 ) group ; and 0.27 ( 0.13 - 0.53 ) for the 12- versus the 4-kcal x kg(-1 ) x wk(-1 ) group . CONCLUSION Women that were younger , less fit , or exercised more during the DREW trial had greater odds of improving their fitness with training . The most important finding of this study was that greater volumes of exercise were associated with a lower probability of being a nonresponder INTRODUCTION In this prospect i ve r and omized trial , we examined the effect of three popular exercise training modalities on maximal oxygen uptake ( V˙O2max ) in overweight and obese individuals . In addition , we examined possible concomitant adaptations in endurance exercise performance ( time to exhaustion ( TTE ) ) , citrate synthase ( CS ) activity , venous and arterial function , blood volume , and calculated stroke volume ( SV ) . METHODS Thirty subjects were recruited ( age , 41 ± 9 yr ; weight , 91 ± 14 kg ; height , 173 ± 8 cm ; body mass index , 30 ± 4 kg·m(-2 ) ) and r and omized to either 6 wk of 4 × 4-min high-intensity interval training ( 4HIIT ) at 85%-95 % of HRmax , 10 × 1-min HIIT ( 1HIIT ) at V˙O2max load , or 45-min moderate-intensity continuous training ( MICT ) at 70 % of HRmax . V˙O2max , TTE , CS activity , venous and arterial function , as well as blood volume were measured before and after the training period . O2 pulse was calculated and used to estimate SV . Analysis was conducted per protocol . RESULTS Only 4HIIT increased V˙O2max ( P < 0.01 ) and significantly more compared with 1HIIT ( P = 0.04 ) and MICT ( P = 0.03 ) ( 4HIIT , 10 % ; 1HIIT , 3.3 % ; and MICT , 3.1 % ) . All groups increased TTE ( 4HIIT , 198 % ; 1HIIT , 116 % ; MICT , 52 % ) , with a higher increase after 4HIIT compared with that after MICT ( P = 0.02 ) . Calculated SV increased only after 4HIIT ( 14.4 % ) . Plasma volume and hemoglobin mass increased after 1HIIT only ( 5.6 % and 6.5 % ) ; however , no group differences were found . All groups increased CS activity ( 4HIIT , 35 % ; 1HIIT , 35 % ; MICT , 56 % ) , with no group differences . Arterial inflow ( 15.7 % ) and venous outflow ( 22.7 % ) decreased after MICT , but there were no group differences . CONCLUSIONS 4HIIT was superior to 1HIIT and MICT in improving V˙O2max likely because of an increased SV Improvement of exercise capacity by continuous ( CT ) versus interval training ( IT ) remains debated . We tested the hypothesis that CT and IT might improve peripheral and /or central adaptations , respectively , by r and omly assigning 10 healthy subjects to two periods of 24 trainings sessions over 8 weeks in a cross-over design , separated by 12 weeks of detraining . Maximal oxygen uptake ( VO2max ) , cardiac output ( Qmax ) and maximal arteriovenous oxygen difference ( Da-vO2max ) were obtained during an exhaustive incremental test before and after each training period . VO2max and Qmax increased only after IT ( from 26.3 + /- 1.6 to 35.2 + /- 3.8 ml min(-1 ) kg(-1 ) and from 17.5 + /- 1.3 to 19.5 + /- 1.8 l min(-1 ) , respectively ; P < 0.01 ) . Da-vO2max increased after both protocol s ( from 11.0 + /- 0.8 to 12.7 + /- 1.0 ; P < 0.01 and from 11.0 + /- 0.8 to 12.1 + /- 1.0 ml 100 ml(-1 ) , P < 0.05 in CT and IT , respectively ) . At submaximal intensity a significant rightward shift of the Q/Da-vO2 relationship appeared only after CT . These results suggest that in isoenergetic training , central and peripheral adaptations in oxygen transport and utilization are training-modality dependant . IT improves both central and peripheral components of Da-vO2max whereas CT is mainly associated with greater oxygen extraction OBJECTIVE To determine the separate effects of exercise intensity and amount on interindividual cardiorespiratory fitness ( CRF ) response . PARTICIPANTS AND METHODS Participants were 121 ( 75 females , 62 % ) sedentary , middle-aged ( mean [ SD ] age , 53.2 [ 7.5 ] years ) , abdominally obese adults who completed at least 90 % of 5 weekly exercise sessions prescribed over a 24-week intervention . Participants were r and omly assigned to ( 1 ) low-amount , low-intensity exercise ( LALI ) ( 180 and 300 kcal per session for women and men , respectively , at 50 % of CRF [ VO 2peak ] ; n=39 ) , ( 2 ) high-amount , low-intensity exercise ( HALI ) ( 360 and 600 kcal per session for women and men , respectively , at 50 % of CRF ; n=51 ) , or high-amount , high-intensity exercise ( HAHI ) ( 360 and 600 kcal per session for women and men , respectively , at 75 % of CRF ; n=31 ) . Cardiorespiratory fitness was measured using a treadmill test at 4 , 8 , 16 , and 24 weeks . The study duration was September 1 , 2009 , through May 31 , 2013 . RESULTS Cardiorespiratory fitness increased within all 3 groups at 24 weeks ( P<.001 ) . At 24 weeks , 38.5 % ( 15 of 39 ) , 17.6 % ( 9 of 51 ) , and 0 % ( 0 of 31 ) of the participants within the LALI , HALI , and HAHI groups , respectively , were CRF nonresponders . At a fixed exercise intensity , increasing exercise amount reduced the rate of nonresponse by 50 % ( P=.02 ) . At a fixed amount of exercise , increasing the exercise intensity eliminated nonresponse ( P=.001 ) . Exposure to exercise decreased the number of CRF nonresponders between 4 and 8 weeks for LALI and by 16 weeks for HALI but plateaued thereafter . For HAHI , the number of CRF nonresponders decreased continually over the 24 weeks . CONCLUSION For a fixed amount of exercise , increasing exercise intensity consistent with consensus recommendations eliminated CRF nonresponse . Low-intensity exercise may not be sufficient to improve CRF for a substantial proportion of sedentary obese adults 5'AMP-activated protein kinase ( AMPK ) is an energy sensor activated by perturbed cellular energy status such as during muscle contraction . Activated AMPK is thought to regulate several key metabolic pathways . We used sex comparison to investigate whether AMPK signalling in skeletal muscle regulates fat oxidation during exercise . Moderately trained women and men completed 90 min bicycle exercise at 60 % VO2peak . Both AMPK Thr172 phosphorylation and alpha2AMPK activity were increased by exercise in men ( approximately 200 % , P < 0.001 ) but not significantly in women . The sex difference in muscle AMPK activation with exercise was accompanied by an increase in muscle free AMP ( approximately 164 % , P < 0.01 ) , free AMP/ATP ratio ( 159 % , P < 0.05 ) , and creatine ( approximately 42 % , P < 0.001 ) in men but not in women ( NS ) , suggesting that lack of AMPK activation in women was due to better maintenance of muscle cellular energy balance compared with men . During exercise , fat oxidation per kg lean body mass was higher in women than in men ( P < 0.05 ) . Regression analysis revealed that a higher proportion of type 1 muscle fibres ( approximately 23 % , P < 0.01 ) and a higher capillarization ( approximately 23 % , P < 0.05 ) in women than in men could partly explain the sex difference in alpha2AMPK activity ( r = -0.54 , P < 0.05 ) and fat oxidation ( r = 0.64 , P < 0.05 ) during exercise . On the other h and , fat oxidation appeared not to be regulated via AMPK . In conclusion , during prolonged submaximal exercise at 60 % VO2peak , higher fat oxidation in women can not be explained by higher AMPK signalling but is accompanied by improved muscle cellular energy balance in women probably due to sex specific muscle morphology |
2,602 | 18,253,971 | There was no evidence that antioxidant vitamin supplementation prevented or delayed the onset of AMD .
Similar results were seen when the analyses were restricted to beta-carotene and alpha-tocopherol .
There is no evidence to date that the general population should take antioxidant vitamin and mineral supplements to prevent or delay the onset of AMD . | BACKGROUND Some observational studies have suggested that people who eat a diet rich in antioxidant vitamins ( carotenoids , vitamins C and E ) or minerals ( selenium and zinc ) may be less likely to develop age-related macular degeneration ( AMD ) .
OBJECTIVES The aim of this review was to examine the evidence as to whether or not taking vitamin or mineral supplements prevents the development of AMD . | In the Physicians ' Health Study , a r and omized , placebo-controlled , double-blind trial of aspirin in the reduction of cardiovascular mortality and beta-carotene in decreasing cancer incidence , 33,223 subjects were eligible and willing to enter the trial . Instead of r and omizing this group immediately , all participants received identical calendar packs that contained active aspirin and beta-carotene placebo . Following an 18-week run-in , only 22,071 subjects who remained eligible and willing and had taken at least 2/3 of their pills were r and omized . We estimated the effect of the run-in as follows : pill taking compliance increased 20 - 41 per cent ; sample size decreased 34 per cent ; duration of follow-up decreased 7 per cent which result ed in a 7 per cent decrease in the expected event rate for the placebo group . To estimate these changes , we made assumptions about compliance and outcome risk for those excluded by the run-in . Our conclusion , however , about the net effect of the run-in on the power of the study remains constant across variations in a number of those assumptions . The power with the run-in , with 22,071 good compliers was typically higher , and never more than negligibly lower , than the power without the run-in , with 33,223 good and poor compliers . In addition , savings from enrolling 11,152 fewer subjects in the trial result ed from the use of the run-in BACKGROUND Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months . Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis We showed previously that natural killer ( NK ) cell activity is significantly greater in elderly men supplemented with beta-carotene than in those taking placebo . In an attempt to determine the mechanism of beta-carotene 's effect , we analyzed the production of NK cell-enhancing cytokines ( interferon alpha , interferon gamma , and interleukin 12 ) . Boston-area participants in the Physicians ' Health Study ( men aged 65 - 88 y ; mean age , 73 y ) who had been supplemented with beta-carotene ( 50 mg on alternate days ) for an average of 12 y were enrolled in a r and omized , placebo-controlled , double-blind study . Elderly subjects taking beta-carotene supplements had significantly greater plasma beta-carotene concentrations than those taking placebo . Beta-carotene-supplemented elderly men had significantly greater NK cell activity than did elderly men receiving placebo . Percentages of NK cells ( CD16+CD56 + ) were not significantly different between the beta-carotene and placebo groups . Production of interleukin 12 , interferon alpha , or concanavalin A-stimulated interferon gamma by cultured peripheral blood mononuclear cells was not significantly different between beta-carotene-supplemented elderly and those taking placebo . Our results indicate that beta-carotene-induced enhancement of NK cell activity is not mediated by changes in percentages of CD16+CD56 + NK cells nor through up-regulation of interleukin 12 or interferon alpha BACKGROUND AND PURPOSE From a physiological perspective , physical activity might be expected to decrease the risk of developing stroke . However , epidemiological studies of physical activity and stroke risk have yielded divergent findings . We therefore sought to examine the association between exercise and stroke risk . METHODS This was a prospect i ve cohort study of 21 823 men , followed up for an average of 11.1 years . Participants were from the Physicians ' Health Study , a r and omized trial of low-dose aspirin and beta carotene . Men , aged 40 to 84 years at baseline , were free of self-reported myocardial infa rct ion , stroke , transient ischemic attack , and cancer . At baseline , they reported on the frequency of exercise vigorous enough to work up a sweat . Stroke occurrence was reported by participants and confirmed after medical record review ( n=533 ) . We used Cox proportional hazards regression to analyze the data . RESULTS With adjustment for age , treatment assignment , smoking , alcohol intake , history of angina , and parental history of myocardial infa rct ion , the relative risks of total stroke associated with vigorous exercise < 1 time , 1 time , 2 to 4 times , and > /=5 times per week at baseline were 1.00 ( referent ) , 0.79 ( 95 % confidence interval [ CI ] , 0.61 to 1 . 03 ) , 0.80 ( 95 % CI , 0.65 to 0.99 ) , and 0.79 ( 95 % CI , 0.61 to 1.03 ) , respectively ; P for trend=0.04 . In subgroup analyses , the inverse association appeared stronger with hemorrhagic than ischemic stroke . When we additionally adjusted for body mass index , history of hypertension , high cholesterol , and diabetes mellitus , corresponding relative risks for total stroke were 1.00 ( referent ) , 0.81 ( 95 % CI , 0.61 to 1.07 ) , 0.88 ( 95 % CI , 0.70 to 1.10 ) , and 0.86 ( 95 % CI , 0.65 to 1.13 ) , respectively ; P for trend=0.25 . CONCLUSIONS Exercise vigorous enough to work up a sweat is associated with decreased stroke risk in men . In the present study , the inverse association with physical activity appeared to be mediated through beneficial effects on body weight , blood pressure , serum cholesterol , and glucose tolerance . Apart from its favorable influences on these variables , physical activity had no significant residual association with stroke incidence Supplementation of healthy elderly persons with beta-carotene has been considered a way to enhance immune responses . In study 1 the short-term effect of beta-carotene ( 90 mg/d for 3 wk ) on immunity was assessed in a r and omized , double-blind , placebo-controlled longitudinal comparison of healthy elderly women . In study 2 the long-term effect of beta-carotene ( 50 mg every other day for 10 - 12 y ) on immunity was assessed in a r and omized , double-blind , placebo-controlled longitudinal comparison of men enrolled in the Physicians ' Health Study . Subjects from both studies taking active supplements had significantly greater plasma beta-carotene concentrations than did subjects taking placebo . The pre- to postintervention change in delayed-type hypersensitivity skin test responses between beta-carotene and placebo groups in the short-term study was not significantly different , nor was the response between treatment groups in the long-term study . There were no significant effects due to beta-carotene supplementation on in vitro lymphocyte proliferation , production of interleukin 2 , or production of prostagl and in E2 as a result of short- or long-term beta-carotene supplementation . In addition , there were no differences in the profiles of lymphocyte subsets [ total T cells ( CD3 + ) , T helper cells ( CD4 + ) , T cytotoxic-suppressor cells ( CD8 + ) , and B cells ( CD19 + ) ] due to short- or long-term beta-carotene supplementation , nor were there differences in percentages of CD16 + natural killer cells or activated lymphocytes ( cells expressing interleukin 2 transferrin receptor ) due to long-term beta-carotene supplementation . Consistent results from these two trials show that beta-carotene supplementation did not have an enhancing or suppressive effect on T cell-mediated immunity of healthy elderly To determine the effects of long-term beta-carotene supplementation on concentrations of carotenoids and tocopherols in plasma and in blood cells , fasting blood was collected from 73 r and omly selected physicians from the Boston area who are participating in the Physicians Health Study ( PHS ) . The PHS is a r and omized , placebo-controlled , double-blind study . In 1982 , 22,071 male physicians were assigned to one of four treatments ( 325 mg aspirin alone , 50 mg beta-carotene alone , both , or neither ) every other day . Plasma , peripheral blood mononuclear cells ( P BMC s ) , and red blood cells ( RBCs ) from physicians who have participated in the study for approximately 12 y were analyzed for carotenoids and tocopherols . Compared with the placebo group , the supplemented group had higher beta-carotene concentrations in plasma ( 1.73+/-0.16 compared with 0.54+/-0.06 micromol/L0 , RBCs ( 91.5+/-9.7 compared with 31.2+/-4.2 pmol/g hemoglobin ) , and P BMC s ( 61.6+/-10.3 compared with 15.5+/-2.5 pmol/10(7 ) cells ) . There were no differences in other carotenoids or tocopherols in plasma , RBCs , and P BMC s between these two groups . The beta-carotene concentrations . Plasma cryptoxanthin correlated with both RBC and P BMC cryptoxanthin concentrations but plasma lycopene correlated only with P BMC lycopene concentrations . These data suggest that plasma may not be the best indicator of carotenoid status . Furthermore , long-term beta-carotene supplementation in men results in higher beta-carotene concentrations in plasma , RBCs and P BMC s without lowering concentrations of other carotenoids or tocopherols Natural killer ( NK ) cell activity has been postulated to be an immunologic link between beta-carotene and cancer prevention . In a cross-sectional , placebo-controlled , double-blind study we examined the effect of 10 - 12 y of beta-carotene supplementation ( 50 mg on alternate days ) on NK cell activity in 59 ( 38 middle-aged men , 51 - 64 y ; 21 elderly men , 65 - 86 y ) Boston area participants in the Physicians ' Health Study . No significant difference was seen in NK cell activity due to beta-carotene supplementation in the middle-aged group . The elderly men had significantly lower NK cell activity than the middle-aged men ; however , there was no age-associated difference in NK cell activity in men supplemented with beta-carotene . beta-carotene-supplemented elderly men had significantly greater NK cell activity than elderly men receiving placebo . The reason for this is unknown ; however , it was not due to an increase in the percentage of NK cells , nor to an increase in interleukin 2 ( IL-2 ) receptor expression , nor to IL-2 production . beta-carotene may be acting directly on one or more of the lytic stages of NK cell cytotoxicity , or on NK cell activity-enhancing cytokines other than IL-2 , such as IL-12 . Our results show that long-term beta-carotene supplementation enhances NK cell activity in elderly men , which may be beneficial for viral and tumoral surveillance The Physicians ' Health Study is a r and omized , double-blind , placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer . To evaluate self-reported compliance with assigned treatment , we measured serum thromboxane B2 , which is decreased after aspirin use , and plasma beta-carotene in sample s of study participants drawn from three geographic locations in three different time periods . Thromboxane B2 levels were markedly lower in those assigned to aspirin ( median = 63.5 pg/mL ) than in those given aspirin placebo ( median = 3,600 pg/mL , P less than .0001 ) . Similarly , those assigned to beta-carotene had significantly higher levels ( median = 1,176 ng/mL ) than those given placebo ( median = 306 ng/mL , P less than .0001 ) . In addition , there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance ( r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene , P less than .0001 ) . These findings support the validity of the self-reported compliance in the Physicians ' Health Study Background An inverse association between height and risk of coronary heart disease ( CHD ) has been reported in several case-control and cohort studies , but the reasons for the association remain uncertain . We evaluated this association among 22071 male physicians , a population homogeneous for high educational attainment and socioeconomic status in adulthood . Methods and Results The study population was comprised of participants in the Physicians ' Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and β-carotene in the primary prevention of cardiovascular disease and cancer among US male physicians , aged 40 to 84 years , in 1982 . Participants were classified into five height categories at study entry , from shortest to tallest , and were followed an average of 60.2 months to determine the incidence of myocardial infa rct ion ( MI ) , stroke , and death from cardiovascular disease . Men in the tallest ( ≥73 in . or 185.4 cm ) compared with the shortest ( ≤67 in . or 170.2 cm ) height category had a 35 % lower risk of MI ( relative risk , 0.65 ; 95 % confidence interval , 0.44 to 0.99 ; P=.04 ) , after adjusting for known cardiovascular risk factors . Further , a marginally significant inverse trend ( P trend=.05 ) across the height categories was observed . Although the relationship was not strictly linear , for every inch of added height , there was an approximate 2 % to 3 % decline in risk of MI . In contrast , men in the tallest compared with the shortest height category had only small and nonsignificant decreases in risk of stroke and cardiovascular death . While no significant trend in risks of these end points across the height categories was observed , the numbers of events for these end points were far less than for MI , and thus the confidence intervals were wide . Conclusions These data indicate that height is inversely associated with subsequent risk of MI . At this time , a few mechanisms are plausible , but none are convincing . Other epidemiological and basic research efforts are needed to explore a variety of physiological correlates of height that may be responsible for mediating the height-MI association . In the meantime , while height is not modifiable , it is easy to measure and may be useful to evaluate CHD disease risk profiles and target lifestyle interventions Objective : To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy ( AMD ) . Design : Prospect i ve r and omised placebo controlled clinical trial . Setting : An urban study centre in a residential area supervised by university research staff . Participants : 1193 healthy volunteers aged between 55 and 80 years ; 73 % completed the trial on full protocol . Interventions : Vitamin E 500 IU or placebo daily for four years . Main outcome measures : Primary outcome : development of early age related macular degeneration in retinal photographs . Other measures included alternative definitions of age related macular degeneration , progression , changes in component features , visual acuity , and visual function Results : The incidence of early age related macular degeneration ( early AMD 3 ) was 8.6 % in those receiving vitamin E versus 8.1 % in those on placebo ( relative risk 1.05 , 95 % confidence interval 0.69 to 1.61 ) . For late disease the incidence was 0.8 % versus 0.6 % ( 1.36 , 0.67 to 2.77 ) . Further analysis showed no consistent differences in secondary outcomes . Conclusion : Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration The 2 x 2 factorial design calls for r and omizing each participant to treatment A or B to address one question and further assignment at r and om within each group to treatment C or D to examine a second issue , permitting the simultaneous test of two different hypotheses . This design can increase the efficiency of large-scale clinical trials . The Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among U.S. physicians , illustrates some features and potential problems in the design and analysis of a factorial trial . The most common concern , interaction between treatments , is generally an advantage rather than a limitation of this design . Although such interactions are relatively uncommon , this design provides a means to measure an effect which otherwise might not be apparent . If the interaction is sufficiently severe , however , then loss of power is possible OBJECTIVE To assess prospect ively the risk of coronary heart disease associated with elevated plasma levels of homocyst(e)ine . DESIGN Nested case-control study using prospect ively collected blood sample s. SETTING Participants in the Physicians ' Health Study . PARTICIPANTS A total of 14,916 male physicians , aged 40 to 84 years , with no prior myocardial infa rct ion ( MI ) or stroke provided plasma sample s at baseline and were followed up for 5 years . Sample s from 271 men who subsequently developed MI were analyzed for homocyst(e)ine levels together with paired controls , matched by age and smoking . MAIN OUTCOME MEASURE Acute MI or death due to coronary disease . RESULTS Levels of homocyst(e)ine were higher in cases than in controls ( 11.1 + /- 4.0 [ SD ] vs 10.5 + /- 2.8 nmol/mL ; P = .03 ) . The difference was attributable to an excess of high values among men who later had MIs . The relative risk for the highest 5 % vs the bottom 90 % of homocyst(e)ine levels was 3.1 ( 95 % confidence interval , 1.4 to 6.9 ; P = .005 ) . After additional adjustment for diabetes , hypertension , aspirin assignment , Quetelet 's Index , and total/high-density lipoprotein cholesterol , this relative risk was 3.4 ( 95 % confidence interval , 1.3 to 8.8 ) ( P = .01 ) . Thirteen controls and 31 cases ( 11 % ) had values above the 95th percentile of the controls . CONCLUSIONS Moderately high levels of plasma homocyst(e)ine are associated with subsequent risk of MI independent of other coronary risk factors . Because high levels can often be easily treated with vitamin supplements , homocyst(e)ine may be an independent , modifiable risk factor BACKGROUND Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease , and earlier basic research suggested plausible mechanisms . Because large r and omized trials of long duration were necessary to test this hypothesis directly , we conducted a trial of beta carotene supplementation . METHODS In a r and omized , double-blind , placebo-controlled trial of beta carotene ( 50 mg on alternate days ) , we enrolled 22,071 male physicians , 40 to 84 years of age , in the United States ; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982 . By December 31 , 1995 , the scheduled end of the study , fewer than 1 percent had been lost to follow-up , and compliance was 78 percent in the group that received beta carotene . RESULTS Among 11,036 physicians r and omly assigned to receive beta carotene and 11,035 assigned to receive placebo , there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease , or in overall mortality . In the beta carotene group , 1273 men had any malignant neoplasm ( except nonmelanoma skin cancer ) , as compared with 1293 in the placebo group ( relative risk , 0.98 ; 95 percent confidence interval , 0.91 to 1.06 ) . There were also no significant differences in the number of cases of lung cancer ( 82 in the beta carotene group vs. 88 in the placebo group ) ; the number of deaths from cancer ( 386 vs. 380 ) , deaths from any cause ( 979 vs. 968 ) , or deaths from cardiovascular disease ( 338 vs. 313 ) ; the number of men with myocardial infa rct ion ( 468 vs. 489 ) ; the number with stroke ( 367 vs. 382 ) ; or the number with any one of the previous three end points ( 967 vs. 972 ) . Among current and former smokers , there were also no significant early or late differences in any of these end points . CONCLUSIONS In this trial among healthy men , 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms , cardiovascular disease , or death from all causes Folate derivatives are important in experimental colorectal carcinogenesis ; low folate intake , particularly with substantial alcohol intake , is associated with increased risk . The enzyme 5,10-methylenetetrahydrofolate reductase ( MTHFR ) catalyzes the conversion of 5,10-methylenetetrahydrofolate , required for purine and thymidine syntheses , to 5-methyltetrahydrofolate , the primary circulatory form of folate necessary for methionine synthesis . A common mutation ( 677C-->T ) in MTHFR reduces enzyme activity , leading to lower levels of 5-methyltetrahydrofolate . To evaluate the role of folate metabolism in human carcinogenesis , we examined the associations of MTHFR mutation , plasma folate levels , and their interaction with risk of colon cancer . We also examined the interaction between genotype and alcohol intake . We used a nested case-control design within the Physicians ' Health Study . Participants were ages 40 - 84 at baseline when alcohol intake was ascertained and blood sample s were drawn . During 12 years of follow-up , we identified 202 colorectal cancer cases and matched them to 326 cancer-free controls by age and smoking status . We genotyped for the MTHFR polymorphism and measured plasma folate levels . Men with the homozygous mutation ( 15 % in controls ) had half the risk of colorectal cancer [ odds ratio ( OR ) , 0.49 ; 95 % confidence interval ( CI ) , 0.27 - 0.87 ] compared with the homozygous normal or heterozygous genotypes . Overall , we observed a marginal significant increased risk of colorectal cancer ( OR , 1.78 ; 95 % CI , 0.93 - 3.42 ) among those whose plasma folate levels indicated deficiency ( <3 ng/ml ) compared with men with adequate folate levels . Among men with adequate folate levels , we observed a 3-fold decrease in risk ( OR , 0.32 ; 95 % CI , 0.15 - 0.68 ) among men with the homozygous mutation compared with those with the homozygous normal or heterozygous genotypes . However , the protection due to the mutation was absent in men with folate deficiency . In men with the homozygous normal genotype who drank little or no alcohol as reference , those with the homozygous mutation who drank little or no alcohol had an 8-fold decrease in risk ( OR , 0.12 ; 95 % CI , 0.03 - 0.57 ) , and for moderate drinkers , a 2-fold decrease in risk ( OR , 0.42 ; 95 % CI , 0.15 - 1.20 ) ; no decrease in risk was seen in those drinking 1 or more drinks/day . Our findings provide support for an important role of folate metabolism in colon carcinogenesis . In particular , these results suggest that the 677C-->IT mutation in MTHFR reduces colon cancer risk , perhaps by increasing 5,10-methylenetetrahydrofolate levels for DNA synthesis , but that low folate intake or high alcohol consumption may negate some of the protective effect PURPOSE To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E , Cataract and Age-Related Maculopathy ( VECAT ) study participants . METHODS A sample of volunteers from an urban area of Melbourne , Australia , were recruited to participate in a r and omized , controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy St and ardized eye examinations involved clinical assessment , which included Wilmer grading of the lens , digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera . All cases of ophthalmic findings were determined on the basis of pathology in the worse eye . RESULTS Most eyes were free from abnormalities . The most frequent findings were cataract and age-related macular changes . Nuclear cataract ( nuclear opacity grade > 2 ) was present in 4.5 % , cortical cataract ( cortical opacity grade > 2 ) in 14.3 % and posterior subcapsular cataract in 3.0 % of participants ; in addition , coronary cataract was observed in 13.6 % . Soft drusen larger than 125 pm were found in 11.4 % , retinal pigment epithelium changes in 9.5 % , epiretinal membrane in 6.6 % and age-related macular degeneration in 0.5 % of participants . SUMMARY Due to the selection criteria , the majority of participants had clear or minor lens changes and /or minor retinal age-related changes . Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation OBJECTIVE To test whether beta carotene supplementation affects the incidence of age-related maculopathy ( ARM ) in a large-scale r and omized trial . DESIGN R and omized , double-masked , placebo-controlled trial among 22 071 apparently healthy US male physicians aged 40 to 84 years . Participants were r and omly assigned to receive beta carotene ( 50 mg every other day ) or placebo . Main Outcome Measure Incident ARM responsible for a reduction in best-corrected visual acuity to 20/30 or worse . RESULTS After 12 years of treatment and follow-up , there were 162 cases of ARM in the beta carotene group vs 170 cases in the placebo group ( relative risk [ RR ] , 0.96 ; 95 % confidence interval [ CI ] , 0.78 - 1.20 ) . The results were similar for the secondary end points of ARM with or without vision loss ( 275 vs 274 cases ; RR , 1.01 ; 95 % CI , 0.86 - 1.20 ) and advanced ARM ( 63 vs 66 cases ; RR , 0.97 ; 95 % CI , 0.69 - 1.37 ) . CONCLUSIONS These r and omized data relative to 12 years of treatment among a large population of apparently healthy men indicate that beta carotene supplementation has no beneficial or harmful effect on the incidence of ARM . Long-term supplemental use of beta carotene neither decreases nor increases the risk of ARM OBJECTIVE To examine whether body mass index is an independent predictor of cataract . ( Body mass index is a st and ardized measure defined as weight in kilograms divided by the square of the height in meters . ) DESIGN Prospect i ve cohort study , with 5 years of follow-up . PARTICIPANTS A total of 17,764 US male physicians participating in the Physicians ' Health Study , aged 40 to 84 years , who were free of cataract , myocardial infa rct ion , stroke , and cancer at baseline and reported complete information about body mass index and other cataract risk factors . MAIN OUTCOME MEASURE Incident cataract , defined as a self-report , confirmed by medical record review , first diagnosed after r and omization , age-related in origin , and responsible for a decrease in best corrected visual acuity to 20/30 or worse . RESULTS Incident cataract occurred during follow-up in 370 participants . In proportional hazards models that adjusted for potential confounding variables , body mass index had a strong , grade d relationship with risk of cataract . Relative to those with body mass index less than 22 , relative risks ( 95 % confidence intervals ) associated with body mass index of 22 to less than 25 , 25 to less than 27.8 , and 27.8 or more were 1.54 ( 1.04 to 2.27 ) , 1.46 ( 0.98 to 2.20 ) , and 2.10 ( 1.35 to 3.25 ) , respectively . Relative to any given level of body mass index , a 2-unit higher level predicted a 12 % increase in risk of cataract ( 95 % confidence interval , 5 % to 19 % ) . Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction . CONCLUSIONS In a prospect i ve cohort study of apparently healthy men , higher body mass index , a potentially modifiable risk factor , was a determinant of cataract . The leanest men had the lowest rates , consistent with experimental evidence that restriction of energy intake slows development of cataract . Although precise mechanisms are unclear , the effect of body mass index on cataractogenesis is apparently independent of other risk factors , including age , smoking , and diagnosed diabetes The Physicians ' Health Study is a r and omized , double-blind , placebo-controlled trial of primary prevention design ed to assess the effects of low-dose aspirin on cardiovascular disease and of beta-carotene on risks of cancer . A total of 22,071 U.S. male physicians 40 to 84 years of age were r and omized to one of four treatment groups : active aspirin and active beta-carotene , active aspirin and beta-carotene placebo , aspirin placebo and active beta-carotene , or both placebos . Whereas the beta-carotene component of the trial is ongoing , the blinded aspirin component was terminated early primarily because of a statistically extreme benefit of aspirin on first myocardial infa rct ion . We obtained data relating to a large number of variables , including demographics , personal medical history , family history , health habits , and diet before r and omization and compared them among the four treatment groups . As expected in a r and omized trial of this sample size , the distribution of baseline characteristics was virtually identical among the treatment groups . This comparison indicates certainly no confounding by the baseline variables that were collected and suggests that other unmeasured or unknown potential confounders are also likely to be distributed evenly between the treatment groups . Thus , any observed differences in outcome between these groups likely result from the effects of the treatments themselves The role of alcohol as a determinant of age-related cataract is largely unexplored , although a possible influence has been suggested by previous retrospective and cross-sectional studies . We used the prospect i ve data base of the Physicians ' Health Study to examine the association between alcohol consumption and incidence of cataract as well as cataract extraction among U.S. male physicians . Participants in the Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among 22,071 male physicians 40 - 84 years of age at entry in 1982 , were included in these analyses if they did not report cataract at baseline and if they provided information about alcohol consumption and other cataract risk factors . A total of 17,824 physicians satisfied these criteria . An incident cataract was defined as a self-report confirmed by medical record review , first diagnosed after r and omization , with an age-related cause , and responsible for a reduction in best corrected visual acuity to 20/30 or worse . During 88,565 person-years of follow-up , 371 participants had a confirmed incident cataract and 110 underwent cataract extraction . Compared to physicians consuming alcohol less than once per month , daily consumers of alcohol had an age-adjusted relative risk ( RR ) of cataract of 1.31 ( 95 % confidence interval [ CI ] = 0.95 , 1.81 ) . For posterior subcapsular ( PSC ) cataract , the most disabling subtype in terms of vision loss , the RR was 1.38 ( 95 % CI = 0.84 , 2.27 ) ; for PSC cataract extraction , the RR was 1.43 ( 95 % CI = 0.71 , 2.88 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES This study evaluated whether increased intake of fish oils ( eicosapentaenoic and docosahexaenoic acids ) might reduce the risk of coronary heart disease . BACKGROUND Observational and clinical studies have suggested that increased intake of fish oils , as reflected in plasma levels of fish oils , may reduce the risk of myocardial infa rct ion . METHODS A nested case-control study was conducted among the 14,916 participants in the Physicians ' Health Study with a sample of plasma before r and omization . Each participant with myocardial infa rct ion occurring during the first 5 years of follow-up was matched by smoking status and age with a r and omly chosen control participant who had not developed coronary heart disease . RESULTS Mean levels of fish oils ( with 95 % confidence interval [ CI ] for paired differences and p values ) in case and control participants , expressed as percent of total fatty acids , were , for eicosapentaenoic acid , 0.26 versus 0.25 ( 95 % CI -0.03 to 0.05 , p = 0.70 ) in cholesterol esters and 0.56 versus 0.54 ( 95 % CI -0.04 to 0.09 , p = 0.44 ) in phospholipids , and for docosahexaenoic acid , 0.23 versus 0.24 ( 95 % CI -0.07 to 0.04 , p = 0.64 ) in cholesterol esters and 2.22 versus 2.14 ( 95 % CI -0.10 to 0.27 , p = 0.36 ) in phospholipids . Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infa rct ion . CONCLUSIONS These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infa rct ion . However , the effect of very high levels of fish oils could not be evaluated The Physicians ' Health Study is a r and omized , placebo-controlled , double-blind clinical trial underway in the United States to assess the effects of aspirin ( 325 mg q.o.d . ) on total cardiovascular mortality , and of beta-carotene ( 50 mg q.o.d . ) on cancer incidence . The participants are 22,071 U.S. male physicians between the ages of 40 - 84 years . The design of the study is 2 x 2 factorial , which enables us to address two important research questions simultaneously . The trial is conducted entirely by mail , which involves sending calendar packs of drugs and question naires on health status and compliance , initially at six-month then at annual intervals . Compliance and follow-up rates to date are excellent . The large size of the trial , its simple design , and the use of highly motivated , dedicated , and health-conscious physicians should allow us to perform definitive tests of whether low-dose aspirin consumption reduces total cardiovascular mortality and beta-carotene decreases cancer incidence in a healthy population BACKGROUND The intercellular adhesion molecule ICAM-1 mediates adhesion and transmigration of leucocytes to the vascular endothelial wall , a step proposed to be critical in the initiation and progression of atherosclerosis . Whether concentrations of soluble ICAM-1 ( sICAM-1 ) are raised in apparently healthy individuals who later suffer acute myocardial infa rct ion is unknown . METHODS We obtained baseline plasma sample s from a prospect i ve cohort of 14,916 healthy men enrolled in the Physicians ' Health Study . With a nested case-control design , we measured sICAM-1 concentrations for 474 participants who developed a first myocardial infa rct ion , and 474 controls ( participants who remained healthy throughout the 9-year follow-up ) . Cases were matched to controls according to age and smoking status at the time of myocardial infa rct ion . FINDINGS We found a significant association between increasing concentration of sICAM-1 and risk of future myocardial infa rct ion ( p = 0.003 ) , especially among participants with baseline sICAM-1 concentrations in the highest quartile ( > 260 ng/mL ; relative risk 1.6 [ 95 % Cl 1.1 - 2.4 ] , p = 0.02 ) . This association was present overall as well as among non-smokers , and persisted after control for lipid and non-lipid risk factors . In multivariate analyses , the risk of future myocardial infa rct ion was 80 % higher for participants with baseline sICAM-1 concentrations in the highest quartile ( relative risk 1.8 [ 1.1 - 2.8 ] , p = 0.02 ) . Similar risk estimates were seen among non-smokers . We found slight but significant correlations between sICAM-1 and fibrinogen , high-density-lipoprotein cholesterol , homocysteine , triglycerides , tissue-type plasminogen-activator antigen , and C-relative protein , but adjustment for these altered the risk little . The risk of myocardial infa rct ion associated with raised concentrations of sICAM-1 seemed to increase with length of follow-up . INTERPRETATION Our data support the hypothesis that cellular mediators of inflammation have a role in atherogenesis and provide a clinical basis to consider antiadhesion therapies as a novel means of cardiovascular disease prevention Cataract is the leading cause of blindness in the world today , while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world . There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions . A 4-year prospect i ve , r and omised , controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55 - 80 years at enrolment is described . This paper outlines the primary aims of the Vitamin E , Cataract and Age-related Macular Degeneration ( VECAT ) Study , the methodology , and the recruitment rates . Additional data on the toxicity and non-ocular effects of vitamin E will also be collected . St and ardised clinical grading of macular and lens features , and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes . Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease . In addition , important data on prevalence and progression rates of cataract and macular degeneration will be collected OBJECTIVE To evaluate the efficacy of low-dose aspirin in the primary prevention of myocardial infa rct ion among patients with chronic stable angina . DESIGN A r and omized , double-blind , trial . PATIENTS The study included 333 men with baseline chronic stable angina but with no previous history of myocardial infa rct ion , stroke , or transient ischemic attack who were enrolled in the Physicians ' Health Study , a trial of aspirin among 22,071 male physicians . INTERVENTION Patients were r and omly assigned to receive alternate-day aspirin therapy ( 325 mg ) or placebo and were followed for an average of 60.2 months for the occurrence of myocardial infa rct ion , stroke , or cardiovascular death . RESULTS During follow-up , 27 patients had confirmed myocardial infa rct ions ; 7 were among the 178 patients with chronic stable angina who received aspirin therapy and 20 were among the 155 patients who received placebo ( relative risk , 0.30 ; 95 % CI , 0.14 to 0.63 ; P = 0.003 ) . While simultaneously controlling for other cardiovascular risk factors in a proportional hazards model , an overall 87 % risk reduction was calculated ( relative risk , 0.13 ; CI , 0.04 to 0.42 ; P less than 0.001 ) . For the subgroup of patients with chronic stable angina but no previous coronary bypass surgery or coronary angioplasty , an almost identical reduction in the risk for myocardial infa rct ion was found ( relative risk , 0.14 ; CI , 0.04 to 0.56 ; P = 0.006 ) . Of 13 strokes , 11 occurred in the aspirin group and 2 in the placebo group ( relative risk , 5.4 ; CI , 1.3 to 22.1 ; P = 0.02 ) . No stroke was fatal , but 4 produced some long-term impairment of function . One stroke , in the aspirin group , was hemorrhagic . CONCLUSION Our data indicated that alternate-day aspirin therapy greatly reduced the risk for first myocardial infa rct ion among patients with chronic stable angina , a group of patients at high risk for cardiovascular death ( P less than 0.001 ) . Although our results for stroke were based on small numbers , they suggested an apparent increase in frequency of stroke with aspirin therapy ; this finding requires confirmation in r and omized trials of adequate sample size OBJECTIVE To examine the association between cigarette smoking and the incidence of cataract . DESIGN , SETTING , AND PARTICIPANTS The design was a prospect i ve cohort study using data from the Physicians ' Health Study , a r and omized trial of aspirin and beta carotene among 22,071 US male physicians aged 40 to 84 years that began in 1982 . This analysis includes the 17,824 physicians who did not report cataract at baseline and did provide complete risk factor information . Based on information reported at baseline , 10 % were current smokers , 39 % were past smokers , and 51 % were never smokers . MAIN OUTCOME MEASURE An incident cataract was defined as a self-report confirmed by medical record review to have been first diagnosed after r and omization , age-related in origin , and responsible for a decrease in best corrected visual acuity to 20/30 or worse . MAIN RESULTS During 60 months of follow-up , 557 incident cataracts among 371 participants were confirmed . Compared with never smokers , current smokers of 20 or more cigarettes per day had a statistically significant increase in the risk of cataract ( relative risk [ RR ] , 2.16 ; 95 % confidence interval [ Cl ] , 1.46 to 3.20 ; P less than .001 ) . Similar results were obtained after simultaneously controlling for other potential cataract risk factors in a logistic regression model ( RR , 2.05 ; 95 % Cl , 1.38 to 3.05 ; P less than .001 ) . Among the 557 eyes with cataract , nuclear sclerotic changes were present in 442 while posterior subcapsular changes were present in 204 . After controlling for other potential cataract risk factors , current smokers of 20 or more cigarettes per day had statistically significant increases in nuclear sclerosis ( RR , 2.24 ; 95 % Cl , 1.47 to 3.41 ; P less than .001 ) and posterior subcapsular ( RR , 3.17 ; 95 % Cl , 1.81 to 5.53 ; P less than .001 ) cataract . Past smokers had an elevated risk of posterior subcapsular ( RR , 1.44 ; 95 % Cl , 0.97 to 2.13 ; P = .07 ) but not nuclear sclerosis cataract . For current smokers of fewer than 20 cigarettes per day , no increased risks were observed of total , nuclear sclerosis , or posterior subcapsular cataract . CONCLUSIONS These data provide support for the hypothesis that cigarette smoking increases the risk of developing both nuclear sclerosis and posterior subcapsular cataract The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospect i ve cohort study of 21,185 US male physicians who are participants in the Physicians ' Health Study . In 4 years of follow-up , there were 281 incident cases of total ( fatal and nonfatal ) myocardial infa rct ion , 173 cases of stroke , and 121 cardiovascular deaths . There was no evidence for association between dietary intake of fish and any cardiovascular endpoint , including myocardial infa rct ion , stroke , and cardiovascular death . The relative risks of total myocardial infa rct ion , adjusted for age and r and omized treatment assignment , for categories of fish intake were : 1.0 for < 1 meal/week ( referent ) , 1.6 ( 95 % confidence interval ( Cl ) 1.1 - 2.3 ) for 1 fish meal/week ; 1.4 ( 95 % Cl 1.0 - 2.0 ) for 2 - 4 fish meals/week ; and 1.2 ( 95 % Cl 0.6 - 2.2 ) for > or = 5 fish meals/week ; chi 2 for trend = 0.9 , p = 0.34 . The relative risks were similar for omega 3 fatty acid intake and for specific types of fish , and did not change after adjustment for history of hypertension , hypercholesterolemia , diabetes mellitus , or angina pectoris , parental history of myocardial infa rct ion before age 60 years , obesity , exercise , smoking , alcohol use , saturated fat intake , and vitamin supplement use . These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease Although cigarette smoking is a risk factor for stroke , results conflict on the strength of the association [ 1 - 13 ] . Estimates of relative risks among current male smokers in cohort studies have ranged from 0.90 [ 14 ] to 4.2 [ 8 ] . Of 25 prospect i ve studies including men , 12 reported no association [ 14 - 25 ] . One prospect i ve study [ 3 ] found a dose-response relation with the number of cigarettes smoked , although 2 others did not [ 6 , 23 ] . Various reference groups have been used in these studies : Some investigations have compared the risk for stroke in current smokers with the risk in never-smokers , and others have compared this risk with the risk in current nonsmokers . Nine of these studies also included women [ 3 - 5 , 8 , 12 - 14 , 17 , 23 ] , generally finding slightly higher relative risks in women . The risk for stroke in female former smokers largely returns to the level of never-smokers within 2 to 4 years after quitting [ 26 ] . Increased alcohol consumption is linked with cigarette smoking [ 27 ] and with stroke [ 28 , 29 ] . However , only five prospect i ve studies in men have controlled for alcohol consumption [ 1 , 4 , 6 , 7 , 16 ] , and none has evaluated the potential modification of the effect of smoking by the level of alcohol intake . The largest of these five studies followed 7895 men [ 7 ] . In this study , we examined the relation of cigarette smoking with stroke in a cohort of 22 071 male physicians participating in the Physician 's Health Study . Methods Study Population The Physicians ' Health Study [ 30 , 31 ] is a r and omized , double-blind , placebo-controlled trial examining the effect of low-dose aspirin on cardiovascular disease and the effect of -carotene on cancer and cardiovascular disease . Briefly , 22 071 U.S. male physicians ( 40 to 84 years of age at entry in 1982 ) were r and omly assigned to aspirin alone , -carotene alone , aspirin and -carotene , or placebo alone , using a 2 2 factorial design . All participants enrolled in the trial were free from self-reported previous myocardial infa rct ion , stroke , and transient ischemic attack . The participants completed a mailed baseline question naire that included information about cigarette smoking status ( never , past only , or current ) and included the number of cigarettes smoked per day if they were currently smoking . Other information collected at baseline included age , history of angina pectoris , history of coronary revascularization procedures ( coronary artery bypass grafting or percutaneous transluminal coronary angioplasty ) , history of diabetes mellitus , history of hypertension , history of high cholesterol levels , height , weight , history of alcohol use , and frequency of vigorous exercise . Every 6 months during the first year and then annually , participants completed brief question naires inquiring about their compliance with the assigned treatment and about the occurrence of any relevant events , including stroke . On 15 January 1988 , the aspirin component of the study was terminated , mainly because of a statistically extreme 44 % decrease in the risk for a first myocardial infa rct ion among participants in the aspirin group . By that date , participants had been followed for an average of 60.2 months . This report includes all available data as of 14 October 1992 . By this date , participants had been followed for an average of 9.7 years ( range , 8.5 to 11.1 years ) . The completeness of follow-up for stroke-associated morbidity and mortality was 100 % . Ascertainment and Definition of Stroke End Points Nonfatal strokes were reported on the semiannual or annual question naires . Deaths were usually reported by the families or postal authorities , and persistent nonresponders to the question naires were telephoned . Strokes were considered confirmed only after medical records and all available information were review ed by the End Points Committee ( which consisted of two internists , a cardiologist , and a neurologist , who did not have knowledge of treatment assignment ) . Unconfirmed events were not used in any of our analyses . A definite case of nonfatal stroke was defined as a typical neurologic deficit that was sudden or rapid in onset , lasted more than 24 hours , and was attributable to a cerebrovascular event . Strokes were classified according to the probable cause ( ischemic or hemorrhagic ) on the basis of medical records , computed tomographic scanning , and the judgment of the neurologist . Computed tomographic scans were available for more than 95 % of all confirmed cases of stroke . Every case of hemorrhagic stroke was confirmed by either a computed tomographic scan or by lumbar puncture . Unknown strokes were those without an imaging study or other clear documentation of stroke subtype . Definite cases of fatal stroke were documented by convincing evidence of a cerebrovascular mechanism from all available sources , including death certificates , hospital records , and for death outside the hospitalobservers ' impressions . Only first cases of stroke were counted . Statistical Analyses Smoking status was defined as never smoked , formerly smoked , currently smoking less than 20 cigarettes per day , or currently smoking 20 or more cigarettes per day . Follow-up began with question naire completion in 1982 to 1983 and ended with the diagnosis of nonfatal or fatal stroke , or other fatal event , or 14 October 1992 , whichever came first . Five participants contributed no follow-up time to the analyses because , after r and omization , they reported strokes that occurred before r and omization . To compute relative risks adjusted for age and other factors , we used the SAS PHREG procedure [ 32 ] to do proportional-hazards regression [ 33 ] . The proportional-hazards assumption was confirmed using log-log plots [ 34 ] . Initial analyses to rule out effect modification by age were done using interaction terms . We then adjusted for age and treatment assignment and then further adjusted for all other covariates , including self-reported hypertension , angina , history of coronary revascularization , diabetes mellitus , high cholesterol level , alcohol consumption , vigorous exercise frequency , and baseline obesity status . These covariates are independent risk indicators for stroke , and all have some association with smoking ( except treatment assignment ) . Adjustment for treatment assignment has been routine in all analyses for the Physicians ' Health Study . Analyses restricted to specific levels of alcohol intake were done to assess the interactive effects of alcohol and smoking . To determine the independent effect of alcohol , we did analyses restricted to never-smokers ( 49.5 % of the cohort ) . Using interaction terms , we also tested for a treatment-assignment interaction for smoking with aspirin ( the -carotene component of the trial is still ongoing and is blinded ) and an interaction for smoking with hypertension . We tested for linear trend in relative risk across smoking categories using an ordinal smoking variable , with values ranging from 0 ( never smoking ) to 3 ( currently smoking 20 or more cigarettes per day ) . We calculated 95 % CIs for each relative risk , and all P values are two-tailed [ 35 ] , with those less than 0.05 declared statistically significant . The population attributable risk percentage for current cigarette smoking in relation to total stroke was calculated as the difference between the stroke incidence rate in the total population and the rate in current nonsmokers divided by the incidence rate in the total population ( x 100 % ) [ 36 ] . Results Baseline Distribution of Smoking and Other Exposure Variables In 1982 , 11.0 % of the physicians in this cohort were current smokers ( 7.1 % of the participants currently smoked 20 or more cigarettes per day and 3.9 % currently smoked less than 20 cigarettes per day ) , 39.3 % formerly smoked , and 49.5 % had never smoked . Information on cigarette smoking habit was missing for 67 ( 0.3 % ) physicians . With the exception of alcohol consumption ( 17.6 % of never-smokers reported daily drinking compared with 37.5 % of current heavy smokers ) , age and most of the other variables had similar distributions among the four groups ( Appendix Table 1 ) . Appendix Table 1 . Comparison of Baseline Characteristics of the Physicians according to Cigarette Smoking Status Total Stroke and Subtypes During 207 579 person-years of follow-up , 312 nonfatal and 28 fatal strokes occurred ( 275 ischemic , 56 hemorrhagic , and 9 of unknown cause ) . Physicians currently smoking 20 or more cigarettes per day had relative risks ( adjusted for age and treatment assignment ) for total nonfatal and fatal stroke of 2.52 and 1.24 , respectively , and in multivariate analyses controlling for other risk factors , these relative risks were 2.71 and 1.46 , respectively ( Table 1 ) . Ischemic stroke was more strongly related to current smoking than was hemorrhagic stroke . For total nonfatal stroke and ischemic stroke , we found linear increases in risk across the four cigarette smoking categories ( P for trend , < 0.0001 ) . Table 1 . Relative Risks for Total , Ischemic , and Hemorrhagic Stroke among U.S. Male Physicians according to Category of Cigarette Smoking Exposure Aspirin treatment assignment was associated with an increased risk for hemorrhagic stroke . In multivariate models , the relative risks associated with aspirin assignment were as follows : total stroke , 1.10 ( 95 % CI , 0.88 to 1.39 ) ; ischemic stroke , 0.99 ( CI , 0.76 to 1.27 ) ; and hemorrhagic stroke , 1.91 ( CI , 1.08 to 3.38 ) . Testing for Interaction We did not find any significant statistical interaction between aspirin treatment and smoking or between hypertensive history and smoking . Data on the effect of smoking within categories of alcohol consumption ( Figure 1 ) were too sparse to permit firm conclusions . In multivariate analyses restricted to never-smokers , we found that the relative risks for total stroke associated with consuming alcohol rarely or never , monthly , weekly , and daily were 1.00 ( referent ) ; 0.95 ( CI , 0.56 to 1.61 ) ; 0.75 ( CI , 0.47 to 1.22 ) ; and 1.14 ( CI , 0.63 to 2.05 ) . Analyses excluding 333 physicians BACKGROUND The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality . METHODS AND RESULTS This was a prospect i ve cohort study with a mean follow-up of 11.7 years . The subjects were a group of 18,682 apparently healthy US men , aged 40 to 84 years , participating in the Physicians ' Health Study , a r and omized trial of low-dose aspirin and beta-carotene . The main outcome measures were total cardiovascular disease , myocardial infa rct ion , stroke , cardiovascular death , and all-cause mortality . Hypertension was associated with substantially increased risks of total cardiovascular disease ( relative risk [ RR ] 1.92 ; 95 % confidence interval [ CI ] , 1.70 to 2.18 ) , myocardial infa rct ion ( RR,1.78 ; 95 % CI , 1.49 to 2.13 ) , stroke ( RR , 2.19 ; 95 % CI , 1.78 to 2.69 ) , and cardiovascular death ( RR , 2.10 ; 95 % CI , 1.68 to 2.63 ) . Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease ( RR , 1.32 ; 95 % CI , 1.09 to 1.59 ) , stroke ( RR , 1.42 ; 95 % CI , 1.04 to 1.93 ) , and cardiovascular death ( RR , 1.56 ; 95 % CI , 1.13 to 2.15 ) , as well as a possible but non-significant increased risk of myocardial infa rct ion ( RR , 1.26 ; 95 % CI , 0.95 to 1.67 ) . Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41 % and 22 % , respectively , for all-cause mortality . CONCLUSIONS Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases , especially stroke and cardiovascular death . Hypertension is associated with an increased risk of myocardial infa rct ion , and borderline isolated systolic hypertension predicts a possible but more modest increase in risk . These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension BACKGROUND Laboratory , clinical , and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality . However , observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used . PURPOSE Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians ' Health Study , a r and omized , double-blinded , placebo-controlled trial of aspirin and beta carotene . We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis . METHODS The Physicians ' Health Study includes 22071 U.S. male physicians . The aspirin arm was terminated in 1988 after a mean follow-up of 5 years . Stage at diagnosis and signs and /or symptoms during presentation were abstract ed from medical records . Cox proportional hazards models were used to estimate relative risk ( RR ) , 95 % confidence intervals ( CIs ) , and the association between aspirin and bleeding . Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves . We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions . RESULTS The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 ( 95 % CI = 0.80 - 1.65 ) . For in situ cancers and polyps , the RR was 0.86 ( 95 % CI = 0.68 - 1.10 ) . There was no significant trend for decreasing RR by year of follow-up for invasive cancers ( P = .09 ) or noninvasive tumors ( P = .96 ) . Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis . CONCLUSIONS Regular aspirin use , at a dose adequate for preventing myocardial infa rct ion , was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of r and omized treatment and follow-up . A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association . Our results suggest that among low-dose aspirin users , ( a ) colorectal cancer mortality is not likely to be reduced by earlier detection and ( b ) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding . IMPLICATION S The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of r and omized participants |
2,603 | 23,740,766 | There was no statistically significant difference in the number of diabetic foot ulcers healed when foam dressings were compared with hydrocolloid ( matrix ) dressings . | BACKGROUND Foot ulcers in people with diabetes are a prevalent and serious global health issue .
Dressings form a key part of ulcer treatment , with clinicians and patients having many different types to choose from .
A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use .
OBJECTIVES The review aim ed to evaluate the effects of foam wound dressings on the healing of foot ulcers in people with diabetes . | Honey dressing has been used to promote wound healing for years but scanty scientific studies did not provide enough evidence s to justify it benefits in the treatment of diabetic foot ulcers . We conducted a prospect i ve study to compare the effect of honey dressing for Wagner 's grade -II diabetic foot ulcers with controlled dressing group ( povidone iodine followed by normal saline ) . Surgical debridement and appropriate antibiotics were prescribed in all patients . There were 30 patients age between 31 to 65-years-old ( mean of 52.1 years ) . The mean healing time in the st and ard dressing group was 15.4 days ( range 9 - 36 days ) compared to 14.4 days ( range 7 - 26 days ) in the honey group ( p < 0.005 ) . In conclusion , ulcer healing was not significantly different in both study groups . Honey dressing is a safe alternative dressing for Wagner grade -II diabetic foot ulcers CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data : In recent years , skin grafting has evolved from the initial autograft and allograft preparations to biosynthetic and tissue-engineered living skin replacements . This review details the pioneering work of numerous investigators that led to the following precursors of tissue-engineered skin replacement : cultured autologous keratinocyte grafts , cultured allogeneic keratinocyte grafts , autologous/allogeneic composites , acellular collagen matrices , and cellular matrices . It also discusses the rationale for the development of the newer products and describes the technical advances leading to the development of Apligraf , a tissue-engineered human skin product OBJECTIVE To compare the efficacy and tolerability of a new ionic silver alginate matrix ( Askina Calgitrol Ag ) with that of a st and ard silver-free alginate dressing ( Algosteril ) . METHOD Patients with locally infected chronic wounds ( pressure ulcers , venous or mixed aetiology leg ulcers , diabetic foot ulcers ) or acute wounds were eligible for this prospect i ve , open-label , controlled and r and omised trial . Patients were r and omised to receive one of the two dressings for a two-week period . Criteria of efficacy were based on the evolution , from day 1 to day 15 , of local signs of infection using a clinical score ranging from 0 to 18 , and the evolution of the bacteriological status for each wound . The latter was determined by ( blind ) bacteriological examinations of results obtained from two biopsies performed at days 1 and 15 . A three-point scale ( deterioration , unchanged , improvement ) was also used . Acceptability , usefulness and tolerance were also assessed . RESULTS Forty-two patients ( 20 women and 22 men , 68.9 + /- 18.8 and 66.5 + /- 15.7 years old respectively ) were r and omly assigned to receive either Askina Calgitrol Ag ( n=20 ) or Algosteril ( n=22 ) . Most had chronic wounds such as pressure ulcers ( 57 % ) or venous or mixed aetiology leg ulcers and diabetic foot ulcers ( 29 % ) ; few had acute wounds ( 14 % ) . Clinical scores of infection were comparable in both groups at inclusion , 8.9 + /- 2.4 and 8.6 + /- 3.2 in the Askina Calgitrol Ag group and the Algosteril group respectively ( not significant ) , but decreased significantly in both groups at day 15 , 3.8 + /- 2.9 in the Askina Calgitrol Ag group ( p=0.001 ) and 3.8 + /- 3.4 in the Algosteril group ( p=0.007 ) . There was no significant difference between the two groups at day 15 . Although there was also no significant difference in bacteriological status between the treatment groups , a trend in favour of Askina Calgitrol Ag was found for the relative risk of improvement , especially in patients who were not treated with antibiotics either at the beginning of the study or during it . No differences between groups were observed regarding local tolerance , acceptability and usefulness of the dressings . CONCLUSION The regression of local signs of infection , local tolerance , acceptability and usefulness were similar for the two dressings . However , Askina Calgitrol Ag improved the bacteriological status of the wounds . Further trials are required to show that it has a positive impact on the healing process Summary The EURODIAB IDDM Complications Study involved the examination of 3250 r and omly selected insulin-dependent diabetic patients , from 31 centres in 16 European countries . Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs , vibration perception threshold , tests of autonomic function and the prevalence of impotence . The prevalence of diabetic neuropathy across Europe was 28 % with no significant geographical differences . Significant correlations were observed between the presence of diabetic peripheral neuropathy with age ( p < 0.05 ) , duration of diabetes ( p < 0.001 ) , quality of metabolic control ( p < 0.001 ) , height ( p < 0.01 ) , the presence of background or proliferative diabetic retinopathy ( p < 0.01 ) , cigarette smoking ( p < 0.001 ) , high-density lipoprotein cholesterol ( p < 0.001 ) and the presence of cardiovascular disease ( p < 0.05 ) , thus confirming previous associations . New associations have been identified from this study – namely with elevated diastolic blood pressure ( p < 0.05 ) , the presence of severe ketoacidosis ( p < 0.001 ) , an increase in the levels of fasting triglyceride ( p < 0.001 ) , and the presence of microalbuminuria ( p < 0.01 ) . All the data were adjusted for age , duration of diabetes and HbA1c . Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction , there was no overall association of alcohol consumption and neuropathy . The reported problems of impotence were extremely variable between centres , suggesting many cultural and attitudinal differences in the collection of such information in different European countries . In conclusion , this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy . [ Diabetologia ( 1996 ) 39 : 1377–1384 OBJECTIVE : A r and omized controlled trial to evaluate the effectiveness of a polyhexamethylene biguanide ( PHMB ) foam dressing compared with a similar non-antimicrobial foam for the treatment of superficial bacterial burden , wound-associated pain , and reduction in wound size . SETTING AND PARTICIPANTS : This study was conducted in 2 wound healing clinics-a university hospital-based clinic and a community-based clinic . Forty-five chronic wound subjects , stratified to either foot or leg ulcers , were followed for 5 weeks . METHODS : A multicenter , prospect i ve , double-blind , pilot , r and omized controlled clinical trial with 3 study visits ( Weeks 0 , 2 , 4 ) documented pain and local wound characteristics using NERDS and STONEES clinical criteria to determine superficial bacterial damage or deep/surrounding infection . RESULTS : The use of PHMB foam dressing was a significant predictor of reduced wound superficial bacterial burden ( P = .016 ) at week 4 as compared with the foam alone . Pain reduction was also statistically significant at week 2 ( P = .0006 ) and at week 4 ( P = .02 ) in favor of the PHMB foam dressings . Polymicrobial organisms were recovered at week 4 in 5.3 % in the PHMB foam dressing group versus 33 % in the control group ( P = .04 ) . Subjects r and omized to the PHMB foam dressing had a 35 % median reduction in wound size by week 4 , compared with 28 % in the control group . CONCLUSIONS : PHMB foam dressing successfully reduced chronic wound pain and bacterial burden OBJECTIVES To determine the comparative effectiveness and cost-effectiveness of three dressing products , N-A , Inadine and Aquacel , for patients with diabetic foot ulcers , as well as the feasibility and consequences of less frequent dressing changes by health-care professionals . DESIGN A multicentre , prospect i ve , observer-blinded , parallel group , r and omised controlled trial , with three arms . SETTING Established expert multidisciplinary clinics for the management of diabetic foot ulcers across the UK . PARTICIPANTS Patients over age 18 with type 1 or type 2 diabetes with a chronic ( present for at least 6 weeks ) full-thickness foot ulcer ( on or below the malleoli ) not penetrating to tendon , periosteum or bone , and with a cross-sectional area between 25 and 2500 mm(2 ) . INTERVENTIONS Participants were r and omised 1:1:1 to treatment with one of N-A ( a non-adherent , knitted , viscose filament gauze ) , Inadine ( an iodine-impregnated dressing ) , both traditional dressings , or Aquacel , a newer product . MAIN OUTCOME MEASURES The primary outcome measure was the number of ulcers healed in each group at week 24 . Secondary measures included time to healing , new ulcerations , major and minor amputations , and episodes of secondary infection . RESULTS A total of 317 patients were r and omised . After 88 withdrawals , 229 remained evaluable . A greater proportion of smaller ( 25 - 100 mm(2 ) ulcers healed within the specified time ( 48.3 % versus 37.3 % ; p = 0.048 ) . There was , however , no difference between the three dressings in terms of percentage healed by 24 weeks , or in the mean time to healing , whether analysed on the basis of intention to treat ( Inadine 44.4 % , N-A 38.7 % , Aquacel 44.7 % ; not significant ) or per protocol ( Inadine 55.2 % , N-A 59.4 % , Aquacel 63.0 % ; not significant ) . There was no difference in the quality of healing , as reflected in the incidence of recurrence within 12 weeks . Likewise , there was no difference in the incidence of adverse events , although a greater proportion of those r and omised to the non-adherent dressings were withdrawn from the study ( 34.9 % versus 29.1 % Aquacel and 19.4 % Inadine ; p = 0.038 ) . The only statistically significant difference found in the health economic analysis was the cost associated with the provision of dressings ( mean cost per patient : N-A 14.85 pounds , Inadine 17.48 pounds , Aquacel 43.60 pounds ) . The higher cost of Aquacel was not offset by the fewer dressings required . There was no difference in measures of either generic or condition-specific measures of quality of life . However , there was a significant difference in the change in pain associated with dressing changes between the first and second visits , with least pain reported by those receiving non-adherent dressings ( p = 0.012 ) . There was no difference in the costs of professional time , and this may relate to the number of dressing changes undertaken by non-professionals . Fifty-one per cent of all participants had at least one dressing change undertaken by themselves or a non-professional carer , although this ranged from 22 % to 82 % between the different centres . CONCLUSIONS As there was no difference in effectiveness , there is no reason why the least costly of the three dressings could not be used more widely across the UK National Health Service , thus generating potentially substantial savings . The option of involving patients and non-professional carers in changing dressings needs to be assessed more formally and could be associated with further significant reductions in health-care costs . TRIAL REGISTRATION Current Controlled Trials IS RCT N78366977 Nonhealing diabetic foot ulcers are a common cause of amputation . Emerging cellular therapies such as platelet-rich plasma gel provide ulcer management options to avoid loss of limb . The purpose of this prospect i ve , r and omized , controlled , blinded , multicenter clinical study was to evaluate the safety and efficacy of autologous platelet-rich plasma gel for the treatment of nonhealing diabetic foot ulcers . One hundred , twenty-nine ( 129 ) patients were screened ; 72 completed a 7-day screening period and met the study inclusion criteria . Patients were r and omized into two groups - the st and ard care with platelet-rich plasma gel or control ( saline gel ) dressing group - and evaluated biweekly for 12 weeks or until healing . Healing was confirmed 1 week following closure and monitored for another 11 weeks . An independent audit led to the exclusion of 32 patients from the final per- protocol analysis because of protocol violations and failure to complete treatment . In this group , 13 out of 19 ( 68.4 % ) of the platelet-rich plasma gel and nine out of 21 ( 42.9 % ) of the control wounds healed . After adjusting for wound size outliers ( n = 5 ) , significantly more platelet-rich plasma gel ( 13 out of 16 , 81.3 % ) than control gel ( eight out of 19 , 42.1 % ) treated wounds healed ( P = 0.036 , Fisher 's exact test ) . Kaplan-Meier time-to-healing also was significantly different between groups ( log-rank , P = 0.0177 ) . No treatment-related serious adverse events were reported and bovine thrombin used in the preparation of PRP did not cause Factor V inhibition . When used with good st and ards of care , the majority of nonhealing diabetic foot ulcers treated with autologous platelet-rich plasma gel can be expected to heal A prospect i ve , multicenter , r and omized , controlled 12-week study was undertaken to evaluate the effectiveness of a human fibroblast-derived dermis for treating foot ulcers in the diabetic patient . This report summarizes the findings from one center . Following a 2-week screening period , patients were r and omized to either human fibroblast-derived dermis ( HFDD ) ( Dermagraft ) plus saline-moistened gauze or to the control group ( CT ) of saline-moistened gauze alone . Effectiveness end points were : 1 ) wound closure by week 12 , 2 ) time to wound closure , and 3 ) percent wound closure by week 12 . Safety was assessed by review of adverse events and laboratory findings . Patients r and omized to HFDD received an application at day 0 and up to seven additional treatments . All patients in each group received shoes with custom-molded inserts and were seen weekly . The study population was comprised of 28 patients ( 14 HFDD/14 CT ) with chronic ulcers ( > 6 weeks ' duration at time of screening ) . By week 12 , significantly more chronic ulcers healed in the HFDD group than in the CT group ( 71.4 % versus 14.3 % , p = .003 ) . Healed HFDD patients achieved wound closure significantly faster than CT patients ( p = .004 ) . Patients treated with HFDD showed a statistically significant higher percent of wound closure by week 12 than did CT patients ( p = .002 ) . The percent of patients who experienced an infection involving their study wound was less in the HFDD group than in the CT group . It was concluded that HFDD is a safe and effective treatment for chronic foot ulcers in diabetic patients Background There are many barriers to patient participation in r and omised controlled trials of cancer treatments . To increase participation in trials , strategies need to be identified to overcome these barriers . Our aim was to assess the effectiveness of interventions to overcome barriers to patient participation in r and omised controlled trials ( RCTs ) of cancer treatments . Methods A systematic review was conducted . Published and unpublished studies in any language were search ed for in fifteen electronic data bases , including MEDLINE , EMBASE , CINAHL and PsycINFO , from inception to the end of 2004 . Studies of any interventions to improve cancer patient participation in RCTs , which reported the change in recruitment rates , were eligible for inclusion . RCTs and non-r and omised controlled trials as well as before and after studies reporting baseline rates specific to the population being investigated were included . Data were extracted by one review er into structured summary tables and checked for accuracy by a second review er . Each included study was assessed against a checklist for method ological quality by one review er and checked by a second review er . A narrative synthesis was conducted . Results Eight studies were identified that met the inclusion criteria : three RCTs , two non-r and omised controlled trials and three observational studies . Six of the studies had an intervention that had some relevance to the UK . There was no robust evidence that any of the interventions investigated led to an increase in cancer patient participation in RCTs , though one good quality RCT found that urologists and nurses were equally effective at recruiting participants to a treatment trial for prostate cancer . Although there was no evidence of an effect in any of the studies , the evidence was not of sufficient quality to be able to conclude that these interventions therefore do not work . Conclusion There is not a strong evidence -base for interventions that increase cancer patient participation in r and omised trials . Further research is required to evaluate the effectiveness of strategies to increase participation in cancer treatment trials Background Diabetes is becoming one of the most common chronic diseases , and ulcers are its most serious complication . Beginning with neuropathy , the subsequent foot wounds frequently lead to lower extremity amputation , even in the absence of critical limb ischemia . In recent years , some research ers have studied external shock wave therapy ( ESWT ) as a new approach to soft tissue wound healing . The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers . Methods We design ed a r and omized , prospect i ve , controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies . One group was treated with st and ard care and shock wave therapy . The other group was treated with only st and ard care . The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization . Results After 20 weeks of treatment , 53.33 % of the ESWT-treated patients had complete wound closure compared with 33.33 % of the control patients , and the healing times were 60.8 and 82.2 days , respectively ( p < 0.001 ) . Significant differences in the index of the re-epithelization were observed between the two groups , with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group ( p < 0.001 ) . Conclusion Therefore , ESWT may be a useful adjunct in the management of diabetic foot ulceration . Trial registration Current Controlled Trials IS RCT Wound closure using topical negative pressure ( TNP ) has been reported to be effective , but equipment costs can be prohibitive in re source -challenged countries . Because nonhealing wounds are exceedingly common in developing countries such as India , the ability to optimize wound care with limited re sources is very important . To investigate the feasibility and efficacy of providing TNP in an Indian medical referral center , a r and omized controlled trial comparing a locally constructed TNP device ( treatment ) to wet-to-dry gauze dressings ( control ) was conducted . Eligible study participants ( N = 48 ) were recruited from the inpatient wards . Wound etiologies included diabetic foot ulcers ( 15 ) , pressure ulcers ( 11 ) , cellulitis/fasciitis ( 11 ) , and " other " ( 11 ) . Following enrollment , wound size was assessed using computer-aided measurements of digital photographs and block-r and omized to the study arms using a concealed allocation table . Wounds in both treatment groups were débrided before dressing application and patients were followed until wound closure or being lost to follow-up for an average of 26.3 days ( + /- 18.5 ) in the control and 33.1 days ( + /- 37.3 ) in the treatment group . No statistically significant differences in time to closure between the two treatment groups were observed except in a subset analysis of pressure ulcers ( mean 10 + /- 7.11 days for treatment and 27 + /- 10.6 days in control group , P = 0.05 ) . Direct costs to close a pressure ulcer also were lower in the TNP than in the control group . A review of the literature suggests the outcomes obtained using a locally constructed TNP device are similar to those obtained using commercially available devices . As a result of this study , a dedicated tissue viability team has been established to identify wounds suitable for TNP , oversee treatment , monitor the need for surgical débridement , and employ wound healing principles and technology appropriately . These results suggest that inexpensive material s can be utilized for TNP wound closure in a developing country Diabetic foot wounds present a great challenge to wound care practitioners . The objective of this pilot study was to determine whether vacuum-assisted closure ( V.A.C. ) therapy would afford quicker wound resolution as compared to saline-moistened gauze in the treatment of postoperative diabetic foot wounds . Ten patients were r and omized into either the experimental V.A.C. group or control saline gauze group . Included in the study were diabetic patients 18 to 75 years of age who had a nonhealing foot ulceration . Excluded were those patients with venous disease , coagulopathy , or those who had active infections not resolved by initial surgical debridement . All foot ulcers were surgically debrided prior to initiation of V.A.C. or gauze treatment . In the experimental group , V.A.C. dressings were applied in accordance with manufacturer 's protocol for chronic wounds and changed every 48 hours . In the control group , saline gauze dressings were applied at the time of surgical debridement and changed twice a day thereafter . Measurements and photos were obtained to document wound progress . Main outcome measures included : 1 ) time to satisfactory healing ( calculated from date of initial debridement to date of definitive closure , and 2 ) change in wound surface area ( calculated from initial wound tracing to final tracing ) . Satisfactory healing in the V.A.C. group was achieved in 22.8 ( + /- 17.4 ) days , compared to 42.8 ( + /- 32.5 ) days in the control group . Surface area changes of 28.4 % ( + /- 24.3 ) average decrease in wound size in the V.A.C. group , compared to a 9.5 % ( + /- 16.9 ) average increase in the control group during measurement period OBJECTIVE To assess the ability of the 4-week healing rate to predict complete healing over a 12-week period in a large prospect i ve multicenter trial of diabetic patients with foot ulceration . RESEARCH DESIGN AND METHODS We examined the change in ulcer area over a 4-week period as a predictor of wound healing within 12 weeks in patients who were seen weekly in a prospect i ve , r and omized controlled trial . RESULTS Wound area measurements at baseline and after 4 weeks were performed in 203 patients . The midpoint between the percentage area reduction from baseline at 4 weeks in patients healed versus those not healed at 12 weeks was found to be 53 % . Subjects with a reduction in ulcer area greater than the 4-week median had a 12-week healing rate of 58 % , whereas those with reduction in ulcer area less than the 4-week median had a healing rate of only 9 % ( P < 0.01 ) . The absolute change in ulcer area at 4 weeks was significantly greater in healers versus nonhealers ( 1.5 versus 0.8 cm2 , P < 0.02 ) . The percent change in wound area at 4 weeks in those who healed was 82 % ( 95 % CI 70 - 94 ) , whereas in those who failed to heal , the percent change in wound area was 25 % ( 15 - 35 ; P < 0.001 ) . CONCLUSIONS The percent change in foot ulcer area after 4 weeks of observation is a robust predictor of healing at 12 weeks . This simple tool may serve as a pivotal clinical decision point in the care of diabetic foot ulcers for early identification of patients who may not respond to st and ard care and may need additional treatment OBJECTIVE To evaluate the utility of a semipermeable polymeric membrane dressing for the treatment of chronic diabetic foot ulcers . RESEARCH DESIGN AND METHODS Nineteen subjects with either insulin- dependent diabetes mellitus ( IDDM ) or non-insulin-dependent diabetes mellitus ( NIDDM ) and foot ulcers were r and omly assigned to the polymeric dressing or conventional wet-to-dry saline dressings . Subjects had foot ulcer site measurements performed every 3 weeks . The subjects using conventional therapy were allowed to cross over to polymeric dressing after 2 months . RESULTS At the end of 2 months , in the patients using the polymeric dressing , ulcer size was reduced to 35 ± 16 % of baseline . The patients on conventional therapy had an ulcer size of 105 ± 28 % of baseline ( P < 0.03 , polymeric vs. conventional ) . Patients initially treated with wet-to-dry saline were crossed over into the polymeric membrane treatment and demonstrated a decrease to 35 ± 11 % of baseline size ( P < 0.02 ) after an additional 2 months . CONCLUSIONS The semipermeable polymeric membrane dressing is a useful therapeutic option for treating uncomplicated chronic diabetic foot ulcers OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) . St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care OBJECTIVE To evaluate the clinical efficacy and safety of HYAFF 11-based autologous dermal and epidermal grafts in the management of diabetic foot ulcers . RESEARCH DESIGN AND METHODS A total of 79 patients with diabetic dorsal ( n = 37 ) or plantar ( n = 42 ) ulcers were r and omized to either the control group with nonadherent paraffin gauze ( n = 36 ) or the treatment group with autologous tissue-engineered grafts ( n = 43 ) . Weekly assessment , aggressive debridement , wound infection control , and adequate pressure relief ( fiberglass off-loading cast for plantar ulcers ) were provided in both groups . Complete wound healing was assessed within 11 weeks . Safety was monitored by adverse events . RESULTS Complete ulcer healing was achieved in 65.3 % of the treatment group and 49.6 % of the control group ( P = 0.191 ) . The Kaplan-Meier mean time to closure was 57 and 77 days , respectively , for the treatment versus control groups . Plantar foot ulcer healing was 55 % and 50 % in the treatment and control groups , respectively . Dorsal foot ulcer healing was significantly different , with 67 % in the treatment group and 31 % in the control group ( P = 0.049 ) . The mean healing time in the dorsal treatment group was 63 days , and the odds ratio for dorsal ulcer healing compared with the control group was 4.44 ( P = 0.037 ) . Adverse events were equally distributed between the two groups , and none were related to the treatments . CONCLUSIONS The autologous tissue-engineered treatment exhibited improved healing in dorsal ulcers when compared with the current st and ard dressing . For plantar ulcers , the off-loading cast was presumably paramount and masked or nullified the effects of the autologous wound treatment . This treatment , however , may be useful in patients for whom the total off-loading cast is not recommended and only a less effective off-loading device can be applied OBJECTIVE To compare the wound healing rate and incidence of infection in wounds treated with either a bioactive dressing ( containing hydrophilic mucopolysaccharide , chitosan ) or conservative treatment ( gauze ) . METHOD Eighty-five patients with diabetic foot ulcers , pressure ulcers or leg ulcers were r and omised to receive either the bioactive study dressing ( n=33 patients , 45 wounds ) or the control dressing ( n=52 patients , 53 wounds ) for 21 days . Wound size , stage where appropriate and the presence of infection were recorded at each dressing change . Thirty-one of these 85 patients dropped out of the study during the three-month post-treatment follow-up , when wound size and grade were assessed on a monthly basis . Data were therefore analysed on 54 patients , of whom 32 ( 34 wounds ) were in the treatment group and 22 ( 26 wounds ) in the control group . RESULTS In the control group , four pressure ulcers healed , but the remaining wounds all deteriorated and became infected , requiring antibiotics . In contrast , in the treatment group 29/34 wounds healed completely , and none became infected ; the remaining five wounds healed during the follow-up period . The difference between the two groups in the number of wounds that healed was statistically significant ( p<0.001 ) , as was that for the number of healed pressure ulcers p<0.05 . CONCLUSION Use of a moist bioactive wound dressing significantly increased the healing rate when compared with the traditional dressings used in the participating hospitals . This will in turn bring significant cost savings OBJECTIVE To assess the effect of a tissue-engineered human dermis ( Dermagraft ) in healing diabetic foot ulcers . RESEARCH DESIGN AND METHODS This controlled prospect i ve multicenter r and omized single-blinded pilot study evaluated healing over a 12-week period in 50 patients with diabetic foot ulcers . These patients were r and omized into four groups ( three different dosage regimens of Dermagraft and one control group ) . All patients received identical care except for the use of Dermagraft tissue . Ulcer healing was assessed by percentage of wounds achieving complete or 50 % closure , time to complete or 50 % closure , and volume and area measurements . RESULTS Ulcers treated with the highest dosage of Dermagraft , one piece applied weekly for 8 weeks ( group A ) , healed significantly more often than those treated with conventional wound closure methods ; 50 % ( 6 of 12 ) of the Dermagraft-treated and 8 % ( 1 of 13 ) of the control ulcers healed completely ( P = 0.03 ) . The percentage of wounds achieving 50 % closure was also significantly higher ( 75 vs. 23 % ; P = 0.018 ) , and the time to complete or 50 % closure was faster ( P = 0.056 ) . The group A regimen was more effective than other treatment regimens . All three were better than the control , however , and a dose-response was observed . There were no safety concerns . After a mean of 14 months of follow-up ( range 11 - 22 months ) , there were no recurrences in the Dermagraft-healed ulcers . CONCLUSIONS Dermagraft was associated with more complete and rapid healing in diabetic foot ulcers . The recurrence data may indicate an improved quality of wound healing Chronic wounds of the lower extremity are a therapeutic dilemma . In India , chronic wounds are caused by factors other than impaired circulation and diabetes , which account for most of this clinical problem in Western societies . A study of 2 topical agents , placental extract and phenytoin powder , is presented in this paper . One hundred fifty patients were r and omly assigned to these treatments or to saline dressings ( control ) . It was observed that patients receiving active topical treatments responded better than those in the control group . The importance of this finding should be viewed with the perspective that these topical treatments are inexpensive and easily available in India . The study also piloted measurements of angiogenic responses in 1 group , and the findings encourage further exploration with the technique and topical agent OBJECTIVE To compare an ibuprofen-releasing foam dressing ( Biatain Ibu , ColoplastA/S ) with local best practice in the treatment of painful exuding wounds . METHOD In this large-scale r and omised comparative study , 853 patients were r and omised to either ibuprofen-releasing foam ( test ) dressing ( n=467 ) or local best practice ( n=386 ) . Primary endpoint was wound pain relief from day 1 - 7 , assessed by the patients twice daily using a five-point verbal rating scale . Secondary endpoints were reduction in pain intensity from day 0 - 7 ( assessed using an 11-point numeric box scale ) , quality of life ( assessed using the WHO-5 well-being index and effect on health-related activities of daily living ) and the incidence of adverse events . RESULTS After seven days significantly more patients in the experimental group experienced relief from temporary and persistent pain and a reduction in pain intensity , when compared with patients in the local best practice group ( p<0.0001 ) . They also experienced a greater improvement in quality of life . The number of adverse events in both groups was low . CONCLUSION The test dressing provided an appropriate wound healing environment , relieved temporary and persistent wound pain , and decreased pain intensity . It was also associated with an improvement in quality of life An open r and omized controlled study was carried out of 44 diabetic patients with necrotic foot ulcers treated with adhesive zinc oxide tape ( MeZinc ) or with an adhesive occlusive hydrocolloid dressing ( DuoDerm ) . Fourteen of the 21 patients treated with MeZinc had their necrotic ulcers improved by at least 50 % compared to six out of 21 with the hydrocolloid dressing ( P < 0·025 ) . Fifteen patients showed an increase in the area of necrosis during the course of the 5‐week study and of these , 10 had been treated with the hydrocolloid dressing AIM This paper is a report of a study to compare a medical grade honey with conventional treatments on the healing rates of wounds healing by secondary intention . BACKGROUND There is an increasing body of evidence to support the use of honey to treat wounds , but there is a lack of robust r and omized trials on which clinicians can base their clinical judgement . METHOD A sample of 105 patients were involved in a single centre , open-label r and omized controlled trial in which patients received either a conventional wound dressing or honey . Data were collected between September 2004 and May 2007 . RESULTS The median time to healing in the honey group was 100 days compared with 140 days in the control group . The healing rate at 12 weeks was equal to 46.2 % in the honey group compared with 34.0 % in the conventional group , and the difference in the healing rates ( 95 % confidence interval , CI ) at 12 weeks between the two groups was 12.2 % ( -13.6 % , 37.9 % ) . The unadjusted hazard ratio ( 95 % CI ) from a Cox regression was equal to 1.30 ( 0.77 , 2.19 ) , P = 0.321 . When the treatment effect was adjusted for confounding factors ( sex , wound type , age and wound area at start of treatment ) , the hazard ratio increased to 1.51 but was again not statistically significant . CONCLUSION Wound area at start of treatment and sex are both highly statistically significant predictors of time to healing . These results support the proposition that there are clinical benefits from using honey in wound care , but further research is needed AIMS Diabetic foot ulcers ( DFUs ) are at risk of infection and impaired healing , placing patients at risk of lower extremity amputation . DFU care requires debridement and dressings . A prospect i ve , multicentre study compared clinical efficacy and safety of AQUACEL Hydrofiber dressings containing ionic silver ( AQAg ) with those of Algosteril calcium alginate ( CA ) dressings in managing out- patients with Type 1 or 2 diabetes mellitus and non-ischaemic Wagner Grade 1 or 2 DFUs . METHODS Patients stratified by antibiotic use on enrolment were r and omly assigned to similar protocol s including off-loading , AQAg ( n = 67 ) or CA ( n = 67 ) primary dressings and secondary foam dressings for 8 weeks or until healing . Clinical efficacy measures were healing outcomes and primarily healing speed . Adverse events were recorded . RESULTS AQAg and CA groups were comparable at baseline . All ulcer healing outcomes improved in both groups . The mean time to healing was 53 days for AQAg ulcers and 58 days for CA ulcers ( P = 0.34 ) . AQAg-treated ulcers reduced in depth nearly twice as much as CA-treated ulcers ( 0.25 cm vs. 0.13 cm ; P = 0.04 ) . There was more overall ulcer improvement and less deterioration in AQAg subjects ( P = 0.058 ) , particularly in the subset initially using antibiotics ( P = 0.02 ) . Safety profiles of both groups were similar . CONCLUSION When added to st and ard care with appropriate off-loading , AQAg silver dressings were associated with favourable clinical outcomes compared with CA dressings , specifically in ulcer depth reduction and in infected ulcers requiring antibiotic treatment . This study reports the first significant clinical effects of a primary wound dressing containing silver on DFU healing This study compared the treatment of total contact casting ( TCC ) with traditional dressing treatment ( TDT ) in the management of diabetic plantar ulcers . Forty patients with diabetes mellitus and a plantar ulcer but with nogross infection , osteomyelitis , or gangrene were r and omly assigned to the TCC group ( n = 21 ) or TDT group ( n = 19 ) . Age , sex , ratio of insulin-dependent diabetes mellitus to non-insulin-dependent diabetes mellitus , duration of diabetes mellitus , vascular status , size and duration of ulcer , and sensation were not significantly different between groups ( P > .05 ) . In the experimental group , TCC was applied on the initial visit , and subjects were instructed to limit ambulation to ∼33 % of their usual activity . Subjects in the control group were prescribed dressing changes and accommodative footwear and were instructed to avoid bearing weight on the involved extremity . Ulcers were considered healed if they showed complete skin closure with no drainage . Ulcers were considered not healed if they showed no decrease in size by 6 wk or if infection developed that required hospitalization . In the TCC group , 19 of 21 ulcers healed in 42 ± 29 days ; in the TDT group , 6 of 19 ulcers healed in 65 ± 29 days . Significantly more ulcers healed ( χ2 = 12.4 , P < .05 ) and fewer infections developed ( χ2 = 4.1 , P < .05 ) in the TCC group . We conclude TCC is a successful method of treating diabetic plantar ulcers but requires careful application , close follow-up , and patient compliance with scheduled appointments to minimize complications BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions HYPOTHESIS Promogran , a wound dressing consisting of collagen and oxidized regenerated cellulose , is more effective that st and ard care in treating chronic diabetic plantar ulcers . DESIGN R and omized , prospect i ve , controlled multicenter trial . SETTING University teaching hospitals and primary care centers . PATIENTS A total of 276 patients from 11 centers were enrolled in the study . The mean age of the patients was 58.3 years ( range , 23 - 85 years ) . All patients had at least 1 diabetic foot ulcer . INTERVENTIONS Patients were r and omized to receive Promogran ( n = 138 ) or moistened gauze ( control group ; n = 138 ) and a secondary dressing . Dressings were changed when clinical ly required . The maximum follow-up for each patient was 12 weeks . MAIN OUTCOME MEASURE Complete healing of the study ulcer ( wound ) . RESULTS After 12 weeks of treatment , 51 ( 37.0 % ) Promogran-treated patients had complete wound closure compared with 39 ( 28.3 % ) control patients s , but this difference was not statistically significant ( P = .12 ) . The difference in healing between treatment groups achieved borderline significance in the subgroup of patients with wounds of less than 6 months ' duration . In patients with ulcers of less than 6 months ' duration , 43 ( 45 % ) of 95 Promogran-treated patients healed compared with 29 ( 33 % ) of 89 controls ( P = .056 ) . In the group with wounds of at least 6 months ' duration , similar numbers of patients healed in the control ( 10/49 [ 20 % ] ) and the Promogran ( 8/43 [ 19 % ] ; P = .83 ) groups . No differences were seen in the safety measurements between groups . Patients and investigators expressed a strong preference for Promogran compared with moistened gauze . CONCLUSIONS Promogran was comparable to moistened gauze in promoting wound healing in diabetic foot ulcers . It showed an additional efficacy for ulcers of less than 6 months ' duration that was of marginal statistical significance . Furthermore , Promogran had a safety profile that was similar to that of moistened gauze , with greater user satisfaction . Therefore , Promogran may be a useful adjunct in the management of diabetic foot ulceration , especially in ulcers of less than 6 months ' duration BACKGROUND It is hypothesized that moisture regulation specific to the area of contact results in local wound conditions more amenable to healing , which would result in faster and more frequent wound closure . TheraGauze is a new polymer-impregnated dressing design ed to regulate moisture to a varying degree over the entire surface of a wound . METHODS This prospect i ve , r and omized , multicenter study examined outcomes from treatment of diabetic foot ulcers with TheraGauze and TheraGauze in conjunction with becaplermin . We also compared these outcomes with historical data from the literature that used saline-moistened gauze and becaplermin . RESULTS The rates of wound closure with TheraGauze and TheraGauze + becaplermin were 0.37 and 0.41 cm(2)/week , respectively ( P = .34 ) . The difference between these values was not statistically significant . We also observed high closure rates at 12 weeks ( 46.2 % in both groups ) and 20 weeks ( 61.5 % with TheraGauze alone and 69.2 % with TheraGauze + becaplermin ) . These data were also compared with historical data for closure rates ( 0.18 cm(2)/week ) and percentage of wounds closed using saline-moistened gauze alone and becaplermin with saline-moistened gauze ( 0.24 cm(2)/week ) from a variety of studies . CONCLUSIONS Wounds in which moisture content was regulated with TheraGauze showed more rapid change in wound area and a higher percentage of wounds achieving closure at 12 and 20 weeks regardless of whether becaplermin was used Bone marrow (BM)-derived mesenchymal stem cells ( MSCs ) represent a promising population for supporting new concepts in cellular therapy . This study was undertaken to assess the efficacy and feasibility of autologous BM-derived MSCs in the treatment of chronic nonhealing ulcers ( diabetic foot ulcers and Buerger disease ) of the lower extremities . A total of 24 patients with nonhealing ulcers of the lower limb were enrolled and r and omized into implant and control groups . In the implant group , the patients received autologous cultured BM-derived MSCs along with st and ard wound dressing ; the control group received only the st and ard wound dressing regimen , followed up for at least a 12-week period . Wound size , pain-free walking distance , and biochemical parameters were measured before therapy and at every 2-week interval following intervention . The implant group had significant improvement in pain-free walking distance and reduction in ulcer size as compared to those in the control group . In the implant group for Buerger disease , the ulcer area decreased from 5.04 + /- 0.70 cm(2 ) to 1.48 + /- 0.56 cm(2 ) ( p < 0.001 ) , whereas the pain-free walking distance increased from 38.33 + /- 17.68 m to 284.44 + /- 212.12 m ( p < 0.001 ) . In the diabetic foot ulcer group , the ulcer size decreased from 7.26 + /- 1.41 cm(2 ) to 2 + /- 0.98 cm(2 ) ( p < 0.001 ) at 12 weeks . Mononuclear cells were cultured for a minimum of five passages and characterized by cell-surface markers showing CD90 + , CD105 + , and CD34(- ) . There was no significant alteration in the biochemical parameters observed during the follow-up period , indicating normal liver and renal function following intervention . Biopsy microsection of implanted tissues showed development of dermal cells ( mainly fibroblasts ) , including mature and immature inflammatory cells . The study indicates that autologous implantation of BM-derived MSCs in nonhealing ulcers accelerates the healing process and improves clinical parameters significantly p < 0.01 ) and the median time to complete wound closure ( 7 vs. 15 weeks , p= 0.0021 , rank-sum test ) . There was no difference in the wound closure rate of meshed and unmeshed graft at 4 , 8 , 12 , or 24 weeks ( p > 0.05 ) . Three indolent localized wound infections in the tissue-engineered skin graft group were the only complication . Tissue-engineered skin grafting can be used safely in previously ischemic wounds after lower extremity revascularization . Treatment with this graft promotes healing more rapidly and in more patients than st and ard moist dressings . It obviates the risk , inconvenience , and expense of donor skin harvesting , anesthesia , and hospitalization associated with autologous skin grafting . This graft may represent an advance in the treatment of previously ischemic lower extremity foot wounds AIM In addition to contemporary compression therapy , one of the therapeutic approaches is the use of a topical wound care agent . The goal of this pilot registry study is to evaluate the efficacy and safety of a uniquely design ed ointment containing multivalent silver oxide ( Ag4O4 ) in the healing of difficult diabetic or venous ulcerations . METHODS Patients who had ulcers result ing from chronic venous insufficiency or diabetes participated in this open-label , r and omized registry study . All patients were evaluated by measuring both the area of the ulceration and microcirculatory parameters . 148 patients were included in the study and categorized into two main groups : venous ulcers and diabetic ulcers . Each main group was then r and omized into two sub-groups : topical treatment with silver oxide ointment and the control group ( st and ard cleaning and compression management methods , without silver ointment ) . All patients were treated with accepted cleaning and compression management . RESULTS . In subjects with venous ulcers : After 4 weeks , the silver treatment was more effective than the control group treatment : Skin PO2 was increased 2.1 times more than the control group ( 17.4 % to 8.2 % ) and skin flux ( RF ) was improved 1.6 times more than the control group ( -38.7 % to -24.2 % ) . The total surface area of the ulcer was significantly reduced in the silver treatment group by 1.9 times the control group ( -88.7 % to -46.9 % ) . In addition , in the silver treatment group we observed complete closure of the ulceration in 42 % of subjects compared to 22 % in the control group ( P=<0.05 ) . In subjects with diabetic ulcers : after 4 weeks , the silver treatment was more effective than the control group treatment : Skin PO2 increased 2.6 times more than the control group ( 23.3 % to 9.1 % ) and skin flux ( RF ) was significantly improved 4.3 times more than the control group(-26.7 % to -6.2 % ) . The total surface area of the ulcer was significantly reduced in the silver treatment group by 3.7 times the control group ( -89.0 % to -23.9 % ) . In addition , in the silver treatment group we observed complete closure of the ulceration in 39 % of subjects compared to 16 % in the control group ( P</=0.05 ) . CONCLUSION This pilot study provides observational data on the efficacy of local treatment of ulcers with a multivalent silver oxide containing ointment . The silver ointment improved microcirculation and the healing rate of all 78 patients that were treated with multivalent silver ointment and closed twice as many ulcers in 4 weeks compared to the control groups ( 40.7 % silver treatment compared to 19.4 % for the control ) . This study demonstrates the feasibility of this type of treatment and provides evidence of efficacy to plan larger r and omized controlled studies . The large number of patients that were helped in this study demonstrates the efficacy of multivalent silver oxide topical ointment and its important role in ulcer therapy The presence of an ulcer beneath callus on the diabetic foot has been a well-documented and common clinical finding . We have conducted a prospect i ve study to examine whether callus can be used to predict plantar intrinsic neuropathic diabetic foot ulcer formation . Sixty-three diabetic patients ( 43 male , 25 Type 1 ) , median age 62 years ( IQ range 52 , 67 ) , median diabetes duration 17 years ( IQ range 8,25 ) participated in the study . All had neuropathy and peak plantar foot pressures ( measured using a dynamic optical pedobarograph ) > or = 10 kg cm-2 . Calluses and previous ulcers were documented and classified . All ulcers occurring prior to and during the study were recorded , re-examination was 15.4 ( range 10 - 22 ) months from baseline . Seven ulcers ( 6 patients ) occurred during the study . Pressures were higher in the ulcer than non-ulcer sub-group ( p = 0.04 ) with a relative risk of developing an ulcer of 4.7 for an area of elevated plantar pressure . This compares with a relative risk of 11.0 for an ulcer developing under an area of callus , and a relative risk of 56.8 for an ulcer developing on a site of previous ulceration . This study confirms that a history of previous ulceration is the highest risk factor for ulceration and demonstrates , for the first time , that the presence of plantar callus is highly predictive of subsequent ulceration . Careful history taking and examination of the foot to detect the presence of callus require no special training or equipment and callus should be recognized as a ' high risk ' factor for foot ulceration AIMS The application of felted foam is a promising method for plantar pressure reduction in the ulcer region of diabetic foot ulcers , but knowledge of its effects on wound healing is sparse . The objective of this study was to evaluate the effects of felted foam on wound healing in diabetic foot ulcers compared with a st and ard method of plantar pressure relief . MATERIAL S AND METHODS A total of 54 Type 1 or Type 2 diabetic patients with neuropathic diabetic foot ulcers were evaluated in this prospect i ve r and omized controlled study . Ulcer healing was assessed by planimetric measurement of the wound area at beginning of the study and after 10 weeks and at least until wound healing . The patients were consecutively enrolled in the study ; 24 patients were r and omized to the felted foam therapy , and 30 patients were r and omized to conventional therapy . RESULTS In the felted foam group , the initial average wound area was 102.3 + /- 45.3 mm2 ( mean + /- sd ) , and 5.4 + /- 3.1 mm2 after 10 weeks with an average healing time of 75 days [ 95 % confidence interval ( CI ) 67 - 84 ] . In the conventional therapy group , the initial average wound area was 112.5 + /- 50.8 mm2 , and 10.6 + /- 4.2 mm2 after 10 weeks with an average healing time of 85 days ( 95 % CI 79 - 92 ) ( P = 0.03 ) . The mean wound radius decreased by 0.48 mm ( 95 % CI 0.42 - 0.56 ) per week in the felted foam group and by 0.39 mm ( 95 % CI 0.35 - 0.42 ) per week in the conventional group ( P = 0.005 ) . CONCLUSIONS The felted foam technique appears to be at least as effective as conventional plantar ulcer treatment . It may be a useful alternative in treating neuropathic foot ulceration , especially in patients who are not able to avoid weight-bearing reliably Efficacy and safety of a collagen-alginate topical wound dressing ( FIBRACOL Collagen-Alginate Wound Dressing ) in the treatment of diabetic foot ulcers was compared with that of regular gauze moistened with normal saline . Seventy-five patients with foot ulcers were assigned r and omly in a 2:1 ratio to the collagen-alginate test dressing or the gauze dressing . At the end of the study , the mean percent reduction of the wound area was 80.6 % + /- 6 % in the collagen-alginate dressing group and 61.1 % + /- 26 % in the gauze dressing group ( p = .4692 ) . Thirty-nine ( 78 % ) patients treated with the collagen-alginate dressing achieved > or = 75 % wound area reduction , compared with 15 ( 60 % ) of gauze-treated patients . Complete healing was achieved in 24 ( 48 % ) of the collagen-alginate dressing group and 9 ( 36 % ) of the gauze dressing group . Wound size , when averaged over the 8-week period and with the duration of the ulcer taken into account , was reduced significantly in the collagen-alginate dressing group , as compared with the gauze dressing group ( df = 1 , p = .0049 ) . It is concluded that the collagen-alginate test dressing is as or more effective and safe as the currently used treatment Diabetic foot ulcers with exposure of tendon , muscle , or bone imply a high probability for deep infections and amputations . Delayed healing times are often described . The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with st and ard treatment in diabetic feet with cavity ulcers . Patients with deep , exudative foot ulcers were included in a 12-week open , r and omised , comparative study . When ulcers stopped exudating , vaseline gauze was used in both groups until the end of the study . Costs were estimated for dressing material , staff and transportation . Clinical ly relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with st and ard treatment . The average weekly cost was SEK 903 and SEK 1,421 , respectively , of which the major part was costs for staff and transportation related to frequency of dressing changes . Treatment with cadexomer iodine ointment ( Iodosorb ) showed no clinical difference compared to topical treatment consisting of gentamicin solution , streptodornase/streptokinase , or dry saline gauze but was associated with considerably lower weekly treatment costs This 12-week , prospect i ve , r and omised , controlled multi-centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix ( AM ) ( study group ) and st and ard of care ( control group ) therapies . Eighty-six patients were r and omised into study ( 47 patients ) and control ( 39 patients ) groups . No significant differences in demographics or pre-treatment ulcer data were calculated . Complete healing and mean healing time were 69.6 % and 5.7 weeks , respectively , for the study group and 46.2 % and 6.8 weeks , respectively , for the control group . The proportion of healed ulcers between the groups was statistically significant ( P = 0.0289 ) , with odds of healing in the study group 2.7 times higher than in the control group . Kaplan-Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate ( P = 0.015 ) for the control group ( 53.9 % ) compared with the study group ( 30.4 % ) . After adjusting for ulcer size at presentation , which was a statistically significant covariate ( P = 0.0194 ) , a statistically significant difference in non healing rate between groups was calculated ( P = 0.0233 ) , with odds of healing 2.0 times higher in the study versus control group . This study supports the use of single-application AM therapy as an effective treatment of diabetic , neuropathic ulcers Optimal treatment for large diabetic foot wounds is ill defined . The purpose of this study was to compare the rate of wound healing with the Vacuum Assisted Closure device ™ ( VAC ) to conventional moist dressings in the treatment of large diabetic foot wounds . Diabetics with significant soft tissue defects of the foot were considered for enrollment . Patients were r and omized to receive either moist gauze dressings or VAC treatments for 2 weeks , after which they were treated with the alternative dressing for an additional 2 weeks . Wounds were photographed weekly and wound dimensions calculated in a blinded fashion with spatial analysis software . Percent change in wound dimensions were calculated and compared for each weekly assessment and over 2 weeks of therapy with each dressing type . Ten patients were enrolled in the trial , but two were lost to follow-up and two were withdrawn . Complete data were available for analysis on seven wounds in six patients . Average length , width , and depth of the wounds at initiation of the trial was 7.7 , 3.5 , and 3.1 cm , respectively . Only the wound depth was significantly decreased over the weeks of the trial to 1.2 cm ( p < 0.05 ) . VAC dressings decreased the wound volume and depth significantly more than moist gauze dressings ( 59 % vs. 0 % and 49 % vs. 8 % , respectively ) . VAC dressings were associated with a decrease in all wound dimensions while wound length and width increased with moist dressings . In summary , over the first several weeks of therapy , VAC dressings decreased wound depth and volume more effectively than moist gauze dressings . Negative-pressure wound treatment may accelerate closure of large foot wounds in the diabetic patient BACKGROUND The study aim ed at comparing the efficacy and tolerance of an alginate wound dressing with a vaseline gauze dressing in the treatment of diabetic foot lesions . METHODS This open-label r and omized multicenter controlled study was design ed to assess the effect of an up to 6-week treatment with either calcium alginate or vaseline gauze dressings . Lesions were either acute or chronic , under cleansing , and with a surface area of 1 - 50 cm(2 ) ; osteomyelitis and severe hypovascularization were non- inclusion criteria . Dressings were changed every day then , once granulation had occurred , every 2 to 3 days . Primary outcome was the proportion of patients with granulation tissue over 75 % of the wound area and having a 40 % decrease in wound surface area ; secondary outcomes were pain on dressing changes , the number of dressing changes , and adverse events . RESULTS Seventy-seven patients were enrolled . Due to the premature cessation of treatment in 13 patients , it was decided to reduce the period of the efficacy analysis to 4 weeks ( without revising the criteria of efficacy ) . The success rate was of 42.8 % in the calcium alginate group and of 28.5 % in the vaseline gauze group ( not significant difference ) . A subsequent analysis of granulation tissue surfaces covering the wounds at week 4 ( all surfaces taken together ) showed a superiority of calcium alginate ( p=0.04 ) . Pain on dressing change was lower in the calcium alginate group ( p=0.047 ) and the total number of dressing changes tended also to be lower ( p=0.07 ) . Adverse events , which occurred 4 times in the calcium alginate group and 6 times in the other , were judged independent of the treatments . CONCLUSIONS As compared with vaseline gauze , calcium alginate appears to be more appropriate for topical treatment of diabetic foot lesions in terms of both healing and tolerance This investigation was conducted to determine if a correlation exists between wound healing outcomes and serial debridement in chronic venous leg ulcers ( VLUs ) and diabetic foot ulcers ( DFUs ) . We retrospectively analyzed the results from two controlled , prospect i ve , r and omized pivotal trials of topical wound treatments on 366 VLUs and 310 DFUs over 12 weeks . Weekly wound surface area changes following debridement and 12-week wound closure rates between centers and patients were evaluated . VLUs had a significantly higher median wound surface area reduction following clinical visits with surgical debridement as compared with clinical visits with no surgical debridement ( 34 % , p=0.019 ) . Centers where patients were debrided more frequently were associated with higher rates of wound closure in both clinical studies ( p=0.007 VLU , p=0.015 DFU ) . Debridement frequency per patient was not statistically correlated to higher rates of wound closure ; however , there was some minor evidence of a positive benefit of serial debridement in DFUs ( odds ratio-2.35 , p=0.069 ) . Our results suggest that frequent debridement of DFUs and VLUs may increase wound healing rates and rates of closure , though there is not enough evidence to definitively conclude a significant effect . Future clinical research in wound care should focus on the relationship between serial surgical wound debridement and improved wound healing outcomes as demonstrated in this study The purpose of this study was to determine the recurrence rate of diabetic neurotrophic foot ulcers that had healed in a treatment protocol using topically applied growth factors released from platelets . Thirty-six patients with diabetic neurotrophic foot ulcers were entered into a r and omized prospect i ve double-blind 20-week trial of topically applied platelet growth factors or buffered saline dressings . Ulcers had been present for 15.5 months ( mean , range 2 to 60 months ) . Sixteen patients ( 44 % ) healed and were followed up for as many as 30 months to determine the rate of ulcer recurrence . Eleven patients ( 68.8 % ) had ulcers that recurred , including 10 treated with platelet growth factors and one treated with buffered saline solution . These ulcers had been present for 20 months ( range 5 to 60 months ) before healing . Average time to ulcer recurrence was 2.2 months ( range 0.25 to 7 months ) . Five ulcers ( 31.2 % ) remained healed , including four treated with platelet growth factors and one treated with buffered saline solution . These healed , nonrecurring ulcers had been present for 5 months ( range 2 to 6 months ) before healing . Average follow up was 25 months ( range 24 to 30 months ) . Ulcers were more likely to recur if they had been present longer before healing . If patients were not compliant in wearing footwear to protect the healed ulcer , the ulcers were prone to early recurrence . These data indicate that ulcers healed by using growth factors in the form of a platelet growth factors did not have more durable skin over the ulcer and were prone to early ulcer recurrence This is the interim analysis of a prospect i ve , r and omized , controlled study comparing diabetic foot ulcer healing in patients being treated with either noncontact normothermic wound therapy ( Warm-UP ; Augustine Medical Inc. Eden Prairie , MN ) applied for 1 hour 3 times daily until healing or 12 weeks , or st and ard care ( saline-moistened gauze applied once a day ) . Surgical debridement and adequate foot off-loading was provided to both groups . Evaluations were performed weekly and consisted of acetate tracings , wound assessment , and serial photography . Twenty patients have completed the trial and both treatment groups were distributed evenly ( N = 10 ) . Ulcers treated with noncontact normothermic wound therapy had a greater mean percent wound closure than control-treated ulcers at each evaluation point ( weeks 1 - 12 ) . After 12 weeks , 70 % of the wounds treated with noncontact normothermic wound therapy were healed compared with 40 % for the control group . In this subset of patients there have been no adverse events associated with noncontact normothermic wound therapy The concept of moist wound healing is not fully implemented in daily practice in Germany . Thus , the objective of this investigation was to evaluate the use of Tielle hydropolymer dressings in chronic exuding wounds in primary care . A total of 6,993 patients with pressure sores ( 26.6 % ) , venous leg ulcers ( 59.8 % ) , diabetic foot disease ( 9.5 % ) and other wounds ( 5.1 % ) were enrolled into three multicentre , open-label , single-arm , prospect i ve phase-IV studies for an observational period of either 4 or 12 weeks . Within the 4 (12)-week study using Tielle , 43.3 % ( 59.1 % ) of the wounds healed and 51.6 % ( 36.9 % ) improved . Wound area was reduced by 78.2 % ( 85.1 % ) . Medium or strong levels of exu date s were reduced from 57.4 % to 6.7 % ( 4.0 % ) . Cosmetic results were excellent or good in 96.3 % . Compared with patients ' previous treatment , efficacy and tolerability were assessed as better or much better in 92.5 % and 70.4 % , respectively . 97.1 % of the patients remained free of adverse events . The frequency of dressing changes was reduced from 5 to 3 per week ( -43 % ) . Tielle provides an effective and safe dressing in the management of chronic exuding wounds in primary care improving patient 's comfort . Due to longer wearing times , Tielle may also be cost saving AIMS To test the safety and effectiveness of carboxyl-methyl-cellulose dressing ( Aquacel ; ConvaTec , UK ) in the management of deep diabetic foot ulcers , a group of consecutive out- patients attending the foot clinic of the Department of Metabolic Diseases was studied . METHODS Patients were selected according to the following inclusion criteria : a foot ulcer deeper than 1 cm for > 3 weeks , good peripheral blood supply ( palpable peripheral pulses or ABPI > 0.9 ) . Exclusion criteria were as follows : active infection , as evident from clinical signs ( purulent discharge , redness , swelling , tenderness ) and confirmed by culture exams , plasma creatinine > 2 mg/dl , recent episodes of ketoacidosis , malignancies , and any therapy or pathology which might interfere with the healing process . Twenty patients were enrolled in the study and having obtained their informed consent , their lesions were surgically debrided with the complete elimination of all necrotic tissue and debris up to the bleeding healthy tissue ; then ulcers were staged and measured , and patients were r and omly assigned to two different treatment groups . Patients in group A were dressed with saline-moistened gauze , while patients in group B were dressed with Aquacel according to the manufacturer 's instructions . All patients in both groups received special post-operative shoes ( Podiabetes ; Zeno Buratto , Treviso , Italy ) and crutches until complete re-epithelialization . Ulcers were all left to heal by secondary intent . After 8 weeks patients were blindly evaluated for : the rate of reduction of lesional volume ( RLV ) , rate of granulation tissue ( GT ) , number of infective complications ( IC ) . Intralesional ( ILTC ) and perilesional ( PLTC ) temperatures were also recorded with a thermocouple surface digital thermometer , and the difference between the two values ( Delta TC ) was calculated . Healing time ( HT , days ) , was then compared between the two groups . Data were compared by analysis of variance ( ANOVA ) , linear regression , Kaplan-Meier survival analysis and Fisher 's exact test . RESULTS HT was significantly shorter in Group B than in Group A ( P < 0.001 ) . RLV was significantly ( P < 0.01 ) higher in Group B patients compared with Group A , as well as GT ( P < 0.05 ) . IC were in 1/10 Group B and in 3/10 Group A ( P = 0.582 ) . In addition , both ILTC and Delta TC were higher in Group B compared with Group A ones ( P < 0.01 ) . CONCLUSIONS Carboxyl-methyl-cellulose dressings were shown to be safe , effective and well tolerated in the management of non-ischaemic , non-infected deep diabetic foot ulcers OBJECTIVE To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers . RESEARCH DESIGN AND METHODS Thirteen patients entered a r and omized , double-blind trial of topically applied CT-102 APST vs. placebo ( normal saline ) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers . CT-102 APST ( Curative Technologies , Setauket , NY ) was prepared from homologous platelets and contained multiple growth factors including PDGF , PDAF , EGF , PF-4 , TGF-β , aFGF , and bFGF . Inclusion criteria for subjects included diabetes , ulcer of > 8 wk duration , peri-wound transcutaneous oxygen tension > 30 mmHg , platelet count > 100,000/mm3 , and no wound infection . Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume , < 100 cm2 in area , and involved subcutaneous tissue . RESULTS In the CT-102 group , 5 of 7 ulcers were healed ( 100 % epithelialized ) by 15 wk , but only 1 of 6 ulcers was healed by 20 wk with placebo ( P < 0.05 ) . Average percent reduction in ulcer area at 20 wk was 94 % for CT-102 vs. 73 % for placebo . Daily reduction in ulcer volume was 73.8 ± 42.4 mm3/day ( mean ± SE ) for CT-102 vs. 21.8 ± 8.1 mm3/day for placebo ( P < 0.05 ) . Daily reduction in ulcer area was 6.2 ± 1.8 mm2/day for CT-102 vs. 1.8 ± 0.4 mm2/day for placebo ( P < 0.05 ) . CONCLUSIONS CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers 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 This study compared the efficacy and safety of Apligraf ( Organogenesis , Inc. , Canton , MA ) in combination with st and ard therapy versus st and ard therapy alone in the treatment of neuropathic diabetic foot ulcers . Efficacy was assessed by time to complete wound healing ( by 12 weeks ) and incidence of complete wound closure ( at 12 weeks ) . This was an international multi-center , r and omized , controlled study . Patients were eligible for entry into the study if the following criteria were met : type 1 or type 2 diabetes mellitus , age 18 to 80 years , adequate glycemic control , and the presence of a full-thickness neuropathic ulcer for at least 2 weeks prior to the initial screening visit . Following the 2-week screening period , the 2 treatment groups received st and ard ulcer care consistent with international treatment guidelines that comprised sharp debridement , saline-moistened dressings , and a non — weight bearing regimen . There were 106 subjects screened for enrollment , 82 r and omized to the treatment groups , and 72 treated ( 33 Apligraf subjects and 39 st and ard therapy subjects ) before the study was terminated . Kaplan — Meier curves indicated a trend for shorter time to complete wound healing in the Apligraf group compared with the st and ard therapy group ( p = .059 ; log-rank test ) . The median time to healing was 84 days in the Apligraf group , whereas no median time to healing could be determined for the st and ard therapy group because < 50 % of the st and ard therapy subjects healed . By 12 weeks , 51.5 % ( 17/33 ) Apligraf subjects had achieved complete wound closure compared with 26.3 % ( 10/38 ) of st and ard therapy subjects ( p = .049 ; Fisher 's exact test ) . Even though the study was halted prematurely , this study suggested that the use of Apligraf result ed in a higher incidence of wound closure by 12 weeks |
2,604 | 22,029,832 | The studies addressing price incentives suggest that such incentives are effective for altering consumption in the school setting .
Other types of economic incentives have been included in combined intervention schemes , but the inclusion of other intervention elements makes it difficult to draw conclusions about the effectiveness of the economic incentive instruments per se in these studies | The aim of the present review was to examine the existing literature on the effectiveness of economic incentives for producing sound nutritional behavior in schools . | Background Schools are the most frequent target for intervention programs aim ed at preventing child obesity ; however , the overall effectiveness of these programs has been limited . It has therefore been recommended that interventions target multiple ecological levels ( community , family , school and individual ) to have greater success in changing risk behaviors for obesity . This study examined the immediate and short-term , sustained effects of the Switch program , which targeted three behaviors ( decreasing children 's screen time , increasing fruit and vegetable consumption , and increasing physical activity ) at three ecological levels ( the family , school , and community ) . Methods Participants were 1,323 children and their parents from 10 schools in two states . Schools were matched and r and omly assigned to treatment and control . Measures of the key behaviors and body mass index were collected at baseline , immediately post-intervention , and 6 months post-intervention . Results The effect sizes of the differences between treatment and control groups ranged between small ( Cohen 's d = 0.15 for body mass index at 6 months post-intervention ) to large ( 1.38 ; parent report of screen time at 6 months post-intervention ) , controlling for baseline levels . There was a significant difference in parent-reported screen time at post-intervention in the experimental group , and this effect was maintained at 6 months post-intervention ( a difference of about 2 hours/week ) . The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant . At the 6-month follow-up , parent-reported screen time was significantly lower , and parent and child-reported fruit and vegetable consumption was significantly increased . There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group . The intervention effects were moderated by child sex ( for fruit and vegetable consumption , physical activity , and weight status ) , family involvement ( for fruit and vegetable consumption ) , and child body mass index ( for screen time ) . The perception of change among the experimental group was generally positive with 23 % to 62 % indicating positive changes in behaviors . Conclusion The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children 's fruit and vegetable consumption and minimizing screen time . The Switch program offers promise for use in youth obesity prevention BACKGROUND Price can influence food purchases , which can influence consumption . Limited laboratory research has assessed the effect of price changes on food purchases , and no research on individual differences that may interact with price to influence purchases exists . OBJECTIVE We aim ed to assess the influence of price changes of low-energy-density ( LED ) and high-energy-density ( HED ) foods on mother 's food purchases in a laboratory food-purchasing analogue . DESIGN Mothers were r and omly assigned to price conditions in which the price of either LED or HED foods was manipulated from 75 % to 125 % of the reference purchase price , whereas the price of the alternative foods was kept at the reference value . Mothers completed purchases for 2 income levels ( $ 15 or $ 30 per family member ) . RESULTS Purchases were reduced when prices of LED ( P < 0.01 ) and HED ( P < 0.001 ) foods were increased . Maternal BMI interacted with price to influence purchases of HED foods when the price of HED foods increased ( P = 0.016 ) and interacted with price to influence purchases of LED foods when the price of HED foods increased ( P = 0.008 ) . CONCLUSION These results show the relevance of considering price change as a way to influence food purchases of LED compared with HED foods and the possibility that individual differences may influence the own-price elasticity of HED foods and substitution of LED for HED foods OBJECTIVES This study examined the effects of pricing and promotion strategies on purchases of low-fat snacks from vending machines . METHODS Low-fat snacks were added to 55 vending machines in a convenience sample of 12 secondary schools and 12 worksites . Four pricing levels ( equal price , 10 % reduction , 25 % reduction , 50 % reduction ) and 3 promotional conditions ( none , low-fat label , low-fat label plus promotional sign ) were crossed in a Latin square design . Sales of low-fat vending snacks were measured continuously for the 12-month intervention . RESULTS Price reductions of 10 % , 25 % , and 50 % on low-fat snacks were associated with significant increases in low-fat snack sales ; percentages of low-fat snack sales increased by 9 % , 39 % , and 93 % , respectively . Promotional signage was independently but weakly associated with increases in low-fat snack sales . Average profits per machine were not affected by the vending interventions . CONCLUSIONS Reducing relative prices on low-fat snacks was effective in promoting lower-fat snack purchases from vending machines in both adult and adolescent population This study reports the effect of a school-r and omized fruit and vegetable intervention consisting of a subscription to the Norwegian School Fruit Programme at no parental cost , and the Fruit and Vegetables Make the Marks ( FVMM ) educational programme , both delivered in the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 517 pupils ( 84 % ; mean age , 11.3 years at baseline ) participated in all three surveys . At both Follow-up 1 and Follow-up 2 , strong intervention effects were observed for all-day fruit and vegetable intake ( effect sizes were 0.6 and 0.5 portions , respectively ) . The sustained effect at Follow-up 2 , 1 year after the end of the intervention , can partly be explained by greater participation rates in the School Fruit Programme ( st and ard paid subscription ) . We conclude that the effects observed are most likely due to the no-cost subscription and not due to the FVMM educational programme , and that providing pupils with a piece of fruit or a vegetable at school at no cost for the parents is an effective strategy to increase school children 's intake of fruit and vegetables . The effect is also sustained 1 year after the end of the no-cost subscription , providing increased health benefits Background / Objectives : Previous research in the United Kingdom , where there is a school canteen system , has shown that the Food Dudes intervention substantially increases children 's fruit and vegetable consumption . The current study evaluated its effectiveness in Irel and where school meals are not provided and children bring food to school in lunchboxes . Subjects/ Methods : Participants were 4- to 11-year-old children attending two primary schools ; the schools were r and omly assigned to experimental or control conditions ( n=228 and 207 , respectively ) . During the 16-day intervention in the experimental school , children watched video adventures featuring the heroic Food Dudes , and received small rewards for eating fruit and vegetables provided . In both schools , parental provision and children 's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up ( Lunchbox measures ) . Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention , and children 's consumption was measured ( school-provided food measures ) . Results : Relative to baseline , consumption of the school-provided foods increased during the intervention in the experimental school ( P<0.001 ) , whereas in the control school it showed a significant decline . At 12-month follow-up , parents in the experimental school provided and their children consumed significantly more lunchbox fruit , vegetables and juice relative to baseline and to the control school ( P<0.001 in all instances ) . Conclusions : The Food Dudes intervention was effective in changing parental provision and children 's consumption of lunchbox fruit and vegetables in Irel and BACKGROUND Our objective was to evaluate the effects of environmental , policy , and social marketing interventions on physical activity and fat intake of middle school students on campus . DESIGN Twenty-four middle schools were r and omly assigned to intervention or control conditions . Baseline measures were collected in spring 1997 , and interventions were conducted during the 1997 - 1998 and 1998 - 1999 school years SETTING /PARTICIPATION : The schools had mean enrollments of 1109 , with 44.5 % nonwhite students . Over 2 years , physical activity interventions were design ed to increase physical activity in physical education classes and throughout the school day . Nutrition interventions were design ed to provide and market low-fat foods at all school food sources , including cafeteria breakfasts and lunches , a la carte sources , school stores , and bag lunches . School staff and students were engaged in policy change efforts , but there was no classroom health education . MAIN OUTCOMES MEASURES Primary outcomes were measured by direct observation and existing records . RESULTS R and omized regression models ( N = 24 schools ) revealed a significant intervention effect for physical activity for the total group ( p < 0.009 ) and boys ( p < 0.001 ) , but not girls ( p < 0.40 ) . The intervention was not effective for total fat ( p < 0.91 ) or saturated fat ( p < 0.79 ) . Survey data indicated that the interventions reduced reported body mass index for boys ( p < 0.05 ) . CONCLUSIONS Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls . The interventions were not effective in reducing fat intake at school . School environmental and policy interventions have the potential to improve health behavior of the student population , but barriers to full implementation need to be better understood and overcome OBJECTIVE To assess dietary costs during a family-based pediatric obesity intervention . DESIGN Families were r and omized to one of two groups . Dietary and cost data were collected from a parent or child using three 24-hour recalls : at baseline , 6 months , and 12 months . SUBJECTS Thirty-one families with an obese 8- to 12-year-old child entered treatment , with complete dietary data provided from 20 families . INTERVENTION The 20-week behavior modification intervention emphasized increasing diet nutrient-density . Families attended group and individual sessions or group sessions . MAIN OUTCOME MEASURES Energy intake ; percent of energy from protein , fat , and carbohydrate ; servings and percent servings from food groups classified by nutrient density ; and daily food costs . STATISTICAL ANALYSES PERFORMED Mixed analyses of variance , with group as the between-subject factor , and time as the within-subject factor . RESULTS No significant effect of group was found in any analyses . Significant decreases in percent overweight were observed at 6 and 12 months for children ( -10.0+/-8.7 and -8.0+/-10.3 , respectively ) ( mean+/-st and ard deviation ) and parents ( -6.7+/-10.3 and -5.3+/-14.1 ) . Energy intake for parents and children combined significantly decreased from baseline ( 1,881+/-462 ) to 6 months ( 1,412+/-284 ) , and 1 year ( 1,338+/-444 ) . Servings from low-nutrient-dense foods significantly decreased from baseline ( 34.7+/-16.2 ) to 6 months ( 16.0+/-8.6 ) and 1 year ( 18.6+/-9.2 ) , causing a significant increase in diet nutrient density . Dietary cost did not change at 6 months , but significantly decreased from baseline to 1 year ( $ 6.77+/-2.41 to $ 5.04+/-1.80 ) . Cost per 1,000 kcal did not significantly change . APPLICATIONS/ CONCLUSIONS Adopting a lower-energy , nutrient-dense diet did not increase dietary costs over time . Consequently , cost should not be a barrier in the adoption of a healthful diet This study examines the feasibility and effectiveness of an environmental intervention for improving diet by comparing the impact of health messages , lowered prices , and their combination on the purchase of healthy food items in a restaurant . Price decreases alone , rather than a combination of price decreases and health messages , were associated with a higher level of increased purchases of some healthy food items as compared with control items over a 4-month period . Price decreases may be a more powerful means than health messages of increasing consumption of healthy foods . Health messages may have paradoxical effects if foods labeled as healthy are assumed to taste bad OBJECTIVE The objective of this study was to identify factors that predict offering and sale of competitive foods , as well as factors that predict average daily participation in school lunch . DESIGN Surveys were distributed to 271 school foodservice directors in a r and om sample of high schools in Pennsylvania that were selected to be representative of the entire population of high schools in Pennsylvania based on chosen demographic characteristics . SUBJECTS Two hundred twenty-eight school foodservice directors ( 84 % ) returned surveys . STATISTICAL ANALYSES Descriptive and multiple regression analyses were done using SPSS version 11.5 ( 2002 , SPSS Inc , Chicago , IL ) . RESULTS Percentage of students eligible for free or reduced-price meals and timing of lunch were significant predictors of a la carte sales . Enrollment was negatively associated with number of vending machines per student . The number of less nutritious food items offered in vending machines and existence of soft drink machines owned by soft drink companies , for which the school receives a percent of sales , both predicted number of vending machines per student . Enrollment was inversely related to average daily participation in school lunch . The percentage of students eligible for free/reduced-price meals and enforcement of a policy prohibiting parents or students from bringing food into the cafeteria from local fast-food establishments positively predicted average daily participation in school lunch . CONCLUSIONS These findings may be useful to school wellness councils in developing wellness policies as m and ated by the Child Nutrition and WIC Reauthorization Act of 2004 , as well as in structuring school environments to promote more healthful food choices by students BACKGROUND This study reports the effect of providing Norwegian school children with free fruit or vegetables every school day and the effect of an existing fee-based School Fruit Programme . METHODS Seventh grade pupils and their parents completed question naires at baseline ( autumn 2001 ) and at follow-up ( spring 2002 ) . Nine schools participated in the School Fruit Programme for free ( Free fruit ) , nine schools took part at st and ard conditions ( Paid fruit ) , and 20 schools did not take part in the subscription programme ( No fruit ) . A total of 795 7th grade rs ( 11 or 12 years old at baseline ) participated both at baseline and at follow-up . RESULTS At follow-up , pupils attending the Free fruit schools had significantly higher intake of fruit and vegetables at school than the pupils at the Paid fruit and No fruit schools ( P < 0.001 , mean intakes were 1.1 , 0.4 and 0.2 portions , respectively ) . Subscribers at the Paid fruit schools had significantly higher intake than the non-subscribers at the same schools . CONCLUSIONS Providing a free piece of fruit or a vegetable is an effective strategy to increase school children 's fruit and vegetable intake . The existing School Fruit Programme appears to increase the intake among the subscribers , but thereby also tends to increase an existing difference in consumption patterns among subscribers and non-subscribers Objective : To test the ability of two levels of modest financial incentives to encourage weight loss among overweight employees . Methods : This study used a r and omized design with measurements at baseline , 3 , and 6 months and two levels of financial incentives ( $ 7 and $ 14 per percentage point of weight lost ) . Payments were structured so that all participants had equal ability to obtain the incentives during the study period . Results : At 3 months , participants with no financial incentive lost 2 pounds , those in the $ 7 group lost approximately 3 pounds , and those in the $ 14 group lost 4.7 pounds . Between baseline and 6 months , when the financial gains were equalized , weight losses were similar across groups . Conclusion : This study revealed that modest financial incentives can be effective in motivating overweight employees to lose weight CONTEXT Identifying effective obesity treatment is both a clinical challenge and a public health priority due to the health consequences of obesity . OBJECTIVE To determine whether common decision errors identified by behavioral economists such as prospect theory , loss aversion , and regret could be used to design an effective weight loss intervention . DESIGN , SETTING , AND PARTICIPANTS Fifty-seven healthy participants aged 30 - 70 years with a body mass index of 30 - 40 were r and omized to 3 weight loss plans : monthly weigh-ins , a lottery incentive program , or a deposit contract that allowed for participant matching , with a weight loss goal of 1 lb ( 0.45 kg ) a week for 16 weeks . Participants were recruited May-August 2007 at the Philadelphia VA Medical Center in Pennsylvania and were followed up through June 2008 . MAIN OUTCOME MEASURES Weight loss after 16 weeks . RESULTS The incentive groups lost significantly more weight than the control group ( mean , 3.9 lb ) . Compared with the control group , the lottery group lost a mean of 13.1 lb ( 95 % confidence interval [ CI ] of the difference in means , 1.95 - 16.40 ; P = .02 ) and the deposit contract group lost a mean of 14.0 lb ( 95 % CI of the difference in means , 3.69 - 16.43 ; P = .006 ) . About half of those in both incentive groups met the 16-lb target weight loss : 47.4 % ( 95 % CI , 24.5%-71.1 % ) in the deposit contract group and 52.6 % ( 95 % CI , 28.9%-75.6 % ) in the lottery group , whereas 10.5 % ( 95 % CI , 1.3%-33.1 % ; P = .01 ) in the control group met the 16-lb target . Although the net weight loss between enrollment in the study and at the end of 7 months was larger in the incentive groups ( 9.2 lb ; t = 1.21 ; 95 % CI , -3.20 to 12.66 ; P = .23 , in the lottery group and 6.2 lb ; t = 0.52 ; 95 % CI , -5.17 to 8.75 ; P = .61 in the deposit contract group ) than in the control group ( 4.4 lb ) , these differences were not statistically significant . However , incentive participants weighed significantly less at 7 months than at the study start ( P = .01 for the lottery group ; P = .03 for the deposit contract group ) whereas controls did not . CONCLUSIONS The use of economic incentives produced significant weight loss during the 16 weeks of intervention that was not fully sustained . The longer-term use of incentives should be evaluated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00520611 School environments that provide consistent and reliable nutrition information promote the development of healthful eating in children . High-energy , nutrient-poor beverages offered for sale to children during the school day compete with healthful choices . The primary objective of this prospect i ve , quasiexperimental study was to encourage children to choose more healthful beverages during the school day without adversely affecting the profits realized from vending sales . Fifteen of 18 schools completed voluntary changes to beverage sales practice s during the school day between August 2005 and May 2006 . Twelve of 15 schools reported increased profits from the previous year ( 2004 - 2005 ) while offering more healthful beverage choices at discounted prices . Units of carbonated soft drinks sold declined when sports drinks , 100 % fruit juice , and water were made available in their place . Passive marketing in the form of vending machine fronts , attractive pricing with a nominal 10 % to 25 % discount , and changing the types and proportions of beverages offered encouraged children to make more healthful choices . Local school administrators were receptive to making changes to beverage sales when local needs were incorporated into the study design . Profit information from this study informed state legislators and the Mississippi State Board of Education in the development and adoption of statewide snack and beverage vending guidelines . Registered dietitians serve as advocates to foster these collaborative efforts , inform key decision makers , and work in their local communities to develop and promote healthful practice s in K-12 school setting |
2,605 | 23,813,844 | There was a significant improvement in haemodynamic profile and functional status after implantation .
CONCLUSIONS MitraClip implantation is an option in managing selected high surgical risk patients with severe MR .
The current evidence suggests that MitraClip can be implanted with reproducible safety and feasibility profile in this subgroup of patients . | BACKGROUND MitraClip implantation has emerged as a viable option in high surgical risk patients with severe mitral regurgitation ( MR ) .
We performed the present systematic review to assess the safety and efficacy of the MitraClip system for high surgical risk c and i date s with severe organic and /or functional MR . | Background Percutaneous mitral valve repair ( MVR ) using the MitraClip system has become a valid alternative for patients with severe mitral regurgitation ( MR ) and high operative risk . Objective To identify clinical and periprocedural factors that may have an impact on clinical outcome . Design Multi-centre longitudinal cohort study . Setting Tertiary referral centres . Patients Here we report on the first 100 consecutive patients treated with percutaneous MVR in Switzerl and between March 2009 and April 2011 . All of them had moderate – severe ( 3 + ) or severe ( 4 + ) MR , and 62 % had functional MR . 82 % of the patients were in New York Heart Association ( NYHA ) class III/IV , mean left ventricular ejection fraction was 48 % and the median European System for Cardiac Operative Risk Evaluation was 16.9 % . Interventions MitraClip implantation performed under echocardiographic and fluoroscopic guidance in general anaesthesia . Main outcome measures Clinical , echocardiographic and procedural data were prospect ively collected . Results Acute procedural success ( APS , defined as successful clip implantation with residual MR grade ≤2 + ) was achieved in 85 % of patients . Overall survival at 6 and 12 months was 89.9 % ( 95 % CI 81.8 to 94.6 ) and 84.6 % ( 95 % CI 74.7 to 91.0 ) , respectively . Univariate Cox regression analysis identified APS ( p=0.0069 ) and discharge MR grade ( p=0.03 ) as significant predictors of survival . Conclusions In our consecutive cohort of patients , APS was achieved in 85 % . APS and residual discharge MR grade are important predictors of mid-term survival after percutaneous MVR OBJECTIVES Corrective surgery for secondary mitral regurgitation ( MR ) by restrictive annuloplasty has proven beneficial in that it improves New York Heart Association ( NYHA ) functional class and induces reverse left ventricular remodelling . However , proof of a survival benefit for these patients is still pending . Percutaneous techniques of mitral valve repair ( MVR ) have become a viable treatment alternative for selected high-risk patients with severe secondary MR . METHODS We retrospectively analysed our prospect i ve hospital data base of patients with severe secondary MR undergoing either surgical MVR or percutaneous treatment using the MitraClip device . Patient characteristics and 6-month clinical and effectiveness outcomes are reported . RESULTS From March 2002 through June 2010 , 76 patients with secondary MR underwent isolated surgical MVR , while 95 were treated using the MitraClip device at our centre . Patients undergoing MitraClip treatment were significantly older ( mean 72.8 ± 8.2 vs 64.5 ± 11.4 years , P < 0.001 ) , had a lower left ventricular ejection fraction ( mean 36.2 ± 12.5 vs 42.1 ± 16.2 % , P = 0.014 ) and were generally more high risk , with a significantly higher mean logistic EuroSCORE I compared with surgical c and i date s ( 33.7 ± 18.7 vs 10.1 ± 8.7 % , P < 0.001 ) . Procedural success was 98.7 ( 75 of 76 ) for MVR and 95.8 % ( 91 of 95 ) for MitraClip treatment ( P = 0.383 ) . Thirty-day mortality was 4.2 ( 4 of 95 ) and 2.6 % ( 2 of 76 ; P = 0.557 ) , and the mean grade of residual MR was 1.4 ± 0.8 and 0.2 ± 0.4 ( P < 0.001 ) after MitraClip treatment and surgical MVR , respectively . Six-month survival rates after adjustment for baseline differences were not significantly different in the respective groups ( P = 0.642 ) . CONCLUSIONS In our experience , characteristics and risk factors of patients with severe secondary MR undergoing surgery differ significantly from those considered for percutaneous therapy . Surgery was more effective compared with MitraClip in reducing MR . However , a large proportion of patients benefits from percutaneous intervention with sustained MR Grade < 2 + and improvement in NYHA functional class at 6 months . MitraClip therapy seems to be an adequate alternative to surgery , especially for elderly patients with reduced left ventricular function and relevant comorbidities . Assessment , treatment and postprocedural care of patients by an interdisciplinary team are of paramount importance for clinical success OBJECTIVES The main objective of this study was to assess if the benefits of biventricular ( BiV ) pacing observed during the crossover phase were sustained over 12 months . BACKGROUND MUltisite STimulation In Cardiomyopathies ( MUSTIC ) is a r and omized controlled study intended to evaluate the effects of BiV pacing in patients with New York Heart Association ( NYHA ) class III heart failure and intraventricular conduction delay . METHODS Of 131 patients included , 42/67 in sinus rhythm ( SR ) and 33/64 in atrial fibrillation ( AF ) were followed up longitudinally at 9 and 12 months by 6-min walked distance , peak oxygen uptake ( peak VO(2 ) ) , quality of life by the Minnesota score , NYHA class , echocardiography , and left ventricular ejection fraction by radionuclide technique . RESULTS At 12 months , all SR and 88 % of AF patients were programmed to BiV pacing . Compared with baseline , the 6-min walked distance increased by 20 % ( SR ) ( p = 0.0001 ) and 17 % ( AF ) ( p = 0.004 ) ; the peak VO(2 ) by 11 % ( SR ) and 9 % ( AF ) ; quality of life improved by 36 % ( SR ) ( p = 0.0001 ) and 32 % ( AF ) ( p = 0.002 ) ; NYHA class improved by 25 % ( SR ) ( p = 0.0001 ) and 27 % ( AF ) ( p = 0.0001 ) . The ejection fraction improved by 5 % ( SR ) and 4 % ( AF ) . Mitral regurgitation decreased by 45 % ( SR ) and 50 % ( AF ) . CONCLUSIONS The clinical benefits of BiV pacing appeared to be significantly maintained over a 12-month follow-up period OBJECTIVE The Endovascular Valve Edge-to-Edge Repair Study ( EVEREST II ) is a prospect i ve , multicenter , r and omized controlled trial comparing percutaneous repair with the MitraClip device to mitral valve ( MV ) surgery in the treatment of mitral regurgitation . The present study analyzed the patient characteristics and treatment effects on mitral repair versus replacement . METHODS Of 279 patients enrolled , 80 surgical patients underwent 82 MV operations and 178 underwent an initial MitraClip procedure , of whom 37 underwent a subsequent MV operation within 1 year of their index the MitraClip procedure . A logistic regression model was used to predict MV replacement according to valve pathology , etiology of mitral regurgitation , age , previous cardiac surgery , and treatment group . RESULTS The rate of percutaneous or surgical MV repair at 1 year was 89 % ( 158/178 ) in patients initially receiving the MitraClip device versus 84 % ( 67/80 ) in the surgical patients ( P = .36 ) . Surgical repair was performed after the MitraClip procedure in 20 ( 54 % ) of 37 patients ( P < .001 vs surgery ) . In both the MitraClip device and surgery groups , MV replacement was significantly associated with anterior leaflet pathology ( P = .035 ) . Logistic regression analysis showed that anterior leaflet pathology predicted MV replacement . In 5 ( 13.5 % ) of 37 patients undergoing surgery after MitraClip therapy , replacement was performed in part because of MV injury associated with the MitraClip procedure . CONCLUSIONS These data suggest that anterior leaflet pathology is strongly associated with MV replacement in patients undergoing either de novo MV surgery or surgery after MitraClip therapy . MitraClip therapy has a repair rate similar to surgery through 1 year but also imparts a risk of replacement of a potentially repairable valve The aims of the echocardiographic sub study of this multicenter trial were to evaluate the use of quantitative assessment of mitral regurgitation ( MR ) severity using serial echocardiography and to assess the efficacy of percutaneous mitral valve repair . Previous surgical repair studies did not use quantitative echocardiographic methods . Results of a percutaneous mitral valve repair clip device in a core echocardiographic laboratory were evaluated . Published parameters for quantifying MR were used in a systematic protocol to qualify patients for study entry and evaluate treatment efficacy at discharge and 6 months after clip repair . Baseline results were presented for 55 patients , and follow-up results , for 49 . Ninety-eight percent of required echocardiographic studies were su bmi tted to the core laboratory , and > 85 % of required measurements were possible . At baseline , mean regurgitant volume was 54.8 + /- 24 ml , regurgitant fraction was 46.9 + /-16.2 % , effective regurgitant orifice area was 0.71 + /- 0.40 cm(2 ) , and vena contracta width was 0.66 + /- 0.20 cm . Based on a severity scale of 1 to 4 , mean color flow grade was 3.4 + /- 0.7 , and mean pulmonary vein flow was 2.8 + /- 1.2 . In patients with a clip at 6 months , all measurements of MR severity were significantly decreased versus baseline , with mean regurgitant volume decreased from 50.3 to 27.5 ml ( change -22.8 ml ; p < 0.0001 ) , regurgitant fraction from 44.6 % to 28.9 % ( change -15.7 % ; p < 0.0001 ) , color flow grade from an average of 3.4 to 1.8 ( change -1.6 ; p < 0.0001 ) , and pulmonary vein flow from 2.8 to 1.8 ( change -1.0 ; p < 0.0018 ) . In conclusion , quantitative assessment of MR is feasible in a multicenter trial , and percutaneous mitral repair with the MitraClip produces a sustained decrease in MR severity to moderate or less for > or = 6 months BACKGROUND In patients with chronic heart failure , the use of carvedilol therapy induces clinical and hemodynamic improvement . However , although the benefits of this beta-blocker have been established in patients with chronic heart failure , the mechanisms underlying them and the changes in left ventricular systolic function , diastolic function , and mitral regurgitation during long-term therapy remain unclear . OBJECTIVE To identify the clinical and functional effects of carvedilol , focusing on diastolic function and mitral regurgitation variations . METHODS Forty-five consecutive patients with chronic heart failure ( ejection fraction 24 % + /- 7 % ) , 17 with dilated ischemic and 28 with nonischemic cardiomyopathy , were treated with carvedilol ( mean dose 44 + /- 30 mg ) and matched for clinical ( New York Heart Association functional class and heart failure duration ) and hemodynamic ( cardiac index and pulmonary wedge pressure ) characteristics to a control group . Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared . RESULTS After 6 months of treatment with carvedilol , left ventricular ejection fraction had increased from 24 % + /- 7 % to 29 % + /- 9 % ( P < .0001 ) ; this change was caused by a reduction in end-systolic volume index ( 106 + /- 41 vs 93 + /- 37 mL/m(2 ) ; P < . 0001 ) . Deceleration time of early diastolic filling increased ( 134 + /- 74 vs 196 + /- 63 ms ; P < .0001 ) . Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern . In the control group , no significant changes in deceleration time of early diastolic filling were found ( 139 + /- 74 vs 132 + /- 45 ms ; P = not significant ) . The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group . These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group ( 50 + /- 25 vs 16 + /- 13 mL ; P < .0001 ) but not in the control group ( 57 + /- 29 vs 47 + /- 24 mL ; P = not significant ) . These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume ( r = -.57 , P < .0001 ) . These findings were not observed in patients in the control group . CONCLUSIONS The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation . The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation , which have been demonstrated to be powerful prognostic predictors in such patients . Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure BACKGROUND Percutaneous mitral repair with the MitraClip device ( Evalve , Menlo Park , CA ) has been reported . Preserving conventional surgical options in the event of percutaneous treatment failure is important . We describe surgical treatment at varying intervals after the MitraClip procedure in 32 patients . METHODS One hundred seven patients with moderate-to-severe or severe mitral regurgitation who were either symptomatic ( 91 % ) or , if asymptomatic ( 9 % ) , had evidence of left ventricular dysfunction were enrolled as part of the Endovascular Valve Edge-to-Edge REpair STudy ( EVEREST ) phase I registry study or as " roll-in " subjects in the EVEREST II study . Thirty-two of the 107 patients ( 30 % ) underwent surgery after an attempted MitraClip procedure . RESULTS Of the 32 patients undergoing post-clip mitral valve surgery , 23 patients ( 72 % ) had one or more clips implanted and 9 patients ( 28 % ) received no clip implant . The indications for mitral valve surgery in the 23 patients with a clip included partial clip detachment ( n = 10 ) , residual or recurrent mitral regurgitation greater than 2 + ( n = 9 ) , and other ( atrial septal defect [ n = 2 ] , device malfunction [ n = 1 ] , and incorrectly diagnosed mitral stenosis [ n = 1 ] ) . Twenty-seven of 31 patients ( 87 % ) underwent the surgical procedure planned before surgery ( planned procedure unknown in 1 patient ) . Four of 25 patients ( 16 % ) with planned repair underwent mitral valve replacement . CONCLUSIONS St and ard surgical options were preserved in patients who had surgery after percutaneous repair with the MitraClip device . Successful repair was feasible in the majority of patients after the MitraClip procedure , with repair performed as late as 18 months after clip implantation Introduction : The Endovascular Valve Edge‐to‐Edge REpair STudies ( EVEREST ) are investigating a percutaneous technique for edge‐to‐edge mitral valve repair with a repositionable clip . The effects on the mitral valve gradient ( MVG ) and mitral valve area ( MVA ) are not known . Methods : Twenty seven patients with moderate to severe or severe mitral regurgitation ( MR ) were enrolled . Echocardiography was performed preprocedure , at discharge , and at 1 , 6 , and 12 months . Mean MVG was measured by Doppler and MVA by planimetry and pressure half‐time , and evaluated in a central core laboratory . Pre‐ and postclip deployment , simultaneous left atrial/pulmonary capillary wedge and left ventricular pressures were obtained in eight patients . Results : Three patients did not receive a clip , six patients had their clip(s ) explanted by 6 months ( none for mitral stenosis ) , and four were repaired with two clips . Results are notable for a slight increase in mean MVG by Doppler postclip deployment ( 1.79 ± 0.89 to 3.31 ± 2.09 mm Hg , P < 0.01 ) and an expected decrease in MVA by planimetry ( 6.49 ± 1.61 to 4.46 ± 2.14 cm2 , P < 0.001 ) and by pressure half time ( 4.35 ± 0.98 to 3.01 ± 1.42 cm2 , P < 0.05 ) . There were no significant changes in hemodynamic parameters postclip deployment by direct pressure measurements . There was no change in MVA by planimetry from discharge to 12 months ( 3.90 ± 1.90 to 3.79 ± 1.54 cm2 , P = 0.78 ) . Conclusions : Echocardiographic and hemodynamic measurements after percutaneous mitral valve repair with the MitraClip show an expected decrease in mitral valve area with no evidence of clinical ly significant mitral stenosis either immediately after clip deployment or after 12 months of follow‐up . © 2006 Wiley‐Liss , BACKGROUND To evaluate the short-term outcome of patients predominantly at high risk treated with the MitraClip ® device for severe mitral valve regurgitation ( MR ) using one or more clips . METHODS We prospect ively analyzed patients with highly symptomatic MR classified as inoperable ( logistic EuroSCORE 24.16 ± 13.64 % ; STS-score 29.9 ± 14.5 % ) but subject to mitral valve repair with MitraClip ® between May 2010 and January 2011 . Thirty-three consecutive patients ( 57.6 % male ; age 77.8 ± 6.7 years ) were enrolled and treated with either 1 ( n = 7 ; 21.2 % ) , 2 ( n = 20 ; 60.6 % ) , 3 ( n = 4 ; 12.1 % ) , or 4 ( n = 2 , 6.1 % ) clips . Grading of MR was performed by two-dimensional transesophageal echocardiography ( 2D-TEE ) prior to TEE-guided clipping and before discharge . RESULTS MR was classified as functional in 23 ( 69.7 % ) and organic in 10 ( 30.3 % ) of the patients with MR- grade ≥ 3 + in 32 ( 97 % ) and = 4 in 1 patients ( 3 % ) before repair . Reduction in MR grade to grade ≤1 + was achieved in 81.7 % and to 2 in 12.1 % ( P = 0.00072 ) . Invasive pulmonary artery systolic pressure ( PAPsyst ) and pulmonary capillary wedge pressure ( PCWP ) v-wave decreased from 59.2 ± 18.6 to 46.9 ± 15.3 mmHg ( P = 0.00014 ) and 21.2 ± 6.7 to 8.0 ± 3.3 mmHg ( P = 0.0093 ) , respectively , as measured immediately after clipping . Functional NYHA class improved from mean 3 ( range 3 [ 90.9 % ] to 4 [ 9.1 % ] ) to 2 in 84.9 % ( P = 0.00081 ) as obtained at discharge . CONCLUSIONS Mitral valve repair with MitraClip ® using multiple clips is appropriate and safe in unselected patients result ing in reduced MR with positive impact on short-term functional capacity AIMS A substantial percentage of patients with mitral regurgitation ( MR ) in need of mitral valve repair are currently considered not suitable for conventional surgery . In Germany , the largest cohort of patients studied to date has been treated using a percutaneous , catheter-based approach . We report the acute outcomes of patients enrolled in the investigator-initiated German transcatheter mitral valve interventions ( TRAMI ) registry . METHODS AND RESULTS Between January 2009 and August 2011 , 486 patients [ median age 75 ( interquartile range 70 - 80 ) years ; 200 women ( 41 % ) ] were enrolled in the registry ( 309 retrospectively and 177 prospect ively ) , with 481 patients ( 99 % ) having undergone percutaneous edge-to-edge therapy for MR using the MitraClip . At baseline , 93 % of patients were in New York Heart Association ( NYHA ) functional class III or IV and 71 % of patients had a left ventricular ejection fraction ( LVEF ) ≤50 % . Two-thirds of patients presented with functional MR . Procedural success was achieved in 94 % of patients , with grade III present in 93 % of patients at baseline yet only 6 % post-intervention . Retrospective patients were followed for a median of 183 days , prospect i ve patients for a median of 44 days . The periprocedural complication rate was low , with only minor bleedings as the most significant event . In-hospital and post-discharge mortality was 2.5 % and 12.5 % , respectively . CONCLUSIONS Data from the German TRAMI registry suggest that MitraClip therapy is a viable treatment option in daily clinical routine for high surgical risk patients with significant MR OBJECTIVES The objective of this study was to evaluate the acute hemodynamic consequences of mitral valve ( MV ) repair with the MitraClip device ( Abbott Vascular , Menlo Park , California ) . BACKGROUND Whether surgical correction of mitral regurgitation ( MR ) results in a low cardiac output ( CO ) state because of an acute increase in afterload remains controversial . The acute hemodynamic consequences of MR reduction with the MitraClip device have not been studied . METHODS We evaluated 107 patients with cardiac catheterization before and immediately following percutaneous MV repair with the MitraClip device . In addition , pre- and post-procedural hemodynamic parameters were studied by transthoracic echocardiography . RESULTS MitraClip treatment was attempted in 107 patients , and in 96 ( 90 % ) patients , a MitraClip was deployed . Successful MitraClip treatment result ed in : 1 ) an increase in CO from 5.0 ± 2.0 l/min to 5.7 ± 1.9 l/min ( p = 0.003 ) ; 2 ) an increase in forward stroke volume ( FSV ) from 57 ± 17 ml to 65 ± 18 ml ( p < 0.001 ) ; and 3 ) a decrease in systemic vascular resistance from 1,226 ± 481 dyn·s/cm(5 ) to 1,004 ± 442 dyn·s/cm(5 ) ( p < 0.001 ) . In addition , there was left ventricular ( LV ) unloading manifested by a decrease in LV end-diastolic pressure from 11.4 ± 9.0 mm Hg to 8.8 ± 5.8 mm Hg ( p = 0.016 ) and a decrease in LV end-diastolic volume from 172 ± 37 ml to 158 ± 38 ml ( p < 0.001 ) . None of the patients developed acute post-procedural low CO state . CONCLUSIONS Successful MV repair with the MitraClip system results in an immediate and significant improvement in FSV , CO , and LV loading conditions . There was no evidence of a low CO state following MitraClip treatment for MR . These favorable hemodynamic effects with the MitraClip appear to reduce the risk of developing a low CO state , a complication occasionally observed after surgical MV repair for severe MR The aim of this study was to report on the 30-day and 1-year outcomes of percutaneous mitral valve repair with the MitraClip technique in patients with grade ≥3 + mitral regurgitation ( MR ) at high risk for conventional surgical therapy enrolled in the prospect i ve Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation ( GRASP ) registry . Acute device success was defined as residual MR ≤2 + after clip implantation . The primary safety end point was the rate of major adverse events at 30 days . The primary efficacy end point was freedom from death , surgery for mitral valve dysfunction , or grade ≥3 + MR at 30 days and 1 year . A total of 117 patients were treated . Eighty-nine patients ( 76 % ) presented with functional MR and 28 patients ( 24 % ) with organic MR . Acute device success was observed in all patients . Device implantation time significantly diminished with experience and varied significantly between cases with 1 versus ≥2 clips . No procedural mortality was recorded . Major adverse events occurred in 4 patients at 30 days ( 4.3 % ) . Deterioration to MR ≥3 + was recorded in 25 % of patients with degenerative MR and 7 % of those with functional MR at 1 year . No surgery for mitral valve dysfunction occurred within 1 year . Freedom from death , surgery for mitral valve dysfunction , or grade ≥3 + MR was 96.4 % and 75.8 % at 30 days and 1 year , respectively . No significant differences were noted in the primary efficacy end point between patients with degenerative MR and those with functional MR . In conclusion , percutaneous mitral valve repair with the MitraClip technique was shown to be safe and reasonably effective in 117 patients from a real-world setting OBJECTIVE Percutaneous mitral repair is rapidly developing as an alternative to cardiac surgery in select patients . The Evalve percutaneous E2E system uses the MitraClip to replicate the surgical suture-based approach . This procedure requires real-time echocardiographic guidance in a unique and significant collaboration between echocardiographer and interventionalist . transesophageal echocardiography ( TEE ) is used as the primary imaging modality to guide this procedure and is essential to its success . METHODS In EVEREST I , the US multicenter phase I safety and feasibility trial , 47 patients with 3 or 4 + mitral regurgitation ( MR ) were enrolled . The trial involved a st and ardized echocardiographic imaging protocol with a st and ardized anatomic-based vocabulary , predetermined st and ard TEE views , preprocedural strategy meetings , and display of echocardiographic aids to optimize communication and procedural efficiency during placement of the clip . RESULTS TEE guidance facilitated the creation of a double-orifice mitral valve in all 47 patients enrolled ( 100 % ) , and 40 patients were discharged with 1 or more clips ( 85 % ) . At discharge , successful placement of a clip and < or= 2 + MR was present in 34 patients ( 74 % ) . The st and ardized approach contributed to a reduction in the time to perform the procedure over the course of the trial at both initial and new sites . CONCLUSIONS TEE is essential to the guidance of percutaneous MitraClip E2E repair . A streamlined approach to echocardiographic guidance , using predetermined st and ardized views , a common anatomic-based vocabulary , preprocedural strategy meetings , and a display of echocardiographic aids in the catheterization laboratory shortens the procedure time and allows for efficient percutaneous repair AIMS Percutaneous repair of mitral regurgitation ( MR ) by leaflet apposition using a clip deployed via transseptal catheterisation is undergoing evaluation . METHODS AND RESULTS In order to detect the potential for clinical ly significant left ventricular inflow obstruction after percutaneous repair , we measured mitral valve area ( MVA ) and mean transmitral gradient ( MVG ) echocardiographically in 96 patients implanted with a clip followed for up to 24 months . By planimetry , the mean MVA decreased from 6.0 + /- 1.3 cm2 to 3.6 + /- 1.2 cm2 ( p < 0.05 ) ( range 1.9 to 7.6 cm2 ) after clip placement , and remained unchanged after 24 months of follow-up ( 3.5 + /- 0.8 cm2 ) . The mean MVG increased after clip placement from 1.7 + /- 0.9 mmHg to 4.1 + /- 2.2 mmHg ( p < 0.05 ) , and did not increase further to 24 months ( 3.8 + /- 1.9 mmHg ) . There were no differences in MVA or MVG between patients who received 1-clip ( 69 % ) and those receiving 2-clips ( 31 % ) . Patients with functional MR ( 23 % ) had a slightly smaller MVA , both at baseline and after clip placement , but did not differ from degenerative MR patients at later follow-up . After 2 years of follow-up , no patient required surgery for LV inflow obstruction . CONCLUSIONS Mitral repair with the MitraClip device for MR decreases MVA without significant mitral obstruction . After 2 years of follow-up , no patient required surgery for LV inflow obstruction , and these results were not influenced by the use of more than 1 clip or the aetiology of MR BACKGROUND Successful mitral valve surgical repair , decreasing volume overload , has been shown to provide reverse left ventricular ( LV ) and /or left atrial remodeling in most patients . Percutaneous mitral valve repair with the MitraClip system ( Abbott , Abbott Park , IL ) has been associated with favorable clinical outcomes in patients with mitral regurgitation at high risk of surgery . However , specific data on left cardiac chambers reverse remodeling after such procedures are limited . METHODS This was a prospect i ve observational study of consecutive patients at high risk of surgery , with moderate-to-severe or severe mitral regurgitation undergoing MitraClip system implantation . Follow-up echocardiography was performed at 6 months . The evaluated parameters were the LV end-diastolic and end-systolic volume indexes , LV sphericity index , LV ejection fraction , and left atrial volume index . Reverse LV remodeling was defined as a decrease of 10 % in the LV end-diastolic volume index . RESULTS The study population included 44 patients : 14 with degenerative and 30 with functional mitral regurgitation . At 6 months of follow-up , significant reductions in the median and interquartile range of the sphericity index ( from 0.57 [ interquartile range 0.54 - 0.62 ] to 0.54 [ interquartile range 0.50 - 0.58 ] ; P < .001 ) , LV end-diastolic volume index ( from 79.4 mL/m(2 ) [ interquartile range 63.0 - 102.2 ] to 60.7 mL/m(2 ) [ 50.8 - 84.4 ] ; P < .001 ) , and LV end-systolic volume index ( from 49.3 mL/m(2 ) [ interquartile range 28.2 - 70.5 ] to 28.9 mL/m(2 ) [ interquartile range 22.2 - 55.8 ] ; P < .001 ) were observed . The LV ejection fraction improved significantly ( from 38.0 % [ interquartile range 30.0 - 55.0 % ] to 46.0 % [ interquartile range 35.0 - 58.0 % ] ; P < .001 ) from baseline to 6 months . Minor differences in the left atrial volume index were observed . Reverse remodeling , according to the specified definition , was observed in 77.3 % of the patients . CONCLUSIONS The present study reports positive LV reshape effects after mitral valve repair with the MitraClip system , showing significant improvements in LV size and function OBJECTIVES We undertook a prospect i ve multicenter single-arm study to evaluate the feasibility , safety , and efficacy of the MitraClip system ( Evalve Inc. , Menlo Park , California ) . BACKGROUND Mitral valve repair for mitral regurgitation ( MR ) has been performed by the use of a surgically created double orifice . Percutaneous repair based on this surgical approach has been developed by use of the Evalve MitraClip device to secure the mitral leaflets . METHODS Patients with 3 to 4 + MR were selected in accordance with the American Heart Association/American College of Cardiology guidelines for intervention and a core echocardiographic laboratory . RESULTS A total of 107 patients were treated . Ten ( 9 % ) had a major adverse event , including 1 nonprocedural death . Freedom from clip embolization was 100 % . Partial clip detachment occurred in 10 ( 9 % ) patients . Overall , 79 of 107 ( 74 % ) patients achieved acute procedural success , and 51 ( 64 % ) were discharged with MR of < or = 1 + . Thirty-two patients ( 30 % ) had mitral valve surgery during the 3.2 years after clip procedures . When repair was planned , 84 % ( 21 of 25 ) were successful . Thus , surgical options were preserved . A total of 50 of 76 ( 66 % ) successfully treated patients were free from death , mitral valve surgery , or MR > 2 + at 12 months ( primary efficacy end point ) . Kaplan-Meier freedom from death was 95.9 % , 94.0 % , and 90.1 % , and Kaplan-Meier freedom from surgery was 88.5 % , 83.2 % , and 76.3 % at 1 , 2 , and 3 years , respectively . The 23 patients with functional MR had similar acute results and durability . CONCLUSIONS Percutaneous repair with the MitraClip system can be accomplished with low rates of morbidity and mortality and with acute MR reduction to < 2 + in the majority of patients , and with sustained freedom from death , surgery , or recurrent MR in a substantial proportion ( EVEREST I ; NCT00209339 . EVEREST II ; NCT00209274 ) OBJECTIVES The purpose of this study was to characterize patients with mitral regurgitation ( MR ) and atrial fibrillation ( AF ) treated percutaneously using the MitraClip device ( Abbott Vascular , Abbott Park , Illinois ) and compare the results with surgery in this population . BACKGROUND The EVEREST II ( Endovascular Valve Edge-to-Edge Repair Study ) r and omized controlled trial compared a less invasive catheter-based treatment for MR with surgery , providing an opportunity to assess the impact of AF on the outcomes of both the MitraClip procedure and surgical repair . METHODS The study population included 264 patients with moderately severe or severe MR assessed by an independent echocardiographic core laboratory . Comparison of safety and effectiveness study endpoints at 30 days and 1 year were made using both intention-to-treat and per- protocol ( cohort of patients with MR ≤2 + at discharge ) analyses . RESULTS Pre-existing AF was present in 27 % of patients . These patients were older , had more advanced disease , and were more likely to have a functional etiology . Similar reduction of MR to ≤2 + before discharge was achieved in patients with AF ( 83 % ) and in patients without AF ( 75 % , p = 0.3 ) . Freedom from death , mitral valve surgery for valve dysfunction , and MR > 2 + was similar at 12 months for AF patients ( 64 % ) and for no-AF patients ( 61 % , p = 0.3 ) . At 12 months , MR reduction to < 2 + was greater with surgery than with MitraClip , but there was no interaction between rhythm and MR reduction , and no difference in all-cause mortality between patients with and patients without AF . CONCLUSIONS Atrial fibrillation is associated with more advanced valvular disease and noncardiac comorbidities . However , acute procedural success , safety , and 1-year efficacy with MitraClip therapy is similar for patients with AF and without AF |
2,606 | 26,535,139 | MRI and PET/CT revealed additional areas of inflammation in the spine and pelvis , including focal areas between the vertebrae and anterior to the hip joint , but the number of controls with inflammatory disease was inadequate for precise specificity estimates . | OBJECTIVES To review the evidence for accuracy of imaging for diagnosis of polymyalgia rheumatica ( PMR ) . | OBJECTIVE To determine the efficacy and safety of shoulder corticosteroid injections in polymyalgia rheumatica ( PMR ) . METHODS Twenty consecutive patients with active PMR were r and omized into a 7 month , double blind , placebo controlled study . Patients received either bilateral shoulder injections of 40 mg of 6-methylprednisolone acetate or placebo ( 1 ml saline solution ) . Responders were treated weekly with the same regimen for a total of 4 bilateral injections and then followed for 6 months . Response was defined as a 70 % reduction in visual analog scale ( VAS ) score for pain and for patient and physician global assessment , and duration of morning stiffness . Bilateral shoulder magnetic resonance imaging ( MRI ) was performed at different times to evaluate the response of lesions to therapy . RESULTS All 10 corticosteroid treated patients responded to the first injection with a significant reduction in duration of morning stiffness , VAS pain scale , patient and physician global assessment , erythrocyte sedimentation rate , and C-reactive protein . Interleukin 6 serum levels were significantly reduced after the 2nd injection . In 5 patients , the response persisted throughout the followup period . The other 5 withdrew within 4 weeks after the 4th injection due to recurrence of symptoms . None of the 10 patients of the placebo group responded to the first injection . The difference between the 2 groups was significant ( p = 0.03 ) . No side effects were recorded . MRI showed marked improvement of shoulder lesions one week after first injection and an almost complete resolution one week after last injection in the responders . CONCLUSION Shoulder corticosteroid injections seem to be an effective and safe therapy for PMR Objective To assess the responsiveness of ultrasound ( US ) inflammatory findings in the shoulder and hip of patients with polymyalgia rheumatica ( PMR ) who started treatment with corticosteroids . Methods Fifty-three patients with active PMR who started treatment with prednisone in six Spanish centres were prospect ively studied . The patients underwent clinical , laboratory and US assessment at baseline , 4 and 12 weeks . The US investigation consisted of detection and quantification of inflammatory findings in the shoulder and hip . The responsiveness of clinical , laboratory and US parameters was tested by the st and ardised response mean . Intraobserver and interobserver reliability between US investigators was assessed . Results At baseline , 34 patients ( 69 % ) had inflammation in at least one bilateral site . During the follow-up period , clinical , laboratory and US variables showed a parallel decrease . A significant decrease in US inflammatory parameters was found at week 4 ( p<0.001 ) . After 4 and 12 weeks of treatment with corticosteroids , US inflammatory findings showed similar or better sensitivity to change than clinical and laboratory markers of PMR activity . Intraobserver and interobserver intraclass correlation coefficients were 0.96 and 0.99 , respectively ( p<0.05 ) . Conclusion US may be a responsive additional tool in monitoring the response to corticosteroids in patients with PMR in daily practice and multicentre trials OBJECTIVES To evaluate the inflammatory involvement of lumbar interspinous bursae in patients with polymyalgia rheumatica ( PMR ) using magnetic resonance imaging ( MRI ) . METHODS Ten consecutive , untreated new patients with PMR and pain in the shoulder and pelvic girdles were investigated . Seven patients with spondyloarthritis ( 4 with psoriatic spondyloarthrits , one with entheropatic spondyloarthritis , and 2 with ankylosing spondylitis ) as well as 2 patients with spinal osteoarthritis and 2 patients with rheumatoid arthritis with lumbar pain served as controls . MRI of lumbar spine was performed in all PMR patients and controls . Nine patients ( 5 PMR patients and 4 controls ) also had MRI of the thoracic spine . RESULTS MRI evidence of interspinous lumbar bursitis was found in 9/10 patients with PMR and in 5/11 controls . A moderate to marked ( grade ≥2 on a semiquantitative 0 - 3 scale ) lumbar bursitis occurred significantly more frequently in patients with PMR than in control patients ( 60 % vs. 9 % , p=0.020 ) . In most of the patients and controls lumbar bursitis was found at the L3-L5 interspaces . Only 2 patients had bursitis at a different level ( one patient had widespread lumbar bursitis , and one control at L2-L4 ) . No interspinous bursitis was demonstrated by MRI of the thoracic spine in patients and controls . CONCLUSIONS Inflammation of lumbar bursae may be responsible for the low back pain reported by patients with PMR . The prominent inflammatory involvement of bursae including those of the lumbar spine supports the hypothesis that PMR may be a disorder affecting predominantly extra-articular synovial structures OBJECTIVE To determine if ultrasonography ( US ) and power Doppler ( PD ) may be useful in identifying polymyalgia rheumatica ( PMR ) patients with relapsing disease . METHODS For a mean of 41 months , 57 consecutive untreated patients with PMR were prospect ively assessed for relapses/recurrences . This cohort represented all the patients diagnosed over a 18-month period in one Italian secondary referral centre . Clinical signs and symptoms as well as ESR and CRP were evaluated . US examination of the shoulders was performed in all 57 patients at diagnosis and after the onset of prednisone treatment ( mean 24 + /- 3 weeks ) . Power Doppler ultrasonography ( PDUS ) was performed in 24 patients . Shoulder sonograms were obtained according to st and ardized techniques . RESULTS Prednisone therapy significantly reduced the frequency and the degree of subacromial/subdeltoid bursitis , long head biceps tenosynovitis and glenohumeral synovitis . At diagnosis , a positive PD signal was observed more frequently in the subacromial/subdeltoid bursae ( 33 % ) . Prednisone therapy significantly reduced the frequency of patients with positive PD signal . Of the 44 patients in remission or with low disease activity at the time of the second US , 26 ( 59 % ) still had evidence of persistent inflammatory lesions . There was no association between the persistence of inflammation at US and relapses/recurrences ; in contrast , a positive PD signal at diagnosis was significantly associated with the occurrence of relapses/recurrences at follow-up . CONCLUSION Sub clinical inflammation detected by US persists in most PMR patients despite glucocorticoid treatment . PDUS may be useful to detect at diagnosis the patients with most active inflammation who have a higher risk of relapses/recurrences Abstract In a prospect i ve study , the glenohumeral joints of 51 patients ( aged 60 or above ) were examined , using ultrasonography . Twenty-two patients were suffering from characteristic polymyalgia rheumatica ( PMR ) symptoms . In contrast , 29 other patients initially had similar complaints , but were diagnosed as having elderly onset rheumatoid arthritis ( EORA , rheumatoid factor negative ) upon development of typical symptoms . Ultrasound examination revealed glenohumeral joint inflammation in 40.9 % ( 9/22 ) of the patients with PMR and 65.5 % ( 19/29 ) of the patients with EORA . A discrete symmetrical biceps tendon sheath effusion was found in only three patients and unilateral in six patients with PMR . In contrast , 12 patients with EORA presented a massive effusion of the biceps tendon sheath , in some cases combined with a bilateral subdeltoid bursitis , and an intraarticular ( i.a . ) effusion/synovitis . To summarize our results : an i.a . effusion/synovitis , subdeltoid bursitis and biceps tendon sheath effusion were more frequent in patients with EORA , with a predominate symmetry and signs for massive inflammation . The typical ultrasonographic result in patients with PMR was a unilateral inflammation of the glenohumeral joint with predominate discrete biceps tendon sheath effusion and , in comparison with the EORA group , with signs of a low grade inflammation . We conclude that the results of our prospect i ve study might be helpful in the differentiation of PMR and a rheumatoid factor negative subgroup of EORA at the first time of manifestation where clinical overlaps can be observed . However , ultrasonography of the glenohumeral joints might be a good and helpful instrument of differentiation in both diseases OBJECTIVE To assess the characteristics of calcium pyrophosphate deposition disease ( CPDD ) with proximal involvement mimicking polymyalgia rheumatica ( PMR ) , and to identify the best predictive factors for the presence of a clinical pattern of CPDD in patients presenting with polymyalgia symptoms . METHODS Patients diagnosed with either PMR or CPDD at the Rheumatology Division of Hospital Meixoeiro ( Vigo , Spain ) over a 7-year period ( 1997 - 2003 ) were prospect ively followed for at least 12 months . RESULTS The study group comprised 118 patients with PMR features and 112 patients with CPDD . Eighty-two of the 118 patients with PMR manifestations were diagnosed as having pure PMR , and 36 met the diagnostic criteria for both PMR and CPDD . Patients with CPDD mimicking PMR were older ( P = 0.02 ) and had peripheral arthritis more frequently ( P = 0.004 ) than those with pure PMR . Radiologic osteoarthritic changes in the h and s and knees , including more advanced radiologic grade of knee osteoarthritis , and tendinous calcifications were more frequent in patients with PMR/CPDD ( P < 0.001 ) . The best predictive factors for the occurrence of this atypical pattern of CPDD in a patient presenting with PMR features were the age at diagnosis and the presence of tibiofemoral osteoarthritis , tendinous calcifications , and ankle arthritis . CONCLUSION Involvement of proximal joints may be the clinical presentation of CPDD . CPDD should be included in the spectrum of diseases mimicking PMR . The presence of tibiofemoral osteoarthritis , tendinous calcifications , and ankle arthritis are clues that may alert the clinician to the presence of CPDD in an elderly patient presenting with PMR manifestations OBJECTIVE Joint inflammation in polymyalgia rheumatica is regarded primarily as a disease of the synovial cavities and bursae , but the adjacent capsules and soft tissues have not been evaluated using sensitive imaging methods . We used fat suppression magnetic resonance imaging ( MRI ) to determine anatomical sites of inflammatory change in the shoulders of patients with early polymyalgia rheumatica ( PMR ) and a control group of patients with rheumatoid arthritis ( RA ) . METHODS Fourteen patients with PMR and 14 with RA ( a total of 20 shoulders in each group ) were evaluated . T2 SPIR ( fat suppressed ) coronal oblique MRI sequences of the shoulders were performed . Scans were assessed for sites of joint effusion , bursitis , tenosynovitis , bone edema , and extracapsular soft tissue edema . Statistical analysis was performed using Fisher 's test . RESULTS Nine of 14 patients ( 10/20 joints ) with PMR but only 2/14 ( 2/20 joints ) with RA had prominent edema at extracapsular sites adjacent to the joint capsule or in the soft tissues ( p = 0.02 ) . Both groups had a comparable degree of joint effusion ( 18 PMR , 17 RA ) , bursitis ( 18 PMR , 16 RA ) , and tenosynovitis ( 3 PMR , 2 RA ) . CONCLUSION The only significant difference between the 2 groups was the presence of inflammatory change outside the joint cavity in patients with PMR . This may contribute to the diffuse nature of symptoms in PMR and have implication s for its pathogenesis OBJECTIVE To evaluate the impact of polymyalgia rheumatica ( PMR ) on clinical outcomes and quality of life ( QOL ) ; the relationship between laboratory measures and clinical outcomes , and changes in QOL ; and agreement between rheumatologists in confirming the initial diagnosis . METHODS We conducted a prospect i ve study of 129 participants in 8 hospitals in Engl and who met a modified version of the Jones and Hazleman criteria and had not started steroid therapy . The main outcome measures were response to steroids after 3 weeks ( minimum 50 % improvement in proximal pain , morning stiffness < 30 minutes , acute-phase response not elevated ) , relapses , QOL as measured by the Short Form 36 and Health Assessment Question naire , and diagnosis re assessment at 1 year . RESULTS At 3 weeks , 55 % of participants failed to meet our definition of a complete response to steroid therapy . Both physical and mental QOL at presentation were substantially lower than general population norms and improved by 12.6 ( 95 % confidence interval [ 95 % CI ] 10.8 , 14.4 ) and 11.2 ( 95 % CI 8.5 , 13.8 ) points , respectively , at 1 year . Proximal pain and longer morning stiffness were significantly associated with lower physical QOL during followup , whereas erythrocyte sedimentation rate was most strongly associated with lower mental QOL during followup . There was moderate agreement between clinicians in confirming the PMR diagnosis ( kappa coefficients 0.49 - 0.65 ) . CONCLUSION PMR is a heterogeneous disease with a major impact on QOL . Ongoing monitoring should include disease activity based on symptoms , emergence of alternative diagnoses , and early referral of atypical and severe cases Objective To compare the performance of published classification/diagnostic criteria for polymyalgia rheumatica ( PMR ) , including the new 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology ( ACR ) criteria , in a single-centre study . Methods We studied all consecutive patients with new-onset PMR seen in our centre over 6 years , whose diagnosis was confirmed during a prospect i ve 12-month follow-up period . Subjects were classified by each of the seven different criteria . Sensitivity and specificity were compared . Control population consisted of all consecutive patients aged ≥50 years seen in a 4-year period in our early arthritis clinic who had a 12-month confirmation of a diagnosis of rheumatoid arthritis ( RA ) or other inflammatory articular diseases . Results Data were collected from 136 cases and 149 controls , including 94 patients with RA . The most sensitive criteria were the new 2012 EULAR/ACR classification criteria ( 92.6 % ) . Adding ultrasound ( US ) specificity increased from 81.5 % to 91.3 % in total cases and from 79.7 % to 89.9 % in RA . Bird criteria had a sensitivity of 89.2 % but the lowest specificity ( 40.2 % in total cases and 72.5 % in RA ) . Jones and Nobunaga criteria were the most specific criteria ( 96.7 % and 97.8 % in total cases and 98.6 % and 99.5 % in RA ) but the less sensitive ( 63.1 % and 58.2 % ) ones . Overall , discriminatory ability , as reflected by the area under the receiver operating characteristic curve , was better for the 2012 US EULAR/ACR criteria ( 0.920 in total cases and 0.910 in RA ) . Conclusions The new EULAR/ACR criteria in new-onset PMR patients perform best in discriminating PMR from RA and other inflammatory articular diseases . Ultrasound further increases the specificity of the criteria Context Patients who take glucocorticoids appear to have an increased risk for cardiovascular disease . However , data about the magnitude of this increased risk are lacking Contribution In this large , population -based study , the use of glucocorticoids was associated with an increased risk for cardiovascular events , with a clear dose-response relationship . Patients who received high-dose glucocorticoids were more than 2.5 times as likely as patients who did not use glucocorticoids to experience a cardiovascular event . Implication s These data will help clinicians estimate cardiovascular risk among patients who require glucocorticoids . The Editors Glucocorticoids are commonly used as anti-inflammatory and immunosuppressive therapy in diseases such as asthma , inflammatory bowel disease , and inflammatory arthritis . Well-known adverse effects of glucocorticoids include hypertension , diabetes mellitus , and obesity ( 1 - 3 ) , all of which are independent risk factors for cardiovascular disease . The principal physiologic glucocorticoid is cortisol . Increased cortisol secretion and action , even within the physiologic range , is associated with several risk factors for cardiovascular disease ( 4 , 5 ) . Indeed , studies have proposed that sub clinical Cushing syndrome may be an important cardiovascular risk factor ( 6 , 7 ) . However , whether , and to what extent , the adverse effects of exogenous glucocorticoids on these risk factors for cardiovascular disease cause cardiovascular morbidity and death has not been established ( 8 , 9 ) . This is not predictable , especially since glucocorticoids may also have cardioprotective effects mediated by their anti-inflammatory and antiproliferative actions in the vessel wall ( 10 , 11 ) . We tested the hypothesis that users of exogenous glucocorticoids have an increased risk for cardiovascular disease . In particular , we hypothesized that high doses will be associated with cardiovascular disease , while doses equivalent to or below the physiologic range of endogenous glucocorticoid secretion may be compensated for by decreased cortisol levels and will not incur excessive risk . We have tested this by using the MEdicines MOnitoring unit ( MEMO ) record linkage data base to compare people who were exposed and not exposed to glucocorticoid therapy . Methods We performed this study in the Tayside region in Scotl and by using the MEMO record linkage data base . The MEMO data base covers a geographically compact population and serves about 400000 patients in the National Health Service ( NHS ) in Scotl and , 97 % of whom are white . The NHS in Scotl and is tax-funded and free at the point of consumption and covers the entire population . In Tayside , almost no health care is delivered without the NHS . The data collection methods for this data base have previously been described ( 12 ) . In brief , this data base contains several data sets , including all dispensed community prescriptions , hospital discharge data , mortality data , biochemistry data , and other data , that are linked by a unique patient identifier , the community health index number . These data are made anonymous for the purpose s of research , as approved by the Tayside Caldicott Guardians ( a group appointed by the government to protect the confidentiality of medical records ) . The Tayside committee on research medical ethics also approved the project . We cleaned and vali date d all data before analysis . We included all patients who resided in Tayside and registered with a general practitioner in January 1993 , who were 40 years of age or older , and who remained a resident in Tayside until December 1997 or who died during the study period . Definitions of Exposure to Glucocorticoids Exposed and Comparator Cohorts All patients who received 1 or more dispensed prescriptions for glucocorticoids ( including inhaled steroids , topical steroids , oral and parenteral steroids , rectal application steroids , and nasal steroids ) between July 1993 and December 1996 formed the exposed cohort . They entered the study at their date of first prescription . The rest of the study sample made up the comparator cohort . We excluded patients who were hospitalized for inflammatory bowel disease and chronic obstructive airways disease during the follow-up period because they may have been given glucocorticoids as hospital in patients without the prescriptions being identified by MEMO . We generated a r and om date of entry to the study for each member of the comparator cohort by using a frequency-matched calendar year generated from the date s of entry to the study in the exposed cohort . We excluded patients from both cohorts if they were hospitalized for cardiovascular disease before study entry . Dose of Glucocorticoids For about two thirds of dispensed oral or systemic glucocorticoid prescriptions , we recorded the date of prescription , dose of tablets , amount dispensed , and instructions on how medication should be taken . For these prescriptions , we could determine daily exposure during prescribed courses . For the remainder , we knew the total dose dispensed but , because prescriptions were marked take as directed , could not accurately determine the daily dose and duration . We therefore calculated the average daily dose by dividing the total amount of glucocorticoid dispensed by the total number of days of observation . For multiple simultaneous formulations ( oral and inhaled ) of glucocorticoids , we used only the oral glucocorticoids to calculate the daily dose . We categorized glucocorticoid exposure according to average daily doses throughout the follow-up period for each patient as high ( oral , parenteral , and rectal steroids with daily dosage 7.5 mg [ that is , supraphysiologic doses ] ) ; medium ( oral , parenteral , and rectal steroids with daily dosage < 7.5 mg [ that is , approximately equivalent to the physiologic range of endogenous glucocorticoid secretion ] ) ; or low ( inhaled , topical , and nasal steroids with daily dosage less than the equivalent physiologic range ) . As a result of this calculation , we included patients who took large dosages for a short period in the medium-dose group . We calculated dose equivalents of prednisolone as follows : 1 mg of prednisolone = 5 mg of cortisone = 4 mg of hydrocortisone = 1 mg of prednisone = 0.8 mg of triamcinolone = 0.8 mg of methylprednisolone = 0.15 mg of dexamethasone = 0.15 mg of betamethasone ( 13 ) . The MEMO data base does not collect information for prescriptions dispensed in hospitals . We considered participants hospitalized for asthma , inflammatory bowel disease , or chronic obstructive pulmonary disease ( disorders usually treated with high-dose glucocorticoids in the hospital ) as being exposed to a typical dosage of glucocorticoids ( 30 mg/d , prednisolone ) during that period . Analysis of Events during Glucocorticoid Exposure ( On Treatment vs. Off Treatment ) We did a subgroup analysis of those patients for whom we had data on daily dose of glucocorticoid exposure . For each patient , we divided exposure to glucocorticoid into the time that the patient was exposed ( on treatment ) and the time that the patient was not exposed ( off treatment ) . We then temporally related these periods to the occurrence of cardiovascular events . Incident versus Prevalent Use For each patient in the cohort exposed to glucocorticoids , we used the 6 months before entry to the study as a screening period . We classified patients who did not receive glucocorticoids during this period as incident users of glucocorticoids and patients who received glucocorticoids during this period as prevalent users . Continuous versus Intermittent Use We did an analysis comparing cardiovascular risk in continuous use ( 180 days between prescriptions ) versus intermittent use ( > 180 days between prescriptions ) . Exposure by Disease Indication We identified patients with chronic obstructive pulmonary disease if they were hospitalized for asthma or chronic obstructive pulmonary disease or were prescribed an inhaled steroid or bronchodilator drug before study entry . We identified patients with inflammatory bowel disease if they were hospitalized for colitis or were prescribed a rectal steroid preparation before study entry . We identified patients with inflammatory arthritis if they were hospitalized for inflammatory arthritis or were prescribed nonsteroidal anti-inflammatory drugs ( NSAIDs ) and disease-modifying antirheumatic drugs before study entry . Outcome Variables We collected the outcome data on each patient until 31 December 1997 . The outcome of the study was a cardiovascular event defined as the composite end point of hospitalization with a primary diagnosis of myocardial infa rct ion , angina , angioplasty or coronary revascularization , stroke , transient ischemic attack , congestive cardiac failure , or cardiovascular death during follow-up . We censored patients at their first event if they had several events . We ascertained diagnoses of myocardial infa rct ion , angina , angioplasty and coronary revascularization , stroke , transient ischemic attack , and congestive cardiac failure from the hospital discharge diagnosis data , which were vali date d ( 14 ) in the Scottish Morbidity Record 1 by primary International Classification of Diseases , Ninth or Tenth Revisions , codes . We also ascertained diagnoses of angioplasty and coronary revascularization by the code of classification of surgical operations and procedures . We also obtained the death certification data for all Tayside residents who died . Statistical Analysis We counted events that occurred during the study period and compared rates of events between cohorts . We used the Poisson regression model to investigate the association between glucocorticoid exposure and cardiovascular outcome . We included the following covariates : age at study entry ; sex ; social deprivation ; use of angiotensin-converting enzyme inhibitors , anticoagulants , antiplatelet agents , -blockers , -blockers , calcium-channel blockers , cardiac glycosides , diuretics , nitrates , lipid-lowering drugs , hormone replacement Objective . To prospect ively evaluate the disease course and the performance of clinical , patient-reported outcome ( PRO ) and musculoskeletal ultrasound measures in patients with polymyalgia rheumatica ( PMR ) . Methods . The study population included 85 patients with new-onset PMR who were initially treated with prednisone equivalent dose of 15 mg daily tapered gradually , and followed for 26 weeks . Data collection included physical examination findings , laboratory measures of acute-phase reactants , and PRO measures . Ultrasound evaluation was performed at baseline and Week 26 to assess for features previously reported to be associated with PMR . Response to corticosteroid treatment was defined as 70 % improvement in PMR on visual analog scale ( VAS ) . Results . At baseline , 77 % had hip pain in addition to shoulder pain and 100 % had abnormal C-reactive protein or erythrocyte sedimentation rate . On ultrasound , 84 % had shoulder findings and 32 % had both shoulder and hip findings . Response to corticosteroid treatment occurred in 73 % of patients by Week 4 and was highly correlated with percentage improvement in other VAS measures . Presence of ultrasound findings at baseline predicted response to corticosteroids at 4 weeks . Factor analysis revealed 6 domains that sufficiently represented all the outcome measures : PMR-related pain and physical function , an elevated inflammatory marker , hip pain , global pain , mental function , and morning stiffness . Conclusion . PRO measures and inflammatory markers performed well in assessing disease activity in patients with PMR . A minimum set of outcome measures consisting of PRO measures of pain and function and an inflammatory marker should be used in practice and in clinical trials in PMR The objective of this study was to develop European League Against Rheumatism/American College of Rheumatology classification criteria for polymyalgia rheumatica ( PMR ) . C and i date criteria were evaluated in a 6-month prospect i ve cohort study of 125 patients with new-onset PMR and 169 non-PMR comparison subjects with conditions mimicking PMR . A scoring algorithm was developed based on morning stiffness > 45 minutes ( 2 points ) , hip pain/limited range of motion ( 1 point ) , absence of rheumatoid factor and /or anti-citrullinated protein antibody ( 2 points ) , and absence of peripheral joint pain ( 1 point ) . A score ≥4 had 68 % sensitivity and 78 % specificity for discriminating all comparison subjects from PMR . The specificity was higher ( 88 % ) for discriminating shoulder conditions from PMR and lower ( 65 % ) for discriminating RA from PMR . Adding ultrasound , a score ≥5 had increased sensitivity to 66 % and specificity to 81 % . According to these provisional classification criteria , patients ≥50 years old presenting with bilateral shoulder pain , not better explained by an alternative pathology , can be classified as having PMR in the presence of morning stiffness > 45 minutes , elevated C-reactive protein and /or erythrocyte sedimentation rate , and new hip pain . These criteria are not meant for diagnostic purpose Objective : To study the usefulness of ultrasonography ( US ) in predicting the diagnostic outcome in patients with polymyalgic symptoms . Methods : Sixty-one elderly patients with polymyalgic syndrome were recruited in a secondary care setting and followed up in a prospect i ve way . Clinical , laboratory , and US data obtained at onset were re-evaluated after 1 year when diagnostic outcome was defined . Results : A diagnostic shift was observed in 32 polymyalgic patients ( 52 % ) . Calcium pyrophosphate deposition disease ( CPDD ) was diagnosed in nine patients , elderly-onset rheumatoid arthritis ( EORA ) in 18 , and elderly-onset spondyloarthritis ( EOSpA ) in five . In polymyalgia rheumatica ( PMR ) patients US demonstrated synovitis in 90 % of cases , in both proximal ( 90 % ) and peripheral joints ( 41 % ) . The best predictive US model for the definitive diagnosis of PMR comprised : the presence of subacromial-subdeltoid bursitis [ odds ratio ( OR ) 5.603 , p = 0.003 ] , low frequency of wrist ( OR 0.074 , p < 0.001 ) , metacarpophalangeal ( OR 0.052 , p < 0.001 ) , and metatarsophalangeal effusion/synovitis ( OR 0.107 , p < 0.027 ) , low frequency of knee menisci chondrocalcinosis ( OR 0.091 , p = 0.013 ) , tendinous calcaneal calcifications ( OR 0.078 , p = 0.006 ) , and Achilles enthesitis ( OR 0.107 , p = 0.027 ) , and low power Doppler US ( PDUS ) scores at wrist ( OR 0.052 , p < 0.001 ) . Conclusions : US and PDUS can be useful in distinguishing , at onset of disease , pure PMR from other diseases mimicking this condition OBJECTIVE To investigate the hip inflammatory lesions and to evaluate the accuracy of clinical examination compared to magnetic resonance imaging ( MRI ) in patients with polymyalgia rheumatica ( PMR ) with pelvic girdle symptoms . Secondary end-point was to evaluate the sensitivity and specificity of ultrasonography ( US ) compared to MRI in the assessment of hip lesions . METHODS Case-control study of 20 consecutive PMR patients and 40 controls with different rheumatic conditions . Both groups were clinical ly assessed for the presence of hip synovitis , trochanteric , iliopsoas and ischiogluteal bursitis . Hip MRI was performed in all case- patients and in 10 controls . Both groups were examined by US . An additional group of 10 healthy controls was examined by hip US . RESULTS Both MRI and US detected trochanteric bursitis in 100 % of PMR patients , bilateral in 18/20 ( 90 % ) , and in 12/40 ( 30 % ) controls ( p < 0.001 ) . Hip synovitis was detected in 17/20 ( 85 % ) by MRI and in 9/20 ( 45 % ) by US ( p < 0.02 ) in case- patients and in 18/40 ( 45 % ) controls . In PMR , MRI and US showed iliopsoas bursitis in 10/20 ( 50 % ) and 6/20 ( 30 % ) and ischiogluteal bursitis in 5/20 ( 25 % ) and 4/20 ( 20 % ) with no differences compared to controls . Clinical examination showed a good accuracy for hip synovitis , trochanteric and ischiogluteal bursitis , while it overestimated the presence of iliopsoas bursitis . US was less sensitive than MRI for the detection of hip synovitis and iliopsoas bursitis ( 53 % and 60 % ) . CONCLUSION Trochanteric bursitis represents the most frequent hip lesion in PMR . A careful physical examination allows to detect all inflammatory lesions excluding iliopsoas bursitis . US is less sensitive than MRI in the assessment of hip synovitis and iliopsoas bursitis OBJECTIVE Magnetic resonance imaging ( MRI ) showed that subacromial/subdeltoid bursitis is the most frequent shoulder lesion in polymyalgia rheumatica ( PMR ) . We evaluated whether shoulder ultrasonography ( US ) was as effective as MRI in the detection of this lesion and assessed the sensitivity and specificity of bilateral subacromial/subdeltoid bursitis in the diagnosis of PMR . METHODS A case-control study of 57 consecutive case patients with untreated PMR and 114 controls seen over a 6 month period in 3 secondary referral rheumatology centers . Control patients consisted of the next 2 consecutive patients with bilateral shoulder aching and stiffness observed after the case patient . In all case and control patients the glenohumeral joint space , bursae , and long head biceps tendon were assessed by bilateral shoulder US . The first 24 case patients were also examined by bilateral shoulder MRI . RESULTS US showed subacromial/subdeltoid bursitis in 55/57 ( 96 % ) patients with PMR and in 25/114 ( 22 % ) controls ( p < 0.001 ) . The lesion was bilateral in 53/55 ( 96 % ) case patients and in 1/25 ( 4 % ) controls ( p < 0.001 ) . The frequency of glenohumeral joint synovitis and biceps tenosynovitis did not differ significantly between case patients and controls . In 100 % of case patients MRI showed subacromial/subdeltoid bursitis confirming US findings . The sonographic evidence of bilateral bursitis had a sensitivity of 92.9 % , specificity of 99 . 1 % , and positive predictive value of 98 . 1 % for the diagnosis of PMR . CONCLUSION US and MRI were equally effective in confirming bilateral subacromial and subdeltoid bursitis in PMR . This finding , in view of its high sensitivity and specificity , could be used as a new diagnostic criterion for PMR |
2,607 | 29,409,466 | Conclusions T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R , which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival | Background Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations , subsequent drug resistance is almost inevitable .
The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy .
Methods To better underst and the clinical characteristics of TKI resistance in NSCLC patients , we retrospectively review ed studies of acquired TKI drug resistance using repeat biopsy from the last decade . | Purpose : All patients with EGF receptor (EGFR)–mutant lung cancers eventually develop acquired resistance to EGFR tyrosine kinase inhibitors ( TKI ) . Smaller series have identified various mechanisms of resistance , but systematic evaluation of a large number of patients to definitively establish the frequency of various mechanisms has not been conducted . Experimental Design : Patients with lung adenocarcinomas and acquired resistance to erlotinib or gefitinib enrolled onto a prospect i ve biopsy protocol and underwent a rebiopsy after the development of acquired resistance . Histology was review ed . Sample s underwent genotyping for mutations in EGFR , AKT1 , BRAF , ERBB2 , KRAS , MEK1 , NRAS and PIK3CA , and FISH for MET and HER2 . Results : Adequate tumor sample s for molecular analysis were obtained in 155 patients . Ninety-eight had second-site EGFR T790 M mutations [ 63 % ; 95 % confidence interval ( CI ) , 55%–70 % ] and four had small cell transformation ( 3 % , 95 % CI , 0%–6 % ) . MET amplification was seen in 4 of 75 ( 5 % ; 95 % CI , 1%–13 % ) . HER2 amplification was seen in 3 of 24 ( 13 % ; 95 % CI , 3%–32 % ) . We did not detect any acquired mutations in PIK3CA , AKT1 , BRAF , ERBB2 , KRAS , MEK1 , or NRAS ( 0 of 88 , 0 % ; 95 % CI , 0%–4 % ) . Overlap among mechanisms of acquired resistance was seen in 4 % . Conclusions : This is the largest series reporting mechanisms of acquired resistance to EGFR-TKI therapy . We identified EGFR T790 M as the most common mechanism of acquired resistance , whereas MET amplification , HER2 amplification , and small cell histologic transformation occur less frequently . More comprehensive methods to characterize molecular alterations in this setting are needed to improve our underst and ing of acquired resistance to EGFR-TKIs . Clin Cancer Res ; 19(8 ) ; 2240–7 . © 2013 AACR Purpose : Somatic mutations in the epidermal growth factor receptor ( EGFR ) have been detected in patients with non – small cell lung cancer ( NSCLC ) and are associated with sensitivity to treatment with gefitinib or erlotinib . Our study explored the relationship between the two most common types of somatic EGFR mutations , exon 19 deletions and the L858R point mutation , and outcomes of patients following treatment with gefitinib or erlotinib . Experimental Design : Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations . Patients with exon 19 deletion or L858R mutations were identified . The response rate , time to progression , and overall survival were determined for the two groups . Results : We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib . Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation ( 38 versus 17 months ; P = 0.04 ) . There were also trends toward higher response rate ( 73 % versus 50 % ) and improved time to progression ( 24 versus 10 months ) for the patients with an exon 19 deletion , although these were not independently significant in a multivariate analysis . A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [ 18 of 23 ( 78 % ) versus 3 of 9 ( 33 % ) ; P = 0.04 ] . No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients . Conclusions : Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation . Pooling of greater numbers of patients and completion of prospect i ve trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib , erlotinib , and other EGFR inhibitors This study was design ed to prospect ively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor ( EGFR ) mutations and to explore the molecular factors affecting the efficacy of gefitinib . Tumor tissue , derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced ( stage IIIB , IV , and recurrent ) pulmonary adenocarcinoma . Tumor genomic DNA underwent direct sequencing for EGFR exons 18 , 19 , 20 , and 21 . Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity . The primary endpoint was objective response rate ( ORR ) . Secondary endpoints were progression free survival ( PFS ) , overall survival ( OS ) and tolerability . Out of 147 screened patients , 45 pts ( 31 % ) had EGFR mutations and received gefitinib . The most common EGFR mutations were in-frame exon 19 deletions ( 29 pts , 64 % ) and L858R point mutation in exon 21 ( 15 pts , 33 % ) . One patient had atypical mutation of L861Q in exon 21 . The ORR was 53.3 % ( 95 % CI , 38.6 - 67.9 ) and disease control rate ( DCR ) including stable disease was 86.7 % . The median progression free survival ( PFS ) was 398 days and the median overall survival ( OS ) was 819 days . Treatment was well tolerated . Grade 3/4 adverse events ( AEs ) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients . There were no treatment-related Grade 4 AEs . Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out . The ORR and DCR were higher in patients with exon 19 deletions than those with L858R ( 62.1 % vs 33.3 % ; P=0.0705 and 96.6 % vs 66.7 % ; P=0.0062 , respectively ) . All 4 patients with progressive disease had a L858R mutation . No secondary resistant mutations such as T790 M mutation or insertions in exon 20 were found in those patients . In addition , OS was significantly better in patients with exon 19 deletions than those with L858R ( 24-month OS rate was 72.1 % vs 32.0 % , P=0.0148 ) . Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated . Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations ( Clinical Trials.gov number , NCT00344773 ) Purpose : Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors ( TKI ) after a median of 10 to 16 months . In half of these cases , a second EGFR mutation , T790 M , underlies acquired resistance . We undertook this study to examine the clinical course of patients harboring the T790 M mutation following progression on TKI . Experimental Design : EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospect i ve rebiopsy protocol in which postprogression tumor specimens were collected for molecular analysis . Postprogression survival and characteristics of disease progression were compared in patients with and without T790 M . Results : We identified T790 M in the initial rebiopsy specimens from 58 of 93 patients ( 62 % , 95 % CI : 52–72 ) . T790 M was more common in biopsies of lung/pleura tissue and lymph nodes than in more distant sites ( P = 0.014 ) . Median postprogression survival was 16 months ( interquartile range = 9–29 months ) ; patients with T790 M had a significantly longer postprogression survival ( P = 0.036 ) . Patients without T790 M more often progressed in a previously uninvolved organ system ( P = 0.014 ) and exhibited a poorer performance status at time of progression ( P = 0.007 ) . Conclusions : Among patients with acquired resistance to EGFR TKIs , the presence of T790 M defines a clinical subset with a relatively favorable prognosis and more indolent progression . Knowledge of T790 M status is therefore important both for the clinical care of these patients and for the optimal design and interpretation of clinical trials in this setting . Clin Cancer Res ; 17(6 ) ; 1616–22 . © 2010 AACR Purpose : In patients with non – small cell lung cancer ( NSCLC ) , mutations in the epidermal growth factor receptor ( EGFR ) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib . We undertook this study to explore the relationship between EGFR mutation type and clinical variables , including treatment with gefitinib and erlotinib . Experimental Design : In patients with NSCLC , EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment . The results were correlated with clinical information ( sex , pathologic subtype , race/ethnicity , treatment , and overall survival ) . Results : The two most common EGFR mutations were identified in 24 % ( 70 of 291 ; 95 % confidence interval , 26%-38 % ) of tumors from patients with NSCLC . EGFR mutation was associated with Asian ethnicity ( P = 0.0023 ) and being a “ never smoker ” ( P = 0.0001 ) . Among patients with EGFR mutations , 39 % ( 27 of 70 ) had EGFR L858R , whereas 61 % ( 43 of 70 ) had an EGFR exon 19 deletion . After treatment with erlotinib ( n = 12 ) or gefitinib ( n = 22 ) , patients with EGFR mutations had a median overall survival of 20 months . After treatment with erlotinib or gefitinib , patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R ( 34 versus 8 months ; log-rank P = 0.01 ) . Conclusions : EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib . Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation . These observations warrant confirmation in a prospect i ve study and exploration of the biological mechanisms of the differences between the two major EGFR mutations BACKGROUND Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor ( TKI ) therapy in non-small-cell lung cancer ( NSCLC ) . The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus st and ard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC . METHODS We undertook an open-label , r and omised , phase 3 trial at 22 centres in China . Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR ( exon 19 deletion or exon 21 L858R point mutation ) received either oral erlotinib ( 150 mg/day ) until disease progression or unacceptable toxic effects , or up to four cycles of gemcitabine plus carboplatin . Patients were r and omly assigned ( 1:1 ) with a minimisation procedure and were stratified according to EGFR mutation type , histological subtype ( adenocarcinoma vs non-adenocarcinoma ) , and smoking status . The primary outcome was progression-free survival , analysed in patients with confirmed disease who received at least one dose of study treatment . The trial is registered at Clinical Trials.gov , number NCT00874419 , and has completed enrolment ; patients are still in follow-up . FINDINGS 83 patients were r and omly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin ; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint . Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy ( 13.1 [ 95 % CI 10.58 - 16.53 ] vs 4.6 [ 4.21 - 5.42 ] months ; hazard ratio 0.16 , 95 % CI 0.10 - 0.26 ; p<0.0001 ) . Chemotherapy was associated with more grade 3 or 4 toxic effects than was erlotinib ( including neutropenia in 30 [ 42 % ] of 72 patients and thrombocytopenia in 29 [ 40 % ] patients on chemotherapy vs no patients with either event on erlotinib ) ; the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations ( three [ 4 % ] of 83 patients ) and skin rash ( two [ 2 % ] patients ) . Chemotherapy was also associated with increased treatment-related serious adverse events ( ten [ 14 % ] of 72 patients [ decreased platelet count , n=8 ; decreased neutrophil count , n=1 ; hepatic dysfunction , n=1 ] vs two [ 2 % ] of 83 patients [ both hepatic dysfunction ] ) . INTERPRETATION Compared with st and ard chemotherapy , erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability . These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC . FUNDING F Hoffmann-La Roche Ltd ( China ) ; Science and Technology Commission of Shanghai Municipality OBJECTIVES Although T790 M mutation is considered to be the major mechanism of acquired resistance to epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors ( TKIs ) in patients with non-small cell lung cancer ( NSCLC ) , its clinical implication remains undetermined . METHODS Post-progression tumor specimens were prospect ively collected for T790 M mutation analysis in NSCLC patients with acquired resistance to initial EGFR TKIs . Clinical features were compared between patients with and without T790 M . RESULTS Out of 70 cases , 36 ( 51 % ) were identified to have T790 M mutation in the rebiopsy specimen . There was no difference in the pattern of disease progression , progression-free survival for initial TKIs ( 12.8 and 11.3 months ) , post-progression survival ( 14.7 and 14.1 months ) , or overall survival ( 43.5 and 36.8 months ) in patients with and without T790 M . In total , 34 patients received afatinib after post-progression biopsy as a subsequent treatment , and the response rate was 18 % . The median progression-free survival for afatinib was 3.7 months for the entire group , and 3.2 and 4.6 months for the groups with and without T790 M , respectively ( P = 0.33 ) . CONCLUSIONS The identification of T790 M as acquired resistance mechanism was clinical ly feasible . Although T790 M had no prognostic or predictive role in the present study , further research is necessary to identify patients with T790M-mutant tumors who might benefit from newly developed T790M-specific TKIs BACKGROUND Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor ( EGFR ) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib , but little is known about how its efficacy and safety profile compares with that of st and ard chemotherapy . METHODS We r and omly assigned 230 patients with metastatic , non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel . The primary end point was progression-free survival ; secondary end points included overall survival , response rate , and toxic effects . RESULTS In the planned interim analysis of data for the first 200 patients , progression-free survival was significantly longer in the gefitinib group than in the st and ard-chemotherapy group ( hazard ratio for death or disease progression with gefitinib , 0.36 ; P<0.001 ) , result ing in early termination of the study . The gefitinib group had a significantly longer median progression-free survival ( 10.8 months , vs. 5.4 months in the chemotherapy group ; hazard ratio , 0.30 ; 95 % confidence interval , 0.22 to 0.41 ; P<0.001 ) , as well as a higher response rate ( 73.7 % vs. 30.7 % , P<0.001 ) . The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group ( P=0.31 ) . The most common adverse events in the gefitinib group were rash ( 71.1 % ) and elevated aminotransferase levels ( 55.3 % ) , and in the chemotherapy group , neutropenia ( 77.0 % ) , anemia ( 64.6 % ) , appetite loss ( 56.6 % ) , and sensory neuropathy ( 54.9 % ) . One patient receiving gefitinib died from interstitial lung disease . CONCLUSIONS First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival , with acceptable toxicity , as compared with st and ard chemotherapy . ( UMIN-CTR number , C000000376 . BACKGROUND Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer ( NSCLC ) with activating EGFR mutations . We aim ed to assess the safety and efficacy of erlotinib compared with st and ard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC . METHODS We undertook the open-label , r and omised phase 3 EURTAC trial at 42 hospitals in France , Italy , and Spain . Eligible participants were adults ( > 18 years ) with NSCLC and EGFR mutations ( exon 19 deletion or L858R mutation in exon 21 ) with no history of chemotherapy for metastatic disease ( neoadjuvant or adjuvant chemotherapy ending ≥ 6 months before study entry was allowed ) . We r and omly allocated participants ( 1:1 ) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of st and ard intravenous chemotherapy of cisplatin 75 mg/m(2 ) on day 1 plus docetaxel ( 75 mg/m(2 ) on day 1 ) or gemcitabine ( 1250 mg/m(2 ) on days 1 and 8) . Carboplatin ( AUC 6 with docetaxel 75 mg/m(2 ) or AUC 5 with gemcitabine 1000 mg/m(2 ) ) was allowed in patients unable to have cisplatin . Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status ( 0 vs 1 vs 2 ) . The primary endpoint was progression-free survival ( PFS ) in the intention-to-treat population . We assessed safety in all patients who received study drug ( ≥ 1 dose ) . This study is registered with Clinical Trials.gov , number NCT00446225 . FINDINGS Between Feb 15 , 2007 , and Jan 4 , 2011 , 174 patients with EGFR mutations were enrolled . One patient received treatment before r and omisation and was thus withdrawn from the study ; of the remaining patients , 86 were r and omly assigned to receive erlotinib and 87 to receive st and ard chemotherapy . The preplanned interim analysis showed that the study met its primary endpoint ; enrolment was halted , and full evaluation of the results was recommended . At data cutoff ( Jan 26 , 2011 ) , median PFS was 9·7 months ( 95 % CI 8·4 - 12·3 ) in the erlotinib group , compared with 5·2 months ( 4·5 - 5·8 ) in the st and ard chemotherapy group ( hazard ratio 0·37 , 95 % CI 0·25 - 0·54 ; p < 0·0001 ) . Main grade 3 or 4 toxicities were rash ( 11 [ 13 % ] of 84 patients given erlotinib vs none of 82 patients in the chemotherapy group ) , neutropenia ( none vs 18 [ 22 % ] ) , anaemia ( one [ 1 % ] vs three [ 4 % ] ) , and increased amino-transferase concentrations ( two [ 2 % ] vs 0 ) . Five ( 6 % ) patients on erlotinib had treatment-related severe adverse events compared with 16 patients ( 20 % ) on chemotherapy . One patient in the erlotinib group and two in the st and ard chemotherapy group died from treatment-related causes . INTERPRETATION Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors . FUNDING Spanish Lung Cancer Group , Roche Farma , Hoffmann-La Roche , and Red Temática de Investigacion Cooperativa en Cancer BACKGROUND The EGFR T790 M mutation is the most common mechanism of drug resistance to epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitors in patients who have lung cancer with an EGFR mutation ( EGFR-mutated lung cancer ) . In pre clinical models , the EGFR inhibitor AZD9291 has been shown to be effective against both EGFR tyrosine kinase inhibitor-sensitizing and T790 M resistance mutations . METHODS We administered AZD9291 at doses of 20 to 240 mg once daily in patients with advanced lung cancer who had radiologically documented disease progression after previous treatment with EGFR tyrosine kinase inhibitors . The study included dose-escalation cohorts and dose-expansion cohorts . In the expansion cohorts , pre study tumor biopsies were required for central determination of EGFR T790 M status . Patients were assessed for safety , pharmacokinetics , and efficacy . RESULTS A total of 253 patients were treated . Among 31 patients enrolled in the dose-escalation cohorts , no dose-limiting toxic effects occurred at the doses evaluated . An additional 222 patients were treated in five expansion cohorts . The most common all-cause adverse events were diarrhea , rash , nausea , and decreased appetite . The overall objective tumor response rate was 51 % ( 95 % confidence interval [ CI ] , 45 to 58 ) . Among 127 patients with central ly confirmed EGFR T790 M who could be evaluated for response , the response rate was 61 % ( 95 % CI , 52 to 70 ) . In contrast , among 61 patients without central ly detectable EGFR T790 M who could be evaluated for response , the response rate was 21 % ( 95 % CI , 12 to 34 ) . The median progression-free survival was 9.6 months ( 95 % CI , 8.3 to not reached ) in EGFR T790M-positive patients and 2.8 months ( 95 % CI , 2.1 to 4.3 ) in EGFR T790M-negative patients . CONCLUSIONS AZD9291 was highly active in patients with lung cancer with the EGFR T790 M mutation who had had disease progression during prior therapy with EGFR tyrosine kinase inhibitors . ( Funded by AstraZeneca ; Clinical Trials.gov number , NCT01802632 . ) |
2,608 | 26,980,554 | PFS was longer with purine analogs compared with chlorambucil with an increased risk of infection .
The risk of secondary malignancies was not increased with chlorambucil .
In conclusion , our study showed that chlorambucil is an acceptable chemotherapy backbone for unfit patients with CLL . | Abstract R and omized clinical trials that compared chlorambucil to different regimens , for patients with chronic lymphocytic leukemia/small lymphocytic lymphoma ( CLL/SLL ) do not support an overall survival ( OS ) benefit . | The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia ( CLL ) was re‐evaluated after a median observation time of 54 months in May 2010 . Overall survival ( OS ) was analysed for the first time . At follow‐up , investigator‐assessed complete response ( CR ) rate ( 21·0 % vs 10·8 % ) , median progression‐free survival ( 21·2 vs 8·8 months ; P < 0·0001 ; hazard ratio 2·83 ) and time to next treatment ( 31·7 vs 10·1 months ; P < 0·0001 ) were improved for bendamustine over chlorambucil . OS was not different between groups for all patients or those ≤65 years , > 65 years , responders and non‐responders . However , patients with objective response or a CR experienced a significantly longer OS than non‐responders or those without a CR . Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine ( 78·3 % vs 63·6 % ; P = 0·004 ) . The benefits of bendamustine over chlorambucil were achieved without reducing quality of life . In conclusion , bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients , with the achievement of a CR or objective response appearing to prolong OS . Bendamustine should be considered as a preferred first‐line option over chlorambucil for CLL patients ineligible for fludarabine , cyclophosphamide and rituximab Although chronic lymphocytic leukemia ( CLL ) is a disease of elderly patients , subjects older than 65 years are heavily underrepresented in clinical trials . The German CLL study group ( GCLLSG ) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil . A total of 193 patients with a median age of 70 years were r and omized to receive fludarabine ( 25 mg/m(2 ) for 5 days intravenously , every 28 days , for 6 courses ) or chlorambucil ( 0.4 mg/kg body weight [ BW ] with an increase to 0.8 mg/kg , every 15 days , for 12 months ) . Fludarabine result ed in a significantly higher overall and complete remission rate ( 72 % vs 51 % , P = .003 ; 7 % vs 0 % , P = .011 ) . Time to treatment failure was significantly shorter in the chlorambucil arm ( 11 vs 18 months ; P = .004 ) , but no difference in progression-free survival time was observed ( 19 months with fludarabine , 18 months with chlorambucil ; P = .7 ) . Moreover , fludarabine did not increase the overall survival time ( 46 months in the fludarabine vs 64 months in the chlorambucil arm ; P = .15 ) . Taken together , the results suggest that in elderly CLL patients the first-line therapy with fludarabine alone does not result in a major clinical benefit compared with chlorambucil . This trial is registered with www.is rct n.org under identifier IS RCT N 36294212 BACKGROUND Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide . We aim ed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine . METHODS 777 patients with chronic lymphocytic leukaemia requiring treatment were r and omly assigned to fludarabine ( n=194 ) or fludarabine plus cyclophosphamide ( 196 ) for six courses , or chlorambucil ( 387 ) for 12 courses . The primary endpoint was overall survival , with secondary endpoints of response rates , progression-free survival , toxic effects , and quality of life . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number NCT 58585610 . FINDINGS There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide , fludarabine , or chlorambucil . Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine ( complete response rate 38%vs 15 % , respectively ; overall response rate 94%vs 80 % , respectively ; p<0.0001 for both comparisons ) , which were in turn better than with chlorambucil ( complete response rate 7 % , overall response rate 72 % ; p=0.006 and 0.04 , respectively ) . Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide ( 36 % ) than with fludarabine ( 10 % ) or chlorambucil ( 10 % ; p<0.00005 ) . Fludarabine plus cyclophosphamide was the best combination for all ages , including patients older than 70 years , and in prognostic groups defined by immunoglobulin heavy chain gene ( V(H ) ) mutation status and cytogenetics , which were tested in 533 and 579 cases , respectively . Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide , or fludarabine , than with chlorambucil . There was less haemolytic anaemia with fludarabine plus cyclophosphamide ( 5 % ) than with fludarabine ( 11 % ) or chlorambucil ( 12 % ) . Quality of life was better for responders , but preliminary analyses showed no significant difference between treatments . A meta- analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival . INTERPRETATION Fludarabine plus cyclophosphamide should now become the st and ard treatment for chronic lymphocytic leukaemia and the basis for new protocol s that incorporate monoclonal antibodies BACKGROUND Chronic lymphocytic leukemia ( CLL ) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression . We conducted an international , open-label , r and omized phase 3 trial to compare two oral agents , ibrutinib and chlorambucil , in previously untreated older patients with CLL or small lymphocytic lymphoma . METHODS We r and omly assigned 269 previously untreated patients who were 65 years of age or older and had CLL or small lymphocytic lymphoma to receive ibrutinib or chlorambucil . The primary end point was progression-free survival as assessed by an independent review committee . RESULTS The median age of the patients was 73 years . During a median follow-up period of 18.4 months , ibrutinib result ed in significantly longer progression-free survival than did chlorambucil ( median , not reached vs. 18.9 months ) , with a risk of progression or death that was 84 % lower with ibrutinib than that with chlorambucil ( hazard ratio , 0.16 ; P<0.001 ) . Ibrutinib significantly prolonged overall survival ; the estimated survival rate at 24 months was 98 % with ibrutinib versus 85 % with chlorambucil , with a relative risk of death that was 84 % lower in the ibrutinib group than in the chlorambucil group ( hazard ratio , 0.16 ; P=0.001 ) . The overall response rate was higher with ibrutinib than with chlorambucil ( 86 % vs. 35 % , P<0.001 ) . The rates of sustained increases from baseline values in the hemoglobin and platelet levels were higher with ibrutinib . Adverse events of any grade that occurred in at least 20 % of the patients receiving ibrutinib included diarrhea , fatigue , cough , and nausea ; adverse events occurring in at least 20 % of those receiving chlorambucil included nausea , fatigue , neutropenia , anemia , and vomiting . In the ibrutinib group , four patients had a grade 3 hemorrhage and one had a grade 4 hemorrhage . A total of 87 % of the patients in the ibrutinib group are continuing to take ibrutinib . CONCLUSIONS Ibrutinib was superior to chlorambucil in previously untreated patients with CLL or small lymphocytic lymphoma , as assessed by progression-free survival , overall survival , response rate , and improvement in hematologic variables . ( Funded by Pharmacyclics and others ; RESONATE-2 Clinical Trials.gov number , NCT01722487 . ) Abstract Health-related quality of life ( HRQoL ) is a key issue for patients with chronic lymphocytic leukemia . The multicenter LRF CLL4 trial , in which 777 patients were r and omized to receive chlorambucil or fludarabine , alone or with cyclophosphamide ( FC ) , assessed HRQoL at baseline , months 3 , 6 and 12 , then annually until 5 years , using the European Organisation for Research and Treatment of Cancer quality of life question naire ( EORTC-QLQ-C30 ) . While on treatment , some HRQoL impairment was seen in patients receiving fludarabine , particularly FC , compared with chlorambucil . Thus at 3 months , role/social functioning and fatigue were ≥ 10 points worse than baseline in 41%/46%/56 % , respectively , of patients receiving fludarabine alone and 48%/54%/60 % receiving FC , compared with only 29%/31%/40 % of those receiving chlorambucil . Thereafter HRQoL appeared similar between treatment groups . Sustained remissions were associated with long-term HRQoL benefit . In the primary HRQoL domains patients still in complete or partial remission at each time-point had scores close to those reported in general population studies , while patients whose disease had progressed had mean scores up to 22 points worse , in spite of subsequent treatments . These data offer support for the use of primary treatment regimens likely to achieve and sustain remission in otherwise medically fit patients of all ages , including those aged > 70 years BACKGROUND The monoclonal anti-CD20 antibody rituximab , combined with chemotherapeutic agents , has been shown to prolong overall survival in physically fit patients with previously untreated chronic lymphocytic leukemia ( CLL ) but not in those with coexisting conditions . We investigated the benefit of the type 2 , glycoengineered antibody obinutuzumab ( also known as GA101 ) as compared with that of rituximab , each combined with chlorambucil , in patients with previously untreated CLL and coexisting conditions . METHODS We r and omly assigned 781 patients with previously untreated CLL and a score higher than 6 on the Cumulative Illness Rating Scale ( CIRS ) ( range , 0 to 56 , with higher scores indicating worse health status ) or an estimated creatinine clearance of 30 to 69 ml per minute to receive chlorambucil , obinutuzumab plus chlorambucil , or rituximab plus chlorambucil . The primary end point was investigator-assessed progression-free survival . RESULTS The patients had a median age of 73 years , creatinine clearance of 62 ml per minute , and CIRS score of 8 at baseline . Treatment with obinutuzumab-chlorambucil or rituximab-chlorambucil , as compared with chlorambucil monotherapy , increased response rates and prolonged progression-free survival ( median progression-free survival , 26.7 months with obinutuzumab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio for progression or death , 0.18 ; 95 % confidence interval [ CI ] , 0.13 to 0.24 ; P<0.001 ; and 16.3 months with rituximab-chlorambucil vs. 11.1 months with chlorambucil alone ; hazard ratio , 0.44 ; 95 % CI , 0.34 to 0.57 ; P<0.001 ) . Treatment with obinutuzumab-chlorambucil , as compared with chlorambucil alone , prolonged overall survival ( hazard ratio for death , 0.41 ; 95 % CI , 0.23 to 0.74 ; P=0.002 ) . Treatment with obinutuzumab-chlorambucil , as compared with rituximab-chlorambucil , result ed in prolongation of progression-free survival ( hazard ratio , 0.39 ; 95 % CI , 0.31 to 0.49 ; P<0.001 ) and higher rates of complete response ( 20.7 % vs. 7.0 % ) and molecular response . Infusion-related reactions and neutropenia were more common with obinutuzumab-chlorambucil than with rituximab-chlorambucil , but the risk of infection was not increased . CONCLUSIONS Combining an anti-CD20 antibody with chemotherapy improved outcomes in patients with CLL and coexisting conditions . In this patient population , obinutuzumab was superior to rituximab when each was combined with chlorambucil . ( Funded by F. Hoffmann-La Roche ; Clinical Trials.gov number , NCT01010061 . ) PURPOSE We sought to determine whether therapy with single-agent fludarabine compared with chlorambucil alone or the combination of both agents had an impact on the incidence and spectrum of infections among a series of previously untreated patients with B-cell chronic lymphocytic leukemia ( CLL ) . PATIENTS AND METHODS Five hundred fifty-four previously untreated CLL patients with intermediate/high-risk Rai-stage disease were enrolled onto an intergroup protocol . Patients were r and omized to therapy with chlorambucil , fludarabine , or fludarabine plus chlorambucil . Data pertaining to infection were available on 518 patients . Differences in infections among treatment arms were tested with the Kruskal-Wallis , Wilcoxon , and chi(2 ) tests . RESULTS A total of 1,107 infections ( 241 major infections ) occurred in 518 patients over the infection follow-up period ( interval from study entry until either reinstitution of initial therapy , therapy with a second agent , or death ) . Patients treated with fludarabine plus chlorambucil had more infections than those receiving either single agent ( P < .0001 ) . Comparing the two single-agent arms , there were more infections on the fludarabine arm ( P = .055 ) per month of follow-up . Fludarabine therapy was associated with more major infections and more herpesvirus infections compared with chlorambucil ( P = .008 and P = .004 , respectively ) . Rai stage and best response to therapy were not associated with infection . A low serum immunoglobulin G was associated with number of infections ( P = .02 ) . Age was associated with incidence of major infection in the combination arm ( P = .004 ) . CONCLUSION Combination therapy with fludarabine plus chlorambucil result ed in significantly more infections than treatment with either single agent . Patients receiving single-agent fludarabine had more major infections and herpesvirus infections compared with chlorambucil-treated patients N 1988 , THE National Cancer Institute-sponsored Working Group ( NCI-WC ) on chronic lymphocytic leukemia ( CLL ) published guidelines for the design and conduct of clinical trials in CLL with two major objectives : first , to facilitate comparisons of results of clinical trials in CLL by providing st and ardized eligibility , response , and toxicity criteria ; and , second , to encourage a framework on which to evaluate new scientific studies related to our increasing underst and ing of the biology and immunology of this disease . ' These guidelines were rapidly adopted by the majority of the clinical trials community , and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine . The differences between these guidelines and those subsequently published by the International Working Group on CLL ( IWCLL ) , which were general- practice recommendations ' are listed in Table 1 . For diagnosis , the NCI-WC requires a lymphocyte count of 5 X loy & which is lower than the 10 X 109/L required by the IWCLL , unless the lymphocytes are B cells and the bone marrow is involved . To be considered a complete remission ( CR ) , the NCI-WC criteria specify that less than 30 % lymphocytes must be present in the bone marrow , with a recommendation that the clinical significance of lymphoid nodules be assessed prospect ively ( Table 1 ) ; the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR . The IWCLL uses a shift in clinical stage as the sole index of partial remission ( PR ) , whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift . The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy , hematologic toxicity , and other important components for clinical trials design . The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years . Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and , also , with the experience following the use of newer , more effective agents , such as fludarabine . " ' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group , it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version The efficacy and toxicity of cladribine ( 2-CdA ) + prednisone ( P ) versus chlorambucil ( Chl ) + P were compared in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia ( CLL ) in a r and omized , multicenter prospect i ve trial . Eligible patients were assigned to either 2-CdA 0.12 mg/kg per day in 2-hour infusions and P 30 mg/m(2 ) per day for 5 consecutive days or Chl 12 mg/m(2 ) per day and P 30 mg/m(2 ) per day for 7 consecutive days . Three courses were administered at 28-day intervals or longer if myelosuppression developed . The therapy was finished if complete response ( CR ) was achieved . Of 229 available patients 126 received 2-CdA+P and 103 received Chl+P as a first-line treatment . CR and overall response rates were significantly higher in the patients treated with 2-CdA+P ( 47 % and 87 % , respectively ) than in the patients treated with Chl+P ( 12 % and 57 % , respectively ) ( P = .001 ) . Progression-free survival was significantly longer in the 2-CdA-treated group ( P = .01 ) , but event-free survival was not statistically different . Thirteen percent of patients were refractory to 2-CdA+P and 43 % to Chl+P ( P = .001 ) . Drug-induced neutropenia was more frequently observed during 2-CdA+P ( 23 % ) than Chl+P therapy ( 11 % ) ( P = .02 ) , but thrombocytopenia occurred with similar frequency in both groups ( 36 % and 27 % , respectively ) . Infections were seen more frequently in the 2-CdA+P-treated group ( 56 % ) than in the Chl+P-treated group ( 40 % ; P = .02 ) . Death rates have so far been similar in patients treated with 2-CdA ( 20 % ) and with Chl ( 17 % ) . The probability of overall survival calculated from Kaplan-Meier curves at 24 months was also similar for both groups ( 78 % and 82 % , respectively ) . ( Blood . 2000;96:2723 - 2729 In recent years , much attention has been paid to the possible efficacy of intensive chemotherapy in the treatment of advanced , progressive B‐cell chronic lymphocytic leukemia ( CLL ) patients . For this reason , the International Society for Chemo‐Immunotherapy , Chronic Lymphocytic Leukemia Cooperative Group , has begun a r and omized multicenter trial comparing Binet 's modified cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) regimen with continuous high dose chlorambucil ( HD‐CLB ) PURPOSE Patients with chronic lymphocytic leukemia ( CLL ) may have disease transformation to non-Hodgkin 's lymphoma or prolymphocytic leukemia ; however , development of therapy-related acute myeloid leukemia ( t-AML ) is unusual . A series of patients enrolled onto an intergroup CLL trial were examined for this complication . PATIENTS AND METHODS A total of 544 previously untreated B-cell CLL patients were enrolled onto a r and omized intergroup study comparing treatment with chlorambucil , fludarabine , or fludarabine plus chlorambucil . Case report forms from 521 patients were review ed for t-AML . RESULTS With a median follow-up of 4.2 years , six patients ( 1.2 % ) to date have developed therapy-related myelodysplastic syndrome ( t-MDS ; n = 3 ) , t-AML ( n = 2 ) , or t-MDS evolving to t-AML ( n = 1 ) , from 27 to 53 months ( median , 34 months ) after study entry . This included five ( 3.5 % ) of 142 patients treated with fludarabine plus chlorambucil and one ( 0.5 % ) of 188 receiving fludarabine ; no chlorambucil-treated patients developed t-MDS or t-AML ( P = .007 ) . At study entry , the median age among these six patients was 56 years ( range , 44 to 72 years ) ; three were male ; the CLL Rai stage was I/II ( n = 4 ) or III/IV ( n = 2 ) . Response to CLL therapy was complete ( n = 4 ) or partial remission ( n = 1 ) and stable disease ( n = 1 ) . Marrow cytogenetics , obtained in three of six cases at diagnosis of t-MDS or t-AML , were complex , with abnormalities in either or both chromosomes 5 and 7 . Other abnormalities involved chromosomes X , 1 , 8 , 12 , 17 , and 19 . Median survival after diagnosis of t-MDS/AML was 3.5 months ( range , 0.5 to 10.1 months ) . CONCLUSION Our findings raise the possibility that alkylator-purine analog combination therapy may increase the risk of therapy-related myeloid malignancies , which is of particular relevance with regard to ongoing trials using these combination therapies This paper summarizes results from clinical trials of the French Cooperative Group in chronic lymphocytic leukemia , CLL 80 and CLL 85 protocol s. These protocol s were based on the ( A , B , C ) classification . Nine hundred and seventy three patients were r and omised in the CLL 80 protocol , 612 in stage A , 289 in stage B and 72 in stage C. Results from the fourth interim analysis were ( 1 ) in stage A , overall survival was better in the untreated group as compared to patients treated by daily chlorambucil with an increased incidence of epithelial cancers in the chlorambucil group ; ( 2 ) in stage B , there was no improvement in overall survival with the COP regimen as compared to daily chlorambucil ; ( 3 ) in stage C , the effectiveness of the CHOP regimen was confirmed . More than 1,400 patients have been r and omised in the CLL 85 protocol but results from the first interim analysis were only available in stage B ( 194 patients ) . At the 6-month evaluation 28 % reached complete remission in the CHOP group versus 12 % in the chlorambucil-prednisone group . More follow-up is needed to assess the benefit from the CHOP regimen in terms of survival in stage B patients The Eastern Cooperative Oncology Group ( ECOG ) conducted a study in which patients with advanced chronic lymphocytic leukemia ( CLL ) were r and omized between a regimen consisting of chlorambucil ( 30 mg/m2 orally day 1 ) and prednisone ( 80 mg orally days 1 to 5 ) ( C + P ) administered every 2 weeks and a more intensive regimen of cyclosphosphamide ( 300 mg/m2 orally days 1 to 5 ) , vincristine ( 1.4 mg/m2 intravenously [ IV ] day 1 ) , and prednisone ( 100 mg/m2 orally days 1 to 5 ) ( CVP ) given every 3 weeks . Treatment was continued for up to 18 months to maximal response . Of the 122 eligible patients , 60 received C + P , while 62 received CVP . With a median follow-up of 7 years , there were no significant differences in survival ( 4.8 v 3.9 years , P = .12 ) , complete remission ( CR ) rate ( 25 % v 23 % ; P = .83 ) , or duration of response ( 2.0 v 1.9 years ; P = .78 ) between C + P and CVP . Toxicity was modest despite the prolonged treatment . The long median survival of 4.1 years for stage III and IV patients is superior to that usually reported . This could stem from continuing treatment to maximal response rather than an increase in intensity of therapy . These results are comparable to those reported with cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) therapy by other investigators . The data suggest that intermittent C + P administered to maximal response continues to be the st and ard treatment approach for advanced CLL The Medical Research Council ( MRC ) Working Party on Leukaemia in Adults has conducted two r and omised trials in CLL since 1978 . CLL 1 ran from 1978 to 1984 and recruited 660 eligible patients . The number of males was twice the number of females and the distribution of cases by stage was different in the sexes : 58 % of females were stage A , 25 % stage B and 17 % stage C ; in males the proportions for stages A , B and C were 40 % , 30 % and 30 % respectively . The most important prognostic factor was stage ( A , B , C ) , followed by age , sex and response to treatment , which were confirmed as independent variables by stratified log-rank and Cox multivariate analyses . Causes unrelated to CLL accounted for 28 % of all deaths and were more common in older patients and in stage A disease . No significant difference was observed between the CLL 1 treatment schedules : chlorambucil , penta Cop and splenic irradiation ( SI ) , although a somewhat better survival was seen for patients treated by SI . ( When CLL deaths only were considered SI appeared superior to chlorambucil ( p less than 0.05 ] . CLL 2 started in 1984 and is still accruing patients ; 556 had been entered by July 1988 . This trial compares early versus delayed therapy for stage A , chlorambucil with and without prednisolone for stages B and C in patients with a small or nonpalpable spleen , and SI vs chlorambucil with or without prednisolone for stages B and C in patients with a larger spleen ( greater than or equal to 5 cm ) . ( ABSTRACT TRUNCATED AT 250 WORDS Bendamustine demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from st and ard alkylating agents . This study assessed its efficacy in patients with chronic lymphocytic leukemia pre-treated with an alkylator , in comparison to fludarabine . Patients with relapsed chronic lymphocytic leukemia requiring treatment after one previous systemic regimen ( usually chlorambucil-based ) were r and omized to either receive bendamustine 100 mg/m2 on days 1 and 2 of a 4-week cycle or st and ard fludarabine treatment consisting of 25 mg/m2 on days 1 to 5 every 4 weeks . The primary objective was to achieve non-inferior progression-free survival ( PFS ) with bendamustine . Out of a total of 96 patients r and omized , 92 were eligible , 49 allocated to bendamustine and 43 to fludarabine . About half of the patients received six or more cycles . Overall response rates were 76 % on bendamustine and 62 % on fludarabine , with clinical complete response rates of 27 and 9 % , respectively . Median PFS was 20.1 and 14.8 months ( hazard ratio , 0.87 ; 90 % confidence interval , 0.60–1.27 ) , median overall survival 43.8 and 41.0 months ( hazard ratio , 0.82 ) . Thrombocytopenia and gastrointestinal toxicities were marginally more frequent on bendamustine , albeit CTC grade 3/4 event incidence was similar . These data suggest at least comparable efficacy of bendamustine vs. fludarabine , pointing to an alternative treatment option in relapsing CLL patients after chlorambucil containing initial chemotherapy Between 1985 and 1990 , the French Cooperative Group on Chronic Lymphocytic Leukemia ( CLL ) r and omized 287 stage B patients between intermittent chlorambucil plus prednisone ( n = 140 ) or CHOP ( n = 147 ) , and 90 stage C patients between CHOP ( n = 44 ) or CHOP plus methotrexate ( n = 46 ) . In stage B , although treatment response was improved with CHOP ( p = 0.007 , chi-square test ) , no difference in survival was observed between the two r and omized groups ( p = 0.33 , score test ) . In stage C , no differences in treatment response and survival were shown , with median survival close to that reported with CHOP in the previous CLL-80 trial . These results associated with those from other groups raise the question whether the CHOP regimen , which has been consistently shown to improve response to therapy , is an effective treatment in advanced CLL patients BACKGROUND On the basis of promising results that were reported in several phase 2 trials , we investigated whether the addition of the monoclonal antibody rituximab to first-line chemotherapy with fludarabine and cyclophosphamide would improve the outcome of patients with chronic lymphocytic leukaemia . METHODS Treatment-naive , physically fit patients ( aged 30 - 81 years ) with CD20-positive chronic lymphocytic leukaemia were r and omly assigned in a one-to-one ratio to receive six courses of intravenous fludarabine ( 25 mg/m(2 ) per day ) and cyclophosphamide ( 250 mg/m(2 ) per day ) for the first 3 days of each 28-day treatment course with or without rituximab ( 375 mg/m(2 ) on day 0 of first course , and 500 mg/m(2 ) on day 1 of second to sixth courses ) in 190 centres in 11 countries . Investigators and patients were not masked to the computer-generated treatment assignment . The primary endpoint was progression-free survival ( PFS ) . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00281918 . FINDINGS 408 patients were assigned to fludarabine , cyclophosphamide , and rituximab ( chemoimmunotherapy group ) and 409 to fludarabine and cyclophosphamide ( chemotherapy group ) ; all patients were analysed . At 3 years after r and omisation , 65 % of patients in the chemoimmunotherapy group were free of progression compared with 45 % in the chemotherapy group ( hazard ratio 0·56 [ 95 % CI 0·46 - 0·69 ] , p<0·0001 ) ; 87 % were alive versus 83 % , respectively ( 0·67 [ 0·48 - 0·92 ] ; p=0·01 ) . Chemoimmunotherapy was more frequently associated with grade 3 and 4 neutropenia ( 136 [ 34 % ] of 404 vs 83 [ 21 % ] of 396 ; p<0·0001 ) and leucocytopenia ( 97 [ 24 % ] vs 48 [ 12 % ] ; p<0·0001 ) . Other side-effects , including severe infections , were not increased . There were eight ( 2 % ) treatment-related deaths in the chemoimmunotherapy group compared with ten ( 3 % ) in the chemotherapy group . INTERPRETATION Chemoimmunotherapy with fludarabine , cyclophosphamide , and rituximab improves progression-free survival and overall survival in patients with chronic lymphocytic leukaemia . Moreover , the results suggest that the choice of a specific first-line treatment changes the natural course of chronic lymphocytic leukaemia . FUNDING F Hoffmann-La Roche BACKGROUND Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable . Chlorambucil remains the st and ard of care in many countries . We aim ed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone , while also being tolerable for patients who have few treatment options . METHODS We carried out a r and omised , open-label , phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries . We included patients who had active disease needing treatment , but in whom fludarabine-based treatment was not possible . We r and omly assigned patients ( 1:1 ) to receive oral chlorambucil ( 10 mg/m(2 ) ) on days 1 - 7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab ( cycle 1 : 300 mg on day 1 and 1000 mg on day 8 ; subsequent cycles : 1000 mg on day 1 ) for three to 12 cycles . Assignment was done with a r and omisation list that was computer generated at GlaxoSmithKline , and was stratified , in a block size of two , by age , disease stage , and performance status . The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment . The study is registered with Clinical Trials.gov , number NCT00748189 . FINDINGS We enrolled 447 patients , median age 69 years ( range 35 - 92 ) . Between Dec 22 , 2008 , and May 26 , 2011 , we r and omly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone . Median progression-free survival was 22·4 months ( 95 % CI 19·0 - 25·2 ) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months ( 10·6 - 13·8 ) in the group assigned to chlorambucil only ( hazard ratio 0·57 , 95 % CI 0·45 - 0·72 ; p<0·0001 ) . Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group ( 109 [ 50 % ] patients ; vs 98 [ 43 % ] given chlorambucil alone ) , with neutropenia being the most common event ( 56 [ 26 % ] vs 32 [ 14 % ] ) . Grade 3 or greater infections had similar frequency in both groups . Grade 3 or greater infusion-related adverse events were reported in 22 ( 10 % ) patients given chlorambucil plus ofatumumab . Five ( 2 % ) patients died during treatment in each group . INTERPRETATION Addition of ofatumumab to chlorambucil led to clinical ly important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities . Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who can not tolerate more intensive therapy . FUNDING GlaxoSmithKline , Genmab Two hundred fifty-nine previously untreated patients with low- grade non-Hodgkin 's lymphomas ( NHLs ) , Ann Arbor stages III and IV , entered a r and omized multicenter trial comparing the therapeutic effect of chlorambucil/prednisone ( ChP ) vs. CHOP . All patients had symptomatic disease . The therapeutic aim was to achieve an asymptomatic state in the ChP group ( n = 132 ) , while in CHOP-treated patients ( n = 127 ) the intention was to reach a complete remission ( CR ) . The response rate ( CR+PR at 8 months ) was 36 % in the ChP and 60 % in the CHOP group ( p < 0.01 ) . Three and 5-year survival rates were 59 % and 41 % in the ChP group and 64 % and 44 % in the CHOP group . The corresponding median survival times were 46 and 52 months . After correction for intercurrent deaths , the overall 5-year survival was 49 % for ChP and 54 % for CHOP-treated patients . The differences were statistically not significant . The time from diagnosis to r and omization ( time with asymptomatic disease ) was longer than one year in half of the patients . The median survival time from diagnosis was 68 months , with no differences between the treatment groups . In all histological subgroups ( CLL , IC , CC , and CB-CC ) , a higher remission rate was seen with the CHOP regimen but with no statistically significant influence on survival . Comparing patients below and above 65 years of age , no significant difference in survival was noted between the two treatment groups . The results do not support the use of intensive chemotherapy as first-line therapy in symptomatic low- grade NHL Ninety-six previously untreated patients ( 67 males/29 females ; mean age : 63 years ; range : 46 - 84 ) with CLL in stage B ( 62 cases ) or C ( 34 cases ) were r and omized to be treated with either chlorambucil ( 0.4 mg/kg orally days 5 and 6 ) plus prednisone ( 60 mg/m2 orally days 1 to 4 ) ( CL + PDN ) every 2 weeks or cyclophosphamide ( 160 mg/m2 orally days 1 to 4 ) , melphalan ( 6 mg/m2 orally days 1 to 4 ) , and prednisone ( 60 mg/m2 orally days 1 to 4 ) ( CMP ) every 3 weeks for 10 months . Forty-eight patients were treated with CLR + PDN , and the remaining 48 with CMP . The following types of response were considered : complete response ( CR ) : total disappearance of symptoms and signs related to the disease . Partial response ( PR ) : shift of the disease to a less advanced stage . Stable disease ( SD ) no change in the stage after treatment . Progressive disease ( PD ) : progression of the disease to a more advanced stage . Thirty-six ( 75 % ) responses ( 27 % CR ) with CLR + PDN and 26 ( 54.5 % , 12.5 % CR ) with CMP were observed ( p = 0.054 ) . Although more responses were achieved in stage B ( 69 % , 24 % CR ) than in stage C ( 54 % , 12 % CR ) this difference did not achieve statistical significance . Survival was statistically not different for those patients treated with LCR + PDN as compared to those receiving CMP . ( ABSTRACT TRUNCATED AT 250 WORDS The impact of the combination therapy fludarabine plus cyclophosphamide ( FC ) in comparison with fludarabine alone regarding the incidence and severity of infections among previously untreated patients with chronic lymphocytic leukaemia ( CLL ) was evaluated within a multicentre phase III study . A total of 375 patients , up to 65 years old , were r and omised between fludarabine or FC for first line therapy . No routine anti‐infective prophylaxis was provided . A total of 196 infectious episodes , including 33 severe infections , were documented . In the fludarabine arm , 32·9 % of the patients developed an infectious complication compared with 39·9 % in the FC arm ( P = 0·2 ) . No difference was observed in the rate of severe infections ( Common Toxicity Crtieria grade s III and IV ) between both treatment arms . Dose reductions were performed more frequently in FC‐treated patients . Granulocyte colony‐stimulating factor ( G‐CSF ) was administered due to leucopenia in 5 % of all patients . A multivariate regression model identified only elevated thymidine kinase , but not the treatment arm , as a statistically independent risk factor for infections . In summary , FC was not associated with a higher rate of infections compared with fludarabine alone . No routine antibiotic or virostatic prophylaxis , or pre‐emptive treatment with G‐CSF , is necessary in first line therapy with fludarabine‐based regimens in younger patients with CLL , if adequate dose reduction is performed . The combination therapy FC is not associated with a higher rate of infections compared with fludarabine alone . No routine antibiotic or virostatic prophylaxis as well as pre‐emptive treatment with G‐CSF is necessary in first line therapy with fludarabine‐based regimen in younger patients with CLL , if adequate dose reductions due to cytopenia or previous infections are performed BACKGROUND Fludarabine is an effective treatment for chronic lymphocytic leukemia that does not respond to initial treatment with chlorambucil . We compared the efficacy of fludarabine with that of chlorambucil in the primary treatment of chronic lymphocytic leukemia . METHODS Between 1990 and 1994 , we r and omly assigned 509 previously untreated patients with chronic lymphocytic leukemia to one of the following treatments : fludarabine ( 25 mg per square meter of body-surface area , administered intravenously daily for 5 days every 28 days ) , chlorambucil ( 40 mg per square meter , given orally every 28 days ) , or fludarabine ( 20 mg per square meter per day for 5 days every 28 days ) plus chlorambucil ( 20 mg per square meter every 28 days ) . Patients with an additional response at each monthly evaluation continued to receive the assigned treatment for a maximum of 12 cycles . RESULTS Assignment of patients to the fludarabine-plus-chlorambucil group was stopped when a planned interim analysis revealed excessive toxicity and a response rate that was not better than the rate with fludarabine alone . Among the other two groups , the response rate was significantly higher for fludarabine alone than for chlorambucil alone . Among 170 patients treated with fludarabine , 20 percent had a complete remission , and 43 percent had a partial remission . The corresponding values for 181 patients treated with chlorambucil were 4 percent and 33 percent ( P < 0.001 for both comparisons ) . The median duration of remission and the median progression-free survival in the fludarabine group were 25 months and 20 months , respectively , whereas both values were 14 months in the chlorambucil group ( P<0.001 for both comparisons ) . The median overall survival among patients treated with fludarabine was 66 months , which was not significantly different from the overall survival in the other two groups ( 56 months with chlorambucil and 55 months with combined treatment ) . Severe infections and neutropenia were more frequent with fludarabine than with chlorambucil ( P=0.08 ) , although , overall , toxic effects were tolerable with the two single-drug regimens . CONCLUSIONS When used as the initial treatment for chronic lymphocytic leukemia , fludarabine yields higher response rates and a longer duration of remission and progression-free survival than chlorambucil Five hundred and fifty consecutive patients with newly diagnosed B-CLL have been registered and classified in a Danish multicenter study . The study includes a protocol for primary treatment of patients in stage B or C ( at diagnosis or after demonstrated progression ) , below 76 years of age , and without complicating serious disease . Until now 144 such patients have been r and omized to either prednisolone ( PRD ) plus chlorambucil ( CLB ) 5 days every 4 weeks or monthly intensive CHOP treatment . Twenty-nine percent of the treated patients achieved CR on PRD + CLB versus 63 % on CHOP ( p less than 0.005 ) . No response was found in 29 % versus 18 % , respectively ( NS ) . A significant difference in survival between patients achieving CR , PR and NR was also demonstrated , whereas to date no difference in survival could be demonstrated between the two regimens . The toxicity was limited , and only 2 treatment-related deaths occurred in approximately 700 CHOP treatment series PURPOSE This r and omized , open-label , parallel-group , multicenter study was design ed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced ( Binet stage B or C ) chronic lymphocytic leukemia ( CLL ) . PATIENTS AND METHODS Patients ( < or= 75 years of age ) were r and omly assigned to receive bendamustine 100 mg/m(2)/d intravenously on days 1 to 2 , or chlorambucil 0.8 mg/kg ( Broca 's normal weight ) orally on days 1 and 15 ; treatment cycles were repeated every 4 weeks for a maximum of six cycles . The response to treatment was assessed according to National Cancer Institute Working Group criteria , and the final determination of response was made by a blinded independent review committee . RESULTS A total of 319 patients were r and omly assigned ( 162 bendamustine , 157 chlorambucil ) . Complete or partial responses were achieved in 110 ( 68 % ) of 162 bendamustine-treated and 48 ( 31 % ) of 157 chlorambucil-treated patients ( P < .0001 ) . More patients showed complete responses with bendamustine than with chlorambucil ( 31 % v 2 % ) . Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil ( P < .0001 ) . Bendamustine was also associated with an improvement in duration of remission , compared with chlorambucil ( median , 21.8 v 8.0 months ) . Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil ( occurring in 40 % v 19 % of patients ) . Severe infections ( grade 3 to 4 ) occurred in 8 % of bendamustine-treated patients and 3 % of chlorambucil-treated patients . CONCLUSION Bendamustine offers significantly greater efficacy than chlorambucil , and a manageable toxicity profile , when used as first-line therapy in patients with advanced CLL PURPOSE We conducted a r and omized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia ( CLL ) . PATIENTS AND METHODS Patients received alemtuzumab ( 30 mg three times per week , for up to 12 weeks ) or chlorambucil ( 40 mg/m(2 ) every 28 days , for up to 12 months ) . The primary end point was progression-free survival ( PFS ) . Secondary end points included overall response rate ( ORR ) , complete response ( CR ) , time to alternative therapy , safety , and overall survival . RESULTS We r and omly assigned 297 patients , 149 to alemtuzumab and 148 to chlorambucil . Alemtuzumab had superior PFS , with a 42 % reduction in risk of progression or death ( hazard ratio [ HR ] = 0.58 ; P = .0001 ) , and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil ( HR = 0.54 ; P = .0001 ) . The ORR was 83 % with alemtuzumab ( 24 % CR ) versus 55 % with chlorambucil ( 2 % CR ) ; differences in ORR and CR were highly statistically significant ( P < .0001 ) . Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil . Adverse events profiles were similar , except for more infusion-related and cytomegalovirus ( CMV ) events with alemtuzumab and more nausea and vomiting with chlorambucil . CMV events had no apparent impact on efficacy . CONCLUSION As first-line treatment for patients with CLL , alemtuzumab demonstrated significantly improved PFS , time to alternative treatment , ORR and CR , and minimal residual disease-negative remissions compared with chlorambucil , with predictable and manageable toxicity Abstract We conducted a r and omized phase III trial to compare the efficacy and safety of two purine analogs , cladribine and fludarabine , with high-dose chlorambucil , in patients with previously untreated chronic lymphocytic leukemia ( CLL ) . Between 1997 and 2004 , 223 patients with CLL were r and omly assigned to cladribine , fludarabine or chlorambucil , for six cycles of therapy with frequent health-related quality of life assessment s. There was no statistical difference for the primary endpoint of overall response with cladribine ( 70 % ) , fludarabine ( 67 % ) and chlorambucil ( 59 % ) , or complete remission ( 12 % , 7 % and 8 % ) , respectively . However , the median progression-free survival ( 25 , 10 , 9 months ) and median time to second treatment ( 40 , 22 , 21 months ) were superior with cladribine . There was no significant difference in overall survival ( 96 , 82 and 91 months ) , nor in toxicity or HRQoL assessment s. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL One hundred and fifty-seven previously untreated stage B or C B-CLL patients were r and omized to treatment with either chlorambucil + prednisolone ( CLBP ) 5 days every 4 weeks or CHOP every 4 weeks . Significantly more patients achieved complete remission on CHOP , but duration of response and survival were equal in the two regimens . Non-responders on CLBP were switched to CHOP , so that finally most patients received nearly the same amount and quality of treatment , which possibly explains the lack of difference in survival . However , compared to previous studies , the study - design ed intensive chemotherapy seems to prolong survival for patients with advanced disease , especially those in stage |
2,609 | 27,342,548 | PAM was less efficacious than clarithromycin-including triple therapies .
However , its efficacy was similar to that of PAC when drugs were administered for 14 days , although ITT cure rates did not reach 90 % .
Use of 14 day , thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate | BACKGROUND Due to clarithromycin resistance , the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low .
It seems reasonable to explore alternative clarithromycin-free therapies .
OBJECTIVES The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor ( PPI ) , amoxicillin and metronidazole ( PAM ) as first-line H. pylori therapy by systematic review and meta- analysis . | Background : Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin ( CLR ) combined with amoxicillin ( AMX ) and a proton pump inhibitor have recently fallen to ⩽80 % because of the increasing incidence of CLR resistance in Japan . This r and omized multicenter trial aim ed to compare the eradication success of 2 first-line triple therapy regimens : rabeprazole , amoxicillin , and clarithromycin ( RAC ) versus rabeprazole , amoxicillin , and metronidazole ( RAM ) . Methods : A total of 124 consecutive patients infected with H. pylori were r and omized into one of two 7-day therapeutic regimens : RAC ( n=60 ) or RAM ( n=64 ) . Eradication was confirmed by the 13C-urea breath test . Adverse effects were also assessed . Results : Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2 % in the RAC group and 90.6%/93.5 % in the RAM group . The eradication rate of RAM therapy was significantly higher than that of RAC therapy . CLR , metronidazole , and AMX resistance was found in 36.2 % , 2.1 % , and 0 % of patients , respectively . In addition , no relevant differences in adverse effects were observed . Conclusions : Metronidazole-based therapy ( RAM ) was superior to st and ard CLR-based therapy ( RAC ) for first-line H. pylori eradication . This reflects the progressive increase in CLR resistance observed in Japan AIM To assess and compare the efficacy and safety of two triple regimes : A ) metronidazole , amoxicillin and omeprazole , which is still widely used in Russia , and B ) azithromycin , amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication . METHODS 100 patients with active duodenal ulcer were included in the open , multicentre , r and omized study with comparative groups . Patients were r and omly assigned to one of the following one-week triple regimes : A ) metronidazole 500 mg bid , amoxicillin 1 g bid and omeprazole 20 mg bid ( OAM , n=50 ) and B ) azithromycin 1 g od for the first 3 days ( total dose 3 g ) , amoxicillin 1 g bid and omeprazole 20 mg bid ( OAA , n=50 ) . Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks . The control endoscopy was performed 8 weeks after the entry . H.pylori infection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test . RESULTS 97 patients completed the study according to the protocol ( 1 patient of the OAM group did not come to the control endoscopy , 2 patients of the OAA group stopped the treatment because of mild allergic urticaria ) . Duodenal ulcers were healed in 48 patients of the OAM group ( 96 % ; CI 90.5 - 100 % ) and in 46 patients of the OAA group ( 92 % ; CI 89.5 - 94.5 % ) ( p = ns ) . H.pylori infection was eradicated in 15 out of 50 patients with OAM ( 30 % ; CI 17 - 43 % ) and in 36 out of 50 patients treated with OAA ( 72 % ; CI 59 - 85 % ) (P<0.001)- ITT analysis . CONCLUSION The triple therapy with omeprazole , amoxicillin and metronidazole failed to eradicate H.pylori in the majority of patients , which is an essential argument to withdraw this regimen out of the national recommendations . Macrolide with amoxicillin are preferable to achieve higher eradication rates . Azithromycin ( 1 g od for the first 3 days ) can be considered as a successful component of the triple PPI-based regimen This study compared high dose ranitidine versus low dose omeprazole with antibiotics for the eradication of H pylori . 80 patients ( mean age 48 years , range 18 - 75 ) who had H pylori infection were r and omised in an investigator-blind manner to either a two-week regime of omeprazole 20 mg daily , amoxycillin 500 mg tid and metronidazole 400 mg tid ( OAM ) , or ranitidine 600 mg bd , amoxycillin 500 mg tid and metronidazole 400 mg tid ( RAM ) , or omeprazole 20 mg daily and clarithromycin 500 mg tid ( OC ) , or omeprazole 20 mg daily and placebo ( OP ) . H pylori was eradicated in 6 of 19 patients in the OAM group ( 32 % ) ; 8 of 18 in the RAM group ( 44 % ) , 4 of 15 in the OC group ( 27 % ) ; none of 18 in the OP group ( 0 % ) . [ < P0.005 for OAM , RAM , OC vs OP ; P = N.S. between OAM , RAM , OC ] . Overall metronidazole resistance was unexpectedly high at 58 % . Eradication rates in metronidazole sensitive patients were 71 % ( 5/7 ) and 100 % ( 3/3 ) for OAM and RAM respectively . In conclusion , H pylori eradication rates using high dose ranitidine plus amoxycillin and metronidazole may be similar to that of low dose omeprazole in combination with the same antibiotics for omeprazole with clarithromycin . Overall eradication rates were low due to a high incidence of metronidazole resistance but were higher in metronidazole-sensitive patients . Even high dose ranitidine with two antibiotics achieves a relatively low eradication rate . These metronidazole-based regimens can not be recommended in areas with a high incidence of metronidazole resistance BACKGROUND & AIMS The currently recommended first-line eradication treatment of Helicobacter pylori in children is usually successful in about 75 % . Recently , in adults , a novel 10-day sequential treatment has achieved an eradication rate of 95 % . The aim of the study was to assess the H pylori eradication rate of the sequential treatment regimen compared with conventional triple therapy in children . METHODS Seventy-eight consecutive children with H pylori infection were r and omized to receive either sequential treatment ( omeprazole plus amoxicillin for 5 days , followed by omeprazole plus clarithromycin plus tinidazole for another 5 days ) ( n = 38 ; 15 boys [ 39.5 % ] ; median age , 11.0 years [ range , 3.3 - 16 years ] ) or triple therapy ( omeprazole , amoxicillin , and metronidazole ) for 1 week ( n = 37 ; 15 boys [ 40.5 % ] ; median age , 9.9 years [ range , 4.3 - 16 years ] ) . H pylori infection was based on 2 out of 3 positive tests results : 13C-urea breath test , rapid urease test , and histologic analysis . Eradication was assessed by 13C-urea breath test 8 weeks after therapy . RESULTS Seventy-four patients completed the study . H pylori eradication was achieved in 36 children receiving sequential treatment ( 97.3 % ; 95 % confidence interval , 86.2 - 99.5 ) and 28 children receiving triple therapy ( 75.7 % ; 95 % confidence interval , 59.8 - 86.7 ) ( P < .02 ) . Compliance with therapy was good ( > 95 % ) in all . CONCLUSIONS Our study shows , for the first time in children , that 10-day sequential treatment achieves a higher eradication rate than st and ard triple therapy , which is consistent with the results of adult studies ABSTRACT Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational , multicenter r and omized clinical trial . Culture was carried out on gastric biopsy sample s obtained from 516 patients at entry and had a sensitivity of 99 % when the [13C]urea breath test was used as a reference . Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test ( Etest ) and for amoxicillin by an agar dilution method only . Resistance to clarithromycin ( > 1 μg/ml ) was found in 3 % of the H. pylori strains , with a perfect correlation between Etest and agar dilution methods . Resistance to metronidazole ( > 8 μl/ml ) was found in 27 % of the strains by agar dilution , but there were important discrepancies between it and the Etest method . No resistance to amoxicillin was found . The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal . The impact of resistance was tested in the four arms of the trial . There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens . For metronidazole-resistant strains , the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added ( 76 % eradication for resistant strains versus 95 % for susceptible strains ) . Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients ( 11.4 % ) after the failure of a clarithromycin-based regimen to effect eradication . The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism . Mutations ( A2142 G and 2143 G ) were found in all strains tested except one . This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments CONTEXT Although chronic Helicobacter pylori infection is associated with gastric cancer , the effect of H pylori treatment on prevention of gastric cancer development in chronic carriers is unknown . OBJECTIVE To determine whether treatment of H pylori infection reduces the incidence of gastric cancer . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , r and omized , placebo-controlled , population -based primary prevention study of 1630 healthy carriers of H pylori infection from Fujian Province , China , recruited in July 1994 and followed up until January 2002 . A total of 988 participants did not have precancerous lesions ( gastric atrophy , intestinal metaplasia , or gastric dysplasia ) on study entry . INTERVENTION Patients were r and omly assigned to receive H pylori eradication treatment : a 2-week course of omeprazole , 20 mg , a combination product of amoxicillin and clavulanate potassium , 750 mg , and metronidazole , 400 mg , all twice daily ( n = 817 ) ; or placebo ( n = 813 ) . MAIN OUTCOME MEASURES The primary outcome measure was incidence of gastric cancer during follow-up , compared between H pylori eradication and placebo groups . The secondary outcome measure was incidence of gastric cancer in patients with or without precancerous lesions , compared between the 2 groups . RESULTS Among the 18 new cases of gastric cancers that developed , no overall reduction was observed in participants who received H pylori eradication treatment ( n = 7 ) compared with those who did not ( n = 11 ) ( P = .33 ) . In a subgroup of patients with no precancerous lesions on presentation , no patient developed gastric cancer during a follow-up of 7.5 years after H pylori eradication treatment compared with those who received placebo ( 0 vs 6 ; P = .02 ) . Smoking ( hazard ratio [ HR ] , 6.2 ; 95 % confidence interval [ CI ] , 2.3 - 16.5 ; P<.001 ) and older age ( HR , 1.10 ; 95 % CI , 1.05 - 1.15 ; P<.001 ) were independent risk factors for the development of gastric cancer in this cohort . CONCLUSIONS We found that the incidence of gastric cancer development at the population level was similar between participants receiving H pylori eradication treatment and those receiving placebo during a period of 7.5 years in a high-risk region of China . In the subgroup of H pylori carriers without precancerous lesions , eradication of H pylori significantly decreased the development of gastric cancer . Further studies to investigate the role of H pylori eradication in participants with precancerous lesions are warranted BACKGROUND Helicobacter pylori eradication with omeprazole , amoxycillin , and metronidazole is both effective and inexpensive . However , eradication rates with different dosages and dosing vary , and data on the impact of resistance are sparse . In this study , three different dosages of omeprazole , amoxycillin , and metronidazole were compared , and the influence of metronidazole resistance on eradication was assessed . METHODS Patients ( n = 394 ) with a positive H. pylori screening test result and endoscopy-proven duodenal ulcer in the past were enrolled into a multicenter study performed in four European countries and Canada . After baseline endoscopy , patients were r and omly assigned to treatment for 1 week with either omeprazole , 20 mg twice daily , plus amoxycillin , 1,000 mg twice daily , plus metronidazole , 400 mg twice daily ( low M ) ; or omeprazole , 40 mg once daily , plus amoxycillin , 500 mg three times daily , plus metronidazole , 400 mg three times daily ( medium M ) ; or omeprazole , 20 mg twice daily , plus amoxycillin , 1,000 mg twice daily , plus metronidazole , 800 mg twice daily ( high M ) . H. pylori status at entry was assessed by a 13C urea breath test and a culture . Eradication was defined as two negative 13C-urea breath test results 4 and 8 weeks after therapy . Susceptibility testing using the agar dilution method was performed at entry and in patients with persistent infection after therapy . RESULTS The eradication rates , in terms of intention to treat ( ITT ) ( population n = 379 ) ( and 95 % confidence interval [ CI ] ) were as follows : low M 76 % ( 68 % , 84 % ) , medium M 76 % ( 68 % , 84 % ) , and high M 83 % ( 75 % , 89 % ) . By per- protocol analysis ( population n = 348 ) , the corresponding eradication rates were : low M 81 % , medium M 80 % , and high M 85 % . No H. pylori strains were found to be resistant to amoxycillin . Pre study resistance of H. pylori strains to metronidazole was found in 72 of 348 ( 21 % ) of the cultures at entry ( range , 10%-39 % in the five countries ) . The overall eradication rate in pre study metronidazole-susceptible strains was 232 of 266 ( 87 % ) and , for resistant strains , it was 41 of 70 ( 57 % ; p < .001 ) . Within each group , the results were as follows ( susceptible/resistant ) : low M , 85%/54 % ; medium M , 86%/50 % ; and high M , 90%/75 % . There were no statistically significant differences among the treatment groups . 23 strains susceptible to metronidazole before treatment were recultured after therapy failed ; 20 of these had now developed resistance . CONCLUSIONS H. pylori eradication rates were similar ( approximately 80 % ) with all three regimens . Metronidazole resistance reduced efficacy ; increasing the dose of metronidazole appeared not to overcome the problem or significantly improve the outcome . Treatment failure was generally associated with either pre study or acquired metronidazole resistance . These findings are of importance when attempting H. pylori eradication in communities with high levels of metronidazole resistance Background —Eradication ofHelicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis . Aim —To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori . Patients —Men or women with H pylori positive duodenal ulceration or gastritis , or both . Methods —A single blind , prospect ively r and omised , parallel group , comparative , multicentre study . After a positive CLO test , patients underwent histology , H pylori culture , and a 13C urea breath test to confirm H pyloristatus . Treatment with one of four regimens : LAC , LAM , LCM , or OAM , where L is 30 mg of lansoprazole twice daily , A is 1 g of amoxycillin twice daily , M is 400 mg of metronidazole twice daily , C is 250 mg of clarithromycin twice daily , and O is 20 mg of omeprazole twice daily , was assigned r and omly . A follow up breath test was done at least 28 days after completing treatment . Results —H pylori eradication ( intention to treat ) was 104/121 ( 86.0 % ) with LAC , 87/131 ( 66.4 % ) with LAM , 103/118 ( 87.3 % ) with LCM , and 94/126 ( 74.6 % ) with OAM . There was a significant difference ( p < 0.001 ) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM , but no significant difference ( p = 0.15 ) between LAM and OAM . Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori . The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori . There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported . Conclusions —All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied . LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori , and was significantly better than LAM and OAM in this group of patients Background Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively . In contrast , only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy . The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial . Objectives To compare the results of two triple-therapy regimens , different only in the antisecretory drugs used , in patients with Helicobacter pylori infection , and to assess the impact of primary resistance to metronidazole on treatment outcome . Methods A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were r and omly assigned to a 2-week course of either : famotidine 40 mg twice a day , amoxycillin 1 g twice a day and tinidazole 500 mg twice a day ( FAT group ; n = 60 ) ; or omeprazole 20 mg twice a day , amoxycillin 1 g twice a day and tinidazole 500 mg twice a day ( OAT group ; n = 60 ) . Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy . H. pylori status was assessed by a biopsy urease test , histology and culture . Results In the intention-to-treat analysis , eradication of H. pylori was achieved in 48 of the 60 patients ( 80 % ; 95 % confidence interval : 70–90 % ) in the FAT group , compared to 50 of the 60 patients ( 83.3 % ; 95 % confidence interval : 74–93 % ) in the OAT group . In the per protocol analysis , eradication therapy was achieved in 48 out of 53 patients ( 90.6 % ; 95 % confidence interval : 83–98 % ) treated with FAT and 50 out of 57 patients ( 87.7 % ; 95 % confidence interval : 79–96 % ) treated with OAT ( not significant ) . The primary metronidazole resistance was present in 28.8 % of strains . Overall , per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3 % and 91.3 % respectively ( P > 0.05 ) . Conclusions Two-week courses of either high-dose famotidine or omeprazole , both combined with amoxycillin and tinidazole , are equally effective for eradication of H. pylori infection . In a 2-week triple therapy , metronidazole resistance has no significant impact on eradication rates ABSTRACT A prospect i ve study was performed with 23 Helicobacter pylori-infected children ( mean age , 9.5 ± 4.4 years ) with clinical symptoms of gastritis and positive results of culture and histologic examination of gastric biopsy specimens to evaluate the influence of antibiotic resistance on eradication . Positive children were treated for 4 weeks with lansoprazole and for 2 weeks with either amoxicillin-metronidazole or spiramycin ( a macrolide)-metronidazole . At endoscopy 1 month after the discontinuation of therapy , the eradication rate and improvement of histologically related gastritis were significantly dependent on the susceptibility or the resistance of the infecting organism to metronidazole ( 83 versus 17 % and 88 versus 16.6 % , respectively ) . Pretreatment determination of the susceptibility is appropriate in any anti-H. pylori regimen , including one with metronidazole BACKGROUND Clarithromycin-resistant Helicobacter pylori is associated with point mutations in the 23S ribosomal RNA ( rRNA ) gene . METHODS A total of 1232 patients participated and were divided into 2 control groups and 1 case group . Patients in the APC control group , which consisted of 308 r and omly assigned participants , were treated with st and ard triple therapy , consisting of amoxicillin , rabeprazole , and clarithromycin ; 308 participants in the APM control group were treated with amoxicillin , rabeprazole , and metronidazole . For the 616 participants in the case group , a test for point mutations in the 23S rRNA gene of H. pylori was conducted . A total of 218 individuals in the case group received a new tailored therapy regimen , in which amoxicillin , rabeprazole , and clarithromycin were given in the absence of a mutation , whereas clarithromycin was replaced by metronidazole if the mutation was detected . RESULTS The rate of eradication of H. pylori in the tailored group was 91.2 % ( 176/193 ) , which was significantly higher than that in the APC ( 75.9 % [ 214/282 ] ; P < .001 ) and APM ( 79.1 % [ 219/277 ] ; P < .001 ) control groups . CONCLUSION The rate of H. pylori eradication among patients who received tailored therapy on the basis of detection of a clarithromycin resistance mutation by polymerase chain reaction was much higher than the rate among patients who received a st and ard triple therapy regimen . CLINICAL TRIALS REGISTRATION NCT0145303 Objectives : Rabeprazole is a new fast acting proton pump inhibitor that has recently been proven to be effective in the treatment of peptic ulceration and reflux esophagitis . The aim of this study was to evaluate rabeprazole in combination with antibiotics for the eradication of Helicobacter pylori ( H. pylori ) in patients with chronic active gastritis with or without peptic ulcer disease . Methods : Seventy-five H. pylori-infected patients were r and omized in a double-blind fashion to receive a 7-day treatment regimen consisting of : RAC , RAM , RCM , or RC ( R = rabeprazole 20 mg b.d . , A = amoxycillin 1 g b.d . , C = clarithromycin 500 mg b.d . , M = metronidazole 400 mg b.d . ) . R and omized patients were H. pylori-positive by gastric biopsy urease test , histology and 13C urea breath test ( 13C-UBT ) . H. pylori eradication was assessed by 13C-UBT , 4 and 8 wk after finishing treatment . Endoscopy with histology and culture for antibiotic sensitivity testing was performed pretreatment and if treatment failed . Results : On an intention-to-treat analysis , treatment success was : RCM 100 % , RAC 95 % , RAM 90 % , and RC 63 % . The most common side effects were loose stools , headache , and taste disturbance , but there were no serious adverse events related to the study medication . The two patients failing RAM treatment had metronidazole-resistant strains before and after treatment . None of the pretreatment H. pylori isolates from six patients failing RC were clarithromycin resistant , but three of five successfully cultured posttreatment had developed clarithromycin resistance . Conclusion : Rabeprazole-based triple therapy with two antibiotics for 1 wk is safe and effective in eradicating H. pylori . Dual therapy with clarithromycin is less successful , and the majority of treatment failures develop clarithromycin resistance BACKGROUND To evaluate whether antral biopsies are enough for confirming Helicobacter pylori eradication with the " new " one week triple therapies with omeprazole . PATIENTS AND METHODS 229 duodenal ulcer patients were treated with omeprazole for 7 days plus two antibiotics . Eradication was confirmed with histology ( two biopsies from both gastric antrum and body ) and 13C-urea breath test one month after the end of therapy . RESULTS H. pylori eradication was achieved in 76.9 % of the patients ( 95 % CI : 71 - 82 % ) . Histology at antrum was highly reliable to detect eradication failure : in all but in one case in which H. pylori was observed at gastric body , was the microogranism also observed at antrum . Infection prevalences at both locations were not homogeneous ( McNemar : 6.4 ; p < 0.05 ) . Concordance between antral biopsies and breath test for H. pylori diagnosis after therapy was excellent ( kappa : 0.91 ; SE : 0.07 ) , and both prevalences were homogeneous ( McNemar : 1.3 ; p > 0.05 ) . CONCLUSIONS Taking antral biopsies is enough for confirming H. pylori eradication with the " new " one week triple therapies BACKGROUND Lafutidine is an H2-receptor antagonist with gastroprotective action through capsaicin-sensitive afferent neurons and relatively inexpensive compare to proton-pump inhibitors ( PPIs ) . A 7-day course of PPIs-amoxicillin-metronidazole is recommended as st and ard second-line Helicobacter pylori therapy and is covered by national health insurance in Japan . The aim of this study was to determine the efficacy and safety of second-line eradication using the H2-receptor antagonist lafutidine as a substitute for a PPI . MATERIAL S AND METHODS Fifty-two patients who failed in first-line eradication using PPI-amoxicillin-clarithromycin were r and omly assigned to a 7-day course of rabeprazole at 10 mg b.i.d . , amoxicillin at 750 mg b.i.d . , and metronidazole at 250 mg b.i.d . ( RPZ-AM ) or a 7-day course of lafutidine at 10 mg t.i.d . , amoxicillin at 750 mg b.i.d . , and metronidazole at 250 mg b.i.d . ( LFT-AM ) as second-line therapy . Eradication was assessed by the ( 13 ) C urea breath test . A drug susceptibility test was performed before the second-line therapy . RESULTS Prior to second-line H. pylori eradication , the rate of resistance to clarithromycin was 86.5 % and the rate of resistance to metronidazole was 3.8 % . The eradication rates for both LFT-AM and RPZ-AM groups were 96 % ( 95%CI = 88.6 - 100 % ) . There were no severe adverse events in either group . CONCLUSIONS Lafutidine plus metronidazole-amoxicillin as second-line therapy provided a high eradication rate and safe treatment similar to a PPI-based regimen . Lafutidine-based eradication therapy is therefore considered to be a promising alternative and is also expected to reduce health care costs in H. pylori eradication BACKGROUND It is known that at least 90 % of duodenal ulcers are caused by infection with the bacterium Helicobacter pylori . Eradicating this organism usually results in complete resolution of the disease . Testing for H pylori was introduced relatively recently , and thus , many patients known to have uncomplicated peptic ulcer disease who continue to need long-term treatment with ulcer-healing drugs have never been tested for the infection or offered eradication therapy . In modern computerized practice s , this subgroup of patients can readily be identified by reference to morbidity and repeat prescribing data . Eradication of H pylori infection in this group of patients has great potential benefit for the individuals concerned as well as cost-saving benefit for the National Health Service . AIM The aim of this prospect i ve study was to determine whether it is worthwhile screening for and treating H pylori infection in patients in a general practice population with previously diagnosed duodenal ulcer disease taking ulcer-healing drugs long term . METHOD In 1994 , in a practice of 7100 patients , morbidity and repeat prescribing data were used to identify 40 patients ( 0.6 % ) with proven duodenal ulcer disease taking ulcer-healing medication long term and with uncertain H pylori status . Twenty-nine of the 40 subjects agreed to undergo serology testing for H pylori antibodies . Of 20 ( 69 % ) who were positive , 18 ( eight women , median age 63.8 years ) were given eradication therapy . Seventeen patients received omeprazole 40 mg once daily and amoxycillin 500 mg three times daily for 14 days with metronidazole 400 mg three times daily for the first 7 days ; for the remaining patient metronidazole was inadvertently omitted . [13C]Urea breath testing was carried out at the local hospital at least one month after therapy to determine whether eradication treatment had been successful . Subjects were also personally followed up by telephone after 1 and 4 months to assess the success of treatment subjectively . RESULTS [13C]Urea breath testing showed that H pylori eradication was successful in all 17 patients ( 100 % ) who received the intended eradication regimen . Helicobacter pylori was not eradicated in the patient who received only omeprazole and amoxycillin . Four months after successful H pylori eradication , 13 of the 17 ( 76 % ) patients remained completely asymptomatic . Two of the four patients who had some recurrent dyspepsia had known gastro-oesophageal reflux and their ongoing symptoms after eradication therapy seemed , on close question ing , to be more attributable to this than to duodenal ulcer disease . CONCLUSION Testing for and eradication of H pylori is worthwhile in general practice in those patients with previous proven duodenal ulceration who need long-term ulcer-healing medication . The high rate of eradication of H pylori achieved with the regimen used in this study compares very favourably with that of other treatment regimens . However , in patients with duodenal ulcers there may be coexisting pathology , and H pylori eradication does not necessarily result in complete disappearance of dyspeptic symptoms . Thus , when monitoring the outcome of treatment it is important to assess improvement of symptoms as well as objective evidence of eradication Objectives Helicobacter pylori ( H. pylori ) cure rates vary in different geographical regions because of differences in hosts as well as in H. pylori strains . In this study we evaluated the efficacy of different treatment regimens for eradication of H. pylori infection in children , in order to select a treatment regimen that is most effective with the least adverse effects and cost . Method Through a r and omized clinical trial study we enrolled 120 pediatric patients ( age ≤ 18 years ) with H. pylori infection confirmed through histopathological examination of their upper endoscopic findings and positive rapid urease test . Patients were r and omized into three groups : group A received omeprazole , amoxicillin , metronidazole , and bismuth subcitrate ; group B received omeprazole , amoxicillin , and clarithromycin ; and group C the most recent regime of omeprazole , amoxicillin-clavulanic acid , and metronidazole . Subjects were followed 6 weeks after completing the antimicrobial therapy and H. pylori eradication was assessed with urea breath test . Results A total of 117 patients with a mean age of 12 ± 4 years completed the study . Eradication rate was 91.9 % in group A , compared with 82.1 % in group B , and 80.5 % in group C ( P = 0.33 ) . Conclusion Considering these data we suggest quadruple therapy as the first line of therapy for eradication of H. pylori infection in children in our geographic area ( Iran ) Metronidazole remains a key component of H. pylori infection therapy . It has been suggested that despite resistance , metronidazole may be effective when given at high dose with bismuth , tetracycline , and a proton pump inhibitor ( quadruple therapy ) The efficacy of omeprazole‐based eradication therapies has been determined mostly in population s with low to moderate prevalence of metronidazole resistant Helicobacter pylori , yet resistance is high in many regions Background : There is currently no optimal second‐line treatment after failure of Helicobacter pylori triple therapy AIM To test the eradication rate of Helicobacter pylori by ranitidine bismuth citrate-based triple therapy , and evaluate the symptomatic response of Helicobacter pylori eradication therapy for non-ulcer dyspepsia . METHODS A total of 59 consecutive Helicobacter pylori infected non-ulcer dyspepsia patients were r and omly selected to receive either one of two triple therapy regimens , including metronidazole , amoxycillin plus ranitidine bismuth citrate ( RAM group ) or omeprazole ( OAM group ) . To determine the success of eradication , patients underwent the 13C-urea breath test , 6 weeks and one year after treatment . The dyspeptic symptom scores were also assessed at the time of enrolment , 6 weeks and one year after treatment . RESULTS Per- protocol and intention-to-treat eradication rates were 77.7 % and 70 % in RAM group and 83.8 % and 68.9 % in OAM group ( p = non significant ) . At both the 6th week and at the first year after treatment , the mean symptom scores were lower than pre-treatment scores in the study population , regardless of whether treatment was successful or not . However , patients , whether eradicated successfully or not-eradicated , presented similar 6-week and 1-year scores . CONCLUSIONS One-week RAM triple therapy , which is cheaper than the OAM regimen , is a relatively effective alternative regimen for Helicobacter pylori eradication in Taiwanese . Triple therapy for Helicobacter pylori eradication was not the whole management for the relief of dyspeptic symptoms of non-ulcer dyspepsia patients BACKGROUND Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease , and eradication rates of more than 90 % have been reported , using omeprazole in combination with two antimicrobials . The choice of antimicrobials , dose regimen and duration of treatment have varied between studies , however , and an optimal treatment still has to be established . MATERIAL S AND METHODS We conducted an international , r and omized , double-blind , placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada , Germany , Irel and , Sweden , and the United Kingdom . Patients ( n = 787 ) with proved duodenal ulcer disease were r and omized to treatment twice daily for 1 week with omeprazole , 20 mg ( O ) , plus either placebo ( P ) or combinations of two of the following antimicrobials : amoxicillin , 1 gm ( A ) , clarithromycin , 250 or 500 mg ( C250 , C500 ) , or metronidazole , 400 mg ( M ) . Eradication of H. pylori was evaluated by 13C-UBT , performed before and 4 weeks after treatment cessation . RESULTS The eradication rates for the all- patients -treated analysis were 96 % , OAC500 ; 95 % , OMC250 ; 90 % , OMC500 ; 84 % , OAC250 ; 79 % , OAM ; and 1 % , OP . OAC500 and OMC250 achieved eradication rates with lower 95 % confidence interval limits exceeding 90 % . All regimens were well-tolerated , 96 % of patients complied with their dose regimen , and 2.3 % of the patients discontinued treatment owing to adverse events . CONCLUSIONS Omeprazole triple therapies given twice daily for 1 week produce high eradication rates , are well-tolerated , and are associated with high patient compliance . The two most effective therapies were those combining omeprazole , 20 mg , with either amoxicillin , 1 gm , plus clarithromycin , 500 mg , or metronidazole , 400 mg , plus clarithromycin , 250 mg , all given twice daily Introduction : A triple therapy consisting of proton pump inhibitor , amoxicillin and metronidazole or tetracycline has been recommended as the second-line regimen for Helicobacter pylori eradication if bismuth is not available . This study compared the efficacy of esomeprazole/amoxicillin/levofloxacin ( EAL ) and esomeprazole/amoxicillin/metronidazole ( EAM ) as second-line therapy for H pylori eradication . Methods : From April 2008 to September 2009 , 90 patients who failed H pylori eradication using the st and ard triple therapy were r and omized to receive either EAL ( 40 mg esomeprazole twice daily , 1 g amoxicillin twice daily and 500 mg levofloxacin once daily for 7 days ) or EAM ( 40 mg esomeprazole twice daily , 1 g amoxicillin twice daily and 250 mg metronidazole 4 times daily for 14 days ) . The primary outcome variables were the rates of eradication , adverse events and compliance . Results : Our results demonstrated no differences in the eradication rates of the EAL and EAM groups in intention-to-treat analysis ( 68.9 % versus 84.4 % , respectively , P = 0.134 ) and per- protocol analysis ( 75.6 % versus 88.4 % , respectively , P = 0.160 ) . Both groups exhibited similar drug compliance ( EAL 95.6 % versus EAM 100 % , P = 0.494 ) and adverse events ( EAL 13.3 % versus EAM 8.9 % , P = 0.739 ) . Conclusions : The 14-day EAM regimen was not inferior to the 7-day EAL regimen for second-line anti-H Pylori therapy in Taiwan . It may be an option in hospitals where bismuth salts are not available . However , regional metronidazole resistance rate and extended length of levofloxacin-base therapy should be considered BACKGROUND AND AIM The purpose of this study was to compare the efficacy of tinidazole- versus clarithromycin-based triple regimens for eradication of Helicobacter pylori in North Indian patients of peptic ulcer disease , and to correlate the outcome with in vitro antibiotic susceptibility . METHODS One hundred and forty-six H. pylori-infected patients with active ulcer were included in the prospect i ve , r and omized study . A total of 70 patients received lansoprazole 30 mg b.d . , amoxycillin 1000 mg b.d . and tinidazole 500 mg b.d . ( LAT ) , and 76 patients received lansoprazole 30 mg b.d . , amoxycillin 1000 mg b.d . and clarithromycin 500 mg b.d . ( LAC ) for 14 days . The H. pylori status was assessed by urea breath test , rapid urease test , and histology and antibiotic sensitivity pattern by Epsilometer test . RESULTS In per- protocol analysis of 112 patients the H. pylori eradication rate was 42.3 % ( 95 % confidence interval ( CI ) : 0.29 - 0.56 ) in LAT , and 64.8 % ( 95%CI : 0.52 - 0.78 ) in LAC ( 95%CI of difference of proportions : 0.13 - 0.33 , P = 0.01 ) . Ulcer healed in 69.2 % in the LAT group ( 95%CI : 0.57 - 0.82 ) and 81.7 % in the LAC group ( 95%CI : 0.72 - 0.92 ; P = 0.02 ) . Antibiotic susceptibility testing was done in 31 patients . Metronidazole resistance was present in 41.9 % isolates but was unrelated to the outcome of the LAT regimen . CONCLUSION Imidazole-based eradication regimens should be ab and oned in North India regardless of in vitro susceptibility results Background s and Aims Development of safe and effective rescue regimens for eradication failure of Helicobacter pylori infection by st and ard regimens is an urgent task . We design ed the prospect i ve study to compare the efficacy of two rescue regimens after eradication failure by the st and ard triple therapy . Methods One hundred and thirty-two patients in whom eradication of H. pylori infection failed initial triple therapy with lansoprazole 30 mg b.i.d , amoxicillin 750 mg b.i.d . and clarithromycin 400 mg b.i.d . for 1 week were r and omized to either the 1–week triple therapy with rabeprazole 10 mg b.i.d . , amoxicillin 750 mg b.i.d . , and metronidazole 250 mg b.i.d . ( RAM ) or the 2–week dual therapy with rabeprazole 10 mg q.i.d . and amoxicillin 500 mg q.i.d . ( RA ) . Eradication of H. pylori was judged by 13C-urea breath test 1 month later . Results The intention-to-treat and per- protocol -based eradication rates were 92.4 % ( 95 % CI : 83.2–97.5 ) and 95.3 % ( 95 % CI : 86.9–99.0 ) for the RAM therapy and 90.9 % ( 95 % CI : 81.2–96.6 ) and 93.8 % ( 95 % CI : 84.8–98.3 ) , respectively , for the RA therapy ( P > 0.2 for both ) . No clinical ly recognizable adverse events were observed with either regimen . Conclusion RA as well as RAM therapy are safe and effective rescue regimens for H. pylori infection after eradication failure by the st and ard triple therapy Background Besides antibiotics , additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori . Objective To assess the significance of acid suppression and , in particular , treatment with proton pump inhibitors ( PPIs ) compared with H2 receptor antagonists ( H2 RAs ) . The primary target parameter for the study was H. pylori eradication . In addition , the ulcer healing rate , speed of pain reduction , score for gastritis in the antrum and gastric body , and rate of side effects were recorded . Design R and omized , double-blinded , multicentre study . Participants A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study . Methods Using a r and omization list , patients were assigned either to a treatment group receiving omeprazole 40 mg once daily , amoxycillin 750 mg three times a day , and metronidazole 500 mg three times a day ( OAM ) , or to a group receiving ranitidine 300 mg once daily , amoxycillin 750 mg three times a day , and metronidazole 500 mg three times a day ( RAM ) . The treatment period was 7 days in both groups . Long-term acid-suppressant treatment was not given . Results The eradication rate was 87.1 % ( 169/194 , intention to treat [ ITT ] ) in the OAM group and 77 % ( 137/178 , ITT ) in the RAM group . The difference of 10.1 % ( 95 % CI 2.5–18 % ) is statistically significant ( P = 0.0104 ) . The ulcer healing rate was 93.3 % in the OAM group ( 181/194 , ITT ) and 92.1 % in the RAM group ( 164/178 , ITT , NS ) . With regard to the speed and intensity of pain reduction , the OAM group was superior to the RAM group . In patients in whom H. pylori eradication was successful , the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication . In the OAM group , 39.1 % of the patients ( n = 90 ) reported one or more side effects , compared with 44.7 % ( n = 101 ) in the RAM group ( P = 1.5449 , NS ) . Conclusion Omeprazole ( 40 mg once daily in the morning ) is significantly more effective than ranitidine ( 300 mg once daily in the morning ) with respect to H. pylori eradication when used together with amoxycillin ( 750 mg three times a day ) and metronidazole ( 500 mg three times a day ) for a 7-day treatment period BACKGROUND Although primary resistance to metronidazole remains high ( 56,8 % ) , it is more widely used than clarithromycin as a firstline Helicobacter pylori ( H. pylori ) treatment in the common Tunisian practice . AIM To compare the eradication rate in two protocol s including clarithromycin versus metronidazole in Tunisian adults . METHODS From July 2005 to December 2007 , 85 patients aged 18 to 75 years presenting with gastro-duodenal lesions with H. pylori infection and requiring its eradication were included in the study . They were r and omized to receive alternatively a seven-day triple therapy including : Omeprazole + Amoxicillin + Clarithromycin ( OAC group ) or Metronidazole ( OAM group ) twice a day . A second endoscopy with new biopsies was carried out 6 weeks after treatment to control eradication . RESULTS Eighty five patients finished the protocol . The OAC and OAM groups included 46 and 39 patients respectively . They were comparable with respect to age , gender , clinical presentation and initial lesions . The total eradication rate was 60 % . It was significantly higher in the clarithromycin group ( 69.6 % ) than in the metronidazole group ( 48.7 % ) : p < 0.05 . CONCLUSION Clarithromycin is more effective than metronidazole in H. pylori eradication . It should be made available in our hospital 's nomenclature . This would prevent iterative eradication courses and probably reduce treatment cost BACKGROUND The object of the study was to study the efficacy and safety of furazolidone and tetracycline compared to metronidazole and amoxicillin in an omeprazole based triple therapy in a prospect i ve r and omized-blind- clinical trial . MATERIAL / METHODS Patients with endoscopically verified active duodenal ulcer disease in the presence of Helicobacter pylori infection were eligible to enter the study . Endoscopy was performed a day before and 6 - 8 weeks after the cessation of treatment . H. pylori status was assessed by histologic examination ( Giemsa stain ) of biopsy specimens were taken from the antrum and corpus . H. pylori eradication was defined as absence in histology of the biopsy specimens at the second endoscopy . Ulcer healing was considered as decrease in ulcer size to less than 20 % of its primary size . Patients were r and omly assigned to receive omeprazole 20 mg , amoxicillin 1000 mg and metronidazole 500 mg ( OAM group ) or omeprazole 20 mg , tetracycline 500 mg and furazolidone 200 mg ( OTF group ) . All medications were taken twice daily , for 2 weeks . RESULTS Out of 111 patients enrolled in the study , 108 completed a course of treatment and underwent a follow-up endoscopy , with 54 patients in each group . H. pylori eradication was achieved in 52 patients ( 96.3 % - 95 % CI : 91.27 - 100 ) in OTF group and 45 patients ( 83.3 % - 95 % CI : 73.35 - 93.25 ) in OAM group ( P=0.015 ) . Our study showed the superiority of OTF vs. OAM regimen with a 13 % increment in eradication rate , with only occasional severe side effect . CONCLUSIONS In conclusion OTF regimen is a safe , cheaper and effective alternative for OTF regimen and we recommend it to be used especially in developing countries BACKGROUND / AIMS To test the hypothesis of equivalence of an omeprazole 7-day triple therapy without subsequent acid suppression and a historical ranitidine 12-day triple therapy ( recruiting phase 1989 - 91 ) with subsequent acid suppression in their effect on the eradication of Helicobacter pylori ( H. pylori ) and the healing of duodenal ulcer . METHODOLOGY Seventy-seven patients with H. pylori-positive duodenal ulcers received a 7-day treatment with amoxicillin 750 mg tid and metronidazole 500 mg tid . Additional omeprazole 20 mg or 40 mg once daily was given to 39 and 38 of the patients , respectively . Endoscopy was performed before treatment and four weeks after cessation of therapy . RESULTS The cumulative intention-to-treat ( ITT ) H. pylori-eradication rate was 66 % ( 51/77 ) as compared to 89 % ( 46/52 ) for the historical control ( p < 0.05 ) . The corresponding ulcer healing rates were 90 % ( 69/77 ) and 92 % ( 48/52 ) . Primary metronidazole resistance ( PMR ) had escalated from 10 % to 27 % within 6 years result ing in eradication rates of 84 % for sensitive and 19 % for resistant strains ( p < 0.001 ) . PMR could be demonstrated in 45 % of all female , but only in 17 % of the male patients ( p < 0.05 ) . In the patients with H. pylori eradication , the ulcers healed in 98 % ( 50/51 ) as compared to 73 % ( 19/26 ) in those with persistent infection ( p < 0.005 ) . Analysis based on the presence of PMR showed ulcer healing rates of 95 % ( 53/56 ) for sensitive and 76 % ( 16/21 ) for resistant strains ( p < 0.05 ) . Improvement of pain also showed a significant correlation with successful eradication . H. pylori-eradication , healing and symptom relief were similar in the omeprazole 20 mg and 40 mg groups . CONCLUSIONS The effect of amoxicillin plus metronidazole plus antisecretory agent on the eradication of H. pylori has decreased markedly during the past 6 years due to the escalation of PMR . Doubling of the omeprazole dose does not affect outcome . Cure of the infection as well as metronidazole susceptibility enhance duodenal ulcer healing and symptom relief . Acid suppression following a successful 1-week anti-HP therapy is not required for duodenal ulcer treatment BACKGROUND Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract , and increasing antibiotic resistance has made alternative treatments necessary . Our aim was to assess the efficacy and safety of a new , single-capsule treatment versus the gold st and ard for H pylori eradication . METHODS We did a r and omised , open-label , non-inferiority , phase 3 trial in 39 sites in Europe , comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium , metronidazole , and tetracycline ( quadruple therapy ) versus 7 days of omeprazole , amoxicillin , and clarithromycin ( st and ard therapy ) in adults with recorded H pylori infection . Patients were r and omly assigned treatment according to a predetermined list independently generated by Quintiles Canada ( Ville St-Laurent , QC , Canada ) . Our study was design ed as a non-inferiority trial but was powered to detect superiority . Our primary outcome was H pylori eradication , established by two negative (13)C urea breath tests at a minimum of 28 and 56 days after the end of treatment . Our assessment for non-inferiority was in the per- protocol population , with subsequent assessment for superiority in the intention-to-treat population ( ie , all participants r and omly assigned treatment ) . This study is registered with Clinical Trials.gov , number NCT00669955 . FINDINGS 12 participants were lost to follow-up and 101 were excluded from the per- protocol analysis . In the per- protocol population ( n=339 ) , the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10 % ( 95 % CI 15·1 - 32·3 ; p<0·0001 ) . In the intention-to-treat population ( n=440 ) , eradication rates were 80 % ( 174 of 218 participants ) in the quadruple therapy group versus 55 % ( 123 of 222 ) in the st and ard therapy group ( p<0·0001 ) . Safety profiles for both treatments were similar ; main adverse events were gastrointestinal and CNS disorders . INTERPRETATION Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori , especially since quadruple therapy provides superior eradication with similar safety and tolerability to st and ard therapy . FUNDING Axcan Pharma : To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer , and to assess healing and relapse of gastric ulcer BACKGROUND Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers , disregarding effects on dyspeptic and reflux symptoms . Profound acid inhibition with a proton pump inhibitor is the gold st and ard therapy in acid-related diseases . We aim ed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition . METHODS Patients with active duodenal ulcer were r and omized either to omeprazole , 20 mg twice daily until healing , followed by omeprazole , 20 mg/ day for 1 year , or to eradication therapy ( metronidazole , amoxicillin , and omeprazole for 2 weeks ) followed by placebo for 1 year . All patients were followed up passively for an additional year . Clinical controls were performed every 2 months the 1st year ( maintenance phase ) and every 6 months during the passive follow-up phase . The study was multicentric and double-blind . The primary end-point was discontinuation of treatment , irrespective of reason . RESULTS Two hundred and seventy-six patients were r and omized ( 139 in the eradication treatment group ) . In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal . In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer , compared with 51 patients initially r and omized to long-term omeprazole . There were no differences in reflux symptoms or in the development of reflux oesophagitis . CONCLUSIONS Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers . One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period . Eradication therapy does not increase the risk of reflux in ulcer patients Abstract Background : Much has been published on the efficacy and cost effectiveness of Helicobacter pylori eradication treatment as an alternative to histamine H2-receptor antagonist maintenance treatment in peptic ulcer disease . However , most studies have analysed and emphasised H. pylori eradication rates rather than management/control of symptoms and the associated cost savings . Although H. pylori eradication therapy is very successful in clearing the infection , dyspeptic symptoms may persist and management of these can be expensive . Objective : The aim of this study was to assess the cost implication s in controlling symptoms using either H2-receptor antagonist maintenance therapy or H. pylori eradication therapy in patients with duodenal ulcer disease . Design : This was a non-blind , prospect i ve , r and omised , parallel-group study comparing maintenance H2-receptor antagonist treatment using ranitidine with H. pylori eradication therapy , with a 1-year follow-up . Setting : This was a study of out patients from general practice s in Dundee , Scotl and , or the Ninewells Hospital , Dundee , gastroenterology clinic . Patients and participants : 119 patients with confirmed duodenal ulcer , free from active ulceration at study entry but positive for H. pylori infection , who were receiving maintenance H2-receptor antagonist therapy . Interventions : Patients were r and omised to receive either continuing maintenance therapy with ranitidine ( initially 150 mg daily ; 58 patients ) or H. pylori eradication therapy using an omeprazole/amoxicillin/metronidazole regimen ( or omeprazole/clarithromycin if allergic to penicillin ) . Main outcome measures and results : Overall , H. pylori eradication rates were 100 % per protocol and 95.1 % intention-to-treat . At completion of 1 year of follow-up , 12 of the 61 ( 19.7 % ) patients successfully eradicated of H. pylori were still dependent on acid suppression for symptom relief . H. pylori eradication treatment was the least-cost strategy in managing/controlling symptoms at 1 year ( £ 168 vs £ 210 per patient ; 1996 values ) . However , over time , post-eradication treatment costs were greater than H2-receptor antagonist therapy costs . Any potential savings were directly related to the proportion of patients needing further treatment post-eradication , the cost of endoscopy and the urea breath test . Conclusions : If dyspepsia persists long term , H. pylori eradication treatment may not be the least-cost option for patients with duodenal ulcer We evaluated eradication of Helicobacter pylori infection in 263 patients by a new 14-day regimen of omeprazole 40 mg mane ( a gastric secretory inhibitor ) plus two antibiotics : amoxycillin 500 mg three-times daily ( tds ) plus metronidazole 400 mg tds . The comparative groups included up date d results of our previous work with a 14-day course of either st and ard triple therapy ( STT , colloidal bismuth subcitrate 120 mg four times daily ( qds ) plus tetracycline 500 mg qds and metronidazole 400 mg tds ) , omeprazole 40 mg once daily plus amoxycillin 500 mg tds ( OA ) , or two modified triple therapy : either Borody 's ( BTT ) of all three components ( colloidal bismuth subcitrate 120 mg , tetracycline 500 mg , metronidazole 200 mg ) qds instead of tds , or Logan 's ( LTT ) seven-day therapeutic regimen of colloidal bismuth subcitrate 120 mg qds , amoxycillin 500 mg qds and , for the last three days , metronidazole 400 mg five times daily . Omeprazole/amoxycillin/metronidazole ( OAM ) therapy was better tolerated than STT ( course completion 98.1 % vs. 81.4 % , p < 0.001 ) . H. pylori was eradicated by OAM therapy in 53/55 ( 96.4 % ) patients with metronidazole-sensitive organisms and in 54/72 ( 75.0 % ) with metronidazole-resistant isolates ( p < 0.01 ) . The respective corresponding rates for STT and OA therapy were 20/22 ( 90.9 % ) and 14/29 ( 48.3 % ) , ( metronidazole-sensitive organisms ) and 7/21 ( 33.3 % ) and 15/31 ( 48.4 % ) ( infections resistant to metronidazole ) . BTT and LTT were also better tolerated than STT . The eradication rate for BTT was 23/26 ( 88.5 % ) but that for LTT , the best tolerated of the five treatment regimens , was only 19/28 ( 67.9 % ) when pretreatment isolates were metronidazole-sensitive . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan . The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor . MATERIAL S AND METHODS Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were r and omly assigned to either second-line therapy including metronidazole : a 7-day course of lansoprazole 30 mg , amoxicillin 750 mg , and metronidazole 250 mg , b.i.d . ( lansoprazole group ) ; or a 7-day course of famotidine 40 mg , amoxicillin 750 mg , and metronidazole 250 mg , b.i.d . ( famotidine group ) . Eradication was assessed for each group at least 4 weeks after completing eradication therapy . Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin , metronidazole , and amoxicillin . RESULTS Prior to second-line H. pylori eradication , the rate of resistance to clarithromycin was high at 84 % ( 48/57 ) . Similarly , resistance to metronidazole was low at 5.3 % ( 3/57 ) ; however , no amoxicillin-resistant strains were found . The eradication rates for both lansoprazole and famotidine treatment groups were high at 97 % ( 29/30 ) and 94 % ( 29/31 ) , respectively . CONCLUSIONS Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy . Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy , an economic benefit in terms of reduced health-care costs is also anticipated OBJECTIVES To compare the efficacy and side effects of st and ard bismuth triple therapy with those of omeprazole-based triple therapy in patients with Helicobacter pylori infection and duodenal ulcer disease . METHODS One hundred patients were prospect ively recruited and r and omized to receive either bismuth subnitrate 75 mg q.i.d . , oxytetracycline 500 mg q.i.d . , and metronidazole 400 mg b.i.d . ( regimen BTM ) , or omeprazole 20 mg b.i.d . , amoxicillin 750 mg b.i.d . , and metronidazole 400 mg b.i.d . ( regimen OAM ) , both for 14 days . Upper endoscopy ( with antral biopsy specimens for microbiology and antral and corpus biopsy specimens for histology ) was performed before treatment , after 2 months , and again 1 yr after treatment . Serum sample s for serology ( IgG ) were taken . Patients with in vitro metronidazole-resistant ( M-R ) H. pylori strains were excluded . In a nonr and omized study , 41 patients with M-R strains were given either BTM or OAM . RESULTS According to intention-to-treat analysis , H. pylori cure rates were 91 % and 96 % with BTM and OAM , respectively ( p = 0.45 ) . In the BTM group , the mean total side effect score was higher ( p < 0.001 ) , and more severe side effects were reported ( 32 % vs. 4 % , p < 0.001 ) . In the nonr and omized group of patients with M-R strains , H. pylori cure rates were 88 % and 67 % with BTM and OAM , respectively . All of the successfully treated patients were still H. pylori-negative after 1 yr . CONCLUSIONS Both treatment regimens were highly effective in curing H. pylori infection in patients with metronidazole-sensitive strains . Omeprazole-based triple therapy was tolerated better than st and ard bismuth-based triple therapy Fourteen patients with Helicobacter pylori infection were treated with 20 mg omeprazole , 1 g amoxycillin and 400 mg metronidazole bd for 7 days ( OAM ) , and 16 patients were treated with 20 mg omeprazole , 250 mg clarithromycin and 400 mg metronidazole bd for 7 days ( OCM ) . Saliva , gastric biopsies and faecal sample s were collected before , during ( day 7 ) and 4 weeks after treatment in order to analyse alterations of the normal microflora and to determine antimicrobial susceptibility . Both treatment regimens result ed in marked quantitative and qualitative alterations . A selection of resistant streptococcal strains were noticed in both treatment groups , most apparent in the OCM group where a shift from susceptible to resistant strains was recorded . In the OAM group , six patients had overgrowth of resistant enterobacteriaceae during treatment compared with none in the OCM group , in the gastric microflora . The MICs for Enterococcus spp . and Enterobacteriaceae in faeces increased significantly during treatment in both groups . Nine patients in the OAM group became intestinally colonized by yeasts during treatment . The total anaerobic microflora was strongly suppressed in both treatment groups , although most pronounced in the OCM group , where the frequency of clarithromycin-resistant bacteroides strains increased from 2 to 76 % during treatment , and remained at 59 % 4 weeks post-treatment . Even if the treatment outcome was better in the OCM group ( 100 % ) than in the OAM group ( 71 % ) , the amoxycillin-based treatment might be preferable from an ecological point of view , since the qualitative alterations in terms of emergence and persistence of resistant strains seemed to be most pronounced in the clarithromycin-treated group Primary and acquired resistance to antibiotics is an important factor in determining the reason for treatment failure in Helicobacter pylori infection . We examined the relationship between the susceptibility of H. pylori isolates and the efficacy of chemotherapy OBJECTIVE : The aim of this study was to compare cure rates of Helicobacter pylori ( H. pylori ) infection , compliance , and side effects in patients given 10 days of omeprazole 20 mg b.d . , amoxycillin 500 mg t.d.s . , and metronidazole 400 mg t.d.s . ( OAM ) or 10 days OAM plus compliance enhancing measures . METHODS : A total of 119 H. pylori-positive patients were prospect ively r and omized to receive either 10 days OAM or 10 days OAM plus compliance enhancing measures ( medication in a dose dispensing unit , medication chart , an information sheet about H. pylori treatment , and phone call 2 days after starting therapy ) . H. pylori eradication was assessed by 13C-UBT at least 4 wk after cessation of therapy , compliance by phone interview on the last day of therapy and returned pill count , and side effects by phone interview and returned side effects form . RESULTS : In 113 patients attending 13C-UBT H. pylori was eradicated in 51 of 57 patients ( 89.5 % ) after 10 days OAM and in 48 of 56 ( 85.7 % ) after 10 days OAM plus compliance enhancing measures ( p= 0.54 ) . In both groups 97 % of medications were taken . Side effects were common ( 82 % of patients ) . Both side effects ( p= 0.001 ) and ulcer versus nonulcer at endoscopy ( p= 0.016 ) were independent predictors of treatment failure ; side effects also predicted noncompliance ( p= 0.02 ) . CONCLUSIONS : Ten days of OAM was effective for H. pylori eradication in our clinical population . Patient compliance was excellent and attempts to increase compliance had no impact on outcome or compliance . Side effects were very common and were significantly associated with treatment failure and decreased compliance Background : The optimum regimen for the eradication of Helicobacter pylori remains unclear . The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks , plus amoxycillin 500 mg t.d.s . and metronidazole 400 mg t.d.s . given for the first 7 days , in the treatment of H. pylori associated peptic ulcer disease Objective : We sought to compare a 2-day quadruple therapy with a 14-day triple therapy in the treatment of Helicobacter pylori infection . Methods : Eighty-one consecutive patients with an endoscopically diagnosed peptic ulcer and demonstrated infection by H. pylori were included in the study . Patients were r and omized to receive omeprazole 40 mg b.i.d . , amoxicillin 2.5 g once daily , metronidazole 500 mg t.i.d . , and bismuth subcitrate 360 mg t.i.d . for 2 days , followed by omeprazole 20 mg once daily for 6 additional days ( Group 1 ) or a 14-day course of omeprazole 20 mg b.i.d . , amoxicillin 1 g t.i.d . , and metronidazole 500 mg t.i.d . ( Group 2 ) . Eradication was evaluated by antral biopsy and rapid urease test at 2 months after therapy and by C13-urea breath test after a year . Results : Two patients were lost to follow-up at 2 months . Intention-to-treat analysis showed that H. pylori infection was cured in 29 of 42 patients ( 69 % ; 95 % CI : 53–82 % ) in Group 1 versus 36 of 39 ( 92 % ; 95 % CI : 78–98 % ) of patients in Group 2 ( p= 0.009 ) . Per- protocol analysis showed a cure rate of 71 % ( 95 % CI : 55–84 % ) ( 29/41 patients ) and 95 % ( 95 % CI : 81–99 % ) ( 36/38 patients ) , respectively ( p= 0.007 ) . Fifty-five of 65 cured patients returned 1 year after treatment ( 26 in Group 1 , 29 in Group 2 ) . All but one in Group 2 remained cured . There were no significant differences in compliance ( 88 % in Group 1 versus 92 % in Group 2 ) or in the presence of side effects ( 27 % ; 95 % CI : 15–43%versus 41 % ; 95 % CI : 26–58 % ; ns ) . Conclusion : Two-day quadruple therapy is significantly less effective than 2-wk triple treatment Background : The widespread use of eradication therapy for Helicobacter pylori in Japan has led to an increase in antibiotic‐resistant strains and the problem of re‐treatment in cases of eradication failure OBJECTIVES Triple therapy and amoxycillin plus omeprazole are the two most widely recommended regimens for the eradication of Helicobacter pylori . However , no controlled studies with a large number of cases are available for the reliable comparison of these two regimens . The aim of this controlled , r and omized , prospect i ve study was to compare the effect of these two regimens and a further regimen for metronidazole-resistant patients on duodenal ulcer healing , H. pylori eradication , and prevention of ulcer relapse . METHODS Patients ( n = 144 ) with proven duodenal ulcer ( DU ) were r and omized to one of the three following regimens : group A , omeprazole ( 2 x 40 mg ) plus amoxycillin ( 4 x 500 mg ) for 2 wk ; group B , triple therapy : bismuth nitrate ( 4 x 375 mg ) plus metronidazole ( 4 x 250 mg ) and tetracycline ( 4 x 500 mg ) daily for 2 wk and ranitidine ( 150 mg ) for the first week and bismuth nitrate ( 4 x 375 mg ) alone for a further 2 wk ; group C , omeprazole ( 20 mg ) plus amoxycillin ( 4 x 500 mg ) and tinidazole ( 2 x 500 mg ) for 2 wk . RESULTS A total of 46 patients in group A , 39 in group B , and 43 in group C completed the study . One patient in group A and three in group B did not tolerate the regimens and dropped out of the study . Control endoscopy was performed 8 wk after the start of treatment and when symptoms appeared ( up to 1 yr after the start of treatment ) . In subjects who completed the study , both the healing rate of DU in group B ( 97 % compared with 74 and 73 % in A and C , respectively , p < 0.02 ) and the H. pylori eradication rate in group B ( 85 compared with 35 % , p < 0.0001 in A and 58 % , p < 0.02 , in C ) were significantly higher than in groups A and C. The symptomatic ulcer relapse during the 1-yr follow-up in patients with initially healed ulcers was similar in all groups ( 18 , 16 , and 19 % in A , B , and C , respectively ) . The predictor of healing using logistic regression analysis was night pain ( p < 0.05 ) . The predictor of H. pylori eradication was sex ( p < 0.05 ) . CONCLUSION The 2-wk triple therapy plus an additional 2-wk treatment with the bismuth derivative ( without a prolonged administration of acid suppressing drugs ) seems to be an effective and economic treatment not only for the eradication of H. pylori but also for the healing of acute DU . The higher incidence of side effects found after triple therapy compared with the other two regimens was tolerated by the patients OBJECTIVE To establish the efficacy of omeprazole combined with two antibiotics for Helicobacter pylori eradication and duodenal ulcer relapse . PATIENTS Thirty-seven patients with endoscopically proven duodenal ulcer and H. pylori infection . METHODS Treatment consisted of 20 mg omeprazole daily for 4 weeks with the addition , during the second and third weeks , of amoxycillin ( 1 g three times daily ) and metronidazole ( 1 g daily ) ( group A ) or placebo ( group B ) . Endoscopy and biopsy to assess ulcer recurrence and H. pylori status were performed at entry to the study , after 4 weeks of therapy , and 1 and 6 months after treatment . RESULTS Duodenal ulcers healed in all patients . H. pylori infection was eradicated in 15 ( 79 % ) out of 19 patients in group A and one ( 6 % ) out of 16 patients in group B ( P < 0.01 ) . One patient in each of the groups was lost to follow-up after 6 weeks . During the 6 month follow-up period , duodenal ulcers recurred in three of the 16 patients with H. pylori eradication , compared with 16 of the 19 patients with persistent H. pylori infection ( 19 versus 84 % ; P < 0.01 ) . CONCLUSION The combination of omeprazole with amoxycillin and metronidazole is effective in H. pylori eradication . This triple therapy , which eradicates H. pylori , also significantly reduced duodenal ulcer relapse Few outcome studies directly compare Helicobacter pylori eradication therapy with maintenance H2‐antagonist therapy in duodenal ulcer disease : In Asian countries with limited re sources , clarithromycin‐based triple therapy may not be readily available . There are also few direct comparisons of different regimens in Asia OBJECTIVES Our objectives were to determine the effect of dual therapy with omeprazole and amoxicillin and of triple therapy with omeprazole , amoxicillin , and metronidazole in the eradication of Helicobacter pylori ( HP ) and to study the long-term results of eradication in these patients . METHODS A prospect i ve , r and omized , controlled trial was performed . Patients who were recruited had unequivocal evidence of HP infection based on culture , histology , rapid urease test , and Gram 's stain of a tissue smear . Eradication was defined as the absence of bacteria in all tests performed on both corpus and antral biopsies . RESULTS The infection was eradicated in 15 of 19 ( 78.9 % ) patients r and omized to receive dual therapy and in 19 of 22 ( 86.4 % ) patients who received triple therapy . We followed the course of 30 patients in whom HP had been eradicated for a prolonged term ( up to 12 months ) . All remained clear of HP . Twenty-five of 28 patients ( 89.3 % ) with duodenal ulcers in whom HP was successfully eradicated remained healed at 12 months . Fewer side effects were reported among patients who received the dual therapy . CONCLUSIONS Combination therapy with omeprazole and amoxicillin with or without metronidazole is effective in the eradication of HP . In particular , the dual therapy regimen with amoxicillin is not only effective but is also well tolerated by patients BACKGROUND / AIMS To evaluate the efficacy and tolerability of a new 1-week triple therapy regimen consisting of pantoprazole , amoxycillin and metronidazole . METHODOLOGY The study involved 51 Helicobacter pylori ( H. pylori ) positive patients ( M:30 , F:21 , mean age : 52.5 years , range : 24 - 75 ) affected with duodenal ulcer in active phase . At baseline and 6 weeks after the completion of treatment , clinical assessment , endoscopy with gastric biopsies , rapid urease test , 13C urea breath test , and serum laboratory analyses were performed . All patients were treated with pantoprazole 40 mg once daily , plus amoxycillin 1 gram tid and metronidazole 250 mg tid for 1 week , and pantoprazole 40 mg once daily for a second week . A clinical diary for daily assessment of symptoms and side effects was completed by patients during the treatment period . RESULTS Three patients were discontinued from the study . Six weeks after therapy , the ulcer was healed in 47 of 48 patients ( 97.9 % , 95 % CI = 93.9 - 100 ) . The cure rates of H. pylori infection , expressed using both the intention-to-treat and per protocol analyses , were 80.4 % ( 95 % CI = 69.5 - 91.3 ) and 85.4 % ( 95 % CI = 75.4 - 95.4 ) , respectively . The therapy led to a significant , rapid disappearance or reduction in daytime epigastric pain , from 68.8 % on day 1 to 82.2 % on day 3 ( p < 0.001 ) and in nocturnal epigastric pain , from 80.6 % on day 1 to 93.3 % on day 3 ( p < 0.001 ) . After 2 weeks of treatment , the percentage of patients completely free of pain was 82.2 % for daytime pain and 90.3 % for nocturnal pain . A rapid improvement in acid regurgitation , heartburn , nausea and vomiting was also observed with a median value of symptom disappearance of 2 days . The percentages of patients completely symptom-free were 37.5 % after 1 day , 54.1 % after 3 days , 75 % after 2 weeks , and 83.3 % after 2 months . H. pylori-cured patients showed a significant decrease in the histological activity of both antral ( p = 0.0001 ) and body ( p < 0.008 ) gastritis . Mild to moderate adverse events were reported by 15 patients . CONCLUSIONS One week triple therapy with pantoprazole in combination with amoxycillin and metronidazole , followed by a second week of pantoprazole , was well tolerated and highly effective for the 1 ) rapid improvement or resolution of symptoms ; 2 ) healing of the DU ; 3 ) eradication of H. pylori infection ; and , 4 ) reduction of histological signs of chronic gastritis activity The incidence and mean score of Helicobacter pylori-related , active antroduodenitis , lesions of superficial antral epithelium and duodenal gastric-type metaplasia were higher in endoscopic biopsies from a large series of patients with duodenal ulcer , when compared with asymptomatic patients or patients with non-ulcer dyspepsia . In 65 out of 73 patients with duodenal ulcer who could be followed up , H. pylori was eradicated using a combination of amoxycillin , 3 g daily , metronidazole , 1 g daily , and omeprazole , 20 mg daily . Rapid and permanent ( 6-month follow-up ) abolition of both gastroduodenitis activity and lesions of the gastric surface epithelium was observed in these 65 patients . There was also a progressive decrease in total immune-inflammatory cells but without a substantial change in duodenal gastric-type metaplasia . Similar , but transient and quantitatively less prominent , improvements were observed in the antroduodenal mucosa , which had been temporarily cleared of H. pylori by treatment with omeprazole alone . Conversely , increased gastritis activity , epithelial lesions and immune-inflammatory cell scores were found in the short term in the corpus mucosa , which was not cleared of H. pylori after omeprazole treatment . It is concluded that , of the various H. pylori-related mucosal changes , antroduodenitis activity and antral epithelial lesions most closely reflect the severity of mucosal damage and are probably the most important factors in duodenal ulcerogenesis . Their complete and rapid suppression after bacterial eradication may be a key factor in preventing ulcer relapse : Triple therapies containing omeprazole and ranitidine have been shown to be equivalent in eradicating H. pylori infection , but have been assessed either separately or head‐to‐head , only in small trials BACKGROUND Eradication of Helicobacter pylori infection in children in developing countries needs further investigations upon which to base treatment recommendations . The aim of the study was to compare two 2-week triple therapies in a r and omized double-blind trial . MATERIAL S AND METHODS In order not to exceed recommended dosages , the 238 H. pylori-infected children , aged 3 to 15 years ( mean 8.6 ) , were divided in two weight categories receiving at weights 13 - 22 kg : lansoprazole 15 mg once-daily and amoxicillin 500 mg twice-daily with metronidazole 250 mg twice-daily or clarithromycin 250 mg once-daily ; at weights 23 - 45 kg : lansoprazole 15 mg and amoxicillin 750 mg with metronidazole 500 mg or clarithromycin 250 mg , all administered twice daily . H. pylori status was assessed by culture and a monoclonal-based antigen-in-stool test ( Premier Platinum HpSA PLUS ) and side effects by structured question naires . RESULTS The overall per- protocol eradication ( n = 233 ) was similar in the two treatment regimens , 62.1 % for the metronidazole and 54.7 % for the clarithromycin-containing therapy . Eradication rate was higher in children > or= 23 kg ( 70.9 % ) than in children < 23 kg ( 45.7 % ) . In children > or= 23 kg ( n = 117 ) that received twice-daily administration of all drugs , efficacy of the metronidazole and clarithromycin-containing treatments were 69.5 % and 72.4 % , respectively . CONCLUSIONS The two treatments gave similar eradication rates . Significant differences for both treatments were found by weight , which could be the result of the once-daily proton pump inhibitor and clarithromycin and /or more antibiotic resistant strains in younger children BACKGROUND The prevalence of Helicobacter pylori increases with age . However , data regarding the effects of anti-H. pylori treatments in the elderly are very scarce . METHODS To evaluate the effect of three lansoprazole-based , 7 day , triple-therapy regimens on H. pylori eradication rates , symptomatology , chronic gastritis activity and serological markers of H. pylori infection in elderly subjects , we studied 150 symptomatic patients over 60 years of age with H. pylori-positive duodenal ulcer ( DU , n = 34 ) , gastric ulcer ( GU , n= 19 ) or chronic gastritis ( CG , n = 97 ) . Patients were consecutively treated with one of the following regimens : ( A ) lansoprazole ( LNS ) 30 mg b.i.d . + clarithromycin ( CLR ) 250 mg b.i.d . + metronidazole ( MTR ) 250 mg q.i.d . ; ( B ) LNS 30 mg b.i.d . + amoxycillin ( AMOX ) 1 g b.i.d . + MTR 250 mg q.i.d . ; and ( C ) LNS 30 mg b.i.d . + CLR 250 mg b.i.d . + AMOX 1 g b.i.d . RESULTS Two months after therapy , the eradication rates of the three treatments , expressed using both intention-to-treat and per- protocol analyses were , respectively ; group A , 86 and 91.5 % ; group B , 80 and 87 % ; group C , 82 and 89.1 % . After therapy , a significant reduction in epigastric pain ( P<0.001 ) , heartburn ( P=0.02 ) , dyspepsia ( P<0.001 ) and vomiting ( P < 0.005 ) was observed independently of the success of H. pylori eradication . A significantly higher percentage of asymptomatic patients were in the GU-DU group than in CG group ( 87.7 vs 70.0 % , P= 0.032 ) . After therapy , 33 subjects still suffered from symptoms . Persistence of symptoms was significantly associated with an endoscopic diagnosis of oesophagitis and not with H. pylori infection . Patients cured of H. pylori infection showed a significant decrease in the histological activity of both antral and body gastritis ( P < 0.0001 ) , a significant drop in immunoglobulin ( Ig ) G anti-H. pylori antibodies ( P < 0.0001 ) and pepsinogen ( PG ) C ( P<0.0001 ) and an increase in the PGA/PGC ratio ( P<0.0001 ) . CONCLUSIONS The 7 day , lansoprazole-based triple therapy was well tolerated and highly effective in the cure of H. pylori infection , the reduction of symptoms , chronic gastritis activity and serum levels of IgG anti-H. pylori antibodies and PGC . Persistence of symptoms after therapy was significantly higher in CG than GU and DU patients and was significantly associated with oesophagitis In this study , the efficacy and tolerability of two different therapeutic schedules in eradicating Helicobacter pylori and healing duodenal ulcer were evaluated . The study included 60 patients with duodenal ulcer and Helicobacter pylori infection . They were r and omly allocated to either of two groups : group 1 ( N = 30 ) received omeprazole 20 mg for 28 days , amoxicillin 3 x 500 mg for 7 days and metronidazole 3 x 500 mg for 5 days , and group 2 ( N = 30 ) received omeprazole 20 mg for 28 days , ACA ( amoxicillin 500 mg plus clavulanic acid 125 mg ) 3 x 625 mg for 7 days and metronidazole 3 x 500 mg for 5 days . Endoscopic examination , bioptic urease test and histologic examination were performed before , and 30 and 90 days after the treatment . Endoscopic examination was also performed one month after the beginning of the treatment , when healing of duodenal ulcer was observed in 90 % ( 27/30 ) of the group 1 patients and in 93.3 % ( 28/30 ) of the group 2 patients . The Helicobacter pylori eradication achieved in group 1 and 2 was 76.7 % ( 23/30 ) and 83.3 % ( 25/30 ) , respectively . Side effects were present in 20 % ( 6/30 ) of the group 1 patients and in 23.3 % ( 7/30 ) of the group 2 patients . Side effects were mild and did not require interruption of the treatment . A higher rate of eradication was achieved in group 2 than in group 1 , but the difference was not statistically significant Helicobacter pylori infection of the lining of the stomach induces an array of inflammatory cytokine production leading to gastritis and peptic ulcer disease . The aim of this study was to investigate the effect of curcumin on the production of interleukin (IL)-8 , IL-1beta , tumor necrosis factor (TNF)-alpha and cyclooxygenase (COX)-2 in gastric mucosa from H. pylori-infected gastritis patients . Patients were r and omly assigned to receive either OAM ( Omeprazole , Amoxicillin and Metronidazole ) treatment or a course of curcumin . Gastric biopsies were collected before and after treatment and were examined for the level of inflammatory cytokines mRNA by semi-quantitative reverse transcription polymerase chain reaction . The eradication rate of H. pylori in patients that received OAM treatment was significantly higher than the patients that received curcumin ( 78.9 % versus 5.9 % ) . The levels of IL-8 mRNA expression in the OAM group significantly decreased after treatment , but no changes of other cytokines were found . This emphasizes an important role of IL-8 in H. pylori infection . The decreases of cytokine production were not found in the curcumin group . We concluded that curcumin alone may have limited anti-bactericidal effect on H. pylori , and on the production of inflammatory cytokines . Nevertheless , other studies have reported that patients treated with curcumin had relieved symptoms . Further investigation should be carried out as the use of curcumin in combination with therapeutic regimens may be beneficial as an alternative treatment OBJECTIVES To compare cure rates of Helicobacter pylori ( H. pylori ) infection , ulcer healing , and side effects of three simplified regimens of triple therapy in patients with peptic ulcer disease . METHODS Two hundred thirty-one patients were prospect ively r and omized to receive either regimen OAM ( omeprazole 20 mg b.i.d . , amoxicillin 750 mg b.i.d . , and metronidazole 400 g b.i.d . ) , OCM ( omeprazole 20 mg b.i.d . , clarithromycin 250 mg b.i.d . , and metronidazole 400 mg b.i.d . ) , or BCM ( bismuth subcitrate 240 mg b.i.d . , clarithromycin 250 mg b.i.d . , and metronidazole 400 mg b.i.d . ) , all for 10 days . Side effects were reported immediately afterward in a self-administered question naire . Upper endoscopy was carried out before treatment and 2 months after treatment . Three antral and three corpus biopsy specimens were analyzed microbiologically and with rapid urease test to determine the presence of H. pylori . Altogether 143 patients ( 62 % ) had an active ulcer at start of treatment . Metronidazole resistant ( M-R ) H. pylori strains were found in 30 % of patients , while none had clarithromycin resistant ( C-R ) strains . RESULTS According to intention-to-treat analysis , H. pylori cure rates were 91 , 95 , and 95 % with OAM , OCM , and BCM , respectively ( p = 0.63 ) . In patients with metronidazole-sensitive ( M-S ) strains versus M-R strains , the cure rates were 96 versus 77 % with OAM ( p = 0.025 ) , 94 versus 94 % with OCM , and 94 versus 96 % with BCM . Ulcer healing rates were 95 , 94 , and 92 % , respectively ( p = 0.91 ) . There were no significant differences in side effects between the regimens , and only five patients ( 2 % ) had to stop the treatment prematurely . CONCLUSIONS All treatment regimens were highly effective for cure of H. pylori infection and for ulcer healing . Metronidazole resistance reduced the efficacy of OAM , but was of no importance for the efficacy of OCM or BCM . Side effects were of minor importance OBJECTIVE It has been reported that pretreatment with omeprazole could decrease the efficacy of Helicobacter pylori eradication . Our aim was to compare the efficacy , safety , and tolerability of the eradicating regimen , omeprazole/amoxicillin/metronidazole . The two antibiotics were scheduled either during the first or during the last 2 wk of omeprazole administration . METHODS In this prospect i ve controlled study conducted in a single center , 78 symptomatic peptic ulcer patients were treated for 4 wk with omeprazole 40 mg o.m . ; the patients were r and omly assigned to receive amoxicillin 1 g t.i.d . postpr and ially and metronidazole 250 mg t.i.d . postpr and ially , either during the first 2 wk ( group A , n = 40 ) or the last 2 wk of therapy with omeprazole ( group B , n = 38 ) . H. pylori status was assessed by culture , histology , urease test , and IgG antibodies . Each patient 's course was followed for 1 yr . RESULTS H. pylori infection was cured in 97.4 % of group A ( 95 % CI : 0.84 - 0.99 ) and in 89 % of group B ( 95 % CI : 0.73 - 0.96 , p = 0.28 ) . Healing was achieved in 80 % of the patients in group A ( 95 % CI : 0.63 - 0.90 ) and in 75.7 % of patients in group B ( 95 % CI : 0.60 - 0.90 , p = 0.60 ) At 12-month follow-up , 72 patients were evaluated : 37/38 ( 97 % ) of patients in group A and 33/33 ( 100 % ) in group B were confirmed as cured of the infection ( NS ) . Peptic ulcer healing rate reached 100 % in the two groups . Furthermore , between the two groups , there were no significant differences in symptom relief or improvement . Both regimens were well tolerated , and no patient had to be withdrawn from therapy because of an adverse event . Minor side-effects appeared to be similar in the two groups ( 40 % vs. 38 % ) . CONCLUSIONS This r and omized study clearly indicates that omeprazole pretreatment does not significantly reduce the efficacy of eradicating therapy for H. pylori in peptic ulcer patients AIM OF STUDY To test whether one week 's triple therapy with omeprazole and two antibiotics is enough to induce healing of a peptic ( gastric and /or duodenal ) ulcer . PATIENTS AND METHODS 112 Patients ( 73 males , 39 females ; median age 55 [ 18 - 88 ] years ) proven by culture or histology to have an Helicobacter ( H. ) pylori infection and uncomplicated peptic ( gastroduodenal ) ulcer . For one week they received omeprazole ( 20 mg once or twice daily ) plus two antibiotics ( clarithromycin/metronidazole , clarithromycin/tetracycline , clarithromycin/amoxycillin or amoxycillin/metronidazole ) to eradicate H. pylori . No further anti-ulcer treatment was given subsequently . Healing of the ulcer and H. pylori status were checked by the urease test , culture and histology ( endoscopic biopsy ) 4 weeks later . RESULTS The 5-week ulcer healing rate was 94.6 % ( 95 % confidence interval : 89 - 98 % ) . Persisting ulcers ( n = 6 ) were associated with either treatment with aspirin or nonsteroidal antiinflammatory drugs ( n = 3 ) , persistent H. pylori infection ( n = 2 ) or persistent H. pylori infection plus treatment with aspirin ( n = 1 ) . The ulcer healing rate was significantly higher in patients with eradicated infection than in those with posttherapy persistence of H. pylori ( 97.0 vs. 76.9 % ; P = 0.02 ) . There were no significant differences after 5 weeks between patients with duodenal and those with gastric ulcer ( 97.4 vs. 89.3 % ) . CONCLUSIONS One-week effective eradication treatment is adequate to induce healing of H. pylori-positive peptic ulcers . Anti-ulcer treatment after eradication of H. pylori should be considered only if the patient is receiving treatment with ulcerogenic drugs or continues to have symptoms BACKGROUND This study was conducted to eluci date the prevalence of Helicobacter pylori in patients with a perforated duodenal ulcer and to determine whether eradication of H. pylori prevent ulcer recurrence following simple repair of the perforation . PATIENTS AND METHOD Eighty-three patients with perforated duodenal ulcer ( 68 males ) ; mean age was 47.8 years+/-7.2 . Antral mucosal biopsies ( to determine the status of HP by rapid urease test , culture and histological examination/staining ) were obtained during laparotomy by passing a biopsy forceps through the perforation site . H. pylori positive patients who had undergone patch repair were r and omized into the eradication group who received amoxicillin , metranidazole plus omperazole and the control group was given omeprazole alone . Follow-up endoscopy and antral biopsies were performed at 8 weeks , 16 weeks and 1 year to show ulcer healing and determine H. pylori state . RESULTS Of 77 patients in the study , 65 patients ( 84.8 % ) had H. pylori . These patients were r and omly divided into the triple therapy group ( 34 patients ) and the control group ( 31 patients ) . Eradication of H. pylori was significantly higher in the triple therapy group than the control group and initial ulcer healing was significantly better in the eradication group . After 1 year , ulcer recurrence was ( 6.1 % ) in the eradication group vs. ( 29.6 % ) in the control group ( P=0.001 ) . CONCLUSION H. pylori was present in a high proportion of patients with duodenal ulcer perforation . Eradication of H. pylori after simple closure of a perforated duodenal ulcer reduced the incidence of recurrent ulcer AIMS To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection . PATIENTS AND METHODS A total of 165 patients with active duodenal ulcer were enrolled in the study . At entry , endoscopy , clinical examination and laboratory tests were performed . Histology and the rapid urease test were used to diagnose Helicobacter pylori infection . Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks ( two-week , dual therapy ) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week ( one-week , triple therapy ) . Two and twelve months after cessation of therapy , endoscopy and clinical assessment s were repeated . RESULTS Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater ( p<0.0001 ) in the triple therapy group ( healing : 98.6 % ; Helicobacter pylori cure rate : 72.6 % ) than in the dual therapy group ( healing : 77.3 % ; Helicobacter pylori cure rate : 33.3 % ) . Ulcers healed more frequently in Helicobacter pyloricured than in Helicobacter pylori-not cured patients ( 94.9 % vs. 77.2 % ; p<0.0022 ) . After one year , Helicobacter pylori eradication was re-confirmed in 46/58 patients previously treated with the triple therapy and in 10/40 patients treated with the dual therapy [ p<0.0001 ] . Only three duodenal ulcer relapses were observed throughout follow-up : all were in Helicobacter pylori-not cured patients . CONCLUSIONS Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers . The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary . Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated BACKGROUND Evidence from Europe , Asia , and North America suggests that st and ard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole . These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-re source setting s. Few studies in Latin America have been done , where the burden of H pylori-associated diseases is high . We therefore did a r and omised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a st and ard 14-day regimen of triple therapy . METHODS Between September , 2009 , and June , 2010 , we did a r and omised trial of empiric 14-day triple , 5-day concomitant , and 10-day sequential therapies for H pylori in seven Latin American sites : Chile , Colombia , Costa Rica , Honduras , Nicaragua , and Mexico ( two sites ) . Participants aged 21 - 65 years who tested positive for H pylori by a urea breath test were r and omly assigned by a central computer using a dynamic balancing procedure to : 14 days of lansoprazole , amoxicillin , and clarithromycin ( st and ard therapy ) ; 5 days of lansoprazole , amoxicillin , clarithromycin , and metronidazole ( concomitant therapy ) ; or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole , clarithromycin , and metronidazole ( sequential therapy ) . Eradication was assessed by urea breath test 6 - 8 weeks after r and omisation . The trial was not masked . Our primary outcome was probablity of H pylori eradication . Our analysis was by intention to treat . This trial is registered with Clinical Trials.gov , registration number NCT01061437 . FINDINGS 1463 participants aged 21 - 65 years were r and omly allocated a treatment : 488 were treated with 14-day st and ard therapy , 489 with 5-day concomitant therapy , and 486 with 10-day sequential therapy . The probability of eradication with st and ard therapy was 82·2 % ( 401 of 488 ) , which was 8·6 % higher ( 95 % adjusted CI 2·6 - 14·5 ) than with concomitant therapy ( 73·6 % [ 360 of 489 ] ) and 5·6 % higher ( -0·04 % to 11·6 ) than with sequential therapy ( 76·5 % [ 372 of 486 ] ) . Neither four-drug regimen was significantly better than st and ard triple therapy in any of the seven sites . INTERPRETATION St and ard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American population s. FUNDING Bill & Melinda Gates Foundation , US National Institutes of Health BACKGROUND Up to 35 % of H. pylori-positive patients remain infected after a first eradication attempt . Lactoferrin , a natural anti-bacterial glycoprotein , seems a promising tool in treating H. pylori infection , but it has never been used in second-line treatment . MATERIAL / METHODS A prospect i ve , r and omized study was conducted on 70 consecutive patients with persistent H. pylori infection after failure of the first st and ard treatment schedule . All patients were r and omly treated with ranitidine bismuth citrate ( RBC , 400 mg b.d . ) , esomeprazole ( 40 mg/day ) , amoxycillin ( 1 g t.d ) , and tinidazole ( 500 mg b.d . ) without ( group A ) or with ( group B ) supplementation of bovine lactoferrin ( 200 mg b.d ) . One month after conclusion of therapy , endoscopy was performed in those patients for whom the examination was clinical ly relevant . The remaining patients were checked by 13C-urea breath test . RESULTS Sixty-seven patients were fully compliant and completed the study ( 33 , i.e. 94.28 % , in group A and 34 , 97.14 % , in group B ) . One group A patient ( 2.85 % ) was excluded for protocol violation and one group B patient ( 2.85 % ) was lost to follow-up . H. pylori eradication was obtained in 31/33 ( on intention-to-treat : 88.57 % , 95%CI : 87 - 99 % ) group A patients and in 33/34 ( on intention-to-treat : 94.28 % , 95%CI : 86 - 100 % ) group B patients ( p = ns ) . 16/68 patients ( 23.53 % ) experienced side effects ( 29.41 % in group A and 17.64 % in group B , p= 0.05 ) . CONCLUSIONS Lactoferrin supplementation was found effective in reducing side-effect incidence . Moreover , it seems capable of achieving a slight ( and not statistically significant ) improvement in eradicating H. pylori when used in second-line treatment Helicobacter pylori infection causes a number of gastrointestinal diseases and its current treatment is based on multidrug regimes including acid suppression and antimicrobials . The success of these regimes is determined by a number of factors including antibiotic resistance , which varies widely but is an increasing problem . Local data are important in establishing the most cost-effective eradication regime . Data have been collected prospect ively on antibiotic resistance at Ipswich Hospital ( Suffolk , UK ) in all consecutive isolates of H. pylori from 1991 to 2001 . The success of regimes consisting of a proton pump inhibitor , amoxycillin and metronidazole ( PPI/A/M ) has also been evaluated in patients found positive on serological testing in primary care using urea breath testing . Overall , metronidazole resistance was found in 31.7 % of isolates and clarithromycin resistance in 5.3 % . A significant increase in metronidazole resistance from 29.1 to 37.0 % ( P = 0.022 ) and a decrease in clarithromycin resistance from 10.3 to 3.8 % ( P = 0.014 ) was seen over the study period . Metronidazole resistance was significantly more common in women ( P < 0.001 ) and young patients ( P < 0.001 ) . Eradication with PPI/A/M was successful in 89.9 % of patients and did not change significantly over the study period . Eradication rates were lower in young patients ( P < 0.001 ) . Whilst metronidazole resistance is increasing in Suffolk , this does not seem to have a significant effect on eradication rates . Metronidazole-based regimes are still effective first-line treatments in most patients Aim : To investigate a repeat treatment regimen with the same antibiotic combination of amoxycillin and metronidazole in patients with continuing Helicobacter pylori infection : The efficacy of proton pump inhibitor based triple therapy in patients from South‐East Asia , where metronidazole resistance is reportedly high , has not been formally assessed in r and omized , multicentre trials BACKGROUND To study the effect of second-line treatment with tetracycline ( T ) combination therapy in patients with Helicobacter pylori ( H. pylori ) infection after failure of triple one-week therapy with a proton pump inhibitor , omeprazole ( O ) with amoxycillin ( A ) and claritromycin ( C ) or metronidazole ( M ) . METHODS Three hundred twenty-five naive patients ( 146 males , 179 females , mean age 50 , range 18 - 76 ) , with H. pylori infection , were r and omised to receive one-week triple therapy b.i.d . with O 20 mg ; A 1 g ; C 500 mg ( OAC7 163 pts ) or O 20 mg ; A 1 g ; M 500 mg ( OAM7 162 pts ) . H. pylori status was determined before therapy by histology and 3 months after the end of treatment by C-13 urea breath test ( UBT ) . When eradication did not occur , the patients were retreated with OTA7 : O 20 mg b.i.d . ; T 500 mg t.i.d . and A1 g b.i.d . for another week . H. pylori was assessed by C-13 UBT 3 months after the end of retreatment . Statistical analysis was done by c2 and Student t test . RESULTS Three hundred and ten patients have completed the study with compliance > 95 % : 15 patients complained of side effects ( diarrhea , nausea , urticaria , abdominal pain ) : 9 group OAC7 , 6 group OAM7 . After the first treatment h. pylori eradication were obtained in 124/154 ( 80.5 % ) ( PP ) OAC7 group and 123/156 ( 78.8 % ) ( PP ) OAM7 group ( ns ) . 49/63 patients ( 77.7 % ) were negative after second-line treatment with OTA7 regimen . CONCLUSIONS In personal experience the drug compliance was excellent . The rate of eradication after one-week therapy-omeprazole combined with A+C or with A+M-was satisfactory . The retreatment with tetracycline combination regimen cured 77.7 % of patients : that seems to be a promising options , in clinical practice , after an eradication failure BACKGROUND Relationships between Helicobacter pylori infection , inflammatory changes in antral region of gastric mucosa , and duodenal ulcer is well known and documented in a large number of studies . This trial is design ed to examine effect of one week regimen of Pantoprazole , Amoxycillinum and Metronidazol to eradication of H. pylori , duodenal ulcer healing and histological changes on gastric mucosa . PATIENTS AND METHODS 30 patients with active duodenal ulcer , H. pylori-positive , 16 male , with average age 47.12 + /- 13.13 yrs ( AVG + /- STD ) and 14 female patients with average age 44.47 + /- 12.29 yrs were included in trial . Biopsy of gastric antral region were performed in each patient . Patients were given Pantoprazole 40 mg bid , Amoxycillinum 1000 mg bid , Metronidazolum 500 mg bid for 7 days . After 7 days of treatment , control endoscopy was performed with repeated rapid ureasa test for H. pylori and antral biopsy and with verification of duodenal ulcer healing . Patients were followed up for 24.3 + /- 9.7 weeks for occasion of subjective symptoms . RESULTS 96.67 % patients were presented with eradicated H. pylori , complete ulcer healing was found in 83.34 % patients after one week regimen ( 13.33 % patients with ulcer reduced on one third of previous described ) , 73.33 % of patients were presented with histologically feature of chronic gastritis turned from active to stationary phase . CONCLUSION One week regiment with Pantoprazole , Amoxycilline and Metronidazole is effective , and beside a high rate ulcer healing and eradication of H. pylori it provides an improvement of histological feature of antral gastritis S‐mephenytoin 4’‐hydroxylase ( CYP2C19 ) catalyses the metabolism of rabeprazole to some extent . Based on the metabolic and pharmacokinetic differences among other proton pump inhibitors such as omeprazole , lansoprazole and pantoprazole , rabeprazole appears to be the least affected proton pump inhibitor by the CYP2C19‐related genetic polymorphism Aims : To compare the efficacy , safety and tolerability of an omeprazole/amoxycillin ( OA ) dual therapy Helicobacter pylori eradication regimen with an omeprazole/amoxycillin/metronidazole ( OAM ) triple therapy regimen Metronidazole is often used to eradicate clarithromycin-resistant Helicobacter pylori . The aim of this study was to determine the appropriate duration of metronidazole-containing treatment for the eradication of H. pylori infection in northern Japan . We enrolled 83 H. pylori-positive patients in whom first-line triple therapy consisting of a proton pump inhibitor , amoxicillin and clarithromycin had failed . Prior to the second-line therapy , patients underwent endoscopy to obtain H. pylori strains to test the susceptibility to antibiotics . Patients were administered lansoprazole ( 30 mg b.d . ) , amoxicillin ( 750 mg b.d . ) and metronidazole ( 250 mg b.d . ) for 5 or 7 days , and the treatment results were tested by (13)C-UBT . None of the isolated H. pylori strains was amoxicillin- or metronidazole-resistant . All the patients completed the regimen without major adverse effects . The eradication rate was 95.1 % ( 39/41 ; 95 % confidence interval [ CI ] , 83.5 - 99.4 % ) in the 41 patients who were treated for 5 days and 95.2 % ( 40/42 ; 95 % CI , 83.8 - 99.4 % ) in the 42 patients treated for 7 days . The results suggest that 5 days could be a sufficient duration for triple therapy of lansoprazole , amoxicillin and metronidazole as a second-line H. pylori eradication therapy in areas where metronidazole-resistant strains are rare AIM to present our experience in eradicating Hp in three consecutive trials performed between 1995 and 1999 . METHODS 320 duodenal ulcer out patients have been enrolled in three open , prospect i ve controlled trials . Hp infection was confirmed by Giemsa stain and Rut . In Trial I , 52 cases received 20 mg omeprazole + 2 x 250 mg clarithromycin + 2 x 500 mg tinidazole ( OCT ) , 48 patients were given 20 mg omeprazole , 2 x 1000 mg amoxicillin + 2 x 500 mg metronidazole ( OAM ) for 7 days ; in Trial II , 48 cases received 40 mg pantoprazole + 2 x 1000 mg amoxicillin + 2 x 500 mg clarithromycin ( PAC ) for 7 days and 5l cases 2 x 400 mg ranitidin bismuth citrate + 2 x 500 mg clarithromycin for 14 days ( RBC-C ) ; in Trial III , 60 cases were treated with 2 x 30 mg lansoprazole + 2 x 250 mg clarithromycin + 2 x 500 mg metronidazole and 6l patients received 2 x 400 mg ranitidin bismuth citrate+2 x 250 mg clarithromycin + 2 x 500 mg metronidazole ( RBC-CM ) . The patients were controlled within 4 - 6 weeks by endoscopy in trials I-II and 13C-urea breath test in trial III . RESULTS Eradication rates on ITT/PP basis were : OCT : 72.3/80.2 % vs OAM 51.2/63.5 % ( P = 0.02/P = 0.03 ) ; PAC : 80.8/88.3 % vs RBC-C 80.3/85.4 % ( P = 0.65/0.67 ) and LCM 78.3/92.1 % vs RBC-CM 78.7/90.5 % ( P = 0.86/P = 0.93 ) . Side effects occurred in 5.2 , 8.6 , 9.5 , 14.5 , 13.5 and 18.3 % of the cases . CONCLUSION Regimens using 2 x l PPI or RBC + 2 antibiotics for l week proved to be the most effective for Hp eradication in duodenal ulcer patients Clarithromycin and nitroimidazoles such as metronidazole and ornidazole are among the most frequently used antibiotics for curing Helicobacter pylori infection . However , controversial data exist on whether their in vitro resistance has a negative impact on treatment outcome Background : Triple therapy involving a proton pump inhibitor and two antibiotics has been suggested as an effective treatment for Helicobacter pylori infection . The impact of imidazole resistance on the efficacy of such regimens is largely unknown AIM Triple therapy consisting of a proton pump inhibitor ( PPI ) and two antibiotics is used as first choice in treating Helicobacter pylori ( H. pylori ) infection . Since in the North Italian population , metronidazole resistance is less than 40 % , this antibiotic would be preferable as first approach . The aim of this r and omized study was to assess the efficacy of a metronidazole-based versus a tinidazole-based treatment , in naïve patients with H. pylori infection . METHODS Diagnosis and eradication of H. pylori infection were assessed by 13C-urea breath test , and by histology when an endoscopic examination was necessary . A total of 171 patients was treated : 91 ( 47 males , mean age 50+/-3 years ) with metronidazole 250 mg q.i.d . , amoxicilline 1 gr b.i.d . and PPI st and ard dose ( MAO ) , and 80 ( 36 males , mean age 52+/-3.8 years ) with tinidazole 500 mg b.i.d . , amoxicilline 1 gr b.i.d . and PPI st and ard dose ( TAO ) regimen for 7 , 10 or 14 days . RESULTS Three patients suspended MAO treatment due to side effects . H. pylori eradication was obtained as follow indicated . After 7 days , in 23/30 ( 76.6 % ) patients in MAO versus 20/27 ( 74.0 % ) in TAO regimen . After 10 days , in 20/26 ( 76.9 % ) patients in MAO versus 20/26 ( 76.9 % ) in TAO regimen . After 14 days , in 25/32 subjects ( 78.1 % ) in MAO versus 21/27 ( 77.7 % ) in TAO treatment . The differences among duration s or between metronidazole-versus tinidazole-based triple therapy were not statistically different . CONCLUSION Treatment with metronidazole is as effective as that with tinidazole in terms of efficacy . Moreover , duration did not influence efficacy of treatment This study compared the efficacy of an H2-receptor antagonist (H2RA)- and a proton-pump inhibitor (PPI)-based triple regimen for the eradication of Helicobacter pylori infection . Chinese patients with H. pylori-associated gastritis or peptic ulcer were r and omized to receive the H2RA-based triple regimen ( 20 mg famotidine , 1.0 g amoxicillin and 0.4 g metronidazole ) or the PPI-based triple regimen ( 20 mg omeprazole , 1.0 g amoxicillin and 0.4 g metronidazole ) both twice daily for 1 or 2 weeks . Successful eradication of H. pylori was determined by the 13C-urea breath test and gastric mucosa histology at least 4 weeks after completion of antibiotic therapy . Eradication rates were 56.0 % and 76.9 % for the 1-week H2RA- and PPI-based triple regimens , respectively , and 81.6 % and 82.1 % for the 2-week regimens , respectively . The H. pylori eradication rate for the 2-week H2RA regimen was significantly higher than that for the 1-week regimen , but there were no significant differences between the 1- and 2-week PPI regimens . The two regimens proved equally effective in eradicating H. pylori infection A number of clinical studies have assessed the efficacy of short‐term twice‐daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens Background Helicobacter pylori is the most important etiologic agent for development of peptic ulcer , chronic gastritis and gastric carcinomas . It is now well established that H. pylori eradication treatment is more cost-effective than acid suppressing therapies alone for the treatment of peptic ulcer disease . However , the comparative cost-effectiveness of various H. pylori eradication regimens is still not clear . Objective This study was design ed to make a pharmacoeconomic comparison of different H. pylori eradication regimens in patients with peptic ulcer disease or chronic gastritis , using real-world cost and effectiveness data . Setting Istanbul University Hospital and Marmara University Hospital . Method A total of 75 patients diagnosed as H. pylori ( + ) by endoscopy were r and omized to receive one of the seven H. pylori treatment protocol s. These protocol s were as follows : ( LAC ) = ‘ lansoprazole 30 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid ’ for 7 days and ( OCM ) = ‘ omeprazole 20 mg bid + clarithromycin 250 mg bid + metronidazole 500 mg bid ’ ; ( OAM ) = ‘ omeprazole 40 mg qd + amoxicillin 500 mg tid + metronidazole 500 mg tid ’ ; ( MARB ) = ‘ metronidazole 250 mg tid + amoxicillin 500 mg qid + ranitidine 300 mg hs + bismuth 300 mg qid ’ ; ( OAC ) = omeprazole 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid ’ ; ( OCA ) = omeprazole 40 mg bid + clarithromycin 500 mg bid + amoxicillin 1 g bid ’ ; ( OAB ) = ‘ omeprazole 20 mg bid + amoxicillin 500 mg tid + bismuth 300 mg qid ’ each for 14 days . Only direct costs were included in the analysis . Effectiveness was measured in terms of “ successful eradication ” . The cost-effectiveness ratios of the regimens were calculated using these effectiveness and cost data . The perspective of the study was assumed as the Government ’s perspective . Main outcome measureCost-effectiveness ratios of eradication regimens . Results MARB and OCA regimens were found to be more cost-effective than the other treatment regimens . The eradication rates and cost-effectiveness ratios calculated for these protocol s were 90 % ( € 158.7 ) for MARB and 90 % ( € 195.8 ) for OCA regimen . Conclusion This study confirms the importance of using local pharmacoeconomic data . Analyses such as this give decision-makers the tools to choose a better treatment option which is both highly effective yet and has a low cost BACKGROUND Acid pump inhibitors combined with antimicrobials cure gastritis and peptic ulcer disease but a st and ard therapy has not yet been established . We therefore investigated a triple therapy with pantoprazole . METHODS The aim of this open-label monocenter trial , involving 30 intention-to-treat patients with peptic ulcer disease or functional dyspepsia , was to assess the H. pylori cure rate after a 7-day triple therapy with pantoprazole ( 40 mg bid ) plus metronidazole ( 500 mg bid ) and amoxicillin ( 1 g bid ) . The H. pylori status was assessed by rapid urease test , histological examination and culture at the initial examination and by histological examination and culture at the study end 4 weeks after ending all therapy . RESULTS At the end of the trial H. pylori was eradicated in 21 of 27 per protocol patients ( 78 % ; 95 % CI 58 - 91 % ) and in 21 of 30 patients included in the trial ( 70 % ; 95 % CI 51 - 85 % ) . In 15 of 16 per protocol patients with metronidazole-sensitive strain ( 94 % ; 95 % CI 70 - 100 % ) the infection was cured , but in contrast eradication was accomplished in only one of 3 patients with a metronidazole-resistant H. pylori strain . Post-treatment resistance to metronidazole was observed in 6 cases , although 4 of them had had H. pylori strains sensitive to metronidazole at the initial visit . The gastritis had clearly been improved , and the activity of gastritis had completely disappeared 4 weeks after treatment . Seven adverse events were observed in 7 patients , the intensity of which was moderate in 6 cases . CONCLUSIONS This short-term triple therapy with pantoprazole , amoxicillin and metronidazole provides an effective regimen especially in patients with metronidazole-sensitive strain Although triple ( omeprazole , amoxicillin , and metronidazole ) and quadruple ( omeprazole , tetracycline , metronidazole , and bismuth subcitrate ) therapeutic regimens for H. pylori eradication has been studied much in the general population , there is a lack of data in renal transplanted patients . So , this study aim ed at comparing regimens in these patients who were considered being immunocompromised . The present clinical trial was carried out in Mashhad , Iran in 2010 . Fifty-five patients who had received a kidney transplant in six months or earlier and referred for chronic dyspepsia were selected . They were resistant to H2-receptor antagonists or proton pump inhibitors therapy and had positive Rapid Urea Test . They r and omly divided into two groups : triple and quadruple therapy . The treatment duration in both groups was similar ( antibiotics for two weeks plus omeprazole for 4 weeks ) . Urea Breath Test ( UBT ) was performed two weeks after treatment for assessment of its result . Total numbers of 39 patients ( 71 % ) were positive for H. Pylori which were divided into triple therapy group ( 21 patients ) and quadruple therapy ( 18 patients ) . Overall , the treatment was successful in 80 % ( 71 % in triple therapy and 89 % in quadruple one ) which was not different significantly between the groups ( p=0.247 ) . The result of this study revealed that the prevalence of H. pylori infection in renal transplant patients is similar to the normal population . In these cases , triple and quadruple therapies were similar in eradication of H. pylori . So , triple therapy can be recommended in renal transplant recipients The aim of this prospect i ve r and omized multicenter study was to find out if there is one or several promising regimens containing lansoprazole with various combinations of antibiotics which have a high eradication rate of Helicobacter pylori , few side-effects , good patient compliance , and relative low cost if possible . Two hundred and ninety-seven patients with H. pylori positive duodenal ulcer were enrolled and r and omly allocated into one of the five treatment groups : 1 ) group A : received lansoprazole 30 mg once daily for 2 weeks plus amoxicillin ( AM ) 500 mg and metronidazole ( MZ ) 500 mg twice daily for one week in the first week ; 2 ) group B : the AM in group A was replaced by clarithromycin ( CM ) 250 mg ; 3 ) group C : the MZ in group A was replaced by CM 250 mg ; 4 ) group D : the AM and CM in group C was used for 2 wk ; 5 ) group E : the CM in group D was doubled to 500 mg twice daily . All patients received endoscopies pre- and 4 - 6 weeks post termination of treatment . H. pylori was detected by culture , histology and rapid urease test ( CLO test ) . 13C-urea breath test was performed if the patients refused the second endoscopy . The E-test was adopted to evaluate the MZ and CM resistance of H. pylori . Totally , 253 patients completed the study . The eradication rate of groups A , B , C , D and E were 75 % , 80 % , 78 % , 92 % , and 96 % , respectively . The eradication rate of group E was significantly higher than that of groups A , B , or C. There were no significant differences of eradication rates between the groups D and E. Sixty-seven cases ( 28.8 % ) were MZ-resistant . The difference of eradication rates between MZ-S and MZ-R patients was significant in group A ( 85.3 % vs. 42.9 % ) and in the combination of groups A and B ( 83.8 % vs. 59.4 % ) . Good compliance ( defined as taking > 90 % of medications ) was seen in more than 90 % of cases in each group . Triple therapy containing lansoprazole 30 mg once daily , AM 500 mg and CM 250 mg twice daily for two weeks is a promising regimen which reaches a high eradication rate , avoids MZ resistance , and has very good patient compliance at an acceptable cost Objectives No trial has compared non-bismuth quadruple ‘ sequential ’ and ‘ concomitant ’ regimens in setting s with increasing clarithromycin rates . The study aims to compare the effectiveness and safety of these therapies for Helicobacter pylori treatment . Design Prospect i ve r and omised clinical trial in 11 Spanish hospitals . Patients naïve to eradication therapy with non-investigated/functional dyspepsia or peptic ulcer disease were included . R and omised ( 1:1 ) to sequential ( omeprazole ( 20 mg/12 h ) and amoxicillin ( 1 g/12 h ) for 5 days , followed by 5 days of omeprazole ( 20 mg/12 h ) , clarithromycin ( 500 mg/12 h ) and metronidazole ( 500 mg/12 h ) ) , or concomitant treatment ( same drugs taken concomitantly for 10 days ) . Eradication was confirmed with 13C-urea breath test or histology 4 weeks after treatment . Adverse events ( AEs ) and compliance were evaluated with question naires and residual medication count . Results 338 consecutive patients were r and omised . Mean age was 47 years , 60 % were women , 22 % smokers and 20 % had peptic ulcer . Concomitant and sequential eradication rates were , respectively , 87 % vs 81 % by intention-to-treat ( p=0.15 ) and 91 % vs 86 % ( p=0.131 ) per protocol . Respective compliances were 83 % vs 82 % . Treatment-emergent AEs were reported in 59 % of patients ( no differences found between treatments ) . AEs were mostly mild ( 60 % ) , and average length was 6.1 days , causing discontinuation only in 12 patients . Multivariate analysis : ‘ concomitant ’ treatment showed an OR of 1.5 towards better eradication rate in a borderline significance CI ( 95 % CI 0.9 to 2.8 ) . Conclusions Concomitant therapy led to a non-statistically significant advantage ( 5 % ) over sequential therapy , coming closer to 90 % cure rates . Both therapies showed an acceptable safety profile . ClincialTrials.gov : NCT01273441 BACKGROUND The study compares the eradication success of st and ard first-line triple therapies of different duration s ( 7 , 10 , and 14 days ) . MATERIAL S AND METHODS A total of 592 naive Helicobacter pylori-positive patients were r and omized to receive pantoprazole , amoxicillin , and clarithromycin or metronidazole for 14 days ( PACl14 or PAM14 ) , 10 days ( PACl10 or PAM10 ) , or 7 days ( PACl7 or PAM7 ) . H. pylori eradication was assessed by histological , microbiological , and rapid urease examination . RESULTS The intention-to-treat ( ITT ) and per- protocol ( PP ) analyses have shown no overall statistically significant differences between the eradication success of PACl and PAM treatment groups ( ITT p = .308 , PP p = .167 ) . Longer treatment duration has yielded statistically significant increase in eradication success for clarithromycin ( ITT p = .004 ; PP p = .004 ) and metronidazole ( ITT p = .010 ; PP p = .034 ) based regimens . Namely , PACl10 , PACl14 , and PAM14 protocol s result ed in eradication success exceeding 80 % in ITT and 90 % in PP analysis . Primary resistance to clarithromycin and metronidazole equals 8.2 % and 32.9 % , respectively . Prolonging the metronidazole-based treatment duration in patients with resistant strains result ed in statistically significant higher eradication success . CONCLUSIONS For all antimicrobial combinations , 14 days protocol s have led to a significant increase of H. pylori eradication success when compared to 10 and 7 days , respectively . Prolonging the treatment duration can overcome the negative effect of metronidazole resistance . Only PAM14 , PACl10 protocol s achieved ITT success > 80 % and should be recommended as the first line eradication treatment in Croatia Aim : To determine the efficacy of three Helicobacter pylori eradication regimens and factors affecting the eradication results in Finl and Objective : We compared the Helicobacter pylori eradication rate after a 14-day treatment with amoxicillin 500 mg t.i.d . and metronidazole 500 mg t.i.d . with or without omeprazole 20 mg once daily . Methods : This was a r and omized , controlled trial in which omeprazole was given in double-blind fashion . Patients with H. pylori-associated gastritis were enrolled in four centers in Canada from July 1991 to January 1994 . Eradication of H. pylori was assessed by histological evaluation and culture of endoscopic biopsies obtained from the antrum and corpus of the stomach . Results : The H. pylori eradication rate was 73 % ( 33 of 45 ) in the omeprazole-amoxicillin-metronidazole group , compared with 66 % ( 31 of 47 ) in the amoxicillin-metronidazole group . This 7 % difference was not statistically significant ( p= 0.43 , 95 % confidence interval for difference –11 % to 26 % ) . Metronidazole primary resistance in the pre study cultures was found more frequently in the omeprazole-amoxicillin-metronidazole group than in the amoxicillin-metronidazole group . Resistance to metronidazole was an important predictor of treatment failure . The H. pylori eradication rate was 61 % ( 19 of 31 ) for patients infected with metronidazole-resistant H. pylori strains , compared with 91 % ( 30 of 33 ) eradication for those infected with metronidazole-sensitive strains ( p < 0.01 ) . Vaginal c and idiasis was reported in four patients . Conclusions : The H. pylori eradication rate was higher ( 73 % ) for omeprazole-amoxicillin-metronidazole than for the dual antibiotic therapy given without omeprazole ( 66 % ) ; however , this difference was not statistically significant . Metronidazole resistance significantly reduces H. pylori eradication rates OBJECTIVES It was our goal to evaluate the efficacy and safety and patient compliance with omeprazole-based dual and triple therapy for eradication of Helicobacter pylori in peptic ulcer disease . MATERIAL S AND METHODS One hundred seventy-five consecutive patients with H. pylori infection and associated active peptic ulcer were included . H. pylori infection was assessed by rapid urease test and histological analysis . Patients were r and omized among three treatments : group 1 ( 56 patients ): omeprazole , 20 mg bid , and amoxicillin , 1 gm bid , for 2 weeks ; group 2 ( 61 patients ): omeprazole , 20 mg bid , plus amoxicillin , 1 gm bid , and metronidazole , 500 mg bid , for 1 week ; and group 3 ( 58 patients ): omeprazole , 20 mg bid , plus amoxicillin , 1 gm bid , and clarithromycin , 500 mg bid , for 1 week . Ulcer healing and cure of infection were evaluated at 4 to 6 weeks after cessation of therapy . Eradication rate was calculated per- protocol and by an intention-to-treat analysis . RESULTS At posttreatment endoscopy , duodenal ulcer was healed in 98.3 % of patients . Eleven patients ( 6 % ) were lost to follow-up . H. pylori infection was treated successfully in 55 % ( 95 % confidence interval [ CI ] = 41%-69 % ) of patients of group 1 ; 86 % ( 95 % CI = 77%-95 % ) of group 2 ( p < .001 vs. group 1 ) ; and 93 % ( 95 % CI = 85%-100 % ) of group 3 ( p < .001 vs. group 1 ) . On intention-to-treat analysis , eradication was 52 % , 80 % , and 86 % in groups 1 , 2 , and 3 , respectively . A good compliance was observed in more than 90 % of patients of all groups . Side effects were reported by 7 % of patients in group 1 , 9 % in group 2 , and 11 % in group 3 . None of the patients stopped therapy because of side effects . CONCLUSIONS Dual-therapy omeprazole-amoxicillin for 2 weeks is associated with significantly lower eradication rate than is 1-week omeprazole-based triple therapies . Triple therapy is well-tolerated and produces side effects similar to those of dual therapy . The highest cure rate of H. pylori infection was achieved with triple therapy of omeprazole , amoxicillin , and clarithromycin for 1 week OBJECTIVE To evaluate the efficacy of triple eradication therapy versus symptomatic therapy in children with Helicobacter pylori-associated chronic active gastritis ( H pylori-ACAG ) . STUDY DESIGN Symptomatic patients with H pylori-ACAG ( n=31 ) were r and omly assigned into two groups : ( 1 ) patients infected with H pylori who were treated with triple eradication therapy ( n = 16 ) ; and ( 2 ) patients infected with H pylori who were treated with symptomatic therapy ( n=15 ) . RESULTS After 1 year of follow-up , macroscopic appearance was significantly different in group B ( P=.023 ) , and chronic inflammation , H Pylori density , and activity were significantly higher in group B than in group A ( P=.022 , .007 , and .002 , respectively ) ; however , we did not find a significant difference in the symptoms comparing both groups ( P=.287 ) . After 1 year of follow-up , we observed the persistence of the H pylori infection in all children who had not received eradication treatment . CONCLUSIONS There is no correlation between eradication of H pylori infection and improvement of dyspeptic symptoms . Self-eradication does not occur within 1 year of follow-up . A trend toward a higher rate of chronic inflammation in noneradicated children at 1 year limited the time of our study OBJECTIVE : We sought to determine the efficacy and tolerability of novel , once-daily therapies in the treatment of Helicobacter pylori infection . METHODS : One hundred sixty subjects with H. pylori infection documented by endoscopic biopsy or serology plus 13C-urea breath test were r and omly assigned to omeprazole 80 mg q.d . and metronidazole extended-release formulation 750 mg q.d . for 10 days ( OM ) ; OM plus amoxicillin 1.5 g q.d . for 10 days ( OMAm ) ; OM plus azithromycin 500 mg q.d . for 7 days ( OMAz ) ; or OM plus clarithromycin 1 g q.d . for 10 days ( OMCl ) . A repeat breath test was done 6 wk after the completion of therapy . Subjects were considered compliant if they took ≥ 80 % of each study medication as prescribed . RESULTS : Intent-to-treat eradication rates were OM = 8 % ( 95 % confidence interval [ CI ] , 2–20 % ) , OMAm = 35 % ( 95 % CI , 21–52 % ) , OMAz = 65 % ( 95 % CI , 48–79 % ) , and OMCl = 78 % ( 95 % CI , 62–89 % ) . Lack of compliance was seen in 5 % of subjects given OM , 8 % given OMAm , 3 % given OMAz , and 15 % given OMCl . CONCLUSIONS : This pilot study demonstrated that once-daily triple therapy with high-dose omeprazole , metronidazole extended-release formulation , and clarithromycin achieved an eradication rate approaching 80 % . Further study may permit development of optimal once-daily dosing and enhance eradication rates Background : Although the ‘ test‐ and ‐treat ’ strategy is suggested as first‐line therapy for uninvestigated dyspepsia , no large‐scale studies in a real‐life setting are available . Methods : 1552 dyspeptic patients aged between 25 and 60 with no alarm symptoms were recruited to the study . After screening with a 13 C‐urea breath test , they were r and omized into three treatment arms : Helicobacter pylori‐positive either to eradication therapy with OAM ( omeprazole , amoxycillin and metronidazole ) ( Hp+/erad ) or omeprazole 20 mg daily ( Hp+/ome ) for 10 days , whereas H. pylori‐negative patients ( Hp−/ome ) were treated with 20 mg omeprazole for 10 days . Gastrointestinal symptoms were registered at baseline at 1 and 2 years on the Gastrointestinal Symptom Rating Scale ( GSRS ) and quality of life with the Psychological General Well‐Being index ( PGWB ) . Additional visits , referrals for and number of endoscopies and their findings were registered during the 2 years ' follow‐up . Results : Of the 1552 patients , 583 were H. pylori‐positive ( 37.6 % ) , and 288 of these were r and omized for omeprazole and 295 to OAM . The Hp−/ome group had fewer general practitioner ( GP ) contacts ( P < 0.0001 ) than the H. pylori‐positive groups . Eradication therapy significantly improved general well‐being and reduced upper gastrointestinal symptoms : abdominal pain ( P = 0.0001 ) , heartburn ( P = 0.0061 ) , acid regurgitation ( P = 0.003 ) , hunger pain ( P = 0.009 ) , especially in Hp+/erad . Peptic ulcer was found in 6.2 % , 1.0 % , 0.2 % in Hp+/ome , Hp−+/erad and Hp−/ome , respectively ( P = 0.0007 ) . Only 3 patients ( 1.0 % ) developed peptic ulcers in Hp−+/erad , all eradication failures . Conclusions : In uninvestigated dyspepsia , a negative test result for H. pylori reduces the number of GP contacts and endoscopy referrals compared to H. pylori‐positive regardless of eradication therapy . Applied in real life , the test‐ and ‐treat strategy failed to reduce the number of endoscopies , but significantly reduced peptic ulcer disease and improved dyspeptic symptoms and quality of life Aim : To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed Aims : The aim of the study was to compare sequential versus tailored triple therapy regimens on Helicobacter pylori ( H pylori ) eradication rates in children and to assess the effect of antimicrobial susceptibility . Patients and Methods : Prospect i ve , open-label , multicenter study . Children received r and omly either a 10-day sequential treatment comprising omeprazole ( OME ) with amoxicillin for 5 days and OME , clarithromycin ( CLA ) , and metronidazole ( MET ) for the remaining 5 days , or a 7-day triple therapy comprising OME with amoxicillin and CLA in cases of a CLA-susceptible strain or MET in cases of CLA-resistant strain . H pylori eradication was assessed by 13C-urea breath test . Results : One hundred sixty-five children , 95 girls and 70 boys , of median age 10.4 years , were included . The intention-to-treat ( ITT ) eradication rate was 76.9 % ( sequential 68/83 = 81.9 % , triple therapy 59/82 = 71.9 % , ns ) , and the per- protocol ( PP ) eradication rate was 84.6 % ( sequential 68/77 = 88.3 % , triple therapy 59/73 = 81.8 % , ns ) . Eradication rates tended to be higher using the sequential treatment , but the difference was only statistically significant for ITT analysis in children harboring both CLA- and MET-susceptible strains ( 87.8 % vs 68.5 % , odds ratio [ OR ] 3.3 , P = 0.03 ) . Both ITT and PP eradication rates were significantly lower with sequential treatment in CLA-resistant compared with CLA-susceptible strains ( ITT : 56.2 % vs 72.7 % , OR 5.5 , P = 0.008 ; PP 64.3 % vs 80.0 % , OR 7.9 , P = 0.009 ) . Both treatments were well tolerated . Conclusions : Sequential treatment is greatly effective for eradicating H pylori in children except in CLA-resistant strains . Sequential treatment can be used as a first-line therapy , but only in areas with a low CLA resistance rate BACKGROUND Data on the efficacy of eradication treatment for Helicobacter pylori gastritis in children are scarce . AIM To evaluate the efficacy of triple therapy with lansoprazole plus amoxicillin and tinidazole vs. dual therapy with amoxicillin and tinidazole in a double-blind r and omized multicentre trial , and the usefulness of eradication in terms of long-term symptom resolution . SUBJECTS We enrolled 43 consecutive children undergoing endoscopy for upper gastrointestinal dyspepsia with H. pylori gastritis . They underwent a 13C-urea breath test , completed a 2-week symptom diary card , and were r and omized . Treatment was given in a Redidose box ( Redidose Company Ltd. , Brighton , UK ) containing either lansoprazole-amoxicillin-tinidazole ( triple therapy ) or placebo plus amoxicillin-tinidazole ( dual therapy ) for 1 week . The completion of a 2-week symptom diary card and the performance of a breath test were repeated 6 weeks and 6 months after the end of therapy . One to two years later , a structured telephone interview was conducted with 36 of the children . RESULTS According to the breath test , 6 weeks after the end of therapy H. pylori was eradicated in 15 of 22 children on triple therapy [ 68.2 % ; 95 % confidence interval ( CI ) = 45 - 88 ] and in 15 of 21 children on dual therapy ( 71 % ; 95 % CI = 48 - 89 ; not significant ) , and 6 months after the end of therapy it was eradicated in 16 of 22 children on triple therapy ( 72.7 % ) and in 15 of 21 children on dual therapy . Six months after therapy , symptoms were analysed in 11 H. pylori-positive and 31 H. pylori-negative children , and it was found that dyspeptic symptoms had disappeared or improved in both groups , with no difference between them . One to two years later , 36 children were interviewed . Epigastric pain had recurred in three of 26 H. pylori-negative and in seven of 10 H. pylori-positive children ( p = .001 ) ; in three of the latter , pain was severe and required additional treatment . CONCLUSION One-week triple or dual therapy with two antibiotics achieved similar eradication rates . Soon after treatment , symptoms disappeared or improved in most children irrespective of eradication , but epigastric pain recurred in the majority of the still-infected children within 2 years BACKGROUND To compare the efficacy of two " new " one-week triple therapies ( with omeprazole , metronidazole and clarithromycin or amoxycillin ) for the eradication of Helicobacter pylori and healing duodenal ulcer . METHODS R and omised therapeutic trial . Eighty-eight consecutive duodenal ulcer patients with H. pylori infection were studied . At endoscopy , biopsies from both gastric antrum and body were obtained for histologic study ( H&E ) . Two different therapies were administered for one week : omeprazole ( O ) ( 20 mg b.i.d . ) and metronidazole ( M ) ( 500 mg b.i.d . ) associated with clarithromycin ( C ) ( 500 mg b.i.d . ) ( group OMC , n = 44 ) or amoxycillin ( A ) ( 1 g b.i.d . ) ( group OMA , n = 44 ) . Endoscopy with biopsies was repeated one month after completing therapy , and a 13C-urea breath test was also performed . Compliance was evaluated by tablet count . Analysis of data : multiple logistic regression , intention-to-treat . Eradication was defined as the absence of H. pylori by all diagnostic methods . RESULTS Mean age ( st and ard deviation ) was 45(14 ) years , 75 % males . Distribution of variables was similar in both therapeutic groups . Forty-two patients in each group completed the protocol . Eradication was achieved in 90.5 % ( 95 % CI = 78 - 96 % ) in group OMC and in 57 % ( 42 - 71 % ) in group OMA ( p < 0.001 ) . In the multivariate analysis the type of therapy was the only variable which influenced on H. pylori eradication ( OR = 7.1 ; CI = 2.2 - 24 ; p = 0.001 ) . Ulcer healing was demonstrated in 88 % ( 75 - 95 % ) of patients in group OMC and in 71 % ( 56 - 83 % ) in group OMA ( p = 0.1 ) . Ulcer healing was higher when eradication was achieved ( 90 % ; 80 - 95 % ) than in H. pylori-positive patients ( 50 % ; 31 - 69 % ) ( p < 0.001 ) . Eradication of H. pylori was the only variable which influenced on ulcer healing ( OR = 9.3 ; CI = 2.8 - 31 ; p < 0.001 ) . CONCLUSION The " new " triple therapy with omeprazole , metronidazole and clarithromycin ( administered in a twice-a-day basis and only for one week ) had an excellent efficacy for the eradication of H. pylori , significantly higher than that obtained with amoxycillin instead of clarithromycin . Both therapies achieved a high ulcer healing rate when H. pylori was eradicated , even with omeprazole administered only for one week Goals We compared the eradication results of retreatment of eradication with proton pump inhibitor ( PPI ) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin . Background In Japan , the guideline proposes that the use of metronidazole in a triple therapy containing PPI , PPI plus amoxicillin and metronidazole is desirable in retreatment . However , there are no reports comparing various retreatment using different PPIs . Methods After initial treatment failure with a PPI plus amoxicillin and clarithromycin , 169 patients were r and omized to a PPI ( rabeprazole , lansoprazole , or omeprazole ) plus amoxicillin and metronidazole given b.i.d . for 7 days . Results Pretreatment susceptibility testing showed a high level of clarithromycin resistance ( 78 % ) . The over all eradication rates were similar with the 3 PPIs , 91.1 % range 90.1 to 91.4 with intention-to-treat analysis . The presence of metronidazole resistance reduced the eradication rate by approximately 40 % ( from 96.6 % to 57.1 % , P<0.05 ) . Conclusions In Japan , the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin . The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase BACKGROUND With the increase in the frequency of clarithromycin-resistant Helicobacter pylori ( H. pylori ) , there is rising concern about the decline of the eradication rate of this infection following treatment . The Tokyo Hp Study Group examined the eradication rate in response to a second-line regimen consisting of proton pump inhibitor ( PPI ) , amoxicillin , and metronidazole by conducting a multicenter study in the Tokyo Metropolitan Area . MATERIAL S AND METHODS Two hundred and twenty-eight patients with H. pylori infection , in whom the first-line therapy with a PPI , amoxicillin , and clarithromycin administered for 1 week had failed to eradicate the infection , were enrolled in this study . These cases were r and omly assigned to one of the two second-line regimens containing metronidazole ( PPI/AM500 or PPI/AM750 ) administered for 1 week . 13C-urea breath test was performed as a diagnostic method test for H. pylori infection not earlier than 8 weeks after the second-line therapy . RESULTS Intention-to-treat ( ITT ) and per- protocol ( PP ) analyses revealed an eradication rate of 87.6 and 90.6 % , respectively , following PPI/AM500 treatment , and 86.9 and 88.6 % , respectively , following PPI/AM750 treatment . Neither analysis revealed any significant difference in the eradication rate between PPI/AM500 and PPI/AM750 ( p = .876 and .621 , respectively ) . According to ITT and PP analyses , the eradication rates following treatment with PPI/AM500 were 85.2 and 88.5 % with the use of lansoprazole , 62.5 and 62.5 % with the use of omeprazole , and 93.2 and 96.5 % with the use of rabeprazole , respectively . There was a significant difference in the eradication rates between PPI (omeprazole)/AM500 and PPI (rabeprazole)/AM500 . In the case of PPI/AM750 , the corresponding eradication rates were 84.8 and 87.0 % with the use of lansoprazole , 92.9 and 92.9 % with the use of omeprazole , and 92.9 and 92.9 % with the use of rabeprazole , respectively . There were no significant differences in the eradication rates obtained with the use of the three PPIs . CONCLUSIONS Both PPI/AM500 and PPI/AM750 administered for 1 week appeared to be highly effective second-line regimens for the treatment of H. pylori infection in Japanese patients . From the viewpoint of adverse events , PPI/AM500 appeared to be safe compared with PPI/AM750 Background : The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens . Second-line antibiotics such as tetracycline or quinolones are not licensed for children . Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake , we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance . Patients and Methods : In this open multicentre trial , 62 children ( < 18 years , body weight > 15 kg ) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin ( ∼75 mg/kg/day ) , metronidazole ( ∼25 mg/kg/day ) and esomeprazole ( ∼1.5 mg/kg/day ) for 2 weeks . Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment . Primary outcome was a negative 13C-urea breath test after 6 weeks . Results : Of 62 patients , 5 were lost to follow-up , 12 were nonadherent , and 45 treated per protocol . Eradication rates were 66 % ( 41/62 ) [ confidence interval 54–78 ] ( intention to treat ) and 73 % ( 33/45 ) [ confidence interval 60–86 ] ( per protocol ) . Success of treatment was not related to dose per kilogram body weight . Mild to moderate adverse events were reported by 21 patients , including nausea ( 10.8 % ) , diarrhoea ( 8.9 % ) , vomiting ( 7.1 % ) , abdominal pain ( 5.4 % ) , and headache ( 3.6 % ) , and led to discontinuation in 1 child . Conclusion : High-dose amoxicillin , metronidazole , and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The influence of CYP2C19 on the kinetics and dynamics of omeprazole , lansoprazole and rabeprazole has been studied in Japanese subjects . * It has been suggested that subjects with * 1/*1 genotype might need stronger acid suppression than * 1/*2 and * 2/*2 subjects . This suggestion comes from data in Japanese subjects and has not been confirmed in Caucasians . * Furthermore , a novel CYP2C19 mutation , * 17 , which mainly occurs in Caucasians has been discovered . This mutation has been associated with clinical failure , but its relevance for therapy with PPIs has not been studied yet . WHAT THIS STUDY ADDS In this study , the influence of CYP2C19 on both the pharmacokinetics and dynamics in Caucasian subjects after single and repeated dosing has been investigated . * This is the first study showing that Caucasian subjects with * 1/*1 and * 1/*17 mutations need stronger acid-inhibition . In this study three proton pump inhibitors ( omeprazole , lansoprazole and pantoprazole , in different doses ) were studied of which pantoprazole had not been studied before in this setting , not even in Japanese . AIMS To investigate the impact of CYP2C19 mutations * 2-*6 and * 17 on acid-inhibition and pharmacokinetics of lansoprazole ( L15 ) , omeprazole ( O10 , O20 ) and pantoprazole ( P40 ) in Caucasians . METHODS CYP2C19 genotyping for * 2-*6 and * 17 mutations was assessed in subjects who were H. pylori negative in two r and omized crossover trials . The influence of CYP2C19 mutations on single and repeated administration of L15 and O10 ( study A ) and O20 and P40 ( study B ) was investigated . Pharmacokinetics and the cumulative percentage of time with intragastric pH above 4 ( % > pH 4 ) were assessed on day 1 and 6 . RESULTS For study A CYP2C19 genotyping found five * 1/*1 , four * 1/*2 , one * 1/*17 and one * 2/*17 . For study B the results were six * 1/*1 , two * 1/*2 , six * 1/*17 , one * 2/*2 and one * 2/*17 . For all PPIs AUC was highest in * 2/*2 and lowest in * 1/*17 . On day 1 , all PPIs significantly increased percentage > pH 4 compared with baseline . * 1/*1 genotype showed no significant acid-inhibition after L15 , O10 and O20 . * 1/*17 genotype showed no significant acid-inhibition after O20 and P40 . * 1/*2 genotype showed significant acid-inhibition after L15 and O10 . On day 6 , all four PPIs showed significantly increased acid-inhibition . * 1/*1 and * 1/*17 showed a significantly increased percentage > pH 4 after treatment with O20 and P40 . However , in * 1/*1 subjects percentage > pH 4 was not significantly increased after L15 and O10 . * 1/*2 genotype showed a significant acid-inhibitory effect after repeated dosing with L15 and O10 . CONCLUSIONS Caucasian subjects with * 1/*1 and * 1/*17 genotype need stronger acid-suppression therapy , especially during the first days of treatment or with on-dem and therapy Background : We have previously shown that ranitidine bismuth citrate‐based , clarithromycin‐containing triple therapy achieves a higher eradication rate than proton pump inhibitor‐based regimens in areas with a high prevalence of metronidazole resistance BACKGROUND Low Helicobacter pylori eradication rates are common in pediatric trials especially in developing countries . The aim of the study was to investigate the role of antibiotic resistance , drug dosage , and administration frequency on treatment outcome for children in Vietnam . MATERIAL S AND METHODS Antibiotics resistance of H. pylori was analyzed by the Etest in 222 pretreatment isolates from children 3 - 15 years of age who were originally recruited in a r and omized trial with two treatment regiments : lansoprazole with amoxicillin and either clarithromycin ( LAC ) or metronidazole ( LAM ) in two weight groups with once- or twice-daily administration . The study design was an observational study embedded in a r and omized trial . RESULTS The overall resistance to clarithromycin , metronidazole , and amoxicillin was 50.9 % , 65.3 % , and 0.5 % , respectively . In LAC , eradication was linked to the strains being susceptible to clarithromycin ( 78.2 % vs 29.3 % , p = .0001 ) . Twice-daily dosage of proton-pump inhibitor ( PPI ) and clarithromycin was more effective for eradication than once-daily dosage for resistant strains ( 50.0 % vs 14.7 % , p = .004 ) and tended to be so also for sensitive strains ( 87.5 % vs 65.2 % , p = .051 ) . Exact antibiotic dose per body weight result ed in more eradication for resistant strains ( 45.3 % vs 8.0 % , p = .006 ) . These differences were less pronounced for the LAM regimen , with twice-daily PPI versus once daily for resistant strains result ing in 69.2 % and 50.0 % eradication ( p = .096 ) , respectively . CONCLUSIONS Helicobacter pylori clarithromycin resistance was unexpectedly high in young children in Vietnam . Clarithromycin resistance was an important cause for eradication treatment failure . Twice-daily administration and exact antibiotic dosing result ed in more eradicated infections when the strains were antibiotic resistant , which has implication s for the study design in pediatric H. pylori eradication trials BACKGROUND Limited Australian data are available on either short duration therapy for Helicobacter pylori infection , or the impact of metronidazole resistance on the outcome of treatment . AIM To compare the efficacy of two treatment regimens and determine the influence metronidazole resistance has on clearing H. pylori infection . METHODS Eighty patients with H. pylori infection proven at upper gastrointestinal endoscopy , none of whom had previously received therapy for H. pylori , were r and omised to one week therapy with either bismuth subcitrate one tablet qid , tetracycline 500 mg qid and metronidazole 400 mg tds ( BTM ) , or lansoprazole 30 mg bd , amoxycillin 500 mg qid and metronidazole 400 mg tds ( LAM ) . Effectiveness of therapy was measured by C14-urea breath test at six weeks . RESULTS On an intention-to-treat basis , clearance of infection was achieved in 17 of 32 ( 53 % ; 95 % CI : 35 - 71 % ) evaluable patients receiving BTM and 32 of 46 ( 70 % , 54 - 82 % ) patients receiving LAM ( p = 0.16 ) . Metronidazole resistance was found in 32 of 65 ( 49 % ) patients in whom H. pylori was isolated by culture . On a per- protocol basis , of patients who had metronidazole sensitive strains of H. pylori 23 of 24 ( 96 % ) cleared infection after therapy with either BTM or LAM , compared with 14 of 24 ( 58 % ) who were metronidazole resistant ( p = 0.004 ) . Clarithromycin resistance was not found in 45 patients tested . CONCLUSIONS In Western Australia clearance rates of H. pylori infection , after one week of BTM or LAM , are lower than in other published series . The high incidence of metronidazole resistance is the main determinant of our relatively poor eradication rates PURPOSE To determine the effect of Helicobacter pylori antimicrobial resistance on the efficacy of different proton pump inhibitor (PPI)-based triple therapies . METHODS One-hundred and twelve dyspeptic patients with H. pylori infection , as demonstrated by positive histology and culture , were r and omized to receive one of the three PPI-based triple therapies . The regimens included lansoprazole ( L ) plus any two of the following three antibiotics : amoxicillin ( A ) , metronidazole ( M ) , and clarithromycin ( C ) ; patients were allocated to ALC , MLC , and ALM subgroups . Six weeks after the start of triple therapy , the 13C-urea breath test ( UBT ) was performed to evaluate the success of H. pylori eradication . Patients with positive UBT results underwent endoscopy for H. pylori culture . The pre- and post-treatment H. pylori isolates were analyzed for initial and acquired resistance using the E-test . RESULTS One hundred patients completed the study . The H. pylori eradication rates were 70 % ( 21/30 ) in the ALM subgroups , 79 % ( 26/33 ) in the MLC subgroup , and 89 % ( 33/37 ) in the ALC subgroup . The frequencies of pretreatment H. pylori antimicrobial resistance were 0 % for amoxicillin resistance ( AR ) , 32 % for metronidazole resistance ( MR ) , and 6 % for clarithromycin resistance ( CR ) . For H. pylori isolates with initial MR , the eradication rates in the ALM ( 40 % ) and MLC ( 67 % ) subgroups were apparently lower than that in the ALC ( 92 % ) subgroup . In the ALM and MLC subgroups ( i.e. , patients who received metronidazole ) , the eradication failure rate was significantly higher for patients with MR isolates than for patients with metronidazole-susceptible isolates ( 47 % vs 16 % , p < 0.05 ) . In the ALC and MLC subgroups ( i.e. , patients who received clarithromycin ) , the eradication failure rate was significantly higher for patients with CR isolates than for those with clarithromycin-susceptible isolates ( 100 % vs 11 % , p < 0.05 ) . CONCLUSIONS The results indicate that H. pylori antimicrobial resistance is relevant to the success of eradication . The high MR but low CR and AR prevalence among H. pylori isolates in this study suggests that PPI-based triple therapy including amoxicillin and clarithromycin may achieve the most favorable eradication rate BACKGROUND The eradication of Helicobacter pylori infection is beneficial in patients with gastric or duodenal ulcers . The value of eradicating the infection in patients with dyspepsia and no evidence of ulcer disease is not known . METHODS We performed a r and omized , placebo-controlled trial comparing the efficacy of treatment for two weeks with 20 mg of omeprazole orally twice daily , 500 mg of amoxicillin three times daily ( with 500 mg of tetracycline three times daily substituted for amoxicillin in patients allergic to penicillin ) , and 400 mg of metronidazole three times daily ( 160 patients ) with that of omeprazole alone ( 158 patients ) for resolving symptoms of dyspepsia in patients with H. pylori infection but no evidence of ulcer disease on upper gastrointestinal endoscopy . Symptoms were assessed with the Glasgow Dyspepsia Severity Score , with resolution of symptoms defined as a score of 0 or 1 in the preceding six months ( maximal score , 20 ) . One year later the patients were assessed to determine the frequency of the resolution of symptoms . RESULTS One month after the completion of treatment , 132 of 150 patients ( 88 percent ) in the group assigned to received omeprazole and antibiotics had a negative test for H. pylori , as compared with 7 of 152 ( 5 percent ) in the group assigned to receive omeprazole alone . One year later , dyspepsia had resolved in 33 of 154 patients ( 21 percent ) in the group given omeprazole and antibiotics , as compared with 11 of 154 ( 7 percent ) in the group given omeprazole alone ( 95 percent confidence interval for the difference , 7 to 22 percent ; P<0.001 ) . Among the patients in the group given omeprazole and antibiotics , the symptoms resolved in 26 of the 98 patients ( 27 percent ) who had had symptoms for five years or less , as compared with 7 of the 56 patients ( 12 percent ) who had had symptoms for more than five years ( P=0.03 ) . CONCLUSIONS In patients with H. pylori infection and nonulcer , or functional , dyspepsia , treatment with omeprazole and antibiotics to eradicate the infection is more likely to resolve symptoms than treatment with omeprazole alone A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection . A three-drug regimen comprising metronidazole , amoxycillin and omeprazole has been proposed as an alternative therapy . In a prospect i ve , r and omized , comparative study , we evaluated these two regimens with respect to safety and efficacy in patients with H. pylori infection . Sixty patients with peptic ulcer ( gastric , 32 patients ; duodenal , 28 patients ) who had a history of ulcer recurrence were r and omly assigned to dual therapy with amoxycillin ( 500 mg three times daily for 2 weeks ) and omeprazole ( 20 mg once daily for 8 weeks ) or to triple therapy with metronidazole ( 500 mg twice daily for 2 weeks ) plus amoxycillin and omeprazole , given in the same dosages as dual therapy . Forty-eight patients completed the protocol ; treatment was discontinued because of side effects in nine patients , and three patients dropped out of the study . On the basis of all patients treated , the rate of H. pylori eradication was significantly higher for triple therapy 20/23 cases , 87.0 % ; 95 % confidence interval ( CI ) , 0.664 - 0.972 ) than for dual therapy 13/25 , 52.0 % ; 0.313 - 0.722 ; P < 0.05 ) . On an intention-to-treat basis , the difference between the groups in the rate of H. pylori eradication was marginally significant ( P = 0.06 [ 0.028 - 0.512 ] ) . Side effects were reported by five patients receiving triple therapy ( skin rash , one ; nausea , two ; headache , one ; abdominal pain , one ) , and four patients receiving dual therapy ( skin rash , two ; abdominal pain , one ; diarrhoea , one ) . All side effects resolved spontaneously after termination of treatment . There was no significant difference in safety between the two regimens . Triple therapy with metronidazole , amoxycillin , and omeprazole was significantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone . The safety of these regimens was similar , and triple therapy was found to be clinical ly acceptable Helicobacter pylori is the main acquired factor in the pathogenesis of duodenal ulcer disease . AIM One-week triple therapy with proton pump inhibitors , clarithromycin and amoxicillin has recently been proposed as the first-line treatment for Helicobacter pylori ( H. pylori ) infection ; however , data regarding the effects of this regimen in China are scarce . The aim of this prospect i ve and r and omized study was to compare the efficacy of clarithromycin and metronidazole when they were combined with omeprazole and amoxicillin on eradication of H. pylori and ulcer healing in Chinese peptic ulcer patients . METHODS A total of 103 subjects with H. pylori-positive peptic ulcer were r and omly divided into two groups , and accepted triple therapy with omeprazole 20 mg , amoxicillin 1000 mg and either clarithromycin 500 mg ( OAC group , n = 58 ) or metronidazole 400 mg ( OAM group , n = 45 ) . All drugs were given twice daily for 7 d. Patients with active peptic ulcer were treated with omeprazole 20 mg daily for 2 - 4 wk after anti-H. pylori therapy . Six to eight weeks after omeprazole therapy , all patients underwent endoscopies and four biopsies ( two from the antrum and two others from the corpus of stomach ) were taken for rapid urease test and histological analysis ( with modified Giemsa staining ) to examine H. pylori . Successful eradication was defined as negative results from both examination methods . RESULTS One hundred patients completed the entire course of therapy and returned for follow-up . The eradication rate of H. pylori for the per- protocol analysis was 89.3 % ( 50/56 ) in OAC group and 84.1 % ( 37/44 ) in OAM group . Based on the intention-to-treat analysis , the eradication rate of H. pylori was 86.2 % ( 50/58 ) in OAC group and 82.2 % ( 37/45 ) in OAM group . There were no significant differences in eradication rates between the two groups on either analysis . The active ulcer-healing rate was 96.7 % ( 29/30 ) in OAC group and 100 % ( 21/21 ) in OAM group ( per- protocol analysis , P>0.05 ) . Six patients in OAC group ( 10.3 % ) and five in OAM group ( 11.1 % ) reported adverse events ( P>0.05 ) . CONCLUSION One-week triple therapy with omeprazole and amoxicillin in combination with either clarithromycin or metronidazole is effective for the eradication of H. pylori . The therapeutic regimen comprising metronidazole with low cost , good compliance and mild adverse events may offer a good choice for the treatment of peptic ulcers associated with H. pylori infection in China Helicobacter pylori ( H. pylori ) is currently considered the most important exogenous factor in the genesis of gastritis and peptic ulcer disease . However , the optimum regimen for the eradication of H. pylori remains unclear . The purpose of this study was to evaluate the eradication rate of H. pylori , the side effects , and the patients ' compliance with regard to various drug regimens . We also analyzed factors influencing the eradication of H. pylori . One hundred and eighty patients were included and divided into four groups : 42 patients ( Group I ) received tripotassium dicitrato bismuthate ( 240 mg b.i.d . ) , metronidazole ( 250 mg t.i.d . ) and amoxicillin ( 500 mg t.i.d . ) for 14 days ; 55 patients ( Group 2 ) received omeprazole ( 20 mg b.i.d . ) and amoxicillin ( 1000 mg b.i.d . ) for 14 days ; 36 patients ( Group 3 ) were treated with omeprazole ( 20 mg b.i.d . ) , metronidazole ( 250 mg t.i.d . ) and amoxicillin ( 500 mg t.i.d . ) for 14 days ; and 47 patients ( Group 4 ) received omeprazole ( 20 mg q.d . ) and amoxicillin ( 500 mg t.i.d . ) for 14 days and then tripotassium dicitrato bismuthate ( 240 mg b.i.d . ) and nizatidine ( 150 mg q.d . ) for 14 days . The diagnosis of H. pylori was made by histology . The eradication of H. pylori was defined both by histology ( H&E and Giemsa stain ) and by rapid urease test ( CLOR ) showing negative for H. pylori 4 weeks after the completion of therapy . Of the 180 patients , 95 patients had non-ulcer dyspepsia , 40 patients had gastric ulcer and 45 patients had duodenal ulcer . The eradication rate of H. pylori was highest ( 89.3 % ) in Group 3 , as compared with Group 1 ( 68.9 % ) , Group 2 ( 65.4 % ) , and Group 4 ( 48.9 % ) . The eradication rate was significantly higher in Group 3 than in Groups 2 and 4 ( p < 0.05 ) . There was no significant difference in the eradication rate among clinical diagnosis , sex and age . But , in the conventional triple therapy ( Group 1 ) , the eradication rate was higher in male ( 78.6 % ) than in female ( 46.2 % ) . The side effects in order , were nausea ( 22.1 % ) , dizziness ( 19.5 % ) , abdominal pain ( 11.6 % ) and diarrhea ( 97 % ) , and there was no difference among the drug regimens . The compliance of the patients was good ( more than 80 % irrespective of drug regimen ) . On the basis of these findings , the side effects of the drugs seemed minimal , and the compliance of patients was good irrespective of the drug regimen . In conclusion , the triple therapy with omeprazole , metronidazole and amoxicillin was the most effective regimen and could be recommended for H. pylori eradication BACKGROUND Helicobacter pylori ( H. pylori ) infection plays an important role in the pathogenesis of duodenal ulcer ( DU ) disease . Low DU recurrences and reinfection rates were universally described , when treatment was effective . It has been suggested that short-term triple therapy , comprising a proton pump inhibitor plus two antibiotics ( clarithromycin , amoxicillin or a nitroimidazole ) , should be used as first choice in treating H. pylori infection . Nevertheless , conflicting results have been reported on using these treatment regimens in different countries , due to the resistance of H. pylori against one or more antibiotics . Our aim was to compare the efficacy , for H. pylori eradication , of 1-week triple therapy versus 10 and 14-day triple schedules , in patients with a history of recurrent DU . METHODS A total of 159 patients ( 85 males , mean age 59.2+/-3.2 years ) was r and omly treated with a triple therapy including a st and ard dose of omeprazole twice daily , amoxicillin 1 g twice daily and metronidazole 500 mg twice daily . Fifty-three patients received 1-week triple therapy ( Group I ) , 53 subjects were treated with 10-day triple therapy ( Group II ) and 53 others with 14-day triple therapy ( Group III ) . H. pylori infection at entry and eradication , at least 4 weeks after therapy had ended , was assessed by 13C urea breath test and histology on biopsies from the antrum and the corpus . RESULTS Of the 159 subjects r and omised into the study , 6 ( 3 in group II and 3 in group III ) were excluded from the per protocol ( PP ) analysis because of discontinuations . At the end of the course of treatment , the overall H. pylori eradication rate in the intention-to-treat analysis , was 73.5 % ( 39/53 ) in group I , 71.6 % ( 38/53 ) in group II and 73.5 % ( 39/53 ) in group III , without any statistically significant difference . Moreover , the PP analysis also showed no statistical differences , with an eradication rate of 73.5 % ( 39/53 ) in group I , 76 % ( 38/50 ) in group II and 78 % ( 39/50 ) in group III . The reported frequency of side-effects was evenly distributed between the groups , but 6 patients ( 3.7 % ) stopped because of adverse events only in groups II and III . CONCLUSIONS The present study shows that there is no significant difference between the three regimens although the 14-day triple therapy shows a slightly higher H. pylori eradication rate . There is a strong need , in our region , to put forward surveillance programmes to monitor the prevalence of local resistant strains and to guide treatment on the basis of resistance patterns OBJECTIVE To compare the efficacies of pantoprazole and omeprazole-based triple regimens in the treatment of H. pylori infection for 1-week or 2-week . METHODS 147 patients with H. pylori associated gastritis were r and omly divided into pantoprazole triple regimen group ( pantoprazole 40 mg , amoxicillin 1 g , and metronidazole 400 mg , bid , for 1-week or 2-weeks ) and omeprazole triple regimen ( omeprazole 20 mg , amoxicillin 1 g , and metronidazole 400 mg , bid , for 1-week or 2-weeks ) . The eradication was determined by (13)C-UBT at least 4 weeks after antibiotic therapy . RESULTS The eradication rate of H. pylori for 1-week pantoprazole triple regimen and omeprazole triple regimen were 85.7 % ( 42/49 ) and 76.9 % ( 20/26 ) respectively ( P > 0.05 ) . The eradication rates of H. pylori for 2-weeks and pantoprazole triple regimen and omeprazole triple regimen were 93.9 % ( 31/33 ) and 82.1 % ( 32/39 ) for 2-week respectively ( P > 0.05 ) . CONCLUSION The eradication rate of H. pylori in pantoprazole ( or omerazole ) triple therapy regimen for 2-weeks was higher than 1-week . However there were no significant difference between in these two groups ( P > 0.05 ) . There were no significant difference between pantoprazole and omeprazole triple therapy regimen in eradication rate of H. pylori for 1-week or 2-weeks ( P > 0.05 ) Objectives : To study the prevalence of Helicobacter pylori infection in patients with erosive duodenitis ( ED ) , the associated gastric histological lesions and their response to eradication therapy with omeprazole plus two antibiotics . Methods : A prospect i ve study was made of 57 patients with ED ( mean age 46±16 years , 72 % males ) . At endoscopy , biopsies from gastric antrum and body were obtained for histological study ( haematoxylin and eosin ) . A 13C‐urea breath test was also performed . Omeprazole 20 mg twice daily plus two antibiotics ( amoxycillin 1 g twice daily , clarithromycin 500 mg twice daily , metronidazole 500 mg twice daily ) were administered for 1 week . Endoscopy and breath test were repeated 1 month after completing therapy , and the breath test was performed again at 6 months . Results : All patients were H. pylori positive . Overall eradication was achieved in 86 % ( 95 % CI 75‐93 % ) . Duodenal erosion healing was obtained in 45 patients ( 79 % ) . Healing was achieved in 86 % ( CI 73‐93 % ) of cases with successful eradication therapy , but only in 3/8 ( 37 % ; CI 8.5‐75 % ) patients with therapy failure ( P<0.01 ) . In the multivariate analysis , H. pylori eradication was the only variable which correlated with erosion healing ( odds ratio 10 ; CI 2‐51 ; P<0.01 ) . Histological improvement , in both the gastric antrum and body , was demonstrated when eradication was achieved ( P<0.001 ) . Six months after diagnosis H. pylori absence was confirmed in all patients with initial therapy success ( all of them asymptomatic ) , and infection was confirmed in the eight patients who were H. pylori positive after therapy ( six of them symptomatic ) . At 6‐month follow‐up , endoscopy was normal in 6/7 H. pylori‐negative patients with previously persistent ED , while erosions were still present in 4/5 H. pylori‐positive patients with previously persistent ED . Conclusion : A high prevalence ( 100 % ) of H. pylori infection in patients with ED was observed . A 1‐week twice daily therapy with omeprazole plus two antibiotics ( clarithromycin plus amoxycillin or metronidazole ) was very effective in H. pylori eradication , duodenal erosion healing , symptomatic improvement , and in disappearance of associated histological gastritis . These observations suggest that ED should be considered a variant form of duodenal ulcer disease and treated accordingly ; that is , with H. pylori eradication therapy BACKGROUND AND OBJECTIVES Although its pathophysiology is not obvious , the discussion on chronic nonspecific pharyngeal symptoms encompasses a broad range of various factors , such as nasal obstruction , extraesophageal reflux disease , some of the chronic upper respiratory infections , and allergy . We found a high seroprevalence of Helicobacter pylori in a group of selected patients with no possible conditions responsible for complaints . To show a possible role of H. pylori infection in chronic pharyngeal complaints , we investigated symptomatic response following eradication therapy . PATIENTS AND METHODS In a prospect i ve cohort study , 72 subjects with H. pylori seropositivity had their symptoms measured by a question naire before and 3 months following H. pylori eradication therapy . The symptomatic response was compared between eradicated and noneradicated groups 3 months after eradication therapy . RESULTS In 39 of 72 patients H. pylori was eradicated successfully . Mann-Whitney U analysis showed the pharyngeal symptom improvement rate , measured using the absolute difference in symptom score . For two major symptoms ( chronic throat irritation , sore throat ) , it was significantly lower for H. pylori-noneradicated cases than for H. pylori-eradicated cases ( p = .003 and p < .001 , respectively ) . CONCLUSION Resolution of the symptoms in the eradicated group suggests that H. pylori has a role in developing chronic nonspecific pharyngeal symptoms . These data may be important for future treatment strategies for this disease BACKGROUND Helicobacter pylori infection is associated with low- grade gastric MALT lymphoma , and available data support that the eradication of the H. pylori can cause histological regression of the lymphoma . PATIENTS AND METHODS Nine patients with low- grade gastric MALT lymphoma were treated with amoxicillin , metronidazole , and omeprazole for 14 days in a prospect i ve study . Patients were followed up with sequential endoscopy , mapping gastric biopsies , and molecular studies with PCR amplification of the IgH gene in order to assess the response to H. pylori eradication and the evolution of the histological molecular responses . RESULTS H. pylori was eradicated in all patients and reinfections were not demonstrated . After H. pylori eradication treatment , the lymphoma regressed both endoscopically and histologically in eight of the nine patients ( 88.8 % ) . In four of the eight histologically cured patients , no clonal b and was detected by PCR ; in the remaining four patients ; PCR identified a clonal b and , which disappeared in all patients after a mean of 12 + /- 4 months . No clonal b and was detected by the PCR analysis in any of the eight patients with histological regression after a median of 7 + /- 6 months ( range 1 - 20 ) . The seven followed-up patients have a persistent clinical and histological remission after a median of 14 + /- 5 months . CONCLUSIONS ( 1 ) Low- grade gastric MALT lymphoma can be histologically cured with eradication therapy for H. pylori . ( 2 ) After histological regression , PCR amplification of the IgH gene can identify an eventually persisting clonal population . ( 3 ) Sequential histological and molecular studies are essential for the assessment of the evolution of the lymphoma . ( 4 ) The clonal population tends to disappear , but its disappearance may be delayed for months . ( 5 ) Patients with histological regression but with a persistent clonal b and should not be treated unless the lymphoma can be histologically demonstrated . All these observations suggest that gastric lymphoma can be effectively cured , but the ultimate fate of these patients is unknown until long-term follow-up studies are available Background / aims : Current Helicobacter pylori eradication therapy for peptic ulcer disease usually involves a 2‐week course of either a bismuth preparation or omeprazole in combination with antibiotics . We have studied a shorter , 7‐day course of treatment to assess efficacy and tolerability Aim : To study the efficacy of three pantoprazole‐based triple therapy regimens for the eradication of Helicobacter pylori infection and gastric ulcer healing BACKGROUND Numerous therapeutic trials aim ed at eradicating Helicobacter pylori ( HP ) from the gastric mucosa and preventing ulcer recurrence have been carried out ; however , an optimal treatment has not yet been established with carefully controlled r and omized studies . OBJECTIVE The aim of our study was to evaluate the efficacy of an association of omeprazole ( OM ) coupled with two antibiotics in the eradication of HP and prevention of duodenal ulcer ( DU ) recurrence . METHODS One hundred and eighty three patients with active DU were r and omized under double-blind conditions to receive either OM 20 mg for 4 wk plus amoxycillin 3 g daily and metronidazole 1 g daily during the 2nd and 3rd wk ( 91 patients , group A ) or OM 20 mg for 4 wk plus matching placebo ( 92 patients , group B ) . Endoscopy was performed before and at the end of the 4-wk treatment as well as 2 , 6 , and 12 months later . Biopsies were taken from the duodenum , antrum , and gastric body at each endoscopic examination for HP histological detection and for evaluation of inflammatory changes according to the Sydney system . RESULTS After 4 wk , 84/86 patients ( 98 % ) of group A and 80/86 ( 93 % ) of group B were healed of their ulcers . The percentage of eradication was 90 % in group A and 1 % in group B. During a 12-month follow-up , DU relapsed in 4/63 ( 6 % , including two of three reinfected cases ) HP-eradicated group A patients , 4/8 ( 50 % ) HP-noneradicated group A patients , and 52/65 ( 80 % ) persistently HP-positive group B patients . Rapid , complete , and persistent suppression of gastroduodenitis activity and gastric surface epithelium lesions was observed in most HP-eradicated group A patients , whereas a transient decrease of bacterial colonization and inflammatory scores in the antrum and a transient worsening of corpus gastritis were found in group B patients . CONCLUSIONS The combined therapy with amoxycillin , metronidazole , and omeprazole is highly effective in both HP eradication and prevention of duodenal ulcer recurrence OBJECTIVES Many of the currently used Helicobacter pylori eradication regimens fail to cure 5 - 20 % of the patients . Those patients will remain at risk of developing a potentially fatal complication of peptic ulcer disease . Therefore , a new attempt to cure H. pylori infection after initial failure of therapy is indicated . We studied the efficacy of three retreatment regimens after initial failure of omeprazole-amoxicillin dual therapy . METHODS Fifty-three patients whose treatment failed were r and omly assigned to receive retreatment with the same regimen of omeprazole 20 mg b.i.d . ( group I ) or omeprazole 40 mg t.i.d . ( group II ) plus amoxicillin 750 mg t.i.d . for 14 days . Forty patients in whom the omeprazole-amoxicillin retreatment failed were assigned to receive omeprazole 20 mg b.i.d . , amoxicillin 750 mg t.i.d . , and metronidazole 500 mg t.i.d . for 14 days ( group III ) or omeprazole 20 mg b.i.d . plus clarithromycin 500 mg t.i.d . for 14 days ( group IV ) . H. pylori infection was assessed by culture and histology of gastric biopsies before and 4 - 6 wk after cessation of therapy . Susceptibility of H. pylori to amoxicillin , clarithromycin , and metronidazole was determined by the E test . RESULTS In groups I ( n = 28 ) and II ( n = 25 ) , cure of H. pylori infection was achieved in 21 % and 28 % of patients , respectively ( not significant ) . In groups III ( n = 20 ) and IV ( n = 20 ) , H. pylori infection was cured in 75 % and 70 % , respectively . CONCLUSIONS Retreatment with an identical omeprazole-amoxicillin dual regimen is of limited benefit , a result that is independent of the omeprazole dose . In contrast , a third H. pylori eradication attempt with omeprazole-clarithromycin dual therapy or omeprazole-amoxicillin-metronidazole triple therapy provides reasonable cure rates after failure of omeprazole-amoxicillin dual therapy Lansoprazole 30 mg , amoxicillin 1000 mg , and tinidazole 500 mg were given twice daily to 39 peptic ulcer patients ( 26 duodenal and 13 gastric ulcer , mean age 52.4 + /- 15.01 ) who had H. pylori infection for two weeks . Additional lansoprazole 30 mg daily was given to duodenal and gastric ulcer patients for another two and six weeks respectively . Follow-up gastroduodenoscope was performed at fourth and eighth week and eighth and twelfth week for all duodenal and gastric ulcer patients , respectively . H. pylori status was evaluated by rapid urease test ( CLO test ) and histology at first and last endoscope . The ulcers were healed at the last endoscopy in 11 ( 85 % ) gastric ulcer patients and 24 ( 92 % ) duodenal ulcers patients . H. pylori infection was eradicated in 31 patients ( 79 % ) . Mild side effects were observed in 15 per cent . In conclusion , 2 week regimen of lansoprazole , amoxicillin , and tinidazole triple therapy result ed in a relatively high healing rate of peptic ulcer ( 90 % ) and an acceptable eradication rate of H. pylori infection ( 79 % ) BACKGROUND Rabeprazole in combination with amoxicillin and metronidazole ( RAM ) has been shown to be an effective second-line treatment of Helicobacter pylori infection . The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients . METHODS Helicobacter pylori-positive dyspeptic patients were r and omized to receive either ( i ) rabeprazole 10 mg , amoxicillin 1000 mg and metronidazole 400 mg ( RAM-10 ) or ( ii ) high-dose rabeprazole 20 mg , amoxicillin 1000 mg and metronidazole 400 mg ( RAM-20 ) , each given twice daily for 7 days . Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications . side-effects of treatments were documented . RESULTS A total of 120 patients were eligible for analysis . By intention-to-treat and per- protocol analysis , the eradication rates were 83 % and 86 % in the RAM-10 group and 75 % and 76 % in the RAM-20 group , respectively ( P = 0.26 and P = 0.17 ) . Both regimens were well-tolerated and compliance was > 98 % in both groups . CONCLUSIONS Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective , economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population BACKGROUND Although combinations of antibiotics and antisecretory drugs are useful for treatment of Helicobacter pylori infection , treatment failure is common . The aim of this study was to evaluate the relation between pretreatment antibiotic resistance and outcome by using six different treatment regimens for H. pylori infection . PATIENTS AND METHODS Three hundred sixty-nine consecutive H. pylori-infected patients with dyspeptic symptoms were enrolled in three consecutive r and omized , controlled , single-center clinical trials : trial A , 128 patients ; trial B , 125 patients ; trial C , 116 patients . Treatments consisted of ( A ) a 15-day course of dual therapy ( omeprazole , 20 mg bid , and amoxicillin , 1 gm bid , or clarithromycin , 500 mg tid ) ( OA vs OC ) ; ( B ) a 7-day triple therapy of omeprazole , 20 mg bid , plus metronidazole , 500 mg bid , and amoxicillin , 1,000 mg bid , or clarithromycin , 500 mg tid ( OMA vs OMC ) ; or ( C ) omeprazole , 20 mg bid , plus metronidazole , 500 mg bid , plus tetracycline , 500 mg qid , or doxycycline , 100 mg tid ( OMT vs OMD ) . Diagnostic endoscopy was made in all patients before and 5 to 6 weeks after therapy . Six biopsies were taken from each patient for histology , rapid urease test , and H. pylori culture ; antibiotic susceptibility testing was performed using the E-test method . RESULTS Overall cure rates were poor for both dual therapies OA and OC ( 38 % and 37 % , respectively ) and for triple therapies OMA , OMC , and OMD ( 57 % , 55 % , and 58 % , respectively ) . The OMT combination was successful in 91 % ( 95 % confidence interval [ CI ] , 80.4%-97 % ) . Metronidazole resistance was present in 29.7 % ( 95 % CI , 24%-35 % ) , amoxicillin resistance was present in 26 % ( 95 % CI , 21%-32 % ) , clarithromycin resistance was present in 23.1 % ( 95 % CI , 18%-29 % ) , tetracycline resistance was present in 14 % ( 95 % CI , 10%-20 % ) , and doxycycline resistance was present in 33.3 % ( 95 % CI , 21%-47 % ) . Antibiotic resistance markedly reduced the cure rates and accounted for most of the poor results with the triple therapies : 89 % versus 23 % ; 77 % versus 26 % ; 100 % versus 60 % ; and 67 % versus 23 % for OMC , OMA , OMT , and OMD , respectively . OMT appeared to be the best because of the high success rate with metronidazole-resistant H. pylori ( 71 % ) and in low-level tetracycline resistance . CONCLUSIONS Pretreatment antibiotic-resistant H. pylori can , in part , explain the low cure rate of the infection and the variability in outcome in reported trials BACKGROUND Studies on eradication therapy in developing countries have shown a success rate of 70 - 85 % , which is suboptimal . Duration of therapy may be an important factor dictating eradication success in such regions . AIMS The study was undertaken to evaluate the effect of increasing the treatment period on eradication of Helicobacter pylori in duodenal ulcer disease . METHODS A r and omized trial was carried out in which 64 consecutive H. pylori-infected patients with duodenal ulcer disease were enrolled . The patients were r and omized to one of the three trial arms . Therapy consisted of lansoprazole 30 mg twice a day ( b.i.d . ) , amoxycillin 1 g b.i.d . and tinidazole 500 mg b.i.d . The treatment period was 1 week in group I , 2 weeks in group II and 3 weeks in group III . At inclusion , patients underwent endoscopy and the presence of H. pylori was documented by a positive urease test and C14 urea breath test . Four weeks after completion of eradication therapy , the patients were subjected to repeat endoscopy to assess ulcer healing and tests for H. pylori infection . RESULTS Sixty-four patients ( 55 male and nine female ; mean age 35.5 years ) were enrolled in each group . The H. pylori eradication rate for group I ( 1 week of therapy ) was 47.6 % , that for group II ( 2 weeks of therapy ) was 80 % , and that for group III ( 3 weeks of therapy ) was 91.3 % ( p = .003 ) . The ulcer healing rates were 71.4 , 80 and 95.6 % in groups I , II and III , respectively ( p = .09 ) . CONCLUSIONS The 3-week regimen significantly improved the eradication rate as compared with the 1-week regime . Increasing the duration of therapy significantly improved the chances of eradication of H. pylori in duodenal ulcer disease While addition of metronidazole to the omeprazole – amoxycillin combination has been shown to be advantageous , the optimal dosage and drug distribution of the antimicrobials has not been sufficiently evaluated The purpose s of this study were to assess the efficacy of a 1-week proton pump inhibitor (PPI)-based triple therapy after failure of dual therapy in Helicobacter pylori eradication , and to compare the effectiveness of clarithromycin and metronidazole in this regimen . Between January 1996 and March 1997 , 67 patients with persistent H. pylori infection after a 2-week course of dual therapy ( amoxicillin plus omeprazole ) were enrolled . They were r and omly assigned to receive amoxicillin ( 1000 mg twice daily ) and omeprazole ( 20 mg twice daily ) plus either metronidazole ( 500 mg twice daily ) or clarithromycin ( 250 mg twice daily ) . Endoscopy was performed in each patient to assess the status of H. pylori using the rapid urease test ( CLOtest ) and the histologic findings before dual therapy , after dual therapy , and after triple therapy . H. pylori isolates were tested for antibiotic resistance when triple therapy failed . The 1-week triple therapy was well tolerated in both groups with no adverse effects severe enough to cause withdrawal from the trial . Residual H. pylori was eradicated in 94 % ( 33/35 ) of patients in the clarithromycin group and 84 % ( 27/32 ) in the metronidazole group ; the difference was not statistically significant . All seven patients in whom triple therapy failed were infected with metronidazole-resistant isolates and two also had clarithromycin-resistant isolates . This 1-week triple therapy is safe and effective in eradicating residual H. pylori after dual therapy failure . Failure of the rescue regimen is related to antimicrobial agent resistance . Because of the high metronidazole resistance rate in Taiwan , clarithromycin appears to be more promising than metronidazole for the control of H. pylori BACKGROUND The ideal second-line treatment regimens for Helicobacter pylori infection may differ between the areas , countries and races . AIM The aim was to confirm which was the better regimen for second-line therapy after treatment failure with a st and ard triple therapy in Japan , a high dosage of levofloxacin- or metronidazole-based therapy . PATIENTS Sixty out patients with persistent H. pylori infection after a st and ard triple therapy were enrolled in this prospect i ve , open-label and r and omised trial . METHODS The subjects were r and omly administered levofloxacin ( 300 mg b.d.)- or metronidazole ( 500 mg b.d.)-based therapy with lansoprazole ( 30 mg b.d . ) and amoxicillin ( 1000 mg b.d . ) for 7 days , and the cure rates and side effects were analysed . Antimicrobial susceptibility was also examined before second-line therapy using the E-test . RESULTS Good compliance was obtained without severe side effects in both the groups except for two patients . The cure rates , expressed as intention-to-treat and per- protocol analyses , respectively , were 70.0 and 72.4 % in the levofloxacin group , and 96.7 and 100 % in the metronidazole group . Each regimen often overcame even clarithromycin-resistant strains . CONCLUSION Metronidazole-based triple therapy is recommended as second-line therapy in Japan , and levofloxacin-based therapy can be an alternative treatment option An open , r and omized trial was performed to compare the efficacy of three Helicobacter pylori eradication regimens in children with peptic ulcer disease . A total of 106 children ( 5–15 years ) were treated for 1 week with metronidazole , 30–40 mg/kg per day depending on age , amoxycillin , 750 mg/day , and one of three anti-secretory agents : proprietary omeprazole , 20–40 mg/day depending on age ; generic omeprazole , 20–40 mg/day ; or ranitidine , 150 mg twice daily . The H. pylori eradication rate was significantly higher in patients receiving proprietary omeprazole ( 88.9 % ) than in those receiving generic omeprazole ( 80.0 % ) or ranitidine ( 74.3 % ) , and this was associated with a trend towards faster ulcer healing . It is concluded that triple therapy consisting of an anti-secretory agent and two antimicrobials produces effective eradication of H. pylori and ulcer healing in children with peptic ulcer disease , and that proprietary omeprazole is more effective than both ranitidine and the generic formulation used in this BACKGROUND The establishment of an optimal second-line regimen for Helicobacter pylori infection is required . Although quadruple therapy should overcome resistance to either clarithromycin or metronidazole , the effects of a quadruple regimen in second-line therapy are unknown . This study aims to evaluate the efficacy of triple therapy composed of proton pump inhibitor/amoxicillin plus metronidazole with the combined additive effects of clarithromycin as a second-line quadruple therapy against H. pylori infection . MATERIAL S AND METHODS Participants were 104 patients in whom first-line therapy containing proton pump inhibitor-amoxicillin-clarithromycin failed . Before starting second-line therapy , patients underwent endoscopy to obtain H. pylori strain for antibiotic susceptibility tests . Patients were r and omized to receive rabeprazole ( 10 mg ) , amoxicillin ( 750 mg ) , and metronidazole ( 250 mg ) , either with clarithromycin ( 200 mg ; RAMC group ) or without ( RAM group ) ; all treatments were administered twice daily for 7 days . H. pylori eradication was confirmed by (13)C-urea breath tests performed 2 to 3 months post-therapy . RESULTS As shown by intention-to-treat/per- protocol analyses , the cure rates for H. pylori infection were 88.5%/93.9 % and 82.7%/84.3 % for the RAMC and RAM groups . Although the study probably had an insufficient power to show a significant difference between the cure rates of the two regimens , the eradication rates showed a clear trend in favor of the RAMC group . There were no severe side-effects in any group . CONCLUSIONS In Japan , the RAMC regimen is thought to be a promising alternative strategy for second-line eradication of H. pylori infection BACKGROUND & AIMS Strategies to eradicate Helicobacter pylori infection could be improved by suppressing acid and extending the duration of therapy ( optimization ) . We compared the efficacy of 2 different optimized nonbismuth quadruple regimens in areas of high resistance to antimicrobial agents . METHODS We performed a prospect i ve noninferiority multicenter trial in which 343 consecutive individuals with H pylori infection were assigned r and omly to groups given hybrid therapy ( 40 mg omeprazole and 1 g amoxicillin , twice daily for 14 days ; 500 mg clarithromycin and 500 mg nitroimidazole were added , twice daily for the final 7 days ) or concomitant therapy ( same 4 drugs taken concurrently , twice daily for 14 days ) . We assessed bacterial resistance to these drugs in a subset of patients using the E-test . Efficacy , side effects , and compliance were determined . RESULTS In per- protocol analysis , rates of eradication for hybrid and concomitant therapies were 92 % ( 95 % confidence interval [ CI ] , 87%-95 % ) and 96.1 % ( 95 % CI , 93%-99 % ) , respectively ( P = .07 ) . In intention-to-treat analysis , rates were 90 % ( 95 % CI , 86%-93 % ) and 91.7 % ( 95 % CI , 87%-95 % ) , respectively ( P = .35 ) . Almost all patients ( 95.5 % ) were fully compliant ; 23.5 % of patients had H pylori strains that were resistant to clarithromycin ( Italy , 26 % ; Spain , 19.5 % ) , 33 % were resistant to metronidazole ( Italy , 33 % ; Spain , 34 % ) , and 8.8 % were resistant to both drugs ( Italy , 7.1 % ; Spain , 11.5 % ) . Side effects ( only mild ) were reported in 51.5 % of patients ( 47 % hybrid vs 56 % concomitant ; P = .06 ) . Compliance greater than 80 % was the only significant predictor of eradication ( odds ratio , 12.5 ; 95 % CI , 3.1 - 52 ; P = .001 ) . Significantly more patients were compliant with hybrid therapy ( 98.8 % ) than concomitant therapy ( 95.2 % ; P = .05 ) . CONCLUSIONS Optimized nonbismuth quadruple hybrid and concomitant therapies cured more than 90 % of patients with H pylori infections in areas of high clarithromycin and metronidazole resistance . Clinical Trials.gov number NCT01464060 OBJECTIVE The aim of this study was to assess and compare the efficacy and safety of sequential treatment with st and ard triple therapies in a located population in Morocco . METHODS Consecutive H. pylori-positive patients with endoscopy-proven ulcer or non ulcer dyspepsia were prospect ively r and omized in the trial into one of three groups : AM and AC group were administered a tri-therapy for 7 days including PPI + amoxicillin + metronidazole ( AM group)/clarithromycin ( AC group ) and SQ group was administered a sequential regimen consisting of PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for the remaining 5 days . Eradication was confirmed by 13C-urea breath test 3 months after the end of the treatment . RESULTS Groups AM , AC and SQ included respectively 104 , 115 and 104 patients . They were comparable in terms of age , sex , clinical and endoscopic presentation . The rate of H. pylori eradication with sequential therapy was found at 94.2 % ( n=98 ) in ITT and 96 % ( n=98 ) in PP . It was higher than those found in the AM group : 70 % ( n=73 ) in ITT and 70.8 % ( n=73 ) in PP and the AC group : 78.2 % ( n=90 ) in ITT and 79.6 % ( n=90 ) in PP ( 0.001 ) . The prevalence of side effects following the sequential treatment was 9.6 % ( n=10 ) versus 22 % ( n=22 ) and 27.8 % ( n=32 ) in the AM and AC groups , respectively , ( P=0.006 ) . CONCLUSIONS Sequential treatment was better tolerated and achieved a significantly higher eradication rate of H. pylori compared with st and ard triple therapies in this population |
2,610 | 27,082,055 | Psychological factors ( depression , self-efficacy , and mental well-being ) were associated with specific self-care facets in patients with chronic HF .
These associations were predominantly observed with self-reported indices of self-care and not objective indices . | OBJECTIVE Psychological distress has been associated with poor outcomes in patients with chronic heart failure ( HF ) , which is assumed to be partly due to poor HF self-care behavior .
This systematic review and meta- analysis describes the current evidence concerning psychological determinants of self-care in patients with chronic HF . | Objective To determine the distribution and importance of various factors , especially the preventable ones , that contribute to cardiac decompensation and subsequent hospital admission for heart failure . Methods During a one year period patients were prospect ively recruited and evaluated during their hospital stay by means of a structured personal interview by trained medical staff and through clinical examination and laboratory investigation . Setting The cardiological department at a teaching affiliated general community hospital in Berlin , Germany . Patients Consecutive sample of 179 patients admitted to hospital with acute decompensation of pre-existing heart failure . Main outcome measures Proportional distribution of causative factors leading to hospital admission for heart failure ; relative importance of preventable factors ; details of patient compliance with diet and medication , and knowledge about medication . Results Mean ( SD ) age was 75.4 ( 9.9 ) years . Potential causative factors for decompensated heart failure were identified in 85.5 % of patients . Lack of adherence to the medical regimen was the most commonly identified factor and was regarded as the cause of the cardiac decompensation in 41.9 % of cases . Non-compliance with drugs was found in 23.5 % of patients . Other factors related to hospital admission were coronary ischaemia ( 13.4 % ) , cardiac arrhythmias ( 6.1 % ) , uncontrolled hypertension ( 5.6 % ) , and inadequate preadmission treatment ( 12.3 % ) . In all , 54.2 % of admissions could be regarded as preventable . Conclusions Many hospital admissions for decompensation of chronic heart failure in patients at a district hospital in Berlin are preventable . Measures are necessary to improve this situation and evaluation of programmes that include patient education , patient follow up , and physician training is needed OBJECTIVE Optimal self-care is crucial in patients with chronic heart failure ( HF ) . While the focus of research has been on negative mood states , adequate psychological re sources may be required to successfully engage in HF self-care . Therefore , the longitudinal associations of multiple positive affect measures in explaining HF self-care including consulting behavior were examined while adjusting for depressive symptoms and potential covariates ( e.g. , disease severity ) . METHODS In this prospect i ve cohort study , 238 patients ( mean age : 66.9 ± 8.6 years , 78 % men ) , with chronic HF completed question naires at baseline and 1-year follow-up . Positive affect was assessed with the Positive and Negative Affect Schedule ( PANAS ) and the Global Mood Scale ( GMS ) . Anhedonia , i.e. diminished interest or pleasure , was assessed with a subscale of the Hospital Anxiety and Depression Scale ( HADS ) . The 9-item European Heart Failure Self-care Behaviour scale was completed to assess HF self-care including consultation behavior . RESULTS Linear mixed modeling results showed that anhedonia was most strongly associated with both poor self-care ( estimate=-.72 , P<.001 ) and consulting behavior ( estimate=-.44 , P<.001 ) over time , after adjustment for covariates and depressive symptoms . GMS positive affect was related to better HF self-care adjusting for st and ard depressive symptoms but not when adjusting for anhedonia . PANAS positive affect was not independently related to self-care . CONCLUSION Anhedonia was associated with worse compliance with self-care among chronic HF patients over time , irrespective of disease severity and depression . Associations between positive affect and self-care were dependent on the measures used in multivariable analyses Objective : Depression is common in heart failure ( HF ) and associated with reduced cognitive function . The current study used Structrual Equation Modeling to examine whether depression adversely impacts cognitive function in HF through its adverse affects on exercise adherence and cardiovascular fitness . Method : 158 HF patients completed neuropsychological testing , physical fitness test , Beck Depression Inventory-II ( BDI-II ) , and measures assessing exercise adherence and physical exertion . Results : The model demonstrated excellent model fit and increased scores on the BDI-II negatively affected exercise adherence and cardiovascular fitness . There was a strong inverse association between cardiovascular fitness and cognitive function . Sobel test showed a significant indirect pathway between the BDI-II and cognitive function through cardiovascular fitness . Discussion : This study suggests depression in HF may adversely impact cognitive function through reduced cardiovascular fitness . Prospect i ve studies are needed to determine whether treatment of depression can lead to better lifestyle behaviors and ultimately improve neurocognitive outcomes in HF The purpose of this paper is to describe electronic monitoring device ( EMD ) ( e.g. , MEMS caps ) use among HIV-infected adults enrolled in a r and omized clinical trial and to make explicit some of the benefits and caveats of using electronic monitoring device technology . This is a descriptive , exploratory study of EMD use among 128 HIV-infected adults treated with at least three antiretroviral agents . Thirty-six percent of the sample admitted that they did not use the EMD consistently . Forty-one percent of the subjects reported taking out more than one dose at a time and 26 % reported opening the EMD but not taking the medication . Special subject-related issues accounted for only a small percentage of all reported problems with EMD use ( e.g. , transient housing , incarceration , substance abuse relapse and drug treatment ) . Results of this study suggest that EMDs may underestimate antiretroviral adherence among HIV-infected adults . Recommendations for improving EMD data quality are presented IMPORTANCE Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events . There has been minimal study of collaborative care ( CC ) management models for mental health disorders in high-risk cardiac in patients , and no prior CC intervention has simultaneously managed depression and anxiety disorders . OBJECTIVE To determine the impact of a low-intensity CC intervention for depression , generalized anxiety disorder , and panic disorder among patients hospitalized for an acute cardiac illness . DESIGN , SETTING , AND PARTICIPANTS Single-blind r and omized clinical trial , with study assessors blind to group assignment , from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome , arrhythmia , or heart failure and found to have clinical depression , generalized anxiety disorder , or panic disorder on structured assessment . INTERVENTIONS Participants were r and omized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders ( n = 92 ) or to enhanced usual care ( serial notification of primary medical providers ; n = 91 ) . The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate . MAIN OUTCOMES AND MEASURES Improvement in mental health-related quality of life ( Short Form-12 Mental Component Score [ SF-12 MCS ] ) at 24 weeks , compared between groups using a r and om-effects model in an intent-to-treat analysis . RESULTS Patients r and omized to CC had significantly greater estimated mean improvements in SF-12 MCS at 24 weeks ( 11.21 points [ from 34.21 to 45.42 ] in the CC group vs 5.53 points [ from 36.30 to 41.83 ] in the control group ; estimated mean difference , 5.68 points [ 95 % CI , 2.14 - 9.22 ] ; P = .002 ; effect size , 0.61 ) . Patients receiving CC also had significant improvements in depressive symptoms and general functioning , and higher rates of treatment of a mental health disorder ; anxiety scores , rates of disorder response , and adherence did not differ between groups . CONCLUSIONS AND RELEVANCE A novel telephone-based , low-intensity model to concurrently manage cardiac patients with depression and /or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01201967 AIMS This paper is a report on the effectiveness of a self-management programme based on the self-efficacy construct , in older people with heart failure . BACKGROUND Heart failure is a major health problem worldwide , with high mortality and morbidity , making it a leading cause of hospitalization . Heart failure is associated with a complex set of symptoms that arise from problems in fluid and sodium retention . Hence , managing salt and fluid intake is important and can be enhanced by improving patients ' self-efficacy in changing their behaviour . DESIGN R and omized controlled trial . METHODS Heart failure patients attending cardiac clinics in northern Taiwan from October 2006-May 2007 were r and omly assigned to two groups : control ( n = 46 ) and intervention ( n = 47 ) . The intervention group received a 12-week self-management programme that emphasized self-monitoring of salt/fluid intake and heart failure-related symptoms . Data were collected at baseline as well as 4 and 12 weeks later . Data analysis to test the hypotheses used repeated- measures anova models . RESULTS Participants who received the intervention programme had significantly better self-efficacy for salt and fluid control , self-management behaviour and their heart failure-related symptoms were significantly lower than participants in the control group . However , the two groups did not differ significantly in health service use . CONCLUSION The self-management programme improved self-efficacy for salt and fluid control , self-management behaviours , and decreased heart failure-related symptoms in older Taiwanese out patients with heart failure . Nursing interventions to improve health-related outcomes for patients with heart failure should emphasize self-efficacy in the self-management of their disease OBJECTIVE Many patients with chronic heart failure ( CHF ) are thought to be non-adherent to their prescribed medications . The objective was to describe perceptions about and adherence to regular medicines and study medication at baseline and study end in CHF patients participating in a clinical trial . METHODS In the carvedilol or metoprolol European trial ( COMET ) , patients ( N = 3029 ) with CHF were r and omised and followed during a 58-month period . Patients at some Swedish centres answered a question naire at baseline and study end concerning their perception of their regular heart medication and study medication . Adherence was established through estimation of drug usage . RESULTS In the Swedish sub- study , 302 patients responded once to the question naire while 107 patients responded both at baseline and at follow-up . At baseline , 94 % of the patients stated that they believed that the study medication would make them feel better and 82 % believed that their regular heart medication would do so . During the study , patients ' belief in their regular cardiac medication significantly increased . Lack of belief in medication at the start of the study was a strong predictor of withdrawal from the trial ( 64 % versus 6.8 % ; p < 0.0001 ) . Those patients with very poor well-being and limited functional ability ( classified as NYHA III-IV ) at baseline significantly ( p = 0.01 ) increased their belief in the regular cardiac medication but not in their study medication . CONCLUSION Belief in medication may be related to how the patient experiences the medication 's impact on functional ability , symptoms and well-being . PRACTICE IMPLICATION S Early identification of patients ' beliefs about medication seem to be an important factor in counselling and information to patients with CHF OBJECTIVES To assess the influence of depressive symptoms on adherence with heart failure medications and to determine whether the effect of a pharmacy-based intervention to improve heart failure medication adherence is modified by depressive symptoms . DESIGN Secondary analysis of data from a r and omized controlled trial . SETTING University-affiliated ambulatory care practice . PATIENTS Patients 50 years or older with congestive heart failure r and omly assigned to usual care ( n = 192 ) or intervention ( n = 122 ) . INTERVENTION Pharmacist-provided intervention to improve heart failure medication adherence . MAIN OUTCOME MEASURES Medication adherence was measured via patient self-report and using electronic prescription lids ; depressive symptoms were measured using the Geriatric Depression Scale . General linear models examined the main effect of depressive symptoms on medication adherence and whether depressive symptoms modified the effectiveness of the intervention . RESULTS At baseline , 37 % ( n = 117 ) of participants screened positive for depression . In the usual care group , mean adjusted self-reported adherence was 75 % for depressed participants and 81 % for nondepressed participants ( P = 0.04 ) ; mean adjusted adherence measured electronically was 71 % for depressed participants and 69 % for nondepressed participants ( P = 0.65 ) . INTERVENTION effectiveness did not differ for depressed compared with nondepressed participants . CONCLUSION The effectiveness of a pharmacy-based intervention to improve adherence does not appear to be influenced by depression . However , the method used to measure adherence ( electronically measured versus self-reported ) influences the interpretation of the relationship between depression and heart failure medication adherence Background : Self-care is an integral component of successful heart failure ( HF ) management . Engaging patients in self-care can be challenging . Methods : Fifteen patients with HF enrolled during hospitalization received a motivational intervention design ed to improve HF self-care . A mixed method , pretest posttest design was used to evaluate the proportion of patients in whom the intervention was beneficial and the mechanism of effectiveness . Participants received , on average , 3.0 ± 1.5 home visits ( median 3 , mode 3 , range 1 - 6 ) over a three-month period from an advanced practice nurse trained in motivational interviewing and family counseling . Quantitative and qualitative data were used to judge individual patients in whom the intervention produced a clinical ly significant improvement in HF self-care . Audiotaped intervention sessions were analyzed using qualitative methods to assess the mechanism of intervention effectiveness . Results : Congruence between quantitative and qualitative judgments of improved self-care revealed that 71.4 % of participants improved in self-care after receiving the intervention . Analysis of transcribed intervention sessions revealed themes of 1 ) communication ( reflective listening , empathy ) ; 2 ) making it fit ( acknowledging cultural beliefs , overcoming barriers and constraints , negotiating an action plan ) ; and , 3 ) bridging the transition from hospital to home ( providing information , building skills , activating support re sources ) . Conclusion : An intervention that incorporates the core elements of motivational interviewing may be effective in improving HF self-care , but further research is needed Background Type D ( distressed ) personality and medication nonadherence have been associated with poor health outcomes . Type D personality is associated with poor medication adherence in patients with coronary artery disease . However , the relationship between type D personality and medication adherence in patients with heart failure ( HF ) remains unknown . Purpose Therefore , the goal of this study was to examine the association between type D personality and medication adherence in patients with HF . Method This was a sub- analysis of baseline data from a r and omized controlled trial with 84 patients with HF in the USA . Demographic , clinical , and psychological data were collected at baseline by interview , question naires , and medical record review . Type D personality was assessed using the Type D Personality Scale ( DS14 ) . Medication adherence was measured using both objective ( Medication Event Monitoring System , MEMS ) and self-reported ( Morisky Medication Adherence Scale , MMAS-4 ) measures . Patients started medication adherence monitoring with the MEMS bottle at baseline and is used continuously for a month . Multiple regressions were used to explore the relationships between type D personality and medication adherence while adjusting for demographic , clinical , and psychological factors . Results Patients with type D personality were more likely to have poor medication adherence . Type D personality was associated with medication adherence before and after adjusting for covariates when it was analyzed as a categorical variable . However , type D personality was not associated with medication adherence when analyzed as a dimensional construct . Negative affectivity , a component of type D personality , was associated with medication adherence . Conclusion As a dimensional construct , type D personality may not reflect the components of the personality associated with poor outcomes . Negative affectivity was associated with medication adherence in patients with HF . Interventions aim ing to improving/enhancing medication adherence need to take into account patients with the negative affectivity component of type D personality who are at higher risk for poor medication adherence , which may lead to adverse health outcomes Introduction : Heart failure patients vary considerably in their self-care management behaviors ( i.e. recognizing and responding to symptoms ) . The goal of this study was to identify unique patterns of change in heart failure self-care management and quantify associations between self-care management and quality of life ( HRQOL ) over time . Methods : A prospect i ve cohort study among adults with symptomatic heart failure was design ed to measure changes in self-care management ( Self-care of Heart Failure Index ) and HRQOL ( Kansas City Cardiomyopathy Question naire ) over six months . Growth mixture modeling was used to identify unique trajectories of change in self-care management . Results : The mean age ( n=146 ) was 57 years , 70 % were male , and 41 % had class II heart failure . Two trajectories of self-care management were identified ( entropy = 0.88 ) . The larger trajectory ( 73.3 % ) was characterized by a significant decline in self-care management over time and no change in HRQOL . The smaller trajectory ( 26.7 % ) was characterized by marked improvements in self-care management and HRQOL . Changes in heart failure self-care management occurred in the absence of change in routine self-care maintenance behaviors , functional classification , and physical and psychological symptoms . Patients with greater physical symptoms at enrollment ( odds ratio ( OR ) = 1.04 , p=0.037 ) , larger left ventricles ( OR=1.50 , p=0.044 ) , and ischemic heart failure ( OR=3.84 , p=0.014 ) were more likely to have the declining trajectory of self-care management . Higher levels of depression at enrollment were associated with reduced odds of having a decline in self-care management over time ( OR=0.85 , p<0.001 ) . Conclusions : There are unique and clinical ly-relevant trajectories of change in heart failure self-care management that are associated with differences in HRQOL Background : Few rigorously design ed studies have documented the efficacy of interventions to improve medication adherence among patients prescribed highly active antiretroviral . Data are needed to justify the use of limited re sources for these programs . Methods : A 2-arm , r and omized , controlled trial evaluated the efficacy of a community-based , home-visit intervention to improve medication adherence . Participants were 171 HIV-infected adults prescribed a minimum of 3 antiretroviral agents . The majority had a past or current history of substance abuse . Subjects were r and omly assigned to receive home visits for 1 year or usual care . Medication adherence was assessed with Medication Event Monitoring stem caps at 3-month intervals from r and omization through 3 months after the conclusion of the intervention . Results : A larger proportion of subjects in the intervention group demonstrated adherence greater than 90 % compared with the control group at each time point after baseline . The difference over time was statistically significant ( Extended Mantel-Haenszel test : 5.80 , P = 0.02 ) . A statistically significant intervention effect on HIV-RNA level or CD4 cell count was not seen , but there was a statistically significant association between greater than 90 % adherence and an undetectable HIV-RNA over time ( P < 0.03 ) . Conclusion : Home visits from a nurse and a community worker were associated with medication adherence greater than 90 % among a cohort of socially vulnerable people living with HIV/AIDS in northeastern United States BACKGROUND A relationship between excessive daytime sleepiness ( EDS ) and poor treatment adherence has been suspected but not confirmed . We hypothesized that medication adherence would be poorer in adults with heart failure ( HF ) and EDS and that cognitive status would be the mechanism of effect . METHODS AND RESULTS A sample of 280 adults with chronic HF were enrolled into a prospect i ve cohort comparison study . We identified a cohort with EDS and a control group without EDS and further divided both groups into those with and without mild cognitive decline . Data on medication adherence were obtained at baseline and 3 and 6 months by using the Basel Assessment of Adherence Scale . Regression analysis was used to clarify the contribution of EDS and cognition to medication adherence and to assess relationships over 6 months after adjusting for age , enrollment site , gender , race , functional class , depression , and premorbid intellect . At baseline , 62 % of subjects were nonadherent to their medication regime . Nonadherence was significantly more common in those with EDS , regardless of cognitive status ( P = .035 ) . The odds of nonadherence increased by 11 % for each unit increase in EDS ( adjusted odds ratio 1.11 ; 95 % confidence interval 1.05 - 1.19 ; P = .001 ) . In longitudinal models , there was a 10 % increase in the odds of nonadherence for each unit increase in EDS ( P = .008 ) . The only cognition measure significantly associated with medication adherence was attention ( P = .047 ) . CONCLUSIONS Adults with HF and EDS are more likely to have problems adhering to their medication regimen than those without EDS , regardless of their cognitive status . Identifying and correcting factors that interfere with sleep may improve medication adherence Introduction : Patients with heart failure ( HF ) vary in their ability to respond to symptoms when they occur . The goal of this study was to classify common patterns of symptom response behaviors among adults with HF and identify biobehavioral determinants thereof . Methods : Consulting behaviors ( i.e. contacting a provider for guidance ) were measured using the European Heart Failure Self-care Behavior Scale consulting behaviors subscale , and self-care management ( i.e. recognizing and engaging in self-initiated treatment of symptoms ) was measured with the Self-Care of HF Index self-care management scale in a prospect i ve cohort study . Latent class mixture modeling was used to identify distinct profiles of consulting and of self-care management behaviors . Results : The mean age ( n=146 ) was 57±13 years , 30 % were female , and 59 % had class III/IV HF . Two distinct profiles of consulting behaviors ( novice and expert ) and three distinct profiles of self-care management ( novice , inconsistent and expert ) were identified . There was a weak association between profiles of consulting behaviors and self-care management ( Kendall ’s tau-b=0.211 ) . Higher levels of anxiety were associated with worse consulting behaviors ( β=1.67±0.60 ) and worse self-care management ( β= −5.82±3.12 ) and lower odds of exhibiting expert level consulting behaviors ( odds ratio (OR)=0.50 ; 95 % confidence interval (CI)=0.26–0.95 ) and self-care management ( OR=0.47 ; 95 % CI=0.24–0.92 ) ( all p<0.05 ) . Higher levels of physical symptoms were associated with better self-care management ( β=0.50±0.12 ; OR = 1.02 , 95 % CI=1.00–1.05 ; both p<0.05 ) . Conclusions : Expertise in consulting behaviors does not necessarily confer expertise in symptom self-care management and vice versa . Physical and psychological symptoms are strong determinants of symptom response behaviors |
2,611 | 29,696,726 | We report evidence for intervention effectiveness , which children might best be served by each tier , the role SLTs could take within each tier and the effectiveness of these roles .
Regarding universal interventions provided to all children ( Tier 1 ) and those targeted at children with language weaknesses or vulnerabilities ( Tier 2 ) , there is growing evidence that approaches led by education services can be effective when staff are highly trained and well supported .
There is currently limited evidence regarding additional benefit of SLT-specific roles at Tiers 1 and 2 .
With regard to individualized intervention ( Tier 3 ) , children with complex or pervasive language disorders can progress following direct individualized intervention ( Tier 3B ) , whereas children with milder or less pervasive difficulties can make progress when intervention is managed by an SLT , but delivered indirectly by others ( Tier 3A ) , provided they are well trained and supported , and closely monitored . | BACKGROUND Paediatric speech and language therapist ( SLT ) roles often involve planning individualized intervention for specific children , working collaboratively with families and education staff , providing advice , training and coaching and raising awareness .
A tiered approach to service delivery is currently recommended whereby services become increasingly specialized and individualized for children with greater needs .
AIMS To stimulate discussion regarding delivery of SLT services by examining evidence regarding the effectiveness of ( 1 ) intervention for children with language disorders at different tiers and ( 2 ) SLT roles within these tiers ; and to propose an evidence -based model of SLT service delivery and a flowchart to aid clinical decision-making . | Mothers whose infants varied in early biological characteristics ( born at term , n = 120 ; born at very low birth weight [ VLBW ] , n = 144 ) were r and omized to a target group ( n = 133 ) or developmental feedback comparison group ( n = 131 ) to determine whether learning responsive behaviors would facilitate infant development . The target condition included videotaped examples , problem-solving activities , and mothers ' critique of their own behaviors through video procedures across 10 home visits . All target versus comparison mothers showed greater increases across multiple responsiveness behaviors observed in 4 assessment s conducted across 6 - 13 months of age ; changes in emotionally supportive behaviors were strongest for target mothers of infants born at VLBW . Increased maternal responsiveness facilitated greater growth in target infants ' social , emotional , communication , and cognitive competence , supporting a causal role for responsiveness on infant development . Although benefits were generally comparable across risk groups , aspects of social and emotional skills showed greater change for those born at VLBW . Evidence for responsiveness as a multidimensional construct was provided as well as the importance of different aspects of responsiveness mediating the effect of the intervention on different infant skill domains Abstract This study examined the impact of teacher professional development aim ed at improving the capacity of primary teachers in disadvantaged schools to strengthen children 's expressive and receptive oral language skills and early literacy success in the first 2 years of school . Fourteen low-SES schools in Victoria , Australia were r and omly allocated to a research ( n = 8) or control arm ( n = 6 ) , result ing in an initial sample of 1254 students , ( n = 602 in research arm and n = 652 in control arm ) . The intervention comprised 6 days of teacher and principal professional development ( delivered by language and literacy experts ) , school-based continuing contact with the research team and completion by one staff member of each research school of a postgraduate unit on early language and literacy . Schools in the control arm received st and ard teaching according to state auspiced curriculum guidelines . Full data were available on 979 students at follow-up ( time 2 ) . Students in the research arm performed significantly better on Test of Language Development : Primary ( Fourth Edition ) sub-tests ( p ≤ .002 ) and the Reading Progress Test ( F = 10.4(1 ) ; p = .001 ) than students in the control arm at time 2 . Narrative scores were not significantly different at time 2 , although students in research schools showed greater gains . Findings provide “ proof of concept ” for this approach , and are discussed with respect to implication s for teacher professional development and pre-service education concerning the psycholinguistic competencies that underpin the transition to literacy PURPOSE This study evaluated the efficacy of a collaborative intervention where a speech- language pathologist ( SLP ) trained mainstream secondary school teachers to make modifications to their oral and written instructional language . The trained teachers ' uptake of techniques in their whole-class teaching practice s and the impact this had on the language abilities of students with language impairment ( LI ) were evaluated . METHOD Two secondary schools were r and omly assigned to either a trained or a control condition . A cohort of 13 teachers ( 7 trained and 6 control ) and 43 Year 8 students with LI ( 21 trained and 22 control ) were tested at pre , post , and follow-up times-teachers by structured interview and students by st and ardized spoken and written language assessment s. RESULTS Significantly increased use of the language modification techniques by the trained teachers was observed when compared to the control group of untrained teachers , with this increased use maintained over time . Results from the trained group of students showed a significant improvement in written expression and listening comprehension relative to the control group of students . CONCLUSION This r and omized controlled trial is one of the first investigations to evaluate a collaborative intervention that links changes in mainstream secondary teachers ' instructional language practice s with improvements in the language abilities of adolescents with LI In 2002 , the National Institutes of Health sponsored a meeting concerning method ological challenges of research in psychosocial interventions in Autism Spectrum Disorders . This paper provides a summary of the presentations and the discussion s that occurred during this meeting . Recommendations to federal and private agencies included the need for r and omized clinical trials of comprehensive interventions for autism as the highest , but not the sole priority . Ongoing working groups were proposed to address psychosocial interventions with a focus on relevant statistics , st and ardized documentation and methods of diagnosis , development of outcome measures , establishment of st and ards in research ; and the need for innovative treatment design s , including application of design s from other research areas to the study of interventions in ASD BACKGROUND A manualized language therapy developed via a r and omized controlled trial had proved efficacious in the short-term in developing expressive language for mainstream primary school children with persistent language impairment . This therapy had been delivered to a predetermined schedule by speech and language therapists or speech and language therapy assistants to children individually or in groups . However , this model of service delivery is no longer the most common model in UK schools , where indirect consultancy approaches with intervention delivered by school staff are often used . AIMS A cohort study was undertaken to investigate whether the therapy was equally efficacious when delivered to comparable children by school staff , rather than speech and language therapists or speech and language therapy assistants . METHODS & PROCEDURES Children in the cohort study were selected using the same criteria as in the r and omized controlled trial , and the same manualized therapy was used , but delivered by mainstream school staff using a consultancy model common in the UK . Outcomes were compared with those of r and omized controlled trial participants . OUTCOMES & RESULTS The gains in expressive language measured in the r and omized controlled trial were not replicated in the cohort study . Less language -learning activity was recorded than had been planned , and less than was delivered in the r and omized controlled trial . Implication s for ' consultancy ' speech and language therapist service delivery models in mainstream schools are outlined . CONCLUSIONS & IMPLICATION S At present , the more efficacious therapy is that delivered by speech and language therapists or speech and language therapy assistants to children individually or in groups . This may be related to more faithful adherence to the interventions schedule , and to a probably greater amount of language -learning activity undertaken . Intervention delivered via school-based ' consultancy ' approaches in schools will require to be carefully monitored by schools and SLT services Summary Background Results of small trials suggest that early interventions for social communication are effective for the treatment of autism in children . We therefore investigated the efficacy of such an intervention in a larger trial . Methods Children with core autism ( aged 2 years to 4 years and 11 months ) were r and omly assigned in a one-to-one ratio to a parent-mediated communication-focused ( Preschool Autism Communication Trial [ PACT ] ) intervention or treatment as usual at three specialist centres in the UK . Those assigned to PACT were also given treatment as usual . R and omisation was by use of minimisation of probability in the marginal distribution of treatment centre , age ( ≤42 months or > 42 months ) , and autism severity ( Autism Diagnostic Observation Schedule-Generic [ ADOS-G ] algorithm score 12–17 or 18–24 ) . Primary outcome was severity of autism symptoms ( a total score of social communication algorithm items from ADOS-G , higher score indicating greater severity ) at 13 months . Complementary secondary outcomes were measures of parent-child interaction , child language , and adaptive functioning in school . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N58133827 . Results 152 children were recruited . 77 were assigned to PACT ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=25 ] ) ; and 75 to treatment as usual ( London [ n=26 ] , Manchester [ n=26 ] , and Newcastle [ n=23 ] ) . At the 13-month endpoint , the severity of symptoms was reduced by 3·9 points ( SD 4·7 ) on the ADOS-G algorithm in the group assigned to PACT , and 2·9 ( 3·9 ) in the group assigned to treatment as usual , representing a between-group effect size of −0·24 ( 95 % CI −0·59 to 0·11 ) , after adjustment for centre , sex , socioeconomic status , age , and verbal and non-verbal abilities . Treatment effect was positive for parental synchronous response to child ( 1·22 , 0·85 to 1·59 ) , child initiations with parent ( 0·41 , 0·08 to 0·74 ) , and for parent-child shared attention ( 0·33 , −0·02 to 0·68 ) . Effects on directly assessed language and adaptive functioning in school were small . Interpretation On the basis of our findings , we can not recommend the addition of the PACT intervention to treatment as usual for the reduction of autism symptoms ; however , a clear benefit was noted for parent-child dyadic social communication . Funding UK Medical Research Council , and UK Department for Children , Schools and Families Background Oral language skills in the preschool and early school years are critical to educational success and provide the foundations for the later development of reading comprehension . Methods In a r and omized controlled trial , 180 children from 15 UK nursery schools ( n = 12 from each setting ; Mage = 4;0 ) were r and omly allocated to receive a 30-week oral language intervention or to a waiting control group . Children in the intervention group received 30 weeks of oral language intervention , beginning in nursery ( preschool ) , in three group sessions per week , continuing with daily sessions on transition to Reception class ( pre-Year 1 ) . The intervention was delivered by nursery staff and teaching assistants trained and supported by the research team . Following screening , children were assessed preintervention , following completion of the intervention and after a 6-month delay . Results Children in the intervention group showed significantly better performance on measures of oral language and spoken narrative skills than children in the waiting control group immediately after the 30 week intervention and after a 6 month delay . Gains in word-level literacy skills were weaker , though clear improvements were observed on measures of phonological awareness . Importantly , improvements in oral language skills generalized to a st and ardized measure of reading comprehension at maintenance test . Conclusions Early intervention for children with oral language difficulties is effective and can successfully support the skills , which underpin reading comprehension BACKGROUND This study compares the efficacy of two school-based intervention programmes ( Phonology with Reading ( P + R ) and Oral Language ( OL ) ) for children with poor oral language at school entry . METHODS Following screening of 960 children , 152 children ( mean age 4;09 ) were selected from 19 schools on the basis of poor vocabulary and verbal reasoning skills and r and omly allocated to either the P + R programme or the OL programme . Both groups of children received 20 weeks of daily intervention alternating between small group and individual sessions , delivered by trained teaching assistants . Children in the P + R group received training in letter-sound knowledge , phonological awareness and book level reading skills . Children in the OL group received instruction in vocabulary , comprehension , inference generation and narrative skills . The children 's progress was monitored at four time points : pre- , mid- and post-intervention , and after a 5-month delay , using measures of literacy , language and phonological awareness . RESULTS The data are clustered ( children within schools ) and robust confidence intervals are reported . At the end of the 20-week intervention programme , children in the P + R group showed an advantage over the OL group on literacy and phonological measures , while children in the OL group showed an advantage over the P + R group on measures of vocabulary and grammatical skills . These gains were maintained over a 5-month period . CONCLUSIONS Intervention programmes design ed to develop oral language skills can be delivered successfully by trained teaching assistants to children at school entry . Training using P + R fostered decoding ability whereas the OL programme improved vocabulary and grammatical skills that are foundations for reading comprehension . However , at the end of the intervention , more than 50 % of at-risk children remain in need of literacy support PURPOSE A r and omized controlled trial was conducted to compare the language and auditory processing outcomes of children assigned to receive the Fast ForWord Language intervention ( FFW-L ) with the outcomes of children assigned to nonspecific or specific language intervention comparison treatments that did not contain modified speech . METHOD Two hundred sixteen children between the ages of 6 and 9 years with language impairments were r and omly assigned to 1 of 4 conditions : ( a ) Fast ForWord Language ( FFW-L ) , ( b ) academic enrichment ( AE ) , ( c ) computer-assisted language intervention ( CALI ) , or ( d ) individualized language intervention ( ILI ) provided by a speech- language pathologist . All children received 1 hr and 40 min of treatment , 5 days per week , for 6 weeks . Language and auditory processing measures were administered to the children by blinded examiners before treatment , immediately after treatment , 3 months after treatment , and 6 months after treatment . RESULTS The children in all 4 conditions improved significantly on a global language test and a test of backward masking . Children with poor backward masking scores who were r and omized to the FFW-L condition did not present greater improvement on the language measures than children with poor backward masking scores who were r and omized to the other 3 conditions . Effect sizes , analyses of st and ard error of measurement , and normalization percentages supported the clinical significance of the improvements on the Comprehensive Assessment of Spoken Language ( E. Carrow-Woolfolk , 1999 ) . There was a treatment effect for the Blending Words subtest of the Comprehensive Test of Phonological Processing ( R. K. Wagner , J. K. Torgesen , & C. A. Rashotte , 1999 ) . Participants in the FFW-L and CALI conditions earned higher phonological awareness scores than children in the ILI and AE conditions at the 6-month follow-up testing . CONCLUSION Fast ForWord Language , the intervention that provided modified speech to address a hypothesized underlying auditory processing deficit , was not more effective at improving general language skills or temporal processing skills than a nonspecific comparison treatment ( AE ) or specific language intervention comparison treatments ( CALI and ILI ) that did not contain modified speech stimuli . These findings call into question the temporal processing hypothesis of language impairment and the hypothesized benefits of using acoustically modified speech to improve language skills . The finding that children in the 3 treatment conditions and the active comparison condition made clinical ly relevant gains on measures of language and temporal auditory processing informs our underst and ing of the variety of intervention activities that can facilitate development Abstract Objective : To compare routine speech and language therapy in preschool children with delayed speech and language against 12 months of “ watchful waiting . ” Design : Pragmatic r and omised controlled trial . Setting : 16 community clinics in Bristol . Participants : 159 preschool children with appreciable speech or language difficulties who fulfilled criteria for admission to speech and language therapy . Main outcome measures : Four quantitative measures of speech and language , assessed at 6 and 12 months ; a binary variable indicating improvement , by 12 months , on the trial entry criterion . Results : Improvement in auditory comprehension was significant in favour of therapy ( adjusted difference in means 4.1 , 95 % confidence interval 0.5 to 7.6 ; P=0.025 ) . No significant differences were observed for expressive language ( 1.4 , −2.1 to 4.8 ; P=0.44 ) ; phonology error rate ( −4.4 , −12.0 to 3.3 ; P=0.26 ) ; language development ( 0.1 , −0.4 to 0.6 ; P=0.73 ) ; or improvement on entry criterion ( odds ratio 1.3 , 0.67 to 2.4 ; P=0.46 ) . At the end of the trial , 70 % of all children still had substantial speech and language deficits . Conclusions : This study provides little evidence for the effectiveness of speech and language therapy compared with watchful waiting over 12 months . Providers of speech and language therapy should reconsider the appropriateness , timing , nature , and intensity of such therapy in preschool children . Continued research into more specific provision to subgroups of children is also needed to identify better treatment methods . The lack of resolution of difficulties for most of the children suggests that further research is needed to identify effective ways of helping this population of children OBJECTIVE The vast majority of children with an autism spectrum disorder ( ASD ) attend public preschools at some point in their childhood . Community preschool practice s often are not evidence based , and almost none target the prelinguistic core deficits of ASD . This study investigated the effectiveness of public preschool teachers implementing a vali date d intervention ( the Joint Attention and Symbolic Play/Engagement and Regulation intervention ; JASP/ER ) on a core deficit of autism , initiating joint attention . METHOD Sixteen dyads ( preschoolers with ASD and the public school teachers who worked in the child 's classroom ) were r and omly assigned to the 6-week JASP/ER intervention or a control group . RESULTS At the end of the intervention , JASP/ER teachers used more JASP/ER strategies than the control teachers , and JASP/ER preschoolers used more joint attention in their classroom than control children . Additionally , JASP/ER children spent more time in supported engagement and less time in object engagement than control preschoolers on a taped play interaction . CONCLUSIONS Findings suggest that teachers were able to improve a core deficit of children with ASD in a public preschool context BACKGROUND Word-finding difficulties ( WFDs ) in children have been hypothesized to be caused at least partly by poor semantic knowledge . Therefore , improving semantic knowledge should decrease word-finding errors . Previous studies of semantic therapy for WFDs are inconclusive . AIMS To investigate the effectiveness of semantic therapy for secondary school-aged pupils with WFDs using a r and omized control trial with blind assessment . METHODS & PROCEDURES Fifteen participants with language impairments and WFDs ( aged 9;11 - 15;11 ) were r and omly assigned to a therapy versus waiting control group . In Phase 1 the therapy group received two 15-min semantic therapy sessions per week for 8 weeks with their usual speech and language therapist . Therapy for each participant targeted words from one of three semantic categories ( animals , food , clothes ) . All participants were tested pre- and post-phase 1 therapy on the brief version of the Test of Adolescent Word Finding ( TAWF ) , semantic fluency and the Test of Word Finding in Discourse ( TWFD ) . In Phase 2 the waiting control group received the same therapy as the original therapy group , which received therapy targeted at other language areas . Testing after Phase 2 aim ed to establish whether the waiting control group made similar progress to the original therapy group and whether the original therapy group maintained any gains . OUTCOMES & RESULTS The original therapy group made significant progress in st and ard scores on the TAWF ( d= 0.94 ) , which was maintained 5 months later . However , they made no progress on the semantic fluency or discourse tests . Participants in the waiting control group did not make significant progress on the TAWF in Phase 1 when they received no word-finding therapy . However , after Phase 2 , when they received the therapy , they also made significant progress ( d= 0.81 ) . The combined effect of therapy over the two groups was d= 1.2 . The mean st and ard scores on the TAWF were 67 pre-therapy and 77 post-therapy . CONCLUSIONS & IMPLICATION S Four hours of semantic therapy on discrete semantic categories led to significant gains on a general st and ardized test of word finding , enabling the participants to begin to close the gap between their performance and that of their typically developing peers . These gains were maintained after 5 months . A small amount of therapy can lead to significant gains even with secondary aged pupils with severe language difficulties . However , further studies are needed to find ways of improving word-finding abilities in discourse PURPOSE In this study , the authors evaluated the efficacy of a Spanish-English versus English-only vocabulary intervention for dual- language learners ( DLLs ) with language impairment compared to mathematics intervention groups and typically developing controls with no intervention . Further , in this study the authors also examined whether the language of instruction affected English , Spanish , and conceptual vocabulary differentially . METHOD The authors r and omly assigned 202 preschool DLLs with language impairment to 1 of 4 conditions : bilingual vocabulary , English-only vocabulary , bilingual mathematics , or English-only mathematics . Fifty-four DLLs with typical development received no intervention . The vocabulary intervention consisted of a 12-week small-group dialogic reading and h and s-on vocabulary instruction of 45 words . Postintervention group differences and linear growth rates were examined in conceptual , English , and Spanish receptive and expressive vocabulary for the 45 treatment words . RESULTS Results indicate that the bilingual vocabulary intervention facilitated receptive and expressive Spanish and conceptual vocabulary gains in DLLs with language impairment compared with the English vocabulary intervention , mathematics intervention , and no-intervention groups . The English-only vocabulary intervention differed significantly from the mathematics condition and no-intervention groups on all measures but did not differ from the bilingual vocabulary intervention . Vocabulary growth rates postintervention slowed considerably . Results support the idea that bilingual interventions support native- and second- language vocabulary development . CONCLUSION English-only intervention supports only English . Use of repeated dialogic reading and h and s-on activities facilitates vocabulary acquisition PURPOSE The authors aim ed to establish whether 2 theoretically motivated interventions could improve use of verb argument structure in pupils with persistent specific language impairment ( SLI ) . METHOD Twenty-seven pupils with SLI ( ages 11;0 - 16;1 ) participated in this r and omized controlled trial with " blind " assessment . Participants were r and omly assigned to 1 of 3 therapy groups : syntactic-semantic , semantic , and control . All pupils received 9 weekly half-hour individual therapy sessions . They were assessed on a specifically design ed video test pretherapy , posttherapy , and at follow-up . RESULTS Pupils receiving the syntactic-semantic and semantic therapies made significant progress ( d>1.0 ) , which was maintained at follow-up and generalized to control verbs . Both therapies improved linking of arguments to syntax , and the syntactic-semantic therapy tended to increase use of optional arguments . Pupils receiving the control therapy made no progress . CONCLUSION Both methods of argument structure therapy were effective . Comparisons of their effectiveness in specific areas led to the hypotheses that the pupils ' initial difficulties with linking result ed from ill-defined semantic representations , whereas their limited use of arguments may have result ed from syntactic difficulties . When therapy is theoretically grounded , it can inform theories , be time limited , and be effective for older children with SLI BACKGROUND Many school-age children with language impairments are enrolled in mainstream schools and receive indirect language therapy , but there have been , to the authors ' knowledge , no previous controlled studies comparing the outcomes and costs of direct and indirect intervention delivered by qualified therapists and therapy assistants , and each delivery mode offered to children individually or in groups . AIMS To investigate the relative effectiveness of indirect and direct intervention therapy modes delivered individually or in groups for children with primary language impairment . METHODS & PROCEDURES A multi-centre r and omized controlled trial investigated 161 children with primary language impairment aged 6 - 11 years r and omized to a usual-therapy control group or to direct individual , indirect individual , direct group or indirect group therapy modes . Intervention was delivered three times a week for 30 - 40-min sessions in mainstream schools over 15 weeks . Language performance was assessed at baseline , post-therapy and at 12 months . Cost analysis was based on salary and travel costs for intervention modes and usual therapy . OUTCOMES & RESULTS Compared with controls , children receiving project therapy made short-term improvements in expressive ( p = 0.031 ) , but not receptive , language immediately following intervention . Children with specific expressive language delay were more likely to show improvement than those with mixed receptive-expressive difficulties . The four project therapy modes did not differ on primary language outcomes ( all p-values>0.392 ) and there were no further improvements evident at follow-up . Indirect group therapy was the least costly mode , with direct individual therapy the most costly . CONCLUSIONS & IMPLICATION S Intervention in this age group can be effective for expressive language and can be delivered equally effectively though speech and language therapy assistants and to children in groups Although response-to-instruction ( RTI ) approaches have received increased attention , few studies have evaluated the potential impacts of RTI approaches with preschool population s. This manuscript presents results of two studies examining impacts of Tier II instruction with preschool children . Participating children were identified as substantially delayed in the acquisition of early literacy skills despite exposure to high- quality , evidence -based classroom instruction . Study 1 included 93 children ( M age = 58.2 months ; SD = 3.62 ) attending 12 Title I preschools . Study 2 included 184 children ( M age = 58.2 months ; SD = 3.38 ) attending 19 Title I preschools . The majority of children were Black/African American , and about 60 % were male . In both studies , eligible children were r and omized to receive either 11 weeks of need-aligned , small-group instruction or just Tier I. Tier II instruction in Study 1 included variations of activities for code- and language -focused domains with prior evidence of efficacy in non-RTI context s. Tier II instruction in Study 2 included instructional activities narrower in scope , more intensive , and delivered to smaller groups of children . Impacts of Tier II instruction in Study 1 were minimal ; however , there were significant and moderate-to-large impacts in Study 2 . These results identify effective Tier II instruction but indicate that the context in which children are identified may alter the nature of Tier II instruction that is required . Children identified as eligible for Tier II in an RTI framework likely require more intensive and more narrowly focused instruction than do children at general risk of later academic difficulties BACKGROUND Early language skills are critical for later academic success . Lower socioeconomic status ( SES ) children tend to start school with limited language skills compared to advantaged peers . We test the hypothesis that this is due in part to differences in caregiver contingent talk during infancy ( how often the caregiver talks about what is in the focus of the infant 's attention ) . METHODS In a r and omised controlled trial with high and low SES families , 142 11-month olds and their caregivers were r and omly allocated to either a contingent talk intervention or a dental health control . Families in the language intervention watched a video about contingent talk and were asked to practise it for 15 min a day for a month . Caregiver communication was assessed at baseline and after 1 month . Infant communication was assessed at baseline , 12 , 15 , 18 and 24 months . RESULTS At baseline , social gradients were observed in caregiver contingent talk to their 11-month olds ( but not in infant communication ) . At posttest , when infants were 12 months old , caregivers across the SES spectrum who had been allocated to the language intervention group engaged in significantly more contingent talk . Lower SES caregivers in this intervention group also reported that their children produced significantly more words at 15 and 18 months . Effects of the intervention did not persist at 24 months . Instead expressive vocabulary at this age was best predicted by baseline infant communication , baseline contingent talk and SES . CONCLUSIONS A social gradient in children 's communication emerges during the second year of life . A low-intensity intervention demonstrated that it is possible to increase caregiver contingent talk and that this is effective in promoting vocabulary growth for lower SES infants in the short term . However , these effects are not long-lasting , suggesting that follow-up interventions may be necessary to yield benefits lasting to school entry BACKGROUND Little evidence exists for the effectiveness of therapy for children with receptive language difficulties , particularly those whose difficulties are severe and persistent . AIMS To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a r and omized control trial with an assessor blind to group status . METHODS & PROCEDURES Fourteen participants ( aged 11;3 - 16;1 ) with severe RELI ( mean st and ard scores : CELF4 ELS = 48 , CELF4 RLS = 53 and TROG-2 = 57 ) , but higher non-verbal ( Matrices = 83 ) and visual perceptual skills ( Test of Visual Perceptual Skills ( TVPS ) = 86 ) were r and omly assigned to two groups : therapy versus waiting controls . In Phase 1 , the therapy group received eight 30-min individual sessions of explicit teaching with visual support ( Shape Coding ) with their usual SLT . In Phase 2 , the waiting controls received the same therapy . The participants ' comprehension was tested pre- , post-Phase 1 and post-Phase 2 therapy on ( 1 ) a specific test of the targeted conjunctions , ( 2 ) the TROG-2 and ( 3 ) a test of passives . OUTCOMES & RESULTS After Phase 1 , the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions ( d = 1.6 ) and overall TROG-2 st and ard score ( d = 1.4 ) . The two groups did not differ on the passives test . After Phase 2 , the waiting controls made similar progress to those in the original therapy group , who maintained their previous progress . Neither group showed progress on passives . When the two groups were combined , significant progress was found on the specific conjunctions ( d = 1.3 ) and TROG-2 raw ( d = 1.1 ) and st and ard scores ( d = 0.9 ) . Correlations showed no measures taken ( including Matrices and TVPS ) correlated significantly with progress on the targeted conjunctions or the TROG-2 . CONCLUSIONS & IMPLICATION S Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months . Given the significant progress at a group level and the lack of reliable predictors of progress , this approach could be offered to other children with similar difficulties to the participants . However , the intervention was delivered one-to-one by speech and language therapists , thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated PURPOSE Preschoolers with language impairment have difficulties with both literal and inferential language , both of which are critical to later reading comprehension . Because these children are known to be at risk for later reading comprehension difficulties , it is important to design and test interventions that foster both literal and inferential language skills . Using a r and omized pretest-posttest control group design , we investigated whether an 8-week , one-on-one book-sharing intervention would improve both the literal and inferential language skills of Head Start preschoolers with language impairments . METHOD Thirty children were r and omly assigned to either a control group that received no intervention or to a treatment group that received twice-weekly 15-min sessions in which adults read books and asked both literal and inferential questions about the books using scripts that were embedded throughout the text . Treatment and control groups were compared using pre- and posttest scores on 2 measures of literal and 1 measure of inferential language skill . RESULTS Significant group differences , and medium to large effect sizes , were found between pre- and posttest scores for all 3 measures . CONCLUSIONS These findings suggest that book sharing with embedded questions that target both literal and inferential language skills can result in gains on both types of language in this population . Future studies with larger number of children are needed to corroborate these findings OBJECTIVE : We have previously shown short-term benefits to phonology , letter knowledge , and possibly expressive language from systematic ally ascertaining language delay at age 4 years followed by the Language for Learning intervention . Here , we report the trial ’s definitive 6-year outcomes . METHODS : R and omized trial nested in a population -based ascertainment . Children with language scores > 1.25 SD below the mean at age 4 were r and omized , with intervention children receiving 18 1-hour home-based therapy sessions . Primary outcome was receptive/expressive language . Secondary outcomes were phonological , receptive vocabulary , literacy , and narrative skills ; parent-reported pragmatic language , behavior , and health-related quality of life ; costs of intervention ; and health service use . For intention-to-treat analyses , trial arms were compared using linear regression models . RESULTS : Of 1464 children assessed at age 4 , 266 were eligible and 200 r and omized ; 90 % and 82 % of intervention and control children were retained respectively . By age 6 , mean language scores had normalized , but there was little evidence of a treatment effect for receptive ( adjusted mean difference 2.3 ; 95 % confidence interval [ CI ] –1.2 to 5.7 ; P = .20 ) or expressive ( 0.8 ; 95 % CI –1.6 to 3.2 ; P = .49 ) language . Of the secondary outcomes , only phonological awareness skills ( effect size 0.36 ; 95 % CI 0.08–0.65 ; P = .01 ) showed benefit . Costs were higher for intervention families ( mean difference AU$4276 ; 95 % CI : $ 3424 to $ 5128 ) . CONCLUSIONS : Population -based intervention targeting 4-year-old language delay was feasible but did not have lasting impacts on language , possibly reflecting resolution in both groups . Long-term literacy benefits remain possible but must be weighed against its cost BACKGROUND Clinical services in the UK are increasingly delivering ' consultative ' methods of intervention rather than ' direct ' intensive input for children with receptive and expressive language difficulties , yet there has been little systematic evaluation of these different intervention models . AIMS To investigate the effectiveness of different models of therapy provision for children with specific language impairment between the ages of 4;00 and 4;06 years . METHODS & PROCEDURES Twenty-four children were selected from a specialist waiting list in the London Borough of Lambeth . They were assessed on a range of verbal and non-verbal skills , and r and omly assigned to three different intervention groups . Group 1 received direct intensive speech and language therapy weekly over an 8-month period at a child development centre ; Group 2 received a nursery-based model of intervention ; and Group 3 received review sessions at their local clinic . OUTCOME & RESULTS Statistical analysis before the intervention phase revealed no significant differences in scores between the three groups on a range of clinical and parental measures of language , non-verbal skills , play and behaviour . At the end of the intervention period the Intensive group showed significantly greater improvement than the No Intervention group on all clinical and parental measures , and significantly greater improvement than the Nursery-based group on all clinical and parental measures except for expressive grammar . CONCLUSIONS & IMPLICATION S The results of this small-scale study demonstrate that intensive direct speech and language therapy delivered by speech and language therapists was a more effective model of intervention for this clinical group with severe speech and language impairment BACKGROUND Oral language skills are a critical foundation for literacy and more generally for educational success . The current study shows that oral language skills can be improved by providing suitable additional help to children with language difficulties in the early stages of formal education . METHODS We conducted a r and omized controlled trial with 394 children in Engl and , comparing a 30-week oral language intervention programme starting in nursery ( N = 132 ) with a 20-week version of the same programme starting in Reception ( N = 133 ) . The intervention groups were compared to an untreated waiting control group ( N = 129 ) . The programmes were delivered by trained teaching assistants ( TAs ) working in the children 's schools/nurseries . All testers were blind to group allocation . RESULTS Both the 20- and 30-week programmes produced improvements on primary outcome measures of oral language skill compared to the untreated control group . Effect sizes were small to moderate ( 20-week programme : d = .21 ; 30-week programme : d = .30 ) immediately following the intervention and were maintained at follow-up 6 months later . The difference in improvement between the 20-week and 30-week programmes was not statistically significant . Neither programme produced statistically significant improvements in children 's early word reading or reading comprehension skills ( secondary outcome measures ) . CONCLUSIONS This study provides further evidence that oral language interventions can be delivered successfully by trained TAs to children with oral language difficulties in nursery and Reception classes . The methods evaluated have potentially important policy implication s for early education The aim of this study was to pilot test a classroom-based intervention focused on facilitating play and joint attention for young children with autism in self-contained special education classrooms . Thirty-three children with autism between the ages of 3 and 6 years participated in the study with their classroom teachers ( n = 14 ) . The 14 preschool special education teachers were r and omly assigned to one of three groups : ( 1 ) symbolic play then joint attention intervention , ( 2 ) joint attention then symbolic intervention , and ( 3 ) wait-list control period then further r and omized to either group 1 or group 2 . In the intervention , teachers participated in eight weekly individualized 1-h sessions with a research er that emphasized embedding strategies targeting symbolic play and joint attention into their everyday classroom routines and activities . The main child outcome variables of interest were collected through direct classroom observations . Findings indicate that teachers can implement an intervention to significantly improve joint engagement of young children with autism in their classrooms . Furthermore , multilevel analyses showed significant increases in joint attention and symbolic play skills . Thus , these pilot data emphasize the need for further research and implementation of classroom-based interventions targeting play and joint attention skills for young children with autism |
2,612 | 24,957,361 | There was no association between pre-LIFT drainage seton and success of LIFT .
Ligation of the intersphincteric fistula tract appears to be an effective and safe treatment for trans-sphincteric or complex anal fistula .
Combining other procedures and a pre-LIFT drainage seton does not seem to confer any added benefit in terms of success . | Sphincter-preserving approaches to treat anal fistula do not jeopardize continence ; however , healing rates are suboptimal .
In this context , ligation of the intersphincteric fistula tract ( LIFT ) can be considered promising offering high success rates and a relatively simple procedure .
This review aim ed to investigate the outcomes of LIFT to treat anal fistula . | PURPOSE : This study was design ed to assess the total anal sphincter – saving technique of ligating the intersphincteric fistula tract for the treatment of fistula-in-ano . METHODS : We performed a prospect i ve observational study of patients with fistula-in-ano treated with the ligation of the intersphincteric fistula tract technique from May 2007 through September 2008 . All patients had fistulas arising from cryptogl and ular infections . Recurrence rate , healing time , and morbidities related to the procedure were determined with a st and ard follow-up protocol . RESULTS : Forty-five patients with transsphincteric ( n = 33 ) or complex ( n = 12 ) fistulas were included in the study . Five patients ( 11.1 % ) had recurrent fistula-in-ano after prior surgery using other recognized treatment procedures . The median age was 41.5 ( range , 27–56 ) years ; median follow-up , 9 ( range , 2–16 ) months . Primary healing was achieved in 37 patients ( 82.2 % ) , with a median healing time of 7 ( range , 4–10 ) weeks . Eight patients ( 17.7 % ) had recurrence of fistula between 3 and 8 months after the operation . No clinical ly significant morbidity was noted in any of the 45 patients . CONCLUSIONS : The ligation of the intersphincteric fistula tract technique for fistula-in-ano surgery , which aims at total anal sphincter preservation , appears to be both safe and easy to perform , with encouraging early outcomes Purpose Long-term closure rates of anorectal fistulas using fibrin glue have been disappointing , possibly because of the liquid consistency of the glue . A suturable bioprosthetic plug ( Surgisis ® , Cook Surgical , Inc. ) was fashioned to close the primary opening of fistula tracts . A prospect i ve cohort study was performed to compare fibrin glue vs. the anal fistula plug . Methods Patients with high transsphincteric fistulas , or deeper , were prospect ively enrolled . Patients with Crohn 's disease or superficial fistulas were excluded . Age , gender , number and type of fistula tracts , and previous fistula surgeries were compared between groups . Under general anesthesia and in prone jackknife position , the tract was irrigated with hydrogen peroxide . Fistula tracts were occluded by fibrin glue vs. closure of the primary opening using a Surgisis ® anal fistula plug . Results Twenty-five patients were prospect ively enrolled . Ten patients underwent fibrin glue closure , and 15 used a fistula plug . Patient 's age , gender , fistula tract characteristics , and number of previous closure attempts was similar in both groups . In the fibrin glue group , six patients ( 60 percent ) had persistence of one or more fistulas at three months , compared with two patients ( 13 percent ) in the plug group ( P < 0.05 , Fisher exact test ) . Conclusions Closure of the primary opening of a fistula tract using a suturable biologic anal fistula plug is an effective method of treating anorectal fistulas . The method seems to be more reliable than fibrin glue closure . The greater efficacy of the fistula plug may be the result of the ability to suture the plug in the primary opening , therefore , closing the primary opening more effectively . Further prospect i ve , long-term studies are warranted Background Ligation of the intersphincteric tract ( LIFT ) , a novel sphincter-saving technique , has been recently described with promising results . Literature data are still scant . In this prospect i ve observational study , we present our experience with this technique . Methods Between October 2010 and April 2011 , 18 patients with ‘ complex ’ fistulas underwent LIFT . All patients were enrolled in the study after a physical examination including digital examination and proctoscopy . For the purpose of this pilot study , fistulas were classified as complex if any of the following conditions were present : tract crossing more than 30 % of the external sphincter , anterior fistula in a woman , recurrent fistula or pre-existing incontinence . Endpoints were healing time , presence of recurrence , faecal incontinence and surgical complications . Results Ten patients were men and 8 were women ; mean age was 39 years ; minimum follow-up was 4 months . Three patients required drainage seton insertion and delayed LIFT . After LIFT , 1 patient experienced haemorrhoidal thrombosis . At the end of the follow-up , 15 patients ( 83 % ) healed with no recurrence . Three patients had persistent symptoms and required further surgical treatment . We did not observe postoperative worsening of continence . Conclusions Results from our pilot study indicate that this novel sphincter-saving approach is effective and safe for treating complex anal fistula Ligation of the intersphincteric fistula tract ( LIFT ) is a novel sphincter‐preserving technique for anal fistula . This pilot study was design ed to evaluate the results in patients with a recurrent fistula Seventy‐four patients who underwent seton treatment of high anal fistulae over a 6‐year period have been review ed . Four different techniques were used : staged fistulotomy ( n = 24 ) , cutting seton ( n = 13 ) , short‐term seton drainage ( n = 14 ) and long‐term seton drainage in patients with Crohn 's disease ( n = 23 ) . Recurrence developed in two patients ( 8 per cent ) undergoing two‐stage fistulotomy ; two patients ( 14 per cent ) undergoing short‐term drainage and nine ( 39 per cent ) of the patients with Crohn 's disease . Three patients with Crohn 's disease required proctectomy for progressive perianal disease . The remaining 11 patients with Crohn 's disease ( 48 per cent ) obtained a good result . None of the patients treated with a cutting seton developed a recurrence . Minor incontinence developed in 13 patients ( 54 per cent ) undergoing two‐stage fistulotomy and seven patients ( 54 per cent ) treated with a cutting seton . When sphincter muscle was not divided , five patients ( 36 per cent ) undergoing short‐term drainage and six patients ( 26 per cent ) undergoing long‐term drainage developed minor incontinence . High complex fistulae can be successfully treated with only minor loss of continence using different seton techniques . In high Crohn 's fistulae , long‐term seton drainage preserves sphincter function , but recurrence is common if the seton is removed BACKGROUND The ligation of intersphincteric fistula tract ( LIFT ) is a relatively new surgical technique for treating complex anorectal fistulas . METHODS LIFT was compared with anorectal advancement flap management ( ARAF ) of complex anorectal fistulas requiring previous seton drainage . Crohn 's patients were excluded . Patients with no confirmed recurrent sepsis after 6 months were r and omized to day surgery performance of LIFT ( 25 ; 17 male ) or ARAF ( 14 ; 10 male ) with removal of the seton . Outcome measures included recurrences , surgical time , complications , hospital readmissions , and fecal incontinence . RESULTS LIFT was 32.5 minutes shorter than ARAF ( P < .001 ) . Complications were similar , with no hospital readmissions . Return to normal activities was 1 week for LIFT patients , 2 weeks for ARAF patients ( P = .016 ) . At 19 months there were 3 recurrences ( 2 in the LIFT group ) . One ARAF patient had minor incontinence . CONCLUSIONS The LIFT procedure was simple , safe , shorter , and patients returned to work earlier . All patients had preliminary seton drainage , possibly contributing to the low recurrence rates OBJECTIVE To describe a new technique for fistula-in-ano surgery aim ed at total sphincter preservation , and evaluate the preliminary results concerning non-healing and intact anal function . MATERIAL AND METHOD A prospect i ve observational study in eighteen fistula-in-ano patients treated by ligation of intersphincteric fistula tract ( LIFT ) technique , from January to June 2006 . RESULTS Fistula-in-ano in seventeen patients healed primarily ( 94.4 % ) . There was one non-healing case ( 5.6 % ) . The mean healing time was four weeks . None had disturbances in clinical anal continence . CONCLUSION The early outcome of the LIFT technique is quite impressive . Results warrant a larger study with long-term evaluation . This technique has the potential to become a viable option for fistula-in-ano surgery INTRODUCTION : The management of complex fistulas is difficult . Maintaining continence while achieving durable fistula closure is the goal of surgical management . This study describes our experience with a novel sphincter-sparing technique called the ligation of the intersphincteric fistula tract , which involves ligation and division of the fistula tract in the intersphincteric space . METHODS : All patients from July 2007 to December 2008 with trans- or suprasphincteric fistula treated with the procedure were prospect ively followed . Procedures were performed by surgeons with fellowship training in a referral center . Demographic data , comorbidities , previous repair attempts , and postoperative data were collected . RESULTS : A total of 39 patients underwent a ligation of the intersphincteric fistula tract during a 17-month period . Median age was 49 years . A total of 29 patients ( 74 % ) had previous attempts at repair , with a median of 2 failed repairs . Follow-up data were available in 90 % ( 35 of 39 ) . Median follow-up was 20 weeks . Successful fistula closure was achieved in 57 % of the patients ( 20 of 35 ) . Median time to failure was 10 weeks ( range , 2–38 weeks ) . No patient reported any subjective decrease in continence after the procedure . CONCLUSION : Ligation of the intersphincteric fistula tract is a new sphincter-sparing procedure for complex transsphincteric fistula . The success rate is comparable with other sphincter-preserving techniques . Importantly , it appeared to effectively preserve continence . Adding safe , muscle-sparing surgical options to our armamentarium for dealing with transsphincteric fistula is essential . Additionally , the procedure is easy to learn and has very low cost . Long-term follow-up and r and omized , controlled trials are necessary to assess efficacy and durability |
2,613 | 16,437,476 | There is insufficient evidence to determine whether antibiotic strategies for the eradication of early P. aeruginosa decrease mortality or morbidity , improve quality of life , or are associated with adverse effects compared to placebo or st and ard treatment .
From the three trials included in this review , there is some evidence that antibiotic treatment of early P. aeruginosa results in short-term eradication but it remains uncertain whether there is clinical benefit to people with cystic fibrosis | BACKGROUND Lower respiratory tract infection with Pseudomonas aeruginosa ( P. aeruginosa ) occurs in most people with cystic fibrosis .
Once chronic infection is established , P. aeruginosa is virtually impossible to eradicate and is associated with increased mortality and morbidity .
Early infection may be easier to eradicate .
OBJECTIVES To determine whether antibiotic treatment of early P. aeruginosa infection in children and adults with cystic fibrosis eradicates the organism and improves clinical and microbiological outcome . | BACKGROUND Aztreonam lysine for inhalation ( AZLI ) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection . METHODS This double-blind , r and omized , placebo-controlled Phase 2 study evaluated the safety , tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow Electronic Nebulizer ( Pari Innovative Manufacturers , Inc. , Midlothian , VA ) . Patients were 13 years and older with FEV1>or=40 % predicted , chronic P. aeruginosa infection , and had used no anti-pseudomonal antibiotics for 56 days . RESULTS Of 131 patients screened , 105 received AZLI or placebo . Mean age was 26 years and mean FEV1 percent predicted was 77 % at baseline . There was a statistically significant reduction , compared to placebo , in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 ( P<0.001 ) . The planned primary analysis , percent change in FEV1 at Day 14 , demonstrated no statistically significant difference . Post hoc analysis demonstrated significant increase in FEV1 at Day 7 for the subset of patients with baseline FEV1<75 % predicted in the 225 mg AZLI group . Bronchodilator use was associated with greater improvement in FEV1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group . Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group . CONCLUSION These data support the further development of AZLI and provide information for the design of subsequent studies Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis ( CF ) patients during a recent clinical trial of inhaled tobramycin . Impermeability , in which bacteria have reduced susceptibility to all aminoglycosides , was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol . Enzymatic resistance mechanisms were found in fewer than 10 % of resistant isolates . P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness . When enzymatic resistance was involved , all isolates in a group had elevated tobramycin MICs . When impermeability occurred , MICs of a genotypic group varied from susceptible to resistant . These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC STUDY OBJECTIVE To determine the effect of long-term suppression of Pseudomonas aeruginosa on lung function and other clinical end points in adolescent patients with cystic fibrosis ( CF ) . DESIGN Two identical , r and omized , placebo-controlled trials followed by three open-label follow-on trials . SETTING Sixty-nine CF study centers in the United States . INTERVENTIONS Active drug consisting of a 300-mg tobramycin solution for inhalation ( TSI ) . PATIENTS One hundred twenty-eight adolescent CF patients ( aged 13 to 17 years ) with P aeruginosa and mild-to-moderate lung disease ( FEV(1 ) percent predicted > or = 25 % and < or = 75 % ) . MEASUREMENTS Pulmonary function , P aeruginosa colony forming unit density , incidence of hospitalization and IV antibiotic use , weight gain , and aminoglycoside toxicity were monitored . RESULTS At the end of the first three 28-day cycles of TSI treatment , patients originally r and omized to TSI and placebo treatments exhibited improvements in FEV(1 ) percent predicted of 13.5 % and 9.4 % , respectively . FEV(1 ) percent predicted was maintained above the value at initiation of TSI treatment in both groups . At the end of the last " on-drug " period ( 92 weeks ) , patients originally r and omized to TSI and placebo treatments showed improvements of 14.3 % and 1.8 % , respectively . Improvement in pulmonary function was significantly correlated with reduction in P aeruginosa colony forming unit density ( p = 0.0001 ) . The average number of hospitalizations and IV antibiotic courses did not increase over time . TSI treatment was associated with increased weight gain and body mass index . P aeruginosa susceptibility to tobramycin decreased slightly over time , but this was not correlated with clinical response . CONCLUSIONS TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term , intermittent use We report the results of a clinical trial . Patients enrolled had serum IgG titres against Pseudomonas aeruginosa above the control range . Assignment to the observation or treatment group was by minimisation . Significant signs or symptoms in any patient prompted antipseudomonal treatment . In addition , the treatment group received antipseudomonal treatment at intervals of four months until the serum IgG titre returned to the control range . P aeruginosa was isolated intermittently from patients in the main trial . Nineteen patients were enrolled ( 12 observation , seven treatment ) . After one year in the trial changes in parameters studied , including forced expiratory volume in one second , IgG titre , serum IgG concentrations , and frequency of P aeruginosa isolation had improved in the treated group and worsened in the observation group OBJECTIVES This r and omized , double-blind , cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis ( CF ) infected with Pseudomonas aeruginosa with and without airway hyperreactivity . DESIGN Of 19 children with CF ( age range , 7 to 16 years ) with mild-to-moderate pulmonary disease , 10 children were at high risk ( HR ) for bronchospasm ( family history of asthma and previous response to bronchodilators ) and 9 children were at low risk ( LR ) for bronchospasm ( no family history of asthma or previous response to bronchodilators ) . Two solutions of tobramycin were administered : ( 1 ) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites ( IV preparation ) ; and ( 2 ) 300 mg in a preservative-free preparation in a 5-mL solution . Following a bronchodilator-free period of 12 h , the patients inhaled either one or the other preparation in r and om order on two different occasions , 2 weeks apart . RESULTS Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1 ) ( DeltaFEV(1 ) ) of 12 + /- 9 % ( mean + /- SD ) for the IV preparation , compared to 4 + /- 5 % for the preservative-free preparation ( p = 0.046 ) . An DeltaFEV(1 ) of > 10 % was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation . For the HR group , the DeltaFEV(1 ) was 17 + /- 13 % for the IV-preparation group , compared to 16 + /- 12 % for the preservative-free group ( p = 0.4 ) . In this group , equal numbers of patients ( 8 of 10 patients ) had an DeltaFEV(1 ) > 10 % after inhaling each preparation . The largest DeltaFEV(1 ) was 44 % ( HR group with the preservative-free preparation that forced the early termination of inhalation ) . CONCLUSIONS Both preparations caused significant bronchoconstriction in the HR group , and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution . Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis ( CF ) , antibiotic therapy generally fails to eradicate the bacterial pathogen . The mucoid bacterial phenotype , high sputum production by the host , and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy . We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection . In a prospect i ve placebo-controlled , double-blind , r and omized multicenter study , 22 CF patients received either 80 mg b.i.d . of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization . Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period . Using life table analysis , the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group ( P < 0.05 , log rank test ) . Lung function parameters and markers of inflammation did not change in either group during treatment . The results of this study suggest that early tobramycin inhalation may prevent and /or delay P. aeruginosa pulmonary infection in CF patients Abstract Background and aim Progressive respiratory failure due to Pseudomonas aeruginosa colonization is the most significant morbidity in patients with cystic fibrosis ( CF ) . This trial was design ed to investigate the efficacy and safety of a highly concentrated ( 300mg/4mL ) tobramycin solution for inhalation ( TSI ) [ Bramitob ® ] in patients with CF and P. aeruginosa infection . Methods Fifty-nine patients were r and omized to receive a 4-week treatment with tobramycin or placebo administered twice daily via the Pari LC Plus ® nebulizer and Pari TurboBoy ™ compressor , followed by a 4-week run-out phase . Pulmonary function ( forced expiratory volume in 1 second [ FEV1 ] , forced vital capacity [ FVC ] , and forced expiratory flow at the midportion of vital capacity [ FEF25–75 % ] ) , P. aeruginosa susceptibility , microbiologic results , and in vitro minimum inhibitory concentration for 90 % of strains ( MIC90 ) were the efficacy outcome measures , while safety was monitored by the recording of adverse events , audiometry ( bone conduction at 250–8000Hz frequency ) , laboratory tests , physical examination and general health condition . The concentration of tobramycin attained in sputum was measured in a cohort of 21 patients . Results FEV1 significantly increased from baseline in the tobramycin group compared with no change in the placebo group : the absolute difference between groups ( intent-to-treat population ) of predicted normal was 13.2 % at week 2 ( p = 0.002 ) and 13.3 % at week 4 ( p = 0.003 ) . Significant differences in favor of the tobramycin group were also observed for FVC and FEF25–75 % . The microbiologic results at the end of the treatment period ( P. aeruginosa-negative culture , persistence , superinfection ) showed a significantly better outcome in the tobramycin group compared with placebo ( p = 0.033 ) . The effects of tobramycin on pulmonary function and microbiology were not maintained at the end of the run-out phase . Mean sputum concentrations of tobramycin after the first dose ( 695.6 ± 817.0 µg/mL ) were similar to those measured after the last dose ( 716.9 ± 799 µg/mL ) and were superior to the detected specific MIC90.The proportion of patients with drug-related adverse events was lower in the tobramycin group and no signs of renal or auditory toxicity were observed . Conclusions The 4-week administration of a highly concentrated TSI significantly improved pulmonary function and microbiologic outcome compared with placebo and was well tolerated . The results of this study should be confirmed in further long-term trials in larger population BACKGROUND AND METHODS We conducted two multicenter , double-blind , placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection . A total of 520 patients ( mean age , 21 years ) were r and omly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks , followed by four weeks with no study drug . Patients received treatment or placebo in three on-off cycles for a total of 24 weeks . The end points included pulmonary function , the density of P. aeruginosa in sputum , and hospitalization . RESULTS The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second ( FEV1 ) of 10 percent at week 20 as compared with week 0 , whereas the patients receiving placebo had a 2 percent decline in FEV1 ( P<0.001 ) . In the tobramycin group , the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units ( CFU ) per gram of expectorated sputum from week 0 to week 20 , as compared with an increase of 0.3 log10 CFU per gram in the placebo group ( P<0.001 ) . The patients in the tobramycin group were 26 percent ( 95 percent confidence interval , 2 to 43 percent ) less likely to be hospitalized than those in the placebo group . Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum . The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group , as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group . CONCLUSIONS In a 24-week study of patients with cystic fibrosis , intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function , decreased the density of P. aeruginosa in sputum , and decreased the risk of hospitalization OBJECTIVE The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin , supplemented by amikacin inhalation therapy . METHODS Twenty-one patients were r and omly assigned to oral ciprofloxacin alone ( Group I ) and 23 received ciprofloxacin plus inhaled amikacin ( Group II ) . RESULTS Negative sputum cultures were achieved in 34 patients ( 77 % ) at the end of intensive therapy ( 19 Group I and 15 Group II ) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I ( 26 % ) and in 8 of the 15 responders in Group II ( 53 % ) . Resistance to ciprofloxacin was found in 7 of 31 ( 23 % ) sputum isolates at the end of ciprofloxacin therapy . During maintenance therapy , continued improvement in clinical symptoms was observed in 14 patients in both treatment groups ; 6 in each group had further improvements whereas only 4 patients were clinical failures . There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance . Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age . There were no severe or serious adverse events , no signs of quinolone-related arthropathy and no growth impairment . CONCLUSION Ciprofloxacin was efficacious , safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients . These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted OBJECTIVE Two identical 24-week , double-blind , placebo-controlled trials of tobramycin solution for inhalation ( TOBI [ PathoGenesis Corporation , Seattle , Washington ] ) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States . The aim of the present study was to extrapolate the US trial data to a Canadian setting , using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces . BACKGROUND Cystic fibrosis is a genetic disease in which persistent respiratory infection , usually due to P. aeruginosa infection , is the major cause of morbidity and mortality . METHODS The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results , reduced sputum levels of P. aeruginosa , and result ed in a 26 % reduction in the probability of hospitalization ( 95 % CI , 2%-43 % vs placebo in the clinical trials ) . Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy . To adjust for Canadian pricing , pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries . Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation . RESULTS Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs ( in Canadian dollars ) of $ 4055 in Ontario and $ 4916 in Quebec , which would substantially offset the Canadian acquisition price of $ 8602 for the same 24-week period . CONCLUSIONS Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting , use of TOBI would reduce the use of health care services , particularly hospital days , and lead to substantial savings in direct medical costs that would offset its acquisition price . Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation STUDY OBJECTIVE Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis ( CF ) patients despite reports of chest tightness and bronchospasm . The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity . DESIGN AND METHODS A prospect i ve placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration . Subjects were recruited as follows : high risk ( HR ) for bronchospasm due to a personal history of recurrent wheezing , a family history of asthma and /or atopy , or bronchial lability , as demonstrated in pulmonary function tests ; or low risk ( LR ) without these characteristics . RESULTS The mean FEV(1 ) ( expressed as the mean [ + /- SD ] fall from baseline ) of the HR group ( n = 12 ) fell 12 + /- 9 % after placebo was administered , and fell 17 + /- 10 % after colistin was administered . For the LR group ( n = 8) , the mean FEV(1 ) fell 9 + /- 4 % following placebo administration and 13 + /- 8 % following colistin administration . There was a greater number of subjects in the HR group compared to the LR group , which had a mean fall in FEV(1 ) of > /= 15 % ( p < 0.01 ) after inhaling colistin . The differences between placebo and colistin therapy in the LR group were not significant . CONCLUSION The results demonstrated that colistin can cause bronchospasm , particularly in those patients with coexisting CF and asthma We examined the effect of inhaled fluticasone diproprionate ( FDP ) on symptoms , lung function ( FEV(0.5 ) ) , and exhaled nitric oxide ( Fe(NO ) ) in infants with recurrent wheeze and raised Fe(NO ) . Thirty-one infants aged 6 - 19 months ( mean , 12.7 months ; 12 girls ) completed the study . All infants had a history of recurrent wheeze and a parental history of atopy . All children had raised Fe(NO ) , as determined by an offline tidal breathing technique prior to r and omization . Lung function and Fe(NO ) were assessed before and after 4 weeks of treatment with FDP or placebo . The parents recorded daily symptoms during the treatment period . Sixteen infants received FDP and 15 the placebo for 4 weeks . At completion of the study , infants treated with FDP had a significant reduction in Fe(NO ) ( 35.0 ppb to 16.5 ppb ) compared to those that received placebo ( 35.2 ppb to 30.2 ppb ) ( P = 0.05 ) . Small increases in FEV(0.5 ) were observed in both groups , but these changes were not different between groups ( P = 0.8 ) . Symptom scores were not significantly different in either group following the intervention . We showed that a moderate dose of inhaled FDP reduces levels of Fe(NO ) , a potential marker of airway inflammation , even in the absence of significant changes in lung function and symptoms The optimal treatment for the eradication of initial P. aeruginosa infection in CF is still unclear . Recently long-term inhaled tobramycin has been proposed . Here we report the results with brief inhaled and /or systemic anti-pseudomonal treatments . Initial P. aeruginosa colonization was successfully eradicated as demonstrated by negative repetitive throat cultures or sputa and serum antipseudomonal antibodies in 15 of 17 patients for at least two years . R and omized , controlled trials are urgently needed to define the optimal protocol for the eradication of P. aeruginosa . Pseudomonas aeruginosa , infection , treatment , antibodies ; inhaled We conducted a double-blind , placebo-controlled , multicenter , r and omized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa ( Pa ) density from the lower airway of young children with cystic fibrosis . Ninety-eight subjects were to be r and omized ; however , the trial was stopped early because of evidence of a significant microbiological treatment effect . Twenty-one children under age 6 years were r and omized ( 8 active ; 13 placebo ) and underwent bronchoalveolar lavage at baseline and on Day 28 . There was a significant difference between treatment groups in the reduction in Pa density ; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients . We observed no differences between treatment groups for clinical indices , markers of inflammation , or incidence of adverse events . No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment . We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis The development of drug resistance is a major theoretical concern with the long-term delivery of aerosolized antibiotics via inhalation . A r and omized , placebo-controlled , double-blind study , which compared inhaled tobramycin plus st and ard cystic fibrosis ( CF ) care to placebo plus st and ard CF care , examined the following microbiological parameters : percentage of patients with at least one Pseudomonas aeruginosa ( PA ) strain with a minimal inhibitory concentration ( MIC ) > 16 microg/mL ( ie , the breakpoint for tobramycin resistance delivered by the parenteral route ) ; changes in the levels of the lowest concentration required to inhibit the growth of 50 % of strains tested ( MIC(50 ) ) and 90 % of strains tested ( MIC(90 ) ) ; the percentage of patients with an increase , decrease , or change in the MIC of the most resistant and most prevalent PA strains ; and the percentage of patients in whom the PA strain with the highest MIC also was the most prevalent . During the first 6 months , which included three on-drug and off-drug cycles of 4 weeks ' duration each , the percentage of tobramycin-treated patients with at least one PA isolate and with an MIC > 16 microg/mL was 13 % at baseline , 26 % at 20 weeks , and 23 % at 24 weeks vs 10 % , 17 % , and 8 % , respectively , for placebo-treated patients . No significant change was observed in MIC(50 ) at 20 and 24 weeks . The increase in MIC(90 ) was not statistically significant . At 24 weeks , there was no increase in the percentage of patients in either group in whom the PA strain with the highest MIC became most the prevalent strain . After the third on-drug cycle , 33 % of the tobramycin group showed an increase in the MIC of the strain with the highest MIC . This decreased to 26 % after 1 month off drug therapy . A preliminary analysis of the 12-month and 18-month data showed a decrease in the proportion of resistant PA isolates after each off-drug cycle . This return to susceptibility following an off-drug cycle was not observed at 24 months . The mechanism of resistance in this setting is believed to be increased impermeability to drug . At all time points , pulmonary function improved even in patients with MICs of > or = 128 microg/mL. At 6 months , no increase was seen in the rates of superinfection with tobramycin-resistant , Gram-negative pathogens . Increases in Stenotrophomonas maltophilia were detected in patients after 18 and 24 months of tobramycin therapy and were similar to those rates in patients receiving placebo . These rates may be independent of inhalation therapy To underst and better the events associated with the initiation of lung disease in young children with cystic fibrosis ( CF ) , we prospect ively performed a longitudinal study examining the early bacteriologic , immunologic , and clinical courses of 42 children with CF diagnosed after identification by neonatal screening . Serial evaluations included history and physical examination , chest radiographs , throat cultures for bacteria , and determinations of serum immunoglobulin levels and circulating immune complexes . At a mean follow-up age of 27 months , 19 % of the children had serial throat cultures positive for Pseudomonas aeruginosa ; the first positive culture was found at a mean age of 21 months . In three infants the initial P. aeruginosa isolates were mucoid . As determined by typing with a DNA probe , serial P. aeruginosa isolates from each patient were identical over time but were genetically distinct from isolates recovered from other patients . Of 11 infants with P. aeruginosa , nine ( 82 % ) had previous isolates of Staphylococcus aureus or Haemophilus influenzae ; all had received prior antibiotic therapy . In comparison with other infants with CF , children with P. aeruginosa grown on serial throat cultures more frequently had daily cough ( p less than 0.01 ) , lower chest radiograph scores ( p less than 0.05 ) , and elevated levels of circulating immune complexes ( p less than 0.01 ) . None of the study infants had persistent hypogammaglobulinemia or hypergammaglobulinemia . We conclude that ( 1 ) S. aureus and H. influenzae remain the isolates most frequently recovered from infants with CF ; ( 2 ) initial recovery of P. aeruginosa by throat culture is often preceded by the onset of chronic respiratory signs ; ( 3 ) elevations of circulating immune complexes can occur early , often after the initial recovery of P. aeruginosa ; and ( 4 ) early P. aeruginosa isolates are genetically distinct , demonstrating the lack of cross-colonization in this newborn population OBJECTIVES To evaluate whether antistaphylococcal prophylaxis in infants and young children with cystic fibrosis ( CF ) would suppress the acquisition of Staphylococcus aureus and delay the onset of the manifestations of bronchopulmonary disease . STUDY DESIGN A 7-year , multicenter , double-blind , placebo-controlled study of continuous antistaphylococcal therapy . Otherwise healthy children < 2 years of age with CF were r and omly assigned to be treated with daily cephalexin ( 80 - 100 mg/kg/day ) or placebo . Clinical , microbiologic , laboratory , radiographic , and anthropometric outcomes were evaluated . RESULTS Of 209 children enrolled , 119 completed a 5- to 7-year course of therapy . Mean age at enrollment was 15.6 and 14.1 months in the cephalexin and placebo groups , respectively . Respiratory cultures from children treated with cephalexin were significantly less likely to be positive for S aureus ( 6.0 % vs 30.4 % ; P < .001 ) . They were , however , much more likely to be positive for Pseudomonas aeruginosa ( 25.6 % vs 13.5 % ; P < .009 ) . These differences became apparent in the first year after enrollment and persisted over the duration of the study . In contrast to these microbiologic differences , there were no differences in clinical outcome measures , including radiographic ( Brasfield score , 23.4 vs 23.2 ) or anthropometric scores or pulmonary function . CONCLUSIONS Although long-term prophylaxis with cephalexin successfully delayed the acquisition of S aureus , it enhanced colonization with P aeruginosa and did not lead to clinical ly significant improvement in major health outcomes . These data do not support routine antistaphylococcal prophylaxisin otherwise healthy infants and young children with CF Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy . We evaluated the pharmacokinetics ( PK ) and safety of tobramycin inhalation powder ( TIP ) , a novel dry-powder formulation design ed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections . This was a multi-center , open-label , sequential-cohort , single-dose , dose-escalation study using the st and ard 300 mg dose of tobramycin solution for inhalation ( TSI ) as an active control . Subjects were r and omized to TIP or TSI in a 3:1 ratio in each of five cohorts . Measurements included serum and sputum tobramycin concentrations , administration time , serum chemistries , acute change in lung function , and adverse events ( AEs ) . Out of 90 r and omized subjects , 86 had data for safety analysis ; and 84 had data for PK analysis . Serum tobramycin PK profiles were similar for TIP and TSI . Four capsules of 28 mg TIP ( total tobramycin dose 112 mg ) produced comparable systemic exposure to 300 mg TSI , in less than one-third the administration time . The most common AEs associated with TIP were cough ( 20 % ) and dysgeusia ( 17 % ) . TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation . The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation . The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections The objective of this study was to assess the diagnostic accuracy of oropharyngeal ( OP ) cultures relative to simultaneous bronchoalveolar lavage ( BAL ) cultures in very young children with CF , and to examine the effects of bacterial density , age , and study cohort on diagnostic accuracy . Respiratory culture data were analyzed from three independent , prospect i ve studies involving simultaneous collection of 286 OP and BAL cultures from 141 children with CF < 5 years of age . For predicting any growth of Pseudomonas aeruginosa ( Pa ) from the lower airway in subjects < /=18 months of age ( mean age , 8 + /- 5 months ) , OP cultures had a sensitivity of 44 % ( 95 % CI 14 % , 79 % ) , specificity of 95 % ( 90 % , 99 % ) , positive predictive value of 44 % ( 14 % , 79 % ) , and negative predictive value of 95 % ( 90 % , 99 % ) . Diagnostic accuracy was similar for Haemophilus influenzae ( Hi ) . Specificity was significantly lower for Staphylococcus aureus ( Sa ) . Sensitivity for all organisms improved if a positive lower airway culture was defined as > /=10(3 ) or > /=10(5 ) cfu/mL. Specificity for Pa declined significantly with increasing age . In children with CF < 5 years of age , the specificity and negative predictive value of OP cultures for Pa are high , while the sensitivity and positive predictive value are poor . Thus , in this age range , a negative throat culture is helpful in " ruling out " lower airway infection with Pa. However , a positive culture does not reliably " rule in " the presence of Pa in the lower respiratory tract . These findings may have implication s for study design and interpretation as well as clinical management of young children with CF BACKGROUND Cystic fibrosis patients have chronic bacterial infections of the respiratory tract , most commonly Pseudomonas aeruginosa . Although controversial , administration of antibiotic therapy during acute pulmonary exacerbations is st and ard practice . Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies . Because of its activity against P. aeruginosa and excellent oral bioavailability , ciprofloxacin offers a unique therapeutic alternative for this patient population . OBJECTIVE This prospect i ve , r and omized , double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection . METHODS One hundred thirty patients ( ages 5 to 17 years ) were r and omized to receive either i.v . ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v . ceftazidime 50 mg/kg every 8 h plus i.v . tobramycin 3 mg/kg every 8 h for a minimum of 10 days . Clinical , bacteriologic and safety responses were assessed throughout the study . RESULTS All 84 patients ( median age , 11 years ; range , 5 to 17 years ) valid for efficacy in both treatment groups demonstrated clinical improvement . Five patients experienced clinical relapses ( 3 ciprofloxacin , 2 ceftazidime/tobramycin ) by the 2- to 4-week follow-up . Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up . Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas . DNA profiles demonstrated that irrespective of colony morphology , usually one clonal strain was associated with each patient 's pulmonary exacerbation . Treatment-associated musculoskeletal events occurred with equal frequency ( 22 % vs. 21 % ) in both study drug groups ( n = 129 ) , and arthralgias were within the range of rates for cystic fibrosis arthropathy . None of these events required study drug discontinuation . CONCLUSION Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to st and ard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable , 26 patients who had never received anti-pseudomonas chemotherapy were r and omly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks , whenever Ps aeruginosa was isolated from routine sputum cultures . During the 27 months of the trial , infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects ( 2 [ 14 % ] vs 7 [ 58 % ] ; p less than 0.05 ) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group ( 49/214 [ 23 % ] vs 64/158 [ 41 % ] ; p = 0.0006 ) . Thus , chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients . Microbiology results from two multicenter , double-blind , placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora , antibiotic susceptibility , and selection of P. aeruginosa isolates with decreased tobramycin susceptibility . Clinical response was examined to determine whether current susceptibility st and ards are applicable to aerosolized administration . Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia , Stenotrophomonas maltophilia , or Alcaligenes xylosoxidans ; however , isolation of C and ida albicans and Aspergillus species did increase . Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group , there was no evidence of selection for the most resistant isolates to become most prevalent . The definition of resistance for parenteral administration does not apply to inhaled tobramycin : too few patients had P. aeruginosa with a tobramycin MIC > /=16 microgram/mL to define a new break point on the basis of clinical response Chronic bronchial infection with Pseudomonas aeruginosa is closely associated with decline in pulmonary function in cystic fibrosis ( CF ) ( 1 ) . It would seem worthwhile to attempt to prevent colonization at the early stages and so halt the progression to chronic infection , when permanent eradication of the bacteria is impossible . However , no aproach in this regard has gained widespread acceptance . We have performed a preliminary trial to assess if early combined systemic and aerosol therapy can delay the onset of chronic infection . In eight CF patient , P . aeruginosa was first grown in a sputum sample between February 1988 and June 1989 . All previous sputum and throat cultures had been negative , and all six whom it was available had a normal ( 01 ) number of serum precipitins against P . aeruginosa surface antigens ( Dr N. Hpliby , Copenhagen ) three to nine months prior to colonization . We review ed the records of the last eight patients with CF under control at our Hospital who first had P . aeruginosa isolated in sputum , before the date of the start of the trial , in order to act as historic controls . They had had 3 - 8 ( mean 4.4 ) negative cultures for P. aeruginasa over the year to colonization . The number of serum precipitins against P. aeruginosa was normal in the only two patients in whom it was available . Every study patient was given a two-week course of oral ciprofloxacin 35 mg/kg/day ( range 30 - 40 mg/kg/day ) in two or three daily doses , and were started on long-term therapy with aerosol colistin ( Colomycin 1090000 U plus tobramycin 100 mg , both administered twice daily using a CR60 highflow compressor with a system-22 nebulizing system ( Medic Aid , Pagham , UK ) . Complete blood count and concentrations of serum GPT , AST , alkaline phosphatase , gamma-GT , BUN , serum creatinine and urine sediment were performed at the start and end of the ciprofloxacin course . The protocol was approved by the local Medical Ethical Committee . The control subjects did not receive either ciprofloxacin or aerosol therapy ; they were given instead a first course of systemic antiPseucomonas antibiotics 5 - 52 ( mean 17 ) months after colonization , because of a respiratory flare-up . Two received ciprofloxacin , and six received various regimes . Statistical analysis included Mann-Whitney , chi-square and Fisher 's exact tests . P < 0.05 was considered significant . There was a non-significant trend for study patients to be older . According to Shwachman scores , all patients were either in excellent or good condition at colonization ( Table 1 ) . Results of cultures after colonization were analysed over a mean span of 27.4f 5 ( range 2238 ) months in patients and 24.2f 1 ( 23 - 26 ) months in controls . A total of 87 cultures ( 60 sputum , 27 throat swabs ) were obtained in study patients and 120 ( 112 sputum , eight throat swabs ) in controls . Only 4 ( 4.6 % ) patients were positive for P . aeruginosa in the study group compared with 109 ( 86 % ) in the controls ( p < 0.001 ) . Two patients had three out of seven and one out of 12 positive cultures , respectively . The rest had negative cultures throughout follow-up . The progress of the number of serum precipitins against P . aeruginosa was assessed 23.4 + 5 ( 17 - 35 ) VontKs after colonization in study patients and 23.4 $ 7 ( 1 8 - 35 ) months in controls . Three controls were excluded as the first determination of serum precipitins was more than three years after colonization . The number of serum precipitins at follow-up was 0.5 f0.7 ( 0 - 2 ) in patients and 10.8 f 7 ( 421 ) in controls ( p ( 0.01 ) . Seven patients compared with no controls had a normal number ( p=0.005 ) . The course of ciprofloxacin was well tolerated and laboratory tests failed to detect any significant change . Only a few papers on early treatment of P . aeruginosa colonization have been published . Littlewood et al. ( 2 ) reported 6 % positive cultures in seven patients treated with aerosol Colomycin over one year . In contrast , two reports on iv antibiotic treatment were dissappointing ( 3 , 4 ) . Positive results with early combined oral ciprofloxacin plus aerosol Colomycin have been reported recently ( 5 ) . The results of this trial are encouraging but should be viewed with caution because of the small number OBJECTIVES Despite the central importance of pulmonary exacerbations ( PExs ) as an outcome measure in cystic fibrosis clinical trials , no st and ardized definition of PEx exists . We conducted a prospect i ve , multicenter study to establish a st and ardized PEx definition and score for use in clinical trials , based on clinical status rather than on treatment decisions . STUDY DESIGN Subjects were 246 patients enrolled in the placebo arm of a r and omized , controlled trial of tobramycin for inhalation . Physician-investigators completed PEx question naires on all subjects at scheduled intervals during the 6-month study , indicating new or worsening symptoms , physical examination findings , and impression of PEx status ( presence or absence and severity ) . Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx . RESULTS We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings ; one also includes change in forced expiratory volume in 1 second over the preceding month . Both scores were sensitive and specific for predicting the presence of a PEx ( sensitivity , 86 % ; specificity , 86 % ) . The scores were vali date d in subjects in the intervention arm of the trial . CONCLUSION We hope that the proposed PEx score might serve as a st and ardized outcome measure for future clinical trials in cystic fibrosis , allowing meaningful comparisons of study results BACKGROUND Cystic fibrosis ( CF ) is characterized by chronic bacterial broncho-pulmonary infection . Although intravenous ( i.v . ) antibiotic therapy is regarded as st and ard treatment in CF , only few r and omised trials comparing different antibiotic compounds exist . METHODS We report on a prospect i ve multicenter interventional trial of i.v . meropenem ( 120 mg/kg/day ) or i.v . ceftazidime ( 200 - 400 mg/kg/day ) , each administered together with i.v . tobramycin ( 9 - 12 mg/kg/day ) . Outcome measures were changes in lung function , microbiological sputum burden and blood inflammatory marker . Liver and renal function values were measured to assess safety . RESULTS One hundred eighteen patients ( 59/59 ) were included into the study with the following indications : first infection of P. aeruginosa ( n=6 ) , acute pulmonary exacerbation ( n=34 ) and suppression therapy of chronic P. aeruginosa colonization ( n=78 ) . Both treatments improved lung function measures , bacterial sputum burden and CRP levels with no differences between treatment groups observed . A significant higher elevation for alkaline phosphatase ( p<0.0001 ) was observed for patients in the meropenem/tobramycin group . CONCLUSIONS i.v . antibiotic therapy in CF patients with meropenem/tobramycin is as effective as with ceftazidime/tobramycin regarding lung function , microbiological sputum burden and systemic inflammatory status . Hepato-biliary function should be monitored carefully during i.v . treatment , possibly important in CF patients with pre-existing liver disease OBJECTIVE To determine the clinical consequences of acquiring Pseudomonas aeruginosa infection during early childhood in children with cystic fibrosis ( CF ) . DESIGN Prospect i ve , observational cohort study of 56 children with CF identified by newborn screening during 1990 - 92 . Each child underwent an annual bronchial lavage during the first 2 to 3 years of life . Clinical outcome was determined at 7 years of age . RESULTS P aeruginosa infection was diagnosed in 24 ( 43 % ) cohort subjects . Four children died before 7 years of age , all of whom had been infected with a multi-resistant , mucoid strain of P aeruginosa ( P = .04 ) . In survivors , P aeruginosa infection was associated with significantly increased morbidity as measured by lower National Institutes of Health scores , greater variability in lung function , increased time in the hospital , and higher rates of recombinant human deoxyribonuclease therapy ( P < .01 ) . In this young CF cohort , best forced expiratory volume in 1 second was an insensitive measure of increased morbidity . CONCLUSIONS Acquisition of P aeruginosa was common by 7 years of age in this CF birth cohort and was associated with increased morbidity and mortality . An improved disease severity score would improve the evaluation and study of early CF lung disease In a previously published placebo-controlled trial , tobramycin solution for inhalation ( TSI ) was shown to improve lung function and other outcomes in patients with cystic fibrosis ( CF ) . The objectives of the current study were to examine the effects of TSI on global ratings of health-related quality of life ( HRQOL ) by patients ( or their parents ) and physicians blind to group assignment , and to determine whether any perceived benefits persisted over time . The global ratings of HRQOL in 520 patients with CF and chronic Pseudomonas aeruginosa infection were analyzed retrospectively . Patients were r and omly assigned to receive 24 weeks of placebo or treatment with TSI 300 mg b.i.d . , both administered in cycles of 28 days on drug ( or placebo ) followed by 28 days off , for a total of three cycles . After each on-drug cycle , patients or parents , and physicians , were asked to rate whether the patient 's condition was better , unchanged , or worse . There was strong agreement between the paired patient/parent and physician global HRQOL ratings across the three cycles . Regression analyses demonstrated that patients in the TSI group were significantly more likely to report improvements in HRQOL than were patients in the placebo group . This effect was found to be both immediate ( end of on-drug cycle 1 ) and delayed ( end of subsequent on-drug cycles 2 and 3 ) ( P < 0.05 ) . In addition , change in forced expired volume in 1 sec ( FEV(1 ) ) % predicted values was a significant predictor of improvement in HRQOL ratings by patients and parents . After controlling for change in FEV(1 ) % predicted , physician ratings showed significant improvement only at the end of cycle 1 . Finally , controlling for initial lung disease severity , longitudinal growth models revealed that patients on TSI and their physicians reported higher HRQOL ratings than did placebo patients and their physicians across the three cycles ; however , the magnitude of this effect decreased over time . Results of this study provided consistent evidence that TSI was associated with improved global ratings of HRQOL completed by both patients or parents , and physicians . Although these results are promising , they are limited by the use of a single-item rating of health . Future studies of the effects of TSI should utilize a well-vali date d , disease-specific measure of HRQOL Tobramycin nebuliser solution ( TNS ) has been investigated in several clinical trials , including a large , placebo-controlled study that demonstrated efficacy over a 24-week period . The open-label extension phase of this trial enabled observations to be conducted for an additional period of almost 18 months . Patients from both treatment arms ( n=396 ) entered the open-label phase and received up to nine 28-day on , 28-day off cycles of TNS 300 mg by aerosol twice daily ( b.i.d . ) . Mean lung function in patients who had received placebo during the double-blind phase improved during the first three cycles of the open-label treatment . However , lung function in these patients did not recover to the levels seen in those patients who had received TNS throughout the double-blind and open-label phases . In both groups of patients , improvement was maintained during the study . Greater improvements were seen in adolescents compared with older patients . Adverse events were generally uncommon , with a notably lower incidence of fever , anorexia , abdominal pain and vomiting than was observed in the double-blind phase among patients who received placebo , and a generally low incidence of tinnitus . We conclude that long-term TNS administration is safe and effective What is meant by intention-to-treat ? Why should data be analyzed in controlled trials in a way that all participants are included in the group to which they were r and omly assigned , regardless of whether they completed the intervention given to the group ? In this Tutorial , the logic of the intention-to-treat principle is outlined . It is shown that study results may be biased by excluding patients post hoc thus producing spurious effects that do not exist in the population under study . The intention-to-treat strategy avoids this bias |
2,614 | 25,634,013 | Of the agents in development , edoxaban holds the most promise due to robust data supporting its clinical benefit with a similar bleeding risk to currently approved agents . | Anticoagulation therapy is often indicated for the treatment and prevention of venous thromboembolism ( VTE ) .
Despite advances in anticoagulant management with parenteral anticoagulants and vitamin K antagonists , limitations to their use still exists , leading to investigation of alternative anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors .
To date , 3 target-specific oral anticoagulants ( TSOACs ) are Food and Drug Administration approved ; several other agents are currently in development to optimize VTE management and minimize bleeding risks .
The objective of this systematic review article is to provide clinicians an overview of the clinical evidence on the investigational TSOACs for the treatment and prevention of VTE . | Edoxaban is an oral direct factor Xa inhibitor approved for the prevention of venous thromboembolism ( VTE ) in Japan . The objectives of this analysis were to characterise the population pharmacokinetics ( PK ) of edoxaban and the relationships between edoxaban exposure and clinical outcomes in a phase IIb study of surgical patients following total hip replacement ( THR ) . A total of 1,795 subjects from a phase IIb study , 10 phase I studies , and three phase IIa studies were included in the PK analysis . The exposure-response analysis included data from surgical patients assigned to edoxaban in the phase IIb study . Edoxaban disposition in healthy and post-surgical patients was well-described with a linear , two-compartment model . Creatinine clearance was significantly correlated with edoxaban clearance and the rate of oral absorption was affected by surgery . The probability of a post-operative VTE was significantly correlated with steady-state metrics of edoxaban exposure estimated for each subject by Bayesian post-hoc methods with age and gender being the significant and expected covariates . The incidence of bleeding was low in these studies and hence no exposure-response relationship could be identified . These analyses suggest that edoxaban has a predictable anticoagulant effect in this patient population leading to dose-proportional reduction in incidence of VTE with low incidence of bleeding This is a clinical safety , tolerability , pharmacokinetics ( PK ) , and pharmacodynamics ( PD ) study of a single ascending dose ( SAD ) and a multiple ascending dose ( MAD ) of the oral direct factor Xa inhibitor edoxaban in healthy males . The placebo-controlled , single-blind , r and omized , 2-part study consists of a SAD arm with 85 subjects ( 10 , 30 , 60 , 90 , 120 , 150 mg ) and a MAD arm with 36 subjects ( 90 mg daily , 60 mg twice daily , 120 mg daily ) . Effects of food and formulation ( tablet vs solution ) are assessed in a crossover sub study . In the SAD , doses are well tolerated up to 150 mg . Exposure is proportional to dose . PK profiles are consistent across dose with rapid absorption , biphasic elimination , and terminal elimination half-life of 5.8 to 10.7 hours . In the MAD , mean accumulation after daily dosing is 1.10 to 1.13 and consistent with elimination half-life of 8.75 to 10.4 hours . Intrasubject variability ranges from 12 % to 17 % for area under the curve . In general , plasma edoxaban concentrations are linearly correlated with coagulation parameters . Edoxaban is safe and well tolerated with no dose-dependent increases in adverse events . It is concluded that single and multiple doses of edoxaban are safe and well tolerated up to 150 mg with predictable PK and PD profiles BACKGROUND The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism . METHODS In a r and omized , double-blind , noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days ( interquartile range , 8 to 11 ) , we compared oral dabigatran , administered at a dose of 150 mg twice daily , with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0 . The primary outcome was the 6-month incidence of recurrent symptomatic , objective ly confirmed venous thromboembolism and related deaths . Safety end points included bleeding events , acute coronary syndromes , other adverse events , and results of liver-function tests . RESULTS A total of 30 of the 1274 patients r and omly assigned to receive dabigatran ( 2.4 % ) , as compared with 27 of the 1265 patients r and omly assigned to warfarin ( 2.1 % ) , had recurrent venous thromboembolism ; the difference in risk was 0.4 percentage points ( 95 % confidence interval [ CI ] , -0.8 to 1.5 ; P<0.001 for the prespecified noninferiority margin ) . The hazard ratio with dabigatran was 1.10 ( 95 % CI , 0.65 to 1.84 ) . Major bleeding episodes occurred in 20 patients assigned to dabigatran ( 1.6 % ) and in 24 patients assigned to warfarin ( 1.9 % ) ( hazard ratio with dabigatran , 0.82 ; 95 % CI , 0.45 to 1.48 ) , and episodes of any bleeding were observed in 205 patients assigned to dabigatran ( 16.1 % ) and 277 patients assigned to warfarin ( 21.9 % ; hazard ratio with dabigatran , 0.71 ; 95 % CI , 0.59 to 0.85 ) . The numbers of deaths , acute coronary syndromes , and abnormal liver-function tests were similar in the two groups . Adverse events leading to discontinuation of the study drug occurred in 9.0 % of patients assigned to dabigatran and in 6.8 % of patients assigned to warfarin ( P=0.05 ) . CONCLUSIONS For the treatment of acute venous thromboembolism , a fixed dose of dabigatran is as effective as warfarin , has a safety profile that is similar to that of warfarin , and does not require laboratory monitoring . ( Clinical Trials.gov number , NCT00291330 . Background — Selectivity , titratability , rapidity of onset , and active reversibility are desirable pharmacological properties of anticoagulant therapy administered for acute indications and collectively represent an attractive platform to maximize patient safety . A novel anticoagulation system ( REG1 , Regado Biosciences ) , developed using a protein-binding oligonucleotide to factor IXa ( drug , RB006 ) and its complementary oligonucleotide antidote ( RB007 ) , was evaluated in healthy volunteers . The primary objective was to determine the safety profile and to characterize the pharmacodynamic responses in this first-in-human study . Methods and Results — Regado 1a was a subject-blinded , dose-escalation , placebo-controlled study that r and omized 85 healthy volunteers to receive a bolus of drug or placebo followed 3 hours later by a bolus of antidote or placebo . Pharmacodynamic sample s were collected serially . Subject characteristics were the following : median age , 32 years ( interquartile range , 23 to 39 years ) ; female gender , 35 % ; and median weight , 79 kg ( interquartile range , 70 to 87 kg ) . No significant differences were found in median hemoglobin , platelet , creatinine , or liver function studies . There were no significant bleeding signals associated with RB006 , and overall , both drug and antidote were well tolerated . One serious adverse event , an episode of transient encephalopathy , occurred in a subject receiving the low intermediate dose of RB006 . The subject 's symptoms resolved rapidly , and no further sequelae occurred . A predictable dose-pharmacodynamic response , reflected in activated partial thromboplastin time measurements , was seen after administration of the bolus of drug , with a clear correlation between the peak posttreatment activated partial thromboplastin time and post hoc weight-adjusted dose of drug ( correlation coefficient , 0.725 ; P<0.001 ) . In subjects treated with drug , antidote administration reversed the pharmacological activity of the drug , with a rapid ( mean time , 1 to 5 minutes across all dose levels ) and sustained return of activated partial thromboplastin time to within the normal range . The activated clotting time followed a similar anticoagulant response and reversal pattern . As anticipated , prothrombin time remained unchanged compared with baseline . Conclusions — These observations represent a first-in-human experience of an RNA aptamer and its complementary oligonucleotide antidote used as an anticoagulant system . The findings contribute to an emerging platform of selective , actively reversible anticoagulant drugs for use among patients with thrombotic disorders of the venous and arterial circulations BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery , or subcutaneous enoxaparin 40 mg once daily ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate 150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery , with a similar safety profile Betrixaban is an oral direct inhibitor of factor Xa ( FXa ) being developed for the prevention of venous thromboembolism ( VTE ) . Its antithrombotic effects had not been previously tested in patients . This exploratory clinical trial in the US and Canada r and omized 215 patients undergoing elective total knee replacement ( TKR ) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o . bid or enoxaparin 30 mg s.c . q12h , respectively , for 10 - 14 days . The betrixaban dosage was blinded , but enoxaparin was not . Primary efficacy outcome was the incidence of VTE , consisting of deep-vein thrombosis ( DVT ) on m and atory unilateral ( operated leg ) venography , symptomatic proximal DVT , or pulmonary embolism ( PE ) through Day 10 - 14 . Safety outcomes included major and clinical ly significant non-major bleeds through 48 h after treatment . All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee . Of 214 treated patients , 175 ( 82 % ) were evaluable for primary efficacy . VTE incidence was 14/70 ( 20 % ; 95 % CI : 11 , 31 ) for betrixaban 15 mg , 10/65 ( 15 % ; 95 % CI : 8 , 27 ) for betrixaban 40 mg , and 4/40 ( 10 % ; 95 % CI : 3 , 24 ) for enoxaparin . No bleeds were reported for betrixaban 15 mg , 2 ( 2.4 % ) clinical ly significant non-major bleeds with betrixaban 40 mg , and one ( 2.3 % ) major and two ( 4.6 % ) clinical ly significant non-major bleeds with enoxaparin . A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed . Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied BACKGROUND The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain . We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin . METHODS In this double-blind , double-dummy , placebo-controlled trial , we r and omly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban , administered orally at a dose of 2.5 mg twice daily for 30 days , or enoxaparin , administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days . The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism , pulmonary embolism , symptomatic deep-vein thrombosis , or asymptomatic proximal-leg deep-vein thrombosis , as detected with the use of systematic bilateral compression ultrasonography on day 30 . The primary safety outcome was bleeding . All efficacy and safety outcomes were independently adjudicated . RESULTS A total of 6528 subjects underwent r and omization , 4495 of whom could be evaluated for the primary efficacy outcome --2211 in the apixaban group and 2284 in the enoxaparin group . Among the patients who could be evaluated , 2.71 % in the apixaban group ( 60 patients ) and 3.06 % in the enoxaparin group ( 70 patients ) met the criteria for the primary efficacy outcome ( relative risk with apixaban , 0.87 ; 95 % confidence interval [ CI ] , 0.62 to 1.23 ; P=0.44 ) . By day 30 , major bleeding had occurred in 0.47 % of the patients in the apixaban group ( 15 of 3184 patients ) and in 0.19 % of the patients in the enoxaparin group ( 6 of 3217 patients ) ( relative risk , 2.58 ; 95 % CI , 1.02 to 7.24 ; P=0.04 ) . CONCLUSIONS In medically ill patients , an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin . Apixaban was associated with significantly more major bleeding events than was enoxaparin . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00457002 . ) BACKGROUND Surgery for hip fracture carries a high risk of venous thromboembolism , despite the use of current thromboprophylactic treatments . Fondaparinux , a synthetic pentasaccharide , is a new antithrombotic agent that may reduce this risk . METHODS In a double-blind study , were r and omly assigned 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily , initiated postoperatively , or 40 mg of enoxaparin once daily , initiated preoperatively , for at least five days . The primary efficacy outcome was venous thromboembolism up to postoperative day 11 . Venous thromboembolism was defined as deep-vein thrombosis detected by m and atory bilateral venography , documented symptomatic deep-vein thrombosis , or documented symptomatic pulmonary embolism . The main safety outcomes were major bleeding and mortality from all causes . The duration of follow-up was six weeks . RESULTS The incidence of venous thromboembolism by day 11 was 8.3 percent ( 52 of 626 patients ) in the fondaparinux group and 19.1 percent ( 119 of 624 patients ) in the enoxaparin group ( P<0.001 ) . The reduction in risk with fondaparinux was 56.4 percent ( 95 percent confidence interval , 39.0 to 70.3 percent ) . There were no significant differences between the two groups in the incidence of death or clinical ly relevant bleeding . CONCLUSIONS In patients undergoing surgery for hip fracture , fondaparinux was more effective than enoxaparin in preventing venous thromboembolism and equally safe BACKGROUND Oral anticoagulants , such as dabigatran etexilate , an oral , direct thrombin inhibitor , that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism ( VTE ) after total knee replacement surgery . METHODS In this r and omized , double-blind study , 2076 patients undergoing total knee replacement received dabigatran etexilate , 150 mg or 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery , for 6 - 10 days . Patients were followed-up for 3 months . The primary efficacy outcome was a composite of total VTE ( venographic or symptomatic ) and mortality during treatment , and the primary safety outcome was the incidence of bleeding events . RESULTS The primary efficacy outcome occurred in 37.7 % ( 193 of 512 ) of the enoxaparin group versus 36.4 % ( 183 of 503 ) of the dabigatran etexilate 220 mg group ( absolute difference , -1.3 % ; 95 % CI , -7.3 to 4.6 ) and 40.5 % ( 213 of 526 ) of the 150 mg group ( 2.8 % ; 95 % CI , -3.1 to 8.7 ) . Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion . The incidence of major bleeding did not differ significantly between the three groups ( 1.3 % versus 1.5 % and 1.3 % respectively ) . No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up . CONCLUSIONS Dabigatran etexilate ( 220 mg or 150 mg ) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery The impact of moderate hepatic impairment on the pharmacokinetics ( PK ) and pharmacodynamics ( PD ) of dabigatran etexilate was evaluated in an open , parallel-group study . Healthy volunteers ( n = 12 ) and patients with hepatic impairment ( Child-Pugh classification B ; n = 12 ) received a single oral dose of 150 mg dabigatran etexilate . The mean values for area under the concentration-time curve , terminal half-life , and renal clearance of dabigatran were comparable between patients with hepatic impairment and healthy volunteers . Conversion of the dabigatran intermediate BIBR1087 to active dabigatran was slower in patients with hepatic impairment , indicating that the liver is partly involved in bioconversion of dabigatran etexilate . However , total drug exposure was comparable between groups ; therefore , this observation is of no clinical relevance with respect to the anticoagulant activity of dabigatran . The extent of dabigatran glucuronidation was unchanged by liver disease ; glucuronidation capacity was maintained in moderate liver disease . The activated partial thromboplastin time , ecarin clotting time , and thrombin time relationships were essentially identical in both groups . This study shows that moderate hepatic impairment does not affect the PK/PD or safety profile of dabigatran . Therefore , patients with moderate hepatic impairment can be given dabigatran etexilate without the need for dose adjustment Edoxaban is a new oral direct factor Xa inhibitor . The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism ( VTE ) in patients undergoing elective total hip replacement . A total of 903 patients were r and omised to oral edoxaban 15 , 30 , 60 or 90 mg once daily or subcutaneous dalteparin once daily ( initial dose 2,500 IU , subsequent doses 5,000 IU ) . Both drugs were begun 6 - 8 hours postoperatively and continued for 7 - 10 days , when bilateral venography was performed . The primary efficacy endpoint was the incidence of total VTE , which included proximal and /or distal deep-vein thrombosis ( DVT ) by venography or symptomatic , objective ly confirmed DVT or pulmonary embolism during the treatment period . The primary safety outcome was the incidence of the composite of major and clinical ly relevant non-major bleeding . All venograms and bleeding events were review ed by a central independent adjudication committee blinded as to treatment allocation . Of the 903 patients r and omised , 776 were evaluable for the primary efficacy analysis . The incidences of VTE were 28.2 % , 21.2 % , 15.2 % , and 10.6 % in patients receiving edoxaban 15 , 30 , 60 and 90 mg , respectively , compared with 43.8 % in the dalteparin group ( p<0.005 ) . There was a statistically significant ( p<0.001 ) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE . The incidence of clinical ly relevant bleeding was low and similar across the groups . Oral edoxaban once daily is effective for preventing VTE after total hip replacement INTRODUCTION Edoxaban is an oral , direct , once-daily factor Xa inhibitor . This study evaluated the safety and efficacy of edoxaban compared to subcutaneous enoxaparin in Japanese patients undergoing hip fracture surgery . MATERIAL S AND METHODS In this multicenter , r and omized , open-label , active-comparator , phase 3 trial , 92 patients were r and omized 2:1 to receive edoxaban 30 mg once daily ( n=62 ) or enoxaparin sodium ( enoxaparin ) 2000IU ( equivalent to 20 mg ) twice daily ( n=30 ) for 11 to 14days . The primary endpoints were the incidence of major or clinical ly relevant non-major ( CRNM ) bleeding and incidence of any bleeding events ( major , CRNM , or minor bleeding ) . Secondary efficacy endpoints included the incidence of thromboembolic events , venous thromboembolism-related deaths , and all-cause deaths . Additional adverse events were recorded throughout the study . RESULTS In the edoxaban and enoxaparin treatment groups , the incidence of major or CRNM bleeding was 3.4 % and 6.9 % , respectively , while any bleeding event occurred in 25.4 % and 17.2 % of patients , respectively . The incidence of thromboembolic events was 6.5 % in the edoxaban group and 3.7 % in the enoxaparin group . All events were asymptomatic deep vein thrombosis . The incidence of adverse events was 72.9 % and 82.8 % in the edoxaban and enoxaparin groups , respectively . CONCLUSIONS Compared to subcutaneous enoxaparin 2000IU twice daily , oral edoxaban 30 mg once daily demonstrated similar safety and efficacy in the prevention of thromboembolic events in Japanese patients undergoing hip fracture surgery . CLINICAL TRIALS REGISTRATION NUMBER NCT01181141 This multicentre dose-finding study compared TAK-442 , an oral factor Xa inhibitor , with enoxaparin for thromboprophylaxis after knee arthroplasty . In this parallel group study , patients were r and omised to oral TAK-442 ( 40 or 80 mg once-daily [ QD ] or 10 , 20 , 40 , or 80 mg twice-daily [ BID ] started 6 - 8 hours postoperatively ) , which was blinded as to dose , or to open-label subcutaneous enoxaparin ( 30 mg BID starting 12 - 24 hours postoperatively ) for 10 days . Treatments were continued until bilateral venography was performed ( maximum of 14 days ) . The primary efficacy endpoint was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism or all-cause mortality , while the primary safety endpoint was major bleeding . Of 1,038 patients r and omised who received at least one dose of study drug , 949 completed the study and 730 ( 76.9 % ) were evaluable for the primary efficacy analysis . Recruitment into the 10 and 20 mg BID dose groups was stopped early because the incidences of the primary efficacy endpoint were significantly higher than that with enoxaparin . The primary efficacy endpoint occurred in 22.0 % of patients given enoxaparin and in 39.0 % , 38.4 % , 23.5 % , 21.4 % , 26.8 % , and 14.3 % of those receiving TAK-442 10 mg BID , 20 mg BID , 40 mg QD , 40 mg BID , 80 mg QD , and 80 mg BID , respectively . The incidences of major and clinical ly relevant non-major bleeding with TAK-442 were not dose-dependent or different from that with enoxaparin . All TAK-442 doses except 10 and 20 mg BID displayed similar efficacy and safety profiles to enoxaparin BACKGROUND Edoxaban ( the free base of DU-176b ) is an oral , direct factor (F)Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events . OBJECTIVES The aim of the present study was to evaluate the efficacy and safety of edoxaban for the prevention of venous thromboembolism ( VTE ) in patients undergoing total knee arthroplasty ( TKA ) . PATIENTS / METHODS This was a r and omized , double-blind , placebo-controlled , multicenter study conducted in Japan . A total of 523 Japanese patients were assigned to receive edoxaban 5 , 15 , 30 or 60 mg once daily or placebo for 11 - 14 days . A placebo control was used as neither low-molecular-weight heparin ( LMWH ) nor fondaparinux had been approved for thromboprophylaxis at the time of the study in Japan . The primary efficacy outcome was the incidence of VTE ( lower-extremity deep vein thrombosis , symptomatic pulmonary embolism or symptomatic deep vein thrombosis ) . The primary safety outcome was the incidence of major and clinical ly relevant non-major bleeding . RESULTS Edoxaban produced a significant dose-related reduction in VTE : the incidence of VTE was 29.5 % , 26.1 % , 12.5 % and 9.1 % in the edoxaban 5- , 15- , 30- and 60-mg treatment groups vs. 48.3 % in the placebo group . The incidence of major and clinical ly relevant non-major bleeding was similar across all groups without any significant differences among edoxaban doses or between edoxaban and placebo . CONCLUSIONS Edoxaban demonstrated significant dose-dependent reductions in VTE in patients undergoing TKA with a bleeding incidence similar to placebo . [ This trial is registered with JAPIC , JapicCTI-060283 ( ja ) . ] AIMS To evaluate the safety , tolerability , pharmacokinetics and pharmacodynamics of edoxaban , an oral direct factor Xa inhibitor , in healthy subjects switching from warfarin . METHODS Seventy-two subjects were r and omized to edoxaban 60 mg once daily ( n = 48 ) or matching placebo ( n = 24 ) for 5 days at 24 h after the last dose of warfarin treatment ( INR 2.0 to 3.0 ) . Safety/tolerability was the primary outcome measure . Pharmacokinetics , INR , aPTT , anti-FXa , thrombin generation and other coagulation assays were assessed . RESULTS Seventy-two subjects were r and omized and 64 subjects received at least one dose of edoxaban ( n = 43 ) or placebo ( n = 21 ) after achieving a target INR of 2.0 to 3.0 on warfarin treatment . Edoxaban 60 mg administered 24 h post-warfarin appeared to be safe and well tolerated . Adverse events were similar across treatments . For bleeding-related adverse events , eight subjects tested positive for faecal occult blood , five subjects during warfarin treatment and three subjects during edoxaban treatment . The mean ( SD ) baseline ( post-dose of warfarin ) INR was 2.31 ( 0.193 ) which increased to 3.84 ( 0.744 ) over 2 h during the edoxaban treatment ( P < 0.0001 vs. placebo ) , returning to post-warfarin baseline within 12 h. A similar time course of effects for the other coagulation assays was observed in accordance with the drugs ' mechanisms of action . CONCLUSION In this study of healthy subjects , edoxaban administered 24 h after the last dose of warfarin was safe and well tolerated with transient increases across the various coagulation assays above post-warfarin baseline levels BACKGROUND LY517717 is an oral direct inhibitor of activated factor X that is currently under clinical development . OBJECTIVES The aims of this proof-of-concept study in patients undergoing total knee replacement ( TKR ) or total hip replacement ( THR ) were to determine whether LY517717 can safely reduce the risk of venous thromboembolism ( VTE ) and to identify at least one dose of LY517717 that is non-inferior to enoxaparin . METHODS In a double-blind , parallel-arm , dose-ranging study , patients undergoing TKR or THR were r and omly allocated to receive once-daily oral LY517717 ( 25 , 50 , 75 , 100 , 125 or 150 mg ) , started 6 - 8 h after wound closure , or s.c . enoxaparin , 40 mg , started in the evening before surgery . The primary efficacy endpoint was the composite of deep venous thrombosis ( DVT ) , detected by m and atory bilateral venography performed at the end of the study treatment ( between days 5 and 9 ) , and objective ly confirmed symptomatic DVT and /or pulmonary embolism ( PE ) , occurring during the treatment period . The combination of major and minor bleeding was the primary safety endpoint . RESULTS Five hundred and seven patients received at least one dose of LY517717 or enoxaparin ( safety population ) . Three hundred and ninety-one patients had evaluable bilateral venography or experienced a clinical DVT and /or PE ( primary efficacy population ) . LY517717 treatment result ed in a dose-dependent decrease in the incidence of thromboembolic events ( P = 0.0001 ) . The incidences of VTE with 100 , 125 , and 150 mg of LY517717 were 19 % , 19 % and 16 % , respectively , compared to 21 % with enoxaparin . The efficacies of 100-mg , 125-mg and 150-mg doses of LY517717 were non-inferior to that of enoxaparin according to prespecified criteria . Bleeding events were uncommon in both LY517717 and enoxaparin patients . CONCLUSIONS Doses of 100 , 125 and 150 mg of LY517717 are non-inferior to enoxaparin for the prevention of VTE after TKR or THR , and are associated with similar low rates of bleeding BACKGROUND Inhibitors of factor ( F ) IXa show potent antithrombotic activity with a low risk of bleeding in pre clinical models . We investigated the anticoagulant potential of oral TTP889 , a small molecule that inhibits up to 90 % of FIXa activity at therapeutic doses , using a clinical model of extended prophylaxis in hip fracture surgery ( HFS ) . METHODS In this multicenter , r and omized , double-blind study , 261 patients received oral TTP889 ( 300 mg once daily ) or placebo starting 6 - 10 days after HFS , and st and ard thromboprophylaxis for 5 - 9 days . Treatment was continued for 3 weeks and all patients then underwent m and atory bilateral venography . The primary efficacy outcome was venous thromboembolism ( VTE ; venographic or symptomatic deep vein thrombosis or pulmonary embolism ) during treatment , and it was evaluated central ly by an independent adjudication panel . The main safety outcome was bleeding ( major , clinical ly relevant non-major , and minor events ) . RESULTS Two hundred and twelve patients with an evaluable venogram were included in the efficacy analysis . The primary efficacy outcome occurred in 32.1 % ( 35/109 ) of patients who had been allocated TTP889 , and 28.2 % ( 29/103 ) of patients on placebo ( P = 0.58 ) . There were no major bleeding events , and only two clinical ly relevant non-major bleeding events with TTP889 . CONCLUSION Partial FIXa inhibition with TTP889 300 mg daily was not effective for extended prevention of VTE after st and ard prophylaxis for up to 9 days . Coupled with the low incidence of bleeding episodes , this suggests a lack of antithrombotic potential . Further investigation of TTP889 in different clinical setting s is needed . ( Clinical trial registration information URL : http://www . clinical trials.gov . Unique identifier : NCT00119457 ) BACKGROUND Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty ; oral regimens could enable shorter hospital stays . We aim ed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty . METHODS In a r and omised , double-blind , phase III study , 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily , beginning 6 - 8 h after surgery , or subcutaneous enoxaparin 30 mg every 12 h , starting 12 - 24 h after surgery . Patients had m and atory bilateral venography between days 11 and 15 . The primary efficacy outcome was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism , or death from any cause up to day 17 after surgery . Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per- protocol population ( absolute non-inferiority limit -4 % ) ; if non-inferiority was shown , we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population . The primary safety outcome was major bleeding . This trial is registered with Clinical Trials.gov , number NCT00362232 . FINDINGS The primary efficacy outcome occurred in 67 ( 6.9 % ) of 965 patients given rivaroxaban and in 97 ( 10.1 % ) of 959 given enoxaparin ( absolute risk reduction 3.19 % , 95 % CI 0.71 - 5.67 ; p=0.0118 ) . Ten ( 0.7 % ) of 1526 patients given rivaroxaban and four ( 0.3 % ) of 1508 given enoxaparin had major bleeding ( p=0.1096 ) . INTERPRETATION Oral rivaroxaban 10 mg once daily for 10 - 14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty . FUNDING Bayer Schering Pharma AG , Johnson & Johnson Pharmaceutical Research & Development Dabigatran , an oral once-daily unmonitored thrombin inhibitor , has been tested elsewhere using enoxaparin 40 mg once daily . We used the North American enoxaparin 30 mg BID regimen as the comparator . This was a double-blind , central ly r and omized trial . Unilateral total knee arthroplasty patients were r and omized to receive oral dabigatran etexilate 220 or 150 mg once daily , or enoxaparin 30 mg SC BID after surgery , blinded . Dosing stopped at contrast venography , 12 to 15 days after surgery . Among 1896 patients , dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin ( venous thromboembolism rates of 31 % [ P = .02 vs enoxaparin ] , 34 % [ P < .001 vs enoxaparin ] , and 25 % , respectively ) . Bleeding rates were similar , and no drug-related hepatic illness was recognized . Dabigatran , effective compared to once-daily enoxaparin , showed inferior efficacy to the twice-daily North American enoxaparin regimen , probably because of the latter 's more intense and prolonged dosing BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P<0.001 ) . Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 . BACKGROUND Apixaban , an oral factor Xa inhibitor that can be administered in a simple , fixed-dose regimen , may be an option for the extended treatment of venous thromboembolism . METHODS In this r and omized , double-blind study , we compared two doses of apixaban ( 2.5 mg and 5 mg , twice daily ) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy . The study drugs were administered for 12 months . RESULTS A total of 2486 patients underwent r and omization , of whom 2482 were included in the intention-to-treat analyses . Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients ( 8.8 % ) who were receiving placebo , as compared with 14 of the 840 patients ( 1.7 % ) who were receiving 2.5 mg of apixaban ( a difference of 7.2 percentage points ; 95 % confidence interval [ CI ] , 5.0 to 9.3 ) and 14 of the 813 patients ( 1.7 % ) who were receiving 5 mg of apixaban ( a difference of 7.0 percentage points ; 95 % CI , 4.9 to 9.1 ) ( P<0.001 for both comparisons ) . The rates of major bleeding were 0.5 % in the placebo group , 0.2 % in the 2.5-mg apixaban group , and 0.1 % in the 5-mg apixaban group . The rates of clinical ly relevant nonmajor bleeding were 2.3 % in the placebo group , 3.0 % in the 2.5-mg apixaban group , and 4.2 % in the 5-mg apixaban group . The rate of death from any cause was 1.7 % in the placebo group , as compared with 0.8 % in the 2.5-mg apixaban group and 0.5 % in the 5-mg apixaban group . CONCLUSIONS Extended anticoagulation with apixaban at either a treatment dose ( 5 mg ) or a thromboprophylactic dose ( 2.5 mg ) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding . ( Funded by Bristol-Myers Squibb and Pfizer ; AMPLIFY-EXT Clinical Trials.gov number , NCT00633893 . ) Edoxaban is an oral direct factor (F)Xa inhibitor in advanced stages of clinical development . The primary objective of the present study was to assess the pharmacodynamics ( PD ) and safety of enoxaparin 1 mg/kg followed 12 hours ( h ) post-dose by edoxaban 60 mg , which is the regimen being used in the phase III study of edoxaban for the treatment of venous thromboembolism ( Hokusai-VTE ) . This was a phase I , open-label , r and omised , four-period , four-treatment cross-over study . Treatments were edoxaban alone ( EDOX ) , enoxaparin alone ( ENOX ) , edoxaban plus enoxaparin ( EDOX+ENOX ) , and enoxaparin followed by edoxaban 12 h later ( ENOX12-EDOX ) . Serial blood sample s were collected for PD ( thrombin generation , anti-FXa ) and pharmacokinetic ( PK ) variables ( edoxaban and its principal metabolite M4 by LC-MS/MS , and anti-FIIa as a surrogate of enoxaparin ) . The highest effect on thrombin AUC ( endogenous thrombin potential , or ETP ) , thrombin ( peak ) , thrombin generation lag time , and velocity index was observed for EDOX+ENOX , followed by ENOX , ENOX12-EDOX , and EDOX . The greatest effect on anti-FXa activity was observed for EDOX+ENOX , followed by ENOX12-EDOX . As expected , neither edoxaban nor enoxaparin significantly altered the PK of the other drug . There were no serious adverse events during the study . It is concluded that a 60-mg dose of edoxaban can be safely administered 12 h following enoxaparin 1 mg/kg BACKGROUND Rivaroxaban , an oral factor Xa inhibitor , may provide a simple , fixed-dose regimen for treating acute deep-vein thrombosis ( DVT ) and for continued treatment , without the need for laboratory monitoring . METHODS We conducted an open-label , r and omized , event-driven , noninferiority study that compared oral rivaroxaban alone ( 15 mg twice daily for 3 weeks , followed by 20 mg once daily ) with subcutaneous enoxaparin followed by a vitamin K antagonist ( either warfarin or acenocoumarol ) for 3 , 6 , or 12 months in patients with acute , symptomatic DVT . In parallel , we carried out a double-blind , r and omized , event-driven superiority study that compared rivaroxaban alone ( 20 mg once daily ) with placebo for an additional 6 or 12 months in patients who had completed 6 to 12 months of treatment for venous thromboembolism . The primary efficacy outcome for both studies was recurrent venous thromboembolism . The principal safety outcome was major bleeding or clinical ly relevant nonmajor bleeding in the initial-treatment study and major bleeding in the continued-treatment study . RESULTS The study of rivaroxaban for acute DVT included 3449 patients : 1731 given rivaroxaban and 1718 given enoxaparin plus a vitamin K antagonist . Rivaroxaban had noninferior efficacy with respect to the primary outcome ( 36 events [ 2.1 % ] , vs. 51 events with enoxaparin-vitamin K antagonist [ 3.0 % ] ; hazard ratio , 0.68 ; 95 % confidence interval [ CI ] , 0.44 to 1.04 ; P<0.001 ) . The principal safety outcome occurred in 8.1 % of the patients in each group . In the continued-treatment study , which included 602 patients in the rivaroxaban group and 594 in the placebo group , rivaroxaban had superior efficacy ( 8 events [ 1.3 % ] , vs. 42 with placebo [ 7.1 % ] ; hazard ratio , 0.18 ; 95 % CI , 0.09 to 0.39 ; P<0.001 ) . Four patients in the rivaroxaban group had nonfatal major bleeding ( 0.7 % ) , versus none in the placebo group ( P=0.11 ) . CONCLUSIONS Rivaroxaban offers a simple , single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation . ( Funded by Bayer Schering Pharma and Ortho-McNeil ; Clinical Trials.gov numbers , NCT00440193 and NCT00439725 . ) BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement . Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety of these drugs after elective total knee replacement . METHODS In ADVANCE-2 , a multicentre , r and omised , double-blind phase 3 study , patients undergoing elective unilateral or bilateral total knee replacement were r and omly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily ( n=1528 ) or subcutaneous enoxaparin 40 mg once daily ( 1529 ) . The r and omisation schedule was generated by the Bristol-Myers Squibb r and omisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four . Investigators , patients , statisticians , adjudicators , and steering committee were masked to allocation . Apixaban was started 12 - 24 h after wound closure and enoxaparin 12 h before surgery ; both drugs were continued for 10 - 14 days , when bilateral ascending venography was scheduled . Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis , non-fatal pulmonary embolism , and all-cause death during treatment . The statistical plan required non-inferiority of apixaban before testing for superiority ; analysis was by intention to treat for non-inferiority testing . The study is registered at Clinical Trials.gov , number NCT00452530 . FINDINGS 1973 of 3057 patients allocated to treatment ( 1528 apixaban , 1529 enoxaparin ) were eligible for primary efficacy analysis . The primary outcome was reported in 147 ( 15 % ) of 976 apixaban patients and 243 ( 24 % ) of 997 enoxaparin patients ( relative risk 0.62 [ 95 % CI 0.51 - 0.74 ] ; p<0.0001 ; absolute risk reduction 9.3 % [ 5.8 - 12.7 ] ) . Major or clinical ly relevant non-major bleeding occurred in 53 ( 4 % ) of 1501 patients receiving apixaban and 72 ( 5 % ) of 1508 treated with enoxaparin ( p=0.09 ) . INTERPRETATION Apixaban 2.5 mg twice daily , starting on the morning after total knee replacement , offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin , without increased bleeding . FUNDING Bristol-Myers Squibb ; Pfizer BACKGROUND Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear . METHODS In a r and omized , double-blind , noninferiority study , we r and omly assigned patients with acute venous thromboembolism , who had initially received heparin , to receive edoxaban at a dose of 60 mg once daily , or 30 mg once daily ( e.g. , in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg ) , or to receive warfarin . Patients received the study drug for 3 to 12 months . The primary efficacy outcome was recurrent symptomatic venous thromboembolism . The principal safety outcome was major or clinical ly relevant nonmajor bleeding . RESULTS A total of 4921 patients presented with deep-vein thrombosis , and 3319 with a pulmonary embolism . Among patients receiving warfarin , the time in the therapeutic range was 63.5 % . Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome , which occurred in 130 patients in the edoxaban group ( 3.2 % ) and 146 patients in the warfarin group ( 3.5 % ) ( hazard ratio , 0.89 ; 95 % confidence interval [ CI ] , 0.70 to 1.13 ; P<0.001 for noninferiority ) . The safety outcome occurred in 349 patients ( 8.5 % ) in the edoxaban group and 423 patients ( 10.3 % ) in the warfarin group ( hazard ratio , 0.81 ; 95 % CI , 0.71 to 0.94 ; P=0.004 for superiority ) . The rates of other adverse events were similar in the two groups . A total of 938 patients with pulmonary embolism had right ventricular dysfunction , as assessed by measurement of N-terminal pro-brain natriuretic peptide levels ; the rate of recurrent venous thromboembolism in this subgroup was 3.3 % in the edoxaban group and 6.2 % in the warfarin group ( hazard ratio , 0.52 ; 95 % CI , 0.28 to 0.98 ) . CONCLUSIONS Edoxaban administered once daily after initial treatment with heparin was noninferior to high- quality st and ard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism , including those with severe pulmonary embolism . ( Funded by Daiichi-Sankyo ; Hokusai-VTE Clinical Trials.gov number , NCT00986154 . ) BACKGROUND The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge . Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin . METHODS 2509 patients scheduled to undergo elective total hip arthroplasty were r and omly assigned , stratified according to centre , with a computer-generated r and omisation code , to receive oral rivaroxaban 10 mg once daily for 31 - 39 days ( with placebo injection for 10 - 14 days ; n=1252 ) , or enoxaparin 40 mg once daily subcutaneously for 10 - 14 days ( with placebo tablet for 31 - 39 days ; n=1257 ) . The primary efficacy outcome was the composite of deep-vein thrombosis ( symptomatic or asymptomatic detected by m and atory , bilateral venography ) , non-fatal pulmonary embolism , and all-cause mortality up to day 30 - 42 . Analyses were done in the modified intention-to-treat population , which consisted of all patients who had received at least one dose of study medication , had undergone planned surgery , and had adequate assessment of thromboembolism . This study is registered at Clinical Trials.gov , number NCT00332020 . FINDINGS The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group . The primary outcome occurred in 17 ( 2.0 % ) patients in the rivaroxaban group , compared with 81 ( 9.3 % ) in the enoxaparin group ( absolute risk reduction 7.3 % , 95 % CI 5.2 - 9.4 ; p<0.0001 ) . The incidence of any on-treatment bleeding was much the same in both groups ( 81 [ 6.6 % ] events in 1228 patients in the rivaroxaban safety population vs 68 [ 5.5 % ] of 1229 patients in the enoxaparin safety population ; p=0.25 ) . INTERPRETATION Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism , including symptomatic events , in patients undergoing total hip arthroplasty |
2,615 | 17,443,540 | Operations using the no-scalpel approach were faster and had a quicker resumption of sexual activity .
Neither trial found differences in vasectomy effectiveness between the two approaches to the vas .
The no-scalpel approach to the vas result ed in less bleeding , hematoma , infection , and pain as well as a shorter operation time than the traditional incision technique .
No difference in effectiveness was found between the two approaches | BACKGROUND Currently , the two most common surgical techniques for approaching the vas during vasectomy are the incisional method and the no-scalpel technique .
Whereas the conventional incisional technique involves the use of a scalpel to make one or two incisions , the no-scalpel technique uses a sharp-pointed , forceps-like instrument to puncture the skin .
The no-scalpel technique aims to reduce adverse events , especially bleeding , bruising , hematoma , infection and pain and to shorten the operating time .
OBJECTIVES The objective of this review was to compare the effectiveness , safety , and acceptability of the incisional versus no-scalpel approach to the vas . | PURPOSE We compare the safety , ease of use and effectiveness of the no scalpel and st and ard incision approaches to vasectomy . MATERIAL S AND METHODS A multicenter , r and omized , partially masked controlled trial was conducted at 8 sites in Brazil , Guatemala , Indonesia , Sri Lanka and Thail and . Semen sample s were collected 10 weeks postoperatively and tested to ascertain sterility using verification of no living spermatozoa . RESULTS The study included 1,429 men seeking vasectomy . The efficacy of the 2 approaches was virtually identical . In the no scalpel group operating time was significantly shorter , and complications and pain were less frequent than in the st and ard incision group . The no scalpel group resumed intercourse sooner , probably as a result of less pain following the procedure . CONCLUSIONS The no scalpel approach is an important advance in the surgical approach to vasectomy , and offers fewer side effects and greater comfort compared to the st and ard incision technique , without compromising efficacy The aim of this study was to introduce a novel male contraceptive method , an intra-vas device ( IVD ) , and to assess the efficacy , safety and satisfaction of recipients compared with no-scalpel vasectomy ( NSV ) . A phase II r and omized controlled trial was conducted in China in 2003 . Two hundred and eighty-eight male subjects seeking vasectomy were r and omly assigned to the IVD or NSV group . Follow up included a telephone question naire on the 14th postoperative day and visits at the third and 12th postoperative months . The follow-up rates at the three time points were 100 % , 100 % and 96.5 % respectively . There was no technical failure in any subject . The surgical conditions were similar in both groups , but the IVD group experienced an additional 5 min of operative time ( p<0.001 ) . The IVD group recovered normal activity and sexual intercourse more rapidly ( both p<0.05 ) . The azoospermia rate was lower in the IVD group than in the NSV group at the third and 12th postoperative months . The rate of contraceptive success based on semen analyses was similar in both groups , especially at the 12th postoperative month ( 94.3 % in the IVD group vs. 98.6 % in the NSV group ; p=0.054 ) . The IVD group had less risk of complications ( i.e. pain , congestive epididymitis and sperm granuloma ) . More subjects reported satisfaction with IVD sterilization than with NSV . The two procedures were similar in terms of surgical complications . The IVD was slightly less effective , but had a lower risk of later adverse events than the NSV technique . The IVD group also reported a higher level of satisfaction Objective To compare the intra-operative experience and postoperative sequelae between the st and ard Marie Stopes scalpel vasectomy procedure and electrocautery non-scalpel vasectomy ( ENSV ) techniques . Design R and omised prospect i ve comparative study . Setting Marie Stopes vasectomy centres in the UK . Participants A total of 325 men undergoing vasectomy between January and June 1999 . Intervention R and om allocation to the two study arms plus question naires at 4 and 14 weeks postoperatively . Main outcome measures Ease and speed of the procedure ; pain levels during and after the procedure ; early postoperative complications and time taken to return to work and sexual activity . Results The ENSV technique was marginally quicker to perform . Pain levels intra-operatively were comparable . Response rates to the question naire were 84.6 % and 37 % at 4 and 14 weeks , respectively . The ENSV group experienced less pain and bleeding from the wound postoperatively and were quicker to heal . For men who experienced postoperative problems , the time taken to return to work was marginally better in the ENSV group . The time taken to return to sexual activity was marginally faster in the ENSV group . Conclusion The ENSV procedure appears to be suitable for mass application in locations where electricity is available INTRODUCTION Studies have shown that the Li vasectomy can match the effectiveness of and reduce the duration of operation and rate of complications compared to st and ard vasectomy with bilateral incision . MATERIAL S AND METHODS A prospect i ve , r and omised trial was conducted to compare the Li vasectomy with the st and ard vasectomy with bilateral incision . Data regarding effectiveness , time of operation , the patient 's pain and discomfort , and peroperative and postoperative complications were recorded . Overall , 99 patients were entered in the trial , 51 with vasectomy with bilateral incision , 48 with the Li vasectomy . RESULTS No significant difference was found between the two methods with regard to effectiveness , time of operation , the patient 's pain and discomfort , and peroperative and postoperative complications . Overall , vasectomy was inadequate in 5 % , haematoma was found in 13 % , infection in 9 % , and scrotal pain or painful ejaculation in 9 % . DISCUSSION The Li vasectomy can be learned and practice d under routine conditions by residents in training with the same effectiveness and the same rate of complications as st and ard vasectomy with bilateral incision . The total morbidity was at the same level as in previous Danish studies , but higher than in the international studies with the Li vasectomy No-scalpel vasectomy was developed to increase acceptability of vasectomy by elimination of the fear of the incision . Although this method has been used for over 8,000,000 men , the technique is largely unknown in developed countries . During the King 's birthday vasectomy festival no-scalpel vasectomy was compared with st and ard incisional vasectomy in 1203 patients . An average of 57 procedures per day could be done by each physician with the no-scalpel method , compared to 33 procedures with the st and ard method ( p less than 0.001 ) . The complication rate was 0.4/100 procedures for no-scalpel vasectomy compared with 3.1/100 for st and ard vasectomy ( p less than 0.001 ) . No-scalpel vasectomy is a rapid and economic alternative to st and ard vasectomy , with fewer complications and increased patient acceptability BACKGROUND AND PURPOSE The simply modified no-scalpel vasectomy ( SMNSV ; percutaneous vasectomy ) technique was reported to simplify the st and ard no-scalpel vasectomy ( SNSV ) procedure . In this report , we introduce our experiences with SMNSV in comparison with the SNSV . MATERIAL S AND METHODS Between July 1999 and June 2002 , 417 men were prospect ively r and omized to be vasectomized at the Taipei Medical University Hospital : 215 acceptors underwent the SNSV and the remaining 202 received the SMNSV . Using the no-scalpel vasectomy instruments in a percutaneous fashion , the sharp no-scalpel hemostat punctures the skin directly instead of fixating the vas to the skin with the use of a ring clamp , as done in SNSV . The vas is then grasped with the ringed instrument instead of piercing the vas and performing the supination maneuver , as described for SNSV . The intraoperative conditions of each group were recorded . The postoperative pain and life conditions were self-reported . The pain level was assessed using a 10-cm visual analogue scale under various situations . RESULTS The time required for the SMNSV technique was less than that for the SNSV technique ( p < .05 ) . There were no significant differences between the two groups with respect to incision length , postoperative pain , pain at coitus , time of return to work , time of resuming intercourse , self-reported satisfaction in sexual life , postoperative psychological status , postoperative body weight change and postoperative complications ( p > .05 for all items ) . CONCLUSIONS The simply modified vasectomy technique simplifies the SNSV technique . It combines the minimally invasive nature of SNSV with the simplicity of classical vasectomy while conserving many comparable advantages An instrument-independent no-scalpel vasectomy ( IINSV ) technique is reported . This technique does not use the st and ard specific instruments , but comparatively retains the advantages of minimally invasive instrument-dependent no-scalpel vasectomy ( IDNSV ) . Between July 1999 and June 2002 , 449 men were prospect ively r and omized to be vasectomized at two hospitals in Taipei . Of those who accepted , 215 underwent IDNSV at one hospital and the remaining 234 underwent IINSV at the other . The intra-operative conditions of each group were recorded . The postoperative pain and life conditions were self-reported through a question naire that had been carefully design ed prior to the operations , in which the pain level was assessed using a 10-cm visual analogue scale under varying situations . Men vasectomized using the IINSV method experienced less operation time and postoperative complications ( haematomas , infections and granulomas ) ( p < 0.05 ) . There were no significant differences between the two groups with respect to incision length , postoperative pain , pain at coitus , time of return to work , time of resuming intercourse , self-reported satisfaction in sexual life , postoperative psychological status , postoperative body weight change and vasectomy failure as evidence d by sperm analysis ( p > 0.05 for all items ) . Thus , the IINSV technique can offer an alternative option for vasectomists whenever the specific instruments of st and ard no-scalpel vasectomy are unavailable . The IINSV technique shortens the operation time and reduces the incidence of operative complications when compared with the IDNSV technique , while still retaining the advantages of minimally invasive vasectomy |
2,616 | 10,796,262 | Based on existing evidence , routine Doppler ultrasound examination in low risk or unselected population s did not result in increased antenatal , obstetric and neonatal interventions , and no overall differences were detected for substantive short term clinical outcomes such as perinatal mortality .
There is no available evidence to assess the effect on substantive long term outcomes such as childhood neurodevelopment .
There is no available evidence to assess maternal outcomes , particularly psychological effects .
REVIEW ER 'S CONCLUSIONS Based on existing evidence , routine Doppler ultrasound in low risk or unselected population s does not confer benefit on mother or baby . | BACKGROUND Doppler ultrasound study of umbilical artery waveforms helps identify the compromised fetus in ' high risk ' pregnancies and , therefore , deserves assessment as a screening test in ' low risk ' pregnancies .
One of the main aims of routine antenatal care is to identify the ' at risk ' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality .
OBJECTIVES To assess the effects on obstetric practice and pregnancy outcome of routine Doppler ultrasound in unselected and low risk pregnancies . | We have done a r and omised controlled trial to assess the effect on primary management and outcome of routine doppler ultrasound examinations of the umbilical and uterine arteries during pregnancy . Over 9 months , 2600 women with singleton pregnancies were recruited from a general obstetric population . Of 2475 women who delivered in hospital after 20 weeks ' gestation , 1246 had been allocated at r and om to receive st and ard antenatal care with routine doppler examinations . The first doppler ultrasound was done at 19 - 22 weeks ' gestation , and thereafter examinations were monthly if the pregnancy was considered high risk ( 192 ) or once at 32 weeks if considered low risk ( 1054 ) . The control group of 1229 women received st and ard , antenatal care without doppler ultrasonography . The study groups did not differ in number of antenatal admissions or cardiotocographs , gestational age at delivery , method of delivery , frequency of deliveries with fetal distress , or need for resuscitation or admission to the neonatal intensive care unit . More perinatal deaths occurred in the doppler group ( 17 vs 7 , relative risk 2.4 , 95 % Cl 1.00 - 5.76 ) , but only 1 of 11 normally formed stillbirths and none of the 4 normally formed neonatal deaths after 24 weeks ' gestation had an abnormal umbilical-artery doppler examination . We did not demonstrate any improvement in neonatal outcome by routine doppler ultrasound screening of a general obstetric population Abstract Despite widespread application of ultrasound imaging and Doppler blood flow studies , the effects of their frequent and repeated use in pregnancy have not been evaluated in controlled trials . From 2834 women with single pregnancies at 16 - 20 weeks gestation , 1415 were selected at r and om to receive ultrasound imaging and continuous-wave Doppler flow studies at 18 , 24 , 28 , 34 , and 38 weeks gestation ( the intensive group ) and 1419 to receive single ultrasound imaging at 18 weeks ( the regular group ) . Outcome data was obtained from 99 % of women who entered the study . The only difference between the two groups was significantly higher intrauterine growth restriction in the intensive group , when expressed both as birthweight 342 : OBJECTIVE Meta- analysis of r and omized trials of Doppler ultrasonography in high-risk pregnancies has showed reduced mortality rates among normally formed fetuses . This trial addressed the impact on outcome of umbilical artery velocimetry in a nonselected population ( i.e. , as a screening test in low-risk and high-risk pregnancies ) . STUDY DESIGN A r and omized , controlled trial with Doppler ultrasonographic investigation was performed at two gestational age windows : 26 to 30 weeks and 34 to 36 weeks . The 2986 women were r and omly allocated to revealed or concealed groups in which the Doppler results were either made available or not made available to clinicians ; 1056 women were studied at only the first window , 544 at only the second , and 1386 at both . RESULTS There were no significant differences between groups in antenatal admissions to hospital , preterm deliveries , rates of cesarean section , admission to the neonatal unit , and need for assisted ventilation . There was , however , a trend toward fewer stillbirths in the " revealed " group ( three vs eight , odds ratio 0.34 , confidence interval 0.10 to 1.07 ) . CONCLUSIONS The incidence of stillbirths was reduced by more than half in the Doppler-revealed group , but the confidence intervals were wide and these findings could be compatible with chance Summary . A prospect i ve blind study assessed the efficacy of Doppler examination of the umbilical arteries ( pulsatility index ) as a screening procedure for predicting small‐for‐gestational‐age and low‐weight‐for‐length ( low ponderal index ) infants . Birthweight below the 2–3rd and 10th centile and ponderal index below the 3rd and 10th ccntiie were chosen as‘cut‐off levels . Of pregnant women from our university hospital population , 400 were examined at 28 and 34 weeks gestation . The sensitivity of the test was low , ranging from 16·9 to 41·7 % for the different indices . The predictive value of a negative screening test also was unsatisfactory , ranging from 79·6 % to 97·9 % . It is concluded that a single umbilical artery Doppler examination at 28 or 34 weeks does not satisfy the need in obstetrics for a simple and accurate technique to screen for small‐for‐gestational‐age and low‐weight‐for‐length infants in an unselected obstetric population Objective To help answer the question : should Doppler ultrasound of the umbilical circulation be made available to all pregnant women as part of their routine antenatal care This paper proposes a new method for planning r and omized clinical trials . This method is especially suited to comparison of a best st and ard or control treatment with an experimental treatment . Patients are allocated into two groups by a r and om or chance mechanism . Patients in the first group receive st and ard treatment ; those in the second group are asked if they will accept the experimental therapy ; if they decline , they receive the best st and ard treatment . In the analyses of results , all those in the second group , regardless of treatment , are compared with those in the first group . Any loss of statistical efficiency can be overcome by increased numbers . This experimental plan is indeed a r and omized clinical trial and has the advantage that , before providing consent , a patient will know whether an experimental treatment is to be used OBJECTIVE To assess the predictive value of Doppler umbilical artery velocimetry in a low-risk population with normal fetal biometry . STUDY DESIGN Multicenter prospect i ve study in 17 hospitals with prenatal clinics in France . Two thous and sixteen women who , before 28 weeks gestation were defined as at low risk after routine consultation and after ultrasound . Doppler umbilical artery velocimetry was performed between 28 and 34 weeks gestation . Confounding factors were used to perform multivariate regression . RESULTS 1903 cases were analysed and 192 ( 10.1 % ) had an abnormal Doppler Resistance Index ( RI ) . The abnormal Doppler group contained a significantly higher frequency of severe and moderate small for gestational age infants ( SGA ) , both severe and moderate with a sensitivity of 25.5 and 18.8 % respectively . There was no difference in hypertensive disorders or criteria of fetal distress . Mean birth weight was very significantly lower in the abnormal group ( 162 g ) . Birth weight was very significantly linked to RI after taking into account confounding variables in the multiple linear regression model ( continuous relationship ) . After multiple logistic regression , the odds ratio associated with an abnormal Doppler result , adjusted for all the confounding factors , was 2.3 ( 95 % CI 1.5 - 3.7 ) for moderate SGA and 3.5 ( 95 % CI of 1.8 - 7.1 ) for severe SGA . CONCLUSION Low umbilical Doppler RI is predictive with moderate or severe SGA in a low-risk population with normal fetal biometry , even when the information generally available in clinical practice and ultrasound parameters are taken into account . There is a continuous relationship between RI and birthweight . This predictive value can not , however , lead to an improvement in neonatal health unless effective measures to prevent SGA exist and umbilical Doppler should not be used in low-risk population on a routine basis |
2,617 | 24,457,121 | Frequently reported Grade 3/4 toxicities were increased AST/ALT , fatigue , hypertension , h and foot skin reaction and diarrhea .
The current evidence from the available clinical trials suggests that sorafenib-based combination with some anticancer agents ( especially mTOR inhibitors ) could be a more effective and tolerable treatment for advanced HCC in the future . | BACKGROUND Hepatocellular carcinoma is the fifth most common cancer worldwide and the third most common cause of cancer mortality .
Advanced HCC is a distinct disease entity with limited approved treatment options and grave prognosis .
So , we will explore in this systematic review the value of using sorafenib-based combination in this poor prognosis subset of HCC . | Purpose Sorafenib improves overall survival and time to progression of advanced hepatocellular ( aHCC ) patients such as demonstrated in 2 phase III trials . However , aHCC patients ’ outcome is still poor despite these results . In order to improve the efficacy of systemic treatment for aHCC , we evaluated the combination of sorafenib plus 5-fluorouacil infusion in a phase II trial . Methods Patients with aHCC not eligible for loco-regional therapies , Child-Pugh A-B , ECOG-PS 0 - 1 , and without history of anti-cancer systemic treatment were enrolled . Treatment schedule was : sorafenib 400 mg/bid continuously and continuum infusion of 5-fluorouracil 200 mg/sqm/daily day 1–14 every 3 weeks . Results Thirty-nine patients were enrolled : ECOG-PS 0 - 1 : 29 - 10 , Child-Pugh A-B : 36 - 3 . Grade 3/4 ( % ) toxicities included : diarrhea 5.1/0 , mucositis 20.5/2.6 , h and foot skin reaction 20.5/0 , skin rash 10.5/0 , hypertension 10.3/0 , hyperbilirubinemia 5.1/2.6 , glutamic-oxaloacetic transaminase increase 10.3/0 , glutamic-pyruvic transaminase increase 7.7/0 , cardiac toxicity ( one heart failure , two atrial fibrillation cases ) 7.7/0 , and bleeding ( melena ) in 2.6/0 . One partial response was observed . Stable disease was obtained in 46.2 % of patients with a median duration of 16.2 months . Median time to progression was 8 months ( CI 95 % = 5.7–10.4 ) , and median overall survival was 13.7 months ( CI 95 % = 9.5–17.9 ) . Conclusions The results show an encouraging disease control rate , time to progression , and overall survival . The combination of sorafenib and 5-fluorouracil was feasible , and the side effects were manageable for patients carefully selected for liver function and performance status BACKGROUND & AIMS Sorafenib , a multi-kinase inhibitor with anti-angiogenic activity , was recently approved for the treatment of advanced hepatocellular carcinoma ( HCC ) . Metronomic chemotherapy using tegafur/uracil ( 4:1 molar ratio ) , an oral fluoropyrimidine , has been shown to enhance the anti-tumor effect of anti-angiogenic agents in pre clinical models . This phase II study evaluated the efficacy and safety of combining metronomic tegafur/uracil with sorafenib in patients with advanced HCC . METHODS Patients with histologically- or cytologically-proven HCC and Child-Pugh class A liver function were treated with sorafenib ( 400 mg twice daily ) and tegafur/uracil ( 125 mg/m(2 ) based on tegafur twice daily ) continuously as first-line therapy for metastatic or locally advanced disease that could not be treated by loco-regional therapies . The primary endpoint was progression-free survival ( PFS ) . RESULTS The study enrolled 53 patients . Thirty-eight patients ( 72 % ) were hepatitis B surface antigen-positive . The median PFS was 3.7 months ( 95 % C.I. , 1.9 - 5.5 ) and the median overall survival was 7.4 months ( 95 % C.I. , 3.4 - 11.4 ) . According to RECIST criteria , 4 patients ( 8 % ) had a partial response and 26 patients ( 49 % ) had a stable disease . Major grade 3/4 toxicities included fatigue ( 15 % ) , abnormal liver function ( 13 % ) , elevated serum lipase ( 10 % ) h and -foot skin reaction ( HFSR ) ( 9 % ) , and bleeding ( 8 % ) . HFSR was the major adverse event result ing in dose reduction ( 19 % ) or treatment delay ( 21 % ) . CONCLUSIONS Metronomic chemotherapy with tegafur/uracil can be safely combined with sorafenib and shows preliminary activity to improve the efficacy of sorafenib in advanced HCC patients Purpose Advanced hepatocellular carcinoma ( HCC ) not eligible for local therapies has limited chances of cure . Sorafenib is a multikinase inhibitor with proven activity in advanced HCC . Octreotide is used in this setting with conflicting results . Treatment with sorafenib and long-acting octreotide was tested in advanced HCC to evaluate safety and activity . Methods Fifty patients with advanced HCC , Child-Pugh A or B , received sorafenib at a dosage of 800 mg/day for 28 days with a following week of rest and long-acting octreotide at a dose of 40 mg , administered every 28 days . Results All patients were assessable for safety and efficacy . Sixteen patients out of 50 ( 34 % ) were naïve from other therapies , while all the others were previously treated with local and /or systemic treatments . We achieved 5 partial responses ( 10 % ) , 33 stable diseases ( 66 % ) and 12 progressions of disease ( 24 % ) . Median time to progression was 7.0 months ( 95 % CI , 3.0–10.9 months ) , and median overall survival was 12 months ( 95 % CI , 6.3–17.4 months ) . Treatment was well tolerated . Diarrhoea ( 6 % ) and hypertension ( 4 % ) were the most frequent grade 3 toxicities . Conclusions Our data suggest that the combination between sorafenib and long-acting octreotide is active and well tolerated in patients with advanced HCC and could represent another efficacious chance for the management of this population Summary Purpose Sorafenib is a multi-kinase inhibitor , which was approved as first-line treatment for patients with advanced hepatocellular carcinoma ( HCC ) . We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC . Experimental design We design ed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib . Four dose levels were as follows : level 1 , D1 - 14 S-1 50 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 2 , D1 - 14 S-1 60 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 3 , , D1 - 14 S-1 70 mg/m2/day + D1 - 21 sorafenib 400 mg bid ; level 4 , D1 - 14 S-1 80 mg/m2/day + D1 - 21 sorafenib 400 mg bid . The treatment was repeated every 3 weeks . Results From August 2009 to July 2010 , 20 patients with advanced HCC were enrolled . The median age was 48 years ( range , 29–74 ) . Eighteen ( 90 % ) patients had hepatitis B viral infection and 19 ( 95 % ) patients were rated as Child-Pugh class A. The dose-limiting toxicities were grade 4 infection and thrombocytopenia . After a median follow-up duration of 8.6 months ( range , 3.7–14.2 months ) , median PFS was 3.9 months ( 95 % CI , 0.8–7.0 months ) and median OS was 10.4 months ( 95 % CI , 0–22.4 months ) . In pharmacokinetic analysis , there was no statistically significant drug interaction between sorafenib and S-1 . Conclusions The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC . The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m2 twice daily , respectively There is currently no consensus on the most suitable treatment for the recurrence of hepatocellular carcinoma ( HCC ) after liver transplantation . This open , multicenter , retrospective , uncontrolled cohort study was design ed to evaluate the safety and preliminary efficacy of the combined use of a mammalian target of rapamycin ( mTOR ) inhibitor and sorafenib in this setting . In 31 patients who suffered from HCC recurrence after liver transplantation , the immunosuppressive therapy was changed to mTOR inhibitors , and systemic treatment with sorafenib was initiated . This combination was maintained until symptomatic tumor progression , death , hepatic decompensation , or unacceptable toxicity occurred . Primary treatment efficacy was determined by overall survival and progression-free survival , and secondary efficacy was determined by the overall response rate . Toxicity parameters associated with the use of sorafenib and mTOR inhibitors were also analyzed . The overall response rate according to the Response Evaluation Criteria in Solid Tumors was 3.8 % ( 1/26 ) , and there was sustained stabilization of the disease in 13 additional cases ( 50.0 % ) . The median overall survival was 19.3 months [ 95 % confidence interval ( CI ) = 13.4 - 25.1 months ] , and the median time to progression was 6.77 months ( 95 % CI = 2.3 - 11.1 months ) . Only 2 grade 3/4 cases of hyperglycemia and 1 case of grade 3/4 mucositis were reported , and they were possibly related to mTOR inhibitors . The most common severe adverse event probably related to sorafenib was diarrhea ( 12.9 % ) . In conclusion , the coadministration of sorafenib and an mTOR inhibitor could be effective despite notable toxicity in patients with post-liver transplant HCC recurrence not suitable for radical therapy . The toxicity and efficacy need to be further evaluated in r and omized controlled studies for this combination to be considered a valid option The only approved systemic therapy for patients with advanced hepatocellular carcinoma ( HCC ) till now is sorafenib . A preliminary study suggested that capecitabine , an oral fluoropyrimidine , may be effective in advanced HCC . We have tested this hypothesis in this phase 2 study . In this single-center , phase 2 , open-label trial , we r and omly assigned 52 patients with advanced HCC who had not received previous systemic treatment to receive either sorafenib ( at a dose of 400 mg twice daily ) or capecitabine ( 1,000 mg/m2 twice daily ) ( day 1–day 14 ) . Primary outcome was progression-free survival . Secondary outcomes included the overall survival and safety . Median overall survival was 7.05 months in the sorafenib group and 5.07 months in the capecitabine group ( hazard ratio in the capecitabine group 2.36 ; 95 % confidence interval 1.174–4.74 ; P < 0.016 ) . The median progression-free survival was 6 months in the sorafenib group and 4 months in the capecitabine group ( P < 0.005 ) . Three patients in the sorafenib group ( 11.5 % ) and one patient in the capecitabine group ( 3 % ) had a partial response ; one patient ( 3 % ) had a complete response in the sorafenib group . H and –foot skin reaction was more frequent in the sorafenib group , hyperbilirubinemia was more common in the capecitabine group , and diarrhea was equivalent between both groups . In patients with advanced HCC , capecitabine is inferior to sorafenib in terms of median progression-free survival and overall survival , and it should not be used alone for the treatment of advanced HCC , but rather , combination therapy with sorafenib should be considered CONTEXT In a r and omized phase 3 trial , 400 mg of sorafenib twice daily prolonged overall survival of patients with advanced hepatocellular carcinoma ( HCC ) and Child-Pugh A disease . In a phase 1 study , sorafenib combined with doxorubicin , 60 mg/m(2 ) , was well tolerated by patients with refractory solid tumors . The combination of sorafenib and doxorubicin in patients with advanced HCC has not been evaluated in a phase 2 or 3 trial . OBJECTIVE To evaluate the efficacy and safety of doxorubicin plus sorafenib compared with doxorubicin alone in patients with advanced HCC and Child-Pugh A disease . DESIGN , SETTING , AND PATIENTS In a double-blind phase 2 multinational study , conducted from April 2005 to October 2006 , 96 patients ( 76 % male ; median age , 65 years [ range , 38 - 82 years ] ) with advanced HCC , Eastern Cooperative Oncology Group performance status 0 to 2 , Child-Pugh A status , and no prior systemic therapy were r and omly assigned to receive 60 mg/m(2 ) of doxorubicin intravenously every 21 days plus either 400 mg of sorafenib or placebo orally twice a day . The date of the last patient 's follow-up was April 2008 . MAIN OUTCOME MEASURE Time to progression as determined by independent review . RESULTS Following complete accrual , an unplanned early analysis for efficacy was performed by the independent data monitoring committee , so the trial was halted . The 2 patients remaining in the placebo group at that time were offered sorafenib . Based on 51 progressions , 63 deaths , and 70 events for progression-free survival , median time to progression was 6.4 months in the sorafenib-doxorubicin group ( 95 % confidence interval [ CI ] , 4.8 - 9.2 ) , and 2.8 months ( 95 % CI , 1.6 - 5 ) in the doxorubicin-placebo monotherapy group ( P = .02 ) . Median overall survival was 13.7 months ( 95 % CI , 8.9 - -not reached ) and 6.5 months ( 95 % CI , 4.5 - 9.9 ; P = .006 ) , and progression-free survival was 6.0 months ( 95 % CI , 4.6 - 8.6 ) and 2.7 months ( 95 % CI , 1.4 - 2.8 ) in these groups , respectively ( P = .006 ) . Toxicity profiles were similar to those for the single agents . CONCLUSIONS Among patients with advanced HCC , treatment with sorafenib plus doxorubicin compared with doxorubicin monotherapy result ed in greater median time to progression , overall survival , and progression-free survival . The degree to which this improvement may represent synergism between sorafenib and doxorubicin remains to be defined . The combination of sorafenib and doxorubicin is not yet indicated for routine clinical use . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108953 4000 Background : The oral multitargeted tyrosine kinase inhibitor Su had antitumor activity in phase II HCC trials , leading to a phase III open-label trial comparing the efficacy and safety of Su with So . METHODS Patients ( pts ) with advanced HCC , Child-Pugh A , ECOG PS 0/1 and no prior systemic chemotherapy were stratified by geographic region , prior TACE and tumor invasion . Pts were r and omized 1:1 to Su 37.5 mg/day or So 400 mg BID . The primary endpoint was overall survival ( OS ; 1-sided log-rank test ; α=0.025 , 90 % power ) with 600 pts/arm required in this superiority/non-inferiority trial design . Secondary endpoints were progression-free survival ( PFS ) , time to progression ( TTP ) and safety . Efficacy and futility boundaries were set using the Lan-DeMets and O'Brien-Fleming methods for interim analyses . RESULTS 1,073 pts were r and omized ( Su 529/So 544 ) from July 2008 to May 2010 . An Independent Data Monitoring Committee stopped the trial early for futility and safety concerns . Pts were notified . Su discontinuation was recommended with the option for investigator discretion in cases of clinical benefit . For Su/So : median follow-up 7.4/7.8 mo ; median age 59/59 yr ; Asian 76/75 % ; male 82/84 % ; ECOG PS 0 53/53 % ; > 3 prior TACE 16/17 % ; tumor invasion 79/76 % ; ≥1 dose interruption 69/55 % and ≥1 dose reduction 47/69 % . Median OS was 8.1/10.0 mo ( HR 1.31 [ 95 % CI : 1.13 - 1.52 ] , P=0.0019 ) ; PFS was 3.6/2.9 mo ( HR 1.12 [ 95 % CI : 0.98 - 1.29 ] , P=0.1386 ) and TTP was 4.1/4.0 mo ( HR 1.13 [ 95 % CI : 0.97 - 1.31 ] , P=0.1785 ) . OS for pts with hepatitis B ( Hep B ; Su 290/So 288 ; post hoc analysis ) was 7.8/7.9 mo ( HR 1.09 [ 95%CI : 0.9 - 1.32 ] , P=0.236 ) . In 526/541 pts evaluable for safety , all-causality , grade 3/4 adverse events ( AEs ) occurred in 82/73 % of pts ; the most common were thrombocytopenia ( 19 % ) and neutropenia ( 16 % ) for Su , and skin disorders ( 21 % ) for So . Discontinuations due to AEs occurred in 26/23 % of pts . Serious AEs were noted in 44/36 % of pts , with grade 5 AEs in 18/16 % . CONCLUSIONS In advanced HCC , Su failed its primary OS endpoint . However , PFS and TTP results were similar between Su and So . In a Hep-B pt subgroup , no significant difference in OS was detected between Su and So . Su was associated with more frequent toxicities vs So . 65 pts ( Su 17/So 48 ) remain on study BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma BACKGROUND & AIMS Sorafenib is the only therapy shown to improve overall survival in advanced hepatocellular carcinoma ( HCC ) . Combination therapy targeting multiple signaling pathways may improve outcomes . This phase I study was design ed to determine the maximum tolerated dose ( MTD ) of everolimus given with sorafenib 400 mg twice daily in patients with advanced HCC of Child-Pugh class A liver function who were naive to systemic therapy . METHODS Everolimus was initiated at 2.5 mg once daily and increased per a Bayesian sequential dose-escalation scheme based on the dose-limiting toxicities experienced within the first 28 days of treatment . Adverse events were assessed continuously . Efficacy was evaluated using the best overall response rate per RECIST . RESULTS Thirty patients were enrolled ; 25 were evaluable for MTD determination . One out of 12 patients treated with everolimus 2.5 mg once daily and 6 out of 13 patients treated with everolimus 5.0 mg once daily experienced a dose-limiting toxicity , most commonly thrombocytopenia ( n=5 ) . All patients experienced 1 adverse event , most commonly diarrhea ( 66.7 % ) , h and -foot skin reaction ( 66.7 % ) , and thrombocytopenia ( 50.0 % ) . Best overall response was stable disease ( 62.5 % and 42.9 % in the 2.5-mg and 5.0-mg cohorts , respectively ) . Median time to progression and overall survival in the 2.5-mg cohort were 4.5 months and 7.4 months , respectively , and 1.8 months and 11.7 months , respectively , in the 5.0-mg cohort . CONCLUSIONS In patients with advanced HCC , the everolimus MTD in combination with st and ard-dose sorafenib was 2.5 mg once daily . The inability to achieve a biologically effective everolimus concentration at the MTD precluded phase II study of this combination |
2,618 | 20,614,449 | The results suggest that rhythmic auditory stimulation ( RAS ) may be beneficial for improving gait parameters in stroke patients , including gait velocity , cadence , stride length and gait symmetry .
RAS may be beneficial for gait improvement in people with stroke . | BACKGROUND Acquired brain injury ( ABI ) can result in impairments in motor function , language , cognition , sensory processing and emotional disturbances .
This may severely reduce a survivor 's quality of life .
Music therapy has been used in rehabilitation to stimulate brain functions involved in movement , cognition , speech , emotions and sensory perceptions .
A systematic review is needed to gauge the efficacy of music therapy as a rehabilitation intervention for people with ABI .
OBJECTIVES To examine the effects of music therapy with st and ard care versus st and ard care alone or st and ard care combined with other therapies on gait , upper extremity function , communication , mood and emotions , social skills , pain , behavioral outcomes , activities of daily living and adverse events . | Experimental and control groups of 10 hemiparetic stroke patients each underwent a 6 week , twice daily gait training program . The control group participated in a conventional physical therapy gait program . The experimental group trained in the same basic program with the addition of rhythmic auditory stimulation ( RAS ) . Patients entered the study as soon as they could complete 5 strides with h and -held assistance . The training program had to be completed within 3 months of the patients ' stroke . In the experimental group RAS was used as a timekeeper to synchronize step patterns and gradually entrain higher stride frequencies . Study groups were equated by gender , lesion site , and age . Motor function was assessed at pretest using Barthel , Fugl-Meyer , and Berg Scales . Walking patterns were assessed during pre- and post-test without RAS present . Pre- vs post-test measures revealed a statistically significant ( P<0.05 ) increase in velocity ( 164 % vs 107 % ) , stride length ( 88 % vs 34 % ) , and reduction in EMG amplitude variability of the gastrocnemius muscle ( 69 % vs 33 % ) for the RAS-training group compared to the control group . The difference in stride symmetry improvement ( 32 % in the RAS-group vs 16 % in the control group ) was statistically not significant . The data offer evidence that RAS is an efficient tool to enhance efforts in gait rehabilitation with acute stroke patients In previous studies , it was shown that there is a need for efficient motor rehabilitation approaches . For this purpose , we evaluated a music-supported training program design ed to induce an auditory – sensorimotor co-representation of movements in 20 stroke patients ( 10 affected in the left and 10 in the right upper extremity ) . Patients without any previous musical experience participated in an intensive step by step training , first of the paretic extremity , followed by training of both extremities . Training was applied 15 times over 3 weeks in addition to conventional treatment . Fine as well as gross motor skills were addressed by using either a MIDI-piano or electronic drum pads . As a control , 20 stroke patients ( 10 affected left and 10 right ) undergoing exclusively conventional therapies were recruited . Assignment to the training and control groups was done pseudo-r and omly to achieve an equal number of left- and right-affected patients in each group . Pre- and post-treatment motor functions were monitored using a computerized movement analysis system ( Zebris ) and an established array of motor tests ( e. g. , Action Research Arm Test , Box & Block Test ) . Patients showed significant improvement after treatment with respect to speed , precision and smoothness of movements as shown by 3D movement analysis and clinical motor tests . Furthermore , compared to the control subjects , motor control in everyday activities improved significantly . In conclusion , this innovative therapeutic strategy is an effective approach for the motor skill neurorehabilitation of stroke patients Purpose . The aim of the study was to identify factors that are significantly related to depression in chronic stroke patients . Methods . Prospect i ve cohort study of stroke patients admitted for rehabilitation . A total of 165 first ever stroke patients over 18 years of age were assessed at one and three years post stroke . Depression was determined by the Centre for Epidemiologic Studies Depression Scale ( CES-D ) . Patients with scores ≥16 were classified as depressed . Bivariate and multivariate logistic regression analyses were used to identify prognostic factors for depression . Results . At three years post stroke , 19 % of the patients were depressed . Bivariate analysis showed significant associations between post-stroke depression and type of stroke , fatigue , motor function of the leg and arm , activities of daily living ( ADL ) independency and instrumental ADL . Multivariate logistic regression analysis showed that depression was predicted by one-year instrumental ADL and fatigue . Sensitivity of the model was 63 % , while specificity was 85 % . Conclusions . The present prospect i ve cohort study showed that depression three years after stroke can be predicted by instrumental ADL and fatigue one year post stroke . Recognition of prognostic factors in patients at risk may help clinicians to apply interventions aim ed at preventing depression in chronic stroke We know from animal studies that a stimulating and enriched environment can enhance recovery after stroke , but little is known about the effects of an enriched sound environment on recovery from neural damage in humans . In humans , music listening activates a wide-spread bilateral network of brain regions related to attention , semantic processing , memory , motor functions , and emotional processing . Music exposure also enhances emotional and cognitive functioning in healthy subjects and in various clinical patient groups . The potential role of music in neurological rehabilitation , however , has not been systematic ally investigated . This single-blind , r and omized , and controlled trial was design ed to determine whether everyday music listening can facilitate the recovery of cognitive functions and mood after stroke . In the acute recovery phase , 60 patients with a left or right hemisphere middle cerebral artery ( MCA ) stroke were r and omly assigned to a music group , a language group , or a control group . During the following two months , the music and language groups listened daily to self-selected music or audio books , respectively , while the control group received no listening material . In addition , all patients received st and ard medical care and rehabilitation . All patients underwent an extensive neuropsychological assessment , which included a wide range of cognitive tests as well as mood and quality of life question naires , one week ( baseline ) , 3 months , and 6 months after the stroke . Fifty-four patients completed the study . Results showed that recovery in the domains of verbal memory and focused attention improved significantly more in the music group than in the language and control groups . The music group also experienced less depressed and confused mood than the control group . These findings demonstrate for the first time that music listening during the early post-stroke stage can enhance cognitive recovery and prevent negative mood . The neural mechanisms potentially underlying these effects are discussed Abstract Purpose : Recovery of skilled upper limb movement remains a critical focus of rehabilitation in individuals post stroke . Conventional treatments , however , have demonstrated limited capability to produce substantial improvements in poststroke quality of movement . Recently , rhythmic auditory stimulation ( RAS ) has emerged as efficacious in improving and normalizing limb movements in neurologically impaired population s. This pilot study examined changes in pre- to post-RAS reach kinematics and functional outcomes in survivors of stroke . Method : Five individuals in the chronic poststroke phase participated in a 2-week program of RAS training . Kinematic reaching variables were trunk , shoulder , and elbow segment contribution ; movement time ; and reach velocity . Functional outcomes were the Wolf Motor Function Test , Motor Activity Log , and Fugl-Meyer Assessment . Results : Post-RAS assessment of reaching kinematics revealed a significant ( p < .05 ) decrease in compensatory trunk movement , increase in shoulder flexion , and a slight increase in elbow extension . Movement time and velocity significantly improved post RAS . Significant gains were observed on all functional assessment s. Conclusions : Post RAS , participants demonstrated substantial decreases in compensatory reaching movements . These changes in motor control strategy were paralleled by gains in functional abilities , suggesting that reduced reliance on compensatory movements may translate to improved performance of daily activities The purpose of this study was to determine the effects of music therapy on pain perception of stroke patients during upper extremity joint exercises . Ten stroke patients ( 1 male and 9 females ) ranging in age from 61 to 73 participated in the study . Music conditions used in the study consisted of : ( a ) song , ( b ) karaoke accompaniment ( same music to condition A except singers ' voices ) , and ( c ) no music . Exercise movements in this study included h and , wrist , and shoulder joints . During the 8-week period music therapy sessions , subjects repeated 3 conditions according to the r and omized orders and subjects rated their perceived pain on a scale immediately after each condition . The General Linear Model ( GLM ) Repeated Measures ANOVA revealed that there were no significant differences in pain rating across the three music conditions . However , positive affects and verbal responses , while performing upper extremity exercises with both music and karaoke accompaniment music , were observed using video observations |
2,619 | 14,736,581 | In general , the review s support short-term benefit of antiviral drugs , but note limited evidence for a reduction in the incidence of PHN .
Famciclovir and valaciclovir , however , were shown to reduce the duration of PHN .
Oral steroids reduced the severity of acute HZ pain , but had no effect on the incidence , severity , or duration of PHN . | Herpes zoster ( HZ ) or shingles is a common disease , with a reported incidence varying from 2.2 to 3.4 per 1000 persons/year ( Donahue et al. , 1995 ) .
For most patients skin healing and pain resolution occur within 3–4 weeks .
Pain can , however , continue after the rash has healed .
This condition , referred to as postherpetic neuralgia ( PHN ) , may last for several months to years .
Depending on the applied definition , 9–34 % of all HZ patients develop PHN ( Dworkin and Portenoy , 1996 ) .
The most important risk factors for this pain syndrome include age and the severity of acute pain and inflammation during HZ ( Whitley et al. , 1999 ) .
PHN has a high impact on the quality of life : many patients develop severe physical , occupational , and social disabilities as a result of the unceasing pain ( Dworkin and Portenoy , 1996 ) .
Since PHN commonly occurs in the elderly , its incidence is expected to increase in our aging society .
Because treatment of PHN has been disappointing , much attention is currently being given to the evaluation of interventions administered to HZ patients to prevent PHN .
Only one small study showed that early treatment of HZ patients with the antidepressant amitriptyline caused a reduction in PHN occurrence ( Bowsher , 1997 ) .
Interventions such as infiltration with local anesthetics and sympathetic and epidural blocks have also been proposed and applied to reduce the risk of PHN development . | Acute neuritis and persistent pain are the most significant clinical manifestations of herpes zoster and are end points for clinical trials therapy . In an acyclovir and prednisone study , patients were categorized according to pain severity and number of lesions at presentation . Risk categories were defined according to the magnitude of risk ratios ( RRs ) and a comparison of Kaplan-Meier survival estimates . For acute neuritis and zoster-associated pain , RRs defined rate of resolution . Patients who presented with severe or incapacitating pain and a large number of lesions were less likely to achieve resolution of both acute neuritis and zoster-associated pain ( RR , 18.0 ; 95 % confidence interval [ CI ] , 6 . 6 - 48.6 , and RR , 5.3 ; 95 % CI , 4.2 - 17.2 , respectively ) . These analyses identify the subgroups of patients for whom aggressive interventions are most strongly indicated We studied the effects of spinal cord stimulation ( SCS ) on postherpetic neuralgia ( PHN ) . Data of 28 patients were prospect ively investigated over a median period of 29 ( quartiles 9–39 ) mo . In addition , four patients with acute herpes zoster ( HZ ) pain were studied simultaneously . After intractable pain for more than 2 yr , long-term pain relief was achieved in 23 ( 82 % ) PHN patients ( median , 70 yr ) during SCS treatment confirmed by a median decrease from 9 to 1 on the visual analog scale ( P < 0.001 ) . In five cases with serious comorbidity , the initial pain alleviation could not be stabilized . Spontaneous improvement was always confirmed or excluded by SCS inactivation tests at quarterly intervals . Eight patients discontinued SCS permanently because of complete pain relief after stimulation periods of 3–66 mo , whereas 2 reestablished SCS because of recrudescence after 2 and 6 mo . Considerable impairments in everyday life , objectified by the pain disability index , were also significantly improved ( P < 0.001 ) . In 4 patients with acute HZ pain , SCS was promptly effective and after periods of 2.5 ( quartiles 2–3 ) months the pain had subsided . SCS seems to offer a therapeutic option for pharmacological nonresponders Objective : The purpose of this study was to investigate the effects of continuous epidural blockade on acute zoster-associated pain , compared with intermittent epidural blocks . Design : The design was a retrospective , nonr and omized study . Setting : The study was conducted at a university hospital in Japan from 1982 through 1992 . Patients : A total of 178 otherwise healthy patients hospitalized with moderate or severe herpes zoster lesions . Interventions : Group A ( n = 66 ) had intermittent epidural blocks using 1 % mepivacaine , 4–6 ml , three to six times daily ; group B ( n = 43 ) were given intermittent epidural blocks and parenteral acyclovir ( 500 mg/day ) or vidara- bine ( 600 mg/day ) for 5 days ; group C ( n = 69 ) were administered a continuous epidural 0.5 % bupivacaine infusion ( 0.3–1.0 ml/h ) for ∼2 weeks and antiviral agents followed by intermittent blocks . Main Outcome Measures : The number of treatment days was used as the outcome measure . Results : The length of treatment was significantly shorter in group C than in groups A or B. For moderate lesions the means ( days ) were 36.2 [ 95 % confidence interval ( CI ) , 31.4–41.7 ) , 45.6 ( 95 % CI , 34.0–61.4 ) , and 26.8 ( 95 % CI , 22.3–32.3 ) for groups A , B , and C , respectively ( p < 0.01 ) . For severe lesions they were 73.3 ( 95 % CI , 55.1–97.7 ) , 81.7 ( 95 % CI , 59.1–113.0 ) , and 44.9 ( 95 % CI , 35.2–57.3 ) for groups A , B , and C , respectively ( p < 0.01 ) . Conclusions : Continuous epidural blockade for patients with acute zoster can shorten the duration of treatment and may reduce the incidence of postherpetic neuralgia OBJECTIVE To evaluate the relief of acute pain and possible preventive effects on postherpetic neuralgia through the use of an epidural blockade in the acute stage of herpes zoster . DESIGN Prospect i ve , nonr and omized , comparative clinical trial . SETTING A dermatologic clinic in a university hospital . PATIENTS Sixty-five consecutive patients with pain due to acute herpes zoster were treated for a 7-day hospitalization period from July 1 , 1996 , through June 30 , 1997 . INTERVENTION The consecutive patients were divided into 2 groups . Group A consisted of 30 patients who were seen from July 1 , 1996 , through December 31 , 1996 , and who were treated with intravenous acyclovir ( 5 mg/kg ) for 7 days . Group B consisted of 35 patients who were seen from January 1 , 1997 , through June 30 , 1997 , and who were treated with intravenous acyclovir ( 5 mg/kg ) and an epidural blockade for 7 days . The changes in the intensity of pain and the total duration of pain in both groups were assessed for 12 to 18 months . MAIN OUTCOME MEASURES The number of days required for relief of pain and the total duration of pain . RESULTS The mean + /- SD number of days required for relief of pain , which was rated on a scale of 100 ( worst pain ) to 0 ( no pain ) , was significantly fewer in group B than in group A : it took 2.6 + /- 1.1 days to go from 100 to 50 on the relief-of-pain scale in group B , but 3.8 + /- 1.1 days in group A ( P = .03 ) , and 12.5 + /- 6.4 days to go from 100 to 10 in group B , but 20.1 + /- 14.6 days in group A ( P = .04 ) . The duration of late residual pain was significantly shorter in group B ( 5.9 + /- 5.8 days ) than in group A ( 11.9 + /- 7.5 days ) ( P = .03 ) . The total duration of pain was also significantly shorter in group B ( 18.5 + /- 9.3 days ) than in group A ( 31.6 + /- 17.6 days ) ( P = .04 ) . CONCLUSIONS We believe that an epidural blockade combined with an antiviral agent is a very effective treatment modality for the pain of acute herpes zoster , and we recommend its use for the prevention of postherpetic neuralgia , with a view to shortening the total duration of pain , especially late residual pain Background : Treatment of herpes zoster ( HZ ) includes the use of acyclovir with or without steroids . An alternative therapy is the epidural administration of local anesthetics with or without steroids . This trial compared the efficacy of these two treatment regimens in the prevention of post‐herpetic neuralgia ( PHN ) Seventy-two patients older than 60 years of age who received a diagnosis of herpes zoster ( HZ ) were entered into a r and omized , double-blind , placebo-controlled trial of daily amitriptyline 25 mg . Treatment with either amitriptyline or placebo continued for 90 days after diagnosis . Pain prevalence at 6 months was the primary outcome . Results showed that early treatment with low-dose amitriptyline reduced pain prevalence by more than one-half ( p < 0.05 ; odds ratio , 2.9:1 ) This finding makes a strong case for the pre-emptive administration of amitriptyline , in combination with an antiviral drug , to elderly patients with acute herpes zoster A ntiviral drugs decrease the pain and enhance the resolution of acute herpes zoster lesions in immunocompetent patients ( l-6 ) . However , the effect of antiviral therapy on postherpetic neuralgia ( PHN ) remains controversial . Whereas some studies reported a lower incidence of prolonged pain with antiviral therapy ( 4 ) , others found no benefit with respect to prolonged pain ( 5 ) . In an attempt to improve patient comfort and long-term outcome with respect to PHN , combinations of different drugs have also been evaluated ( 5 - 7 ) . Anecdotal reports have suggested that electroacupuncture may be helpful in the management of herpes-related pain ( 8,9 ) . Clinical experience with a novel form of electroanalgesia known as percutaneous electrical nerve stimulation ( PENS ) in the treatment of patients with acute herpes zoster suggested that it is effective in decreasing herpes-related pain and is associated with rapid resolution of the cutaneous lesions ( Craig WF , Taylor SM , Fort Worth Center for Pain Management , personal communication , 1997 ) . Therefore , we design ed this clinical study to compare PENS therapy with a st and ard antiviral regimen with respect to the severity of the associated pain , impact on the patient ’s physical activity and quality of sleep , resolution of the herpes lesions , and incidence and severity of PHN |
2,620 | 30,368,808 | Manualized treatment is not empirically supported as more effective than nonmanualized treatment . | OBJECTIVE Institutional promotion of psychotherapy manuals as a requirement for evidence -based treatments ( EBTs ) yields the assumption that manualized treatment is more effective than nonmanualized treatment .
This systematic review examines empirical evidence for this cl aim . | Does higher level of individualization increase treatment efficacy ? Fifty patients with bulimia nervosa were r and omized into either manual-based ( focused ) or more individualized ( broader ) cognitive behavioral therapy guided by logical functional analysis . Eating disorders Examination and a series of self-report question naires were used for assessment at pre- , and post-treatment as well as at follow-up . Both conditions improved significantly at post-treatment , and the results were maintained at the 6 months follow-up . There were no statistically and clinical ly significant differences between the two conditions at post-treatment with the exception of abstinence from objective bulimic episodes , eating concerns , and body shape dissatisfaction , all favoring the individualized , broader condition . Both groups improved concerning self-esteem , perceived social support from friends , and depression . The improvements were maintained at follow-up . Ten patients ( 20 % ) did not respond to the treatment . Notably , a majority of non-responders ( 80 % ) were in the manual-based condition . Non-responders showed extreme dominance of rule-governed behavior , and lack of contact with actual contingencies compared to responders . The study provided preliminary support for the superiority of higher level of individualization ( i.e. broader CBT ) in terms of the response to treatment , and relapses . However , the magnitude of effects was moderate , and independent replications , with blind assessment procedures , and a larger sample sized are needed before more clear cut conclusions can be drawn UNLABELLED Although associations with outcome have been inconsistent , therapist adherence and competence continues to garner attention , particularly within the context of increasing interest in the dissemination , implementation , and sustainability of evidence -based treatments . To date , research on therapist adherence and competence has focused on average levels across therapists . With a few exceptions , research has failed to address multiple sources of variability in adherence and competence , identify important factors that might account for variability , or take these sources of variability into account when examining associations with symptom change . OBJECTIVE ( a ) statistically demonstrate between- and within-therapist variability in adherence and competence ratings and examine patient characteristics as predictors of this variability and ( b ) examine the relationship between adherence/competence and symptom change . METHOD R and omly selected audiotaped sessions from a r and omized controlled trial of cognitive-behavioral therapy for panic disorder were rated for therapist adherence and competence . Patients completed a self-report measure of panic symptom severity prior to each session and the Inventory of Interpersonal Problems-Personality Disorder Scale prior to the start of treatment . RESULTS Significant between- and within-therapist variability in adherence and competence were observed . Adherence and competence deteriorated significantly over the course of treatment . Higher patient interpersonal aggression was associated with decrements in both adherence and competence . Neither adherence nor competence predicted subsequent panic severity . CONCLUSIONS Variability and " drift " in adherence and competence can be observed in controlled trials . Training and implementation efforts should involve continued consultation over multiple cases in order to account for relevant patient factors and promote sustainability across sessions and patients OBJECTIVE This study explores the relationships between therapist variables ( cognitive behavioral therapy [ CBT ] competence , and CBT adherence ) and clinical outcomes of computer-assisted CBT for anxiety disorders delivered by novice therapists in a primary care setting . METHODS Participants were recruited for a r and omized controlled trial of evidence -based treatment , including computer-assisted CBT , versus treatment as usual . Therapists ( anxiety clinical specialists ; ACSs ) were nonexpert clinicians , many of whom had no prior experience in delivering psychotherapy ( and in particular , very little experience with CBT ) . Trained raters review ed r and omly selected treatment sessions from 176 participants and rated therapists on measures of CBT competence and CBT adherence . Patients were assessed at baseline and at 6- , 12- , and 18-month follow-ups on measures of anxiety , depression , and functioning , and an average Reliable Change Index was calculated as a composite measure of outcome . CBT competence and CBT adherence were entered as predictors of outcome , after controlling for baseline covariates . RESULTS Higher CBT competence was associated with better clinical outcomes whereas CBT adherence was not . Also , CBT competence was inversely correlated with years of clinical experience and trended ( not significantly , though ) down as the study progressed . CBT adherence was inversely correlated with therapist tenure in the study . CONCLUSIONS Therapist competence was related to improved clinical outcomes when CBT for anxiety disorders was delivered by novice clinicians with technology assistance . The results highlight the value of the initial training for novice therapists as well as booster training to limit declines in therapist adherence This study evaluated the short-term effectiveness of cognitive-behavioral treatment ( CBT ) for substance abuse delivered in a community setting . At entry into outpatient community substance abuse treatment , participants ( N = 252 ) were r and omly assigned to 3 conditions : high-st and ardization CBT , low-st and ardization CBT , and treatment as usual . Treatment consisted of 12 weekly individual therapy sessions . There was a significant decrease in substance use from baseline , with participants reporting being abstinent on 90 % of within-treatment days and 85 % of days during the 6 months posttreatment . However , there were no significant differences in outcomes across conditions . Findings do not support the hypothesis that disseminating CBT to community setting s will improve outcomes and suggest that st and ard substance abuse counseling may be more effective than previously thought Although r and omized controlled trials examining the efficacy of attachment-based interventions have been increasing in recent years , adequate measurement of treatment integrity , integrity- outcome associations , and mechanisms of change has been rare . The aim of this investigation was to conduct a rigorous test of proposed mechanisms of change in the Mothers and Toddlers Program ( MTP ) treatment model , a 12-session , attachment-based individual therapy for substance-using mothers of children birth to 3 years of age . The MTP aims to improve maternal reflective functioning ( RF ) and representation quality ( RQ ) to bring about second-order change in maternal caregiving behavior . Following guidelines from M.K. Nock ( 2007 ) , it was hypothesized that ( a ) therapist adherence to unique MTP treatment components would uniquely predict improvement in RF and RQ and that ( b ) improvement in RF and RQ would function as unique mechanisms of change ( when compared with other potential mechanisms-reduction in depression and increase in abstinence from drug use ) in the improvement of caregiving behavior . Findings supported each hypothesis , confirming the proposed mechanisms of the treatment model . However , improvement in maternal depression also uniquely predicted improvement in caregiving behavior . Results underscore the potential value of attachment-based parenting interventions for improving mother-child relations and the importance of providing these interventions in clinic setting s where mothers have access to comprehensive care ( e.g. , psychiatric services ) Abstract This modest clinical pilot study was intended to provide preliminary data on the effects of hypnotic inductions tailored to an irritable bowel syndrome patient at each session compared to Palsson ’s manualized protocol . Patients ( N = 8) who had not previously responded to any form of treatment were assigned r and omly to either a tailored or manualized induction condition . Other than pretesting for hypnotizability , the procedure followed for the manualized group ( n = 4 ) was exactly as prescribed by O. Palsson ( 1998 ) . The identical procedure was used for the other 4 patients except that the inductions were individualized . All 8 patients showed favorable responses to treatment immediately posttreatment and at 10-month follow-up . Only the tailored group showed no incapacitating pain at posttreatment but greater emotional stress than the manualized group . The tailored group continued to improve and showed better results than the manualized group at 10 months , and the posttreatment emotional distress was significantly attenuated OBJECTIVES Treatment failure is a common phenomenon , but little is known about the reasons . Therapeutic alliance , therapist adherence , and therapist competence are considered important aspects of treatment success and formed the focus of the current investigation . DESIGN Three r and omized controlled trials for the treatment of depression , social phobia , and hypochondriasis were the basis of the current study . METHODS The role of therapeutic alliance , as well as therapist adherence and competence , were investigated in 61 patients , which were classified either as treatment failure or as treatment success . Process variables were evaluated by independent raters on the basis of videotapes of the first three treatment sessions . RESULTS Therapists ' adherence and therapeutic alliance differed significantly between successful treatments and those classified as failures , whereas therapists ' competence did not . In cross-sectional analysis , we found a moderating effect of adherence with alliance on treatment outcome , indicating that the better the therapeutic alliance , the stronger the effect of adherence on treatment outcome . Moreover , higher therapists ' competence was found to affect treatment outcome positively , only mediated by therapeutic alliance . Higher therapists ' adherence affected treatment outcome positively , only mediated by the competence-alliance relationship . In additional longitudinal analyses , we found evidence that the therapeutic alliance within one session influences therapists ' adherence and competence in the subsequent session , but not the other way around . CONCLUSIONS Therapeutic alliance proved to be an important variable for the prediction of treatment failure . Furthermore , in our longitudinal analyses , we found evidence that the therapeutic alliance is a precondition for the adherent and competent implementation of therapeutic techniques , which questions the results of our cross-sectional analysis and of previous research . PRACTITIONER POINTS Clinical implication s Treatment failure is associated with a lower therapeutic alliance in cognitive-behavioural treatment . Therapeutic alliance seems to be an important precondition for the adherent and competent implementation of therapeutic techniques . Therapeutic alliance should be monitored during psychotherapeutic treatment . Caution s or limitations Results are limited to cognitive-behavioural therapy and may not be representative for other treatment approaches . Process analyses are based on highly st and ardized r and omized controlled trials and may not be generalizable to routine care This article provides a critical review of the assumptions and findings of studies used to establish psychotherapies as empirically supported . The attempt to identify empirically supported therapies ( ESTs ) imposes particular assumptions on the use of r and omized controlled trial ( RCT ) methodology that appear to be valid for some disorders and treatments ( notably exposure-based treatments of specific anxiety symptoms ) but substantially violated for others . Meta-analytic studies support a more nuanced view of treatment efficacy than implied by a dichotomous judgment of supported versus unsupported . The authors recommend changes in reporting practice s to maximize the clinical utility of RCTs , describe alternative method ologies that may be useful when the assumptions underlying EST methodology are violated , and suggest a shift from validating treatment packages to testing intervention strategies and theories of change that clinicians can integrate into empirically informed therapies OBJECTIVE Therapist adherence has been shown to predict clinical outcomes in family therapy . In prior studies , adherence has been represented broadly by core principles and a consistent family ( vs. individual ) focus . To date , these studies have not captured the range of clinical skills that are represented in complex family-based approaches or examined how variations in these skills predict different clinical ly relevant outcomes over the course of treatment . In this study , the authors examined the reliability and validity of an observational adherence measure and the relationship between adherence and outcome in a sample of drug-using adolescents who received brief strategic family therapy within a multisite effectiveness study . METHOD Participants were 480 adolescents ( age 12 - 17 ) and their family members , who were r and omized to the Brief Strategic Family Therapist treatment condition ( J. Szapocznik , U. Hervis , & S. Schwartz , 2003 ) or treatment as usual . The adolescents were mostly male ( 377 vs. 103 female ) and Hispanic ( 213 ) , whereas 148 were White , and 110 were Black . Therapists were also r and omly assigned to treatment condition within agencies . RESULTS Results supported the proposed factor structure of the adherence measure , providing evidence that it is possible to capture and discriminate between distinct dimensions of family therapy . Analyses demonstrated that the mean levels of the factors varied over time in theoretically and clinical ly relevant ways and that therapist adherence was associated with engagement and retention in treatment , improvements in family functioning , and reductions in adolescent drug use . CONCLUSIONS Clinical implication s and future research directions are discussed , including the relevance of these findings on training therapists and studies focusing on mechanisms of action in family therapy OBJECTIVE Previous research has found that therapist adherence to concrete , problem-focused cognitive therapy ( CT ) techniques predicts depressive symptom change ( e.g. , Feeley , DeRubeis , & Gelf and , 1999 ) . More recently , Strunk , DeRubeis , Chui , and Alvarez ( 2007 ) demonstrated that in-session evidence of patients ' use of CT skills was related to a lower rate of relapse in the year following CT for depression . The current investigation attempts to integrate and extend these findings within 2 separate sample s of patients and therapists . METHOD Drawing from the CT sample s ( N = 105 , mean age = 40 years , female = 62 % , White = 82 % ) of 2 published r and omized clinical trials of depression treatment , we conducted analyses to examine whether therapist adherence to concrete CT techniques ( Collaborative Study Psychotherapy Rating Scale ) and the quality of the therapeutic alliance ( Working Alliance Inventory ) predict patients ' use of CT skills ( Performance of Cognitive Therapy Strategies ) and subsequent Beck Depression Inventory symptom change . RESULTS Results indicated a differential pattern of prediction in the 2 sample s. In one , CT techniques exhibited a stronger association with patient CT skills and symptom change than did the alliance , whereas the reverse pattern emerged in the second sample . A baseline symptom severity × CT techniques interaction indicated that between- study differences in intake depression severity might in part explain the process- outcome differences . CONCLUSIONS The present findings suggest that the nature of the therapy sample examined may moderate process- outcome findings in psychotherapy research . The implication s of these results and directions for future research are discussed OBJECTIVE The research on the association between the working alliance and therapist competence/adherence and outcome from cognitive behavioral therapy ( CBT ) is limited and characterized by inconclusive findings . This study investigates the working alliance and competence/adherence as predictors of outcome of CBT for social anxiety disorder ( SAD ) and panic disorder ( PD ) . METHOD Eighty-two clinical ly referred patients ( 58.5 % female ; age : M = 33.6 years , SD = 10.3 ) with PD ( n = 31 ) or SAD ( n = 51 ) were treated with 12 sessions of manualized CBT by 22 clinicians with limited CBT experience in a r and omized controlled effectiveness trial . Independent assessors rated the CBT competence/adherence of the therapists using a revised version of the Cognitive Therapy Adherence and Competence Scale , and the patients rated the quality of the working alliance using the Working Alliance Inventory-short form in therapy sessions 3 and 8 . The outcome was assessed by independent assessors as well as by patients self-report . A total of 20.7 % of the patients ( 27.5 % SAD , 9.7 % PD ) dropped out during treatment . The association between the alliance , competence/adherence , outcome and dropout was investigated using multiple regression analyses . RESULTS Higher therapist ' competence/adherence early in the therapy was associated with a better outcome among PD patients , lower competence/adherence was associated with dropout among SAD patients . Higher rating of the alliance late in the therapy was associated with a better outcome , whereas lower alliance rating late in the therapy was associated with dropout . CONCLUSION The findings indicate that the therapist competence/adherence and the working alliance have independent contributions to the outcome from CBT for anxiety disorders , but in different phases of the treatment The evaluation of treatment integrity ( therapist adherence and competence ) is a necessary condition to ensure the internal and external validity of psychotherapy research . However , the evaluation process is associated with high costs , because therapy sessions must be rated by experienced clinicians . It is debatable whether rating session segments is an adequate alternative to rating entire sessions . Four judges evaluated treatment integrity ( i.e. , therapist adherence and competence ) in 84 r and omly selected videotapes of cognitive-behavioral therapy for major depressive disorder , social anxiety disorder , and hypochondriasis ( from three different treatment outcome studies ) . In each case , two judges provided ratings based on entire therapy sessions and two on session segments only ( i.e. , the middle third of the entire sessions ) . Interrater reliability of adherence and competence evaluations proved satisfactory for ratings based on segments and the level of reliability did not differ from ratings based on entire sessions . Ratings of treatment integrity that were based on entire sessions and session segments were strongly correlated ( r=.62 for adherence and r=.73 for competence ) . The relationship between treatment integrity and outcome was comparable for ratings based on session segments and those based on entire sessions . However , significant relationships between therapist competence and therapy outcome were only found in the treatment of social anxiety disorder . Ratings based on segments proved to be adequate for the evaluation of treatment integrity . The findings demonstrate that session segments are an adequate and cost-effective alternative to entire sessions for the evaluation of therapist adherence and competence |
2,621 | 28,230,899 | This review suggests that shared care improves depression outcomes and probably has mixed or limited effects on other outcomes .
Review findings support the growing evidence base for shared care in the management of depression , particularly stepped care models of shared care . | BACKGROUND Shared care has been used in the management of many chronic conditions with the assumption that it delivers better care than primary or specialty care alone ; however , little is known about the effectiveness of shared care .
OBJECTIVES To determine the effectiveness of shared care health service interventions design ed to improve the management of chronic disease across the primary /specialty care interface .
Which shared care interventions or portions of shared care interventions are most effective?2 .
What do the most effective systems have in common ? | Objective : To investigate the lifelong health effects , costs , and cost-effectiveness of a quality improvement collaborative focusing on improving diabetes management in an integrated care setting . Study Design and Methods : Economic evaluation from a healthcare perspective with lifetime horizon alongside a nonr and omized , controlled , before-after study in the Netherl and s. Analyses were based on 1861 diabetes patients in 6 intervention and 9 control regions , representing 37 general practice s and 13 out-patient clinics . Change in the United Kingdom Prospect i ve Diabetes Study score , remaining lifetime , and costs per quality -adjusted life year gained were calculated . Probabilistic life tables were constructed using the United Kingdom Prospect i ve Diabetes Study risk engine , a vali date d diabetes model , and nonparametric bootstrapping of individual patient data . Results : Annual United Kingdom Prospect i ve Diabetes Study risk scores reduced for cardiovascular events ( hazard ratio : 0.83 and 0.98 ) and cardiovascular mortality ( hazard ratio : 0.78 and 0.88 ) for men and women , respectively . Life expectancy improved by 0.97 and 0.76 years for men and women , and quality -adjusted life years by 0.44 and 0.37 , respectively . Higher life expectancy in the intervention group increased lifelong costs by & OV0556;860 for men and & OV0556;645 for women . Initial program costs were about & OV0556;22 per patient . The incremental costs per quality -adjusted life year were & OV0556;1937 for men and & OV0556;1751 for women compared with usual care costs . There is a probability > 95 % that the collaborative is cost-effective , using a threshold of & OV0556;20,000 per quality -adjusted life year . Conclusion : Optimizing integrated and patient-centered diabetes care through a quality -improvement collaborative is cost-effective compared with usual care An evaluation was undertaken on the effectiveness and efficiency of care coordination as a means of delivering health services to Australian veterans with a diagnosis of congestive heart failure . The veterans participated in a r and omized controlled trial of care coordination that was supported by the Department of Veterans ' Affairs ( DVA ) . Of 490 veterans who were recruited , 409 were surveyed at baseline ( 214 in the intervention group and 195 controls ) . At follow-up , 288 were surveyed ( 155 intervention and 133 controls ) . Information on cost of care and quality of life ( QOL ) was collected before the commencement of coordinated care and at follow-up after 12 months . Cost of care data were obtained from DVA records . Information on QOL was obtained from telephone interviews , using the Short Form ( SF-12 ) Health Survey and the EuroQol Group EQ-5D survey . There were no significant differences in costs of care between the intervention ( coordinated care ) and control groups of veterans . Nor were there significant differences between the intervention and control groups in QOL measurements with either of the evaluation tools that were used . Because evidence of benefit from coordinated care may be slow to emerge in patients with chronic disease , it would be desirable for future work in this area to include long term , good quality comparative studies on selected veteran population s. Such studies should measure QOL and economic outcomes in addition to clinical indicators Abstract Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes . In the United Kingdom , clinical care is primarily provided by general practitioners ( GPs ) rather than hospital specialists . Intermediate care clinics for diabetes ( ICCD ) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors . This study aims to ( 1 ) compare patients with type 2 diabetes registered with practice s that have access to an ICCD service with those that have access only to usual hospital care ; ( 2 ) assess the cost-effectiveness of the intervention ; and ( 3 ) explore the views and experiences of patients , health professionals and other stakeholders . Methods / Design This two-arm cluster r and omized controlled trial ( with integral economic evaluation and qualitative study ) is set in general practice s in three UK Primary Care Trusts . Practice s are r and omized to one of two groups with patients referred to either an ICCD ( intervention ) or to hospital care ( control ) . Intervention group : GP practice s in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist . Patients are review ed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice .or Control group : St and ard GP care , with referral to secondary care as required , but no access to ICCD . Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control . The primary outcome is the proportion of participants reaching three risk factor targets : HbA1c ( ≤7.0 % ) ; blood pressure ( < 140/80 ) ; and cholesterol ( < 4 mmol/l ) , at the end of the 18-month intervention period . The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD ) and stroke assessed by the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) risk engine . Other secondary outcomes include body mass index and waist circumference , use of medication , reported smoking , emotional adjustment , patient satisfaction and views on continuity , costs and health related quality of life . We aim ed to r and omize 50 practice s and recruit 2,555 patients . Discussion Forty-nine practice s have been r and omized , 1,997 patients have been recruited to the trial , and 20 patients have been recruited to the qualitative study . Results will be available late 2012.Trial registration [ Clinical Trials.gov : Identifier NCT00945204 Objective : To assess the cost effectiveness and cost effectiveness acceptability of symptom control delivered by shared care ( SCSC ) and aggressive treatment delivered in hospital ( ATH ) for established rheumatoid arthritis ( RA ) . Methods : Economic data were collected within the British Rheumatoid Outcome Study Group r and omised controlled trial of SCSC and ATH . A broad perspective was used ( UK National Health Service , social support services and patients ) . Cost per quality adjusted life year ( QALY ) gained , net benefit statistics and cost effectiveness acceptability curves were estimated . Costs and outcomes were discounted at 3.5 % . Sensitivity analysis tested the robustness of the results to analytical assumptions . Results : The mean ( SD ) cost per person was £ 4540 ( 4700 ) in the SCSC group and £ 4440 ( 4900 ) in the ATH group . The mean ( SD ) QALYs per person for 3 years were 1.67 ( 0.56 ) in the SCSC group and 1.60 ( 0.60 ) in the ATH group . If decision makers are prepared to pay ⩾£2000 to gain 1 QALY , SCSC is likely to be cost effective in 60–90 % of cases . Conclusions : The primary economic analysis and sensitivity analyses indicate that SCSC is likely to be more cost effective than ATH in 60–90 % of cases . This result seems to be robust to assumptions required by the analysis . This study is one of a limited number of r and omised controlled trials to collect detailed re source use and health status data and estimate the costs and QALYs of treatment for established RA . This trial is one of the largest RA studies to use the EuroQol Background To estimate the proportion of diabetic patients ( DPts ) with peripheral vascular disease treated at a primary health care site after an endocrinologist-based intervention , who meet ATP III and Steno targets of metabolic control , as well as to compare the outcome with the results of the patients treated by endocrinologists . Methods A controlled , prospect i ve over 30-months period study was conducted in area 7 of Madrid . One hundred twenty six eligible diabetic patients diagnosed as having peripheral vascular disease between January 2003 and June 2004 were included in the study . After a treatment period of three months by the Diabetes team at St Carlos Hospital , 63 patients were r and omly assigned to continue their follow up by diabetes team ( Group A ) and other 63 to be treated by the family physicians ( FP ) at primary care level with continuous diabetes team coordination ( Group B ) . 57 DPts from Group A and 59 from Group B , completed the 30 months follow-up period . At baseline both groups were similar in age , weight , time from diagnosis and metabolic control . The main outcomes of this study were the proportion of patients meeting ATP III and Steno goals for HbA1c ( % ) , Cholesterol , HDL cholesterol , LDL cholesterol , triglycerides , blood pressure , albumine-to-creatinine excretion ratio ( ACR ) , body mass index ( BMI ) , waist circumference ( WC ) , anti-aggregation treatment and smoking status . Results At the end of the follow up , no differences were found between the groups . More than 37 % of diabetic patients assigned to be treated by FP achieved a HbA1c < 6.5 % , more than 50 % a ACR < 30 mg/g , and more than 80 % reached low risk values for cholesterol , LDL cholesterol , triglycerides , diastolic blood pressure and were anti-aggregated , and 12 % remained smokers . In contrast , less than 45 % achieved a systolic blood pressure < 130 mm Hg , less than 12 % had a BMI < 25 Kg.m-2 ( versus 23 % in group A ; p < 0.05 ) and 49%/30 % ( men/women ) had a waist circumference of low risk . Conclusion Improvements in metabolic control among diabetic patients with peripheral vascular disease treated at a primary health care setting is possible , reaching similar results to the patients treated at a specialized level . Despite such an improvement , body weight control remains more than poor in both levels , mainly at primary care level . General practitioner and endocrinologist coordination care may be important to enhance diabetes management in primary care setting s . Trial registration Clinical Trial number IS RCT Objective : Despite evidence demonstrating that risk-factor management is effective in reducing recurrent cerebrovascular disease , there are very few structured care programmes for stroke survivors . The aim was to implement and evaluate an integrated care programme in stroke . Methods : 186 patients with stroke were r and omised to either the treatment ( integrated care ) or control ( usual care ) group and were followed up over 12 months . The Integrated Care for the Reduction of Secondary Stroke ( ICARUSS ) model of integrated care involved collaboration between a specialist stroke service , a hospital coordinator and a patient ’s general practitioner . The primary aim was to promote the management of vascular risk factors through ongoing patient contact and education . Results : In the 12 months poststroke , systolic blood pressure ( sBP ) decreased in the treatment group but increased in controls . The group difference was significant , and remained so when age , sex , disability and sBP at discharge were accounted for ( p = 0.04 ) . Treatment patients also exhibited better modification of body mass index ( p = 0.007 ) and number of walks taken ( p<0.001 ) than controls . Rankin scores indicated significantly reduced disability in treatment patients relative to controls in the year poststroke ( p = 0.003 ) . Conclusions : Through an integrated system of education , advice and support to both patient and GP , the ICARUSS model was effective in modifying a variety of vascular risk factors and therefore should decrease the likelihood or recurrent stroke or vascular event Background Evidence -based practice s design ed for large urban clinics are not necessarily portable into smaller isolated clinics . Implementing practice -based collaborative care for depression in smaller primary care clinics presents unique challenges because it is often not feasible to employ on-site psychiatrists . Objective The purpose of the Telemedicine Enhanced Antidepressant Management ( TEAM ) study was to evaluate a telemedicine-based collaborative care model adapted for small clinics without on-site psychiatrists . Design Matched sites were r and omized to the intervention or usual care . Participants Small VA Community-based outpatient clinics with no on-site psychiatrists , but access to telepsychiatrists . In 2003–2004 , 395 primary care patients with PHQ9 depression severity scores ≥12 were enrolled , and followed for 12 months . Patients with serious mental illness and current substance dependence were excluded . Measures Medication adherence , treatment response , remission , health status , health-related quality of life , and treatment satisfaction . Results The sample comprised mostly elderly , white , males with substantial physical and behavioral health comorbidity . At baseline , subjects had moderate depression severity ( Hopkins Symptom Checklist , SCL-20 = 1.8 ) , 3.7 prior depression episodes , and 67 % had received prior depression treatment . Multivariate analyses indicated that intervention patients were more likely to be adherent at both 6 ( odds ratio [ OR ] = 2.1 , p = .04 ) and 12 months ( OR = 2.7 , p = .01 ) . Intervention patients were more likely to respond by 6 months ( OR = 2.0 , p = .02 ) , and remit by 12 months ( OR = 2.4 , p = .02 ) . Intervention patients reported larger gains in mental health status and health-related quality of life , and reported higher satisfaction . Conclusions Collaborative care can be successfully adapted for primary care clinics without on-site psychiatrists using telemedicine technologies To test the feasibility and efficacy of a multifaceted model of shared care for men after completion of treatment for prostate cancer Background A new model of complex diabetes care is provided by a multidisciplinary team which incorporates general practitioner ( GP ) Clinical Fellows supported by an Endocrinologist and diabetes educator within a community-based general practice setting . This study evaluates the health and clinical benefits of the new model of care , assesses the acceptability of the model to patients , GPs and other health professionals , and examines the cost-effectiveness of the model . Methods / Design The study is an open , non-inferiority r and omised controlled trial with data collected at baseline , 6 and 12 months . Participants are identified from new patients on hospital-based diabetes outpatient clinic waiting lists and new GP referrals . Eligible consenting patients are r and omised to either a community practice site ( intervention ) or a hospital site ( usual care ) . In the intervention model , medical care is led by a GP Clinical Fellow in partnership with an Endocrinologist . Quantitative measures include clinical indicators with HbA1c as the primary outcome ; patient-reported outcomes include health-related quality of life , mental health and satisfaction with care . Qualitative methods will be used to explore the perspectives and experiences of patients and providers regarding the new model of care . An economic evaluation will also be undertaken . Discussion This model of care seeks to improve the quality and safety of healthcare at the interface between the hospital and primary care sectors for patients with complex diabetes . The study will provide empirical evidence about the impact of the model of care on health outcomes , patient and clinician satisfaction , as well as any economic impacts . Trial registration Clinical Trials Registry Number : OBJECTIVE Generalized anxiety and panic disorders are a burden on the society because they are costly and have a significant adverse effect on quality of life . The aim of this study was to evaluate the cost-utility of a collaborative stepped care intervention for panic disorder and generalized anxiety disorder in primary care compared to care as usual from a societal perspective . METHODS The design of the study was a two armed cluster r and omized controlled trial . In total 43 primary care practice s in the Netherl and s participated in the study . Eventually , 180 patients were included ( 114 collaborative stepped care , 66 care as usual ) . Baseline measures and follow-up measures ( 3 , 6 , 9 and 12 months ) were assessed using question naires . We applied the TiC-P , the SF-HQL and the EQ-5D respectively measuring health care utilization , production losses and health related quality of life . RESULTS The average annual direct medical costs in the collaborative stepped care group were 1854 Euro ( 95 % C.I. , 1726 to 1986 ) compared to € 1503 ( 95 % C.I. , 1374 to 1664 ) in the care as usual group . The average quality of life years ( QALYs ) gained was 0.05 higher in the collaborative stepped care group , leading to an incremental cost effectiveness ratio ( ICER ) of 6965 Euro per QALY . Inclusion of the productivity costs , consequently reflecting the full societal costs , decreased the ratio even more . CONCLUSION The study showed that collaborative stepped care was a cost effective intervention for panic disorder and generalized anxiety disorder and was even dominant when a societal perspective was taken . TRIAL REGISTRATION trialregister.nl , Netherl and s Trial Register NTR107 CONTEXT Chronic pain is common in primary care patients and is associated with distress , disability , and increased health care use . OBJECTIVE To assess whether a collaborative intervention can improve chronic pain-related outcomes , including comorbid depression severity , in a Department of Veterans Affairs primary care setting . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized controlled trial of a collaborative care assistance with pain treatment intervention vs treatment as usual at 5 primary care clinics of 1 Department of Veterans Affairs Medical Center . Forty-two primary care clinicians were r and omized to the assistance with pain treatment intervention group or the treatment as usual group . The 401 patients had musculoskeletal pain diagnoses , moderate or greater pain intensity , and disability lasting 12 weeks or longer and were assigned to the same treatment groups as their clinicians . Recruitment occurred from January 2006 to January 2007 and follow-up concluded in January 2008 . INTERVENTION Assistance with pain treatment included a 2-session clinician education program , patient assessment , education and activation , symptom monitoring , feedback and recommendations to clinicians , and facilitation of specialty care . MAIN OUTCOME MEASURES Changes over 12 months in pain-related disability ( Rol and -Morris Disability Question naire , range of 0 - 24 ) , pain intensity ( Chronic Pain Grade [ CPG ] Pain Intensity subscale , range of 0 - 100 ) , and depression ( Patient Health Question naire 9 [ PHQ-9 ] , range of 0 - 27 ) , measured as beta coefficients ( difference in slopes in points per month ) . RESULTS Intervention patients had a mean ( SD ) of 10.6 ( 4.5 ) contacts with the assistance with pain treatment team . Compared with the patients receiving treatment as usual , intervention patients showed greater improvements in pain-related disability ( Rol and -Morris Disability Question naire beta , -0.101 [ 95 % confidence interval { CI } , -0.163 to -0.040 ] ; P = .004 and CPG Pain Intensity subscale beta , -0.270 [ 95 % CI , -0.480 to -0.061 ] ; P = .01 ) . Among patients with baseline depression ( PHQ-9 score > or = 10 ) , there was greater improvement in depression severity in patients receiving the intervention compared with patients receiving treatment as usual ( PHQ-9 beta , -0.177 [ 95 % CI , -0.295 to -0.060 ] ; P = .003 ) . The differences in scores between baseline and 12 months for the assistance with pain treatment intervention group and the treatment as usual group , respectively , were -1.4 vs -0.2 for the Rol and -Morris Disability Question naire , -4.7 vs -0.6 for the CPG Pain Intensity subscale , and -3.7 vs -1.2 for PHQ-9 . CONCLUSION The assistance with pain treatment collaborative intervention result ed in modest but statistically significant improvement in a variety of outcome measures . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00129480 BACKGROUND Recent national guidelines emphasize the requirement for all general practitioners to manage drug users within a shared care scheme and suggest that a primary health care liaison worker ( PHCLW ) may facilitate these arrangements . We undertook a group-r and omized , r and omized controlled trial to determine the effectiveness of a PHCLW in promoting shared care . METHODS Primary health care teams in Stockport Health Authority , North West Engl and , were r and omly allocated to either an intervention arm , who were offered the services of a PHCLW , or to a control arm , who were offered st and ard support from the community drug team ( CDT ) . The proportion of CDT clients with a history of regular opiate misuse who were in shared care 12 months after r and omization was compared across study arms . RESULTS Eighteen ( 24.0 per cent ) of the 75 CDT clients in the intervention arm but none of the 80 CDT clients in the control arm were in shared care at 12 months ( chi2 = 9.37 , df = 1 , p < 0.01 ; 95 per cent confidence interval 8.6 - 39.4 per cent ) . CONCLUSION A PHCLW can significantly increase the number of CDT clients in shared care arrangements Background Depression constitutes a significant public health burden and is associated is with high level of individual suffering . Insufficient human and material re sources impede the provision of adequate care for persons with the condition in low- and middle-income countries . It is commonly recognized that , to bridge this treatment gap , it is essential to integrate the treatment of depression into primary health care system . Methods / Design STEPCARE is a two-arm parallel cluster r and omized controlled trial to compare a stepped-care intervention package for depression in primary health care with care as usual in Nigeria . R and omization was conducted at the level of the participating primary health care clinics , while interventions are delivered to consenting individual participants who screen positive on the 9-item patient health question naire ( PHQ-9 score ≥ 11 ) and fulfil the DSM-IV criteria for major depression . Intervention delivered by trained primary health care workers ( PHCW ) supported by general physicians and psychiatrists as needed is in 3 steps determined by response to treatment . Each step consists of psychological interventions ( including psychoeducation , activity scheduling , social network reactivation and problem solving treatment ) offered to all participants and , depending on severity and response , medication . Primary outcome , assessed at 12 months following recruitment into the trial , is recovery from depression as shown by a PHQ-9 score of less than 6 . Secondary outcomes include changes in disability , quality of life and service utilization assessed at 6 and 12 months . Discussion The stepped care model examines the effectiveness of an intervention package for depression in which the intensity of treatment is determined by the clinical need of the patients . This approach is design ed to make the most efficient use of available re sources .Trial registration IS RCT N46754188 ( ISRTCN registry at isrtcn.com ; registered 23 September 2013 The objective of this study was to evaluate the effect of integrated health management model on the health of older adults with diabetes . The 100 older adults with diabetes who gave informed consent were r and omly allocated 1:1 into management and control groups . The integrated health management model was applied in the former while the latter was only given usual care . This model included the following components : health record establishment , health evaluation and health management ( such as : diet advice , psychological aspects of health , education/skills training on health self-management , regular blood glucose monitoring , long-term diabetes drug monitoring , etc . ) . After 18 months , differences in three categories of variables ( subjective grading items , objective measurement health indices and health service utilization ) between the two groups before and after the intervention were assessed with t-test , χ(2)-test and mixed model analysis . The management group demonstrated improvement on the following variables : health knowledge score , self-evaluated psychological conditions , overall self-evaluated health conditions , diet score , physical activity duration per week , regular blood sugar monitoring , waist-to-hip ratio , diastolic blood pressure and fasting blood sugar , the days of hospital admissions in the preceding 6 months . Mixed model analysis showed that gender , age , self-evaluated health status , self-evaluated psychological status , education level and resident status were important factors affecting health indices . This study demonstrated that integrated health management model was effectiveness in improving the health of older adults with diabetes BACKGROUND Chronic kidney disease ( CKD ) is highly prevalent in patients with diabetes or hypertension in primary care . A shared care model could improve quality of care in these patients AIM To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension . Design and setting A cluster r and omised controlled trial in nine general practice s in The Netherl and s. METHOD Five practice s were allocated to the shared care model and four practice s to usual care for 1 year . Primary outcome was the achievement of blood pressure targets ( 130/80 mmHg ) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m(2 ) . RESULTS Data of 90 intervention and 74 control patients could be analysed . Blood pressure in the intervention group decreased with 8.1 ( 95 % CI = 4.8 to 11.3)/1.1 ( 95 % CI = -1.0 to 3.2 ) compared to -0.2 ( 95 % CI = -3.8 to 3.3)/-0.5 ( 95 % CI = -2.9 to 1.8 ) in the control group . Use of lipid-lowering drugs , angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group ( 73 % versus 51 % , 81 % versus 64 % , and 15 % versus 1 % , respectively , [ P = 0.004 , P = 0.01 , and P = 0.002 ] ) . CONCLUSION A shared care model between GP , nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care Objective . To investigate the effect of a primary care model for COPD on process of care and patient outcome . Design . Controlled study with delayed intervention in control group . Setting . The GP delegates tasks to a COPD support service ( CSS ) and a practice nurse . The CSS offers logistic support to the practice through a patient register and recall system for annual history-taking and lung function measurement . It also forms the link with the chest physician for diagnostic and therapeutic advice . The practice nurse 's most important tasks are education and counselling . Subjects . A total of 44 practice s ( n = 22 for intervention and n = 22 for control group ) and 260 of their patients ≥40 years with obstructive lung diseases . Results . Within the intervention group planned visits increased from 16 % to 44 % and from 19 % to 25 % in the control condition ( difference between groups p = 0.014 ) . Annual lung function measurement rose from 17 % to 67 % in the intervention and from 11 % to 18 % in the control group ( difference between groups p = 0.001 ) . Compared with control , more but not statistically significant smokers received periodic advice to quit smoking ( p = 0.16 ) . At baseline 41 % of the intervention group were using their inhalers correctly and this increased to 54 % after two years ; it decreased in the control group from 47 to 29 % ( difference between groups p = 0.002 ) . The percentage of patients without exacerbation did not change significantly compared with the control condition . The percentage of the intervention group not needing emergency medication rose from 79 % to 84 % but decreased in the controls from 81 to 76 % ( difference between groups p = 0.08 ) . Conclusion . Combining different disciplines in one model has a positive effect on compliance with recommendations for monitoring patients , and improves the care process and some patient outcomes Objective To compare the clinical effectiveness of collaborative care with usual care in the management of patients with moderate to severe depression . Design Cluster r and omised controlled trial . Setting 51 primary care practice s in three primary care districts in the United Kingdom . Participants 581 adults aged 18 years and older who met ICD-10 ( international classification of diseases , 10th revision ) criteria for a depressive episode on the revised Clinical Interview Schedule . We excluded acutely suicidal patients and those with psychosis , or with type I or type II bipolar disorder ; patients whose low mood was associated with bereavement or whose primary presenting problem was alcohol or drug abuse ; and patients receiving psychological treatment for their depression by specialist mental health services . We identified potentially eligible participants by search ing computerised case records in general practice s for patients with depression . Interventions Collaborative care , including depression education , drug management , behavioural activation , relapse prevention , and primary care liaison , was delivered by care managers . Collaborative care involved six to 12 contacts with participants over 14 weeks , supervised by mental health specialists . Usual care was family doctors ’ st and ard clinical practice . Main outcome measures Depression symptoms ( patient health question naire 9 ; PHQ-9 ) , anxiety ( generalised anxiety disorder 7 ; GAD-7 ) , and quality of life ( short form 36 question naire ; SF-36 ) at four and 12 months ; satisfaction with service quality ( client satisfaction question naire ; CSQ-8 ) at four months . Results 276 participants were allocated to collaborative care and 305 allocated to usual care . At four months , mean depression score was 11.1 ( st and ard deviation 7.3 ) for the collaborative care group and 12.7 ( 6.8 ) for the usual care group . After adjustment for baseline depression , mean depression score was 1.33 PHQ-9 points lower ( 95 % confidence interval 0.35 to 2.31 , P=0.009 ) in participants receiving collaborative care than in those receiving usual care at four months , and 1.36 points lower ( 0.07 to 2.64 , P=0.04 ) at 12 months . Quality of mental health but not physical health was significantly better for collaborative care than for usual care at four months , but not 12 months . Anxiety did not differ between groups . Participants receiving collaborative care were significantly more satisfied with treatment than those receiving usual care . The number needed to treat for one patient to drop below the accepted diagnostic threshold for depression on the PHQ-9 was 8.4 immediately after treatment , and 6.5 at 12 months . Conclusions Collaborative care has persistent positive effects up to 12 months after initiation of the intervention and is preferred by patients over usual care . Trial registration number IS RCT N32829227 Papers p 1135 This week we publish an economic evaluation of screening for abdominal aortic aneurysms.1 It is based on a r and omised trial . At the same time the Lancet is publishing the clinical results .2 Unfortunately this is a common pattern — for the Lancet to publish the clinical results and us to publish the economic evaluation . We have decided that this ca n't continue . We will now consider for publication economic evaluations based on clinical trials only if the clinical results are su bmi tted to us as well . This is partly petulance , but we think our policy is reasonable . The clinical world BACKGROUND Patients with depression and poorly controlled diabetes , coronary heart disease , or both have an increased risk of adverse outcomes and high health care costs . We conducted a study to determine whether coordinated care management of multiple conditions improves disease control in these patients . METHODS We conducted a single-blind , r and omized , controlled trial in 14 primary care clinics in an integrated health care system in Washington State , involving 214 participants with poorly controlled diabetes , coronary heart disease , or both and coexisting depression . Patients were r and omly assigned to the usual-care group or to the intervention group , in which a medically supervised nurse , working with each patient 's primary care physician , provided guideline -based , collaborative care management , with the goal of controlling risk factors associated with multiple diseases . The primary outcome was based on simultaneous modeling of glycated hemoglobin , low-density lipoprotein ( LDL ) cholesterol , and systolic blood-pressure levels and Symptom Checklist-20 ( SCL-20 ) depression outcomes at 12 months ; this modeling allowed estimation of a single overall treatment effect . RESULTS As compared with controls , patients in the intervention group had greater overall 12-month improvement across glycated hemoglobin levels ( difference , 0.58 % ) , LDL cholesterol levels ( difference , 6.9 mg per deciliter [ 0.2 mmol per liter ] ) , systolic blood pressure ( difference , 5.1 mm Hg ) , and SCL-20 depression scores ( difference , 0.40 points ) ( P<0.001 ) . Patients in the intervention group also were more likely to have one or more adjustments of insulin ( P=0.006 ) , antihypertensive medications ( P<0.001 ) , and antidepressant medications ( P<0.001 ) , and they had better quality of life ( P<0.001 ) and greater satisfaction with care for diabetes , coronary heart disease , or both ( P<0.001 ) and with care for depression ( P<0.001 ) . CONCLUSIONS As compared with usual care , an intervention involving nurses who provided guideline -based , patient-centered management of depression and chronic disease significantly improved control of medical disease and depression . ( Funded by the National Institute of Mental Health ; Clinical Trials.gov number , NCT00468676 . ) OBJECTIVE To determine whether evidence -based socioculturally adapted collaborative depression care improves receipt of depression care and depression and diabetes outcomes in low-income Hispanic subjects . RESEARCH DESIGN AND METHODS This was a r and omized controlled trial of 387 diabetic patients ( 96.5 % Hispanic ) with clinical ly significant depression recruited from two public safety-net clinics from August 2005 to July 2007 and followed over 18 months . Intervention ( INT group ) included problem-solving therapy and /or antidepressant medication based on a stepped-care algorithm ; first-line treatment choice ; telephone treatment response , adherence , and relapse prevention follow-up over 12 months ; plus systems navigation assistance . Enhanced usual care ( EUC group ) included st and ard clinic care plus patient receipt of depression educational pamphlets and a community re source list . RESULTS INT patients had significantly greater depression improvement ( ≥50 % reduction in Symptom Checklist-20 depression score from baseline ; 57 , 62 , and 62 % vs. the EUC group 's 36 , 42 , and 44 % at 6 , 12 , and 18 months , respectively ; odds ratio 2.46–2.57 ; P < 0.001 ) . Mixed-effects linear regression models showed a significant study group – by – time interaction over 18 months in diabetes symptoms ; anxiety ; Medical Outcomes Study Short-Form Health Survey ( SF-12 ) emotional , physical , and pain-related functioning ; Sheehan disability ; financial situation ; and number of social stressors ( P = 0.04 for disability and SF-12 physical functioning , P < 0.001 for all others ) but no study group – by – time interaction in A1C , diabetes complications , self-care management , or BMI . CONCLUSIONS Socioculturally adapted collaborative depression care improved depression , functional outcomes , and receipt of depression treatment in predominantly Hispanic patients in safety-net clinics CONTEXT Most older adults with dementia will be cared for by primary care physicians , but the primary care practice environment presents important challenges to providing quality care . OBJECTIVE To test the effectiveness of a collaborative care model to improve the quality of care for patients with Alzheimer disease . DESIGN , SETTING , AND PATIENTS Controlled clinical trial of 153 older adults with Alzheimer disease and their caregivers who were r and omized by physician to receive collaborative care management ( n = 84 ) or augmented usual care ( n = 69 ) at primary care practice s within 2 US university-affiliated health care systems from January 2002 through August 2004 . Eligible patients ( identified via screening or medical record ) met diagnostic criteria for Alzheimer disease and had a self-identified caregiver . INTERVENTION Intervention patients received 1 year of care management by an interdisciplinary team led by an advanced practice nurse working with the patient 's family caregiver and integrated within primary care . The team used st and ard protocol s to initiate treatment and identify , monitor , and treat behavioral and psychological symptoms of dementia , stressing nonpharmacological management . MAIN OUTCOME MEASURES Neuropsychiatric Inventory ( NPI ) administered at baseline and at 6 , 12 , and 18 months . Secondary outcomes included the Cornell Scale for Depression in Dementia ( CSDD ) , cognition , activities of daily living , re source use , and caregiver 's depression severity . RESULTS Initiated by caregivers ' reports , 89 % of intervention patients triggered at least 1 protocol for behavioral and psychological symptoms of dementia with a mean of 4 per patient from a total of 8 possible protocol s. Intervention patients were more likely to receive cholinesterase inhibitors ( 79.8 % vs 55.1 % ; P = .002 ) and antidepressants ( 45.2 % vs 27.5 % ; P = .03 ) . Intervention patients had significantly fewer behavioral and psychological symptoms of dementia as measured by the total NPI score at 12 months ( mean difference , -5.6 ; P = .01 ) and at 18 months ( mean difference , -5.4 ; P = .01 ) . Intervention caregivers also reported significant improvements in distress as measured by the caregiver NPI at 12 months ; at 18 months , caregivers showed improvement in depression as measured by the Patient Health Question naire-9 . No group differences were found on the CSDD , cognition , activities of daily living , or on rates of hospitalization , nursing home placement , or death . CONCLUSIONS Collaborative care for the treatment of Alzheimer disease result ed in significant improvement in the quality of care and in behavioral and psychological symptoms of dementia among primary care patients and their caregivers . These improvements were achieved without significantly increasing the use of antipsychotics or sedative-hypnotics . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00246896 Background Meta-analyses show collaborative care models ( CCMs ) with nurse care management are effective for improving primary care for depression . This study aim ed to develop CCM approaches that could be sustained and spread within Veterans Affairs ( VA ) . Evidence -based quality improvement ( EBQI ) uses QI approaches within a research / clinical partnership to re design care . The study used EBQI methods for CCM re design , tested the effectiveness of the locally adapted model as implemented , and assessed the context ual factors shaping intervention effectiveness . Methods The study intervention is EBQI as applied to CCM implementation . The study uses a cluster r and omized design as a formative evaluation tool to test and improve the effectiveness of the re design process , with seven intervention and three non-intervention VA primary care practice s in five different states . The primary study outcome is patient antidepressant use . The context evaluation is descriptive and uses subgroup analysis . The primary context evaluation measure is naturalistic primary care clinician ( PCC ) predilection to adopt CCM.For the r and omized evaluation , trained telephone research interviewers enrolled consecutive primary care patients with major depression in the evaluation , referred enrolled patients in intervention practice s to the implemented CCM , and re-surveyed at seven months . Results Interviewers enrolled 288 CCM site and 258 non-CCM site patients . Enrolled intervention site patients were more likely to receive appropriate antidepressant care ( 66 % versus 43 % , p = 0.01 ) , but showed no significant difference in symptom improvement compared to usual care . In terms of context , only 40 % of enrolled patients received complete care management per protocol . PCC predilection to adopt CCM had substantial effects on patient participation , with patients belonging to early adopter clinicians completing adequate care manager follow-up significantly more often than patients of clinicians with low predilection to adopt CCM ( 74 % versus 48%% , p = 0.003 ) . Conclusions Depression CCM design ed and implemented by primary care practice s using EBQI improved antidepressant initiation . Combining QI methods with a r and omized evaluation proved challenging , but enabled new insights into the process of translating research -based CCM into practice . Future research on the effects of PCC attitudes and skills on CCM results , as well as on enhancing the link between improved antidepressant use and symptom outcomes , is needed . Trial Registration Clinical Trials.gov : Background : Specialist medical practitioners have conducted clinics in primary care and rural hospital setting s for a variety of reasons in many different countries . Such clinics have been regarded as an important policy option for increasing the accessibility and effectiveness of specialist services and their integration with primary care services . Objectives : To undertake a descriptive overview of studies of specialist outreach clinics and to assess the effectiveness of specialist outreach clinics on access , quality , health outcomes , patient satisfaction , use of services , and costs . Search strategy : We search ed the Cochrane Effective Practice and Organisation of Care ( EPOC ) specialised register ( March 2002 ) , the Cochrane Controlled Trials Register ( CCTR ) ( Cochrane Library Issue 1 , 2002 ) , MEDLINE ( including HealthStar ) ( 1966 to May 2002 ) , EMBASE ( 1988 to March 2002 ) , CINAHL ( 1982 to March 2002 ) , the Primary - Secondary Care Data base previously maintained by the Centre for Primary Care Research in the Department of General Practice at the University of Manchester , a collection of studies from the UK collated in Specialist Outreach Clinics in General Practice ( Rol and 1998 ) , and the reference lists of all retrieved articles . Selection criteria : R and omised trials , controlled before and after studies and interrupted time series analyses of visiting specialist outreach clinics in primary care or rural hospital setting s , either providing simple consultations or as part of complex multifaceted interventions . The participants were patients , specialists , and primary care providers . The outcomes included objective measures of access , quality , health outcomes , satisfaction , service use , and cost . Data collection and analysis : Four review ers working in pairs independently extracted data and assessed study quality . Main results : 73 outreach interventions were identified covering many specialties , countries and setting s. Nine studies met the inclusion criteria . Most comparative studies came from urban non-disadvantaged population s in developed countries . Simple ‘ shifted out patients ’ styles of specialist outreach were shown to improve access , but there was no evidence of impact on health outcomes . Specialist outreach as part of more complex multifaceted interventions involving collaboration with primary care , education or other services was associated with improved health outcomes , more efficient and guideline -consistent care , and less use of inpatient services . The additional costs of outreach may be balanced by improved health outcomes . Authors ' conclusions : This review supports the hypothesis that specialist outreach can improve access , outcomes and service use , especially when delivered as part of a multifaceted intervention . The benefits of simple outreach models in urban non-disadvantaged setting s seem small . There is a need for good comparative studies of outreach in rural and disadvantaged setting s where outreach may confer most benefit to access and health outcomes Background and objectives In And alusia there were no studies including a representative sample of children and adolescent population assessing growth and weight increase . Our objectives were to develop reference st and ards for weight , height and BMI for the And alusian pediatric population , from 3 to 18 years of age for both genders , and to identify the final adult height in And alusia . Subjects and methods Two sample s were collected . The first included individuals from 3 to 18 years of age ( 3592 girls and 3605 boys ) . They were stratified according type of study center , size of population of origin , age ( 32 categories of 0.5 years ) and gender , using cluster sampling . Subjects from > 18 to 23 years of age ( 947 women and 921 men ) were sample d in 6 non-university educational centers and several university centers in Granada . Exclusion criteria included sons of non-Spanish mother or father , and individuals with chronic conditions and /or therapies affecting growth . Two trained fellows collected the data through February to December 2004 , for the first sample , and through January to May 2005 , for the second . Reference curves were adjusted using Cole 's LMS method , and the quality of the adjustment was assessed using the tests proposed by Royston . In addition , a sensitivity analysis was applied to the final models obtained . Results Data for 9065 cases ( 4539 women and 4526 men ) were obtained ; 79.39 % ( n = 7197 ) in the up to 18 years of age group . In the first sampling only 0.07 % ( 3 girls and 2 boys ) refused to participate in the study . In addition , 327 students ( 4.5 % ) were absent when sampling was done . We present mean and st and ard deviation fort height , weight and BMI at 0.5 years intervals , from 3 to 23 years of age , for both genders . After adjustment with the different models , percentiles for height , weight ( percentiles 3 , 5 , 10 , 25 , 50 , 75 , 90 , 95 , and 97 ) and BMI ( percentiles 3 , 5 , 50 , 85 , 95 , and 97 ) are presented for both genders . Conclusion This is the first study in And alusia with a representative sample from the child-juvenile population to investigate weight , height and BMI in subjects from 3 to 23 years of age . The great variability observed in the values from sample of 18 to 23 years of age individuals , ensures the inclusion of extreme values , although r and om sampling was not used . There still is a lack of st and ard reference values for the And alusian population younger done 3 years of age Background Millions of people who need treatment for substance use disorders ( SUD ) do not receive it . Evidence -based practice s for treating SUD exist , and some are appropriate for delivery outside of specialty care setting s. Primary care is an opportune setting in which to deliver SUD treatment because many individuals see their primary care providers at least once a year . Further , the Patient Protection and Affordable Care Act ( PPACA ) increases coverage for SUD treatment and is increasing the number of individuals seeking primary care services . In this article , we present the protocol for a study testing the effects of an organizational readiness and service delivery intervention on increasing the uptake of SUD treatment in primary care and on patient outcomes . Methods / design In a r and omized controlled trial , we test the combined effects of an organizational readiness intervention consisting of implementation tools and activities and an integrated collaborative care service delivery intervention based on the Chronic Care Model on service system ( patient-centered care , utilization of substance use disorder treatment , utilization of health care services and adoption and sustainability of evidence -based practice s ) and patient ( substance use , consequences of use , health and mental health , and satisfaction with care ) outcomes . We also use a repeated measures design to test organizational changes throughout the study , such as acceptability , appropriateness and feasibility of the practice s to providers , and provider intention to adopt the practice s. We use provider focus groups , provider and patient surveys , and administrative data to measure outcomes . Discussion The present study responds to critical gaps in health care services for people with substance use disorders , including the need for greater access to SUD treatment and greater uptake of evidence -based practice s in primary care . We design ed a multi-level study that combines implementation tools to increase organizational readiness to adopt and sustain evidence -based practice s ( EBPs ) and tests the effectiveness of a service delivery intervention on service system and patient outcomes related to SUD services . Trial registration Current controlled trials : CONTEXT Few depressed older adults receive effective treatment in primary care setting s. OBJECTIVE To determine the effectiveness of the Improving Mood-Promoting Access to Collaborative Treatment ( IMPACT ) collaborative care management program for late-life depression . DESIGN R and omized controlled trial with recruitment from July 1999 to August 2001 . SETTING Eighteen primary care clinics from 8 health care organizations in 5 states . PARTICIPANTS A total of 1801 patients aged 60 years or older with major depression ( 17 % ) , dysthymic disorder ( 30 % ) , or both ( 53 % ) . INTERVENTION Patients were r and omly assigned to the IMPACT intervention ( n = 906 ) or to usual care ( n = 895 ) . Intervention patients had access for up to 12 months to a depression care manager who was supervised by a psychiatrist and a primary care expert and who offered education , care management , and support of antidepressant management by the patient 's primary care physician or a brief psychotherapy for depression , Problem Solving Treatment in Primary Care . MAIN OUTCOME MEASURES Assessment s at baseline and at 3 , 6 , and 12 months for depression , depression treatments , satisfaction with care , functional impairment , and quality of life . RESULTS At 12 months , 45 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline compared with 19 % of usual care participants ( odds ratio [ OR ] , 3.45 ; 95 % confidence interval [ CI ] , 2.71 - 4.38 ; P<.001 ) . Intervention patients also experienced greater rates of depression treatment ( OR , 2.98 ; 95 % CI , 2.34 - 3.79 ; P<.001 ) , more satisfaction with depression care ( OR , 3.38 ; 95 % CI , 2.66 - 4.30 ; P<.001 ) , lower depression severity ( range , 0 - 4 ; between-group difference , -0.4 ; 95 % CI , -0.46 to -0.33 ; P<.001 ) , less functional impairment ( range , 0 - 10 ; between-group difference , -0.91 ; 95 % CI , -1.19 to -0.64 ; P<.001 ) , and greater quality of life ( range , 0 - 10 ; between-group difference , 0.56 ; 95 % CI , 0.32 - 0.79 ; P<.001 ) than participants assigned to the usual care group . CONCLUSION The IMPACT collaborative care model appears to be feasible and significantly more effective than usual care for depression in a wide range of primary care practice Background Mood and anxiety disorders are highly prevalent and have a large impact on the lives of the affected individuals . Therefore , optimal treatment of these disorders is highly important . In this study we will examine the effectiveness of a stepped care program for primary care patients with mood and anxiety disorders . A stepped care program is characterized by different treatment steps that are arranged in order of increasing intensity . Methods This study is a r and omised controlled trial with two conditions : stepped care and care as usual , whereby the latter forms the control group . The stepped care program consists of four evidence based interventions : ( 1 ) Watchful waiting , ( 2 ) Guided self-help , ( 3 ) Problem Solving Treatment and ( 4 ) Medication and /or specialized mental health care . The study population consists of primary care attendees aged 18–65 years . Screeners are sent to all patients of the participating general practitioners . Individuals with a Diagnostic and Statistical Manual of mental disorders ( DSM ) diagnosis of major depression , dysthymia , panic disorder ( with or without agoraphobia ) , generalized anxiety disorder , or social phobia are included as well as individuals with minor depression and anxiety disorders . Primary focus is the reduction of depressive and anxiety symptoms . Both conditions are monitored at 8 , 16 and 24 weeks . Discussion This study evaluates the effectiveness of a stepped care program for patients with depressive and anxiety disorder . If effective , a stepped care program can form a worthwhile alternative for care as usual . Strengths and limitations of this study are discussed . Trial Registration Current Controlled Trails : IS RCT N17831610 Background : Chronic obstructive pulmonary disease ( COPD ) generates a high burden on health care , and hospital admissions represent a substantial proportion of the overall costs of the disease . Integrated care ( IC ) has shown efficacy to reduce hospitalisations in COPD patients at a pilot level . Deployment strategies for IC services require assessment of effectiveness at the health care system level . Aims : The aim of this study was to explore the effectiveness of a community-based IC service in preventing hospitalisations and emergency department ( ED ) visits in stable frail COPD patients . Methods : From April to December 2005 , 155 frail community-dwelling COPD patients were r and omly allocated either to IC ( n=76 , age 73 ( 8) years , forced expiratory volume during the first second , FEV1 41(19 ) % predicted ) or usual care ( n=84 , age 75(9 ) years , FEV1 44 ( 20 ) % predicted ) and followed up for 12 months . The IC intervention consisted of the following : ( a ) patient ’s empowerment for self-management ; ( b ) an individualised care plan ; ( c ) access to a call centre ; and ( d ) coordination between the levels of care . Thereafter , hospital admissions , ED visits and mortality were monitored for 6 years . Results : IC enhanced self-management ( P=0.02 ) , reduced anxiety – depression ( P=0.001 ) and improved health-related quality of life ( P=0.02 ) . IC reduced both ED visits ( P=0.02 ) and mortality ( P=0.03 ) but not hospital admission . No differences between the two groups were seen after 6 years . Conclusion : The intervention improved clinical outcomes including survival and decreased the ED visits , but it did not reduce hospital admissions . The study facilitated the identification of two key requirements for adoption of IC services in the community : appropriate risk stratification of patients , and preparation of the community-based work force A r and omized controlled trial was conducted to compare three forms of diabetes follow-up : ( 1 ) general practitioner care , ( 2 ) a system of care shared between the general practitioner ( GP ) and clinic and ( 3 ) conventional clinic care . Two hundred and six diabetic patients without significant diabetes-related or other medical complications were r and omized to one of these follow-up systems . Metabolic control and blood pressure improved significantly and equally in all three groups ( p < 0.05 ) . The shared care group performed as well as or better than either of the other two groups in all other outcome measures . In particular , final attendance rates were 72 % for shared care compared with only 35 % for GP care and 53 % for clinic care . Data collection rates for shared care were comparable with the clinic group for r and om blood glucose ( 88.9 % vs 95.1 % ) , weight ( 93.5 % vs 98.3 % ) , and blood pressure ( 94.8 % vs 92.7 % ) . Only in the case of glycosylated haemoglobin did shared care have poorer data collection ( 66.0 % vs 98.4 % ) . In all these parameters , except blood pressure , shared care out-performed the GP group . We conclude that with adequate support from and communication with hospital-based diabetes services , GPs are capable of providing care appropriate to the needs of uncomplicated diabetic patients BACKGROUND Medical conditions are often complicated by major depression , with consequent additional impairment of quality of life . We aim ed to compare the effectiveness of an integrated treatment programme for major depression in patients with cancer ( depression care for people with cancer ) with usual care . METHODS SMaRT Oncology-2 is a parallel-group , multicentre , r and omised controlled effectiveness trial . We enrolled out patients with major depression from three cancer centres and their associated clinics in Scotl and , UK . Participants were r and omly assigned in a 1:1 ratio to the depression care for people with cancer intervention or usual care , with stratification ( by trial centre ) and minimisation ( by age , primary cancer , and sex ) with allocation concealment . Depression care for people with cancer is a manualised , multicomponent collaborative care treatment that is delivered systematic ally by a team of cancer nurses and psychiatrists in collaboration with primary care physicians . Usual care is provided by primary care physicians . Outcome data were collected up until 48 weeks . The primary outcome was treatment response ( ≥50 % reduction in Symptom Checklist Depression Scale [ SCL-20 ] score , range 0 - 4 ) at 24 weeks . Trial statisticians and data collection staff were masked to treatment allocation , but participants could not be masked to the allocations . Analyses were by intention to treat . This trial is registered with Current Controlled Trials , number IS RCT N40568538 . FINDINGS 500 participants were enrolled between May 12 , 2008 , and May 13 , 2011 ; 253 were r and omly allocated to depression care for people with cancer and 247 to usual care . 143 ( 62 % ) of 231 participants in the depression care for people with cancer group and 40 ( 17 % ) of 231 in the usual care group responded to treatment : absolute difference 45 % ( 95 % CI 37 - 53 ) , adjusted odds ratio 8·5 ( 95 % CI 5·5 - 13·4 ) , p<0·0001 . Compared with patients in the usual care group , participants allocated to the depression care for people with cancer programme also had less depression , anxiety , pain , and fatigue ; and better functioning , health , quality of life , and perceived quality of depression care at all timepoints ( all p<0·05 ) . During the study , 34 cancer-related deaths occurred ( 19 in the depression care for people with cancer group , 15 in the usual care group ) , one patient in the depression care for people with cancer group was admitted to a psychiatric ward , and one patient in this group attempted suicide . None of these events were judged to be related to the trial treatments or procedures . INTERPRETATION Our findings suggest that depression care for people with cancer is an effective treatment for major depression in patients with cancer . It offers a model for the treatment of depression comorbid with other medical conditions . FUNDING Cancer Research UK and Chief Scientist Office of the Scottish Government CONTEXT Improving the quality of mental health care requires moving clinical interventions from controlled research setting s into real-world practice setting s. Although such advances have been made for depression , little work has been performed for anxiety disorders . OBJECTIVE To determine whether a flexible treatment-delivery model for multiple primary care anxiety disorders ( panic , generalized anxiety , social anxiety , and posttraumatic stress disorders ) would be better than usual care ( UC ) . DESIGN , SETTING , AND PATIENTS A r and omized controlled effectiveness trial of Coordinated Anxiety Learning and Management ( CALM ) compared with UC in 17 primary care clinics in 4 US cities . Between June 2006 and April 2008 , 1004 patients with anxiety disorders ( with or without major depression ) , aged 18 to 75 years , English- or Spanish-speaking , were enrolled and subsequently received treatment for 3 to 12 months . Blinded follow-up assessment s at 6 , 12 , and 18 months after baseline were completed in October 2009 . INTERVENTION CALM allowed choice of cognitive behavioral therapy ( CBT ) , medication , or both ; included real-time Web-based outcomes monitoring to optimize treatment decisions ; and a computer-assisted program to optimize delivery of CBT by nonexpert care managers who also assisted primary care clinicians in promoting adherence and optimizing medications . MAIN OUTCOME MEASURES Twelve-item Brief Symptom Inventory ( BSI-12 ) anxiety and somatic symptoms score . Secondary outcomes included proportion of responders ( > or = 50 % reduction from pretreatment BSI-12 score ) and remitters ( total BSI-12 score < 6 ) . RESULTS A significantly greater improvement for CALM vs UC in global anxiety symptoms was found ( BSI-12 group mean differences of -2.49 [ 95 % confidence interval { CI } , -3.59 to -1.40 ] , -2.63 [ 95 % CI , -3.73 to -1.54 ] , and -1.63 [ 95 % CI , -2.73 to -0.53 ] at 6 , 12 , and 18 months , respectively ) . At 12 months , response and remission rates ( CALM vs UC ) were 63.66 % ( 95 % CI , 58.95%-68.37 % ) vs 44.68 % ( 95 % CI , 39.76%-49.59 % ) , and 51.49 % ( 95 % CI , 46.60%-56.38 % ) vs 33.28 % ( 95 % CI , 28.62%-37.93 % ) , with a number needed to treat of 5.27 ( 95 % CI , 4.18 - 7.13 ) for response and 5.50 ( 95 % CI , 4.32 - 7.55 ) for remission . CONCLUSION For patients with anxiety disorders treated in primary care clinics , CALM compared with UC result ed in greater improvement in anxiety symptoms , depression symptoms , functional disability , and quality of care during 18 months of follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00347269 OBJECTIVE This study compared the effectiveness of treating common mental disorders in a collaborative care program in a primary care setting and the effectiveness of treating such disorders through traditional referral of patients to mental health services . METHODS In a cluster r and omized controlled trial , 27 general practitioner practice s in the Netherl and s were design ated to provide either collaborative care or usual care . In the collaborative care condition , a mental health care professional worked on site at the primary care practice and was available to provide patients a maximum of five appointments if they were referred by the general practitioner . If indicated , referral to specialized mental health services followed . In the usual care condition , if indicated , general practitioners would refer patients to off-site specialized mental health services . The study included 165 patients . At baseline and at three , six , and 12 months , the study assessed patients ' psychopathology , patients ' quality of life , and patients ' and general practitioners ' satisfaction with the treatment provided . Delay in seeing a mental health provider , duration of treatment , number of appointments , and related treatment costs were assessed at 12 months . The data were analyzed with hierarchical linear models . RESULTS Level of patients ' psychopathology and quality of life significantly improved over time , and there were no significant differences between models of care . There was no significant difference in patients ' satisfaction with care in either condition . The collaborative care condition result ed in significantly higher satisfaction with services among general practitioners , shorter referral delay , reduced time in treatment , fewer appointments , and consequently lower treatment costs . CONCLUSIONS Collaborative care for a heterogeneous group of persons with common mental disorders seems to be as effective as the usual practice of referral to mental health services for reducing psychopathology , but it is significantly more efficient regarding referral delay , duration of treatment , number of appointments , and related treatment costs A two year follow-up of two matched groups of subjects with chronic severe mental illness was performed in order to evaluate a new psychiatric case management system . One group ( n=59 ) received care through psychiatric case management , using an assertive community treatment model that directly involved general practitioners . The other group , matched for age , sex , diagnostic group and number of hospital admissions , received st and ard outpatient care . Comparing the two years before and after case management , the experimental group showed a dramatic fall in inpatient admission days while the control group admission days remained the same ( median difference in admission days across matched subject pairs = 64.5 , 95 % C.I. from 134.5 to 16 ) . The experimental group remained out of hospital longer before first readmission ( Kaplan-Meier survival analysis , P=0.002 ) . This type of case management programme can shorten or prevent admissions to psychiatric hospitals of patients with chronic mental illness , and increase their time before readmission Background Chronic obstructive pulmonary disease ( COPD ) is a significant health problem worldwide . This r and omised controlled trial aims at testing a new approach that involves a registered nurse working in partnership with patients , general practitioners ( GPs ) and other health professionals to provide care to patients according to the evidence -based clinical practice guidelines . The aim is to determine the impact of this partnership on the quality of care and patient outcomes . Methods A cluster r and omised control trial design was chosen for this study . R and omisation occurred at practice level . GPs practising in South Western Sydney , Australia and their COPD patients were recruited for the study .The intervention was implemented by nurses specifically recruited and trained for this study . Nurses , working in partnership with GPs , developed care plans for patients based on the Australian COPD X guidelines . The aim was to optimise patient management , improve function , prevent deterioration and enhance patient knowledge and skills . Control group patients received ' usual ' care from their GPs . Data collection includes patient demographic profiles and their co-morbidities . Spirometry is being performed to assess patients ' COPD status and CO analyser to vali date their smoking status . Patients ' quality of life and overall health status are being measured by St George 's Respiratory Question naire and SF-12 respectively . Other patient measures being recorded include health service use , immunisation status , and knowledge of COPD . Qualitative methods will be used to explore participants ' satisfaction with the intervention and their opinion about the value of the partnership . Analysis Analysis will be by intention to treat . Intra-cluster ( practice ) correlation coefficients will be determined and published for all primary outcome variables to assist future research . The effect of the intervention on outcomes measured on a continuous scale will be estimated and tested using mixed model analysis of variance in which time and treatment group will be fixed effects and GP practice and subject nested within practice will be r and om effects . The effect of the intervention on the dichotomous variables ( such as smoking status , patient knowledge ) will be analysed using generalised estimating equations with a logistic link and a model structure that is analogous to that described above . Trial registration PURPOSE Scale-up and spread of evidence -based practice s is one of the most important challenges facing health care . We tested whether a statewide initiative , Depression Improvement Across Minnesota – Offering a New Direction ( DIAMOND ) , to implement the collaborative care model for depression in 75 primary care clinics result ed in patient outcome improvements corresponding to those reported in r and omized controlled trials . METHODS Health plans provided a new monthly payment to participating clinics after a 6-month intensive training program with ongoing data su bmi ssion , networking , and consultation . Implementation was staggered , with 5 sequences of 10 to 40 clinics every 6 months . Payers provided weekly contact information for members from participating clinics who were filling antidepressant prescriptions , and we conducted baseline and 6-month surveys of 1,578 patients about their care and outcomes . RESULTS There were 466 patients in DIAMOND clinics who received usual care before implementation ( UCB ) , 559 who received usual care in DIAMOND clinics after implementation ( UCA ) , 245 who received DIAMOND care after implementation ( DCA ) , and 308 who received usual care in comparison clinics ( UC ) . Patients who received DIAMOND care after implementation reported more collaborative care depression services than the 3 comparison groups ( 10.9 vs 6.4–6.7 , on a scale of 0 of 14 , where higher numbers indicate more services ; P < .001 ) and more satisfaction with their care ( 4.0 vs 3.4 on a scale 1 to 5 , in which higher scores indicate higher satisfaction ; P ≤.001 ) . Depression remission rates , however , were not significantly different among the 4 groups ( 36.4 % DCA vs 35.8 % UCB , 35.0 % UCA , 33.9 % UC ; P = .94 ) . CONCLUSIONS Despite the incentive of a supporting payment change and intensive training and support for clinics volunteering to participate , no difference in depression outcomes was documented . Specific unmeasured actions present in trials but not present in these clinics may be critical for successful outcome improvement Background Type 2 diabetes ( T2D ) brings significant human and healthcare costs . Its progressive nature means achieving normoglycaemia is increasingly difficult , yet critical to avoiding long term vascular complications . Nearly one-half of people with T2D have glycaemic levels out of target . Insulin is effective in achieving glycaemic targets , yet initiation of insulin is often delayed , particularly in primary care . Given limited access to specialist re sources and the size of the diabetes epidemic , primary care is where insulin initiation must become part of routine practice . This would also support integrated holistic care for people with diabetes . Our Stepping Up Program is based on a general practitioner ( GP ) and practice nurse ( PN ) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses . Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care . Methods This protocol is for a cluster r and omized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D . 224 patients between the ages of 18 and 80 years with T2D , on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5 % in the last six months will be recruited from 74 general practice s. The unit of r and omization is the practice . Primary outcome is change in glycated haemoglobin HbA1c ( measured as a continuous variable ) . We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5 % lower than control group at 12 months follow up . Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of < 7.0 % . We will also collect data on patient psychosocial outcomes and healthcare utilization and costs . Discussion The study is a pragmatic translational study with important potential implication s for people with T2D , healthcare professionals and funders of healthcare though making better use of scarce healthcare re sources , improving timely access to therapy that can improve disease outcomes .Trial registration Australian and New Zeal and Clinical Trials Registry Background Given the current lack of disease-modifying therapies , it is important to explore new models of longitudinal care for older adults with dementia that focus on improving quality of life and delaying functional decline . In a previous clinical trial , we demonstrated that collaborative care for Alzheimer ’s disease reduces patients ’ neuropsychiatric symptoms as well as caregiver stress . However , these improvements in quality of life were not associated with delays in subjects ’ functional decline . Trial design Parallel r and omized controlled clinical trial with 1:1 allocation . Participants A total of 180 community-dwelling patients aged ≥45 years who are diagnosed with possible or probable Alzheimer ’s disease ; subjects must also have a caregiver willing to participate in the study and be willing to accept home visits . Subjects and their caregivers are enrolled from the primary care and geriatric medicine practice s of an urban public health system serving Indianapolis , Indiana , USA . Interventions All patients receive best practice s primary care including collaborative care by a dementia care manager over two years ; this best practice s primary care program represents the local adaptation and implementation of our prior collaborative care intervention in the urban public health system . Intervention patients also receive in-home occupational therapy delivered in twenty-four sessions over two years in addition to best practice s primary care . The focus of the occupational therapy intervention is delaying functional decline and helping both subjects and caregivers adapt to functional impairments . The in-home sessions are tailored to the specific needs and goals of each patient-caregiver dyad ; these needs are expected to change over the course of the study . Objective To determine whether best practice s primary care plus home-based occupational therapy delays functional decline among patients with Alzheimer ’s disease compared to subjects treated in the control group . Outcomes The primary outcome is the Alzheimer ’s Disease Cooperative Studies Group Activities of Daily Living Scale ; secondary outcome measures are two performance-based measures including the Short Physical Performance Battery and Short Portable Sarcopenia Measure . Outcome assessment s for both the caregiver-reported scale and subjects ’ physical performance scales are completed in the subject ’s home . R and omizationEligible patient-care giver dyads will be stratified by clinic type and block r and omized with a computer developed r and omization scheme using a 1:1 allocation ratio . BlindingSingle blinded . Research assistants completing the outcome assessment s were blinded to the subjects ’ treatment group . Trial statusOngoing Clinical Trial . Gov identifierNCT01314950 ; date of completed registration 10 March 2011 ; date first patient r and omized 9 March AIMS To determine the effect of an integrated heart failure management programme , involving patient and family , primary and secondary care , on quality of life and death or hospital readmissions in patients with chronic heart failure . METHODS AND RESULTS This trial was a cluster r and omized , controlled trial of integrated primary / secondary care compared with usual care for patients with heart failure . The intervention involved clinical review at a hospital-based heart failure clinic early after discharge , individual and group education sessions , a personal diary to record medication and body weight , information booklets and regular clinical follow-up alternating between the general practitioner and heart failure clinic . Follow-up was for 12 months . One hundred and ninety-seven patients admitted to Auckl and Hospital with an episode of heart failure were enrolled in the study . There was no significant difference between the intervention and control groups for the combined end-point of death or hospital readmission . The physical dimension of quality of life showed a greater improvement in the intervention group from baseline to 12 months compared with the control group ( -11.1 vs -5.8 respectively , 2 P=0.015 ) . The main effect of the intervention was attributable to the prevention of multiple admissions ( 56 intervention group vs 95 control group , 2 P=0.015 ) and associated reduction in bed days . CONCLUSIONS This integrated management programme for patients with chronic heart failure improved quality of life and reduced total hospital admissions and total bed days IMPORTANCE Posttraumatic stress disorder ( PTSD ) is prevalent , persistent , and disabling . Although psychotherapy and pharmacotherapy have proven efficacious in r and omized clinical trials , geographic barriers impede rural veterans from engaging in these evidence -based treatments . OBJECTIVE To test a telemedicine-based collaborative care model design ed to improve engagement in evidence -based treatment of PTSD . DESIGN , SETTING , AND PARTICIPANTS The Telemedicine Outreach for PTSD ( TOP ) study used a pragmatic r and omized effectiveness trial design with intention-to-treat analyses . Out patients were recruited from 11 Department of Veterans Affairs ( VA ) community-based outpatient clinics serving predominantly rural veterans . Inclusion required meeting diagnostic criteria for current PTSD according to the Clinician-Administered PTSD Scale . Exclusion criteria included receiving PTSD treatment at a VA medical center or a current diagnosis of schizophrenia , bipolar disorder , or substance dependence . Two hundred sixty-five veterans were enrolled from November 23 , 2009 , through September 28 , 2011 , r and omized to usual care ( UC ) or the TOP intervention , and followed up for 12 months . INTERVENTIONS Off-site PTSD care teams located at VA medical centers supported on-site community-based outpatient clinic providers . Off-site PTSD care teams included telephone nurse care managers , telephone pharmacists , telepsychologists , and telepsychiatrists . Nurses conducted care management activities . Pharmacists review ed medication histories . Psychologists delivered cognitive processing therapy via interactive video . Psychiatrists supervised the team and conducted interactive video psychiatric consultations . MAIN OUTCOMES AND MEASURES The primary outcome was PTSD severity as measured by the Posttraumatic Diagnostic Scale . Process-of-care outcomes included medication prescribing and regimen adherence and initiation of and adherence to cognitive processing therapy . RESULTS During the 12-month follow-up period , 73 of the 133 patients r and omized to TOP ( 54.9 % ) received cognitive processing therapy compared with 16 of 132 r and omized to UC ( 12.1 % ) ( odds ratio , 18.08 [ 95 % CI , 7.96 - 41.06 ] ; P < .001 ) . Patients in the TOP arm had significantly larger decreases in Posttraumatic Diagnostic Scale scores ( from 35.0 to 29.1 ) compared with those in the UC arm ( from 33.5 to 32.1 ) at 6 months ( β = -3.81 ; P = .002 ) . Patients in the TOP arm also had significantly larger decreases in Posttraumatic Diagnostic Scale scores ( from 35.0 to 30.1 ) compared with those in the UC arm ( from 33.5 to 31.7 ) at 12 months ( β = -2.49 ; P=.04 ) . There were no significant group differences in the number of PTSD medications prescribed and adherence to medication regimens were not significant . Attendance at 8 or more sessions of cognitive processing therapy significantly predicted improvement in Posttraumatic Diagnostic Scale scores ( β = -3.86 [ 95 % CI , -7.19 to -0.54 ] ; P = .02 ) and fully mediated the intervention effect at 12 months . CONCLUSIONS AND RELEVANCE Telemedicine-based collaborative care can successfully engage rural veterans in evidence -based psychotherapy to improve PTSD outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00821678 Background In developing countries , accessibility to specialists , and physician to patient contact time is limited . In Thail and , A unique community health service is provided by subdistrict health care officers and Village Health Volunteers ( VHVs ) . If the personnel were trained on proper chronic kidney disease ( CKD ) care , CKD progression would be delayed . Methods / Design We conducted a community-based , cluster r and omized controlled trial at Kamphaeng Phet Province , located about 400 kilometers north of Bangkok . Two out of eleven districts of the province were r and omly selected . Approximatly 500 stage 3–4 CKD patients from 2 districts were enrolled . Patients in both groups will be treated with st and ard guidelines . The patients in intervention group were provided the additional treatments by multidisciplinary team in conjunction with community CKD care network ( subdistrict health care officers and VHVs ) which will provide group counseling during each hospital visit and quarterly home visits to monitor dietary protein and sodium intake , blood pressure measurement and drug compliance . Duration of the study is 2 years . The primary outcome is the difference of rate of eGFR decline . The secondary outcomes are laboratory parameters and incidence of clinical endpoints such as mortality rate and cardiovascular events , end-stage renal disease ( ESRD ) , etc . Discussion Insights of this study may set forth a new st and ard of community-based CKD care . Trial registration NCT01978951 BACKGROUND Despite improvements in the accuracy of diagnosing depression and use of medications with fewer side effects , many patients treated with antidepressant medications by primary care physicians have persistent symptoms . METHODS A group of 228 patients recognized as depressed by their primary care physicians and given antidepressant medication who had either 4 or more persistent major depressive symptoms or a score of 1.5 or more on the Hopkins Symptom Checklist depression items at 6 to 8 weeks were r and omized to a collaborative care intervention ( n = 114 ) or usual care ( n = 114 ) by the primary care physician . Patients in the intervention group received enhanced education and increased frequency of visits by a psychiatrist working with the primary care physician to improve pharmacologic treatment . Follow-up assessment s were completed at 1 , 3 , and 6 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of medication for 90 days or more and were more likely to rate the quality of care they received for depression as good to excellent compared with usual care controls . Intervention patients showed a significantly greater decrease compared with usual care controls in severity of depressive symptoms over time and were more likely to have fully recovered at 3 and 6 months . CONCLUSIONS A multifaceted program targeted to patients whose depressive symptoms persisted 6 to 8 weeks after initiation of antidepressant medication by their primary care physician was found to significantly improve adherence to antidepressants , satisfaction with care , and depressive outcomes compared with usual care OBJECTIVE Major depression is a great burden on society , as it is associated with high disability/costs . The aim of this study was to evaluate the cost-utility of Collaborative Care ( CC ) for major depressive disorder compared to Care As Usual ( CAU ) in a primary health care setting from a societal perspective . METHODS A cluster r and omized controlled trial was conducted , including 93 patients that were identified by screening ( 45-CC , 48-CAU ) . Another 57 patients were identified by the GP ( 56-CC , 1-CAU ) . The outcome measures were TiC-P , SF-HQL and EQ-5D , respectively measuring health care utilization , production losses and general health related quality of life at baseline three , six , nine and twelve months . A cost-utility analysis was performed for patients included by screening and a sensitivity analysis was done by also including patients identified by the GP . RESULTS The average annual total costs was € 1131 ( 95 % C.I. , € -3158 to € 750 ) lower for CC compared to CAU . The average quality of life years ( QALYs ) gained was 0.02 ( 95 % C.I. , -0.004 to 0.04 ) higher for CC , so CC was dominant from a societal perspective . Taking a health care perspective , CC was less cost-effective due to higher costs , € 1173 ( 95 % C.I. , € -216 to € 2726 ) , of CC compared to CAU which led to an ICER of 53,717 Euro/QALY . The sensitivity analysis showed dominance of CC . CONCLUSION The cost-utility analysis from a societal perspective showed that CC was dominant to CAU . CC may be a promising treatment for depression in the primary care setting . Further research should explore the cost-effectiveness of long-term CC . TRIAL REGISTRATION Netherl and s Trial Register IS RCT N15266438 Abstract Objective To determine the long term effectiveness of collaborative care management for depression in late life . Design Two arm , r and omised , clinical trial ; intervention one year and follow-up two years . Setting 18 primary care clinics in eight US healthcare organisations . Patients 1801 primary care patients aged 60 and older with major depression , dysthymia , or both . Intervention Patients were r and omly assigned to a 12 month collaborative care intervention ( IMPACT ) or usual care for depression . Teams including a depression care manager , primary care doctor , and psychiatrist offered education , behavioural activation , antidepressants , a brief , behaviour based psychotherapy ( problem solving treatment ) , and relapse prevention geared to each patient 's needs and preferences . Main outcome measures Interviewers , blinded to treatment assignment , conducted interviews in person at baseline and by telephone at each subsequent follow up . They measured depression ( SCL-20 ) , overall functional impairment and quality of life ( SF-12 ) , physical functioning ( PCS-12 ) , depression treatment , and satisfaction with care . Results IMPACT patients fared significantly ( P < 0.05 ) better than controls regarding continuation of antidepressant treatment , depressive symptoms , remission of depression , physical functioning , quality of life , self efficacy , and satisfaction with care at 18 and 24 months . One year after IMPACT re sources were withdrawn , a significant difference in SCL-20 scores ( 0.23 , P < 0.0001 ) favouring IMPACT patients remained . Conclusions Tailored collaborative care actively engages older adults in treatment for depression and delivers substantial and persistent long term benefits . Benefits include less depression , better physical functioning , and an enhanced quality of life . The IMPACT model may show the way to less depression and healthier lives for older adults Background Collaborative care is an effective treatment for the management of depression but evidence on its cost-effectiveness in the UK is lacking . Aims To assess the cost-effectiveness of collaborative care in a UK primary care setting . Methods An economic evaluation alongside a multi-centre cluster r and omised controlled trial comparing collaborative care with usual primary care for adults with depression ( n = 581 ) . Costs , quality -adjusted life-years ( QALYs ) , and incremental cost-effectiveness ratios ( ICER ) were calculated over a 12-month follow-up , from the perspective of the UK National Health Service and Personal Social Services ( i.e. Third Party Payer ) . Sensitivity analyses are reported , and uncertainty is presented using the cost-effectiveness acceptability curve ( CEAC ) and the cost-effectiveness plane . Results The collaborative care intervention had a mean cost of £ 272.50 per participant . Health and social care service use , excluding collaborative care , indicated a similar profile of re source use between collaborative care and usual care participants . Collaborative care offered a mean incremental gain of 0.02 ( 95 % CI : –0.02 , 0.06 ) quality -adjusted life-years over 12 months , at a mean incremental cost of £ 270.72 ( 95 % CI : –202.98 , 886.04 ) , and result ed in an estimated mean cost per QALY of £ 14,248 . Where costs associated with informal care are considered in sensitivity analyses collaborative care is expected to be less costly and more effective , thereby dominating treatment as usual . Conclusion Collaborative care offers health gains at a relatively low cost , and is cost-effective compared with usual care against a decision-maker willingness to pay threshold of £ 20,000 per QALY gained . Results here support the commissioning of collaborative care in a UK primary care setting BACKGROUND Practice variation in the primary care treatment of depression may be considerable in the Netherl and s , due to relatively small and unregulated practice s. We adapted the collaborative care model for the treatment of Major Depressive Disorder ( MDD ) to accommo date existing practice variation and tested whether this had added value over Care as Usual ( CAU ) . METHODS A cluster r and omized controlled trial was conducted to compare an adapted target driven collaborative care model with Care as Usual ( CAU ) . R and omization was at the level of 18 (sub)urban primary care centers . The care manager and GP were supported by a web-based tracking and decision aid system that advised targeted treatment actions to achieve rapid response and if possible remission , and that warned the consultant psychiatrist if such treatment advice was not followed up . Eligible patients had a score of 10 or higher on the PHQ9 , and met diagnostic criteria for major depression at the subsequent MINI Neuropsychiatric interview . A total of 93 patients were identified by screening . They received either collaborative care ( CC ) or CAU . Another 56 patients received collaborative care after identification by the GP . The outcome measures were response to treatment ( 50 % or greater reduction of the PHQ9-total score from baseline ) at three , six , nine and twelve months , and remission ( a score of 0 - 4 on the PHQ9 at follow-up ) . RESULTS Treatment response and remission in CAU were low . Collaborative care was more effective on achieving treatment response than CAU at three months for the total group of patients who received collaborative care [ OR 5.2 ( ( 1.41 - 16.09 ) , NNT 2 ] and at nine months [ OR 5.6 ( ( 1.40 - 22.58 ) ) , NNT 3 ] . The effect was not statistically significant at 6 and 12 months . LIMITATIONS A relatively high percentage of patients ( 36.5 % ) did not return one or more follow-up question naires . There was no evidence for selective non response . CONCLUSIONS Our adapted target driven CC was considerably more effective than CAU for MDD in primary care in the Netherl and s. The Numbers Needed To Treat ( NNT ) to achieve response in one additional patient were low ( 2 - 3 ) , which suggest that introducing CC at a larger scale may be beneficial . The relatively large effects may be due to our focus on reducing practice variation through the introduction of easy to use web based tracking and decision aids . The findings are highly relevant for the application of the model in areas where practice s tend to be small and for mixed healthcare systems such as in many countries in Europe . TRIAL REGISTRATION Dutch trial register IS RCT N15266438 ( http://www.trialregister.nl/trialreg/admin/ rct view.asp?TC=820 ) Abstract OBJECTIVE : A previous study described the effect of a collaborative care intervention on improving adherence to antidepressant medications and depressive and functional outcomes of patients with persistent depressive symptoms 8 weeks after the primary care physician initiated treatment . This paper examined the 28-month effect of this intervention on adherence , depressive symptoms , functioning , and health care costs . DESIGN : R and omized trial of stepped collaborative care intervention versus usual care . SETTING : HMO in Seattle , Wash. PATIENTS : Patients with major depression were stratified into severe and moderate depression groups prior to r and omization . INTERVENTIONS : A multifaceted intervention targeting patient , physician , and process of care , using collaborative management by a psychiatrist and a primary care physician . MEASURES AND MAIN RESULTS : The collaborative care intervention was associated with continued improvement in depressive symptoms at 28 months in patients in the moderate-severity group ( F1,87=8.65 ; P=.004 ) , but not in patients in the high-severity group ( F1,51=0.02 ; P=.88 ) Improvements in the intervention group in antidepressant adherence were found to occur for the first 6 months ( χ2(1)=8.23 ; P<.01 ) and second 6-month period ( χ2(1)=5.98 ; P<.05 ) after r and omization in the high-severity group and for 6 months after r and omization in the moderate-severity group(χ2(1)=6.10 ; P<.05 ) . There were no significant differences in total ambulatory costs between intervention and control patients over the 28-month period ( F1,180=0.77 ; P=.40 ) . CONCLUSIONS : A collaborative care intervention was associated with sustained improvement in depressive outcomes without additional health care costs in approximately two thirds of primary care patients with persistent depressive symptoms BACKGROUND Hospital admissions among patients with congestive heart failure ( CHF ) are a major contributor to health-care costs . Previous investigations suggest that the therapeutic efficacy of pharmacotherapy in CHF may be improved by strategies incorporating home visits to identify and address factors precipitating deterioration and result ant readmission . METHODS Chronic CHF patients discharged home after acute hospital admission were r and omly assigned usual care ( n=100 ) or a multidisciplinary , home-based intervention ( n=100 ) , consisting of a home visit by a cardiac nurse 7 - 14 days after discharge . The primary endpoint of the study was frequency of unplanned readmission plus out-of-hospital death within 6 months . FINDINGS During 6 months ' follow-up there were 129 primary endpoint events in the usual-care group and 77 in the intervention group ( p=0.02 ) . More intervention-group than usual-care patients remained event-free ( 38 vs 51 ; p=0.04 ) . Overall , there were fewer unplanned readmissions ( 68 vs 118 ; p=0.03 ) and associated days in hospital ( 460 vs 1173 ; p=0.02 ) among intervention-group patients . Hospital-based costs were Australian $ 490,300 for the intervention group and A$ 922,600 for the usual-care group ( p=0.16 ) ; the mean cost of the intervention was A$ 350 per patient , and other community-based costs were similar for both groups . INTERPRETATION A home-based intervention has the potential to decrease the rate of unplanned readmissions and associated health-care costs , prolong event-free and total survival , and improve quality of life among patients with chronic CHF Background : Collaborative stepped care ( CSC ) may be an appropriate model to provide evidence -based treatment for anxiety disorders in primary care . Methods : In a cluster r and omised controlled trial , the effectiveness of CSC compared to care as usual ( CAU ) for adults with panic disorder ( PD ) or generalised anxiety disorder ( GAD ) in primary care was evaluated . Thirty-one psychiatric nurses who provided their services to 43 primary care practice s in the Netherl and s were r and omised to deliver CSC ( 16 psychiatric nurses , 23 practice s ) or CAU ( 15 psychiatric nurses , 20 practice s ) . CSC was provided by the psychiatric nurses ( care managers ) in collaboration with the general practitioner and a consultant psychiatrist . The intervention consisted of 3 steps , namely guided self-help , cognitive behavioural therapy and antidepressants . Anxiety symptoms were measured with the Beck Anxiety Inventory ( BAI ) at baseline and after 3 , 6 , 9 and 12 months . Results : We recruited 180 patients with a DSM-IV diagnosis of PD or GAD , of whom 114 received CSC and 66 received usual primary care . On the BAI , CSC was superior to CAU [ difference in gain scores from baseline to 3 months : -5.11 , 95 % confidence interval ( CI ) -8.28 to -1.94 ; 6 months : -4.65 , 95 % CI -7.93 to -1.38 ; 9 months : -5.67 , 95 % CI -8.97 to -2.36 ; 12 months : -6.84 , 95 % CI -10.13 to -3.55 ] . Conclusions : CSC , with guided self-help as a first step , was more effective than CAU for primary care patients with PD or GAD OBJECTIVE The aim of this study was to determine sustained effectiveness in reducing depression symptoms and improving depression care 1 year following intervention completion . METHOD Of 387 low-income , predominantly Hispanic diabetes patients with major depression symptoms r and omized to 12-month socioculturally adapted collaborative care ( psychotherapy and /or antidepressants , telephone symptom monitoring/relapse prevention ) or enhanced usual care , 264 patients completed 2-year follow-up . Depression symptoms ( Symptom Checklist-20 [ SCL-20 ] , Patient Health Question naire-9 [ PHQ-9 ] ) , treatment receipt , diabetes symptoms and quality of life were assessed 24 months postenrollment using intent-to-treat analyses . RESULTS At 24 months , more intervention patients received ongoing antidepressant treatment ( 38 % vs. 25 % , χ(2)=5.11 , df=1 , P=.02 ) ; sustained depression symptom improvement [ SCL-20 < 0.5 ( adjusted odds ratio=2.06 , 95 % confidence interval=1.09 - 3.90 , P=.03 ) , SCL-20 score ( adjusted mean difference -0.22 , P=.001 ) and PHQ-9 ≥50 % reduction ( adjusted odds ratio=1.87 , 95 % confidence interval = 1.05 - 3.32 , P=.03 ) ] . Over 2 years , improved effects were found in significant study group by time interaction for Short Form-12 mental health , Sheehan Disability Scale ( SDS ) functional impairment , diabetes symptoms , anxiety and socioeconomic stressors ( P=.02 for SDS ; P<.0001 for all others ) ; however , group differences narrowed over time and were no longer significant at 24 months . CONCLUSIONS Socioculturally tailored collaborative care that included maintenance antidepressant medication , ongoing symptom monitoring and behavioral activation relapse prevention was associated with depression improvement over 24 months for predominantly Hispanic patients in primary safety net care Editorial by Toop and Richards St and ards one to four of the national service framework for coronary heart disease require general practitioners in Engl and to identify all patients with established coronary heart disease or stroke , record their coronary risk factors , and offer appropriate treatment and to identify and treat patients at high risk of developing coronary heart disease.1 We estimated the general practice workload involved in meeting these goals . We invited 65 practice s r and omly selected from the 51 primary care groups in the Trent region to participate ; 24 practice s volunteered and 18 were recruited.2 Ethical approval was obtained . We identified two target groups of high risk patients aged 35 - 74 : patients with a Read code for ischaemic heart disease or stroke or at least one prescription for a nitrate ( group 1),3 and patients with a computer recorded Read code for diabetes or hypertension ( excluding those in group 1 ) who would be at high risk of developing coronary BACKGROUND War-related trauma , posttraumatic stress disorder ( PTSD ) , depression and suicide are common in US military members . Often , those affected do not seek treatment due to stigma and barriers to care . When care is sought , it often fails to meet quality st and ards . A r and omized trial is assessing whether collaborative primary care improves quality and outcomes of PTSD and depression care in the US military health system . OBJECTIVE The aim of this study is to describe the design and sample for a r and omized effectiveness trial of collaborative care for PTSD and depression in military members attending primary care . METHODS The STEPS-UP Trial ( STepped Enhancement of PTSD Services Using Primary Care ) is a 6 installation ( 18 clinic ) r and omized effectiveness trial in the US military health system . Study rationale , design , enrollment and sample characteristics are summarized . FINDINGS Military members attending primary care with suspected PTSD , depression or both were referred to care management and recruited for the trial ( 2592 ) , and 1041 gave permission to contact for research participation . Of those , 666 ( 64 % ) met eligibility criteria , completed baseline assessment s , and were r and omized to 12 months of usual collaborative primary care versus STEPS-UP collaborative care . Implementation was locally managed for usual collaborative care and central ly managed for STEPS-UP . Research re assessment s occurred at 3- , 6- , and 12-months . Baseline characteristics were similar across the two intervention groups . CONCLUSIONS STEPS-UP will be the first large scale r and omized effectiveness trial completed in the US military health system , assessing how an implementation model affects collaborative care impact on mental health outcomes . It promises lessons for health system change OBJECTIVE To assess the effect of a specialist telemedicine intervention for improving diabetes care using the chronic care model ( CCM ) . PARTICIPANTS AND METHODS As part of the CCM , 97 primary care physicians at 6 primary care practice s in Rochester , MN , referred 639 patients to an on-site diabetes educator between July 1 , 2001 , and December 31 , 2003 . On first referral , physicians were central ly r and omized to receive a telemedicine intervention ( specialty advice and evidence -based messages regarding medication management for cardiovascular risk ) or no intervention , keeping outcome assessors and data analysts blinded to group assignment . After each subsequent clinical encounter , endocrinologists review ed an abstract from the patient 's electronic medical record and provided management recommendations and supporting evidence to intervention physicians via e-mail . Control physicians received e-mail with periodic generic information about cardiovascular risk reduction in diabetes . Outcome measures included diabetes care processes ( diabetes test completion ) , outcomes ( metabolic and cardiovascular risk factors , estimated coronary artery disease risk ) , and patient costs ( payer perspective ) . RESULTS During the intervention , 951 ( 70 % ) of the 1361 endocrinology review s detected performance gaps and result ed in a message ; primary care physicians reported using 49 % of messages in patient care . With a mean of 21 months ' follow-up , the intervention , compared with control , did not significantly enhance metabolic outcomes or reduce estimated risk of coronary artery disease ( adjusted mean difference , -1 % ; 95 % confidence interval , -19 % to 17 % ) . The intervention group incurred lower costs ( P=.02 ) but not in diabetes-related costs . CONCLUSION Specialty telemedicine did not significantly enhance the value of CCM in primary care CONTEXT Care of patients with depression in managed primary care setting s often fails to meet guideline st and ards , but the long-term impact of quality improvement ( QI ) programs for depression care in such setting s is unknown . OBJECTIVE To determine if QI programs in managed care practice s for depressed primary care patients improve quality of care , health outcomes , and employment . DESIGN R and omized controlled trial initiated from June 1996 to March 1997 . SETTING Forty-six primary care clinics in 6 US managed care organizations . PARTICIPANTS Of 27332 consecutively screened patients , 1356 with current depressive symptoms and either 12-month , lifetime , or no depressive disorder were enrolled . INTERVENTIONS Matched clinics were r and omized to usual care ( mailing of practice guidelines ) or to 1 of 2 QI programs that involved institutional commitment to QI , training local experts and nurse specialists to provide clinician and patient education , identification of a pool of potentially depressed patients , and either nurses for medication follow-up or access to trained psychotherapists . MAIN OUTCOME MEASURES Process of care ( use of antidepressant medication , mental health specialty counseling visits , medical visits for mental health problems , any medical visits ) , health outcomes ( probable depression and health-related quality of life [ HRQOL ] ) , and employment at baseline and at 6- and 12-month follow-up . RESULTS Patients in QI ( n = 913 ) and control ( n = 443 ) clinics did not differ significantly at baseline in service use , HRQOL , or employment after nonresponse weighting . At 6 months , 50.9 % of QI patients and 39.7 % of controls had counseling or used antidepressant medication at an appropriate dosage ( P<.001 ) , with a similar pattern at 12 months ( 59.2 % vs 50.1 % ; P = .006 ) . There were no differences in probability of having any medical visit at any point ( each P > or = .21 ) . At 6 months , 47.5 % of QI patients and 36.6 % of controls had a medical visit for mental health problems ( P = .001 ) , and QI patients were more likely to see a mental health specialist at 6 months ( 39.8 % vs 27.2 % ; P<.001 ) and at 12 months ( 29.1 % vs 22.7 % ; P = .03 ) . At 6 months , 39.9 % of QI patients and 49.9 % of controls still met criteria for probable depressive disorder ( P = .001 ) , with a similar pattern at 12 months ( 41.6 % vs 51.2 % ; P = .005 ) . Initially employed QI patients were more likely to be working at 12 months relative to controls ( P = .05 ) . CONCLUSIONS When these managed primary care practice s implemented QI programs that improve opportunities for depression treatment without m and ating it , quality of care , mental health outcomes , and retention of employment of depressed patients improved over a year , while medical visits did not increase overall OBJECTIVES To evaluate the effect of a shared care programme ( SCP ) , defined as a scheme based on shared responsibility , enhanced information exchange , continues medical education and explicit clinical guidelines , between general practitioners ( GPs ) and a hospital outpatient clinic ( HOC ) , on oral anticoagulant therapy ( OAT ) . DESIGN The study was a 2-year prospect i ve , r and omized , controlled trial , preceded by a 1-year period of observation . SETTING The HOC , GPs , and OAT patients in the admission area of Aarhus University Hospital , Aarhus County , Denmark , covering 310 300 inhabitants . SUBJECTS A total of 207 GPs , including their enlisted patients on OAT , were invited , and 61.4 % accepted participation . They were r and omized into an intervention group [ group-INT : 64 GPs and 453 patients ( 170 patients on OAT throughout the study period , i.e. full follow-up ) ] , and a control group [ group-CON : 63 GPs and 422 patients ( 173 with full follow-up ) ] . The remaining 80 GPs served as a nonresponder group ( group-NON ) of 485 patients ( 184 with full follow-up ) . MAIN OUTCOME MEASURE Therapeutic control of OAT in terms of time spent by the patients within the therapeutic interval ( TI ) of an international normalized ratio ( INR ) between 2.0 and 3.5 . RESULTS The groups did not differ significantly with regard to age , sex , OAT indication , anticoagulant drug used , or the therapeutic control at baseline . In a comparison based on intention-to-treat principles , the therapeutic control increased statistical significance amongst patients with full follow-up in group-INT compared with group-CON ( median time within TI : group INT = 86.6 % vs. 80.5 % , P = 0.007 ) . CONCLUSION An SCP of anticoagulant management is effective in reducing patient time outside the therapeutic INR interval in OAT patients r and omly assigned to an SCP , as compared with a control group OBJECTIVE The authors compared treatment and outcomes for depressed primary care patients with and without comorbid medical conditions and assessed the impact of quality improvement programs for these patients . METHOD The study group included 1,356 patients with major depression , dysthymia , or subthreshold depression from 46 managed primary care clinics . Clinics were r and omly assigned depression treatment programs consisting of usual care for depression or one of two quality improvement programs for depression . The quality improvement programs included training experts and nurse specialists to provide education and assessment , plus access to nurse specialists for medication follow-up or access to psychotherapists . Outcomes were assessed at 6 and 12 months . RESULTS At 6- and 12-month follow-up , the likelihood of having a probable depressive disorder was higher , but the rates of use of antidepressant medication and specialty counseling were similar , for depressed patients with comorbid medical disorders than for depressed patients who did not have comorbid medical disorders . Among the depressed patients with comorbid medical disorders , the combined quality improvement programs result ed in greater use of antidepressant medications and psychotherapy and lower rates of probable depressive disorders at both 6- and 12-month follow-up than did the usual care depression treatment program . CONCLUSIONS Depressed patients with comorbid medical disorders tend to have similar rates of treatment but worse depression outcomes than depressed patients without comorbid medical illness . Quality improvement programs for depression can improve treatment rates and outcomes for depressed primary care patients with comorbid medical illness . The authors discuss the implication s of these findings for clinical practice BACKGROUND A new diabetes shared care service was introduced in North Dublin . It was design ed as a r and omized controlled trial with a complex intervention comprising education of participating practitioners , the introduction of a community-based diabetes nurse specialist , local agreement on clinical protocol s and structured communication across the primary - secondary care interface . OBJECTIVES Our aim was to assess the feasibility and effectiveness of a structured diabetes shared care service in a mixed health care system and to analyse the impact on total patient care . METHODS A Cluster r and omized controlled trial lasting 18 months was carried out in 183 patients with type 2 diabetes from 30 general practice s in North Dublin . Biophysical outcomes ( HbA1c , blood pressure , body mass index ) , psychosocial measures ( smoking status and Diabetes Clinic Treatment Satisfaction and Diabetes Well-being scores ) and process outcomes were collected . RESULTS There were significant improvements in diabetes care delivery and in psychosocial outcomes , but no significant improvements in biomedical outcomes . Process data collection revealed a significant increase in diabetes care-related activity for participating patients with an increase in structured annual review s and fewer patients defaulting from care . There were also significant improvements in information exchange between primary and secondary care . CONCLUSION Structured diabetes shared care , in a mixed health care system , can produce significant improvements in diabetes care delivery and in psychosocial outcomes for patients , with improved information exchange across the primary - secondary care interface UNLABELLED An integrated care intervention including education , coordination among levels of care , and improved accessibility , reduced hospital readmissions in chronic obstructive pulmonary disease ( COPD ) after 1 year . This study analyses the effectiveness of this intervention in terms of clinical and functional status , quality of life , lifestyle , and self-management , under the hypothesis that changes in these factors could explain the observed reduction in readmissions . A total of 113 exacerbated COPD patients ( 14 % female , mean ( SD ) age 73(8 ) years , FEV(1 ) 1.2(0.5 ) l ) were recruited after hospital discharge in Barcelona , Spain , and r and omly assigned ( 1:2 ) to integrated care ( IC ) ( n=44 ) or usual care ( UC ) ( n=69 ) . The intervention consisted of an individually tailored care plan at discharge shared with the primary care team and access to a specialized case manager nurse through a web-based call centre . After 1 year of intervention , subjects in the intervention group improved body mass index by 1.34 kg/m(2 ) . Additionally , they scored better in self-management items : COPD knowledge 81 % vs. 44 % , exacerbation identification 85 % vs. 22 % , exacerbation early treatment 90 % vs. 66 % , inhaler adherence 71 vs. 37 % , and inhaler correctness 86 vs. 24 % . There were no differences in the evolution of dyspnea , lung function , quality of life scores , lifestyle factors , or medical treatment . CONCLUSIONS This IC trial improved disease knowledge , and treatment adherence , after 1 year of intervention , suggesting that these factors may play a role in the prevention of severe COPD exacerbations triggering hospital admissions OBJECTIVE This article describes the patient management processes developed during the Council of Australian Governments ( COAG ) coordinated care trial and use of health outcome measures to monitor changes in utilisation patterns and patient well-being over time for a subgroup of 398 patients with type 2 diabetes . DESIGN The Eyre component of the South Australian ( SA ) HealthPlus coordinated care trial was a matched geographically controlled study in which the outcomes for the intervention group of 1350 patients were compared with those of a similar control group of 500 patients in another rural health region in SA . SETTING The trial was carried out on Eyre Peninsula in SA across population s in rural communities and in the main centres of Whyalla , Port Lincoln and Ceduna . Care planning was organised through general practitioner practice s and services negotiated with allied health services and hospitals to meet patient needs . SUBJECTS The SA HealthPlus trial included 1350 patients with chronic and complex illness . A subset of this group comprising 398 patients with type 2 diabetes is described in this report . Patients recruited into the three-year trial were care planned using a patient centred care planning model through which patient goals were generated along with medical management goals developed by clinicians and primary health care professionals . Relevant health services were scheduled in line with best practice and care plans were review ed each year . Patient service utilisation , progress towards achieving health related goals and patient health outcomes were recorded and assessed to determine improvements in health and well-being along with the cost and profile of the services provided . RESULTS Significant numbers of patients experienced improved health outcomes as a consequence of their involvement in the trial , and utilisation data showed reductions in hospital and medical expenditure for some patients . These results suggest that methods applied in the SA HealthPlus coordinated care trial have led to improvements in health outcomes for patients with diabetes and other chronic illnesses . In addition , the processes associated with the COAG trial motivated significant organisational change in the Regional Health Service as well as providing an opportunity to study the health and well-being outcomes result ing from a major community health intervention . CONCLUSIONS The importance of the SA HealthPlus trial has been the demonstrated link between a formal research trial and significant developments in the larger health system with the trial not only leading to improvements in clinical outcomes for patients , but also acting as a catalyst for organisational reform . We now need to look beyond the illness focus of health outcome research to develop population based health approaches to improving overall community well-being BACKGROUND A collaborative care programme for depression in primary care has proven clinical effectiveness over a 12-months period . Because depression tends to relapse and to chronic course , our aim was to determine whether the effectiveness observed in the first year persists during 3 years of monitoring . METHODS R and omised controlled trial with twenty primary care centres were allocated to intervention group or usual care group . The intervention consisted of a collaborative care programme with clinical , educational and organisational procedures . Outcomes were monitored by a blinded interviewer at baseline , 12 and 36 months . Clinical outcomes were response to treatment and remission rates , depression severity and health-related quality of life . TRIAL REGISTRATION IS RCT N16384353 . RESULTS A total of 338 adult patients with major depression ( DSM-IV ) were assessed at baseline . At 36 months , 137 patients in the intervention group and 97 in the control group were assessed ( attrition 31 % ) . The severity of depression ( mean Patient Health Question naire-9 score ) was 0.95 points lower in the intervention group [ 6.31 versus 7.25 ; p=0.324 ] . The treatment response rate was 5.6 % higher in the intervention group than in the control group [ 66.4 % versus 60.8 % ; p=0.379 ] and the remission rate was 9.2 % higher [ 57.7 % versus 48.5 % ; p=0.164 ] . No difference reached statistical significance . LIMITATIONS The number of patients lost ( 31 % ) before follow-up may have introduced a bias . CONCLUSIONS Clinical benefits shown in the first year were not maintained beyond : at 36 months the differences between the control group and the intervention group reduced in all the analysed variables Abstract Objective : To evaluate the effectiveness of a population based , multifaceted shared care intervention for late life depression in residential care . Design : R and omised controlled trial , with control and intervention groups studied one after the other and blind follow up after 9.5 months . Setting : Population of residential facility in Sydney living in self care units and hostels . Participants : 220 depressed residents aged ≥65 without severe cognitive impairment . Intervention : The shared care intervention included : ( a ) multidisciplinary consultation and collaboration , ( b ) training of general practitioners and carers in detection and management of depression , and (c)depression related health education and activity programmes for residents . The control group received routine care . Main outcome measure : Geriatric depression scale . Results : Intention to treat analysis was used . There was significantly more movement to “ less depressed ” levels of depression at follow up in the intervention than control group ( Mantel-Haenszel stratification test , P=0.0125 ) . Multiple linear regression analysis found a significant intervention effect after controlling for possible confounders , with the intervention group showing an average improvement of 1.87 points on the geriatric depression scale compared with the control group ( 95 % confidence interval 0.76 to 2.97 , P=0.0011 ) . Conclusions : The outcome of depression among elderly people in residential care can be improved by multidisciplinary collaboration , by enhancing the clinical skills of general practitioners and care staff , and by providing depression related health education and activity programmes for residents . Key messages Large numbers of depressed elderly people live in residential care but few receive appropriate management A population based , multifaceted shared care intervention for late life depression was more effective than routine care in improving depression outcome The outcome of late life depression can be improved by enhancing the clinical skills of general practitioners and care staff and by providing depression related health education and activity programmes for residents The intervention needs further refining and evaluation to improve its effectiveness and to determine how best to implement it in other residential care setting BACKGROUND Collaborative care programmes lead to better outcomes in the management of depression . A programme of this nature has demonstrated its effectiveness in primary care in Spain . Our objective was to evaluate the cost-effectiveness of this programme compared to usual care . METHODS A bottom-up cost-effectiveness analysis was conducted within a r and omized controlled trial ( 2007 - 2010 ) . The intervention consisted of a collaborative care programme with clinical , educational and organizational procedures . Outcomes were monitored over a 12 months period . Primary outcomes were incremental cost-effectiveness ratios ( ICER ) : mean differences in costs divided by quality -adjusted life years ( QALY ) and mean differences in costs divided by depression-free days ( DFD ) . Analyses were performed from a healthcare system perspective ( considering healthcare costs ) and from a society perspective ( including healthcare costs plus loss of productivity costs ) . RESULTS Three hundred and thirty-eight adult patients with major depression were assessed at baseline . Only patients with complete data were included in the primary analysis ( 166 in the intervention group and 126 in the control group ) . From a healthcare perspective , the average incremental cost of the programme compared to usual care was € 182.53 ( p<0.001 ) . Incremental effectiveness was 0.045 QALY ( p=0.017 ) and 40.09 DFD ( p=0.011 ) . ICERs were € 4,056/QALY and € 4.55/DFD . These estimates and their uncertainty are graphically represented in the cost-effectiveness plane . LIMITATIONS The amount of 13.6 % of patients with incomplete data may have introduced a bias . Available data about non-healthcare costs were limited , although they may represent most of the total cost of depression . CONCLUSIONS The intervention yields better outcomes than usual care with a modest increase in costs , result ing in favourable ICERs . This supports the recommendation for its implementation We sought to develop and implement collaborative depression care in human immunodeficiency virus ( HIV ) clinics in a project called HIV Translating Initiatives for Depression into Effective Solutions ( HITIDES ) . Here we describe : ( i ) the formative evaluation ( FE ) conducted prior to implementation ; ( ii ) the process used to adapt the primary care collaborative care model for depression to specialty HIV clinics ; and ( iii ) the intervention itself . The overall design of HITIDES was a multi-site r and omized trial in United States Department of Veterans Affairs ( VA ) HIV clinics comparing the depression collaborative care intervention to usual depression care . Qualitative methods were used for the FEs and informed the evidence -based quality improvement ( EBQI ) methods that were used for adapting and implementing the intervention . Baseline assessment s were completed by 249 depressed HIV participants . Summaries of respective key informant interviews with eight HIV patients who were receiving depression treatment and 25 HIV or mental health ( MH ) providers were presented to each site . EBQI methods were used to tailor the HITIDES intervention to each site while maintaining true to the evidence base for depression collaborative care . EBQI methods provided a useful framework for intervention adaptation and implementation . The HITIDES study provides the opportunity to evaluate collaborative depression care in a specialty physical health clinic setting with a population that has a high prevalence of depression and MH comorbidity CONTEXT Collaborative care interventions for depression in primary care setting s are clinical ly beneficial and cost-effective . Most prior studies were conducted in urban setting s. OBJECTIVE To examine the cost-effectiveness of a rural telemedicine-based collaborative care depression intervention . DESIGN R and omized controlled trial of intervention vs usual care . SETTING Seven small ( serving 1000 to 5000 veterans ) Veterans Health Administration community-based outpatient clinics serving rural catchment areas in 3 mid-South states . Each site had interactive televideo dedicated to mental health but no psychiatrist or psychologist on site . Patients Among 18 306 primary care patients who were screened , 1260 ( 6.9 % ) screened positive for depression ; 395 met eligibility criteria and were enrolled from April 2003 to September 2004 . Of those enrolled , 360 ( 91.1 % ) completed a 6-month follow-up and 335 ( 84.8 % ) completed a 12-month follow-up . Intervention A stepped-care model for depression treatment was used by an off-site depression care team to make treatment recommendations via electronic medical record . The team included a nurse depression care manager , clinical pharmacist , and psychiatrist . The depression care manager communicated with patients via telephone and was supported by computerized decision support software . MAIN OUTCOME MEASURES The base case cost analysis included outpatient , pharmacy , and intervention expenditures . The effectiveness outcomes were depression-free days and quality -adjusted life years ( QALYs ) calculated using the 12-Item Short Form Health Survey st and ard gamble conversion formula . RESULTS The incremental depression-free days outcome was not significant ( P = .10 ) ; therefore , further cost-effectiveness analyses were not done . The incremental QALY outcome was significant ( P = .04 ) and the mean base case incremental cost-effectiveness ratio was $ 85 634/QALY . Results adding inpatient costs were $ 111 999/QALY to $ 132 175/QALY . CONCLUSIONS In rural setting s , a telemedicine-based collaborative care intervention for depression is effective and expensive . The mean base case result was $ 85 634/QALY , which is greater than cost per QALY ratios reported for other , mostly urban , depression collaborative care interventions SUMMARY AIMS To describe the rationale and design of the Which Heart failure Intervention is most Cost-effective & consumer friendly in reducing Hospital care ( WHICH ? ) trial . METHODS WHICH ? is a pragmatic , multicentre , r and omized controlled trial that seeks to determine if multidisciplinary management of chronic heart failure ( CHF ) patients post-acute hospitalization delivered in a patient 's own home is superior to care delivered via a specialist CHF outpatient clinic . The composite primary endpoint is all-cause , unplanned recurrent hospitalization or death during 12 - 18 months of follow-up . Of 688 eligible patients , 280 patients ( 73 % male and 66 % principal diagnosis of CHF ) with a mean age of 71 ± 14 years have been r and omized to home- ( n = 143 ) or clinic-based ( n = 137 ) post-discharge management . This will provide 80 % power ( two-sided alpha of 0.05 ) to detect a 15 % absolute difference in both the primary end-point and rate of all-cause hospital stay . Preliminary data suggest that the two groups are well matched in nearly all baseline socio-economic and clinical parameters . The majority of patients have significant co-morbidity , including hypertension ( 63 % ) , coronary artery disease ( 55 % ) , and atrial fibrillation ( 53 % ) with an accordingly high Charlson Index of Comorbidity Score ( 6.1 ± 2.4 ) . PERSPECTIVE Despite its relatively small size , the WHICH ? trial is well placed to examine the relative impact of two of the most commonly applied forms of face-to-face management design ed to reduce recurrent hospitalization and prolong survival in CHF patients Abstract Objective : To evaluate integrated care for asthma in clinical , social , and economic terms . Design : Pragmatic r and omised trial . Setting : Hospital outpatient clinics and general practice s throughout the north east of Scotl and . Patients : 712 adults attending hospital outpatient clinics with a diagnosis of asthma confirmed by a chest physician and pulmonary function reversibility of at least 20 % . Main outcome measures : Use of bronchodilators and inhaled and oral steroids ; number of general practice consultations and hospital admissions for asthma ; sleep disturbance and other restrictions on normal activity ; pyschological aspects of health including perceived asthma control ; patient satisfaction ; and financial costs . Results : After one year there were no significant overall differences between those patients receiving integrated asthma care and those receiving conventional outpatient care for any clinical or psycho-social outcome . For pulmonary function , forced expiratory volume was 76 % of predicted for integrated care patients and 75 % for conventional out patients ( 95 % confidence interval for difference -3.6 % to 5.0 % ) . Patients who had experienced integrated care were more likely to select it as their preferred course of future management ( 75 % ( 251/ 333 ) v 62 % ( 207/333 ) ( 6 % to 20 % ) ; they saved pounds sterling 39.52 a year . This was largely because patients in conventional outpatient care consulted their general practioner as many times as those in integrated care , who were not also visiting hospital . Conclusion : Integrated care for moderately severe asthma patients is clinical ly as effective as conventional outpatient care , cost effective , and an attractive management option for patients , general practioners , and hospital consultants Objective : To examine the effectiveness of integrating generalist and specialist care for veterans with depression . Method : We conducted a r and omized trial of patients screening positive for depression at two Veterans Affairs Medical Center general medicine clinic firms . Control firm physicians were notified prior to the encounter when eligible patients had PRIME-MD depression diagnoses . In the intervention firm , a mental health clinical nurse specialist ( CNS ) was to : design a treatment plan ; implement that plan with the primary care physician ; and monitor patients via telephone or visits at two weeks , one month and two months . Primary outcomes ( depressive symptoms , patient satisfaction with health care ) were collected at 3 and 12 months . Results : Of 268 r and omized patients , 246 ( 92 % ) and 222 ( 83 % ) completed 3- and 12-month follow-up interviews . There were no between-group differences in depressive symptoms or satisfaction at 3 or 12 months . The intervention group had greater chart documentation of depression at baseline ( 63 % versus 33 % , p = 0.003 ) and a higher referral rate to mental health services at 3 months ( 27 % versus 9 % , p = 0.019 ) . There was no difference in the rate of new prescriptions for , or adequate dosing of , anti-depressant medications . In 40 % of patients , CNSs disagreed with the PRIME-MD depression diagnosis , and their rates of watchful waiting were correspondingly high . Conclusions : Implementing an integrated care model did not occur as intended . Experienced CNSs often did not see the need for treatment in many primary care patients identified by the PRIME-MD . Integrating integrated care models in actual practice may prove challenging BACKGROUND Primary care clinicians have a considerable amount of contact with patients suffering from long-term mental illness . The United Kingdom 's National Health Service now requires general practice s to contribute more systematic ally to care for this group of patients . AIMS To determine the effects of Mental Health Link , a facilitation-based quality improvement programme design ed to improve communication between the teams and systems of care within general practice . DESIGN OF STUDY Exploratory cluster r and omised controlled trial . SETTING Twenty-three urban general practice s and associated community mental health teams . METHOD Practice s were r and omised to service development as usual or to the Mental Health Link programme . Question naires and an audit of notes assessed 335 patients ' satisfaction , unmet need , mental health status , processes of mental and physical care , and general practitioners ' satisfaction with services and beliefs about service development . Service use and intervention costs were also measured . RESULTS There were no significant differences in patients ' perception of their unmet need , satisfaction or general health . Intervention patients had fewer psychiatric relapses than control patients ( mean = 0.39 versus 0.71 , respectively , P = 0.02 ) but there were no differences in documented processes of care . Intervention practitioners were more satisfied and services improved significantly for intervention practice s. There was an additional mean direct cost of pound 63 per patient with long-term mental illness for the intervention compared with the control . CONCLUSION Significant differences were seen in relapse rates and practitioner satisfaction . Improvements in service development did not translate into documented improvements in care . This could be explained by the intervention working via the improvements in informal shared care developed through better link working . This type of facilitated intervention tailored to context has the potential to improve care and interface working TRIAL DESIGN This was a multicenter cluster-r and omized controlled trial . PARTICIPANTS A total of 227 patients ≥18 years old with a new onset of depressive symptoms who screened positive on the first two items of the Patient Health Question naire-9 ( PHQ-9 ) were recruited by primary care physicians ( PCPs ) of eight health districts of three Italian regions from September 2009 to June 2011 . INTERVENTION PCPs of the intervention group received a specific collaborative care program including 2 days of intensive training , implementation of a stepped care protocol , depression management toolkit and scheduled meetings with a dedicated consultant psychiatrist . OBJECTIVE The objective was to determine whether a collaborative care program for depression management in primary care leads to higher remission rate than usual PCP care . OUTCOMES Outcome was clinical remission as expressed on PHQ-9 < 5 at 3 months . R AND OMIZATION An independent research er used computer-generated r and omization to assign involved primary care groups to the two alternative arms . BLINDING PCPs and research personnel were not blinded . RESULTS The 223 PCPs enrolled recruited 227 patients ( 128 in collaborative care arm , 99 in the usual care arm ) . At 3 months ( n=210 ) , the proportion of patients who achieved remission was higher , though the difference was not statistically significant , in the collaborative care group . The effect size was of 0.11 . When considering only patients with minor/major depression , collaborative care appeared to be more effective than usual care ( P=.015 ) . CONCLUSIONS The present intervention for managing depression in primary care , design ed to be applicable to the Italian context , appears to be effective and feasible The aim of this study was to evaluate the effect of an individual support ( IS ) intervention including intensified primary healthcare on the utilisation of specialist care among cancer patients , and to investigate if such an effect was modified by the patient 's age ( less than 70 years or 70 years and more ) . Newly diagnosed cancer patients ( n=416 ) were r and omised between the intervention and a control condition , and data were collected on the utilisation of specialist care within 3 months from inclusion . Intensified primary healthcare comprised extended information from the specialist clinics , and education and supervision in cancer care for general practitioners ( GPs ) and home-care nurses . The support given also included interventions design ed to diminish problems of weight loss and psychological distress . The intervention reduced the number of admissions ( NoA ) and the days of hospitalisation ( DoH ) after adjustment for weight loss and psychological distress , but only for older patients . Older patients r and omised to the intervention ( n=82 ) experienced 393 fewer DoH than the older control patients ( n=79 ) . In addition , the proportion of older patients in the IS group who utilised acute specialist care was smaller compared with older control patients group . The conclusion is that older cancer patients ' utilisation of specialist care may be reduced by intensified primary healthcare services BACKGROUND Patient-held records can improve communication across the primary - secondary interface . There has been no previous rigorous assessment of the utility of patient-held records for people with schizophrenia from a primary care perspective and their value for this population is unclear . AIM To evaluate the effectiveness of a patient-held record for patients with schizophrenia receiving shared care . DESIGN OF STUDY Cluster r and omised controlled trial . SETTING Seventy-four general practice s and six community mental health localities in Birmingham , Engl and between June 1998 and June 1999 . METHOD A sample of 201 patients with schizophrenia ( ICD-10 classification F20 ) was recruited ; of these , 100 were intervention and 101 were control . Patient-held records were given to the intervention patients . At 12-month follow-up , all patients were accounted for and 191 ( 95 % ) were revisited . Primary outcomes were the Verona Service Satisfaction Scale-54 ( VSSS-54 ) and the Krawiecka and Goldberg ( K & G ) rating scale of psychopathology at 12-month follow-up . Secondary outcomes were use of primary and secondary care services . RESULTS A total of 63/92 ( 68.5 % ) patients still had the patient-held record , 64/92 ( 69.6 % ) had used it , and 39 ( 60.9 % ) of the 64 who had used it said the patient-held record was regularly used by their keyworker . However the patient-held record had no significant effect on primary outcomes ( VSSS-54 : F1,116 = 0.06 , P = 0.801 , K & G : F1,116 = 0.6 , P = 0.439 ) or on use of services . A higher symptom score was associated with not using the patient-held record . CONCLUSIONS The trial provides no good evidence to suggest that patient-held records should be introduced as part of routine shared care for all patients with schizophrenia . However , the patient-held record was acceptable to patients with schizophrenia and acted as a communication tool , particularly between patients and keyworkers BACKGROUND Accumulating evidence suggests that collaborative models of care enhance communication among primary care providers , improving quality of care and outcomes for patients with chronic conditions . We sought to determine whether a multifaceted intervention that used a collaborative care model and was directed through primary care providers would improve symptoms of angina , self-perceived health , and concordance with practice guidelines for managing chronic stable angina . METHODS We conducted a prospect i ve trial , cluster r and omized by provider , involving patients with symptomatic ischemic heart disease recruited from primary care clinics at 4 academically affiliated Department of Veterans Affairs health care systems . Primary end points were changes over 12 months in symptoms on the Seattle Angina Question naire , self-perceived health , and concordance with practice guidelines . RESULTS In total , 183 primary care providers and 703 patients participated in the study . Providers accepted and implemented 91.6 % of 701 recommendations made by collaborative care teams . Almost half were related to medications , including adjustments to β-blockers , long-acting nitrates , and statins . The intervention did not significantly improve symptoms of angina or self-perceived health , although end points favored collaborative care for 10 of 13 prespecified measures . While concordance with practice guidelines improved 4.5 % more among patients receiving collaborative care than among those receiving usual care ( P < .01 ) , this was mainly because of increased use of diagnostic testing rather than increased use of recommended medications . CONCLUSION A collaborative care intervention was well accepted by primary care providers and modestly improved receipt of guideline -concordant care but not symptoms or self-perceived health in patients with stable angina BACKGROUND There is a high prevalence of depression in patients with diabetes mellitus . Depression has been shown to be associated with poor self-management ( adherence to diet , exercise , checking blood glucose levels ) and high hemoglobin A1c ( HbA1c ) levels in patients with diabetes . OBJECTIVE To determine whether enhancing quality of care for depression improves both depression and diabetes outcomes in patients with depression and diabetes . DESIGN R and omized controlled trial with recruitment from March 1 , 2001 , to May 31 , 2002 . SETTING Nine primary care clinics from a large health maintenance organization . PARTICIPANTS A total of 329 patients with diabetes mellitus and comorbid major depression and /or dysthymia . Intervention Patients were r and omly assigned to the Pathways case management intervention ( n = 164 ) or usual care ( n = 165 ) . The intervention provided enhanced education and support of antidepressant medication treatment prescribed by the primary care physician or problem-solving therapy delivered in primary care . MAIN OUTCOME MEASURES Independent blinded assessment s at baseline and 3 , 6 , and 12 months of depression ( Hopkins Symptom Checklist 90 ) , global improvement , and satisfaction with care . Automated clinical data were used to evaluate adherence to antidepressant regimens , percentage receiving specialty mental health visits , and HbA1c levels . RESULTS When compared with usual care patients , intervention patients showed greater improvement in adequacy of dosage of antidepressant medication treatment in the first 6-month period ( odds ratio [ OR ] , 4.15 ; 95 % confidence interval [ CI ] , 2.28 - 7.55 ) and the second 6-month period ( OR , 2.90 ; 95 % CI , 1.69 - 4.98 ) , less depression severity over time ( z = 2.84 , P = .004 ) , a higher rating of patient-rated global improvement at 6 months ( intervention 69.4 % vs usual care 39.3 % ; OR , 3.50 ; 95 % CI , 2.16 - 5.68 ) and 12 months ( intervention 71.9 % vs usual care 42.3 % ; OR , 3.50 ; 95 % CI , 2.14 - 5.72 ) , and higher satisfaction with care at 6 months ( OR , 2.01 ; 95 % CI , 1.18 - 3.43 ) and 12 months ( OR , 2.88 ; 95 % CI , 1.67 - 4.97 ) . Although depressive outcomes were improved , no differences in HbA1c outcomes were observed . CONCLUSION The Pathways collaborative care model improved depression care and outcomes in patients with comorbid major depression and /or dysthymia and diabetes mellitus , but improved depression care alone did not result in improved glycemic control BACKGROUND Depression is the most common mental health disorder in people aged over 65 years . Late-life depression is associated with chronic illness and disability . AIM To investigate the feasibility of a collaborative care model for depression in older people in a primary care setting . DESIGN OF STUDY R and omised controlled trial with 16-weeks follow up . SETTING A primary care trust in Manchester . METHOD Participants were 105 people aged 60 years or older who scored 5 or more on the Geriatric Depression Scale ; 53 were r and omly allocated to an intervention group and 52 to a usual care group . The intervention group received care managed by a community psychiatric nurse who delivered an intervention comprising a facilitated self-help programme with close liaison with primary care professionals and old-age psychiatry according to a defined protocol . The usual care group received usual GP care . A nested qualitative study explored the views of the health professionals and patients regarding the acceptability and effectiveness of the intervention . RESULTS The main outcome measure was recovery from depression . Patients in the intervention group were less likely to suffer from major depressive disorder at follow up compared with usual care ( 0.32 , 95 % confidence = interval = 0.11 to 0.93 , P = 0.036 ) . The qualitative component of the study demonstrated the acceptability of the intervention to patients . CONCLUSION A model of collaborative care for older people with depression , used in a primary care setting with a facilitated self-help intervention is more effective than usual GP care . This study demonstrates that the implementation of a collaborative care model is feasible in UK primary care and that the intervention is effective and acceptable to patients Objectives To compare patient outcomes of three regimes of follow-up care for rheumatoid arthritis ( RA ) out patients with low disease activity . Methods RA out patients ( n=287 ) with Disease Activity Score (DAS28-CRP)<3.2 and Health Assessment Question naire<2.5 from two Danish rheumatology clinics were r and omised to 2-year follow-up by either : ( 1 ) planned rheumatologist consultations , ( 2 ) shared care without planned consultations or ( 3 ) planned nursing consultations . The primary outcome was change in disease activity . DAS28-CRP , Health Assessment Question naire , visual analogue scale (VAS)-pain , fatigue , global health , confidence and satisfaction , quality -of-life by the Short Form 12 and self-efficacy measured by the RA Self-Efficacy question naire and the Arthritis Self-Efficacy Scale , were recorded annually and safety measures were recorded . x-Rays of h and s and feet were taken at baseline and at 2-year follow-up . Mixed effect models were used to explore differences between the three groups over time . Results At 2-year follow-up , the group allocated to nursing consultations had lower disease activity than the group that underwent rheumatologist consultations ( DAS28-CRP −0.3 , p=0.049 ) . The nursing group increased their self-efficacy ( Arthritis Self-Efficacy Scale 18.8 , p=0.001 ) , confidence ( 10.7 , p=0.001 ) and satisfaction ( 10.8 , p<0.001 ) compared with the rheumatologist group . The shared care group reported a transient lower satisfaction compared with the rheumatologist group after 1 year ( −8.8 , p=0.004 ) . No statistically significant differences were seen in other outcome variables . Conclusions It is safe to implement shared care and nursing consultations as alternatives to rheumatologist consultations for RA out patients with low disease activity without deterioration in disease control . Nursing consultations can enhance patients ’ self-efficacy , confidence and satisfaction BACKGROUND The long-term outcome of major depression is often unfavorable , and because most cases of depression are managed by general practitioners ( GPs ) , this places stress on the need to improve treatment in primary care . This study evaluated the long-term effects of enhancing the GP 's usual care ( UC ) with three experimental interventions . METHOD A r and omized controlled trial was conducted from 1998 to 2003 . The main inclusion criterion was receiving GP treatment for a depressive episode . We compared : ( 1 ) UC ( n=72 ) with UC enhanced with : ( 2 ) a psycho-educational prevention ( PEP ) program ( n=112 ) ; ( 3 ) psychiatrist-enhanced PEP ( n=37 ) ; and ( 4 ) brief cognitive behavioral therapy followed by PEP ( CBT-enhanced PEP ) ( n=44 ) . We assessed depression status quarterly during a 3-year follow-up . RESULTS Pooled across groups , depressive disorder-free and symptom-free times during follow-up were 83 % and 17 % respectively . Almost 64 % of the patients had a relapse or recurrence , the median time to recurrence was 96 weeks , and the mean Beck Depression Inventory ( BDI ) score over 12 follow-up assessment s was 9.6 . Unexpectedly , PEP patients had no better outcomes than UC patients . However , psychiatrist-enhanced PEP and CBT-enhanced PEP patients reported lower BDI severity during follow-up than UC patients [ mean difference 2.07 ( 95 % confidence interval ( CI ) 1.13 - 3.00 ) and 1.62 ( 95 % CI 0.70 - 2.55 ) respectively ] and PEP patients [ 2.37 ( 95 % CI 1.35 - 3.39 ) and 1.93 ( 95 % CI 0.92 - 2.94 ) respectively ] . CONCLUSIONS The PEP program had no extra benefit compared to UC and may even worsen outcome in severely depressed patients . Enhancing treatment of depression in primary care with psychiatric consultation or brief CBT seems to improve the long-term outcome , but findings need replication as the interventions were combined with the ineffective PEP program BACKGROUND The long-term management of patients with chronic conditions such as hypertension presents problems for the health services . Shared care addresses these by coordinating care and defining responsibilities . AIM This study set out to investigate the feasibility , acceptability and cost effectiveness of shared general practitioner-hospital care for well-controlled hypertensive patients in an urban area by comparing three matched groups of patients . METHOD A total of 554 outpatient clinic attenders , considered suitable for shared care by their consultant , were r and omly allocated to shared care or follow up in the outpatient clinic ; a third group of 277 patients was selected from a nurse practitioner clinic . Main outcome measures were the proportion of patients in the second year of follow up who had undergone a complete review ( blood pressure measurement , serum creatinine level result and electrocardiograph report ) , acceptability to patients and general practitioners as assessed by question naire , and cost per complete review in year two ( National Health Service and patient costs ) . RESULTS After two years 220 ( 82 % ) shared care patients had had a complete review compared with 146 ( 54 % ) outpatient clinic attenders and 202 ( 75 % ) nurse practitioner clinic attenders . Blood pressure control was similar in each group . Of 297 general practitioners invited , 85 % wished to participate in the study ; 61 % of question naire respondents subsequently wanted shared care to continue while 25 % were unsure . Half of the patients receiving shared care preferred this method of follow up . The rank order of cost-effectiveness ratios was shared care , nurse practitioner care and conventional outpatient care , relative differences being most marked when only patient costs were considered . CONCLUSION Shared care for hypertension is feasible in an urban setting , acceptable to the majority of participants and is a cost-effective method of long-term follow up BACKGROUND Few formalized shared care schemes exist within psychiatry and the evidence base for sharing psychiatric care is weak . AIMS To evaluate the utility of patient-held shared care records for individuals with long-term mental illness . METHOD Cluster-r and omised controlled parallel-group 12-month trial involving 90 patients with long-term mental illness drawn from 28 general practice s. RESULTS Carrying a shared care record had no significant effect on mental state or satisfaction with psychiatric services . Compared with controls , patients in the shared care group were no more likely to be admitted ( relative risk 1.2 , 95 % CI 0.86 - 1.67 ) and attend clinic ( relative risk 0.96 , 95 % CI 0.67 - 1.36 ) over the study period . Uptake of the shared care scheme was low by patients and professionals alike . Subjects with psychotic illness were significantly less likely to use their records ( relative risk 0.51 , 95 % CI 0.27 - 0.99 ) . CONCLUSIONS Patient-held records may not be helpful for patients with long-term mental illness IMPORTANCE Chronic musculoskeletal pain is among the most prevalent , costly , and disabling medical disorders . However , few clinical trials have examined interventions to improve chronic pain in primary care . OBJECTIVE To determine the effectiveness of a telecare intervention for chronic pain . DESIGN , SETTING , AND PARTICIPANTS The Stepped Care to Optimize Pain Care Effectiveness ( SCOPE ) study was a r and omized trial comparing a telephone-delivered collaborative care management intervention vs usual care in 250 patients with chronic ( ≥3 months ) musculoskeletal pain of at least moderate intensity ( Brief Pain Inventory [ BPI ] score ≥5 ) . Patients were enrolled from 5 primary care clinics in a single Veterans Affairs medical center from June 2010 through May 2012 , with 12-month follow-up completed by June 2013 . INTERVENTIONS Patients were r and omized either to an intervention group ( n = 124 ) or to a usual care group whose members received all pain care as usual from their primary care physicians ( n = 126 ) . The intervention group received 12 months of telecare management that coupled automated symptom monitoring with an algorithm-guided stepped care approach to optimizing analgesics . MAIN OUTCOMES AND MEASURES Primary outcome was the BPI total score , which ranges from 0 ( " no pain " ) to 10 ( " pain as bad as you can imagine " ) and for which a 1-point change is considered clinical ly important . Secondary pain outcomes included BPI interference and severity , global pain improvement , treatment satisfaction , and use of opioids and other analgesics . RESULTS Overall , mean ( SD ) baseline BPI scores in the intervention and control groups were 5.31 ( 1.81 ) and 5.12 ( 1.80 ) , respectively . Compared with usual care , the intervention group had a 1.02-point lower ( 95 % CI , -1.58 to -0.47 ) BPI score at 12 months ( 3.57 vs 4.59 ) . Patients in the intervention group were nearly twice as likely to report at least a 30 % improvement in their pain score by 12 months ( 51.7 % vs 27.1 % ; relative risk , 1.9 [ 95 % CI , 1.4 to 2.7 ] ) , with a number needed to treat of 4.1 ( 95 % CI , 3.0 to 6.4 ) for a 30 % improvement . Secondary pain outcomes also improved . Few patients in either group required opioid initiation or dose escalation . CONCLUSIONS AND RELEVANCE Telecare collaborative management increased the proportion of primary care patients with improved chronic musculoskeletal pain . This was accomplished by optimizing nonopioid analgesic medications using a stepped care algorithm and monitoring . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00926588 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 Depression is a common disorder in the elderly population ; with significant elevated rates in terms of morbidity and mortality . Nonetheless it continues to be a subdiagnosticated disease with poor outcomes due to lack in the effectiveness of follow up . We developed collaborative intervention programs for elderly people in primary care at Hospital Italiano de Buenos Aires design ing a r and omized controlled trial in the ambulatory setting . Patients were recruited for an initial comprehensive geriatric evaluation , and then r and omly assigned to the program intervention ( n=18 ) or usual care ( n=19 ) . At 6 months , 55.5 % of intervention patients had a 50 % or greater reduction in depressive symptoms from baseline compared with 31.5 % of those on usual care . Although the reduction of the outcomes of depressive symptoms is not statistically significative , these are preliminary data . We believe there is a trend toward better results with regard to improvements in depressive symptoms in patients in the intervention group , and that this will achieve statistical significance as the number of subjects recruited is increased in the course of the trial BACKGROUND In the treatment of depression , primary care teams play an important role , whose effectiveness improves when inserted into a collaborative model of disease management . AIM To report the results of a clinical trial carried out to test the effectiveness of a collaborative program between primary health teams and specialists supported by an electronic platform . MATERIAL AND METHODS Physicians from four community hospitals belonging to the Reloncavi Health Service network , recruited 81 patients with depression aged 37 to 43 years , 84 % of whom were female . Participants were divided in an active group , which participated in the collaborative program and a control group , which received the usual care , according to the Ministry of Health's Guidelines for Depression . The main outcome was the Beck Depression Inventory ( BDI-I ) score at three months of intervention . RESULTS Participants had an average of 29.6 points ( 95 % CI : 27.6 - 31.6 ) in the BDI-I and 38 % of them had a high suicide risk . There were no statistically significant baseline differences between active and control group . In the intervention group , the BDI-I score changed from 30.0 ( 95 % CI 27.0 to 32.8 ) to 15.3 ( 95 % CI 11.8 to 18.8 ) . In the control group the score changed from 29.2 ( 95 % CI : 26.4 - 31.9 ) points to 20.8 ( 95 % CI 16.8 to 24.7 ) . The decrease was significantly higher in the intervention groups . CONCLUSIONS A program of this kind may be useful to assist primary care teams in remote areas of the country to improve treatment outcomes for depression CONTEXT Patients with depression and poorly controlled diabetes mellitus , coronary heart disease ( CHD ) , or both have higher medical complication rates and higher health care costs , suggesting that more effective care management of psychiatric and medical disease control might also reduce medical service use and enhance quality of life . OBJECTIVE To evaluate the cost-effectiveness of a multicondition collaborative treatment program ( TEAMcare ) compared with usual primary care ( UC ) in out patients with depression and poorly controlled diabetes or CHD . DESIGN R and omized controlled trial of a systematic care management program aim ed at improving depression scores and hemoglobin A(1c ) ( HbA(1c ) ) , systolic blood pressure ( SBP ) , and low-density lipoprotein cholesterol ( LDL-C ) levels . SETTING Fourteen primary care clinics of an integrated health care system . PATIENTS Population -based screening identified 214 adults with depressive disorder and poorly controlled diabetes or CHD . INTERVENTION Physician-supervised nurses collaborated with primary care physicians to provide treatment of multiple disease risk factors . MAIN OUTCOME MEASURES Blinded assessment s evaluated depressive symptoms , SBP , and HbA(1c ) at baseline and at 6 , 12 , 18 , and 24 months . Fasting LDL-C concentration was assessed at baseline and at 12 and 24 months . Health plan accounting records were used to assess medical service costs . Quality -adjusted life-years ( QALYs ) were assessed using a previously developed regression model based on intervention vs UC differences in HbA(1c ) , LDL-C , and SBP levels over 24 months . RESULTS Over 24 months , compared with UC controls , intervention patients had a mean of 114 ( 95 % CI , 79 to 149 ) additional depression-free days and an estimated 0.335 ( 95 % CI , -0.18 to 0.85 ) additional QALYs . Intervention patients also had lower mean outpatient health costs of $ 594 per patient ( 95 % CI , -$3241 to $ 2053 ) relative to UC patients . CONCLUSIONS For adults with depression and poorly controlled diabetes , CHD , or both , a systematic intervention program aim ed at improving depression scores and HbA(1c ) , SBP , and LDL-C levels seemed to be a high-value program that for no or modest additional cost markedly improved QALYs . TRIAL REGISTRATION clinical trials.gov Identifier : BACKGROUND Despite high rates of relapse and recurrence , few primary care patients with recurrent or chronic depression are receiving continuation and maintenance-phase treatment . We hypothesized that a relapse prevention intervention would improve adherence to antidepressant medication and improve depression outcomes in high-risk patients compared with usual primary care . METHODS Three hundred eighty-six patients with recurrent major depression or dysthymia who had largely recovered after 8 weeks of antidepressant treatment by their primary care physicians were r and omized to a relapse prevention program ( n = 194 ) or usual primary care ( n = 192 ) . Patients in the intervention group received 2 primary care visits with a depression specialist and 3 telephone visits over a 1-year period aim ed at enhancing adherence to antidepressant medication , recognition of prodromal symptoms , monitoring of symptoms , and development of a written relapse prevention plan . Follow-up assessment s were completed at 3 , 6 , 9 , and 12 months by a telephone survey team blinded to r and omization status . RESULTS Those in the intervention group had significantly greater adherence to adequate dosage of antidepressant medication for 90 days or more within the first and second 6-month periods and were significantly more likely to refill medication prescriptions during the 12-month follow-up compared with usual care controls . Intervention patients had significantly fewer depressive symptoms , but not fewer episodes of relapse/recurrence over the 12-month follow-up period . CONCLUSIONS A relapse prevention program targeted to primary care patients with a high risk of relapse/recurrence who had largely recovered after antidepressant treatment significantly improved antidepressant adherence and depressive symptom outcomes BACKGROUND A steady increase in chronic obstructive pulmonary disease ( COPD ) admissions was addressed by enhancing primary care to provide intensive chronic disease management . AIM To compare the effect of a disease management programme , including a COPD management guideline , a patient-specific care plan and collaboration between patients , general practitioners , practice nurses , hospital physicians and nurse specialists with conventional care , on hospital admissions and quality of life . METHODS One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records . General practice s were r and omized to either conventional care ( CON ) , or the intervention ( INT ) . Pre- and post- study assessment included spirometry , Shuttle Walk Test , Short Form-36 , and the Chronic Respiratory Question naire ( CRQ ) . Admission data were compared for 12 months prior to and during the trial . RESULTS For respiratory conditions , mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1 , whereas those for the CON group increased from 3.5 to 4.0 ( group difference , P = 0.030 ) The INT group also showed an improvement for two dimensions of the CRQ , fatigue ( P = 0.010 ) and mastery ( P = 0.007 ) . CONCLUSIONS A chronic disease management programme for COPD patients that incorporated a variety of interventions , including pulmonary rehabilitation and implemented by primary care , reduced admissions and hospital bed days . Key elements were patient participation and information sharing among healthcare providers IMPORTANCE Among older home health care patients , depression is highly prevalent , is often inadequately treated , and contributes to hospitalization and other poor outcomes . Feasible and effective interventions are needed to reduce this burden of depression . OBJECTIVE To determine whether , among older Medicare Home Health recipients who screen positive for depression , patients of nurses receiving r and omization to an intervention have greater improvement in depressive symptoms during 1 year than patients receiving enhanced usual care . DESIGN , SETTING , AND PARTICIPANTS This cluster r and omized effectiveness trial conducted at 6 home health care agencies nationwide assigned nurse teams to an intervention ( 12 teams ) or to enhanced usual care ( 9 teams ) . Between January 13 , 2009 , and December 6 , 2012 , Medicare Home Health patients 65 years and older who screened positive for depression on routine nursing assessment s were recruited , underwent assessment , and were followed up at 3 , 6 , and 12 months by research staff blinded to intervention status . Patients were interviewed at home and by telephone . Of 502 eligible patients , 306 enrolled in the study . INTERVENTIONS The Depression Care for Patients at Home ( Depression CAREPATH ) trial requires nurses to manage depression at routine home visits by weekly symptom assessment , medication management , care coordination , education , and goal setting . Nurses ' training totaled 7 hours ( 4 onsite and 3 via the web ) . Research ers telephoned intervention team supervisors every other week . MAIN OUTCOMES AND MEASURES Depression severity , assessed by the 24-item Hamilton Scale for Depression ( HAM-D ) . RESULTS The 306 participants were predominantly female ( 69.6 % ) , were racially/ethnically diverse ( 18.0 % black and 16.0 % Hispanic ) , and had a mean ( SD ) age of 76.5 ( 8.0 ) years . In the full sample , the intervention had no effect ( P = .13 for intervention × time interaction ) . Adjusted HAM-D scores ( Depression CAREPATH vs control ) did not differ at 3 months ( 10.5 vs 11.4 , P = .26 ) or at 6 months ( 9.3 vs 10.5 , P = .12 ) but reached significance at 12 months ( 8.7 vs 10.6 , P = .05 ) . In the sub sample with mild depression ( HAM-D score , < 10 ) , the intervention had no effect ( P = .90 ) , and HAM-D scores did not differ at any follow-up points . Among 208 participants with a HAM-D score of 10 or higher , the Depression CAREPATH demonstrated effectiveness ( P = .02 ) , with lower HAM-D scores at 3 months ( 14.1 vs 16.1 , P = .04 ) , at 6 months ( 12.0 vs 14.7 , P = .02 ) , and at 12 months ( 11.8 vs 15.7 , P = .005 ) . CONCLUSION AND RELEVANCE Home health care nurses can effectively integrate depression care management into routine practice . However , the clinical benefit seems to be limited to patients with moderate to severe depression . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01979302 OBJECTIVE The aims of this study were ( 1 ) to assess the long-term effects of a collaborative care intervention for patients with depression on process of care outcomes , and ( 2 ) to describe whether case management was continued after the end of the original one-year intervention . METHODS This 24-month follow-up of a r and omized controlled trial took place 12 months after the end of the 1-year intervention . Data collection occurred by means of self-rating question naires and from medical records . We calculated linear mixed and logistic generalized estimating equation models . RESULTS Of the 626 patients included at baseline , 439 ( 70.1 % ) participated in this follow-up . Intervention recipients gave higher ratings than control recipients in terms of mean overall Patient Assessment of Chronic Illness Care ( PACIC ) scores ( 3.12 vs. 2.86 ; P = .019 ) , but no difference was found in medication adherence ( mean Morisky score 2.59 vs. 2.65 , P = .56 ) , prescribed antidepressant medications ( 60.2 % vs. 55.1 % ; P = .25 ) , visits to the family physician ( 15.96 vs. 14.46 , P = .58 ) or mental health specialist ( 3.01 vs. 2.94 , P = .94 ) over the 12 month follow-up period . Case management was continued for 47 ( 22.5 % ) selected intervention patients after the original intervention had ended . CONCLUSION At 24 months , intervention and control recipients had different PACIC ratings , but other process of care outcomes did not differ . PRACTICE IMPLICATION S The main effects of the intervention are apparent at 12 months AIMS Chronic heart failure ( CHF ) patients are frequently rehospitalized within 6 months after an episode of fluid retention . Rehospitalizations are preventable , but this requires an extensive organization of the healthcare system . In this study , we tested whether intensive follow-up of patients through a telemonitoring-facilitated collaboration between general practitioners ( GPs ) and a heart failure clinic could reduce mortality and rehospitalization rate . METHODS AND RESULTS One hunderd and sixty CHF patients [ mean age 76 ± 10 years , 104 males , mean left ventricular ejection fraction ( LVEF ) 35 ± 15 % ] were block r and omized by sealed envelopes and assigned to 6 months of intense follow-up facilitated by telemonitoring ( TM ) or usual care ( UC ) . The TM group measured body weight , blood pressure , and heart rate on a daily basis with electronic devices that transferred the data automatically to an online data base . Email alerts were sent to the GP and heart failure clinic to intervene when pre-defined limits were exceeded . All-cause mortality was significantly lower in the TM group as compared with the UC group ( 5 % vs. 17.5 % , P = 0.01 ) . The total number of follow-up days lost to hospitalization , dialysis , or death was significantly lower in the TM group as compared with the UC group ( 13 vs. 30 days , P = 0.02 ) . The number of hospitalizations for heart failure per patient showed a trend ( 0.24 vs. 0.42 hospitalizations/patient , P = 0.06 ) in favour of TM . CONCLUSION Telemonitoring-facilitated collaboration between GPs and a heart failure clinic reduces mortality and number of days lost to hospitalization , death , or dialysis in CHF patients . These findings need confirmation in a large trial AIMS To evaluate the effectiveness of a two-arm quality improvement program ( QIP ) to support general practice with limited tradition in chronic care on type 2 diabetes patient outcomes . METHODS During 18 months , we performed a cluster r and omized trial with r and omization of General Practice s. The usual QIP ( UQIP : 53 GPs , 918 patients ) merged st and ard interventions including evidence -based treatment protocol , annual benchmarking , postgraduate education , case-coaching for GPs and patient education . The advanced QIP ( AQIP : 67 GPs , 1577 patients ) introduced additional interventions focussing on intensified follow-up , shared care and patient behavioural changes . Main outcomes were HbA1c , systolic blood pressure ( SBP ) , and low density lipoprotein cholesterol ( LDL-C ) , analyzed by generalized estimating equations and linear mixed models . RESULTS In UQIP , endpoints improved significantly after intervention : HbA1c -0.4 % , 95 % CI [ -0.4 ; -0 . 3 ] ; SBP -3mmHg , 95 % CI [ -4 ; -1 ] ; LDL-C -13mg/dl , 95 % CI [ -15 ; -11 ] . In AQIP , there were no significant additional improvements in outcomes : HbA1c -0.4 % , 95 % CI [ -0.4 ; -0.3 ] ; SBP -4mmHg , 95 % CI [ -5 ; -2 ] ; LDL-C -14mg/dl , 95 % CI [ -15 ; -11 ] . CONCLUSIONS A multifaceted program merging st and ard interventions in support of general practice induced significant improvements in the quality of diabetes care . Intensified follow-up in AQIP with focus on shared care and patient behaviour changes did not yield additional benefit OBJECTIVE This study examined whether a collaborative care model for depression would improve clinical and functional outcomes for depressed patients with chronic general medical conditions in primary care practice s in Puerto Rico . METHODS A total of 179 primary care patients with major depression and chronic general medical conditions were r and omly assigned to receive collaborative care or usual care . The collaborative care intervention involved enhanced collaboration among physicians , mental health specialists , and care managers paired with depression-specific treatment guidelines , patient education , and follow-up . In usual care , study personnel informed the patient and provider of the diagnosis and encouraged patients to discuss treatment options with their provider . Depression severity was assessed with the Hopkins Symptom Checklist ; social functioning was assessed with the 36-item Short Form . RESULTS Compared with usual care , collaborative care significantly reduced depressive symptoms and improved social functioning in the six months after r and omization . Integration of collaborative care in primary care practice s considerably increased depressed patients ' use of mental health services . CONCLUSIONS Collaborative care significantly improved clinical symptoms and functional status of depressed patients with coexisting chronic general medical conditions receiving treatment for depression in primary care practice s in Puerto Rico . These findings highlight the promise of the collaborative care model for strengthening the relationship between mental health and primary care services in Puerto Rico |
2,622 | 21,712,233 | The MIDHS technique result ed in less blood loss , shorter hospitalization , lower pain level , faster fracture healing , and better hip function when compared with the CDHS technique .
There was no significance difference between the 2 groups with regard to postoperative complications and implant position .
The MIDHS technique may achieve perioperative benefits when compared with the CDHS technique | The classic dynamic hip screw fixation of intertrochanteric fractures may be associated with significant blood loss and soft tissue damage , which may worsen existing comorbidities of frail elderly patients .
Recently , minimally invasive dynamic hip screw ( MIDHS ) technique was developed for osteo synthesis of intertrochanteric fractures . | One hundred thirty-one patients ( 135 fractures ) who sustained an intertrochanteric fracture were assigned r and omly to treatment with either a sliding hip screw or an intramedullary hip screw and followed up prospect ively . In patients with unstable intertrochanteric fractures , the intramedullary device was associated with 23 % less surgical time and 44 % less blood loss ; however , use of the intramedullary hip screw in patients who had a stable fracture pattern required 70 % greater fluoroscopic time . Intraoperative complications occurred exclusively in patients in the intramedullary hip screw group . There were no differences in the rates of functional recovery between the two fixation groups OBJECTIVE To compare minimally invasive dynamic hip screw ( MIDHS ) fixation with conventional dynamic hip screw ( CDHS ) fixation for treatment of intertrochanteric femoral fracture . METHODS Of the 66 participants in this double-blind study , 35 were r and omised to MIDHS and 31 to CDHS fixation . Main outcome measurements were wound size , haemoglobin decrease , blood transfusion rate , pain score , analgesic consumption , Elderly Mobility Scale score , hip screw position , tip-apex distance , union rate , time to healing and complication rate . RESULTS The groups had similar preoperative clinical data . Postoperatively the MIDHS group had significantly smaller wound size , less blood loss , lower blood transfusion rates , pain scores and rates of analgesic consumption , and higher early Elderly Mobility Scale scores . There were no significant differences in fracture alignment , hip screw position , tip-apex distance , union rate , time to healing or complication rate . CONCLUSION MIDHS fixation of intertrochanteric fractures is effective and safe and significantly reduces blood loss , pain and rehabilitation period , without sacrificing reduction alignment , screw position , fixation stability or bone healing OBJECTIVE To observe and report the clinical results of the treatment of intertrochanteric hip fractures treated with a 135-degree hip screw with a two-hole side plate . DESIGN Prospect i ve consecutive . SETTING Community private practice . PATIENTS A consecutive series of seventy primarily older patients with intertrochanteric hip fractures treated in a community hospital setting . INTERVENTION Surgical treatment with a 135-degree sliding hip screw and a two-hole side plate . MAIN OUTCOME MEASUREMENTS Healing rate and time , operative blood loss and time , incidence of hardware failure , and complications including loss of side plate fixation and amount of collapse . RESULTS Sixty-nine patients , with seventy intertrochanteric hip fractures , underwent surgical treatment with a 135-degree sliding hip screw and a two-hole side plate . There were twenty-one ( 30 percent ) A1.1 , sixteen ( 23 percent ) A1.2 , twenty-one ( 30 percent ) A2.1 , and twelve ( 17 percent ) A2.2 fractures in twenty-three ( 33 percent ) men and forty-six ( 67 percent ) women . Average age was seventy-nine years . The average estimated blood loss was seventy-seven cubic centimeters ( range 10 to 300 cubic centimeters ) , and the average surgical time was thirty-one minutes ( range 8 to 90 minutes ) . The average time to union was fifteen weeks ( range 8 to 17 weeks ) . There were three failures : two from screw cut-out and one from screw plate dissociation . No cases failed due to loss of fixation of the two-hole side plate . Collapse was minimum in fifty-five patients ( 79 percent ) , moderate in twelve patients ( 17 percent ) , and severe in two patients ( 3 percent ) . CONCLUSIONS Use of the 135-degree sliding hip screw with a two-hole side plate produces satisfactory healing and results in relatively low blood loss and short surgical times without the loss of side plate fixation Objective This study evaluates the safety and outcome of a minimally invasive technique for inserting a st and ard dynamic hip screw for intertrochanteric fractures . Hypothesis The use of st and ard plate in a minimally invasive technique is both possible and advantageous to patient outcome . Design and Methods Prospect i ve surgeon-r and omized blinded outcome clinical study comparing new technique to conventional technique . Main Outcome Measure Pain , operative time and mean hemoglobin drop in percutaneous hip fixation . Results The minimally invasive technique had significantly less blood loss ( P < 0.001 ) , operative time ( P < 0.001 ) and a trend to less morphine use . Conclusions Minimal invasive technique significantly reduces blood loss and operative time for fixation of intertrochanteric hip fractures without sacrifice of fixation stability or bone healing The study is a prospect i ve evaluation and comparison . A minimally invasive Dynamic Hip Screw ( MIDHS ) technique is presented . One hundred and two patients with intertrochanteric fractures were treated with either a MIDHS or a conventional dynamic hip screw ( CDHS ) . We used the Singh index as a measure of osteoporosis and also classified the fractures according to three different systems ( OTA , Boyd-Griffin , and Evans ) . All patients were followed up for 12 months with a hip score evaluation . The patients were divided into two groups , based on the method of treatment . The MIDHS group includes 42 patients with an average age of 72.6 years . The CDHS group includes 60 patients , with an average age of 71.3 years . Both groups were similar in injury mechanism , fracture types , mean Singh index and confounding medical condition ( all p values > 0.05 ) . The CDHS group had significantly larger wound incision , greater haemoglobin level drop , higher pain level , more total analgaesic use and longer hospital stay than the MIDHS group ( all p values<0.05 ) . The hip score , union rate , healing time , adequate reduction and adequate screw position rate was not significantly different between the two groups ( all p values > 0.05 ) . In conclusion , either a MIDHS or a CDHS in the treatment of intertrochanteric fractures is an effective , simple and safe method . The mini-invasive technique as opposed to the conventional technique has smaller wound size , lower pain level , and lower blood loss . Hospital stay and total analgaesic use were decreased , benefitting the patient and reducing hospital cost . RésuméEtude prospect i ve de 102 patients avec une fracture intertrochantérienne traitée par une vis-plaque dynamique soit avec une technique mini-invasive ( MIDHS ) soit avec une technique conventionnelle ( CDHS ) . L’index de Singh était utilisé pour la mesure de l’ostéoporose et les fractures étaient classées selon trois systèmes : OTA , Boyd-Griffin et Evans . Tous les patients étaient suivi 1 an . Le groupe MIDHS comprenait 42 patients d’âge moyen 72,6 ans et le groupe CDHS comprenait 60 patients d’âge moyen 71,3 ans . Les 2 groupes étaient similaires pour le mécanisme du traumatisme , le type de la fracture , l’index de Singh et les conditions médicales générales ( toujours p<0,05 ) . Le groupe CDHS avait une plus longue incision cutané , une plus gr and e chute du taux d’hémoglobine , un plus haut niveau de douleurs , et un séjour hospitalier plus long que l’autre groupe ( p<0,05 ) . En conclusion les 2 méthodes de traitement étaient efficaces et sûres . La technique mini-invasive permettait une incision plus courte , un niveau de douleurs et une perte sanguine plus faibles . La durée de séjour et la consommation d’analgésiques etaient diminuées au profit du patient et du coût hospitalier Introduction Intertrochanteric fractures of femur are common in elderly patients . The compression hip screw has become the predominant method for osteo synthesis of intertrochanteric fractures . However , the conventional dynamic hip screws ( CDHS ) technique has some disadvantages . Recently , we have used a minimally invasive dynamic hip screws ( MIDHS ) technique to reduce these disadvantages . This prospect i ve study is to compare curative effect of MIDHS with that of CDHS with open reduction on Evans type 1 intertrochanteric fractures . Material s and methods All 97 fractures were classified according to the Evans systems . The MIDHS group included 47 patients with an average age of 68.7 years , and the CDHS group included 50 patients with an average age of 68.7 years . The Singh index was used as a measure of osteoporosis . Results Both groups were similar in injury mechanism , fracture types , mean Singh index and medical diseases ( all P > 0.50 ) . All fractures were healed within 4 months in both groups except three cases who were implant failure and nonunion in the CDHS group . The MIDHS group had significantly smaller wound size , shorter surgery time , less blood loss , lower blood transfusion rate , earlier active mobilization of fractured hip joint , shorter hospital stay , lower serious complication rate and higher Harris hip score than the CDHS group ( all P < 0.05 ) . The satisfactory reduction , adequate screw position , healing time and union rate was not significantly difference between two groups ( all P > 0.05 ) . Conclusion When the fractures are treated adequately , either the MIDHS or the CDHS with open reduction is an effective and safe method , but the MIDHS is superior to the CDHS with open reduction for the treatment of Evans type 1 intertrochanteric fractures of femur The aim of this prospect i ve matched-pair ( age , sex , fracture type , residential status , and walking ability at fracture ) study was to analyse the short-term outcome after Gamma nail ( GN ) and dynamic hip screw ( DHS ) fixation , focusing especially on functional aspects ( St and ardised Audit of Hip Fractures in Europe [ SAHFE ] hip fracture follow-up forms ) , reoperations , and mortality . Both groups consisted of 134 patients . DHS and GN groups did not differ significantly with respect to location of residence at 4 months or returning to the prefracture dwelling ( 78 % vs. 73 % , P = 0.224 ) . The change in walking ability at 4 months compared to prefracture situation was better in the DHS group ( p = 0.042 ) , although there was no difference in the change of use of walking aids . The frequency of reoperations during the first year was somewhat lower in the DHS group ( 8.2 % vs. 12.7 % , p = 0.318 ) . Mortality was lower in the DHS group both at 4 months ( 6.0 % vs. 13.4 % , p = 0.061 ) and 12 months ( 14.9 % vs. 23.9 % , p = 0.044 ) . Although walking ability was better and mortality lower in the DHS group , both methods are useful in the treatment of trochanteric femoral fractures . RésuméLe but de cette étude prospect i ve est de comparer et d’analyser le devenir à long terme des fractures du col fémoral traitées par clou Gamma ( GN ) ou par le vis plaque ( DHS ) , notamment en ce qui concerne leurs aspects fonctionnels , les ré interventions et la mortalité . Deux groupes de 134 patients ont été comparés . Il n’y a pas de différence significative entre ces deux groupes à 4 mois en ce qui concerne le retour aux activités pré-opératoires ( 78 % vs. 73 % , P = 0.224 ) entre DHS et GN . Néanmoins , la marche à 4 mois est bien meilleure dans le groupe DHS ( p = 0.042 ) , il n’y a pas de différence en ce qui concerne l’utilisation d’aide à la marche , moins de ré interventions dans le groupe DHS ( 8,2 % vs. 12,7 % , p = 0.318 ) , de même en ce qui concerne la mortalité ( 6,0 % vs. 13,4 % , p = 0.061 ) et à 12 mois ( 14,9 % vs 23,9 % , p = 0.044 ) . Ces deux méthodes sont utiles dans le traitement des fractures cervico trochantériennes , néanmoins , l’amélioration de la marche et la mortalité sont bien meilleures dans le groupe GHS que dans le groupe clou gamma 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 We present the results of a technique of dynamic hip screw insertion through a very small incision , typically 2 - 2.5 cm . The technique is performed using a st and ard dynamic hip screw set and requires no additional equipment . We compared the results to those of an age and sex-matched group who had undergone the operation through a traditional approach . We compared the time spent in theatre , the pre- and post-operative haemoglobin concentration , haematocrit and prevalence of wound infection . Thirteen consecutive cases were performed by one surgeon using the percutaneous technique . There were nine females and four males with a mean age of 84 years ( range 62 - 96 years ) . Each had a 135 degrees four-hole plate . The mean post-operative drop in haemoglobin concentration in the percutaneous group was 2.2 g/dl ( range 0 - 4.4 g/dl ) compared to 3.5 g/dl ( range 1.2 - 5.4 g/dl ) in the control group ( p = 0.014 ) . The mean haematocrit drop was 0.07 ( range 0 - 0.12 ) in the percutaneous group compared to 0.10 ( range 0.03 - 0.17 ) in the control group ( p = 0.017 ) . The mean theatre time with the percutaneous technique was 57 min ( range 40 - 75 min ) and in the control group , 60 min ( range 30 - 95 min ) . There were no wound problems . It is likely that this minimally invasive technique offers a better clinical outcome at no extra expense and warrants further evaluation in a larger study The aim of this study was design ed to assess the risk factors of lag-screw cutout in the treatment of intertrochanteric fracture with a dynamic hip screw ( DHS ) . From 2003 to 2007 , 1,150 patients who had acute unilateral intertrochanteric fractures of the femur were enrolled to the study . All fractures were managed by closed reduction and internal fixation with 135 ° DHS devices . Patient demographics , fracture patterns , reduction and fixation and perioperative course parameters were all recorded . The follow-up period was 38 months on average ( range 16–60 months ) . Finally , 937 patients were available for evaluation of final results in which we focused on lag-screw cutout . Excluding complications not related to screw position , 64 patients ( 6.8 % ) with screw cutout were encountered , and the remaining 873 patients had uneventful union , with the average union time of 17.5 weeks ( range15–24 weeks ) . Upon analysis with logistic regression , the tip−apex distance ( TAD ) was shown to be the most important predictive factor for cutout , followed by screw position , fracture pattern , reduction and patient age . In order to decrease the risk of lag-screw cutout , it is important to ensure good fracture reduction and to place the lag screw in either the middle/middle or inferior/middle position with appropriate TAD OBJECTIVE Intertrochanteric hip fractures are very common and early mobilisation correlates with a better outcome . The ideal surgical procedure should protect the soft tissue envelope , thereby preserving blood supply and reducing blood loss . Furthermore , occupational exposure to fluoroscopy that is used in hip fracture fixation remains a concern amongst orthopaedic surgeons . Computer-aided surgery can help to reduce reliance on fluoroscopy . We therefore combined the principles of minimally invasive plate osteo synthesis ( MIPO ) and computer navigation to describe a new procedure . We also present our results using this technique of minimally invasive computer-navigated dynamic hip screw fixation ( navMIS-DHS ) , and compare it to computer-navigated open DHS fixation ( nav-DHS ) and to conventional open DHS fixation ( conv-DHS ) . MATERIAL S AND METHODS This paper has three parts . In the first part , we describe the procedure of navMIS-DHS in detail . In the second part , we present our initial retrospective pilot series of 35 cases . Amongst them we performed 5 navMIS-DHS , 3 nav-DHS and 27 conv-DHS . There were also two cases of conv-DHS deliberately performed with a mini-incision in an attempt to see if we could duplicate the 5 cm incision that we achieved with navMIS-DHS . All patients were followed up for a minimum of 6 months . In the third part , we performed a single surgeon prospect i ve evaluation of navMIS-DHS versus conv-DHS involving 43 fractures in two arms . RESULTS We were able to achieve reduction in fluoroscopy time . There was also reduction in opiate requirement post-operatively in the minimally invasive procedure . The incision sizes were also smaller . The prospect i ve study also showed less wound-related complications in navMIS-DHS and a shorter time to ambulation . Implant positions were acceptable but we have also described how it may be improved . CONCLUSIONS Navigated MIS-DHS , by virtue of less pain , better healing , earlier rehabilitation and potentially shorter hospital stay , would benefit both the patients and reduce the economic strain on the health care system . It is a safe and reproducible procedure . Technical difficulties are present and these need to be addressed with further modifications of technique , and instrumentation |
2,623 | 26,321,946 | In addition , prospect i ve analysis including four studies showed pooled ES of 0.033 ( 95 % CI -0.001 - 0.067 ) for MMSE ( I ( 2 ) < 0.001 % ) , indicating that sub clinical hypothyroidism was not significantly associated with accelerated cognitive decline .
This systematic review and meta- analysis provides no evidence that supports an association between SCH and cognitive impairment in relatively healthy older adults | Sub clinical hypothyroidism ( SCH ) , defined as elevated thyroid stimulating hormone ( TSH ) and normal thyroid hormone levels , and cognitive impairment are both common in older people .
While the relation between overt hypothyroidism and cognitive impairment is well established , data on the association between SCH and cognitive impairment are conflicting .
This systematic review and meta- analysis was performed to assess available evidence on the association of SCH with cognition in community dwelling , relatively healthy older adults . | OBJECTIVE Sub clinical thyroid disorders are common in older individuals . Health risks associated with sub clinical hypothyroidism in older adults are unclear . The aim of the study is to evaluate whether thyroid status in elderly subjects correlates with physical and cognitive function at baseline and with 3-year mortality . DESIGN A population -based , prospect i ve cohort of the OCTABAIX study ( 307 inhabitants aged 85 years at baseline ) . METHODS Chronic drug prescription , functional status ( Barthel and Lawton indices ) and cognitive status according to the Spanish version of the Mini-Mental State Examination were recorded . Quality of life was assessed using the visual analogue scale of the quality of life test . Concentrations of TSH and thyroxine were measured . Participants were classified in accordance with clinical categories of thyroid function . RESULTS Twenty ( 6.5 % ) individuals had sub clinical hypothyroidism and five ( 1.6 % ) had sub clinical hyperthyroidism . Compared with euthyroid subjects ( n=280 ; 91.8 % ) , sub clinical hypo- and hyperthyroidism subjects were not significantly associated with poor physical or cognitive function at baseline . Fifty-one ( 15.1 % ) subjects died during the 36 months of follow-up . TSH values and sub clinical hypo- and hyperthyroidism were not associated with an increased overall mortality risk ( hazard ratio ( HR ) 1.086 , 95 % CI 0.987 - 1.196 and HR 0.905 , 95 % CI 0.902 - 1.053 respectively ) . CONCLUSIONS This study does not support the association of TSH or thyroid disorders with physical or cognitive function at baseline or with 3-year mortality in the oldest old subjects BACKGROUND AND OBJECTIVE The original Whlckham Survey documented the prevalence of thyroid disorders in a r and omly selected sample of 2779 adults which matched the population of Great Britain in age , sex and social class . The aim of the twenty‐year follow‐up survey was to determine the Incidence and natural history of thyroid disease in this cohort OBJECTIVE To what extent endogenous sub clinical thyroid disorders contribute to impaired physical and cognitive function , depression , and mortality in older individuals remains a matter of debate . DESIGN A population -based , prospect i ve cohort of the Longitudinal Aging Study Amsterdam . METHODS TSH and , if necessary , thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older . Participants were classified according to clinical categories of thyroid function . Participants with overt thyroid disease or use of thyroid medication were excluded , leaving 1219 participants for analyses . Outcome measures were physical and cognitive function , depressive symptoms ( cross-sectional ) , and mortality ( longitudinal ) RESULTS Sixty-four ( 5.3 % ) individuals had sub clinical hypothyroidism and 34 ( 2.8 % ) individuals had sub clinical hyperthyroidism . Compared with euthyroidism ( n=1121 ) , sub clinical hypo- , and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function , or depression . On the contrary , participants with sub clinical hypothyroidism did less often report more than one activity limitation ( odds ratio 0.44 , 95 % confidence interval ( CI ) 0.22 - 0.86 ) . After a median follow-up of 10.7 years , 601 participants were deceased . Sub clinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk ( hazard ratio 0.89 , 95 % CI 0.59 - 1.35 and 0.69 , 95 % CI 0.40 - 1.20 respectively ) . CONCLUSIONS This study does not support disadvantageous effects of sub clinical thyroid disorders on physical or cognitive function , depression , or mortality in an older population Background Sub clinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age , but results are inconsistent . We investigated the association between sub clinical thyroid dysfunction and cognitive decline in the PROspect i ve Study of Pravastatin in the Elderly at Risk ( PROSPER ) . Methods Prospect i ve longitudinal study of men and women aged 70–82 years with pre-existing vascular disease or more than one risk factor to develop this condition ( N = 5,154 ) . Participants taking antithyroid medications , thyroid hormone supplementation and /or amiodarone were excluded . Thyroid function was measured at baseline : sub clinical hyper- and hypothyroidism were defined as thyroid stimulating hormones ( TSH ) < 0.45 mU/L or > 4.50 mU/L respectively , with normal levels of free thyroxine ( FT4 ) . Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years , using five neuropsychological performance tests . Results Sub clinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants , respectively . We found no consistent association of sub clinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests . Similarly , there was no association with rate of cognitive decline during follow-up . Conclusion We found no consistent evidence that sub clinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age . Although our data are not in support of treatment of sub clinical thyroid dysfunction to prevent cognitive dysfunction in later life , only large r and omized controlled trials can provide definitive evidence CONTEXT Sub clinical hypothyroidism ( SCH ) and cognitive dysfunction are both common in the elderly and have been linked . It is important to determine whether T4 replacement therapy in SCH confers cognitive benefit . OBJECTIVE Our objective was to determine whether administration of T4 replacement to achieve biochemical euthyroidism in subjects with SCH improves cognitive function . DESIGN AND SETTING We conducted a double-blind placebo-controlled r and omized controlled trial in the context of United Kingdom primary care . PATIENTS Ninety-four subjects aged 65 yr and over ( 57 females , 37 males ) with SCH were recruited from a population of 147 identified by screening . INTERVENTION T4 or placebo was given at an initial dosage of one tablet of either placebo or 25 microg T4 per day for 12 months . Thyroid function tests were performed at 8-weekly intervals with dosage adjusted in one-tablet increments to achieve TSH within the reference range for subjects in treatment arm . Fifty-two subjects received T4 ( 31 females , 21 males ; mean age 73.5 yr , range 65 - 94 yr ) ; 42 subjects received placebo ( 26 females , 16 males ; mean age 74.2 yr , 66 - 84 yr ) . MAIN OUTCOME MEASURES Mini-Mental State Examination , Middlesex Elderly Assessment of Mental State ( covering orientation , learning , memory , numeracy , perception , attention , and language skills ) , and Trail-Making A and B were administered . RESULTS Eighty-two percent and 84 % in the T4 group achieved euthyroidism at 6- and 12-month intervals , respectively . Cognitive function scores at baseline and 6 and 12 months were as follows : Mini-Mental State Examination T4 group , 28.26 , 28.9 , and 28.28 , and placebo group , 28.17 , 27.82 , and 28.25 [ not significant ( NS ) ] ; Middlesex Elderly Assessment of Mental State T4 group , 11.72 , 11.67 , and 11.78 , and placebo group , 11.21 , 11.47 , and 11.44 ( NS ) ; Trail-Making A T4 group , 45.72 , 47.65 , and 44.52 , and placebo group , 50.29 , 49.00 , and 46.97 ( NS ) ; and Trail-Making B T4 group , 110.57 , 106.61 , and 96.67 , and placebo group , 131.46 , 119.13 , and 108.38 ( NS ) . Linear mixed-model analysis demonstrated no significant changes in any of the measures of cognitive function over time and no between-group difference in cognitive scores at 6 and 12 months . CONCLUSIONS This RCT provides no evidence for treating elderly subjects with SCH with T4 replacement therapy to improve cognitive function CONTEXT Data regarding the association between sub clinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospect i ve cohort studies . This might reflect differences in participants ' age , sex , thyroid-stimulating hormone ( TSH ) levels , or preexisting cardiovascular disease . OBJECTIVE To assess the risks of coronary heart disease ( CHD ) and total mortality for adults with sub clinical hypothyroidism . DATA SOURCES AND STUDY SELECTION The data bases of MEDLINE and EMBASE ( 1950 to May 31 , 2010 ) were search ed without language restrictions for prospect i ve cohort studies with baseline thyroid function and subsequent CHD events , CHD mortality , and total mortality . The reference lists of retrieved articles also were search ed . DATA EXTRACTION Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospect i ve cohorts in the United States , Europe , Australia , Brazil , and Japan . The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data . Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Sub clinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations . RESULTS Among 55,287 adults , 3450 had sub clinical hypothyroidism ( 6.2 % ) and 51,837 had euthyroidism . During follow-up , 9664 participants died ( 2168 of CHD ) , and 4470 participants had CHD events ( among 7 studies ) . The risk of CHD events and CHD mortality increased with higher TSH concentrations . In age- and sex-adjusted analyses , the hazard ratio ( HR ) for CHD events was 1.00 ( 95 % confidence interval [ CI ] , 0.86 - 1.18 ) for a TSH level of 4.5 to 6.9 mIU/L ( 20.3 vs 20.3/1000 person-years for participants with euthyroidism ) , 1.17 ( 95 % CI , 0.96 - 1.43 ) for a TSH level of 7.0 to 9.9 mIU/L ( 23.8/1000 person-years ) , and 1.89 ( 95 % CI , 1.28 - 2.80 ) for a TSH level of 10 to 19.9 mIU/L ( n = 70 events/235 ; 38.4/1000 person-years ; P < .001 for trend ) . The corresponding HRs for CHD mortality were 1.09 ( 95 % CI , 0.91 - 1.30 ; 5.3 vs 4.9/1000 person-years for participants with euthyroidism ) , 1.42 ( 95 % CI , 1.03 - 1.95 ; 6.9/1000 person-years ) , and 1.58 ( 95 % CI , 1.10 - 2.27 , n = 28 deaths/333 ; 7.7/1000 person-years ; P = .005 for trend ) . Total mortality was not increased among participants with sub clinical hypothyroidism . Results were similar after further adjustment for traditional cardiovascular risk factors . Risks did not significantly differ by age , sex , or preexisting cardiovascular disease . CONCLUSIONS Sub clinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels , particularly in those with a TSH concentration of 10 mIU/L or greater OBJECTIVE Sub- clinical hypothyroidism ( SCH ) is a common disorder . People with this condition may have symptoms which could affect their perception of health . Therefore , the perceived health status of people with SCH was assessed and compared with population -matched norms . DESIGN A prospect i ve cross-sectional survey . METHODS Seventy-one adults with SCH , age range 18 - 64 years were studied . Perceived health status was measured by the Short Form-36 ( SF-36 ) version 2 question aire , which has been vali date d in a UK population setting . The SF-36 has eight scales measuring physical functioning , role physical , bodily pain , general health , vitality , social functioning , role emotional and mental health . Their SF-36 scores were compared with UK normative data after matching for age and sex and are reported as z-scores . RESULTS Scores of all eight SF-36 scales were significantly lower in people with SCH compared with the normative population . A negative score ( compared with zero of the normative population ) indicates worse health status . The most significantly impaired aspects of health status were vitality and role limitations due to physical problems ( role physical scale ) with z-scores ( 95 % confidence intervals ) of -1.01 ( -0.74 to -1.29 ) and -0.73 ( -0.43 to -1.04 ) respectively . Thyroid autoimmunity did not influence the results . CONCLUSION Perceived health status is significantly impaired in people with SCH when compared with UK normative population scores . This needs to be taken into consideration by clinicians when managing patients with this disease UNLABELLED This work was aim ed at determining and comparing the frequency of abnormal levels of thyroid stimulating hormone ( TSH ) in geriatric out patients with and without dementia . This cross-sectional study enrolled patients , aged 60 years and older with or without dementia ( established on the basis of DSM-IV-R ) , from geriatric outpatient unit with third level of medical care . Comparisons were between 33 ( 34 % ) patients without dementia versus 26 ( 58 % ) with dementia ; both among 142 ( 24 % ) r and omly selected sample ( RSS ) from unit 's register ; and the 101 ( 89 % ) in the memory-clinic case series ( MCCS ) of dementia were contrasted with the former . MEASUREMENTS TSH , total/free thyroxine , mini-mental-state examination ( MMSE ) , geriatric depression scale ( GDS ) , Hachinski ischemic-score ( HIS ) , and clinical data from the patients ' charts . In the above order , high TSH was found in 9 ( 27.3 % , confidence interval (CI)=12.1 - 42.5 % ) , 6 ( 23.1 % , CI=6.9 - 46.5 % ) , and 30 ( 29.7 % , CI=20.8 - 38.6 % ) , respectively . Low-normal free thyroxine levels accompanied 76 % of individuals with elevated TSH ; in contrast of Gaussian distribution of free thyroxine in those with TSH in normal range . In conclusion , the high frequency found of hypothyroidism in patients with and without dementia warrants further studies . Treatment is only being recommended for patients with below range thyroxin levels ; while treatment of sub clinical hypothyroidism in the presence of cognitive decline will be addressed in the forthcoming studies BACKGROUND Thyroid dysfunction may impair the quality of life ( QoL ) and may cause psychological symptoms . The aim of this study is to investigate prospect ively the effects of thyroid dysfunction on quality of life , levels of depression/anxiety and the changes in these variables after treatment . METHODS A total of 160 subjects , consisting of an overt hypothyroidism group ( n = 33 ) , a sub clinical hypothyroidism group ( n = 43 ) , an overt hyperthyroidism group ( n = 51 ) , a sub clinical hyperthyroidism group ( n = 13 ) , and a healthy control group ( n = 20 ) were included in the study . All groups were evaluated with the Hamilton Depression Rating Scale ( HDRS ) , Hamilton Anxiety Rating Scale ( HARS ) , Short Form-36 ( SF-36 ) , and Brief Disability Question naire ( BDQ ) . Health-related quality of life ( HRQL ) was measured by SF-36 . RESULTS Anxiety and depressive symptoms were more severe in patients with overt hypo- and hyperthyroidism ( p < 0.001 ) . The QoL was worse in overt or sub clinical hyper- and hypothyroidism groups than in the control group [ p = 0.013 for physical composite score ( PCS ) ; p = 0.002 for mental composite score ( MCS ) ] . Psychological symptoms and QoL were improved in overt and sub clinical hypothyroidism and overt hyperthyroidism groups as a result of the treatment . The overt hyper- and hypothyroidism groups showed more improvement than the sub clinical groups . CONCLUSIONS This study suggests that restoration of euthyroidism is accompanied by improvement on QoL and psychological symptoms in all groups except the sub clinical hyperthyroidism group . Controlled , r and omized studies in larger groups are , however , necessary IMPORTANCE An association of clinical and sub clinical hypothyroidism with mild cognitive impairment ( MCI ) has not been established . OBJECTIVE To evaluate the association of clinical and sub clinical hypothyroidism with MCI in a large population -based cohort . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional , population -based study was conducted in Olmsted County , Minnesota . R and omly selected participants were aged 70 to 89 years on October 1 , 2004 , and were without documented prevalent dementia [ CORRECTED ] . A total of 2050 participants were evaluated and underwent in-person interview , neurologic evaluation , and neuropsychological testing to assess performance in memory , attention/executive function , and visuospatial and language domains . Participants were categorized by consensus as being cognitively normal , having MCI , or having dementia according to published criteria . Clinical and sub clinical hypothyroidism were ascertained from a medical records linkage system . MAIN OUTCOMES AND MEASURES Association of clinical and sub clinical hypothyroidism with MCI . RESULTS Among 1904 eligible participants , the frequency of MCI was 16 % in 1450 individuals with normal thyroid function , 17 % in 313 persons with clinical hypothyroidism , and 18 % in 141 individuals with sub clinical hypothyroidism . After adjusting for covariates ( age , educational level , sex , apolipoprotein E ε4 , depression , diabetes mellitus , hypertension , stroke , body mass index , and coronary artery disease ) we found no significant association between clinical or sub clinical hypothyroidism and MCI ( odds ratio [ OR ] , 0.99 [ 95 % CI , 0.66 - 1.48 ] and 0.88 [ 0.38 - 2.03 ] , respectively ) . No effect of sex interaction was seen on these effects . In stratified analysis , the odds of MCI with clinical and sub clinical hypothyroidism among men was 1.02 ( 95 % CI , 0.57 - 1.82 ) and 1.29 ( 0.68 - 2.44 ) and , among women , was 1.04 ( 0.66 - 1.66 ) and 0.86 ( 0.37 - 2.02 ) , respectively . CONCLUSIONS AND RELEVANCE In this population -based cohort of elderly people , neither clinical nor sub clinical hypothyroidism was associated with MCI . Our findings need to be vali date d in a separate setting using the published criteria for MCI and confirmed in a longitudinal study CONTEXT Despite the equivocal outcomes of r and omized controlled trials , general clinical opinion favors screening and treatment of elderly individuals with sub clinical thyroid disorders . OBJECTIVES To determine whether sub clinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , observational , population -based follow-up study within the Leiden 85-Plus Study of 87 % of a 2-year birth cohort ( 1912 - 1914 ) in the municipality of Leiden , the Netherl and s. A total of 599 participants were followed up from age 85 years through age 89 years ( mean [ SD ] follow-up , 3.7 [ 1.4 ] years ) . MAIN OUTCOME MEASURES Complete thyroid status at baseline ; disability in daily life , depressive symptoms , cognitive function , and mortality from age 85 years through 89 years . RESULTS Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life , depressive symptoms , and cognitive impairment at baseline or during follow-up . Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status . The hazard ratio ( HR ) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 ( 95 % confidence interval [ CI ] , 0.63 - 0.94 ; P = .009 ) . The HR for mortality per SD increase of 0.21 ng/dL ( 2.67 pmol/L ) of free thyroxine increased 1.16-fold ( 95 % CI , 1.04 - 1.30 ; P = .009 ) . CONCLUSIONS In the general population of the oldest old , elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span . However , evidence for not treating elderly individuals can only come from a well- design ed , r and omized placebo-controlled clinical trial CONTEXT Declarative memory largely depends upon normal functioning temporal lobes ( hippocampal complex ) and prefrontal cortex . Animal studies suggest abnormal hippocampal function in hypothyroidism . OBJECTIVE The aim of the study was to assess declarative memory in overt and sub clinical ( SCH ) hypothyroid patients before and after l-T(4 ) ( LT4 ) replacement and in matched normal subjects . DESIGN AND SETTING A prospect i ve , open-labeled interventional study was conducted at a teaching hospital . PARTICIPANTS AND INTERVENTION Hypothyroid ( n = 21 ) and SCH ( n = 17 ) patients underwent neuropsychological tests at baseline and 3 and 6 months after LT4 replacement . Normal subjects were studied at the same time-points . MAIN OUTCOME Tests of spatial , verbal , associative , and working memory ; attention ; and response inhibition and the Hospital Anxiety and Depression Scale were administered . RESULTS Baseline deficits in spatial , associative , and verbal memory , which rely upon the integrity of the hippocampal and frontal areas , were identified in patients with overt hypothyroidism . Spatial and verbal memory were impaired in SCH patients ( P < 0.05 ) . TSH levels correlated negatively ( P < 0.05 ) with these deficits . After LT4 replacement , verbal memory normalized . Spatial memory normalized in the SCH group but remained impaired in the hypothyroid group . Associative memory deficits persisted in the overt hypothyroid group . Hospital Anxiety and Depression Scale scores did not correlate with cognitive function . Measures of attention and response inhibition did not differ from control subjects . CONCLUSION Cognitive impairment occurs in SCH and more markedly in overt hypothyroidism . These impairments appear predominantly mnemonic in nature , suggesting that the etiology is not indicative of general cognitive slowing . We propose that these deficits may reflect an underlying disruption of normal hippocampal function and /or connectivity BACKGROUND Isolated TSH increase--"sub clinical hypothyreosis " ( SH ) appears to be comparatively common . Its incidence among women over sixty has been estimated up to 17 % . Though SH was assumed to be entirely asymptomatic , recent findings revealed various fine subjective and objective symptoms of the disease . METHODS AND RESULTS Twenty otherwise healthy female patients with SH diagnosis were examined . Using personality question naire MMPI/100 eight different clinical scales and two control scales were evaluated , using Wechsler 's memory scale WM-R 5 memory quotients were tested . The group was r and omised into a subgroup treated for six month with placebo and a subgroup where thyroxin was administrated and thyroidal test normalised . Psychological testing repeated before and after the treatment , results evaluated using paired t-test . Results indicate that : 1 . Patients with SH did not differ in personality features , they only had a higher tendency to the depressive mood , which could be positively influenced by thyroxin ( significance at 5 % level ) . 2 . Thyroxin treatment brought about improvement of some cognitive parameters of the verbal ( p < 0.01 ) , visual ( p < 0.05 ) , and general memory ( p < 0.01 ) . 3 . Results of psychological and cognitive tests correlate better with FT4 than TSH level . CONCLUSIONS Though SH can not be associated with changes in personality features , TSH normalisation results in statistically significant improvement of cognitive function -- verbal , visual and general memory |
2,624 | 28,560,261 | Structural neuroimaging studies suggest white matter integrity deficits that are consistent across the illnesses , while gray matter reductions appear more widespread in schizophrenia compared to bipolar disorder .
Spectroscopy studies in cortical gray matter report evidence of decreased neuronal integrity in both disorders .
Functional neuroimaging studies typically report similar functional architecture of brain networks in healthy controls and patients across the psychosis spectrum , but find differential extent of alterations in task related activation and resting state connectivity between illnesses .
The very limited imaging-genetic literature suggests a relationship between psychosis risk genes and brain structure , and possible gene by diagnosis interaction effects on functional imaging markers . | Since Emil Kraepelin ’s conceptualization of endogenous psychoses as dementia praecox and manic depression , the separation between primary psychotic disorders and primary affective disorders has been much debated .
We conducted a systematic review of case – control studies contrasting magnetic resonance imaging studies in schizophrenia and bipolar disorder . | Medication management in schizophrenia is a lengthy process , as the lack of clinical response can only be confirmed after at least 4 weeks of antipsychotic treatment at a therapeutic dose . Thus , there is a clear need for the discovery of biomarkers that have the potential to accelerate the management of treatment . Using resting-state functional MRI , we examined the functional connectivity of the ventral tegmental area ( VTA ) , the origin of the mesocorticolimbic dopamine projections , in 21 healthy controls and 21 unmedicated patients with schizophrenia at baseline ( pre-treatment ) and after 1 week of treatment with the antipsychotic drug risperidone ( 1-week post-treatment ) . Group-level functional connectivity maps were obtained and group differences in connectivity were assessed on the groups ’ participant-level functional connectivity maps . We also examined the relationship between pre-treatment/1-week post-treatment functional connectivity and treatment response . Compared with controls , patients exhibited significantly reduced pre-treatment VTA/midbrain connectivity to multiple cortical and subcortical regions , including the dorsal anterior cingulate cortex ( dACC ) and thalamus . After 1 week of treatment , VTA/midbrain connectivity to bilateral regions of the thalamus was re-established . Pre-treatment VTA/midbrain connectivity strength to dACC was positively correlated with good response to a 6-week course of risperidone , whereas pre-treatment VTA/midbrain connectivity strength to the default mode network was negatively correlated . Our findings suggest that VTA/midbrain resting-state connectivity may be a useful biomarker for the prediction of treatment response 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 IMPORTANCE Previous evidence has implicated corticostriatal abnormalities in the pathophysiology of psychosis . Although the striatum is the primary target of all efficacious antipsychotics , the relationship between its functional connectivity and symptomatic reduction remains unknown . OBJECTIVE To explore the longitudinal effect of treatment with second-generation antipsychotics on functional connectivity of the striatum during the resting state in patients experiencing a first episode of psychosis . DESIGN , SETTING , AND PARTICIPANTS This prospect i ve controlled study took place at a clinical research center and included 24 patients with first-episode psychosis and 24 healthy participants matched for age , sex , education , and h and edness . Medications were administered in a double-blind r and omized manner . INTERVENTIONS Patients were scanned at baseline and after 12 weeks of treatment with either risperidone or aripiprazole . Their symptoms were evaluated with the Brief Psychiatric Rating Scale at baseline and follow-up . Healthy participants were scanned twice within a 12-week interval . MAIN OUTCOMES AND MEASURES Functional connectivity of striatal regions was examined via functional magnetic resonance imaging using a seed-based approach . Changes in functional connectivity of these seeds were compared with reductions in ratings of psychotic symptoms . RESULTS Patients had a median exposure of 1 day to antipsychotic medication prior to being scanned ( mean [ SD ] = 4.5 [ 6.1 ] ) . Eleven patients were treated with aripiprazole and 13 patients were treated with risperidone . As psychosis improved , we observed an increase in functional connectivity between striatal seed regions and the anterior cingulate , dorsolateral prefrontal cortex , and limbic regions such as the hippocampus and anterior insula ( P < .05 , corrected for multiple comparisons ) . Conversely , a negative relationship was observed between reduction in psychosis and functional connectivity of striatal regions with structures within the parietal lobe ( P < .05 , corrected for multiple comparisons ) . CONCLUSIONS AND RELEVANCE Our results indicated that corticostriatal functional dysconnectivity in psychosis is a state-dependent phenomenon . Increased functional connectivity of the striatum with prefrontal and limbic regions may be a biomarker for improvement in symptoms associated with antipsychotic treatment BACKGROUND The adaptability of the human brain to the constantly changing environment is reduced in patients with psychotic disorders , leading to impaired cognitive functions . Brain signal complexity , which may reflect adaptability , can be readily quantified via resting-state functional magnetic resonance imaging ( fMRI ) signals . We hypothesized that resting-state brain signal complexity is altered in psychotic disorders , and is correlated with cognitive impairment . METHODS We assessed 156 healthy controls ( HC ) and 330 prob and s , including 125 patients with psychotic bipolar disorder ( BP ) , 107 patients with schizophrenia ( SZ ) , 98 patients with schizoaffective disorder ( SAD ) and 230 of their unaffected first-degree relatives ( 76 BPR , 79 SADR , and 75 SZR ) from four sites of the Bipolar-Schizophrenia Network on Intermediate Phenotypes ( B-SNIP ) consortium . Using multi-scale entropy analysis , we determined whether patients and /or relatives had pathologic differences in complexity of resting-state fMRI signals toward regularity ( reduced entropy in all time scales ) , or toward uncorrelated r and omness ( increased entropy in fine time scales that decays as the time scale increases ) and how these complexity differences might be associated with cognitive impairment . RESULTS Compared to HC subjects , prob and groups showed either decreased complexity toward regularity or toward r and omness . SZ prob and s showed decreased complexity toward regular signal in hypothalamus , and BP prob and s in left inferior occipital , right pre central and left superior parietal regions , whereas no brain region with decreased complexity toward regularity was found in SAD prob and s. All prob and groups showed significantly increased brain signal r and omness in dorsal and ventral prefrontal cortex ( PFC ) , and unaffected relatives showed no complexity differences in PFC regions . SZ had the largest area of involvement in both dorsal and ventral PFC . BP and SAD prob and s shared increased brain signal r and omness in ventral medial PFC , BP and SZ prob and s shared increased brain signal r and omness in ventral lateral PFC , whereas SAD and SZ prob and s shared increased brain signal r and omness in dorsal medial PFC . Only SZ showed increased brain signal r and omness in dorsal lateral PFC . The increased brain signal r and omness in dorsal or ventral PFC was weakly associated with reduced cognitive performance in psychotic prob and s. CONCLUSION These observations support the loss of brain complexity hypothesis in psychotic prob and s. Furthermore , we found significant differences as well as overlaps of pathologic brain signal complexity between psychotic prob and s by DSM diagnoses , thus suggesting a biological approach to categorizing psychosis based on functional neuroimaging data Recently , independent component analysis ( ICA ) has been widely used in the analysis of brain imaging data . An important problem with most ICA algorithms is , however , that they are stochastic ; that is , their results may be somewhat different in different runs of the algorithm . Thus , the outputs of a single run of an ICA algorithm should be interpreted with some reserve , and further analysis of the algorithmic reliability of the components is needed . Moreover , as with any statistical method , the results are affected by the r and om sampling of the data , and some analysis of the statistical significance or reliability should be done as well . Here we present a method for assessing both the algorithmic and statistical reliability of estimated independent components . The method is based on running the ICA algorithm many times with slightly different conditions and visualizing the clustering structure of the obtained components in the signal space . In experiments with magnetoencephalographic ( MEG ) and functional magnetic resonance imaging ( fMRI ) data , the method was able to show that expected components are reliable ; furthermore , it pointed out components whose interpretation was not obvious but whose reliability should incite the experimenter to investigate the underlying technical or physical phenomena . The method is implemented in a software package called Icasso IMPORTANCE Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis . Whether this increase would persist after effective antipsychotic treatment is unknown . OBJECTIVES To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects . DESIGN , SETTING , AND PARTICIPANTS Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age , sex , h and edness , and cigarette smoking . INTERVENTIONS Participants underwent 2 proton magnetic resonance spectroscopy studies : patients were imaged at baseline and after 4 weeks of antipsychotic treatment , while controls were imaged at baseline and at 4 weeks after the baseline measurement . Patients were treated with oral risperidone ( open label ) for 4 weeks with dosages that were titrated on the basis of clinical judgment . MAIN OUTCOMES AND MEASURES Glutamate levels were estimated using LCModel ( version 6.2 - 1 T ) and were corrected for the cerebrospinal fluid proportion within the voxel . RESULTS Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls . After clinical ly effective antipsychotic treatment , glutamate levels significantly decreased in the associative striatum , with no significant change in the cerebellum . No differences in glutamate levels were observed between groups at 4 weeks . CONCLUSIONS AND RELEVANCE Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinical ly effective antipsychotic treatment . These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels |
2,625 | 15,653,704 | Dopexamine may have beneficial effects on renal perfusion in patients undergoing cardiac surgery but appears to have little or no benefit on gastric mucosal pHi in the same patient population .
In critically ill patients none of the studies demonstrated a beneficial effect of dopexamine on either hepatosplanchnic or renal perfusion .
There is insufficient evidence to offer reliable recommendations on the clinical use of dopexamine for the protection of either hepatosplanchnic or renal perfusion in high-risk surgical patients .
Furthermore , there is no current evidence to support a role for dopexamine in protecting either hepatosplanchnic or renal perfusion in critically ill patients | BACKGROUND Dopexamine is increasingly being used in high-risk surgical and critically ill patients to preserve hepatosplanchnic and renal perfusion .
This systematic review of r and omized controlled trials was undertaken to investigate the clinical evidence for using dopexamine in this role . | Objectives : To compare the effects of dobutamine and dopexamine on systemic hemodynamics , lactate metabolism , renal function and the intramucosal-arterial PCO2 gap in norepinephrine-treated septic shock . Design : A prospect i ve , interventional , r and omized clinical trial . Setting : Adult medical/surgical intensive care unit in a university hospital . Patients : After volume resuscitation , 24 patients were treated with norepinephrine alone titrated to obtain a mean arterial pressure of 75 mmHg and a cardiac index greater than 3.5 l/min-1 · m-2 . Interventions : Patients were r and omized to receive an infusion of dobutamine ( n = 12 ) ( 5 μg/kg per min ) or dopexamine ( n = 12 ) ( 1 μg/kg per min ) . Measurements and main results : Baseline measurements included : hemodynamic parameters , renal parameters ( diuresis , creatinine clearance and urinary sodium excretion ) , gastric mucosal-arterial PCO2 gap , arterial and mixed venous gases and arterial lactate and pyruvate levels . These measurements were repeated after 1 ( H1 ) , 4 ( H4 ) and 24 ( H24 ) h. No difference was found between dobutamine and dopexamine among H0 and H1 , H4 and H24 values for hemodynamics . Dobutamine and dopexamine at low doses had no significant effect on mean arterial pressure , heart rate , cardiac index , oxygen delivery , oxygen consumption and pulmonary artery occlusion pressure . No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia . After 4 and 24 h lactate concentration decreased in the dobutamine group from 2.4 ± 1 mmol/l to 1.7 ± 0.7 mmol/l and 1.5 ± 0.4 mmol/l , respectively , while it increased in the dopexamine group from 2.3 ± 1 mmol/l to 2.7 ± 1 mmol/l after 4 h and returned to baseline values after 24 h ( 2.2 ± 0.6 ) . After 24 h the lactate/pyruvate ratio decreased in the dobutamine group from 15 ± 5 to 12 ± 3 ( p < 0.05 ) while it was unchanged in the dopexamine group ( from 16 ± 6 to 17 ± 4 ) . Arterial pH increased in the dobutamine group from 7.35 ± 0.05 to 7.38 ± 0.07 ( p < 0.05 ) while it was unchanged in the dopexamine group ( from 7.34 ± 0.01 to 7.35 ± 0.10 ) . The PCO2 gap decreased after 1 and 4 h in both the dobutamine and dopexamine groups ( p < 0.05 with respect to baseline ) . When looking at individual responses , however , patients from both groups exhibited an increased gastric PCO2 gap . No difference was found between dobutamine and dopexamine for renal parameters . Conclusions : In norepinephrine-treated septic shock , low doses of neither dobutamine nor dopexamine caused significant effects on systemic hemodynamics and renal function and both dobutamine and dopexamine inconsistently improved the PCO2 gap . The present results support the need for individual measurement of the effects of catecholamine on the PCO2 gap PURPOSE Colonic ischemia after aortic surgery is associated with increased mortality and morbidity rates . This study was conducted as a single-center side arm to a multicenter , r and omized , placebo-controlled study to evaluate the effect of dopexamine hydrochloride on its incidence . METHODS Thirty patients , mean age 65.1 years ( range , 46 - 84 ) , undergoing elective infrarenal aortic surgery were entered . Preoperative hemodynamic and respiratory parameters were optimized . Patients were then r and omly assigned to receive a perioperative infusion of dopexamine at 2 microg/kg per minute ( n = 12 ) or 0.9 % saline placebo ( n = 18 ) . All patients underwent colonoscopy and biopsy preoperatively and 1 week postoperatively . Specimens were assessed for evidence of mucosal ischemia , presence of mast cell tryptase , myeloperoxidase activity , and both the inducible and endothelial isoforms of nitric oxide synthase . RESULTS There was no significant difference in perioperative fluid and blood requirements or hemodynamic and respiratory parameters between the two groups . However , there was significantly less evidence of mucosal ischemic changes in dopexamine-treated patients ( n = 1 ) compared with placebo ( n = 8) ( P = .049 ) . Furthermore , when preoperative biopsies were compared with those performed 1 week postoperatively , nine ( 50 % ) patients in the placebo group and two ( 16.7 % ) in the dopexamine group scored worse . Although there was no significant difference in inflammatory markers between the two groups , both mast cell tryptase and myeloperoxidase expression were increased in patients with histologic evidence of ischemia ( P < .05 ) . Furthermore , inducible nitric oxide synthase staining within the vascular ( P = .001 ) and lamina propria ( P < .05 ) components of the mucosa was also significantly greater . CONCLUSION A perioperative dopexamine infusion affords significant histologic protection to colonic mucosa after aortic surgery Abstract Objective : To determine whether a ) pre-operative measurement of gastric intramucosal pHi is predictive for mortality and morbidity in high-risk surgical patients and b ) peri-operative improvement of global oxygen delivery ( DO2 ) with fluids and dopexamine leads to increased gastric pHi and c ) either improved global perfusion or improved splanchnic perfusion is related to the prevention of multiple organ failure ( MOF ) . Design : Retrospective analysis of a double-blind , placebo-controlled , r and omised study . Setting : General intensive care units from 14 hospitals . Patients : Two hundred eighty-six high-risk surgical patients . Interventions : Swan-Ganz and tonometer catheter placement ; patients were stabilised pre-operatively using fluids , blood and /or oxygen to preset goals before receiving placebo or two doses of dopexamine ( 0.5 or 2.0 µg·kg·min ) peri-operatively . Measurements and results : Haemodynamic assessment ( including DO2 and oxygen consumption ( VO2 ) ) was performed together with measurement of gastric mucosal pHi pre-operatively and directly , 2 , 6 , 12 , 24 and 36 h post-operatively . Retrospectively , patients were divided pre-operatively into two sub-groups based on the optimal cut-off value for mortality of the first pHi measurement after induction of anaesthesia as calculated by a receiver operator characteristic ( ROC ) curve analysis – low pHi group ( < 7.35 ) and normal pHi ( ≥7.35 ) . Mortality in the low pHi , was higher than in the normal pHi , group ( 16.8 vs 2.3 % ; p=0.0001 ) . In the normal pHi group dopexamine , which was given prior to the first pHi measurement , had no effect on pHi , while DO2 increased significantly . In this group MOF score and number of patients with MOF remained similar for the treatment sub-groups . In the low pHi group gastric pHi increased significantly during dopexamine infusion ( p=0.008 ) , despite the lack of an increase in DO2 and VO2 . In this group the MOF score and the number of patients developing MOF decreased significantly with the use of dopexamine ( p=0.04 ) . In both groups bicarbonate levels remained similar for the treatment sub-groups . Conclusions : In high-risk surgical patients pre-operative measurement of pHi was predictive for mortality . The peri-operative response of pHi to dopexamine seemed to be dependent on pre-operative gastric pHi Abstract Objective : To compare the effects of dopexamine and dopamine on the mucosal permeability of the gastrointestinal tract ( GIT ) . Design : Prospect i ve , r and omised clinical trial . Setting : Intensive care unit of a postgraduate teaching hospital , London , Engl and . Patients : Thirty patients undergoing elective surgery involving cardiopulmonary bypass , performed by a single surgeon . Interventions : Patients were r and omly assigned to receive either dopexamine 2.0 μg/kg per min or dopamine 2.5 μg/kg per min for the duration of the study period . Measurements and main results : Hemodynamic parameters and gastric intramucosal pH ( pHi ) were measured at intervals throughout the study . GIT permeability was measured once , post-operatively , using the ratio of absorbed lactulose to L-rhamnose . The groups were similar with respect to demographics , pre- and post-operative risk factors . The lactulose/rhamnose ratio was ( mean ± SEM ) 0.44 ± 0.10 in the dopexamine group vs 0.65 ± 0.08 in that receiving dopamine ( p < 0.05 ) . The dopexamine group had a significantly higher oxygen delivery preoperatively ( 479.5 ± 32.0 ml/min per m2 vs 344.4 ± 23.9 ml/min per m2 for dopamine , p < 0.01 ) , but no other significant differences emerged between the groups . Conclusions : Compared to dopamine , dopexamine reduces GIT permeability following surgery involving cardiopulmonary bypass . The mechanism of this effect remains unclear STUDY OBJECTIVE To assess the effect of low dose dopexamine and dopamine on splanchnic blood flow as measured by gastric intramucosal pH , hepatic metabolism of lidocaine ( lignocaine ) to monoethylglycinexy-lidide ( MEGX ) , and plasma disappearance rate of indocyanine green ( ICG ) . DESIGN Single-blind r and omization of patients with a gastric intramucosal acidosis to receive dopexamine ( ten patients ) , dopamine ( ten patients ) , or saline solution ( five control patients ) for 2 h. SETTING All 25 patients were in the ICU of Guys ' Hospital . PATIENTS All patients met the criteria for the diagnosis of the systemic inflammatory response syndrome , were mechanically ventilated , and had pulmonary artery catheters placed . All had a low gastric intramucosal pH and had a median first 24-h acute physiology and chronic health evaluation ( II ) score of 22 ( range , 7 to 40 ) . MEASUREMENTS AND INTERVENTIONS Baseline measurements of gastric intramucosal pH , MEGX formation from lidocaine , ICG plasma disappearance rate , heart rate , mean arterial pressure , pulmonary artery occlusion pressure , cardiac index , oxygen delivery index , oxygen uptake index , systemic vascular resistance , and arterial pH were taken . Dopexamine ( 1 mg.kg-1.min-1 ) , dopamine ( 2.5 mg.kg-1.min-1 ) , or 0.9 % saline solution was then infused for 2 h , after which a repeated set of the measurements was taken . RESULTS Dopexamine at a low dose had no effect on any of the systemic measurements . The median intramucosal pH rose from 7.23 to 7.35 ( p < 0.005 ) , the median ICG plasma disappearance rate from 7.6 to 11.3%.min-1 ( p < 0.02 ) , and the median MEGX concentration from 4 to 10.2 ng.mL-1 ( p < 0.005 ) . Dopamine had no effect on any of the measured variables . There were no changes in the control group . CONCLUSIONS Low-dose dopexamine increases splanchnic blood flow as measured by gastric intramucosal pH , MEGX formation from lidocaine , and ICG clearance . The lack of any change in the systemic measurements suggests that these effects are the result of a selective vasodilatation of the splanchnic vessels . At the dose used in this study , dopamine had no effect on splanchnic blood flow . Dopexamine may be useful in the management of splanchnic ischemia in the critically ill Correction of the splanchnic oxygen deficit indicated by low gastric intramucosal pH ( pHi < 7.35 ) appears to reduce ICU mortality . Dopexamine hydrochloride is in clinical use for this purpose but its efficacy has not been fully investigated . We report the results of a prospect i ve , r and omized , placebo-controlled study with a crossover design to assess the efficacy of dopexamine in correcting low pHi . Twelve patients in whom pHi < 7.32 was detected during eight-hourly monitoring were r and omized to receive either incremental dopexamine ( 4 - 6 μg/kg/min ) with colloid or 5 % dextrose for three hours prior to crossover . There was no difference in pHi between treatments despite cardiovascular effects during dopexamine infusion . There was , however , a time-related increase in pHi suggesting a beneficial effect of conventional therapy . Dopexamine hydrochloride at 4 - 6 μg/kg/min in conjunction with colloid is not a clinical ly useful therapy to correct the splanchnic oxygen deficit indicated by low pHi Forty critically ill patients fulfilling the definitions of systemic inflammatory response syndrome were enrolled in a double‐blind cross‐over interventional study assessing the effects of dopexamine and prostacyclin on splanchnic perfusion , cardiovascular function and oxygen flux . The cross‐over design involved either dopexamine ( 1.25 μg.kg−1.min−1 ) or prostacyclin ( 0.5 ng.kg−1.min−1 ) being infused for 6 h followed by a 12‐h washout period prior to an identical infusion sequence using the other agent . Preliminary analysis revealed a significant period effect , so data from the second infusion period were excluded from further analysis . Dopexamine caused a significant increase in heart rate ( 116 vs. 106 beat.min−1 ) , and urine output ( 103 vs. 69 ml.h−1 ) . Dopexamine produced a significant increase in oxygen delivery ( infusion 548 ml O2.min−1.m−2 ; no infusion 492 ml O2.min−1.m−2 ) while prostacyclin caused a decrease ( infusion 460 ml O2.min−1.m−2 ; no infusion 547 ml O2.min−1.m−2 ) . The results indicate that dopexamine improves oxygen delivery and urine output more effectively than prostacyclin Objective To evaluate the potential differential effects of dopamine , dopexamine , and dobutamine on jejunal mucosal perfusion , assessed by endoluminal laser Doppler flowmetry in uncomplicated postcardiac surgical patients . Design A prospect i ve , blinded , r and omized , crossover study . Setting A cardiothoracic intensive care unit in a tertiary care center . Patients A total of ten postoperative cardiac surgical patients were studied . Interventions Each patient received sequentially , r and omly , and in a blinded fashion 2.7 ± 0.2 & mgr;g·kg−1·min−1 dopamine , 0.7 ± 0.1 & mgr;g·kg−1·min−1 dopexamine , and 2.7 ± 0.1 & mgr;g·kg−1·min−1 dobutamine . Each inotropic agent was titrated to increase cardiac output by 25 % from baseline . Data on jejunal mucosal perfusion , splanchnic lactate , and oxygen extraction were obtained during a 5-min control period and a 5-min drug infusion period after the target cardiac output was reached . The procedure was sequentially repeated for each agent , and there was a 20- to 30-min washout period between each agent . Measurements and Main Results Dopamine , dopexamine , and dobutamine increased jejunal mucosal perfusion by 27 % ( p < .01 ) , 20 % ( p < .001 ) , and 7 % ( p < .001 ) , respectively . The increase in jejunal mucosal perfusion by dopamine and dopexamine were significantly more pronounced compared with dobutamine ( p < .05 and p < .01 , respectively ) , whereas there was no difference between dopamine and dopexamine . Splanchnic oxygen extraction decreased to the same extent with all three drugs . Splanchnic lactate extraction did not change for any of the drugs . The effects on central hemodynamics were similar for the three inotropic agents . Conclusions Endoluminal laser Doppler flowmetry is a new tool for the detection of perfusion changes at the local intestinal mucosal level . Dopamine , dopexamine , and dobutamine have differential effects on jejunal mucosal perfusion probably because of their different receptor stimulating properties . These findings may be of clinical importance when the therapeutic goal is to improve gut mucosal perfusion Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass ( CPB ) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses . We examined the effects of dopexamine on hemodynamic parameters , creatinine clearance , systemic and splanchnic oxygenation , gastric mucosal pH ( pHi ) , and mixed and hepatic venous plasma levels of endotoxin , interleukin-6 ( IL-6 ) , serum amyloid A ( SAA ) , and C-reactive protein ( CRP ) in 44 patients scheduled for coronary artery bypass grafting . Patients were r and omized to receive continuous infusions of 0.5 , 1.0 , or 2 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( n = 10 per group ) or placebo ( n = 14 ) prior to surgery , intraoperatively , and postoperatively . Dopexamine infusion increased systemic oxygen delivery ( P < or = to 0.01 ) . Hepatic venous oxygen saturation did not change , and pHi decreased during and after CPB in all patients ( P < or = to 0.01 ) . Postoperative increases in IL-6 were smallest in patients who received 2.0 micro g [ centered dot ] kg-1 [ centered dot ] min-1 dopexamine ( P < or = to 0.02 ) . SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study . Creatinine clearance was elevated in all dopexamine groups ( P < or = to 0.025 ) . This elevation was higher with lower dopexamine doses ( P < or = to 0.025 ) . We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation . ( Anesth Analg 1997;84:950 - 7 A r and omized double-blind study was carried out on 20 patients after coronary artery bypass surgery to investigate the effects of grade d doses of dopexamine hydrochloride or placebo on systemic haemodynamic responses and renal vascular resistance index ( RVRI ) measured using Doppler ultrasound . Pre-operatively , all patients had good left ventricular function and normal renal function . Eleven were allocated r and omly to receive incremental infusions of dopexamine 0.5 , 1 , 2 , and 4 micrograms kg-1 min-1 for 40 min each , and nine received corresponding infusions of placebo . One patient was withdrawn from the dopexamine group because of tachycardia . In the remaining 19 , heart rate ( HR ) and cardiac index ( CI ) were significantly ( P < 0.05 ) increased from base-line with dopexamine : the HR values with dopexamine differed significantly from those with placebo at the 2 and 4 micrograms kg-1 min-1 dose and at 4 micrograms kg-1 min-1 for CI . Systemic vascular resistance index ( SVRI ) fell significantly in both groups : the reduction was significantly greater with dopexamine 4 micrograms kg-1 min-1 than with the corresponding infusion of placebo . RVRI increased and urine output decreased significantly during the infusions in both groups , but with no significant difference between groups . There were no changes in systemic arterial pressures , pulmonary artery occlusion pressures , stroke volume index or left ventricular stroke work index . Where changes from base-line occurred in either group , they had not returned to base-line within 40 min of stopping the infusions ( except perhaps for CI in the dopexamine group ) . Dopexamine appears to offer no particular protection to the renal vascular bed Introduction : The objective of this study was to evaluate the effects of dopexamine on renal function in 4 groups of patients either with or without renal dysfunction . Transient renal dysfunction is often not clinical ly relevant in patients with normal renal function , but it is an important clinical factor in patients with pre-existing renal failure . Dopexamine ( DX ) is a commonly used catecholamine which probably exerts a selective effect at the splanchnic bed . Material and Methods : 24 patients with normal renal function and 24 patients with impaired renal function ( creatinine in serum ≥ 1.5 mg/dL ) were each r and omly allocated to 2 groups . Group 1 ( control ) without renal dysfunction and group 3 ( control/dysfunction ) with renal dysfunction were considered as control groups , while the patients in DX and DX/dysfunction groups received 1 μg/kg/min dopexamine until the end of surgery . Kidney function was investigated using st and ard parameters and by investigating specific proteins and enzymes . Results : All patients showed pathologic excretions of the investigated parameters during cardiopulmonary bypass ( CPB ) with no differences between the study groups . The distal tubule , the lysosomal regions , Henle 's loop and the glomerular tuft were all damaged . Heart rate and cardiac index increased significantly in the DX-groups , first until the end of surgery , second until the start of ECC . Conclusion : Dopexamine at a dose of 1 μg/kg/min had no influence on renal function and protein excretion and can not be regarded as a kidney function protecting substance Gastric tonometry was used to study the possible effect of dopexamine infusion on a low calculated intramucosal pH ( pHi ) as a sign of splanchnic ischemia We have studied the effects of dopexamine and dopamine on systemic and renal haemodynamics in 20 male patients undergoing elective coronary artery bypass surgery . Patients were allocated r and omly to two groups ( n = 10 ) who were treated with incremental doses of either dopexamine 1 , 2 and 4 micrograms kg-1 min-1 , or dopamine 2.5 and 5 micrograms kg-1 min-1 , each dose being maintained for 15 min . Measurements were performed before administration of the drug and at the end of the infusion period at each dose . Fentanyl and midazolam were used as anaesthetic agents . Renal blood flow was measured with the argon washin technique . Dopexamine 4 micrograms kg-1 min-1 produced an increase in cardiac index of 117 % caused by a 65 % reduction in afterload and an increase in heart rate by 61 % . Dopamine 5 micrograms kg-1 min-1 caused a 40 % increase in cardiac index as a result of an increase in stroke volume . Renal vascular resistance decreased more than systemic vascular resistance with dopamine . With dopexamine , the increase in renal blood flow ( 66 % ) was less than the increase in cardiac index , while renal vascular resistance and systemic vascular resistance declined to almost the same extent . The results show that dopexamine exerts systemic and renal effects mainly via stimulation of beta 2-receptors . An action of dopexamine at renal DA1-receptors could not be demonstrated in this study Purpose : To assess the effects of intraoperative infusion of dopexamine ( a DA-1 and B2 adrenoreceptor agonist ) on hemodynamic function , tissue oxygen delivery and consumption , splanchnic perfusion and gut permeability following aortic cross-clamp and release . Methods : In a r and omised double blind controlled trial 24 patients scheduled for elective infrarenal abdominal aortic aneurysm repair were studied in two centres and were assigned to one of two treatment groups . Group I received a dopexamine infusion starting at 0.5 µg·kg−1·min−1 increased to 2 µg·kg−1·min−1 maintaining a stable heart rate : Group II received a placebo infusion titrated in the same volumes following induction of anesthesia . Measured and derived hemodynamic data , tissue oxygen delivery and extraction and gut permeability were recorded at set time points throughout the procedure . Results : Dopexamine infusion ( 0.5–2 µg·kg−1·min−1 ) was associated with enhanced hemodynamic function ( MAP 65±5.5vs92±5.7 mm Hg , P=<0.05 ) only during the period of aortic cross clamping . However , during the most part of infrarenal abdominal aortic surgery , dopexamine did not reduce systemic vascular resistance index , mean arterial pressure nor oxygen extraction compared with the control group . The lactulose/ rhamnose permeation ratio was elevated above normal in both groups ( 0.22 and 0.29 in groups I and II respectively ) . Conclusions : Dopexamine infusion ( 0.5 −2 µg·kg−1 ) did not enhance hemodynamic function and tissue oxygenation values during elective infrarenal abdominal aortic aneurysm repair . RésuméObjectif : Évaluer les effets d’une perfusion peropératoire de dopexamine , un agonist edes adrénorécepteurs DA-1 et B2 , sur l’heémodynamie , l’apport et la consommation d’oxygène tissulaire , la perfusion splanchnique et la perméabilité intenstinale à la suite d’un clampage total de l’aorte et de son retrait . Méthode : Il s’agit d’un essai ranomisé , contrôlé et à double insu auprès de 24 patients , provenant de deux centres et répartis en deux groupes , qui ont subi la réparation d’un anévrysme aortique abdominal sous-rénal . Le groupe I a reçu une perfusion de dopexamine amorcée à 0,5 µg·kg−1·min−1 , augmentée à 2 µg·kg−1·min−1 , maintenant une fréquence cardiaque stable ; le groupe II a reçu une perfusion placebo de même volume après l’induction de l’anesthésie . Les données hémodynamiques mesurées et dérivées , l’apport et la consommation d’oxygène tissuulaire et la permeábilité intestinale ont été notés à des moments de mesure déterminés au cours de l’intervention . Résultats : La perfusion de dopexamine ( 0,5 –2µg·kg−1 ) a stimulé la fonction hémodynamique ( TAM 65±5,5vs 92±5,7 mm Hg , P=<0,05 ) pendant le clampage aortique seulement . Cependant , pendant la majeure partie de l’intervention aortique abdominale sous-rénale , la dopexamine n’a pas réduitl l’indice de résistance vasculaire générale , la tension artŕielle moyenne ou la consommation d’oxygène , ce sdonnées étant comparées avec celles du groupe témoin . Le ratio de dissémination de lactulose / rhamnose s’est élevé au-dessus de la normale dans les deux groupes ( 0,22 et 0,29 dans les groupes I et II respectivement ) . Conclusion : La perfusion de dopexamine ( 0,5 –µg·kg−1·min−1 ) n’a pas amélioré l’hémodynamie ni haussé les valeurs d’oxygénation tissulaire pendant la réparation d’un anévrysme aortique abdominal sous-rénal Abstract Objective . To determine whether an infusion of dopexamine for up to 7 days has an effect on gastrointestinal ( GIT ) absorption and permeability , renal function or organ dysfunction in the critically ill . Design and setting . Prospect i ve , r and omised controlled clinical trial in two general adult intensive care units . Patients . 102 critically ill adult patients predicted to require organ support for at least 4 days . Interventions . After resuscitation patients were r and omly assigned to receive an infusion of up to 2g/kg per minute of dopexamine or control . Measurements and results . GIT absorption and permeability were measured using the ratio of absorbed rhamnose to 3-O-methyl-D-glucose and the ratio of lactulose to rhamnose on days 1 , 4 and 7 . Creatinine clearance was measured concurrently . Daily Sequential Organ Failure Assessment scores were calculated . Fifty-two patients received dopexamine . No significant difference between the two groups emerged on any of the measured parameters during the study period . Conclusions . No benefit was seen from a prolonged infusion of dopexamine in this group of critically ill patients in terms of GIT absorption and permeability , creatinine clearance or organ dysfunction The effect of low-dose dopexamine and dopamine on gastric intramucosal pH ( pHi ) during cardiac surgery and 16 hours postoperatively was studied in 35 adults patients ( coronary artery bypass grafting and /or valve replacement ) . The patients were assigned r and omly to treatment groups with either dopexamine ( 1 microgram.kg-1.min-1 ( n = 12 ) , dopamine 2.5 micrograms.kg-1.min-1 ( n = 11 ) or to a control group ( n = 12 ) . The infusions were started after induction of anaesthesia and were continued until 16 hours after CPB . pHi and arterial pH ( pHa ) did not differ between groups and remained unchanged during cardiopulmonary by-pass and for the first four postoperative hours . Both the carbon dioxide tension of arterial blood ( PaCO2 ) and of the saline in the tonometer ( PtonCO2 ) changed in parallel with a decrease during CPB and an increase after CPB and surgery with maximal values 12 hours after termination of CPB . A significant correlation was noted between pHi and pHa and between arterial and tonometric PCO2 . It is concluded that low dose dopexamine and dopamine have no influence on pHi during and after cardiac surgery . The observed changes in pHi and PtonCO2 were due to changes in pHa and in PaCO2 and not a sign of gastric mucosal ischemia Thirty-two patients undergoing elective infrarenal aortic surgery were r and omly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 μg/kg/min ( n = 15 ) or 0.9 % saline solution as placebo ( n = 17 ) . Renal function was monitored by regular measurements of serum creatinine levels . There were significant mean percentage increases in serum creatinine ( p < 0.001 ) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group . It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction OBJECTIVE To study the influence of low-dose dopexamine on splanchnic oxygenation during major abdominal surgery . DESIGN Prospect i ve , r and omized , placebo-controlled study . SETTING University hospital . PATIENTS Eighteen adult patients undergoing elective major abdominal surgery . INTERVENTIONS The patients received either dopexamine at 1 microg/kg/min ( group A , n = 9 ) or 0.90 % saline as control ( group B , n = 9 ) . MEASUREMENTS AND RESULTS To assess the splanchnic oxygenation , intestinal tissue PO2 ( PtissO2 ) and gastric intramucosal Pco2 ( PmucCO2 ) were measured , and the PCO2 gap ( PmucCO2 - PaCO2 ) was calculated at baseline ( T1 ) and after an infusion period of 60 mins ( T2 ) . There was no difference between the groups in the global oxygen transport parameters . Low-dose dopexamine increases PtissO2 on the serosal side of the small bowel ( deltaPtissO2 , 17+/-24 mm Hg in group A vs. -5+/-10 in group B ) . The changes in PtissO2 at the serosal side of the colon after dopexamine demonstrated a nonsignificant increase ( deltaPtissO2 , 7+/-11 mm Hg in group A vs. -11+/-23 mm Hg in group B ) . In both groups , the Pco2 gap ( group A , 6+/-7 mm Hg [ T1 ] and 5+/-6 mm Hg [ T2 ] , vs. group B , 9+/-10 mm Hg [ T1 ] and 12+/-10 mm Hg [ T2 ] ) remained unchanged compared with the baseline . CONCLUSION It is concluded that low-dose dopexamine improves PtissO2 at the serosal side of the gut , preferably at the small bowel . However , low-dose dopexamine did not improve gastric PmucCO2 OBJECTIVE To investigate whether dopexamine hydrochloride beneficially influences splanchnic perfusion and regulators of the macrocirculation and microcirculation in patients undergoing surgery of the abdominal aorta . DESIGN Prospect i ve , blinded , and r and omized study . SETTING University-affiliated hospital . PARTICIPANTS Twenty patients undergoing elective abdominal aortic surgery . INTERVENTIONS The patients were r and omized to one of two groups . In the dopexamine group ( DOP , n = 10 ) , dopexamine , 1 microg/kg/min , was started before surgery and continued for 24 hours . In the control group ( COG , n = 10 ) , patients received saline solution as placebo . Extensive hemodynamic monitoring was carried out using a pulmonary artery catheter , and intramucosal pH was measured using a gastric tonometer . From arterial blood sample s , important regulators of the circulation were measured before dopexamine was administered ( T0 ) , before aortic clamping ( T1 ) , 20 minutes after aortic clamping ( T2 ) , after declamping the first leg ( T3 ) , at the end of surgery ( T4 ) , 1 hour postoperatively ( T5 ) , and 24 hours postoperatively ( T6 ) . MEASUREMENTS AND MAIN RESULTS Heart rate increased significantly in DOP ( 63+/-16 to 84+/-18 beats/min ) . At T5 , mean pulmonary artery pressure was significantly lower in DOP ( 15+/-6 mmHg ) than in COG ( 22+/-6 mmHg ) . During aortic clamping , pulmonary capillary wedge pressure increased significantly in both groups . Cardiac index increased significantly from baseline only in the dopexamine patients . No significant differences between the groups were seen with regard to oxygenation parameters and intramucosal pH. Renin plasma levels increased significantly only in COG ( 46+/-32 to 99+/-55 microU/mL ) . Endothelin and atrial natriuretic peptide plasma levels showed no significant differences between the two groups . Atrial natriuretic peptide increased significantly only in DOP ( 366+/-171 pg/mL ; COG , 159+/-71 pg/mL ) . Antidiuretic hormone , norepinephrine , and epinephrine plasma levels increased significantly from baseline in both groups , without showing significant differences between the groups . CONCLUSIONS In patients undergoing abdominal aortic surgery , prophylactic perioperative administration of dopexamine hydrochloride produced effects on hemodynamics but without improving oxygenation and intramucosal pH. From the measured regulators of the circulation , only renin was beneficially affected Objective To measure the clinical effects of dopexamine on systemic and splanchnic perfusion in critically ill patients . Design Prospect i ve study . Setting General intensive care unit . Patients Ten patients with sepsis syndrome , acute respiratory failure , and at least one other organ system in failure . The median age of the patients was 62.5 yrs ( range 29 to 78 ) , and the median admission Acute Physiology and Chronic Health Evaluation ( APACHE ) II score was 24 points ( range 14 to 38 ) . Interventions Timed infusion of dopexamine to a maximum dose of 6 μg/kg/min . Measurements and Main Results Systemic hemodynamics and oxygen transport variables were obtained from measurements after arterial and pulmonary artery catheterization . Gastric intramucosal pH and hepatic blood flow/ function measurements were made by tonometry and indocyanine green clearance , respectively . All measurements were made before dopexamine infusion , after 1 hr of dopexamine infusion , and again 1 hr after the infusion ended . Cardiac index increased with dopexamine from a baseline median of 4.0 L/min/m2 ( range 1.2 to 5.5 ) to 4.8 L/min/m2 ( range 1.5 to 8.03 ) ( p < .01 ) , and returned to its previous level 1 hr after the infusion ended ( median 4.0 L/min/m2 [ range 1.4 to 5.8 ] , p < .01 ) . During dopexamine infusion , gastric intramucosal pH improved significantly from a median baseline level of 7.21 ( range 7.04 to 7.50 ) to 7.28 ( range 7.13 to 7.46 , p < .05 ) . This improvement in gastric intramucosal pH was maintained ( median 7.36 [ range 7.13 to 7.46 ] ) after the infusion ended . Indocyanine green halflife decreased but not significantly with dopexamine ( medians before and during the infusion were 6.6 and 6.3 mins , respectively ) . Indocyanine green half-life increased significantly 1 hr after the infusion ended ( median 7.4 mins [ range 4.4 to 14.8 ] , p < .05 ) , and changes in cardiac index correlated with changes in indocyanine green half-life ( R82 = 0.60 , p < .001 ) . Changes in gastric intramucosal pH were unrelated to all other measurements . Conclusions Dopexamine improves gastric intramucosal pH , and thus , splanchnic oxygenation . This improvement in gastric intramucosal pH appears to be independent of dopexamine 's systemic effects . ( Crit Care Med 1994 ; 22:789–795 OBJECTIVE To assess the effects of dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients . DESIGN A prospect i ve , controlled trial . SETTING A ten-bed intensive care unit ( ICU ) in a university hospital . PATIENTS Twelve patients with severe sepsis ( according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference ) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion . INTERVENTIONS Infusion of increasing dosages of dopexamine ( 0.5 , 1.0 , 2.0 , and 4.0 microg/kg/min ) . MEASUREMENTS AND MAIN RESULTS Systemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH ( pHi ) were measured . A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow . Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption ( VO2 ) . Splanchnic blood flow increased proportionally to cardiac output , indicating that there was no selective effect of dopexamine on the splanchnic flow . Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients . CONCLUSIONS In hemodynamically stable , hyperdynamic septic patients being treated with dobutamine , dopexamine has no selective effect on splanchnic blood flow . In fact , a decreased pHi suggests a harmful effect on gastric mucosal perfusion Liver blood flow is reduced after cardiopulmonary bypass ( CPB ) and both dopamine and dopexamine are used to overcome this . This study compares the effects of these agents on liver blood flow . Thirty patients undergoing elective coronary artery bypass graft surgery were r and omized into three groups ( n = 10 per group ) . Six hours after surgery baseline liver blood flow was determined by the percentage disappearance rate of indocyanine green measured by dichromatic auricular densitometery . Patients then received infusions of either : ( 1 ) placebo ( dextrose 5 % ) ; ( 2 ) dopamine ( 4 μg/kg/min ) ; ( 3 ) dopexamine ( 1 μg/kg/min increasing to 2 μg/kg/min ) . One hour after infusion , liver blood flow measurements were repeated . In the dopexamine group the infusion was increased and the measurements repeated another hour later . We found that patient-specific variables and operative details were similar for all groups . Postoperative cardiac index and heart rate were increased significantly by dopamine ( cardiac index 2.82 ± 0.46 l/m/m2 vs 3.28 ± 0.67 l/m/m2 : p < 0.001 and heart rate 87.5 ± 13.2 vs 96 ± 16 : p < 0.05 ) and dopexamine at 2 μg/kg/min ( cardiac index 2.71 ± 0.53 l/m/m2 vs 3.45 ± 0.67 l/m/m2 : p < 0.05 and heart rate 89.0 ± 18.9 vs 107.4 ± 13.6 : p < 0.001 ) compared to placebo ( cardiac index 2.97 ± 0.8 l/m/m2 vs 3.18 ± 0.9 l/m/m2 : p > 0.05 and heart rate 77.2 ± 7.4 vs 77.3 ± 8 : p > 0.05 ) despite similar atrial and systemic arterial pressures . The disappearance rate of indocyanine green was not altered during infusion of placebo group ( 9.0 ± 3.2%/min vs 7.9 ± 3.0%/min : p > 0.05 ) or dopexamine at 1 μg/kg/min ( 9.7 ± 3.1%/min vs 11.2 ± 4.1%/min : p > 0.05 ) . The disappearance rate was increased with dopamine ( 6.7 ± 3.7%/min vs 11.8 ± 3.0%/min : p < 0.05 ) and dopexamine 2 μg/kg/min ( 9.7 ± 3.1%/min vs 13.5 ± 3.2%/min : p < 0.05 ) . This indicates a 76 % increase in liver blood flow with dopamine and a 38 % increase with dopexamine . We conclude that dopamine 4 μg/kg/min and dopexamine 2 μg/kg/min increase liver blood flow , although this may , in part , be related to an increase in cardiac output . Dopexamine shows no advantage over dopamine in enhancing liver blood flow after CPB Background : Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery . Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties Background : Beta‐adrenergic agents are frequently used to improve cardiac performance in surgical and intensive care patients . Beta‐adrenergic agents have metabolic and anti‐inflammatory effects in addition to their cardiovascular effects . Splanchnic metabolic activity increases in response to surgery and inflammation . Dopexamine is believed to favor blood flow distribution to the splanchnic region OBJECTIVE Dopexamine hydrochloride is a novel synthetic adrenergic agonist that combines the renal effects of dopamine with the hemodynamic effects of dobutatmine . Our study is design ed to compare the hemodynamic , diuretic , and natriuretic effects of dopexamine and dobutamine in patients with reduced cardiac index following heart surgery . DESIGN Prospect ively r and omized , blinded study . SETTING Operating room and intensive care unit of a large , urban , academic medical center . PATIENTS Twenty-eight patients undergoing elective coronary artery bypass grafting ( CABG ) with preoperative ejection fraction of at least 40 percent gave informed consent . The study group consisted of the ten patients who had a cardiac index < or = 2.5 L/min/m2 ( while receiving no inotropic medication ) immediately after separation from cardiopulmonary bypass . INTERVENTIONS AND MEASUREMENTS Study patients were r and omly given a starting dose of either 5 micrograms/kg/min of dobutamine ( n = 5 ) or 2 micrograms/kg/min of dopexamine ( n = 5 ) . During the initial 30 min following separation from bypass , dosages were titrated incrementally to maintain cardiac index > or = 3.0/L/min/m2 . Further titrations of the drug were done only if cardiac index fell below 3.0 L/min/m2 or if sustained tachycardia occurred during the 24-h study period . Data were collected at 5- and 10-min intervals for the first 30 min after separation from bypass , hourly for the next 8 h , then every 2 h for the remainder of the study period . RESULTS Both drugs increased cardiac index by more than 50 percent over baseline ( dobutamine 2.2 + /- 0.1 to 3.5 + /- 0.2 [ p < 0.05 ] ; dopexamine , 2.3 + /- 0.1 to 3.5 + /- 0.1 [ p < 0.05 ] L/min/m2 ) . The mean dose required to maintain cardiac index > or = 3.0L/min/m2 was 1.5 micrograms/kg/min for dopexamine and 3.5 micrograms/kg/min for dobutamine . There were no significant differences in either urinary output or net sodium excretion in the dopexamine group compared with the dobutamine group , and tachycardia ( heart rate > 120 beats/min ) was more common in the dopexamine group . CONCLUSIONS Our study demonstrates that dopexamine produces hemodynamic , diuretic , and natriuretic effects similar to dobutamine in patients with reduced cardiac index following CABG Background : Hepatic dysfunction is a common problem in patients after hemihepatectomy . Treatment with low‐dose dopamine has been shown to be beneficial in hemihepatectomy patients . We hypothesized that dopexamine , a synthetic vasoactive catecholamine , due to its specific pharmocodynamic profile may be more effective in reducing hidden ischaemic episodes in the hepato‐splanchnic region during and after temporary total cross‐clamping of hepatic inflow in these patients Background : Cardiopulmonary bypass ( CPB ) induces a systemic inflammatory reaction . Microcirculation‐dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response . This study was design ed to eluci date whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB OBJECTIVE To evaluate the effect of dopexamine on the incidence of acute inflammation in the stomach/duodenum in patients undergoing abdominal surgery > or = 1.5 hrs with a minimum of one high-risk criterion . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . This study was conducted as a side arm to a multicenter , multinational study . SETTING University hospital in an adult intensive care unit . PATIENTS Thirty-eight patients . INTERVENTIONS Patients were stabilized with fluid , blood products , and supplementary oxygen to achieve predetermined goals : cardiac index > 2.5 L/min/m2 , mean arterial blood pressure of 70 mm Hg , pulmonary arterial occlusion pressure of 10 mm Hg , hemoglobin of 100 g/L , and arterial saturation of 94 % . After stabilization , the study drug ( either placebo [ group A ] , dopexamine 0.5 microg/kg/min [ group B ] , or dopexamine 2.0 microg/kg/min [ group C ] ) was commenced . The study drug infusion was started 2 to 12 hrs before surgery and infused for 24 hrs after surgery . Estimation of upper gut blood flow was assessed using a gastric tonometer , and gastroscopy with biopsy was performed before surgery ( after induction of anesthesia ) and 72 hrs after surgery . Comparisons were made between endoscopic findings and histologic proof of acute inflammatory changes . In addition , biopsies were assessed for the presence in the mucosa of mast cells , myeloperoxidase activity , and inducible nitric oxide synthase . MEASUREMENTS AND MAIN RESULTS Intramucosal pH decreased significantly with time in all three groups ( p < .001 ) , reaching the lowest point at the end of surgery . There was no difference among the groups . Endoscopy visualized acute inflammatory changes in 58.3 % of group A patients , 46.2 % of group B patients , and 53.90 % of group C patients after hemodynamic optimization . At 72 hrs , dopexamine-treated patients compared with placebo-treated patients had a significantly lower incidence of gastric and duodenal acute inflammatory changes , as defined by myeloperoxidase activity ( 37.5 % in groups B and C vs. 86 % in group A ; p < .05 ) . CONCLUSION Dopexamine in doses of 0.5 and 2.0 microg/kg/min affords significant histologic protection to the upper gastrointestinal tract mucosa 72 hrs after operation in high-risk surgical patients undergoing abdominal surgery |
2,626 | 27,240,188 | CONCLUSION Guidelines were implemented in a heterogeneous way and the interventions were delivered once and mainly on a local basis .
RELEVANCE TO CLINICAL PRACTICE Educational interventions to implement guidelines could be beneficial in enhancing nurses ' evidence -based decision-making and care practice .
The combination of teaching and learning methods proved useful , and educational interventions should be supported with simultaneous strategies . | AIMS AND OBJECTIVES To systematic ally review the literature on the outcomes of educational interventions relevant to nurses with regard to guideline implementation .
BACKGROUND Previous review s on interventions to implement guidelines have focused on particular clinical problems , but only one included nursing studies . | Background There has been considerable interest recently in developing and evaluating interventions to increase research use by clinicians . However , most work has focused on medical practice s ; and nursing is not well represented in existing systematic review s. The purpose of this article is to report findings from a systematic review of interventions aim ed at increasing research use in nursing . Objective To assess the evidence on interventions aim ed at increasing research use in nursing . Methods A systematic review of research use in nursing was conducted using data bases ( Medline , CINAHL , Healthstar , ERIC , Cochrane Central Register of Controlled Trials , and Psychinfo ) , grey literature , ancestry search ing ( Cochrane Data base of Systematic Review s ) , key informants , and manual search ing of journals . R and omized controlled trials and controlled before- and after- studies were included if they included nurses , if the intervention was explicitly aim ed at increasing research use or evidence -based practice , and if there was an explicit outcome to research use . Method ological quality was assessed using pre-existing tools . Data on interventions and outcomes were extracted and categorized using a pre-established taxonomy . Results Over 8,000 titles were screened . Three r and omized controlled trials and one controlled before- and after- study met the inclusion criteria . The method ological quality of included studies was generally low . Three investigators evaluated single interventions . The most common intervention was education . Investigators measured research use using a combination of surveys ( three studies ) and compliance with guidelines ( one study ) . Research er-led educational meetings were ineffective in two studies . Educational meetings led by a local opinion leader ( one study ) and the formation of multidisciplinary committees ( one study ) were both effective at increasing research use . Conclusion Little is known about how to increase research use in nursing , and the evidence to support or refute specific interventions is inconclusive . To advance the field , we recommend that investigators : ( 1 ) use theoretically informed interventions to increase research use , ( 2 ) measure research use longitudinally using theoretically informed and psychometrically sound measures of research use , as well as , measuring patient outcomes relevant to the intervention , and ( 3 ) use more robust and method ologically sound study design s to evaluate interventions . If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use This descriptive survey assessed the perception of evidence -based practice ( EBP ) among nurses in the United States . Although evidence -based healthcare results in improved patient outcomes and reduced costs , nurses do not consistently implement evidence -based best practice s. A descriptive survey was conducted with a r and om sample of 1015 RNs who are members of the American Nurses Association . Although nurses believe in evidence -based care , barriers remain prevalent , including resistance from colleagues , nurse leaders , and managers . Differences existed in responses of nurses from Magnet ® versus non-Magnet institutions as well as nurses with master ’s versus nonmaster ’s degrees . Nurse leaders and educators must provide learning opportunities regarding EBP and facilitate supportive cultures to achieve the Institute of Medicine ’s 2020 goal that 90 % of clinical decisions be evidence -based The choice of study design for guideline implementation studies will determine the confidence with which the observed effects can be attributed to the interventions under study . In general , cluster r and omized trials , of which there are different types , provide the most robust design . However , the use of these design s has implication s for the power , conduct and analysis of studies . Wherever possible , design s allowing head-to-head comparisons , which incorporate baseline measures of performance , should be used BACKGROUND The Quality in Acute Stroke Care ( QASC ) trial evaluated systematic implementation of clinical treatment protocol s to manage fever , sugar , and swallow ( FeSS protocol s ) in acute stroke care . This cluster-r and omised controlled trial was conducted in 19 stroke units in Australia . AIM To describe perceived barriers and enablers preimplementation to the introduction of the FeSS protocol s and , postimplementation , to determine which of these barriers eventuated as actual barriers . METHODS Preimplementation : Workshops were held at the intervention stroke units ( n = 10 ) . The first workshop involved senior clinicians who identified perceived barriers and enablers to implementation of the protocol s , the second workshop involved bedside clinicians . Postimplementation , an online survey with stroke champions from intervention sites was conducted . RESULTS A total of 111 clinicians attended the preimplementation workshops , identifying 22 barriers covering four main themes : ( a ) need for new policies , ( b ) limited workforce ( capacity ) , ( c ) lack of equipment , and ( d ) education and logistics of training staff . Preimplementation enablers identified were : support by clinical champions , medical staff , nursing management and allied health staff ; easy adaptation of current protocol s , care-plans , and local policies ; and presence of specialist stroke unit staff . Postimplementation , only five of the 22 barriers identified preimplementation were reported as actual barriers to adoption of the FeSS protocol s , namely , no previous use of insulin infusions ; hyperglycaemic protocol s could not be commenced without written orders ; medical staff reluctance to use the ASSIST swallowing screening tool ; poor level of engagement of medical staff ; and doctors ' unawareness of the trial . LINKING EVIDENCE TO ACTION The process of identifying barriers and enablers preimplementation allowed staff to take ownership and to address barriers and plan for change . As only five of the 22 barriers identified preimplementation were reported to be actual barriers at completion of the trial , this suggests that barriers are often overcome whilst some are only ever perceived rather than actual barriers Venous thromboembolism ( VTE ) is a significant cause of morbidity and mortality in hospitalized medical patients . Evidence -based guidelines exist for preventing VTE ; unfortunately , these guidelines are not always adhered to by clinicians . The aim of this study was to evaluate the acceptability , utility and clinical impact of an educational outreach visit ( EOV ) on nurses ' provision of mechanical prophylaxis to hospitalized medical patients using a prospect i ve , uncontrolled , before- and -after design . Nurses received a 1-to-1 educational session on mechanical VTE prevention by a trained nurse facilitator . The EOV intervention was design ed by a multidisciplinary group of healthcare professionals using social marketing theory . Eighty-five of the 120 eligible nurses ( 71 % ) attended the EOV . The median length of each visit was 11.5 minutes ( interquartile range [ IQR ] , 10 - 15 ) and the median time spent arranging and conducting each visit was 63 minutes ( IQR , 49 - 85 ) . Eighty-four ( 99 % ) of the 85 participants gave a verbal commitment to trial the new evidence -based mechanical VTE prevention practice s. However , there were no measurable improvements in the proportion of patients risk assessed ( -1.7 % improvement ; 95 % confidence interval [ CI ] , -7.0 to 10.3 ; P = .68 ) or provided appropriate mechanical prophylaxis ( -0.3 % improvement ; 95 % CI , -13.4 to 14 ; P = .96 ) . Research ers conclude that EOV should not be used to improve nurses ' use of mechanical VTE prevention because it has no measurable impact on clinical practice and is re source intensive , requiring 4.5 minutes of preparation for every minute spent face to face with participants . Further research into the specific mechanism of action is required to explain the variability in clinical effect seen with this intervention AIM To assess the impact of leadership facilitation strategies on nurses ' beliefs of the importance and frequency of using evidence in daily nursing practice and the perception of organizational readiness in an acute care hospital . BACKGROUND Integrating evidence in practice is a prominent issue for hospital nursing as knowledge and skills , beliefs , organizational infrastructure and nursing leadership must all be addressed . DESIGN Prospect i ve , descriptive comparative . METHOD Three surveys were used in this prospect i ve descriptive comparative study . Evidence -Based Practice Beliefs Scale , the Implementation Scale and Organizational Culture & Readiness for System-Wide Integration Survey measured change before and after facilitating strategies for evidence -based practice enculturation . Data were collected in December 2008 ( N = 427 ) and in December 2010 ( N = 469 ) . RESULTS Leadership facilitated infrastructure development in three major areas : incorporating evidence -based practice outcomes in the strategic plan ; supporting mentors ; and advocating for re sources for education and outcome dissemination . With the interventions in place , the total group scores for beliefs and organizational readiness improved significantly . Analyses by job role showed that direct care nurses scores improved more than other role types . No differences were found in the implementation scores . CONCLUSION Successful key strategies were evidence -based practice education and establishing internal opportunities to disseminate findings . Transformational nursing leadership drives organizational change and provides vision , human and financial re sources and time that empowers nurses to include evidence in practice Nurses play a critical role in managing a patient 's pain , from initial evaluation to ongoing patient education . However , little information exists on current gaps in nurses ' knowledge and their pain-related decision making . To this end , an educational intervention-the INROADS initiative-was design ed to improve the knowledge of nurses involved in patient management as well as to guide them toward practice s that are consistent with currently available evidence . The results from an evaluation of this intervention show that nurses participating in the INROADS program were 52 % more likely to make evidence -based care choices for their patients , compared with a control group of demographically similar nurses . The effect of this program may reinforce it as a model for the design of future interventions for pain management INTRODUCTION Primary care providers , particularly pediatric nurse practitioners , are an integral force involved in tackling the obesity epidemic among youth . The majority of nurse practitioners , however , report low proficiency regarding their ability to adequately prevent and treat pediatric overweight . In response , the National Association of Pediatric Nurse Practitioners ( NAPNAP ) developed the evidence -based Healthy Eating and Activity Together ( HEAT ) Clinical Practice Guideline ( CPG ) to improve provider behavior and efficacy . METHOD Thirty-five nurse practitioners attending the NAPNAP Annual Conference participated in an intensive 4-hour HEAT CPG training session . Pre-training and post-training data were collected on provider knowledge , practice behaviors , and barriers in relation to the prevention of overweight among youth . RESULTS Post-training results revealed significant improvements in ( a ) practitioner knowledge ( assessment of patient growth , family history , psychosocial functioning , nutrition , and physical activity ) ; ( b ) practitioners ' intent to improve behavior ( i.e. , increased intent to use behavior modification and counseling aim ed at patient and family behavior change ) ; and ( c ) practitioners ' report of increased confidence in ability to address barriers . DISCUSSION Study findings demonstrate preliminary support for the HEAT CPG as an effective tool aim ed at helping providers to improve their ability to maintain patients ' healthy weight . Future research is needed to verify the effects of HEAT CPG on long-term improvements in care |
2,627 | 29,096,431 | All OHAs were effective when added to metformin or metformin and sulfonylurea , although the effects of each agent on body weight and hypoglycemia were different . | The Korean Diabetes Association ( KDA ) recently up date d the Clinical Practice Guidelines on antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus ( T2DM ) .
In combination therapy of oral hypoglycemic agents ( OHAs ) , general recommendations were not changed from those of the 2015 KDA guidelines .
In this review , we address the results of meta-analyses and systematic review s , comparing the effectiveness and safety among OHAs . | OBJECTIVE To evaluate the effects of canagliflozin , a sodium-glucose cotransporter 2 inhibitor , in type 2 diabetes mellitus inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This was a double-blind , placebo-controlled , parallel-group , multicenter , dose-ranging study in 451 subjects r and omized to canagliflozin 50 , 100 , 200 , or 300 mg once daily ( QD ) or 300 mg twice daily ( BID ) , sitagliptin 100 mg QD , or placebo . Primary end point was change in A1C from baseline through week 12 . Secondary end points included change in fasting plasma glucose ( FPG ) , body weight , and overnight urinary glucose-to-creatinine ratio . Safety and tolerability were also assessed . RESULTS Canagliflozin was associated with significant reductions in A1C from baseline ( 7.6–8.0 % ) to week 12 : −0.79 , −0.76 , −0.70 , −0.92 , and −0.95 % for canagliflozin 50 , 100 , 200 , 300 mg QD and 300 mg BID , respectively , versus −0.22 % for placebo ( all P < 0.001 ) and −0.74 % for sitagliptin . FPG was reduced by −16 to −27 mg/dL , and body weight was reduced by −2.3 to −3.4 % , with significant increases in urinary glucose-to-creatinine ratio . Adverse events were transient , mild to moderate , and balanced across arms except for a non – dose-dependent increase in symptomatic genital infections with canagliflozin ( 3–8 % ) versus placebo and sitagliptin ( 2 % ) . Urinary tract infections were reported without dose dependency in 3–9 % of canagliflozin , 6 % of placebo , and 2 % of sitagliptin arms . Overall incidence of hypoglycemia was low . CONCLUSIONS Canagliflozin added onto metformin significantly improved glycemic control in type 2 diabetes and was associated with low incidence of hypoglycemia and significant weight loss . The safety/tolerability profile of canagliflozin was favorable except for increased frequency of genital infections in females OBJECTIVE To evaluate the efficacy and safety of combinations of empagliflozin/linagliptin as second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin . RESEARCH DESIGN AND METHODS Subjects were r and omized to a combination of empagliflozin 25 mg/linagliptin 5 mg ( n = 137 ) , empagliflozin 10 mg/linagliptin 5 mg ( n = 136 ) , empagliflozin 25 mg ( n = 141 ) , empagliflozin 10 mg ( n = 140 ) , or linagliptin 5 mg ( n = 132 ) as add-on to metformin for 52 weeks . The primary end point was change from baseline in HbA1c at week 24 . RESULTS At week 24 , reductions in HbA1c ( mean baseline 7.90–8.02 % [ 62.8–64.1 mmol/mol ] ) with empagliflozin/linagliptin were superior to those with empagliflozin or linagliptin alone as add-on to metformin ; adjusted mean ( SE ) changes from baseline were −1.19 % ( 0.06 ) ( −13.1 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg/linagliptin 5 mg , −1.08 % ( 0.06 ) ( −11.8 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg/linagliptin 5 mg , −0.62 % ( 0.06 ) ( −6.8 mmol/mol [ 0.7 ] ) with empagliflozin 25 mg , −0.66 % ( 0.06 ) ( −7.2 mmol/mol [ 0.7 ] ) with empagliflozin 10 mg , and −0.70 % ( 0.06 ) ( −7.6 mmol/mol [ 0.7 ] ) with linagliptin 5 mg ( P < 0.001 for all comparisons ) . In these groups , respectively , 61.8 , 57.8 , 32.6 , 28.0 , and 36.1 % of subjects with baseline HbA1c ≥7 % ( ≥53 mmol/mol ) had HbA1c < 7 % ( < 53 mmol/mol ) at week 24 . Efficacy was maintained at week 52 . The proportion of subjects with adverse events ( AEs ) over 52 weeks was similar across treatment arms ( 68.6–73.0 % ) , with no hypoglycemic AEs requiring assistance . CONCLUSIONS Combinations of empagliflozin/linagliptin as second-line therapy for 52 weeks significantly reduced HbA1c compared with the individual components and were well tolerated OBJECTIVE Insulin adjustments to maintain glycemic control in individuals with type 1 diabetes often lead to wide glucose fluctuations , hypoglycemia , and increased body weight . Dapagliflozin , an insulin-independent sodium – glucose cotransporter 2 ( SGLT2 ) inhibitor , increases glucosuria and reduces hyperglycemia in individuals with type 2 diabetes . The primary objective of this study was to assess short-term safety of dapagliflozin in combination with insulin ; secondary objectives included pharmacokinetic , pharmacodynamic , and efficacy parameters . RESEARCH DESIGN AND METHODS A 2-week , dose-ranging , r and omized , double-blind , placebo-controlled proof-of-concept study r and omly assigned 70 adults with type 1 diabetes ( HbA1c 7–10 % ) , who were receiving treatment with stable doses of insulin , to one of four dapagliflozin doses ( 1 , 2.5 , 5 , or 10 mg ) or placebo . The insulin dose was not proactively reduced at r and omization but could be adjusted for safety reasons . RESULTS Sixty-two patients ( 88.6 % ) completed the study . Any hypoglycemia was common across all treatments ( 60.0–92.3 % ) ; one major event of hypoglycemia occurred with dapagliflozin 10 mg . No diabetic ketoacidosis occurred . Pharmacokinetic parameters were similar to those observed in patients with type 2 diabetes . Glucosuria increased by 88 g/24 h ( 95 % CI 55 to 121 ) with dapagliflozin 10 mg and decreased by −21.5 g/24 h ( 95 % CI −53.9 to 11.0 ) with placebo . Changes from baseline with dapagliflozin 10 mg by day 7 were as follows : −2.29 mmol/L ( 95 % CI −3.71 to −0.87 [ −41.3 mg/dL ; 95 % CI −66.9 to −15.7 ] ) for 24-h daily average blood glucose ; −3.77 mmol/L ( 95 % CI −6.09 to −1.45 [ −63.1 mg/dL ; 95 % CI −111.5 to −14.8 ] ) for mean amplitude of glycemic excursion ; and −16.2 % ( 95 % CI −29.4 to −0.5 ) for mean percent change in total daily insulin dose . Corresponding changes with placebo were as follows : −1.13 mmol/L ( 95 % CI −3.63 to 1.37 ) , −0.45 mmol/L ( 95 % CI −4.98 to 4.08 ) , and 1.7 % ( 95 % CI −22.8 to 33.9 ) , respectively . However , for every efficacy parameter , the 95 % CIs for all dapagliflozin doses overlapped those for placebo . CONCLUSIONS This exploratory study of dapagliflozin in adults with type 1 diabetes demonstrated acceptable short-term tolerability and expected pharmacokinetic profiles and increases in urinary glucose excretion . Within the dapagliflozin groups , dose-related reductions in 24-h glucose , glycemic variability , and insulin dose were suggested , which provide hope that SGLT2 inhibition may prove in larger r and omized controlled trials to be efficacious in reducing hyperglycemia in type 1 diabetes ABSTRACT Review of : Neal B , Perkovic V , Mahaffey K , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes . N Engl J Med . 2017;377:644–657 . The report combines the data from two trials , CANVAS and CANVAS-Renal , which were design ed to evaluate the safety and effect of canagliflozin , an SGLT-2 inhibitor , on the appearance of cardiovascular and renal events in patients with type 2 diabetes . Enrollees were patients with type 2 diabetes of at least 30 years of age , with a glycated hemoglobin of > or equal to 7.0 % and < or equal to 10.5 % . Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease , and to have an estimated glomerular filtration rate ( eGFR ) of > 30 ml/min . Patients were r and omized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS , and to canagliflozin 100 mg with a possible increase to 300 mg , or placebo , in CANVAS-Renal . Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practice s in their community . There was a significant 14 % reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke in the canagliflozin treated patients . There was also a pattern of improvement in markers of renal disease , including the change in the level and nature of albuminuria , a 40 % decrease in the glomerular filtration rate , the need for renal replacement therapy , or death from renal causes . This study exp and s the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study , raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most , if not all , type 2 diabetes patients , not only to control hyperglycemia but also to reduce cardiovascular and renal events BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) We aim ed to compare the efficacy and safety of lobeglitazone and pioglitazone as add‐ons to metformin in patients with type 2 diabetes . Patients who were inadequately controlled by metformin were r and omized and treated once daily with either lobeglitazone ( 0.5 mg , n = 128 ) or pioglitazone ( 15 mg , n = 125 ) for 24 weeks , with a 28‐week extension trial of lobeglitazone treatment in patients who consented . The primary endpoint was the change in glycated haemoglobin ( HbA1c ) concentration from baseline to week 24 . At week 24 , the mean change from baseline in HbA1c was −0.74 % for the lobeglitazone group and −0.74 % for the pioglitazone group , with a mean difference of 0.01 % [ 95 % confidence interval ( CI ) of difference , −0.16 to 0.18 ] . The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone . Lobeglitazone was not inferior to pioglitazone as an add‐on to metformin in terms of their efficacy and safety Aims /hypothesisThe aim of this work was to evaluate the efficacy and safety of canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who were being treated with background metformin . Methods This r and omised , double-blind , four-arm , parallel-group , Phase 3 study was conducted at 169 centres in 22 countries between April 2010 and August 2012 . Participants ( N = 1,284 ) with type 2 diabetes aged ≥18 and ≤80 years who had inadequate glycaemic control ( HbA1c ≥7.0 % [ 53 mmol/mol ] and ≤10.5 % [ 91 mmol/mol ] ) on metformin therapy received canagliflozin 100 mg or 300 mg , sitagliptin 100 mg , or placebo ( n = 368 , 367 , 366 , 183 , respectively ) for a 26 week , placebo- and active-controlled period followed by a 26 week , active-controlled period ( placebo group switched to sitagliptin [ placebo/sitagliptin ] ) and were included in the modified intent-to-treat analysis set . R and omisation was performed using a computer-generated schedule ; participants , study centres and the sponsor were blinded to group assignment . The primary endpoint was change from baseline in HbA1c at week 26 ; secondary endpoints included changes in HbA1c ( week 52 ) and fasting plasma glucose ( FPG ) , body weight , and systolic blood pressure ( BP ; weeks 26 and 52 ) . Adverse events ( AEs ) were recorded throughout the study . Results At week 26 , canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo ( −0.79 % , –0.94 % , –0.17 % , respectively ; p < 0.001 ) . At week 52 , canagliflozin 100 mg and 300 mg demonstrated non-inferiority , and canagliflozin 300 mg demonstrated statistical superiority , to sitagliptin in lowering HbA1c ( −0.73 % , –0.88%,–0.73 % , respectively ) ; differences ( 95 % CI ) vs sitagliptin were 0 % ( −0.12 , 0.12 ) and −0.15 % ( −0.27 , –0.03 ) , respectively . Canagliflozin 100 mg and 300 mg reduced body weight vs placebo ( week 26 : –3.7 % , –4.2 % , –1.2 % , respectively ; p < 0.001 ) and sitagliptin ( week 52 : –3.8 % , –4.2 % , –1.3 % , respectively ; p < 0.001 ) . Both canagliflozin doses reduced FPG and systolic BP vs placebo ( week 26 ) and sitagliptin ( week 52 ) ( p < 0.001 ) . Overall AE and AE-related discontinuation rates were generally similar across groups , but higher with canagliflozin 100 mg . Genital mycotic infection and osmotic diuresis-related AE rates were higher with canagliflozin ; few led to discontinuations . Hypoglycaemia incidence was higher with canagliflozin . Conclusions /interpretationCanagliflozin improved glycaemia and reduced body weight vs placebo ( week 26 ) and sitagliptin ( week 52 ) and was generally well tolerated in patients with type 2 diabetes on metformin . Clinical trial registry Clinical Trials.gov NCT01106677 Funding This study was supported by Janssen Research & Development , LLC Background We compared the efficacies of vildagliptin ( 50 mg twice daily ) relative to pioglitazone ( 15 mg once daily ) as an add-on treatment to metformin for reducing glycosylated hemoglobin ( HbA1c ) levels in Korean patients with type 2 diabetes . Methods The present study was a multicenter , r and omized , active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control . Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin . Results The mean changes in HbA1c levels from baseline were –0.94 % in the vildagliptin group and –0.6 % in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3 % . The mean changes in postpr and ial plasma glucose ( PPG ) levels were –60.2 mg/dL in the vildagliptin group and –38.2 mg/dL in the pioglitazone group and these values significantly differed ( P=0.040 ) . There were significant decreases in the levels of total , low density lipoprotein , high density lipoprotein ( HDL ) , and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group . The mean change in body weight was –0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group , which were also significantly different ( P=0.002 ) . Conclusion As an add-on to metformin , the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes . In addition , add-on treatment with vildagliptin had beneficial effects on PPG levels , lipid profiles , and body weight compared to pioglitazone BACKGROUND Patients with type 2 diabetes are at high risk of fatal and non-fatal myocardial infa rct ion and stroke . There is indirect evidence that agonists of peroxisome proliferator-activated receptor gamma ( PPAR gamma ) could reduce macrovascular complications . Our aim , therefore , was to ascertain whether pioglitazone reduces macrovascular morbidity and mortality in high-risk patients with type 2 diabetes . METHODS We did a prospect i ve , r and omised controlled trial in 5238 patients with type 2 diabetes who had evidence of macrovascular disease . We recruited patients from primary -care practice s and hospitals . We assigned patients to oral pioglitazone titrated from 15 mg to 45 mg ( n=2605 ) or matching placebo ( n=2633 ) , to be taken in addition to their glucose-lowering drugs and other medications . Our primary endpoint was the composite of all-cause mortality , non fatal myocardial infa rct ion ( including silent myocardial infa rct ion ) , stroke , acute coronary syndrome , endovascular or surgical intervention in the coronary or leg arteries , and amputation above the ankle . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N NCT00174993 . FINDINGS Two patients were lost to follow-up , but were included in analyses . The average time of observation was 34.5 months . 514 of 2605 patients in the pioglitazone group and 572 of 2633 patients in the placebo group had at least one event in the primary composite endpoint ( HR 0.90 , 95 % CI 0.80 - 1.02 , p=0.095 ) . The main secondary endpoint was the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke . 301 patients in the pioglitazone group and 358 in the placebo group reached this endpoint ( 0.84 , 0.72 - 0.98 , p=0.027 ) . Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified . 6 % ( 149 of 2065 ) and 4 % ( 108 of 2633 ) of those in the pioglitazone and placebo groups , respectively , were admitted to hospital with heart failure ; mortality rates from heart failure did not differ between groups . INTERPRETATION Pioglitazone reduces the composite of all-cause mortality , non-fatal myocardial infa rct ion , and stroke in patients with type 2 diabetes who have a high risk of macrovascular events BACKGROUND Diabetes confers an increased risk of adverse cardiovascular and renal events . In the EMPA-REG OUTCOME trial , empagliflozin , a sodium-glucose cotransporter 2 inhibitor , reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events . We wanted to determine the long-term renal effects of empagliflozin , an analysis that was a prespecified component of the secondary microvascular outcome of that trial . METHODS We r and omly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2 ) of body-surface area to receive either empagliflozin ( at a dose of 10 mg or 25 mg ) or placebo once daily . Prespecified renal outcomes included incident or worsening nephropathy ( progression to macroalbuminuria , doubling of the serum creatinine level , initiation of renal-replacement therapy , or death from renal disease ) and incident albuminuria . RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients ( 12.7 % ) in the empagliflozin group and in 388 of 2061 ( 18.8 % ) in the placebo group ( hazard ratio in the empagliflozin group , 0.61 ; 95 % confidence interval , 0.53 to 0.70 ; P<0.001 ) . Doubling of the serum creatinine level occurred in 70 of 4645 patients ( 1.5 % ) in the empagliflozin group and in 60 of 2323 ( 2.6 % ) in the placebo group , a significant relative risk reduction of 44 % . Renal-replacement therapy was initiated in 13 of 4687 patients ( 0.3 % ) in the empagliflozin group and in 14 of 2333 patients ( 0.6 % ) in the placebo group , representing a 55 % lower relative risk in the empagliflozin group . There was no significant between-group difference in the rate of incident albuminuria . The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population . CONCLUSIONS In patients with type 2 diabetes at high cardiovascular risk , empagliflozin was associated with slower progression of kidney disease and lower rates of clinical ly relevant renal events than was placebo when added to st and ard care . ( Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance ; EMPA-REG OUTCOME Clinical Trials.gov number , NCT01131676 . ) OBJECTIVE This study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin . RESEARCH DESIGN AND METHODS This was a double-blind trial in adults with HbA1c ≥8.0 % and ≤12.0 % ( 64–108 mmol/mol ) , r and omized to saxagliptin ( SAXA ) ( 5 mg/day ) plus dapagliflozin ( DAPA ) ( 10 mg/day ; n = 179 ) , or SAXA ( 5 mg/day ) and placebo ( n = 176 ) , or DAPA ( 10 mg/day ) and placebo ( n = 179 ) on background metformin extended release ( MET ) ≥1,500 mg/day . Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET . RESULTS Patients had a mean baseline HbA1c of 8.9 % ( 74 mmol/mol ) , diabetes duration of 7.6 years , and a BMI of 32 kg/m2 . At week 24 , the adjusted mean change from the baseline HbA1c was –1.5 % ( –16.1 mmol/mol ) with SAXA+DAPA+MET versus –0.9 % ( –9.6 mmol/mol ) with SAXA+MET ( difference −0.59 % [ –6.4 mmol/mol ] , P < 0.0001 ) and –1.2 % ( –13.1 mmol/mol ) with DAPA+MET ( difference −0.27 % [ 3.0 mmol/mol ] , P < 0.02 ) . The proportion of patients achieving HbA1c < 7 % ( 53 mmol/mol ) was 41 % with SAXA+DAPA+MET versus 18 % with SAXA+MET and 22 % with DAPA+MET . Urinary and genital infections occurred in ≤1 % of patients receiving SAXA+DAPA+MET . Hypoglycemia was infrequent , with no episodes of major hypoglycemia . CONCLUSIONS In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin , greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone We investigated the efficacy and safety of empagliflozin over 24 weeks in Asian patients with type 2 diabetes ( T2DM ) using pooled data from four phase III trials . In these trials , patients were r and omized to receive empagliflozin 10 mg , empagliflozin 25 mg or placebo as monotherapy or add-on to metformin , metformin plus sulphonylurea or pioglitazone ± metformin . In total , 1326 patients from Asia received ≥1 dose of study drug . At week 24 , adjusted mean differences versus placebo in change from baseline in glycated haemoglobin ( HbA1c ) were -0.66 % [ 95 % confidence interval ( CI ) -0.76 , -0.56 ] and -0.73 % ( 95 % CI -0.83 , -0.64 ) and in weight were -1.6 kg ( 95 % CI -1.9 , -1.3 ) and -1.8 kg ( 95 % CI -2.1 , -1.5 ) with empagliflozin 10 and 25 mg , respectively ( all p < 0.001 ) . Empagliflozin significantly reduced systolic and diastolic blood pressure . The proportion of patients reporting ≥1 adverse event was similar across treatment groups , but events consistent with genital infection were more common in patients treated with empagliflozin 10 mg ( 3.4 % ) or 25 mg ( 2.3 % ) than placebo ( 0.9 % ) . Thus in Asian patients with T2DM , empagliflozin reduced HbA1c , weight and blood pressure , and was well tolerated BACKGROUND The efficacy of thiazolidinediones , as compared with other oral glucose-lowering medications , in maintaining long-term glycemic control in type 2 diabetes is not known . METHODS We evaluated rosiglitazone , metformin , and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind , r and omized , controlled clinical trial involving 4360 patients . The patients were treated for a median of 4.0 years . The primary outcome was the time to monotherapy failure , which was defined as a confirmed level of fasting plasma glucose of more than 180 mg per deciliter ( 10.0 mmol per liter ) , for rosiglitazone , as compared with metformin or glyburide . Prespecified secondary outcomes were levels of fasting plasma glucose and glycated hemoglobin , insulin sensitivity , and beta-cell function . RESULTS Kaplan-Meier analysis showed a cumulative incidence of monotherapy failure at 5 years of 15 % with rosiglitazone , 21 % with metformin , and 34 % with glyburide . This represents a risk reduction of 32 % for rosiglitazone , as compared with metformin , and 63 % , as compared with glyburide ( P<0.001 for both comparisons ) . The difference in the durability of the treatment effect was greater between rosiglitazone and glyburide than between rosiglitazone and metformin . Glyburide was associated with a lower risk of cardiovascular events ( including congestive heart failure ) than was rosiglitazone ( P<0.05 ) , and the risk associated with metformin was similar to that with rosiglitazone . Rosiglitazone was associated with more weight gain and edema than either metformin or glyburide but with fewer gastrointestinal events than metformin and with less hypoglycemia than glyburide ( P<0.001 for all comparisons ) . CONCLUSIONS The potential risks and benefits , the profile of adverse events , and the costs of these three drugs should all be considered to help inform the choice of pharmacotherapy for patients with type 2 diabetes . ( Clinical Trials.gov number , NCT00279045 [ Clinical Trials.gov ] . ) BACKGROUND Metformin is the recommended first-line pharmacotherapy for patients with type 2 diabetes . There is no consensus on the optimum second-line pharmacotherapy . We compared the efficacy and safety of the sodium glucose cotransporter 2 inhibitor empagliflozin and the sulfonylurea glimepiride as add-on to metformin in patients with type 2 diabetes . METHODS In this double-blind phase 3 trial , patients ( aged ≥18 years ) with type 2 diabetes and HbA1c concentrations of 7 - 10 % , despite metformin treatment and diet and exercise counselling , were r and omly assigned in a 1:1 ratio with a computer-generated r and om sequence , stratified by HbA1c , estimated glomerular filtration rate ( eGFR ) , and region , to empagliflozin ( 25 mg once daily , orally ) or glimepiride ( 1 - 4 mg once daily , orally ) as add-on to metformin for 104 weeks . Patients and investigators were masked to treatment assignment . The primary endpoint was change from baseline in HbA1c levels at weeks 52 and 104 . Differences in the primary endpoint were first tested for non-inferiority ( based on a margin of 0·3 % ) . If non-inferiority was shown , differences in the primary endpoint at week 104 were then tested for superiority . Analysis was done on the full- analysis set-ie , patients who were treated with at least one dose of study drug and had a baseline HbA1c value . This study is registered with Clinical Trials.gov , number NCT01167881 . A 104-week extension is ongoing . FINDINGS Between August , 2010 , and June , 2011 , 1549 patients were r and omly assigned to receive empagliflozin ( n=769 ) or glimepiride ( n=780 ) ; four patients in the empagliflozin group did not receive the assigned treatment . Empagliflozin was non-inferior to glimepiride at both timepoints . At week 104 , adjusted mean difference in change from baseline in HbA1c with empagliflozin versus glimepiride was -0·11 % ( 95 % CI -0·19 to -0·02 ; p=0·0153 for superiority ) . Adverse events were reported in 661 ( 86 % ) patients treated with empagliflozin and 673 ( 86 % ) patients treated with glimepiride . Severe adverse events were reported in 72 ( 9 % ) patients in the empagliflozin group and 68 ( 9 % ) in the glimepiride group . Serious adverse events were reported in 119 ( 16 % ) patients in the empagliflozin group and 89 ( 11 % ) in the glimepiride group . Confirmed hypoglycaemic adverse events ( plasma glucose ≤3·9 mmol/L or requiring assistance ) at week 104 were reported in 19 ( 2 % ) patients treated with empagliflozin and 189 ( 24 % ) patients treated with glimepiride . INTERPRETATION Empagliflozin might be an effective and a well tolerated second-line treatment option for patients with type 2 diabetes who have not achieved good glycaemic control on metformin . FUNDING Boehringer Ingelheim and Eli Lilly OBJECTIVE Although initially effective , sulfonylureas are associated with poor glycemic durability , weight gain , and hypoglycemia . Dapagliflozin , a selective inhibitor of sodium-glucose cotransporter 2 ( SGLT2 ) , reduces hyperglycemia by increasing urinary glucose excretion independent of insulin and may cause fewer of these adverse effects . We compared the efficacy , safety , and tolerability of dapagliflozin with the sulfonylurea glipizide in patients with type 2 diabetes inadequately controlled with metformin monotherapy . RESEARCH DESIGN AND METHODS This 52-week , double-blind , multicenter , active-controlled , noninferiority trial r and omized patients with type 2 diabetes ( baseline mean HbA1c , 7.7 % ) , who were receiving metformin monotherapy , to add-on dapagliflozin ( n = 406 ) or glipizide ( n = 408 ) up-titrated over 18 weeks , based on glycemic response and tolerability , to ≤ 10 or ≤ 20 mg/day , respectively . RESULTS The primary end point , adjusted mean HbA1c reduction with dapagliflozin ( -0.52 % ) compared with glipizide ( -0.52 % ) , was statistically noninferior at 52 weeks . Key secondary end points : dapagliflozin produced significant adjusted mean weight loss ( -3.2 kg ) versus weight gain ( 1.2 kg ; P < 0.0001 ) with glipizide , significantly increased the proportion of patients achieving ≥ 5 % body weight reduction ( 33.3 % ) versus glipizide ( 2.5 % ; p < 0.0001 ) , and significantly decreased the proportion experiencing hypoglycemia ( 3.5 % ) versus glipizide ( 40.8 % ; p < 0.0001 ) . Events suggestive of genital infections and lower urinary tract infections were reported more frequently with dapagliflozin compared with glipizide but responded to st and ard treatment and rarely led to study discontinuation . CONCLUSIONS Despite similar 52-week glycemic efficacy , dapagliflozin reduced weight and produced less hypoglycemia than glipizide in type 2 diabetes inadequately controlled with metformin . Long-term studies are required to further evaluate genital and urinary tract infections with SGLT2 inhibitors BACKGROUND Sodium-glucose cotransporter 2 ( SGLT2 ) inhibitors improve glycaemia in patients with type 2 diabetes by enhancing urinary glucose excretion . We compared the efficacy and safety of canagliflozin , an SGLT2 inhibitor , with glimepiride in patients with type 2 diabetes inadequately controlled with metformin . METHODS We undertook this 52 week , r and omised , double-blind , active-controlled , phase 3 non-inferiority trial at 157 centres in 19 countries between Aug 28 , 2009 , and Dec 21 , 2011 . Patients aged 18 - 80 years with type 2 diabetes and glycated haemoglobin A1c ( HbA1c ) of 7·0 - 9·5 % on stable metformin were r and omly assigned ( 1:1:1 ) by computer-generated r and om sequence via an interactive voice or web response system to receive canagliflozin 100 mg or 300 mg , or glimepiride ( up-titrated to 6 mg or 8 mg per day ) orally once daily . Patients , study investigators , and local sponsor personnel were masked to treatment . The primary endpoint was change in HbA1c from baseline to week 52 , with a non-inferiority margin of 0·3 % for the comparison of each canagliflozin dose with glimepiride . If non-inferiority was shown , we assessed superiority on the basis of an upper bound of the 95 % CI for the difference of each canagliflozin dose versus glimepiride of less than 0·0 % . Analysis was done in a modified intention-to-treat population , including all r and omised patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT00968812 . FINDINGS 1450 of 1452 r and omised patients received at least one dose of glimepiride ( n=482 ) , canagliflozin 100 mg ( n=483 ) , or canagliflozin 300 mg ( n=485 ) . For lowering of HbA1c at 52 weeks , canagliflozin 100 mg was non-inferior to glimepiride ( least-squares mean difference -0·01 % [ 95 % CI -0·11 to 0·09 ] ) , and canagliflozin 300 mg was superior to glimepiride ( -0·12 % [ -0·22 to -0·02 ] ) . 39 ( 8 % ) patients had serious adverse events in the glimepiride group versus 24 ( 5 % ) in the canagliflozin 100 mg group and 26 ( 5 % ) in the 300 mg group . In the canagliflozin 100 mg and 300 mg groups versus the glimepiride group , we recorded a greater number of genital mycotic infections ( women : 26 [ 11 % ] and 34 [ 14 % ] vs five [ 2 % ] ; men : 17 [ 7 % ] and 20 [ 8 % ] vs three [ 1 % ] ) , urinary tract infections ( 31 [ 6 % ] for both canagliflozin doses vs 22 [ 5 % ] ) , and osmotic diuresis-related events ( pollakiuria : 12 [ 3 % ] for both doses vs one [ < 1 % ] ; polyuria : four [ < 1 % ] for both doses vs two [ < 1 % ] ) . INTERPRETATION Canagliflozin provides greater HbA1c reduction than does glimepiride , and is well tolerated in patients with type 2 diabetes receiving metformin . These findings support the use of canagliflozin as a viable treatment option for patients who do not achieve sufficient glycaemic control with metformin therapy . FUNDING Janssen Research & Development , LLC AIMS To assess the efficacy and safety of gemigliptin , a dipeptidyl peptidase-4 inhibitor , added to metformin and sulphonylurea in patients with type 2 diabetes ( T2DM ) . MATERIAL S AND METHODS We conducted a r and omized , double-blind , placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride . Participants were r and omized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride . The primary endpoint was change in glycated haemoglobin ( HbA1c ) level from baseline to week 24 . RESULTS The baseline HbA1c was 8.2 % in both groups . The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo ( between-group difference in adjusted mean change -0.87 % , 95 % confidence interval [ CI ] -1.09 % to -0.64 % ) . Fasting plasma glucose level was also significantly reduced with gemigliptin ( -0.93 mmol/L , 95 % CI -1.50 to -0.35 mmol/L ) , and a higher proportion of participants achieved an HbA1c level of < 7 % ( 39.3 % vs 5.5 % ; P < .001 ) in the gemigliptin group than in the placebo group . Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group ( -0.21 mmol/L , 95 % CI -0.38 to -0.03 mmol/L for total cholesterol , -0.18 mmol/L , 95 % CI -0.34 to -0.01 mmol/L for LDL cholesterol ) . The incidence of hypoglycaemia was 9.4 % in the gemigliptin group and 2.7 % in the placebo group . CONCLUSIONS Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea . The incidence of hypoglycaemia was higher with gemigliptin than with placebo , which highlights the importance of optimal dose adjustment for sulphonylurea BACKGROUND Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin , a dipeptidyl peptidase 4 inhibitor , to usual care in patients with type 2 diabetes and cardiovascular disease . METHODS In this r and omized , double-blind study , we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy . Open-label use of antihyperglycemic therapy was encouraged as required , aim ed at reaching individually appropriate glycemic targets in all patients . To determine whether sitagliptin was noninferior to placebo , we used a relative risk of 1.3 as the marginal upper boundary . The primary cardiovascular outcome was a composite of cardiovascular death , nonfatal myocardial infa rct ion , nonfatal stroke , or hospitalization for unstable angina . RESULTS During a median follow-up of 3.0 years , there was a small difference in glycated hemoglobin levels ( least-squares mean difference for sitagliptin vs. placebo , -0.29 percentage points ; 95 % confidence interval [ CI ] , -0.32 to -0.27 ) . Overall , the primary outcome occurred in 839 patients in the sitagliptin group ( 11.4 % ; 4.06 per 100 person-years ) and 851 patients in the placebo group ( 11.6 % ; 4.17 per 100 person-years ) . Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome ( hazard ratio , 0.98 ; 95 % CI , 0.88 to 1.09 ; P<0.001 ) . Rates of hospitalization for heart failure did not differ between the two groups ( hazard ratio , 1.00 ; 95 % CI , 0.83 to 1.20 ; P=0.98 ) . There were no significant between-group differences in rates of acute pancreatitis ( P=0.07 ) or pancreatic cancer ( P=0.32 ) . CONCLUSIONS Among patients with type 2 diabetes and established cardiovascular disease , adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events , hospitalization for heart failure , or other adverse events . ( Funded by Merck Sharp & Dohme ; TECOS Clinical Trials.gov number , NCT00790205 . ) BACKGROUND To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes , regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies . We assessed cardiovascular outcomes with alogliptin , a new inhibitor of dipeptidyl peptidase 4 ( DPP-4 ) , as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome . METHODS We r and omly assigned patients with type 2 diabetes and either an acute myocardial infa rct ion or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy . The study design was a double-blind , noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS A total of 5380 patients underwent r and omization and were followed for up to 40 months ( median , 18 months ) . A primary end-point event occurred in 305 patients assigned to alogliptin ( 11.3 % ) and in 316 patients assigned to placebo ( 11.8 % ) ( hazard ratio , 0.96 ; upper boundary of the one-sided repeated confidence interval , 1.16 ; P<0.001 for noninferiority ) . Glycated hemoglobin levels were significantly lower with alogliptin than with placebo ( mean difference , -0.36 percentage points ; P<0.001 ) . Incidences of hypoglycemia , cancer , pancreatitis , and initiation of dialysis were similar with alogliptin and placebo . CONCLUSIONS Among patients with type 2 diabetes who had had a recent acute coronary syndrome , the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo . ( Funded by Takeda Development Center Americas ; EXAMINE Clinical Trials.gov number , NCT00968708 . ) |
2,628 | 17,661,578 | The breastfeeding group had significantly less increase in the heart rate , reduced proportion of crying time and reduced duration of crying compared to the swaddled or pacifier group .
Premature Infant Pain Profile scores were lower in the breastfeeding group when compared to the placebo and the group positioned in mother 's arms , but were not different compared to the no-treatment and the glucose groups .
Neonates in the supplemental breastmilk group had a significantly less increase in the heart rate and Neonatal Facial Coding Score but no significant difference in the duration of crying time and oxygen saturation change compared to the placebo .
CONCLUSIONS If available , breastfeeding or breastmilk should be used to alleviate pain in neonates undergoing painful procedure compared to placebo , positioning , or no intervention .
Administration of glucose/sucrose had a similar effectiveness as breastfeeding for reducing pain . | OBJECTIVES To ( 1 ) compare breastfeeding with control ( placebo , no treatment , sucrose , glucose , pacifiers , or positioning ) and ( 2 ) compare breastmilk with control for procedural pain in neonates . | There is evidence that newborn babies feel pain even at the lowest gestational ages when they can survive . Because sweet solutions such as sucrose , given orally , may relieve pain in neonates , we decided to compare the effects of two concentrations of glucose ( normally used for intravenous infusions ) and of breast milk in a r and omized controlled trial in 120 babies requiring heel‐prick tests . Glucose solutions and breast milk are readily available in the neonatal department . No other treatment was given . Our results strongly suggest that 1 ml of a 30 % glucose solution given orally alleviates mild pain significantly and can be used for this purpose in newborns . Breast milk and 10 % glucose did not have a similar effect OBJECTIVE To determine whether milk and its components reduce crying in newborns during and after blood collection for phenylketonuria evaluation . METHODOLOGY Seventy-two normal newborns ingested 2 mL of milk ( Similac ) , Ross Special Formula , fat , protein , lactose , sucrose , or water for the 2 minutes preceding blood collection via heel lance . Crying duration during and for the 3 minutes after the procedure was determined by scorers who were blind to the ingestive substance . RESULTS Sucrose and Similac each reduced crying during the blood collection procedure . Sucrose , fat , protein , and Ross Special Formula were effective during the 3-minute recovery period . Neither water nor lactose were effective during or after blood collection . CONCLUSION Milk and some of its components are antinociceptive in human newborns . Based on previous studies , reduced crying during and after painful stimulation may be mediated through endogenous opioids . These findings are of potential clinical significance : natural protective mechanisms , normally engaged during suckling , may safely and noninvasively be activated to reduce newborn crying to painful stimulation OBJECTIVE To determine the efficacy of sucrose analgesia for procedural pain during the first week of life in preterm neonates in neonatal intensive care units on enhancing later clinical outcomes . METHODS A total of 107 preterm neonates who were born at < 31 weeks ' postconceptional age ( PCA ) entered this double-blind , r and omized , controlled trial within 48 hours of birth at 3 level III university-affiliated neonatal intensive care units in Canada , and 103 completed the study . Sucrose ( 0.1 mL of 24 % ) or sterile water was administered orally up to 3 times , 2 minutes apart , for every invasive procedure during a 7-day period . Motor development and vigor , and alertness and orientation components of the Neurobehavioral Assessment of the Preterm Infant were measured at 32 , 36 , and 40 weeks ' PCA ; Score for Neonatal Acute Physiology was measured on the last day of intervention ; and Neuro-Biological Risk Score ( NBRS ) was measured at 2 weeks of age and at discharge . Primary analyses of covariance were applied for each outcome to compare group differences followed by secondary analyses using st and ard linear regression within each group to determine predictors of outcomes . RESULTS Although there were no differences between the groups on any outcomes , there were significant dose-related effects within each group . In the sucrose group only , higher number of doses of sucrose predicted lower scores on motor development and vigor , and alertness and orientation at 36 weeks ' , lower motor development and vigor at 40 weeks ' , and higher NBRS at 2 weeks ' postnatal age . Higher number of invasive procedures was predictive of higher NBRS both times in the water group . CONCLUSIONS Repeated use of sucrose analgesia in infants < 31 weeks ' PCA may put infants at risk for poorer neurobehavioral development and physiologic outcomes . Additional study is needed to determine the most appropriate age and duration of sucrose analgesia in preterm infants CONTEXT This study identifies a behavioral and nonpharmacologic means of preventing newborn pain . OBJECTIVE To determine whether breastfeeding is analgesic in newborn infants undergoing heel lance-a routine , painful , hospital procedure . DESIGN A prospect i ve , r and omized , controlled trial . SETTING Hospital maternity services at Boston Medical Center , Boston , Massachusetts , and Beverly Hospital , Beverly , Massachusetts . PARTICIPANTS A r and om sample of 30 full-term , breastfed infants . INTERVENTIONS Infants in the intervention group were held and breastfed by their mothers during heel lance and blood collection procedures for the Newborn Screening Program Blood Test . Infants in the control group experienced the same blood test while receiving the st and ard hospital care of being swaddled in their bassinets . OUTCOMES MEASURES Crying , grimacing , and heart rate differences were analyzed between the breastfeeding and the control infants before , during , and after blood collection . RESULTS Crying and grimacing were reduced by 91 % and 84 % , respectively , from control infant levels during the blood collection . Heart rate was also substantially reduced by breastfeeding . CONCLUSIONS Breastfeeding is a potent analgesic intervention in newborns during a st and ard blood collection Aim : To assess the effectiveness of expressed breast milk ( EBM ) in reducing pain due to venepuncture , in term neonates , as measured by behavioural and physiological observations . Methods : This r and omized , placebo‐controlled , double‐blind trial involved 81 full‐term neonates , up to 4wk of postnatal age , who needed venepuncture for blood investigations . Two minutes before the venepuncture , in the intervention arm , 40 babies received 5 ml of EBM , while 41 babies in control group received 5 ml of distilled water ( DW ) as placebo . Two observers who were blinded to the intervention recorded the physiological ( heart rate and oxygen saturation ) and behavioural parameters [ duration of crying and modified Neonatal Facial Coding Scores ( NFCS ) ] after the venepuncture . Results : There was no difference in the baseline characteristics of the neonates in the two groups . The duration of crying was significantly shorter in babies fed EBM [ median 38.5 s , interquartile range ( IQR ) 9.5–57.5 s ] than in those fed DW ( median 90 s , IQR 28–210 s ) . The mean duration of crying in EBM group was shorter by 70.7 ( 95 % confidence interval 36.6–104.9 ) s. The modified NFCS at 0 , 1 and 3 min was significantly lower ( p > 0.01 ) in the EBM than in the DW group . The change in heart rate and oxygen saturation was significantly lower in the EBM group and returned to baseline values sooner than in the DW group OBJECTIVE Inadequate assessment of pain in premature infants is a persistent clinical problem . The objective of this research was to develop and vali date a measure for assessing pain in premature infants that could be used by both clinicians and research ers . DESIGN The Premature Infant Pain Profile ( PIPP ) was developed and vali date d using a prospect i ve and retrospective design . Indicators of pain were identified from clinical experts and the literature . Indicators were retrospectively tested using four existing data sets . PATIENTS AND SETTING S Infants of varying gestational ages undergoing different painful procedures from three different setting s were utilized to develop and vali date the measure . METHODS AND RESULTS The largest data set ( n = 124 ) was used to develop the PIPP . The development process included determining the factor structure of the data , developing indicators and indicator scales and establishing internal consistency . The remaining three data sets were utilized to establish beginning construct validity . CONCLUSIONS The PIPP is a newly developed pain assessment measure for premature infants with beginning content and construct validity . The practicality and feasibility for using the PIPP in clinical practice will be determined in prospect i ve research in the clinical setting This study evaluates the effects of colostrum , delivered via syringe or on a pacifier , on the pain and heart rate reactions of newborns undergoing routine heel-lance . This was achieved by following a quasi-r and omized , controlled trial in which 60 newborn infants at Boston Medical Center , Boston , MA , were r and omly assigned to receive colostrum , sucrose , or water , by syringe or on a pacifier , for a total of 6 groups ( n = 10 per group ) . The effectiveness of an intervention was determined by comparing crying , grimacing , and heart rate differences among groups during and following blood collection . We report that colostrum , delivered by syringe or on a pacifier , did not reduce crying or grimacing relative to control infants who received water . As has been previously reported , sucrose markedly reduced both crying and grimacing , and attenuated the rise in heart rate that normally accompanies blood collection ( p < .002 ) . Water , via syringe or on a pacifier , did not prevent the increase in heart rate , nor did colostrum via syringe . In contrast , colostrum delivered on a pacifier prevented the increase in heart rate despite pain reactivity and extreme crying . The implication s of this dissociation are discussed OBJECTIVE To identify the effectiveness of " facilitated tucking , " a nonpharmacologic nursing intervention , as a comfort measure in modulating preterm neonates ' physiologic and behavioral responses to minor pain . DESIGN Prospect i ve , repeated measure , r and om sequencing , and experimental . SETTING Level III neonatal intensive-care unit of a tertiary care university pediatric hospital . PARTICIPANTS Thirty preterm neonates , 25 - 35 weeks gestation . INTERVENTIONS Heart rate , oxygen saturation , and sleep state were recorded 12 minutes before , during , and 15 minutes after two heelsticks , one with and one without facilitated tucking . HYPOTHESIS Premature neonates will have less variation in heart rate and hemoglobin oxygen saturation , shorter crying and sleep disruption times , and less fluctuation in sleep states in response to the painful stimulus of a heelstick with facilitated tucking than without . RESULTS Neonates demonstrated a lower mean heart rate 6 - 10 minutes post-stick ( p < 0.04 ) , shorter mean crying time ( p < 0.001 ) , shorter mean sleep disruption time ( p < 0.001 ) , and fewer sleep-state changes ( p = 0.003 ) after heelstick with facilitated tucking than without . CONCLUSION Facilitated tucking is an effective comfort measure in attenuating premature neonates ' psychologic and behavioral responses to minor pain BACKGROUND Physiologic and behavioral responses to procedural pain are influenced by gestational age ( GA ) . Compared with term neonates , hospitalized preterm neonates are subjected to more painful procedures aim ed at improving their clinical outcome . Although several trials to determine the efficacy of sucrose for managing procedural pain have been conducted , none have examined the influence of GA . OBJECTIVES To examine the influence of GA on the efficacy and short-term safety of oral sucrose for relieving procedural pain associated with heel lances . To explore GA differences in behavioral and physiologic indicators of pain . METHODS As part of a larger r and omized controlled trial ( RCT ) to examine the efficacy and safety of sucrose during heel lance , 190 neonates were stratified by GA : ( a ) 27 to 31 6/7 weeks ( group 1 ; n = 63 ) , ( b ) 32 to 35 6/7 weeks ( group 2 ; n = 63 ) , and ( c ) > 36 weeks ( group 3 ; n = 64 ) . They were then r and omized to receive ( a ) oral sucrose and non-nutritive sucking ( NNS ) , ( b ) sucrose alone , or ( c ) sterile water and NNS ( control ) for a heel lance . The influence of GA was determined by examining the short-term safety , as defined by the number of associated adverse events ( choking , coughing or vomiting , sustained tachycardia , sustained tachypnea or dyspnea , or sustained oxygen desaturation ) . The efficacy was measured by changes in a vali date d pain measure , scored during each phase of the intervention and analyzed according to GA groups . RESULTS Significant differences in pain response existed in each GA group , with the lowest mean pain scores in the sucrose and NNS group . Significant GA differences in behavioral and physiologic responses were found , with the most mature neonates demonstrating the greatest magnitude of pain response . The greatest number of short-term adverse effects to treatment occurred in the lowest GA group . CONCLUSIONS In a secondary analysis of a larger RCT , sucrose and NNS was the most efficacious intervention for single heel lances in each of 3 GA groups . However , infants of lower GA experienced more adverse events . Research on the efficacy and safety of repeated doses of oral sucrose , tested in infants from a wide range of GA , is required Abstract Objectives : To investigate whether breast feeding is effective for pain relief during venepuncture in term neonates and compare any effect with that of oral glucose combined with a pacifier . Design : R and omised controlled trial . Participants : 180 term newborn infants undergoing venepuncture ; 45 in each group . Interventions : During venepuncture infants were either breast fed ( group 1 ) , held in their mother 's arms without breast feeding ( group 2 ) , given 1 ml of sterile water as placebo ( group 3 ) , or given 1 ml of 30 % glucose followed by pacifier ( group 4 ) . Video recordings of the procedure were assessed by two observers blinded to the purpose of the study . Main outcome measures : Pain related behaviours evaluated with two acute pain rating scales : the Douleur Aiguë Nouveau-né scale ( range 0 to 10 ) and the premature infant pain profile scale ( range 0 to 18 ) . Results : Median pain scores ( interquartile range ) for breast feeding , held in mother 's arms , placebo , and 30 % glucose plus pacifier groups were 1 ( 0–3 ) , 10 ( 8.5 - 10 ) , 10 ( 7.5 - 10 ) , and 3 ( 0–5 ) with the Douleur Aiguë Nouveau-né scale and 4.5 ( 2.25 - 8 ) , 13 ( 10.5 - 15 ) , 12 ( 9–13 ) , and 4 ( 1–6 ) with the premature infant pain profile scale . Analysis of variance showed significantly different median pain scores ( P<0.0001 ) among the groups . There were significant reductions in both scores for the breast feeding and glucose plus pacifier groups compared with the other two groups ( P<0.0001 , two tailed Mann-Whitney U tests between groups ) . The difference in Douleur Aiguë Nouveau-né scores between breast feeding and glucose plus pacifier groups was not significant ( P=0.16 ) . Conclusions : Breast feeding effectively reduces response to pain during minor invasive procedure in term neonates . What is already known on this topic Current pharmacological treatments are not appropriate for pain relief during minor procedures like venepuncture or heel prick in newborn infants Oral sweet solutions , non-nutritive sucking , and skin to skin contact reduce procedural pain in newborn infants What this study adds Breast feeding during a painful procedure effectively reduces the response to pain in newborn infants The analgesic properties of breast feeding are at least as potent as the combination of sweet solutions and a Newborns endure many heel pricks and other uncomfortable procedures during their first hospital stay . The aim of this study was to investigate the effectiveness of breast-feeding in reducing pain in newborns undergoing heel prick tests . One hundred thirty healthy term infants requiring a heel prick blood sampling for the Guthrie test were studied . Infants were r and omly allocated to 1 of the following treatment groups : group 1 , 25 % sucrose ( n = 35 ) ; group 2 , breast milk ( n = 33 ) ; group 3 , sterile water ( n = 34 ) ; and group 4 , breast-feeding ( n = 28 ) . The median values of crying and recovery time and percent change in heart rate at 1 , 2 , and 3 minutes were recorded . A behavioral pain scale was applied according to the infant body coding system . The median crying time was 36 , 62 , 52 , and 51 seconds in groups 1 , 2 , 3 , and 4 , respectively ( P = .002 ) . Similarly , there was a significant overall difference among groups for the duration of recovery time ( P = .006 ) and the percent change in heart rate at 1 ( P = .03 ) , 2 ( P = .01 ) , and 3 ( P = .009 ) minutes favoring the sucrose group . But when we compared the groups , the significance remained for the sucrose versus breast milk ( P = .007 ) and water ( P = .001 ) groups for the recovery time and sucrose versus all other groups for the percent change in heart rate at 3 minutes . The infant body coding system showed that babies in the sucrose group had significantly lower scores followed by the breast-fed and breast milk groups ( P = .0001 ) . Our study revealed that 25 % sucrose is superior to breast-feeding in pain relief , which is reflected mainly in crying time and behavioral variables . The behavioral effects of breast-feeding did not provide any additional benefit Abstract The aim of this study was to compare the analgesic effect of 2 ml 25 % sucrose and human milk in a group of healthy term newborns . Healthy infants ( n = 102 ) were r and omly allocated to receive one of three solutions ( sucrose , human milk , sterile water ) 2 min prior to taking a heel prick blood sample . The median values of crying time , recovery time and percentage change in heart rate at 1 , 2 and 3 min were recorded in response to the heel prick . Median crying times were 36 , 52 , and 62 s in the sucrose , placebo and human milk groups , respectively ( P = 0.0009 ) . In the sucrose group , there was a significant reduction in crying time compared to human milk and placebo groups . Similarly , the median recovery time in the sucrose group ( 72 s ) was shorter than that in the human milk ( 112 s ) and placebo groups ( 124 s ) ( P = 0.004 ) . The percentage change in heart rate at 1 , 2 and 3 min was also significantly lower in the sucrose group ( P = 0.008 , P = 0.01 , P = 0.002 at 1 , 2 , and 3 min respectively ) . Conclusion The orosensorial antinociceptive effect of human milk is not as effective as an analgesic as a 25 % sucrose solution OBJECTIVES First , to compare analgesic effects of breast-feeding versus pacifier use in newborn infants undergoing blood collection via heel sticks . Second , to compare analgesic effects of pacifier use with maternal holding versus nonmaternal holding . DESIGN A prospect i ve , r and omized , controlled trial . SETTING Normal newborn nursery at academic teaching hospital . PARTICIPANTS Full-term breast-feeding infants scheduled for routine newborn screening blood test via heel stick ( n = 96 ) . Interventions .-Infants r and omized to 3 groups for analgesia : 1 ) breast-feeding , 2 ) pacifier use while held by mothers , 3 ) pacifier use while held by research assistants ( nonmothers ) . OUTCOME MEASURES Primary outcome was crying ( percent of infants who cried during the procedure and mean percent of procedure time that infants cried ) . Secondary outcomes were physiologic measures . RESULTS Fewer breast-feeding infants cried than infants using a pacifier while held by nonmothers both during the procedure ( 69 % vs 100 % , P < .01 ) and after the procedure ( 28 % vs 60 % , P = .03 ) . Those infants crying during the procedure cried for less time if held by their mothers either breast-feeding ( 33 % , P < .01 ) or using a pacifier ( 45 % , P = .03 ) than those using a pacifier while being held by nonmothers ( 66 % ) . CONCLUSION Breast-feeding is more analgesic than pacifier use with nonmaternal holding . Maternal holding with either breast-feeding or pacifier use is more analgesic than nonmaternal holding with pacifier use , suggesting that maternal holding itself has an analgesic effect . Breast-feeding and maternal holding should be considered as pain-control measures for the neonate during heel-stick procedures BACKGROUND Infants are exposed to painful stimuli during routine medical care in the first few days of life . The aim of the present study was to compare the effect of foremilk ; hindmilk , which has been known to have more fat content than foremilk ; and sterile water in reducing pain in newborns undergoing minor painful procedures . METHODS Sixty-two healthy term infants requiring a heel prick blood sample for screening tests were r and omly allocated to receive 2 mL of foremilk , hindmilk or sterile water . Median crying time , duration of the first cry , percent change in heart rate , maximum heart rate and neonatal facial coding system scores were recorded to assess the infants ' response to pain . RESULTS Statistically significant differences between the three groups were not found in terms of crying time , duration of the first cry , percent change in heart rate or maximum heart rate ( P = 0.19 , P = 0.08 , P = 0.22 and P = 0.91 , respectively ) . When the mean pain scores of the groups were compared at 0 , 1 , 2 and 3 min , there was no statistically significant difference between the three groups ( P = 0.58 , P = 0.55 , P = 0.58 and P = 0.84 for 0 , 1 , 2 and 3 min , respectively ) . CONCLUSION Although hindmilk has a minor superiority in terms of crying time , duration of the first cry and percent change in heart rate , it does not reach statistical significance . It is concluded that neither foremilk nor hindmilk is superior in relieving pain when compared to placebo AIMS The aims of this study were to compare the pain reducing effect of oral glucose with that of being breast-fed shortly before venipuncture in newborns , and also the pain score and crying time with parents ' assessment . DESIGN R and omised , controlled trial . SUBJECTS 120 full term newborns undergoing venipuncture r and omly assigned to on of four groups : I , Breast-fed and 1-ml placebo ; II , Breast-fed and 1-ml 30 % glucose ; III , Fasting and 1-ml placebo ; and IV , Fasting and 1-ml 30 % glucose . OUTCOME MEASURES Pain during venipuncture was measured with the Premature Infant Pain Profile ( PIPP ) . Crying time was recorded . The parents assessed their babies ' pain on a Visual Analogue Scale ( VAS ) . RESULTS The PIPP score was significantly lower in the infants receiving glucose , than in those not given glucose ( p=0.004 ) . There was no significant difference in PIPP score between the infants who were fed and the fasting infants . The PIPP score was lower in group II ( median 7 ) than in group I ( md 10 ) . There was a similar difference between group IV ( md 9 ) and group III ( md 11 ) . The median crying times during the first 3 min in groups I , II , III , and IV were 63 , 18 , 142 and 93 s , respectively . There was low agreement between the parents ' assessment of pain and the PIPP score and crying time . CONCLUSION Breast-feeding shortly before venipuncture has no major impact on the pain score but on crying time . The combination of oral glucose and breast-feeding shows the lowest pain score and significantly shorter duration of crying Eighteen , healthy male newborns , 2–5 days old , were subjects in this study of the effects of a pacifier on the newborn 's behavioral and adrenocortical responses to circumcision . Half of the subjects were r and omly assigned to a condition in which they were encouraged to suck on a pacifier during circumcision , while half served in a no pacifier , control condition . Behavioral observations were made for 1/2 hour before , during , and after circumcision ; while blood sample s for serum cortisol determination were obtained immediately before circumcision and 30 min later . The results showed that stimulating the newborn with the pacifier reduced crying by about 40 % . Reducing crying , however , had no significant effect on the adrenocortical response . Elevations of serum cortisol predicted average behavioral state following circumcision , whereas crying during circumcision did not . Furthermore , there was evidence that the neonatal adrenocortical system was sensitive to variations in surgical procedures . The results indicate the importance of obtaining data on both behavioral and hormonal systems in studies of stress and coping in human newborns BACKGROUND Sucrose has been shown to have an analgesic effect in preterm and term neonates . Sucrose , however , has a high osmolarity and may have deleterious effects in infants with fructose intolerance . Furthermore , it may favour caries . We therefore investigated the effects of a commercially available artificial sweetener ( 10 parts cyclamate and 1 part saccharin ) , glycine ( sweet amino acid ) or breast milk in reducing reaction to pain as compared with a placebo . SUBJECTS Eighty healthy term infants , four days old , with normal birth weight . INTERVENTIONS The infants were r and omly assigned to one of four groups : 2 ml sweetener , glycine , expressed breast milk or water were given 2 min before a heel prick for the Guthrie test . The procedure was filmed with a video camera and analysed by two observers who did not know which medication the infant had received . RESULTS Using a multivariate regression analysis , the following variables had significant correlation with relative crying time and recovery time : behavioural state before the intervention , the pricking nurse , and the type of medication . Relative crying time and recovery time were significantly less in the sweetener group but not in the glycine and the breast milk group . CONCLUSIONS The artificial sweetener used in our study reduces pain reaction to a heel prick in term neonates , and thus provides an alternative to sucrose . In contrast , glycine tends to increase pain reaction whereas breast milk has no effect |
2,629 | 19,426,466 | Results From a programmatic perspective , none of the interventions achieved clear evidence of benefit .
Evidence for some socially mediated risk factors were identified , such as exposure to indoor air pollution and birth spacing , but still require the development of appropriate interventions .
Balanced protein-energy supplementation was associated with reduced stillbirth rates , but larger well- design ed trials are required to confirm findings .
Peri-conceptional folic acid supplementation significantly reduces neural tube defects , yet no significant associated reductions in stillbirth rates have been documented .
Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak , suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths .
Many antepartum stillbirths are potentially preventable in low- and middle-income countries , particularly through dietary and environmental improvement , and through improving the quality of antenatal care – particularly including diagnosis and management of high-risk pregnancies – that pregnant women receive | Background The vast majority of global stillbirths occur in low- and middle-income countries , and in many setting s , the majority of stillbirths occur antenatally , prior to the onset of labour .
Poor nutritional status , lack of antenatal care and a number of behaviours increase women 's risk of stillbirth in many re source -poor setting s. Interventions to reduce these risks could reduce the result ing burden of stillbirths , but the evidence for the impact of such interventions has not yet been comprehensively evaluated .
Conclusion Antenatal care is widely used in low- and middle-income countries , and provides a natural facility-based contact through which to provide or educate about many of the interventions we review ed . | BACKGROUND Reliable evidence about the effect of female genital mutilation ( FGM ) on obstetric outcome is scarce . This study examines the effect of different types of FGM on obstetric outcome . METHODS 28 393 women attending for singleton delivery between November , 2001 , and March , 2003 , at 28 obstetric centres in Burkina Faso , Ghana , Kenya , Nigeria , Senegal , and Sudan were examined before delivery to ascertain whether or not they had undergone FGM , and were classified according to the WHO system : FGM I , removal of the prepuce or clitoris , or both ; FGM II , removal of clitoris and labia minora ; and FGM III , removal of part or all of the external genitalia with stitching or narrowing of the vaginal opening . Prospect i ve information on demographic , health , and reproductive factors was gathered . Participants and their infants were followed up until maternal discharge from hospital . FINDINGS Compared with women without FGM , the adjusted relative risks of certain obstetric complications were , in women with FGM I , II , and III , respectively : caesarean section 1.03 ( 95 % CI 0.88 - 1.21 ) , 1.29 ( 1.09 - 1.52 ) , 1.31 ( 1.01 - 1.70 ) ; postpartum haemorrhage 1.03 ( 0.87 - 1.21 ) , 1.21 ( 1.01 - 1.43 ) , 1.69 ( 1.34 - 2.12 ) ; extended maternal hospital stay 1.15 ( 0.97 - 1.35 ) , 1.51 ( 1.29 - 1.76 ) , 1.98 ( 1.54 - 2.54 ) ; infant resuscitation 1.11 ( 0.95 - 1.28 ) , 1.28 ( 1.10 - 1.49 ) , 1.66 ( 1.31 - 2.10 ) , stillbirth or early neonatal death 1.15 ( 0.94 - 1.41 ) , 1.32 ( 1.08 - 1.62 ) , 1.55 ( 1.12 - 2.16 ) , and low birthweight 0.94 ( 0.82 - 1.07 ) , 1.03 ( 0.89 - 1.18 ) , 0.91 ( 0.74 - 1.11 ) . Parity did not significantly affect these relative risks . FGM is estimated to lead to an extra one to two perinatal deaths per 100 deliveries . INTERPRETATION Women with FGM are significantly more likely than those without FGM to have adverse obstetric outcomes . Risks seem to be greater with more extensive FGM In a prospect i ve community based study of the distribution and determinants of stillbirths in a rural area of Maharashtra , India , that was carried out for two years , 3129 singleton and 22 twin births were recorded in a population of 47 000 . Of the 3173 babies , 85 singletons and five of the twins were stillborn giving a stillbirth rate of 28.4/1000 births . The causes of stillbirths are analysed and the possibility of reducing the unacceptably high stillbirth rate by adequate training of grassroot level workers in screening pregnant women for detection of " at risk " mothers and their timely referral is discussed At an antenatal clinic in St. Thomas 's Hospital , London , 246 expectant mothers were r and omly allocated to hold either their own maternity case notes or the st and ard co-operation card . Information was collected on three occasions during their care on attitudes and health behaviour . Clinical outcomes were recorded and the effects of the two systems on clinic administration were observed . More of the notes group expressed satisfaction with most aspects of their care and delivery and significantly more of the notes group felt well informed and satisfied with their companion during labour . There were no differences in clinical outcomes between the two groups except that , for no identifiable systematic reason , there were more assisted deliveries among the notes group . A number of administrative advantages result ed from mothers holding their own notes and although initial reservations were found amongst professional staff interviewed at the start of the study , the results proved persuasive and the practice of giving mothers their own notes is now to be extended throughout the department The effects on pregnancy outcome and maternal iron status of powdered milk ( PUR ) and a milk-based fortified product ( V-N ) were compared in a group of underweight gravidas . These take-home products were distributed during regular prenatal visits . Women in the V-N group had greater weight gain ( 12.29 vs 11.31 kg , p less than 0.05 ) and mean birth weights ( 3178 vs 3105 g , p less than 0.05 ) than those in the PUR group . Values for various indicators of maternal Fe status were also higher in the V-N group . Compared with self-selected noncompliers , similar in all control variables to compliers , children of women who consumed powdered milk or the milk-based fortified product had mean birth weights that were higher by 258 and 335 g , respectively . Data indicate a beneficial effect of the fortified product on both maternal nutritional status and fetal growth BACKGROUND Multiple micronutrient deficiencies may contribute to low birth weight , which is a major global determinant of mortality . OBJECTIVE We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size . DESIGN We conducted a r and omized , placebo-controlled , double-blind effectiveness trial among antenatal care attendees in Harare , Zimbabwe . Pregnant women ( 22 - 35 wk of gestation ) were r and omly allocated to receive a multimicronutrient or placebo supplement daily until delivery . Supplementation with iron and folic acid was part of antenatal care . RESULTS Of 1669 women , birth data were available from 1106 ( 66 % ) , of whom 360 ( 33 % ) had HIV infection . The mean gestational length was 39.1 wk , and 16.6 % of the women had a gestational length < 37 wk . The mean birth weight was 3030 g , and 10.5 % of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length ( 0.3 wk ; 95 % CI : -0.04 , 0.6 wk ; P = 0.06 ) , birth weight ( 49 g ; -6 , 104 g ; P = 0.08 ) , and head circumference ( 0.2 cm ; -0.02 , 0.4 cm ; P = 0.07 ) but was not associated with low birth weight ( birth weight < 2500 g ) ( relative risk : 0.84 ; 0.59 , 1.18 ; P = 0.31 ) . The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected ( 26 g ; -38 , 91 g ) and HIV-infected ( 101 g ; -3 , 205 g ) subjects ( interaction , P > 0.10 ) . CONCLUSION Antenatal multimicronutrient supplementation may be one strategy to increase birth size An intervention program was undertaken to assess dietary habits and the impact of nutrition education among pregnant women in the rural county of Florina , northern Greece . Analysis of dietary habits , nutrient intake , hemoglobin , and serum vitamin concentrations in an intervention and control group indicated that the population was adequately nourished although nutrient intake was below recommended levels for pregnant women . Nutrition counseling was associated with improvements in dietary intake and significantly greater maternal weight gain ( p less than 0.05 ) . Mean birth weight was slightly higher in the intervention group but so was the incidence of low birth weight ( 4.5 % vs 3.9 % ) . The prematurity rate was marginally lower in the intervention group ( p less than 0.04 ) , as was the number of perinatal deaths ( 9 vs 11 ) . The results indicate that nutrition counseling during pregnancy can improve dietary intake and maternal weight gain but the mediating influence on low frequency pregnancy outcomes is indeterminate in a population that is not nutritionally at risk BACKGROUND The effect of vitamin A supplementation on the survival of infants aged < 6 mo is unclear . Because most infant deaths occur in the first few month of life , maternal supplementation may improve infant survival . OBJECTIVES The objective was to assess the effect of maternal vitamin A or beta-carotene supplementation on fetal loss and survival of infants < 6 mo of age . DESIGN Married women of reproductive age in 270 wards of Sarlahi district , Nepal , were eligible to participate . Wards were r and omly assigned to have women receive weekly doses of 7000 microg retinol equivalents as retinyl palmitate ( vitamin A ) , 42 mg all-trans-beta-carotene , or placebo . Pregnancies were followed until miscarriage , stillbirth , maternal death , or live birth of one or more infants , who were followed through 24 wk of age . RESULTS A total of 43559 women were enrolled ; 15832 contributed 17373 pregnancies and 15987 live born infants to the trial . The rate of fetal loss was 92.0/1000 pregnancies in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.06 ( 95 % CI : 0.91 , 1.25 ) and 1.03 ( 95 % CI : 0.87 , 1.19 ) , respectively . The 24-wk mortality rate was 70.8/1000 live births in the placebo group , comparable with rates in the vitamin A and beta-carotene groups , which had relative risks of 1.05 ( 95 % CI : 0.87 , 1.25 ) and 1.03 ( 95 % CI : 0.86 , 1.22 ) , respectively . CONCLUSIONS Small weekly doses of vitamin A or beta-carotene given to women before conception , during pregnancy , and through 24 wk postpartum did not improve fetal or early infant survival in Nepal Maternal night blindness is common during pregnancy in many developing countries . Previous studies have demonstrated important consequences of maternal night blindness during pregnancy on the health of the mother and newborn infant . We compared birthweight , 6-mo infant mortality , morbidity , and growth among infants of women who did and did not report a history of night blindness from a community-based , r and omized trial of newborn vitamin A supplementation in south India . Birthweight was measured within 72 h of delivery . Infants were followed until 6 mo of age for mortality and morbidity was assessed at household visits every 2 wk . Anthropometry was assessed at 6 mo of age . A total of 12,829 live-born infants were included , 680 of whom were infants of mothers with night blindness during the index pregnancy . Maternal night blindness was associated with an increased risk of low birthweight in a dose-dependent fashion based on birthweight cut-offs : < 2500 g , adjusted relative risk ( RR ) = 1.13 ( 95 % CI = 1.01 , 1.26 ) ; < 2000 g , adjusted RR = 1.70 ( 95 % CI = 1.27 , 2.26 ) ; < 1500 g , adjusted RR = 3.38 ( 95 % CI = 1.18 , 6.33 ) ; with an increased risk of diarrhea ( adjusted RR = 1.16 , 95 % CI = 1.03 , 1.30 ) , dysentery ( adjusted RR = 1.25 , 95 % CI = 1.03 , 1.53 ) , acute respiratory illness ( adjusted RR = 1.32 , 95 % CI = 1.21 , 1.44 ) , and poor growth at 6 mo ; underweight ( adjusted RR = 1.14 , 95 % CI = 1.02 , 1.26 ) , stunting ( adjusted RR = 1.19 , 95 % CI = 1.05 , 1.34 ) . Maternal night blindness was not associated with 6-mo infant mortality or wasting at 6 mo . This study demonstrates that there are important consequences to the infant of maternal vitamin A deficiency during pregnancy OBJECTIVE To evaluate the impact of a sustained , community-based collaborative approach to antenatal care services for Indigenous women . DESIGN Prospect i ve quality improvement intervention , the Mums and Babies program , in a cohort of women attending Townsville Aboriginal and Isl and ers Health Service , 1 January 2000 - 31 December 2005 ( MB group ) , compared with a historical control group ( PreMB group ) , 1 January 1998 - 30 June 1999 . MAIN OUTCOME MEASURES Proportion of women having inadequate antenatal care and screening ; perinatal indicators . RESULTS The number of antenatal visits per pregnancy increased from three ( interquartile range [ IQR ] , two to six ) in the PreMB group to six ( IQR , four to ten ) in the MB group ( P < 0.001 ) . There were significant improvements in care planning , completion of cycle-of-care , and antenatal education activities throughout the study period . About 90 % of all women attending for antenatal care were screened for sexually transmitted diseases , 89 % had measurement of haemoglobin level , and serological tests for hepatitis B and syphilis ( minimum antenatal screening ) . There was increased attendance for dating and morphology scans . In the MB group compared with the PreMB group , there was a significant reduction in perinatal mortality ( 14 v 60 per 1000 births ; P = 0.014 ) . CONCLUSION Sustained access to a community-based , integrated , shared antenatal service has improved perinatal outcomes among Indigenous women in Townsville OBJECTIVE To determine risk factors for poor birth outcome and their population attributable fractions . METHODS 1688 women who attended for antenatal care were recruited into a prospect i ve study of the effectiveness of syphilis screening and treatment . All women were screened and treated for syphilis and other reproductive tract infections ( RTIs ) during pregnancy and followed to delivery to measure the incidence of stillbirth , intrauterine growth retardation ( IUGR ) , low birth weight ( LBW ) and preterm live birth . FINDINGS At delivery , 2.7 % of 1536 women experienced a stillbirth , 12 % of live births were preterm and 8 % were LBW . Stillbirth was independently associated with a past history of stillbirth , short maternal stature and anaemia . LBW was associated with short maternal stature , ethnicity , occupation , gravidity and maternal malaria whereas preterm birth was associated with occupation , age of sexual debut , untreated bacterial vaginosis and maternal malaria . IUGR was associated with gravidity , maternal malaria , short stature , and delivering a female infant . In the women who had been screened and treated for syphilis , in between 20 and 34 % of women with each outcome was estimated to be attributable to malaria , and 63 % of stillbirths were estimated as being attributable to maternal anaemia . Screening and treatment of RTIs was effective and no association was seen between treated RTIs and adverse pregnancy outcomes . CONCLUSION Maternal malaria and anaemia continue to be significant causes of adverse pregnancy outcome in sub-Saharan Africa . Providing reproductive health services that include treatment of RTIs and prevention of malaria and maternal anaemia to reduce adverse birth outcomes remains a priority A r and omised double-blind prevention trial with a factorial design was conducted at 33 centres in seven countries to determine whether supplementation with folic acid ( one of the vitamins in the B group ) or a mixture of seven other vitamins ( A , D , B1,B2,B6,C and nicotinamide ) around the time of conception can prevent neural tube defects ( anencephaly , spina bifida , encephalocele ) . A total of 1817 women at high risk of having a pregnancy with a neural tube defect , because of a previous affected pregnancy , were allocated at r and om to one of four groups -- namely , folic acid , other vitamins , both , or neither . 1195 had a completed pregnancy in which the fetus or infant was known to have or not have a neural tube defect ; 27 of these had a known neural tube defect , 6 in the folic acid groups and 21 in the two other groups , a 72 % protective effect ( relative risk 0.28 , 95 % confidence interval 0.12 - 0.71 ) . The other vitamins showed no significant protective effect ( relative risk 0.80 , 95 % Cl 0.32 - 1.72 ) . There was no demonstrable harm from the folic acid supplementation , though the ability of the study to detect rare or slight adverse effects was limited . Folic acid supplementation starting before pregnancy can now be firmly recommended for all women who have had an affected pregnancy , and public health measures should be taken to ensure that the diet of all women who may bear children contains an adequate amount of folic acid Objective To assess the effect of nicotine patches on continine-vali date d smoking cessation in pregnant women and the effect of nicotine on birth weight and preterm delivery . Methods Pregnant women who smoked ten or more cigarettes after the first trimester ( N = 250 ) were r and omly assigned to receive nicotine patches ( n = 124 ) or placebo patches ( n = 126 ) . Women r and omized to nicotine were treated with 15-mg patches ( 16 hours/day ) for 8 weeks , and 10-mg patches ( 16 hours/day ) for 3 weeks . Results Overall , 26 % stopped smoking and 14 % were nonsmokers 1 year after delivery . There was no difference between nicotine and placebo groups . At the end of the intervention , the mean value of cotinine in saliva in women assigned to nicotine was 120 ng/mL and placebo 153 ng/mL ( mean difference −33 ; 95 % CI −72 , 6 ng/mL ) . Mean birth weight difference was 186 g ( 95 % CI 35 , 336 g ) higher in the nicotine than placebo group , and there was an insignificantly lower rate of low birth weight ( under 2500 g ) in the former group . There was no difference in the rate of preterm delivery between the two groups . Conclusion Nicotine patches had no influence on smoking cessation during pregnancy , although they might increase birth weight in comparison with placebo Objective To test whether a new community‐based model of continuity of care provided by midwives and obstetricians improved maternal clinical outcomes , in particular a reduced caesarean section rate Abstract Objective : To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system . Design : 5 year controlled trial of all pregnant women in 28 villages r and omised to daily supplementation with high energy groundnut biscuits ( 4.3MJ/day ) for about 20 weeks before delivery ( intervention ) or after delivery ( control ) . Setting : Rural Gambia . Subjects : Chronically undernourished women ( twin bearers excluded ) , yielding 2047 singleton live births and 35 stillbirths . Main outcome measures : Birth weight ; prevalence of low birth weight ( < 2500 g ) ; head circumference ; birth length ; gestational age ; prevalence of stillbirths ; neonatal and postneonatal mortality . Results : Supplementation increased weight gain in pregnancy and significantly increased birth weight , particularly during the nutritionally debilitating hungry season ( June to October ) . Weight gain increased by 201 g ( P<0.001 ) in the hungry season , by 94 g ( P<0.01 ) in the harvest season ( November to May ) , and by 136 g ( P<0.001 ) over the whole year . The odds ratio for low birthweight babies in supplemented women was 0.61 ( 95 % confidence interval 0.47 to 0.79 , P<0.001 ) . Head circumference was significantly increased ( P<0.01 ) , but by only 3.1 mm . Birth length and duration of gestation were not affected . Supplementation significantly reduced perinatal mortality : the odds ratio was 0.47 ( 0.23 to 0.99 , P<0.05 ) for stillbirths and 0.54 ( 0.35 to 0.85 , P<0.01 ) for all deaths in first week of life . Mortality after 7 days was unaffected . Conclusion : Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers . This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality . The intervention can be successfully delivered through a primary healthcare system . Key messages In developing countries chronic maternal undernutrition is a prime contributor to the birth of over 25 million low birthweight babies annually and to high rates of neonatal mortality . An absence of well design ed field trials has created uncertainty about the potential efficacy of maternal feeding programmes This large scale r and omised controlled trial shows that dietary supplementation in pregnancy can be highly effective in reducing the proportion of low birthweight babies and perinatal mortality Incorporating supplementary feeding into a rural primary healthcare system is feasible Late pregnancy is the period most amenable to Background : Maternal cigarette smoking has been causally associated with an increased risk for stillbirth . Preliminary reports suggest an increased risk for stillbirth with smokeless tobacco use during pregnancy . Methods : We conducted a population -based prospect i ve cohort study to investigate this association by using a house-to-house approach to recruit 1217 women who were between 3 and 7 months ' gestation . Of these , 96 % were contacted after delivery to determine the pregnancy outcome . Demographic and maternal variables which were apparently associated either with stillbirth or with smokeless tobacco use ( OR ≥ 1.5 ) were included as potential confounders . Stillbirth was defined as any delivery of a dead fetus after 20 completed weeks of gestation . We used time-to-event methods to analyze the risk of stillbirth . Results : Overall occurrence of stillbirth among singleton deliveries in this population was 4.1 % . Smokeless tobacco use was reported by 17 % of women ; 8.9 % of smokeless tobacco users had a stillbirth compared with 3.1 % among nonusers ( life-table adjusted hazard ratio = 3.1 ; 95 % confidence interval = 1.7–5.6 ) . After adjustment by the Cox proportional hazards procedure for age , educational and socioeconomic background , working status of mother , parity , prenatal care variables , and place of delivery , the risk for stillbirth in users was 2.6 ( 95 % confidence interval-1.4–4.8 ) . Most women used mishri ( a pyrolyzed tobacco product often used as dentifrice ) , and there was a dose – response relationship between the daily frequency of use and stillbirth risk . The risk of stillbirth associated with smokeless tobacco use was greater in earlier gestational periods . Conclusions : Smokeless tobacco use during pregnancy increases stillbirth risk , with a risk at least as great as that associated with maternal cigarette smoking This r and omized controlled trial of nutritional supplementation in pregnancy , in a poor black urban population in the United States , aim ed to increase the birth weight and influence the postnatal development of the offspring of mothers at high risk of having low birth weight infants . The execution of the research design and adherence to the treatment regimen among the experimental population appeared adequate for a reasonable test of the treatments . At birth , the only significant favorable effect of supplementation observed was the prevention of depressed birth weight among the offspring of mothers who smoked heavily . With balanced protein-calorie supplementation , length of gestation was increased , the proportion of low-birth-weight infants reduced , and mean birth weight raised by 41 gm ( not statistically significant ) . With high protein supplementation , there was an excess of very early premature births and associated neonatal deaths , and there was significant growth retardation up to 37 weeks of gestation . At 1 year of age , significant effects of high protein supplement were found on three psychological measures : visual habituation , visual dishabituation , and mean length of free play episodes . These measures were unrelated to measures of growth at birth and at 1 year of age . There were no detectable residual adverse effects of high protein supplementation at 1 year of age Background Micronutrient deficiencies during pregnancy are associated with adverse pregnancy outcomes , including reduced birthweight . Low birthweight is associated with increased risk of infant mortality and growth failure . Objectives To assess the effects of prenatal supplementation with UNIMMAP ( United Nations International Multiple Micronutrient Preparation ) compared with iron/folic acid on average birthweight and incidence of low birthweight . Methods Pregnant women from 78 villages in Niger were included in a cluster-r and omized , double-blinded , controlled supplementation trial . Baseline , monthly follow-up , and birth data were collected . Cluster analysis was conducted to assess differences in mean birthweight and incidence of low birthweight between groups using multiple linear regression models . Analyses were stratified by nutrition status and duration of supplementation . Results Of the 3,670 women recruited , 2,550 completed the study and provided complete birthweight data ( 1,328 received multiple micronutrients and 1,222 received iron/folic acid ) . Mean birthweight was significantly higher ( 67 g , p < .001 ) with multiple micronutrients ( 3,092 ± 190 g ) than with iron/folic acid ( 3,025 ± 205 g ) ; this corresponded to a 14 % fall in the incidence of low birthweight ( from 8.4 % with multiple micronutrients to 7.2 % with folic acid fortification ) . The impact of multiple micronutrients was greater when the supplements were taken for more than 150 days . The incidence of low birthweight was further reduced in women who entered pregnancy with a poorer nutrition status . Conclusions Prenatal supplementation with multiple micronutrients had a greater positive impact on birthweight than supplementation with iron/folic acid . Our data suggest that prenatal supplementation with multiple micronutrients as part of a prenatal care package in addition to interventions to promote improved maternal prepregnancy nutrition status is an important strategy to increase birthweight and reduce the incidence of low birthweight This study was prompted by the poor maternal and foetal outcome at Harare Maternity Hospital , Zimbabwe , in unbooked mothers compared to women who had booked for antenatal care . Comparison was made of 195 recently delivered unbooked mothers with 196 booked mothers . Unbooked mothers were significantly more likely to be younger , of lower parity , be single , have lower socio-economic status , live in or migrate from rural areas , be uneducated and have an unwanted pregnancy . Their infants were significantly more likely to preterm and /or of low birth weight and had a higher perinatal mortality . The major reasons cited by the women for not booking were lack of money and delivery occurring before the intended time of booking . Discussion focuses on how to improve outcome in unbooked mothers BACKGROUND Prematurity and low birth weight are associated with high perinatal and infant mortality , especially in developing countries . Maternal micronutrient deficiencies may contribute to these adverse outcomes . METHODS In a double-blind trial in Dar es Salaam , Tanzania , we r and omly assigned 8468 pregnant women ( gestational age of fetus , 12 to 27 weeks ) who were negative for human immunodeficiency virus infection to receive daily multivitamins ( including multiples of the recommended dietary allowance ) or placebo . All the women received prenatal supplemental iron and folic acid . The primary outcomes were low birth weight ( < 2500 g ) , prematurity , and fetal death . RESULTS The incidence of low birth weight was 7.8 % among the infants in the multivitamin group and 9.4 % among those in the placebo group ( relative risk , 0.82 ; 95 % confidence interval [ CI ] , 0.70 to 0.95 ; P=0.01 ) . The mean difference in birth weight between the groups was modest ( 67 g , P<0.001 ) . The rates of prematurity were 16.9 % in the multivitamin group and 16.7 % in the placebo group ( relative risk , 1.01 ; 95 % CI , 0.91 to 1.11 ; P=0.87 ) , and the rates of fetal death were 4.3 % and 5.0 % , respectively ( relative risk , 0.87 ; 95 % CI , 0.72 to 1.05 ; P=0.15 ) . Supplementation reduced both the risk of a birth size that was small for gestational age ( < 10th percentile ; 10.7 % in the multivitamin group vs. 13.6 % in the placebo group ; relative risk , 0.77 ; 95 % CI , 0.68 to 0.87 ; P<0.001 ) and the risk of maternal anemia ( hemoglobin level , < 11 g per deciliter ; relative risk , 0.88 ; 95 % CI , 0.80 to 0.97 ; P=0.01 ) , although the difference in the mean hemoglobin levels between the groups was small ( 0.2 g per deciliter , P<0.001 ) . CONCLUSIONS Multivitamin supplementation reduced the incidence of low birth weight and small-for-gestational-age births but had no significant effects on prematurity or fetal death . Multivitamins should be considered for all pregnant women in developing countries . ( Clinical Trials.gov number , NCT00197548 [ Clinical Trials.gov ] . ) The objective in the Hungarian r and omised double-blind controlled trial was to study the preventive effect of periconceptional multivitamin supplementation on neural tube-defects and other congenital abnormalities . There were 2,471 and 2,391 informative offspring ( prenatally diagnosed and terminated malformed fetuses , stillborn fetuses , and liveborn infants ) in the multivitamin and placebo-like trace element groups , respectively . A single tablet either of a multivitamin containing 0.8 mg of folic acid or trace element supplement was given daily for at least one month before conception and at least until the date of the second missed menstrual period . The total rate of major congenital abnormalities was 20.6/1,000 in the multivitamin and 40.6/1,000 in the trace element group . After the exclusion of six cases of neural-tube defects in the trace element group the difference was very highly significant [ P = 0.0003 ; relative risk of 0.54 ( 95 % CI 0.39 , 0.76 ) ] . Multivitamin supplementation appeared to result in a significant reduction in the rate of urinary tract abnormalities , mainly obstructive defects , and in the rate of sporadic cardiovascular malformations , mainly ventricular septal defects . This report is regarded as a hypothesis-generating study encouraging others to see if the result can be repeated OBJECTIVE Bupropion was developed for the treatment of depression , but subsequently was found to be effective for smoking cessation . To date , there are no prospect i ve comparative studies examining its safety in pregnancy . The primary objective was to determine whether bupropion increases the risks for major malformations above baseline . The secondary objective was to examine the rates of live births , stillbirths , spontaneous and therapeutic abortions , mean birth weight , and gestational age at birth . STUDY DESIGN Women who were pregnant or planning a pregnancy and taking bupropion were enrolled in the study . Follow-up of pregnancy outcome was carried out between 4 months and 1 year after delivery . Three comparisons were carried out : 1 ) women exposed to bupropion vs a nonteratogen group ; 2 ) those taking for depression vs other antidepressants , vs a nonteratogen group ; 3 ) spontaneous abortions were compared between those taking for depression , vs another antidepressant group vs a nonteratogen group . RESULTS We completed follow-up on 136 women exposed to bupropion during the first trimester of pregnancy . There were ( 105 ) live births , no major malformations , the mean birth weight was ( 3450 g ) , the mean gestational age at delivery was ( 40 weeks ) , the number of spontaneous abortions was 20 , there were 10 therapeutic abortions , there was 1 stillbirth , and 1 neonatal death . There were no statistically significant differences between any of the end points we examined between the exposed and comparison groups , with the exception of significantly more spontaneous abortions in the bupropion group ( P = .009 ) . CONCLUSION These results suggest that bupropion does not increase the rates of major malformation above baseline . The higher rates of spontaneous abortions are similar to other studies examining the safety of antidepressants during pregnancy Objective : Micronutrient deficiencies during pregnancy may be linked to poor newborn health and poor host defences against infection . We assessed newborn morbidity to determine the effect of four combinations of antenatal micronutrient supplements . Design : Cluster-r and omised , double-masked , controlled trial . Setting : Rural community in Nepal . Interventions : Women received daily supplements from early pregnancy through to 3 months postpartum of vitamin A alone ( control ) or vitamin A with folic acid , folic acid plus iron , folic acid plus iron plus zinc or a multiple micronutrient supplement containing these and 11 other nutrients . Main outcome measures : Infants were visited in their home at birth ( n = 3927 ) and for each of 9 days thereafter to elicit a 24-h history of nine infant morbidity symptoms , measure infant respiratory rate and axial temperature , and assess the infant for chest indrawing . At 6 weeks of age , infants were visited again in their homes to elicit a 30-day and 7-day history of 10 morbidity symptoms using parental recall . Results : Maternal micronutrient supplementation had no effect on 10-day morbidity or morbidity 30-day and 7-day morbidity assessed at 6 weeks of age all relative risks were close to 1 . Symptoms of birth asphyxia increased by about 60 % ( p<0.05 ) in infants of women who received the multiple micronutrient supplement compared with the control . Symptoms of combinations of sepsis , preterm and birth asphyxia were associated with 8- to 14-fold increased odds of 6-month infant mortality . Conclusions : None of the combinations of antenatal micronutrient supplements tested improved symptoms of neonatal morbidity in the first 10 days of life or at 6 weeks of age . Further research is needed to eluci date the association and mechanism of increased risk of birth asphyxia following maternal multiple micronutrient supplementation . Trial registration numbers : NCT00115271 |
2,630 | 27,748,320 | The common toxicities were fatigue , nausea/vomiting , abdominal pain , mostly not requiring medical intervention needed no medication intervention .
90 Y radioembolization is a safe and effective treatment for HCC and PVTT | BACKGROUND / AIM Over the past two decades , several advances have been made in the management of patients with hepatocellular carcinoma ( HCC ) and portal vein tumor thrombosis ( PVTT ) .
Yttrium-90 ( 90 Y ) radioembolization has recently been made a treatment option for patients with HCC and PVTT .
However , there is still a need to systematic ly evaluate the outcomes of 90 Y radioembolization for HCC and PVTT .
We aim ed to assess the safety and effectiveness of 90 Y radioembolization for HCC and PVTT . | Purpose To investigate early diffusion-weighted imaging ( DWI ) at 30-days post-yttrium-90 ( Y-90 ) radioembolization as a predictor of treatment response and survival in unresectable infiltrative hepatocellular carcinoma ( HCC ) with portal vein thrombosis ( PVT ) . Material s and methods In a prospect i ve study , 18 consecutive patients with unresectable infiltrative HCC and PVT underwent Y-90 therapy . MR imaging was obtained pre Y-90 , and at 1 and 3 months post-therapy with DWI fat-suppressed tri-directional diffusion gradient ( b = 50 , 400 , 800 s/mm2 ) . Response was evaluated using target mRECIST and EASL . Relative change in apparent diffusion coefficient ( ADC ) value of tumors was evaluated . Statistical analysis using receiver operator characteristic curves was performed . Paired t test and Pearson correlation coefficient ( r ) were used to assess intra- and inter-observer variability . Survival analysis was performed using Kaplan-Meier estimation and log-rank test . Results Mean ADC values of all HCC ’s at baseline and at 30-days post-Y90 therapy was 0.86 × 10−3 and 1.17 × 10−3 mm2/s , respectively ( p < 0.001 ) . Tumors with objective response by mRECIST had significantly increased ADC value when compared to “ non-responders ” ( 1.27 vs. 1.05 × 10−3 mm2/s , p = 0.002 ) . A > 30 % increase in ADC value at 30-days was found to be at least 90 % sensitive in predicting response at 90 days . A > 30 % increase in ADC value at 30-days predicted significantly prolonged survival . Conclusion A 30 % increase in ADC value at 30-days measured post Y90 is a reproducible early imaging response biomarker predicting tumor response and prolonged survival following Y-90 therapy in infiltrative HCC with PVT UNLABELLED Yttrium-90 radioembolization ( Y90RE ) is a novel approach to radiation therapy for hepatocellular carcinoma ( HCC ) , never tested in phase 2 studies . Fifty-two patients with intermediate ( n.17 ) to advanced ( n.35 ) HCC were prospect ively recruited to assess , as the primary endpoint , efficacy of Y90RE on time-to-progression ( TTP ) . Secondary endpoints were tumor response , safety , and overall survival ( OS ) . All patients were Eastern Cooperative Oncology Group ( ECOG ) score 0 - 1 , Child-Pugh class A-B7 . Y90RE treatments aim ed at a lobar delivery of 120 Gy . Retrospective dosimetric correlations were conducted and related to response . Fifty-eight treatments were performed on 52 patients . The median follow-up was 36 months . The median TTP was 11 months with no significant difference between portal vein thrombosis ( PVT ) versus no PVT ( 7 versus 13 months ) . The median OS was 15 months ( 95 % confidence interval [ CI ] , 12 - 18 months ) with a nonsignificant trend in favor of non-PVT versus PVT patients ( 18 versus 13 months ) . Five complete responses occurred ( 9.6 % ) , and the 2 year-progression rate was 62 % . Objective response was 40.4 % , whereas the disease control rate ( 78.8 % ) significantly affected survival ( responders versus nonresponders : 18.4 % versus 9.1 % ; P = 0.009 ) . Tumor response significantly correlated with absorbed dose in target lesions ( r = 0.60 , 95 % CI , 0.41 - 0.74 , P < 0.001 ) and a threshold of 500 Gy predicted response ( area under the curve , 0.78 ) . Mortality at 30 - 90 days was 0%-3.8 % . Various grade s of reduction in liver function occurred within 6 months in 36.5 % of patients , with no differences among stages . On multivariate analysis , tumor response was the sole variable affecting TTP ( P < 0.001 ) and the second affecting survival ( after Child-Pugh class ) . CONCLUSION Y90RE is an effective treatment in intermediate to advanced HCC , particularly in the case of PVT . Further prospect i ve evaluations comparing Y90RE with conventional treatments are warranted Purpose There was no st and ard treatment for hepatocellular carcinoma with portal vein tumour thrombosis ( PVTT ) . This prospect i ve , r and omised , two-arm clinical trial aims to investigate the feasibility , safety and effectiveness of transarterial chemoembolisation ( TACE ) combined with the endovascular implantation of an iodine-125 seed str and for the treatment of hepatocellular carcinoma with portal vein tumour thrombosis versus conventional TACE . Patients and methods Eighty-five patients who met the eligibility requirements were r and omly assigned to receive the treatment of TACE combined with the endovascular implantation of an iodine-125 seed str and ( 43 cases ) or conventional TACE ( 42 cases ) . The end points were survival time , complications related to the procedure and adverse events . Results No significant differences in baseline characteristics were observed between groups . The mean and median survival times were 221.7 ± 16.3 days [ 95 % confidence interval ( CI ) 189.8–253.6 days ] and 210.0 ± 17.5 days ( 95 % CI 175.8–244.2 days ) in group A and 155.1 ± 7.9 days ( 95 % CI 139.6–170.5 days ) and 154.0 ± 11.2 days ( 95 % CI 133.2–176.0 days ) in group B ( P = 0.000 ) . The 90- , 180- and 360-day cumulative survival rates were 97.6 , 58.9 and 12.3 % in group A and 92.5 , 30.7 and 0 % in group B ( P = 0.000 ) . Conclusion Transarterial chemoembolisation combined with the endovascular implantation of an iodine-125 seed str and is feasible , safe and effective in the treatment for hepatocellular carcinoma with PVTT BACKGROUND The goal of this study was to examine the safety and efficacy of selective internal radioembolization ( SIR ) for hepatocellular carcinoma ( HCC ) with portal vein or caval thrombosis ( VT ) , or both . Recent reports have demonstrated that SIR is safe for patients with HCC , but the impact on efficacy of venous thrombosis is unknown . STUDY DESIGN Prospect i ve single-arm study of the use of Therasphere in patients with unresectable HCC enrolled from January 2004 to June 2007 . Patients were categorized into three groups based on VT status and therapy . RESULTS Fifty-two patients were enrolled : 20 patients without VT who received SIR , 15 patients with VT who were treated , and 17 patients ( 10 with VT ) who were not treated because of preprocedure screening failure . Fifty-eight treatments were administered , with a median of two treatments per patient ( range of one to three treatments ) . Child 's score was different between groups . Of the VT patients treated , 67 % had portal VT , 7 % had cava VT , and 26 % had both . There were no treatment-related deaths . There was no difference in complications among groups ( p = 0.34 ) . Treated patients without thrombosis had a median overall survival of 13.9 months versus 2.7 months for those treated with thrombosis and 5.2 months for the untreated group given best supportive care only ( p = 0.01 ) . CONCLUSIONS SIR is safe in patients with HCC . Although SIR can be delivered with minimal morbidity , there might be no benefit for patients with VT . Continued emphasis on multimodality therapy in this population is needed to improve survival Disease Control Rate ( DCR ) and Clinical Benefit Rate ( CBR ) are defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response , partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents . DCR and CBR are commonly reported in many clinical trials in abstract s , papers , meeting presentations and media releases . The frequent use of these measures of drug activity presents the question of whether DCR and CBR are useful additional endpoints in early clinical trials , and if they can reasonably predict the success of an agent in subsequent , adequately powered , r and omized trials . There are no comprehensive analyses to demonstrate that CBR and DCR add to the value of traditional response/activity endpoints in early clinical trials . Data from phase II clinical trials in which the DCR or CBR are reported suggest that DCR or CBR provides ambiguous information that likely exaggerates the anticancer activity of the therapy . The terms ' disease control ' and ' clinical benefit ' in the context of non-r and omized trials are themselves disingenuous because neither tumor regression nor stable disease , defined without any consideration of duration of effect or reduction of symptoms appropriate for the specific patient population , are evidence of these endpoints in an individual patient UNLABELLED Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies . The aim of this study was to vali date evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma ( HCC ) . Therefore , 108 consecutive patients with advanced HCC and liver cirrhosis were included . Yttrium-90 ( Y-90 ) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery . The response to treatment was evaluated by computed tomography ( CT ) imaging applying Response Evaluation Criteria in Solid Tumors ( RECIST ) and World Health Organization ( WHO ) criteria with recent European Association for the Study of the Liver / National Cancer Institute ( EASL/NCI ) amendments . Time to progression ( TTP ) and overall survival were estimated by the Kaplan-Meier method . In all , 159 treatment sessions were performed ranging between one to three treatments per patient . The mean radiation dose per treatment was 120 ( ± 18 ) Gy . According to EASL criteria , complete responses were determined in 3 % of patients , partial responses in 37 % , stable disease 53 % , and primary progression in 6 % of patients . TTP was 10.0 months , whereas the median overall survival was 16.4 months . No lung or visceral toxicity was observed . The most frequently observed adverse events was a transient fatigue-syndrome . CONCLUSION Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function . Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC , r and omized controlled trials in combination with systemic therapy are warranted This is a retrospective study on the safety and efficacy of gamma knife radiosurgery ( GKR ) in treating hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) . Patients with confirmed HCC and PVTT were allocated into two groups based on the treatments they received ( palliative or GKR ) . A total of 138 patients were included ( 74 in the palliative group , 64 in GKR group ) . No significant differences in baseline characteristics existed between the two groups . Treatment-related adverse events ( AEs ) were recorded and compared between groups . The majority of AEs were mild to moderate and subsided naturally or after medication . There was no AE-induced death . The influences of baseline characteristics and treatment options on patients ' OS were analyzed . The median OS of patients in the palliative and GKR group were 3.0 months ( 95 % CI : 2.719 - 3.281 ) and 6.1 months ( 95 % CI : 4.706 - 7.494 ) respectively ( p = 0.003 ) . Multivariate analysis revealed that GKR treatment , performance status 0 - 1 , Child A , smaller tumor diameter and monolobar distribution were significant favorable prognosticators . Subgroup analyses showed OS benefit of GKR regardless of PVTT location ( main or branch of PVTT ) . In conclusion , GKR is well tolerated in selected HCC-PVTT patients and can confer OS benefit , which needs validation in future prospect i ve studies PURPOSE Intraarterial delivery of yttrium-90 ( (90)Y)-bound microspheres ( ie , radioembolization ) is a promising treatment for hepatocellular carcinoma ( HCC ) . An early concern was the " embolic " nature of the microspheres , and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion ( PVT ) . In this situation , the risk of liver failure could be enhanced , particularly in patients with cirrhosis who have increased hepatic arterial blood flow . This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with (90)Y resin microspheres in HCC with branch or main PVT . MATERIAL S AND METHODS A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental , lobar , or whole-liver infusion of (90)Y resin microspheres . For the analysis of tumor response , changes in target lesions , appearance of new lesions , and changes in portal vein thrombus were studied . Controlled disease was defined by absence of progression in all these components . RESULTS Globally , controlled disease was achieved in 66.7 % of patients at 2 months and 50 % of patients at 6 months . No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria ( version 3.0 ) at 1 and 2 months after treatment . Median survival time was 10 months ( 95 % CI , 6.6 - 13.3 months ) . CONCLUSIONS Radioembolization of unresectable HCC and branch or main PVT with (90)Y resin microspheres was associated with minimal toxicity and a favorable median survival time . Further prospect i ve studies are warranted to vali date the findings in this clinical ly challenging patient population The objective of this study was to evaluate the response rate and survival of hepatocellular carcinoma portal vein thrombosis ( PVT ) patients treated with 90Y-loaded glass microspheres using a personalized dosimetry and intensification concept . Methods : The microspheres were administered to 41 hepatocellular carcinoma PVT patients ( main = 12 ; lobar/segmental = 29 ) . 99mTc-macroaggregated albumin SPECT/CT quantitative analysis was used to calculate the tumor dose ( TD ) , healthy injected liver dose ( HILD ) , and injected liver dose ( ILD ) . Response was evaluated at 3 mo using the criteria of the European Association for the Study of the Liver , with CT follow-up lasting until disease progression or death . Survival was assessed using the Kaplan – Meier method . Results : The mean injected activity was 3.1 ± 1.5 GBq , and mean ILD was 143 ± 49 Gy . When a TD threshold of 205 Gy was applied , 99mTc-macroaggregated albumin SPECT/CT achieved a 100 % sensitivity and 90 % overall accuracy ( 0 false-negatives ; 4 false-positives ) in response prediction . On the basis of TD and HILD values , 37 % of patients received an intensification of the treatment ( increased injected activity with the aim of achieving a TD ≥ 205 Gy and HILD < 120 Gy , applying an ILD > 150 Gy ) . This intensification result ed in a high response rate ( 85 % ) without increased liver toxicity of grade 3 or higher ( 6 % vs. 12 % in the patients who did not receive treatment intensification ; not statistically significant ) . For the total 41 patients , median overall survival ( OS ) was 18 mo ( 95 % confidence interval , 11–25 mo ) . For patients with a TD of less than 205 Gy , median OS was 4.3 mo ( 3.7–5 mo ) , versus 18.2 mo ( 8.5–28.7 mo ) for those with a TD of 205 Gy or more ( P = 0.005 ) . Median OS was 20.9 mo for patients with a TD of 205 Gy or more and good PVT targeting ( n = 36 ) . OS was 12 mo ( 3 mo to ∞ ) for patients with main PVT , versus 21.5 mo ( 12–28.7 mo ) for those with segmental or lobar PVT ( not statistically significant ) . For the 5 patients with complete portal vein revascularization who underwent lobar hepatectomy , median OS was not reached yet exceeded 24.5 mo and was significantly higher than that of other patients ( P = 0.0493 ) . Conclusion : Using a 99mTc-macroaggregated albumin SPECT/CT personalized dosimetry and intensification concept with 90Y-loaded glass microspheres induced prolonged OS for PVT patients as compared with the st and ard of care ( sorafenib ) , without increasing liver toxicity . Prospect i ve r and omized studies are therefore warranted INTRODUCTION This study compares radioembolization ( (90)Y ) versus doxorubicin drug eluting beads ( DEBDOX ) in the treatment of unresectable hepatocellular carcinoma with portal vein thrombosis . METHODS Using our prospect ively maintained , multi-center , non-controlled intra-arterial therapy registry , we identified 28 consecutive patients with hepatocellular carcinoma ( HCC ) and portal vein thrombosis ( PVT ) treated with DEBDOX and 20 with (90)Y. Follow-up protocol consisted of a 3-phase CT scan of the liver within 3 months post-treatment . Tumor response rates were measured according to modified Response Evaluation Criteria in Solid Tumors ( mRECIST ) criteria . RESULTS There were 65 and 29 treatments in the DEBDOX and (90)Y groups respectively . Median age of DEBDOX was 59.8 ( 35 - 81 ) and (90)Y was 66.5 ( 49 - 82 ) years . A defined number of lesions were seen in 78 % DEBDOX and 50 % (90)Y patients . Patients were similar in the remaining 8 baseline characteristics including performance status , Child Pugh and extent of PVT . There were fewer overall side effects in the DEBDOX group compared to the (90)Y group ( 11 % vs 39 % ; P = 0.03 ) . There was better disease control ( mRECIST ) in the DEBDOX group compared to the (90)Y group ( 67 % vs 20 % ; P = 0.0014 ) . Median survival times were 10 months in DEBDOX and 3 months in the (90)Y group respectively from first treatment ( log-rank , P = 0.037 ) . CONCLUSION DEBDOX is safe for patients with HCC and PVT and may have lower toxicity than (90)Y. It may also provide better disease control and survival benefit . Further studies are warranted to vali date our observations and to determine if current clinical practice should be altered BACKGROUND There is no st and ard treatment for unresectable hepatocellular carcinoma . Arterial embolisation is widely used , but evidence of survival benefits is lacking . METHODS We did a r and omised controlled trial in patients with unresectable hepatocellular carcinoma not suitable for curative treatment , of Child-Pugh class A or B and Okuda stage I or II , to assess the survival benefits of regularly repeated arterial embolisation ( gelatin sponge ) or chemoembolisation ( gelatin sponge plus doxorubicin ) compared with conservative treatment . 903 patients were assessed , and 112 ( 12 % ) patients were finally included in the study . The primary endpoint was survival . Analyses were by intention to treat . FINDINGS The trial was stopped when the ninth sequential inspection showed that chemoembolisation had survival benefits compared with conservative treatment ( hazard ratio of death 0.47 [ 95 % CI 0.25 - 0.91 ] , p=0.025 ) . 25 of 37 patients assigned embolisation , 21 of 40 assigned chemoembolisation , and 25 of 35 assigned conservative treatment died . Survival probabilities at 1 year and 2 years were 75 % and 50 % for embolisation ; 82 % and 63 % for chemoembolisation , and 63 % and 27 % for control ( chemoembolisation vs control p=0.009 ) . Chemoembolisation induced objective responses sustained for at least 6 months in 35 % (14)of cases , and was associated with a significantly lower rate of portal-vein invasion than conservative treatment . Treatment allocation was the only variable independently related to survival ( odds ratio 0.45 [ 95 % CI 0.25 - 0.81 ] , p=0.02 ) . INTERPRETATION Chemoembolisation improved survival of stringently selected patients with unresectable hepatocellular carcinoma UNLABELLED This study was undertaken to present data from a phase 2 study in which patients with unresectable hepatocellular carcinoma ( HCC ) with and without portal vein thrombosis underwent radioembolization with Yttrium ( (90)Y ) microspheres . Patients treated were stratified by Okuda , Child-Pugh , baseline bilirubin , tumor burden , Eastern Cooperative Oncology Group ( ECOG ) , presence of cirrhosis and portal vein thrombosis ( PVT ) ( none , branch , and main ) . Clinical and biochemical data were obtained at baseline and at 4-week intervals following treatment for up to 6 months . Tumor response was obtained using computed tomography ( CT ) . Patients were followed for survival . One hundred eight patients were treated during the study period . Thirty-seven ( 34 % ) patients had PVT , 12 ( 32 % ) of which involved the main PV . The cumulative dose for those with and without PVT was 139.7 Gy and 131.9 Gy , respectively . The partial response rate using world Health Organization ( WHO ) criteria was 42.2 % . Using European Association for the Study of the Liver ( EASL ) , the response rate was 70 % . Kaplan-Meier survival varied depending on location of PVT and presence of cirrhosis . The adverse event ( AE ) rates were highest in patients with main PVT and cirrhosis . There were no cases of radiation pneumonitis . CONCLUSION The use of minimally embolic (90)Y glass microspheres to treat patients with HCC complicated by branch/lobar PVT may be clinical ly indicated and appears to have a favorable toxicity profile . Further investigation is warranted in patients with main PVT BACKGROUND & AIMS Hepatocellular carcinoma ( HCC ) has limited treatment options ; long-term outcomes following intra-arterial radiation are unknown . We assessed clinical outcomes of patients treated with intra-arterial yttrium-90 microspheres ( Y90 ) . METHODS Patients with HCC ( n = 291 ) were treated with Y90 as part of a single-center , prospect i ve , longitudinal cohort study . Toxicities were recorded using the Common Terminology Criteria version 3.0 . Response rate and time to progression ( TTP ) were determined using World Health Organization ( WHO ) and European Association for the Study of the Liver ( EASL ) guidelines . Survival by stage was assessed . Univariate/multivariate analyses were performed . RESULTS A total of 526 treatments were administered ( mean , 1.8 ; range , 1 - 5 ) . Toxicities included fatigue ( 57 % ) , pain ( 23 % ) , and nausea/vomiting ( 20 % ) ; 19 % exhibited grade 3/4 bilirubin toxicity . The 30-day mortality rate was 3 % . Response rates were 42 % and 57 % based on WHO and EASL criteria , respectively . The overall TTP was 7.9 months ( 95 % confidence interval , 6 - 10.3 ) . Survival times differed between patients with Child-Pugh A and B disease ( A , 17.2 months ; B , 7.7 months ; P = .002 ) . Patients with Child-Pugh B disease who had portal vein thrombosis ( PVT ) survived 5.6 months ( 95 % confidence interval , 4.5 - 6.7 ) . Baseline age ; sex ; performance status ; presence of portal hypertension ; tumor distribution ; levels of bilirubin , albumin , and alpha-fetoprotein ; and WHO/EASL response rate predicted survival . CONCLUSIONS Patients with Child-Pugh A disease , with or without PVT , benefited most from treatment . Patients with Child-Pugh B disease who had PVT had poor outcomes . TTP and overall survival varied by patient stage at baseline . These data can be used to design future Y90 trials and to describe Y90 as a potential treatment option for patients with HCC The safety and efficacy of yttrium 90 ( 90Y ) therapy for unresectable infiltrative hepatocellular carcinoma ( HCC ) with portal vein thrombosis ( PVT ) requires further evaluation Administration of yttrium-90 microspheres via the hepatic artery is an attractive approach to selectively deliver therapeutic doses of radiation to liver malignancies . This procedure allows delivering radiation absorbed doses in excess of 100 Gy to the tumors without significant liver toxicity . The microsphere therapy involves different specialties including medical oncology , radiation oncology , nuclear medicine , interventional radiology , medical physics , and radiation safety . We have treated 80 patients with nonresectable hepatic tumors with yttrium-90 microspheres during the past two years on an institutional study protocol . The nominal radiation absorbed dose to the tumor in this study was 150 Gy . Required activity was calculated based on the nominal radiation absorbed dose and patient 's liver volume obtained from the CT scan , assuming a uniform distribution of the microspheres within the liver . Microspheres were administered via a catheter placed into the hepatic artery . The actual radiation absorbed doses to tumors and normal liver tissue were calculated retrospectively based on the patient 's 99mTc-MAA study and CT scans . As expected , the activity uptake within the liver was found to be highly nonuniform and multifold tumor to nontumor uptake was observed . A partition model was used to calculate the radiation absorbed dose within each region . For a typical patient the calculated radiation absorbed doses to the tumor and liver were 402 and 118 Gy , respectively . The radiation safety procedure involves confinement of the source and proper disposal of the contaminated material s. The average exposure rates at 1 m from the patients and on contact just anterior to the liver were 6 and 135 uSv/h , respectively . The special physics and dosimetry protocol developed for this procedure is presented |
2,631 | 28,050,898 | The restrictive RBCT strategy was not associated with harm or benefit compared to liberal strategy .
As a result , the safety of a RBCT restrictive strategy was confirmed , although only one study specifically focused on ICU patients with sepsis .
Then , RBCT was not associated with increased mortality rate , but was associated with increased in occurrence of NI , ALI and AKI . | Red blood cell transfusion ( RBCT ) threshold in patients with sepsis remains a matter of controversy .
A threshold of 7 g/dL for stabilized patients with sepsis is commonly proposed , although debated .
The aim of the study was to compare the benefit and harm of restrictive versus liberal RBCT strategies in order to guide physicians on RBCT strategies in patients with severe sepsis or septic shock . | Background : Several studies have indicated that a restrictive erythrocyte transfusion strategy is as safe as a liberal one in critically ill patients , but there is no clear evidence to support the superiority of any perioperative transfusion strategy in patients with cancer . Methods : In a r and omized , controlled , parallel-group , double-blind ( patients and outcome assessors ) superiority trial in the intensive care unit of a tertiary oncology hospital , the authors evaluated whether a restrictive strategy of erythrocyte transfusion ( transfusion when hemoglobin concentration < 7 g/dl ) was superior to a liberal one ( transfusion when hemoglobin concentration < 9 g/dl ) for reducing mortality and severe clinical complications among patients having major cancer surgery . All adult patients with cancer having major abdominal surgery who required postoperative intensive care were included and r and omly allocated to treatment with the liberal or the restrictive erythrocyte transfusion strategy . The primary outcome was a composite endpoint of mortality and morbidity . Results : A total of 198 patients were included as follows : 101 in the restrictive group and 97 in the liberal group . The primary composite endpoint occurred in 19.6 % ( 95 % CI , 12.9 to 28.6 % ) of patients in the liberal- strategy group and in 35.6 % ( 27.0 to 45.4 % ) of patients in the restrictive- strategy group ( P = 0.012 ) . Compared with the restrictive strategy , the liberal transfusion strategy was associated with an absolute risk reduction for the composite outcome of 16 % ( 3.8 to 28.2 % ) and a number needed to treat of 6.2 ( 3.5 to 26.5 ) . Conclusion : A liberal erythrocyte transfusion strategy with a hemoglobin trigger of 9 g/dl was associated with fewer major postoperative complications in patients having major cancer surgery compared with a restrictive strategy Objectives : To assess the transfusion practice in the intensive care unit ( ICU ) in a general hospital in Kuwait relative to indications , pretransfusion hemoglobin , red blood cell ( RBC ) use and outcome . Subjects and Methods : 475 patients were admitted to the ICU during the study period ( January 2009 to February 2010 ) . Ninety-nine received RBC transfusion . Demographic , clinical and transfusion data were prospect ively collected for the 99 patients who were followed up for 30 days , until hospital discharge , or death , whichever occurred first . Indications for RBC transfusion included hemorrhage in 39 patients , improving oxygen-carrying capacity in 55 , and hemolysis in 5 . Results : Of the 99 transfused patients , 22 ( 22.22 % ) were also transfused after discharge from the ICU . Transfusions were more frequent in patients admitted with respiratory failure ( 30 , 30.3 % ) , hemorrhagic shock ( 24 , 24.2 % ) , and septic shock ( 18 , 18.4 % ) . The mean pretransfusion hemoglobin in ICU transfusions was statistically different ( 70.9 ± 12.7 g/l ) from transfusions after discharge ( 79.7 ± 9.4 g/l ) ( p < 0.001 ) . Longer ICU stay was associated with more RBC units transfused per transfusion episode per patient ( p < 0.001 ) . The Sequential Organ Failure Assessment ( SOFA ) score was significantly associated with the number of RBC units transfused per patient ( p = 0.006 ) . Mortality was significantly associated with Acute Physiology and Chronic Health Evaluation II and SOFA scores , the need and duration for mechanical ventilation , and the length of stay in hospital . Conclusion : Intensivists in our center followed a restrictive transfusion practice , by adopting a low pretransfusion hemoglobin threshold . Decisions on RBC transfusions seemed in most cases to be based on a ‘ transfusion trigger ’ rather than a physiologic need Background Although the optimum hemoglobin ( H ) concentration for patients with septic shock ( SS ) has not been specifically investigated , current guidelines suggest that H of 7 - 9 g/dL , compared with 10 - 12 g/dL , was not associated with increased mortality in critically ill adults . This contrasts with early goal -directed resuscitation protocol s that use a target hematocrit of 30 % in patients with low central venous oxygen saturation ( ScvO2 ) during the first 6 hours of resuscitation of SS . Methods Data elements were prospect ively collected on all patients with SS patients ( lactic acid ( LA ) > 4 mmol/L , or hypotension ) . Out of a total of 396 SS patients , 46 patients received red blood cell ( RBC ) transfusion for ScvO2 < 70 % ( RBC group ) . We then matched 71 SS patients that did not receive RBC transfusion ( NRBC group ) on the following goals ( G ) : LA obtained within 6 hours ( G1 ) , antibiotics given within 3 hours ( G2 ) , 20 mL/kg fluid bolus followed by vasopressors ( VP ) if needed to keep mean arterial pressure > 65 mm Hg ( G3 ) , central venous pressure > 8 mm Hg within 6 hours ( G4 ) and ScvO2 > 70 % within 6 hours ( G5 ) . Results In the RBC group , after one unit of RBC transfusion , ScvO2 improved from average of 63 % ( ± 12 % ) to 68 % ( ± 10 % ) ( P = 0.02 ) . Sixteen patients required another unit of RBC , and this result ed in increase of ScvO2 to 78 % ( ± 11 % ) ( P < 0.01 ) . The RBC and NRBC groups were matched on sequential organ failure assessment ( SOFA ) scores and all five goals . There was no difference in mortality between the two groups : 41 % vs. 39.4 % ( OR : 0.8 , 95 % CI : 0.4 - 1.7 , P = 0.6 ) . Conclusions In our study , transfusion of RBC was not associated with decreased mortality in SS patients CONTEXT Anemia is a common problem in critically ill patients admitted to intensive care units ( ICUs ) , but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined . OBJECTIVES To prospect ively define the incidence of anemia and use of red blood cell ( RBC ) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU . DESIGN Prospect i ve observational study conducted November 1999 , with 2 components : a blood sampling study and an anemia and blood transfusion study . SETTING AND PATIENTS The blood sampling study included 1136 patients from 145 western European ICUs , and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs . Patients were followed up for 28 days or until hospital discharge , interinstitutional transfer , or death . MAIN OUTCOME MEASURES Frequency of blood drawing and associated volume of blood drawn , collected over a 24-hour period ; hemoglobin levels , transfusion rate , organ dysfunction ( assessed using the Sequential Organ Failure Assessment score ) , and mortality , collected throughout a 2-week period . RESULTS The mean ( SD ) volume per blood draw was 10.3 ( 6.6 ) mL , with an average total volume of 41.1 ( 39.7 ) mL during the 24-hour period . There was a positive correlation between organ dysfunction and the number of blood draws ( r = 0.34 ; P<.001 ) and total volume drawn ( r = 0.28 ; P<.001 ) . The mean hemoglobin concentration at ICU admission was 11.3 ( 2.3 ) g/dL , with 29 % ( 963/3295 ) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0 % ( 1307/3534 ) . Older patients and those with a longer ICU length of stay were more commonly transfused . Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion ( ICU rates : 18.5 % vs 10.1 % , respectively ; chi(2 ) = 50.1 ; P<.001 ; overall rates : 29.0 % vs 14.9 % , respectively ; chi(2 ) = 88.1 ; P<.001 ) . For similar degrees of organ dysfunction , patients who had a transfusion had a higher mortality rate . For matched patients in the propensity analysis , the 28-day mortality was 22.7 % among patients with transfusions and 17.1 % among those without ( P = .02 ) ; the Kaplan-Meier log-rank test confirmed this difference . CONCLUSIONS This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients . Additionally , this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) Background Treating anaemia with red blood cell ( RBC ) transfusion is frequent , but controversial , in patients with septic shock . Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients . Methods We did a prospect i ve cohort study at 7 general intensive care units ( ICUs ) including all adult patients with septic shock in a 5-month period . Results Ninety-five of the 213 included patients ( 45 % ) received median 3 ( interquartile range 2–5 ) RBC units during shock . The median pre-transfusion haemoglobin level was 8.1 ( 7.4–8.9 ) g/dl and independent of shock day and bleeding . Patients with cardiovascular disease were transfused at higher haemoglobin levels . Transfused patients had higher Simplified Acute Physiology Score ( SAPS ) II ( 56 ( 45 - 69 ) vs. 48 ( 37 - 61 ) , p = 0.0005 ) , more bleeding episodes , lower haemoglobin levels days 1 to 5 , higher Sepsis-related Organ Failure Assessment ( SOFA ) scores ( days 1 and 5 ) , more days in shock ( 5 ( 3 - 10 ) vs. 2 ( 2 - 4 ) , p = 0.0001 ) , more days in ICU ( 10 ( 4 - 19 ) vs. 4 ( 2 - 8 ) , p = 0.0001 ) and higher 90-day mortality ( 66 vs. 43 % , p = 0.001 ) . The latter association was lost after adjustment for admission category and SAPS II and SOFA-score on day 1 . Conclusions The decision to transfuse patients with septic shock was likely affected by disease severity and bleeding , but haemoglobin level was the only measure that consistently differed between transfused and non-transfused patients BACKGROUND Early goal -directed therapy ( EGDT ) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock . However , its effectiveness is uncertain . METHODS In this trial conducted at 51 centers ( mostly in Australia or New Zeal and ) , we r and omly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care . The primary outcome was all-cause mortality within 90 days after r and omization . RESULTS Of the 1600 enrolled patients , 796 were assigned to the EGDT group and 804 to the usual-care group . Primary outcome data were available for more than 99 % of the patients . Patients in the EGDT group received a larger mean ( ±SD ) volume of intravenous fluids in the first 6 hours after r and omization than did those in the usual-care group ( 1964±1415 ml vs. 1713±1401 ml ) and were more likely to receive vasopressor infusions ( 66.6 % vs. 57.8 % ) , red-cell transfusions ( 13.6 % vs. 7.0 % ) , and dobutamine ( 15.4 % vs. 2.6 % ) ( P<0.001 for all comparisons ) . At 90 days after r and omization , 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group , for rates of death of 18.6 % and 18.8 % , respectively ( absolute risk difference with EGDT vs. usual care , -0.3 percentage points ; 95 % confidence interval , -4.1 to 3.6 ; P=0.90 ) . There was no significant difference in survival time , in-hospital mortality , duration of organ support , or length of hospital stay . CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock , EGDT did not reduce all-cause mortality at 90 days . ( Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation ; ARISE Clinical Trials.gov number , NCT00975793 . ) 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 . ) CONTEXT It is unclear if blood transfusion in anemic patients with acute coronary syndromes is associated with improved survival . OBJECTIVE To determine the association between blood transfusion and mortality among patients with acute coronary syndromes who develop bleeding , anemia , or both during their hospital course . DESIGN , SETTING , AND PATIENTS We analyzed 24,112 enrollees in 3 large international trials of patients with acute coronary syndromes ( the GUSTO IIb , PURSUIT , and PARAGON B trials ) . Patients were grouped according to whether they received a blood transfusion during the hospitalization . The association between transfusion and outcome was assessed using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate and the propensity to receive blood , and a l and mark analysis . MAIN OUTCOME MEASURE Thirty-day mortality . RESULTS Of the patients included , 2401 ( 10.0 % ) underwent at least 1 blood transfusion during their hospitalization . Patients who underwent transfusion were older and had more comorbid illness at presentation and also had a significantly higher unadjusted rate of 30-day death ( 8.00 % vs 3.08 % ; P<.001 ) , myocardial infa rct ion ( MI ) ( 25.16 % vs 8.16 % ; P<.001 ) , and death/MI ( 29.24 % vs 10.02 % ; P<.001 ) compared with patients who did not undergo transfusion . Using Cox proportional hazards modeling that incorporated transfusion as a time-dependent covariate , transfusion was associated with an increased hazard for 30-day death ( adjusted hazard ratio [ HR ] , 3.94 ; 95 % confidence interval [ CI ] , 3.26 - 4.75 ) and 30-day death/MI ( HR , 2.92 ; 95 % CI , 2.55 - 3.35 ) . In the l and mark analysis that included procedures and bleeding events , transfusion was associated with a trend toward increased mortality . The predicted probability of 30-day death was higher with transfusion at nadir hematocrit values above 25 % . CONCLUSIONS Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality , and this relationship persists after adjustment for other predictive factors and timing of events . Given the limitations of post hoc analysis of clinical trials data , a r and omized trial of transfusion strategies is warranted to resolve the disparity in results between our study and other observational studies . We suggest caution regarding the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease Introduction Studies in intensive care unit ( ICU ) patients have suggested that anemia and blood transfusions can influence outcomes , but these effects have not been widely investigated specifically in surgical ICU patients . Methods We retrospectively analyzed the prospect ively collected data from all adult patients ( > 18 years old ) admitted to a 50-bed surgical ICU between 1st March 2004 and 30th July 2006 . Results Of the 5925 patients admitted during the study period , 1833 ( 30.9 % ) received a blood transfusion in the ICU . Hemoglobin concentrations were < 9 g/dl on at least one occasion in 57.6 % of patients . Lower hemoglobin concentrations were associated with a higher Simplified Acute Physiology Score II and Sequential Organ Failure Assessment score , greater mortality rates , and longer ICU and hospital lengths of stay . Transfused patients had higher ICU ( 12.5 vs. 3.2 % ) and hospital ( 18.3 vs. 6.5 % ) mortality rates ( both p < 0.001 ) than non-transfused patients . However , ICU and in-hospital mortality rates were similar among transfused and non-transfused matched pairs according to a propensity score ( n = 1184 pairs ) , and after adjustment for possible confounders in a multivariable analysis , higher hemoglobin concentrations ( RR 0.97[0.95 - 0.98 ] , per 1 g/dl , p < 0.001 ) and blood transfusions ( RR 0.96[0.92 - 0.99 ] , p = 0.031 ) were independently associated with a lower risk of in-hospital death , especially in patients aged from 66 to 80 years , in patients admitted to the ICU after non-cardiovascular surgery , in patients with higher severity scores , and in patients with severe sepsis . Conclusions In this group of surgical ICU patients , anemia was common and was associated with higher morbidity and mortality . Higher hemoglobin concentrations and receipt of a blood transfusion were independently associated with a lower risk of in-hospital death . R and omized control studies are warranted to confirm the potential benefit of blood transfusions in these sub population BACKGROUND Blood transfusions are frequently given to patients with septic shock . However , the benefits and harms of different hemoglobin thresholds for transfusion have not been established . METHODS In this multicenter , parallel-group trial , we r and omly assigned patients in the intensive care unit ( ICU ) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less ( lower threshold ) or when the level was 9 g per deciliter or less ( higher threshold ) during the ICU stay . The primary outcome measure was death by 90 days after r and omization . RESULTS We analyzed data from 998 of 1005 patients ( 99.3 % ) who underwent r and omization . The two intervention groups had similar baseline characteristics . In the ICU , the lower-threshold group received a median of 1 unit of blood ( interquartile range , 0 to 3 ) and the higher-threshold group received a median of 4 units ( interquartile range , 2 to 7 ) . At 90 days after r and omization , 216 of 502 patients ( 43.0 % ) assigned to the lower-threshold group , as compared with 223 of 496 ( 45.0 % ) assigned to the higher-threshold group , had died ( relative risk , 0.94 ; 95 % confidence interval , 0.78 to 1.09 ; P=0.44 ) . The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per- protocol population s. The numbers of patients who had ischemic events , who had severe adverse reactions , and who required life support were similar in the two intervention groups . CONCLUSIONS Among patients with septic shock , mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold ; the latter group received fewer transfusions . ( Funded by the Danish Strategic Research Council and others ; TRISS Clinical Trials.gov number , NCT01485315 . ) Introduction We sought to investigate whether treatment of subnormal ( < 70 % ) central venous oxygen saturation ( ScvO2 ) with inotropes or red blood cell ( RBC ) transfusion during early goal -directed therapy ( EGDT ) for septic shock is independently associated with in-hospital mortality . Methods Retrospective analysis of a prospect i ve EGDT patient data base drawn from 21 emergency departments with a single st and ardized EGDT protocol . Patients were included if , during EGDT , they concomitantly achieved a central venous pressure ( CVP ) of ≥8 mm Hg and a mean arterial pressure ( MAP ) of ≥65 mm Hg while registering a ScvO2 < 70 % . Treatment propensity scores for either RBC transfusion or inotrope administration were separately determined from independent patient sub-cohorts . Propensity-adjusted logistic regression analyses were conducted to test for associations between treatments and in-hospital mortality . Results Of 2,595 EGDT patients , 572 ( 22.0 % ) met study inclusion criteria . The overall in-hospital mortality rate was 20.5 % . Inotropes or RBC transfusions were administered for an ScvO2 < 70 % to 51.9 % of patients . Patients were not statistically more likely to achieve an ScvO2 of ≥70 % if they were treated with RBC transfusion alone ( 29/59 , 49.2 % , P = 0.19 ) , inotropic therapy alone ( 104/226 , 46.0 % , P = 0.15 ) or both RBC and inotropic therapy ( 7/12 , 58.3 % , P = 0.23 ) as compared to no therapy ( 108/275 , 39.3 % ) . Following adjustment for treatment propensity score , RBC transfusion was associated with a decreased adjusted odds ratio ( aOR ) of in-hospital mortality among patients with hemoglobin values less than 10 g/dL ( aOR 0.42 , 95 % CI 0.18 to 0.97 , P = 0.04 ) while inotropic therapy was not associated with in-hospital mortality among patients with hemoglobin values of 10 g/dL or greater ( aOR 1.16 , 95 % CI 0.69 to 1.96 , P = 0.57 ) . Conclusions Among patients with septic shock treated with EGDT in the setting of subnormal ScvO2 values despite meeting CVP and MAP target goals , treatment with RBC transfusion may be independently associated with decreased in-hospital mortality Introduction In this study , we sought to determine the association between red blood cell ( RBC ) transfusion and outcomes in patients with acute lung injury ( ALI ) , sepsis and shock . Methods We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial ( 2000 to 2005 ) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria ( mean arterial pressure ( MAP ) < 60 mmHg or vasopressor use ) within 24 hours of r and omization . Using multivariable logistic regression , we examined the association between RBC transfusion and 28-day mortality after adjustment for age , sex , race , r and omization arm and Acute Physiology and Chronic Health Evaluation III score . Secondary end points included 90-day mortality and ventilator-free days ( VFDs ) . Finally , we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators : hemoglobin < 10.2 g/dL , central or mixed venous oxygen saturation < 70 % , central venous pressure ≥ 8 mmHg , MAP ≥ 65 mmHg , and vasopressor use . Results We identified 285 subjects with ALI , sepsis , shock and transfusion data . Of these , 85 also met the above prespecified transfusion criteria . Fifty-three ( 19 % ) of the two hundred eighty-five subjects with shock and twenty ( 24 % ) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of r and omization . We found no independent association between RBC transfusion and 28-day mortality ( odds ratio = 1.49 , 95 % CI ( 95 % confidence interval ) = 0.77 to 2.90 ; P = 0.23 ) or VFDs ( mean difference = -0.35 , 95 % CI = -4.03 to 3.32 ; P = 0.85 ) . Likewise , 90-day mortality and VFDs did not differ by transfusion status . Among the subset of patients meeting the transfusion criteria , we found no independent association between transfusion and mortality or VFDs . Conclusions In patients with new-onset ALI , sepsis and shock , we found no independent association between RBC transfusion and mortality or VFDs . The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion 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 PURPOSE The aim of the study was to document transfusion practice s in a cross section of general intensive care units ( ICUs ) in Israel and to determine whether current guidelines are being applied . MATERIAL S AND METHODS This prospect i ve study was performed in 5 general ICUs in Israel over a 3-month period . Red cell transfusion data collected on consecutive patients included the trigger , units transfused per transfusion event , and indications , categorized either to treat a specified condition for which transfusions may be beneficial ( acute hemorrhage , acute myocardial ischemia , or severe sepsis ) or to treat a low hemoglobin concentration . RESULTS Of the 238 patients studied , 50 % received at least one red blood cell transfusion . The main indication for transfusion ( 43.7 % , or 162/368 U transfused ) was to treat a low hemoglobin concentration , in the absence of one of the specified conditions . Total red cell use was 3.0 ± 2.9 U per admission , and patients received a mean of 1.2 ± 0.4 U per transfusion event . The transfusion trigger for the whole group was 7.9 ± 1.1 g/dL. This did not differ significantly between the indications apart from a significantly higher trigger for patients with acute myocardial ischemia ( 8.8 ± 0.9 g/dL ) . In addition , patients with a history of heart disease had a higher trigger irrespective of the primary indication for transfusion and received significantly more units per transfusion event . Patients receiving a transfusion had significantly longer ICU stay and hospital mortality . CONCLUSIONS Our study showed that evidence - practice gaps continue to exist , and it appears that physician behavior is mainly driven by the absolute level of hemoglobin . Educational interventions focused on these factors are required to limit the widespread and often unnecessary use of this scarce and potentially harmful re source 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 BACKGROUND The Protocol ised Management in Sepsis ( ProMISe ) trial is an open , multicentre , r and omised controlled trial ( RCT ) of the clinical effectiveness and cost-effectiveness of early , goal directed , protocol ised resuscitation compared with usual resuscitation for patients presenting to emergency departments ( EDs ) in the United Kingdom with early signs of severe sepsis or septic shock . The rationale for the ProMISe trial derives from a single-centre United States RCT that reported a reduction in hospital mortality from 46.5 % to 30.5 % . OBJECTIVE To describe the proposed statistical analyses for the evaluation of clinical effectiveness for the ProMISe trial . It is important to complete this plan before inspecting the data , and before completion of two related international studies , so that post-hoc , data -derived decisions are avoided . METHODS The primary and secondary outcomes were defined precisely , and the approach to safety monitoring and data collection summarised , with a description of the planned statistical analyses including prespecified subgroup and secondary analyses . RESULTS The primary outcome is all-cause mortality at 90 days . The primary analysis will be reported as a relative risk and absolute risk reduction and tested with the Fisher exact test . Prespecified subgroup analyses will be based on age , baseline Medical Emergency Department Sepsis score , baseline Sequential Organ Failure Assessment score , and time from ED presentation to r and omisation . Secondary analyses include adjustment for baseline covariates , estimation of learning curve effects and adjustment for noncompliance . CONCLUSION In keeping with best practice , we have developed a statistical analysis plan for the ProMISe trial and place it in the public domain before inspecting data from the trial STUDY OBJECTIVE To identify predictors of hospital mortality among patients with severe sepsis who were treated with drotrecogin alfa ( activated ) . DESIGN Prospect i ve observational cohort study . SETTING A 1400-bed academic medical center . PATIENTS One hundred two patients treated with drotrecogin alfa ( activated ) for severe sepsis . MEASUREMENTS AND MAIN RESULTS To identify potential risk factors for hospital mortality , the main outcome evaluated , all patients who received drotrecogin alfa ( activated ) were segregated according to hospital survival . The following characteristics were recorded : age , sex , weight , surgical or nonsurgical , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , number of acquired organ-system derangements , mechanical ventilation , use of vasopressors or dobutamine , patient location 24 hours before receiving drotrecogin alfa ( activated ) , source of infection , microbiologically positive culture , and other process-of-care variables . Of the 102 patients , 43 ( 42.2 % ) died during their hospitalization . Potential predictors of hospital mortality identified by univariate analysis included greater APACHE II scores , administration of vasopressin or dobutamine , number of acquired organ-system derangements , time to treatment with drotrecogin alfa ( activated ) , intravenous fluid administered before receiving vasopressors or drotrecogin alfa ( activated ) , number of red blood cell transfusions , and administration of inappropriate initial antimicrobial treatment . Multivariate analysis revealed that vasopressin administration ( odds ratio [ OR ] 3.72 , 95 % confidence interval [ CI ] 1.95 - 7.10 ) , number of acquired organ-system derangements ( OR 2.30 , 95 % CI 1.59 - 3.31 ) , and administration of inappropriate initial antimicrobial treatment ( OR 15.5 , 95 % CI 6.78 - 35.6 ) were independently associated with hospital mortality . CONCLUSION Number of acquired organ-system derangements , vasopressin administration , and treatment with an inappropriate initial antimicrobial regimen are independently associated with an increased risk of hospital mortality among patients treated with drotrecogin alfa ( activated ) for severe sepsis . These findings suggest that other specific medical interventions may increase survival in this patient population Objective To quantify the incidence of anemia and red blood cell ( RBC ) transfusion practice in critically ill patients and to examine the relationship of anemia and RBC transfusion to clinical outcomes . Design Prospect i ve , multiple center , observational cohort study of intensive care unit ( ICU ) patients in the United States . Enrollment period was from August 2000 to April 2001 . Patients were enrolled within 48 hrs of ICU admission . Patient follow-up was for 30 days , hospital discharge , or death , whichever occurred first . Setting A total of 284 ICUs ( medical , surgical , or medical-surgical ) in 213 hospitals participated in the study . Patients A total of 4,892 patients were enrolled in the study . Measurements and Main Results The mean hemoglobin level at baseline was 11.0 ± 2.4 g/dL. Hemoglobin level decreased throughout the duration of the study . Overall , 44 % of patients received one or more RBC units while in the ICU ( mean , 4.6 ± 4.9 units ) . The mean pretransfusion hemoglobin was 8.6 ± 1.7 g/dL. The mean time to first ICU transfusion was 2.3 ± 3.7 days . More RBC transfusions were given in study week 1 ; however , in subsequent weeks , subjects received one to two RBC units per week while in the ICU . The number of RBC transfusions a patient received during the study was independently associated with longer ICU and hospital lengths of stay and an increase in mortality . Patients who received transfusions also had more total complications and were more likely to experience a complication . Baseline hemoglobin was related to the number of RBC transfusions , but it was not an independent predictor of length of stay or mortality . However , a nadir hemoglobin level of < 9 g/dL was a predictor of increased mortality and length of stay . Conclusions Anemia is common in the critically ill and results in a large number of RBC transfusions . Transfusion practice has changed little during the past decade . The number of RBC units transfused is an independent predictor of worse clinical outcome Fifty-four patients with systemic sepsis and signs of circulatory shock were prospect ively investigated immediately before and after 1 of 3 therapeutic interventions chosen to increase systemic oxygen delivery ( DO2 ) : colloidal fluid loading ( Group I , n = 20 ) , blood transfusion ( Group II , n = 17 ) , or catecholamine infusion ( dopamine or dobutamine , Group III , n = 17 ) . Patients in Groups I and II with normal blood lactate concentrations ( less than 2.2 mmol/L ) exhibited no significant increases in systemic oxygen consumption ( VO2 ) in response to the increases in DO2 . However , significant increases in VO2 were noted in patients in Groups I and II with elevated lactate concentrations ( greater than 2.2 mmol/L ) . In contrast to patients in Groups I and II , patients in Group III with and without lactic acidosis exhibited significant increases in VO2 after catecholamine administration . Lactic acidosis , a clinical marker of anaerobic metabolism or oxygen debt , appears to predict increases in VO2 in response to increases in DO2 in septic patients receiving fluid and catecholamines increase VO2 without regard for the presence or absence of anaerobic metabolism . The results of this clinical trial therefore suggest that catecholamines may exert a direct effect on oxidative metabolism Objectives : To evaluate the effects of transfusions in patients with severe sepsis and septic shock on mortality . Design : Propensity-matched analysis of a prospect i ve observational data base ( April 2005 to February 2009 ) . Setting : Twenty-two medical and surgical intensive care units in 12 teaching hospitals in Korea . Patients : One thous and fifty-four patients with community-acquired severe sepsis and septic shock . Interventions None . Measurements and Main Results : Of the 1,054 patients , 407 ( 38.6 % ) received a blood transfusion . The mean pretransfusion hemoglobin level was 7.7 ± 1.2 g/dL. Transfused patients had higher 28-day and in-hospital mortality rates ( 32.7 % vs. 17.3 % ; p < .001 , 41.3 % vs. 20.3 % ; p < .001 , respectively ) and a longer duration of hospital stay ( 21 [ interquartile range , 10–35 ] vs. 13 [ interquartile range , 8–24 ] days ; p < .001 ) , but were more severely ill at admission ( lower systolic blood pressure , higher Acute Physiology and Chronic Health Evaluation II score , and Sequential Organ Failure Assessment score at admission ) . In 152 pairs matched according to the propensity score depending on patient transfusion status , transfused patients had a lower risk of 7-day ( 9.2 % vs. 27.0 % ; p < .001 ) , 28-day ( 24.3 % vs. 38.8 % ; p = .007 ) , and in-hospital mortality rates ( 31.6 % vs. 42.8 % ; p = .044 ) . After adjusting for blood transfusion as a time-dependent variable in multivariable analysis , blood transfusion was independently associated with lower risk of 7-day ( hazard ratio 0.42 , 95 % confidence interval 0.19–0.50 , p = .026 ) , 28-day ( hazard ratio 0.43 , 95 % confidence interval 0.29–0.62 , p < .001 ) , and in-hospital mortality ( hazard ratio 0.51 , 95 % confidence interval 0.39–0.69 , p < .001 ) . Conclusions : In this observational study of patients with community-acquired severe sepsis and septic shock , red blood cell transfusions were associated with lower risk of mortality OBJECTIVE To examine the impact of implementing sepsis bundle in multiple Asian countries , having ' team ' vs. ' non-team ' models of patient care . DESIGN Prospect i ve cohort study . SETTING Eight urban hospitals , five countries in Asia . PARTICIPANTS Adult patients with severe sepsis or septic shock . INTERVENTIONS Implementation was divided into six quartiles : Baseline , Education and four Quality Improvement quartiles . MAIN OUTCOME MEASURES Quarterly bundle compliance and in-hospital mortality with respect to bundle completion and implementation model . METHODS In the team model , the implementation was championed by intensivists , where the bundle was completed in the intensive care unit . The non-team model led by emergency physicians completed the bundle in the emergency department as part of st and ard care . RESULTS Five hundred and fifty-six patients were enrolled . The overall in-hospital mortality rate was 29.9 % , and 67.1 % of the patients had septic shock . Compliance to the bundle was 13.3 , 26.9 , 37.5 , 45.9 , 48.8 and 54.5 % over the six quartiles of implementation ( P < 0.01 ) . With team model , compliance increased from 37.5 % baseline to 88.2 % in the sixth quartile ( P < 0.01 ) , whereas hospitals with a non-team model increased compliance from 5.2 to 39.5 % ( P < 0.01 ) . Crude in-hospital mortality was better in the patients who received the entire bundle ( 24.5 vs. 32.7 % , P = 0.04 ) . Bundle completion was associated with crude in-hospital mortality reduction ( odds ratio 0.67 , 95 % confidence interval 0.45 - 0.99 ) , but this survival benefit disappeared after adjustment for confounding variables . CONCLUSIONS Through education and quality improvement efforts , initially low sepsis bundle compliance was improved in Asia . A team model was more effective in achieving bundle compliance compared with a non-team model Background : Acute kidney injury is a common occurrence in intensive care unit patients with a reported incidence of 11–67 % and is associated with an increased risk of death . In other patient population s , erythrocyte transfusion has been associated with increased risk of adverse outcomes including sepsis , multisystem organ dysfunction , and death . The purpose of this study was to determine the effect of erythrocyte transfusion on the development of acute kidney injury . Methods : This was a retrospective analysis of prospect ively collected data that used propensity matched transfused and nontransfused patients . Propensity matching was done using semiparsimonious logistic regression . McNemar test for nonindependent data sets was used to compare groups . Results : Four hundred two patients from a trial on fluid management in patients with acute lung injury were matched . 38 % of transfused patients had a rise in creatinine the day after transfusion compared with 33 % of their nontransfused matches ( P = 0.315 ) . By day 7 , creatinine had increased in 51 % of transfused patients compared with 52 % in nontransfused patients ( P = 0.832 ) . The incidences of renal risk , injury , and failure were 39 ( 19 % ) , 27 ( 13 % ) , and 11 ( 5 % ) in the transfused group and 38 ( 19 % ) , 24 ( 12 % ) , and 11 ( 5 % ) in the nontransfused group , P = 1.00 , 0.785 , and 1.00 , respectively . Conclusions : Transfusion of erythrocytes to patients with acute lung injury had no effect on the development of acute kidney injury Objectives : To compare hemoglobin concentration ( Hb ) , RBC use , and patient outcomes when restrictive or liberal blood transfusion strategies are used to treat anemic ( Hb ⩽ 90 g/L ) critically ill patients of age ≥ 55 years requiring ≥ 4 days of mechanical ventilation in ICU . Design : Parallel-group r and omized multicenter pilot trial . Setting : Six ICUs in the United Kingdom participated between August 2009 and December 2010 . Patients : One hundred patients ( 51 restrictive and 49 liberal groups ) . Interventions : Patients were r and omized to a restrictive ( Hb trigger , 70 g/L ; target , 71–90 g/L ) or liberal ( 90 g/L ; target , 91–110 g/L ) transfusion strategy for 14 days or the remainder of ICU stay , whichever was longest . Measurements and Main Results : Baseline comorbidity rates and illness severity were high , notably for ischemic heart disease ( 32 % ) . The Hb difference among groups was 13.8 g/L ( 95 % CI , 11.5–16.0 g/L ) ; p < 0.0001 ) ; mean Hb during intervention was 81.9 ( SD , 5.1 ) versus 95.7 ( 6.3 ) g/L ; 21.6 % fewer patients in the restrictive group were transfused postr and omization ( p < 0.001 ) and received a median 1 ( 95 % CI , 1–2 ; p = 0.002 ) fewer RBC units . Protocol compliance was high . No major differences in organ dysfunction , duration of ventilation , infections , or cardiovascular complications were observed during intensive care and hospital follow-up . Mortality at 180 days postr and omization trended toward higher rates in the liberal group ( 55 % ) than in the restrictive group ( 37 % ) ; relative risk was 0.68 ( 95 % CI , 0.44–1.05 ; p = 0.073 ) . This trend remained in a survival model adjusted for age , gender , ischemic heart disease , Acute Physiology and Chronic Health Evaluation II score , and total non-neurologic Sequential Organ Failure Assessment score at baseline ( hazard ratio , 0.54 [ 95 % CI , 0.28–1.03 ] ; p = 0.061 ) . Conclusions : A large trial of transfusion strategies in older mechanically ventilated patients is feasible . This pilot trial found a nonsignificant trend toward lower mortality with restrictive transfusion practice |
2,632 | 25,599,296 | Non-steroidal anti-inflammatory drugs and lumbar plexus block were demonstrated to provide reductions in postoperative pain scores .
Intrathecal opioids increased pruritus , and lumbar plexus block reduced nausea and pruritus .
This review demonstrated , that some analgesic interventions may have the capacity to reduce mean opioid requirements and /or mean pain intensity compared with controls , but the available r and omized placebo-controlled trials does not allow a design ation of a " best proven intervention " for THA | Treatment of postoperative pain should rely on results from r and omized controlled trials and meta-analyses of high scientific quality .
The efficacy of a particular intervention may depend on the type of surgical procedure , which supports the reporting of " procedure-specific " interventions .
The aim of this systematic review was to document the procedure-specific evidence for analgesic interventions after total hip arthroplasty ( THA ) . | & NA ; Adverse events in r and omized controlled trials of noninvasive , pharmacologic analgesics are frequently incompletely or inconsistently reported . A comprehensive reporting checklist is proposed to improve disclosure of adverse effects . & NA ; The development of valid and informative treatment risk – benefit profiles requires consistent and thorough information about adverse event ( AE ) assessment and participants ’ AEs during r and omized controlled trials ( RCTs ) . Despite a 2004 extension of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement recommending the specific AE information that investigators should report , there is little evidence that analgesic RCTs adequately adhere to these recommendations . This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinical ly important AE information . Using this checklist , we coded AE assessment methods and reporting in all 80 double‐blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain , Journal of Pain , and PAIN ® from 2006 to 2011 . Across all trials , reports of AEs were frequently incomplete , inconsistent across trials , and , in some cases , missing . For example , > 40 % of trials failed to report any information on serious adverse events . Trials of participants with acute or chronic pain conditions and industry‐sponsored trials typically provided more and better‐ quality AE data than trials involving pain‐free volunteers or trials that were not industry sponsored . The results of this review suggest that improved AE reporting is needed in analgesic RCTs . We developed an ACTTION ( Analgesic , Anesthetic , and Addiction Clinical Trial Translations , Innovations , Opportunities , and Networks ) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications BACKGROUND We studied the efficacy of local infiltration analgesia in surgical wounds with 0.2 % ropivacaine ( 50 mL ) , ketorolac ( 15 mg ) , and adrenaline ( 0.5 mg ) compared with that of local infiltration analgesia combined with continuous infusion of 0.2 % ropivacaine as a method of pain control after total hip arthroplasty . We hypothesized that as a component of multimodal analgesia , local infiltration analgesia followed by continuous infusion of ropivacaine would result in reduced postoperative opioid consumption and lower pain scores compared with infiltration alone , and that both of these techniques would be superior to placebo . METHODS In this prospect i ve , double-blind , placebo-controlled study , 105 patients were r and omized into three groups : Group I , in which patients received infiltration with ropivacaine , ketorolac , and adrenaline followed by continuous infusion of 0.2 % ropivacaine at 5 mL/hr ; Group II , in which patients received infiltration with ropivacaine , ketorolac , and adrenaline followed by continuous infusion of saline solution at 5 mL/hr ; and Group III , in which patients received infiltration with saline solution followed by continuous infusion of saline solution at 5 mL/hr . All patients received celecoxib , pregabalin , and acetaminophen perioperatively and patient-controlled analgesia ; surgery was performed under general anesthesia . Before wound closure , the tissues and periarticular space were infiltrated with ropivacaine , ketorolac , and adrenaline or saline solution and a fenestrated catheter was placed . The catheter was attached to a pump prefilled with either 0.2 % ropivacaine or saline solution set to infuse at 5 mL/hr . The primary outcome measure was postoperative opioid consumption and the secondary outcome measures were pain scores , adverse side effects , and patient satisfaction . RESULTS There were no differences between groups in the administration of opioids in the operating room , in the recovery room , or on the surgical floor . The pain scores on recovery room admission and discharge and the floor were low and similar between groups . There were no differences in the incidence of adverse side effects among groups . Patient satisfaction with pain management was similar in all groups . CONCLUSIONS Local infiltration analgesia alone or followed by continuous infusion of ropivacaine as part of multimodal analgesia provides no additional analgesic benefit or reduction in opioid consumption compared with placebo following total hip arthroplasty . LEVEL OF EVIDENCE Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence Background : The analgesic effect of perioperative low doses of intravenous lidocaine has been demonstrated after abdominal surgery . This study aim ed to evaluate whether a continuous intravenous low-dose lidocaine infusion reduced postoperative pain and modified nociceptive pain threshold after total hip arthroplasty . Methods : Sixty patients participated in this r and omized double-blinded study . Patients received lidocaine 1 % ( lidocaine group ) with a 1.5 mg/kg−1 intravenous bolus in 10 min followed by a 1.5 mg · kg−1 · h−1 intravenous infusion or saline ( control group ) . These regimens were started 30 min before surgical incision and stopped 1h after skin closure . Lidocaine blood concentrations were measured at the end of administration . In both groups , postoperative analgesia was provided exclusively by patient-controlled intravenous morphine . Pain scores , morphine consumption , and operative hip flexion were recorded over 48 h. In addition , pressure pain thresholds and the extent of hyperalgesia around surgical incision were systematic ally measured at 24 and 48 h. Results : In comparison with the placebo , lidocaine did not induce any opioid-sparing effect during the first 24 h ( median [ 25–75 % interquartile range ] ; 17 mg [ 9–28 ] vs. 15 mg [ 8–23 ] ; P = 0.54 ) . There was no significant difference regarding the effects of lidocaine and placebo on pain score , pressure pain thresholds , extent in the area of hyperalgesia , and maximal degree of active hip flexion tolerated . Mean plasma lidocaine concentration was 2.1 ± 0.4 & mgr;g/ml . Conclusion : Low dose perioperative intravenous lidocaine after total hip arthroplasty offers no beneficial effect on postoperative analgesia and does not modify pressure and tactile pain thresholds Background Several reports have confirmed the ability of intraoperative periarticular injections to control pain after THA . However , these studies used differing combinations of analgesic agents and the contribution of each , including the local anesthetic agent , is uncertain . Underst and ing the independent effects of the various agents could assist in improved pain management after surgery . Questions / purpose sWe therefore determined the ability of intraoperative periarticular infiltration of levobupivacaine to ( 1 ) reduce postoperative pain , ( 2 ) reduce postoperative morphine requirements , and ( 3 ) reduce the incidence of nausea and urinary retention . Patients and Methods A double-blinded , r and omized , placebo-controlled trial of patients undergoing primary THAs was performed . Patients were r and omized to receive a periarticular infiltration of 150 mg levobupivacaine in 60 mL 0.9 % saline ( n = 45 ) or a placebo consisting of 60 mL 0.9 % saline ( n = 46 ) . We obtained a short-form McGill pain score , visual analog scale ( VAS ) , and morphine requirements via patient-controlled analgesia ( PCA ) as primary measures . Postoperative antiemetic requirements and need for catheterization for urinary retention were determined as secondary measures . Results Subjectively reported pain scores and the overall intensity scores were similar for both groups in the postoperative period . At the same time the mean morphine consumption was less in the levobupivacaine group , most notable in the first 12 hours after surgery : treatment group 11.5 mg vs control group 21.2 mg . We observed no differences in the frequency of postoperative nausea and vomiting or urinary retention . Conclusions Our observations suggest periarticular injection of levobupivacaine can supplement available postoperative analgesic techniques and reduce postoperative morphine requirements after THA.Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Background and Objectives : High-volume local infiltration analgesia ( LIA ) is widely applied as part of a multimodal pain management strategy in total hip arthroplasty ( THA ) . However , method ological problems hinder the exact interpretation of previous trials , and the evidence for LIA in THA remains to be clarified . Therefore , we evaluated whether intraoperative high-volume LIA , in addition to a multimodal oral analgesic regimen , would further reduce acute postoperative pain after THA . Methods : Patients scheduled for unilateral , primary THA under spinal anesthesia were included in this r and omized , double-blind , placebo-controlled trial receiving high-volume ( 150 mL ) wound infiltration with ropivacaine 0.2 % with epinephrine ( 10 & mgr;g/mL ) or saline 0.9 % . A multimodal oral analgesic regimen consisting of slow-release acetaminophen 2 g , celecoxib 400 mg , and gabapentin 600 mg was instituted preoperatively . Rescue analgesic consisted of oral oxycodone . Pain was assessed repeatedly the first 8 hrs after surgery using the 100-mm visual analog scale . The primary end point was pain during walking ( 5 m ) 8 hrs after surgery . Secondary end points were pain at rest , pain on 45 degrees of passive flexion of the hip with the leg straight , and cumulative consumption of oxycodone . Results : A total of 120 patients were included . Pain during walking ( median [ interquartile range ] [ 95 % confidence interval ] ) was low in the ropivacaine versus the placebo group ( 20 [ 14 - 38 ] [ 0 - 93 ] vs 22 [ 10 - 40 ] [ 0 - 83 ] ) and did not differ significantly ( P = 0.71 ) . Consumption of rescue oxycodone ( 5 mg [ 0 - 10 mg ] [ 0 - 24 mg ] vs 10 mg [ 0 - 15 mg ] [ 0 - 29 mg ] ) did not differ ( P = 0.45 ) . Conclusions : Intraoperative high-volume LIA with ropivacaine 0.2 % provided no additional reduction in acute pain after THA when combined with a multimodal oral analgesic regimen consisting of acetaminophen , celecoxib , and gabapentin and is therefore not recommended BACKGROUND : Ketamine has been shown to have a morphine-sparing effect soon after surgery . Nevertheless , whether this effect still exists after being combined with nonsteroidal antiinflammatory drugs and acetaminophen , and whether ketamine can decrease chronic pain after nononcologic surgery remain unclear . Thus , we design ed a study to assess ketamine ’s effect on acute and chronic postoperative pain when combined with multimodal analgesia after total hip arthroplasty ( THA ) . METHODS : Patients scheduled for primary nononcologic THA using st and ardized general anesthesia were r and omized . They received IV ketamine before incision ( 0.5 mg/kg ) , and a 24-h infusion ( 2 & mgr;g · kg−1 · min−1 ) or a similar blinded saline bolus and infusion . Postoperative analgesia included IV acetaminophen , ketoprofen , plus morphine/droperidol patient-controlled analgesia for 48 h. Data pertaining to pain scores , morphine consumption , and need for crutches were collected for 6 mo after THA . Our primary outcome was 24-h morphine consumption . RESULTS : One hundred fifty-four patients were included ( placebo , 75 ; ketamine , 79 ) . Patients and operative data were similar in both groups . Ketamine decreased morphine consumption at 24 h from 19 ± 12 mg to 14 ± 13 mg ( P = 0.004 ) . At Day 30 , ketamine decreased the proportion of patients needing 2 crutches or a walking frame from 56 % to 31 % ( P = 0.0035 ) . From Day 30 to Day 180 , ketamine decreased the proportion of patients with persistent pain at rest in the operated hip ( P = 0.008 ) . At Day 180 , 21 % of placebo group patients ( 15 of 70 ) experienced pain at rest in the operated hip versus 8 % ( 6 of 72 ) in the ketamine group ( P = 0.036 , odds ratio 0.33 , 95 % confidence interval 0.12–0.91 , risk reduction 67 % ) . CONCLUSIONS : Ketamine had a morphine-sparing effect after THA , even when morphine was combined with multimodal systemic analgesia . It also facilitated rehabilitation at 1 mo and decreased postoperative chronic pain up to 6 mo after surgery Postoperative pain can have a significant effect on patient recovery . An underst and ing of patient attitudes and concerns about postoperative pain is important for identifying ways health care professionals can improve postoperative care . To assess patients ’ postoperative pain experience and the status of acute pain management , we conducted a national study by using telephone question naires . A r and om sample of 250 adults who had undergone surgical procedures recently in the United States was obtained from National Family Opinion . Patients were asked about the severity of postsurgical pain , treatment , satisfaction with pain medication , patient education , and perceptions about postoperative pain and pain medications . Approximately 80 % of patients experienced acute pain after surgery . Of these patients , 86 % had moderate , severe , or extreme pain , with more patients experiencing pain after discharge than before discharge . Experiencing postoperative pain was the most common concern ( 59 % ) of patients . Almost 25 % of patients who received pain medications experienced adverse effects ; however , almost 90 % of them were satisfied with their pain medications . Approximately two thirds of patients reported that a health care professional talked with them about their pain . Despite an increased focus on pain management programs and the development of new st and ards for pain management , many patients continue to experience intense pain after surgery . Additional efforts are required to improve patients ’ postoperative pain experience BACKGROUND High-dose glucocorticoid may reduce postsurgical pain and improve recovery . We hypothesized that 125 mg methylprednisolone ( MP ) would reduce time to meet functional discharge criteria after total hip arthroplasty ( THA ) . METHODS Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this r and omized , double-blind , placebo-controlled trial receiving preoperative i.v . MP or saline . All patients received a st and ardized , multimodal analgesic regime with paracetamol , celecoxib , and gabapentin . The primary outcome was time to meet well-defined functional discharge criteria . Secondary outcomes were h and grip strength and endurance , pain , nausea , vomiting , fatigue , sleep quality , and rescue analgesic- , antiemetic- , and hypnotic medicine requirements . The inflammatory response measured by C-reactive protein ( CRP ) and actual length of stay were also registered . Discharge criteria were assessed twice daily ( at 09:00 and 14:00 h ) until discharge . Other outcomes were assessed at 2 , 4 , 6 , 8 , and 24 h after operation , and also in a question naire from postoperative day ( POD ) 1 - 4 . RESULTS Time to meet discharge criteria was [ median ( IQR ) ( 95 % CI ) , MP vs placebo ] : 23.5 ( 23.3 - 23.7 ) ( 17.8 - 43.8 ) vs 23.5 ( 23.0 - 23.8 ) ( 20.0 - 46.8 ) h , the mean difference ( 95 % CI ) being -1.3 ( -4.7 to 2.2 ) h , P=0.65 . Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group ( P<0.01 ) , as was CRP at 24 h ( P<0.0001 ) . No other between-group differences were observed . No drug-related complications were observed at follow-up on POD30 . CONCLUSIONS MP 125 mg i.v . before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA , but improved analgesia for the first 24 Background This study examined the opioid-sparing effectiveness , analgesic efficacy , and tolerability of postoperative administration of the parenteral cyclooxygenase 2 selective inhibitor , parecoxib sodium , in total hip arthroplasty patients . Methods This was a multicenter , multiple-dose , r and omized , double-blind , placebo-controlled study to compare the opioid-sparing effects , analgesic efficacy , and tolerability of postoperative 20 and 40 mg intravenous parecoxib sodium with placebo in hip arthroplasty patients . The first dose of study medication was administered after surgery with an intravenous bolus dose of 4 mg morphine when patients first requested pain medication ; remedication with the study medication occurred at 12 and 24 h. Subsequent morphine doses ( 1–2 mg ) were administered by patient-controlled analgesia . Efficacy was assessed by total morphine used , pain relief and pain intensity , time to last dose of morphine , and Global Evaluation rating of the study medication . Results Parecoxib sodium , 20 and 40 mg , reduced the total amount of morphine required over 36 h by 22.1 % ( 56.5 mg morphine ) and 40.5 % ( 43.1 mg morphine ) , respectively , compared with placebo ( 72.5 mg morphine;P < 0.01 ) . Patients receiving 20 and 40 mg parecoxib sodium experienced significantly greater maximum pain relief compared with those in the placebo group ( P < 0.05 ) . Patients who received 20 and 40 mg parecoxib sodium discontinued PCA morphine earlier than patients receiving placebo and had significantly higher Global Evaluation ratings . Parecoxib sodium , 40 mg , plus morphine demonstrated a significantly lower incidence of fever and vomiting compared with placebo plus morphine . Conclusions Administration of parecoxib sodium with PCA morphine result ed in significantly improved postoperative analgesic management as defined by reduction in opioid requirement , lower pain scores , reduced time on PCA morphine , and higher Global Evaluation ratings Background and Objectives . The postoperative pain scores and analgesic requirements were assessed in 60 patients who had undergone total hip replacement under bupivacaine spinal anesthesia . Methods . Thirty of the patients had intrathecal diamorphine injected after the bupivacaine , and the remaining 30 received saline . Results . Superior postoperative pain relief was obtained in the diamorphine group , whose average postoperative morphine requirements were 12 ± 11.4 mg compared to 31 ± 18.7 mg ( mean ± SD ) in the control group . Despite the lower doses of morphine , their pain scores over the first 24 hours postoperatively were consistently lower . No differences were seen between the groups with respect to respiratory depression , nausea , pruritus , postoperative sedation , headache , or urinary retention . Conclusion . Pain control after intrathecal diamorphine supplemented by intravenous morphine from a patient controlled analgesia system is superior to intravenous morphine alone 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 : Ropivacaine is a new long‐acting local anesthetic . Laboratory trials have demonstrated a synergistic analgesic effect between intrathecal opioids and local anesthetics . We tested the hypothesis that addition of ropivacaine 1 mg · ml−1 to epidural fentanyl ( 10 μg · ml−1 ) postoperatively decreases the need for fentanyl , improves the quality of analgesia and decreases the side‐effects of fentanyl Background Periarticular infiltration of local anesthetic , NSAIDs , and adrenaline have been reported to reduce postoperative pain , improve mobility , and reduce hospital stay for patients having THAs , but available studies have not determined whether local anesthetic infiltration alone achieves similar improvements . Questions We therefore asked whether periarticular injection of a local anesthetic during THA reduced postoperative pain and opioid requirements and improved postoperative mobility . Methods We r and omized 96 patients to either treatment ( n = 50 ) or control groups ( n = 46 ) . Before wound closure , the treatment group received local infiltration of 160 mL of levobupivacaine with adrenaline . The control group received no local infiltration . We assessed postoperative morphine consumption and pain during the 24 hours after surgery . Mobilization was assessed 24 hours postoperatively with supine-to-sit and sit-to-st and transfers , timed 10-m walk test , and timed stair ascent and descent . Patients and assessing physiotherapists were blind to study status . Result We observed no differences in postoperative morphine consumption , time to ascend and descend stairs , or ability to transfer between treatment and control groups . The treatment group reported more pain 7 to 12 hours postoperatively , but there were no differences in pain scores between groups at all other postoperative intervals . The treatment group showed increased postoperative walking speed greater than 6 m , but not greater than 10 m , compared with the control group . Conclusions Periarticular infiltration of local anesthetic during THA did not reduce postoperative pain or length of hospital stay and did not improve early postoperative mobilization . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence Intrathecal ( IT ) morphine provides excellent postoperative analgesia but may result in many side effects , including postoperative nausea and vomiting , pruritus , and respiratory depression , particularly at larger doses . Older patients may be at particular risk . The optimal dose of spinal morphine in older patients undergoing hip arthroplasty is not known . We design ed this prospect i ve , r and omized , controlled , double-blinded study to evaluate the analgesic efficacy and side effect profile of 50–200 & mgr;g of IT morphine in older patients undergoing elective hip arthroplasty . Sixty patients older than 65 years undergoing elective hip arthroplasty were enrolled . Patients were r and omized to receive spinal anesthesia with 15 mg of bupivacaine and IT morphine in four groups : 1 ) 0 & mgr;g , 2 ) 50 & mgr;g , 3 ) 100 & mgr;g , and 4 ) 200 & mgr;g . IT morphine 100 and 200 & mgr;g produced effective pain relief and decreased the postoperative requirement for morphine compared with control . IT morphine 50 & mgr;g did not provide effective pain relief . Both 100 and 200 & mgr;g of IT morphine provided comparable levels of postoperative analgesia . There were no between-group differences in postoperative nausea and vomiting , sedation , respiratory depression , or urinary retention . Pruritus was significantly more frequent with 200 & mgr;g of IT morphine . In conclusion , 100 & mgr;g of IT morphine provided the best balance between analgesic efficacy and side effect profile in older patients undergoing hip arthroplasty Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects . Valdecoxib is a new , highly selective cyclooxygenase (COX)-2–specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain . The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty . This multicenter , multiple-dose , double-blind , parallel-group study compared the opioid-sparing effects , analgesic efficacy , and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty . Study medication was first administered 1 to 3 hours preoperatively . The total amount of morphine administered , pain intensity , and patient 's global evaluation of study medication were assessed over a period of 48 hours . Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40 % less morphine than those receiving placebo after hip arthroplasty . Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo . Valdecoxib and placebo were equally well tolerated . Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone . Thus , valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients This prospect i ve , r and omized , double-blind trial evaluated the efficacy of rectal indomethacin as an adjunct to morphine for controlling postoperative pain . Fifty healthy patients undergoing elective hip arthroplasty were investigated . Group 1 ( n = 25 ) received placebo suppositories . Group 2 ( n = 25 ) received indomethacin suppositories , 100 mg q8hr for five doses , starting at the end of the procedure . Both groups received morphine via a PCA pump , which recorded the amount of morphine delivered each hour . After a st and ardized general anaesthetic , PCA was begun in the recovery room . Pain was measured with a st and ard 100 mm VAS at 2 , 6 , 20 , 28 , 42 hr after surgery and the morphine consumption recorded . Over the 42-hr study period , patients in Group 2 required less morphine than those in Group 1 ( 34.8 ± 21.8 mg vs 89.6 ± 43.7 , P < 0.01 ) . Pain scores were lower in Group 2 at 20 , 28 , 42 hr postoperatively . The incidence of side-effects did not differ between groups and no patient had excessive postoperative bleeding . The combination of indomethacin and morphine provided superior pain relief to morphine alone even though the control group had liberal access to morphine . This synergistic effect would make indomethacin a useful adjunct to intramuscular or epidural narcotics . RésuméCette étude prospect i ve r and omisée et à double insu a évalué l’efficacité de l’indométhacine par voie rectale comme adjuvant à la morphine pour contrôler la douleur postopératoire . Cinquante patients en bonne samé devant subir une arthroplastie de la hanche élective furent investigués . Le Groupe 1 ( n = 25 ) a reçu des suppositoires de placebo le Groupe ( n = 25 ) a reçu des suppositoires d’indométhacine , 100 mg q8hre pour cinq doses debutant à la fin de la procédure . Les deux groupes ont reçu de la morphine à travers une pompe PCA qui a enregistre la quantité de morphine délivrée à chaque heure . Après st and ardisation de l’anesthésie générate , le PCA fut commencé en salle de réveil . La douleur fut mesurée avec un VAS st and ard 100 mm en 2 , 6 , 20 , 28 , 42 heures après la chirurgie et la consommation générate de morphine fut enregistrée . Pour une période d’étude de 42 heures , les patients du Groupe 2 ont requis moins de morphine que ceux du Groupe 1 ( 34.8 ± 21.8 mg vs 89.6 ± 43,7 , P < 0.01 ) . Les échelles de douleur étaient plus basses dans le Groupe 2 avant 20 , 28 , 42 heures après la chirurgie . L’incidence des effets secondaires n’était pas différente entre les deux groupes et aucun patient n’a demontré de saignement postoperatoire excessif . La combinaison de l’indométhacine et de la morphine a fourni un soulagement de la douleur supérieur à la morphine seule même si le groupe contrôle avait accès d’une manière libérate à la morphine . Les effets sénergétiques pourraient rendre à l’indométhacine une addition utile aux narcotiques intramusculaires ou une injection épidurale BACKGROUND In this double-blind , r and omized , placebo-controlled trial , the safety and analgesic efficacy of perioperative dexketoprofen were evaluated . METHODS Thirty ASA I or II patients undergoing elective hip arthroplasty were r and omized to one of two groups . One group ( D ) received dexketoprofen 25 mg tds for 24 h before and 48 h after surgery ; the second group ( P ) received placebo tablets at equivalent times . Hyperbaric 0.5 % bupivacaine ( 17.5 mg if greater than 70 kg and 15 mg if less than 70 kg ) and preservative-free morphine ( 0.6 mg ) were administered intrathecally . Postoperatively , PCA was provided ( bolus morphine sulphate 1 mg ; lockout 5 min ; no continuous infusion ) . RESULTS The two groups were similar in terms of age , gender , weight , height , ASA class , duration of operation , and level of sensory block on arrival to the recovery room . Groups were also similar in terms of blood loss , transfusion requirements , ventilatory frequency , and haemodynamic variables . According to visual analogue pain scores patients in group D experienced less pain at 15 h ( P=0.02 ) postoperatively . Cumulative morphine consumption was also less in group D compared with group P at 6 ( 0.06 ( 0.2 ) vs 0.85 ( 1.4 ) mg , P=0.04 ) and 48 h postoperatively ( 10.1 ( 8) vs 26.2 ( 20 ) mg , P<0.01 ) . Plasma interleukin 6 concentrations increased postoperatively to a significantly lesser extent in group D than in group P ( P=0.02 ) . Nausea and vomiting were less ( P<0.01 ) in group D compared with group P at 18 h postoperatively . Sedation scores were less ( P=0.03 ) in group D. CONCLUSIONS Perioperative administration of dexketoprofen 25 mg 8 hourly markedly improves analgesia and decreases opioid requirements ( and associated adverse effects ) following hip arthroplasty . It appears that this regimen decreases the postoperative pro-inflammatory response BACKGROUND In a r and omized , double-blind , prospect i ve study , we have evaluated the effect of i.v . infusion of magnesium sulphate during spinal anaesthesia on postoperative analgesia and postoperative analgesic requirements . METHODS Forty patients undergoing total hip replacement arthroplasty under spinal anaesthesia were included . After the induction of spinal anaesthesia , the magnesium group ( Group M ) received magnesium sulphate 50 mg kg(-1 ) for 15 min and then 15 mg kg(-1 ) h(-1 ) by continuous i.v . infusion until the end of surgery . The saline group ( Group S ) received the same volume of isotonic saline over the same period . After surgery , a patient-controlled analgesia ( PCA ) device containing morphine and ketorolac was provided for the patients . Postoperative pain scores , PCA consumption , and the incidences of shivering , postoperative nausea , and vomiting were evaluated immediately after surgery , and at 30 min , 4 , 24 , and 48 h after surgery . Serum magnesium concentrations were checked before the induction of anaesthesia , immediately after surgery , and at 1 and 24 h after surgery . RESULTS Postoperative pain scores were significantly lower in Group M at 4 , 24 , and 48 h after surgery ( P<0.05 ) . Cumulative postoperative PCA consumptions were also significantly lower in Group M at 4 , 24 , and 48 h after surgery ( P<0.05 ) . Postoperative magnesium concentrations were higher in Group M ( P<0.05 at 4 , 24 , and 48 h after surgery ) , but no side-effects associated with hypermagnesemia were observed . Haemodynamic variables and the incidences of shivering , nausea , and vomiting were similar in the two groups . CONCLUSIONS I.V. magnesium sulphate administration during spinal anaesthesia improves postoperative analgesia Background and purpose Postoperative analgesia after primary total hip arthroplasty ( THA ) using opioids is associated with troublesome side effects such as nausea and dizziness , and epidural analgesic means delayed mobilization . Thus , local infiltration analgesia ( LIA ) during surgery prolonged with local infusion analgesia ( LINFA ) into the soft tissue in the hip region through a catheter in the first postoperative days has gained major interest in THA fast-track setting s within a short period of time . LIA at the time of surgery is a vali date d treatment . We investigated the additional effect of giving postoperative LINFA after THA in patients already having LIA during surgery . Patients and methods 60 consecutive patients undergoing non-cemented THA were r and omized into two groups in a double-blind and controlled study . During surgery , all patients received st and ardized pain treatment with LIA . Postoperatively , they were treated either with a solution of Ropivacain , Ketorolac , and Adrenaline ( LINFA group ) or placebo ( placebo group ) administered through a catheter to the hip 10 and 22 h after surgery . Pain score , opioid consumption , and length of stay ( LOS ) were evaluated . Results After adjustment for multiple testing , there was no statistically significant postoperative difference between the LINFA group and the placebo group regarding pain and tiredness . We found some evidence of a short-term effect on nausea and vomiting . Opioid consumption and length of stay were similar in the two groups . Interpretation We found some evidence of a short-term effect of LINFA on nausea and vomiting , but no evidence of an effect on postoperative pain and tiredness . Thus , LINFA can not be recommended as a st and ard pain treatment in patients with THA Co-administration of pethidine 0.75 mg kg-1 and clonidine 75 micrograms intrathecally provided good intraoperative anaesthesia for total hip replacement , similar to that obtained using 0.5 % isobaric bupivacaine . Sensory and motor block were of shorter duration than that after 0.5 % isobaric bupivacaine and 0.5 % isobaric bupivacaine with morphine 0.5 mg ( P < 0.001 sensory block , P < 0.001 motor block ) . Postoperative morphine consumption , measured using a patient-controlled system , was similar to that in patients in the bupivacaine only group ( pethidine-clonidine : median 39 mg/24 h ; bupivacaine : median 34 mg/24 h ) but greater than that in the bupivacaine-morphine group ( median 8 mg/24 h ) ( P < 0.001 ) . Visual analogue pain scores after operation were similar to those with bupivacaine alone at all but one of the recording times but were greater than those in patients who received bupivacaine and morphine at 4 , 6 and 10 h after operation ( P < 0.001 , P < 0.04 , P < 0.02 ) . The combination did not offer any major advantage over conventional agents BACKGROUND The infiltration of local anaesthetic ( LA ) , ketorolac , and epinephrine has been suggested to be effective for analgesia after total hip arthroplasty ( THA ) . The part of action of each component of the mixture remains unclear . We investigated the contribution of infiltration of ropivacaine alone on the morphine consumption during the first 24 h after surgery . METHODS Sixty patients undergoing primary THA were included in this prospect i ve r and omized double-blinded placebo-controlled trial , after IRB approval and informed consent . Surgical and general anaesthetic management were st and ardized . At the end of surgery , 80 ml of ropivacaine 0.2 % ( 160 mg ) or saline was infiltrated . The primary endpoint was morphine consumption 24 h after surgery . The secondary endpoints were : visual analogue scale scores and opioid side-effects at H2 , H4 , H8 , H12 , H24 , D1 , D2 , D3 , D4 , D5 , rehabilitation programme progress , chronic pain level , analgesic consumption , and surgical result at 3 months and 1 yr after surgery . The observation period was 1 yr . RESULTS Groups were similar for patient characteristic and perioperative characteristics . The ropivacaine wound infiltration did not reduce morphine consumption at 24 h [ median ( 25th and 75th inter-quartile ) 27 ( 17 - 37 ) mg in the ropivacaine group vs 24 ( 18 - 34 ) mg in the placebo group , P=0.51 ] or its side-effects . No effect was found on rehabilitation progress or chronic pain after 3 months or 1 yr , but these were not the main endpoints of the study . CONCLUSIONS Ropivacaine infiltration alone did not reduce morphine consumption at 24 h after operation nor did it improve postoperative rehabilitation BACKGROUND Balanced postoperative analgesia combines non-narcotic drugs and opioids . We organized a large study to evaluate nefopam analgesia and tolerance in combination with morphine for patient-controlled analgesia ( PCA ) after orthopaedic surgery . METHODS Two hundred and one patients scheduled to undergo hip arthroplasty were included in this multicentre ( n=24 ) , double-blind , r and omized study comparing nefopam ( 20 mg every 4 h for 24 h ) with placebo , the first dose being infused peroperatively . The primary outcome measure was the cumulative morphine dose received postoperatively by PCA over 24 h. Secondary outcome measures were the amount of morphine received as a loading dose in the postanaesthesia care unit ( PACU ) and during the 24-h observation period , and pain assessment s using a visual analogue scale ( VAS ) and a verbal pain scale ( VPS ) , patient 's satisfaction with analgesia and treatment tolerance . RESULTS The two groups were comparable with respect to their characteristics and preoperative pain assessment . PCA-administered morphine over 24 h was significantly less for the nefopam group than the control group ( 21.2 ( 15.3 ) and 27.3 ( 19.2 ) mg respectively ; P=0.02 ) . This morphine-sparing effect was greater ( 35.1 % ) for patients with severe preoperative pain ( VAS>30/100 ) . For the entire study period ( loading dose and PCA ) , morphine use was less for the nefopam group ( 34.5 ( 19.6 ) vs 42.7 ( 23.6 ) mg ; P=0.01 ) . Pain VAS at PACU arrival and during the whole PACU period was significantly lower for the nefopam than for the placebo group ( P=0.002 and 0.04 respectively ) . Patient satisfaction was similar for the nefopam and placebo groups . CONCLUSION In combination with PCA morphine , nefopam gives significant morphine-sparing with lower immediate postoperative pain scores without major side-effects . This analgesic effect seems to be particularly notable for patients with intense preoperative pain The postoperative analgesic effect of ibuprofen was compared with a combination of ibuprofen and codeine versus placebo . The study was prospect i ve , r and omized , double blind with 123 consecutive hip arthroplasly operations . All the patients received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3–4 ml Background Comfort and lack of pain are important for optimal mobilization after hip replacement . We investigated the efficacy of double wound infiltration . Patients and methods 40 consecutive patients undergoing total hip replacement were r and omized into two groups in this double-blinded study . They received wound infiltration at the end of surgery and through an intraarticular catheter 24 h postoperatively . The catheter was placed at the end of surgery . One group received solutions of ropivacaine , ketorolac , and adrenaline . Patients in the control group were injected with saline instead . The observation period was 6 weeks . Results The patients who received the analgesic solution had less pain up to 2 weeks postoperatively . They reached an earlier and lower pain minimum during the first days postoperatively , had lower use of analgesia up to day 4 postoperatively , and were more satisfied . Use of analgesic solution result ed in less joint stiffness and better function 1 week postoperatively . Interpretation Operative and postoperative wound infiltration with multimodal drugs reduces pain and the requirement for analgesics after hip replacement , leading to faster postoperative mobilization OBJECTIVES To determine the minimum clinical ly significant difference in visual analog scale ( VAS ) pain scores for acute pain in the ED setting and to determine whether this difference varies with gender , age , or cause of pain . METHODS A prospect i ve , descriptive study of 152 adult patients presenting to the ED with acute pain . At presentation and at 20-minute intervals to a maximum of three measurements , patients marked the level of their pain on a 100-mm , nonhatched VAS . At each follow-up they also gave a verbal rating of their pain as " a lot better , " " much the same , " " a little worse , " or " much worse . " The minimum clinical ly significant difference in VAS pain scores was defined as the mean difference between current and preceding scores when pain was reported as a little worse or a little better . Data were compared based on gender , age more than or less than 50 years , and traumatic vs nontraumatic causes of pain . RESULTS The minimum clinical ly significant difference in VAS pain scores is 9 mm ( 95 % CI , 6 to 13 mm ) . There is no statistically significant difference between the minimum clinical ly significant differences in VAS pain scores based on gender ( p=0.172 ) , age ( p=0.782 ) , or cause of pain ( p=0.84 ) . CONCLUSIONS The minimum clinical ly significant difference in VAS pain scores was found to be 9 mm . Differences of less than this amount , even if statistically significant , are unlikely to be of clinical significance . No significant difference in minimum significant VAS scores was found between gender , age , and cause-of-pain groups A number of pharmacologic treatments examined in recent r and omized clinical trials ( RCTs ) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated . Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies , such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ( “ assay sensitivity ” ) . Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development . Therefore , an Initiative on Methods , Measurement , and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was review ed and discussed . On the basis of this meeting and subsequent discussion s , the authors recommend consideration of a number of patient , study design , study site , and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments . Increased attention to and research on method ological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence ‐based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine . In a double-blind , controlled study , patients , undergoing total hip replacement were allocated r and omly to receive one of two doses of extradural clonidine ( 25 micrograms h-1 or 50 micrograms h-1 ) , low dose extradural morphine or a combination of morphine and clonidine . Pain scores in the morphine group were significantly greater than in the clonidine groups ( P less than 0.01 ) and the combination group ( P less than 0.05 ) during the first 1 h after surgery . The requirements for systemic analgesia were least in the combination and larger dose clonidine group , and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups ( P less than 0.05 ) . Arterial pressure was reduced in the clonidine groups , although the incidence of clinical hypotension was low . There were no significant differences between the groups in emetic symptoms or urinary retention Background Patient-controlled analgesia is a widely used and effective method of controlling pain after THA . This method is associated with substantial undesirable side effects . Local infiltration has been introduced in an attempt to reduce opioid requirements postoperatively , but its ability to reduce pain without complications is still question ed . Questions / Purpose sWe evaluated patient-controlled analgesia use , pain and satisfaction scores , complication rates , and ropivacaine levels associated with the use of periarticular multimodal drug infiltration in THA . Patients and Methods We r and omized 64 patients undergoing THA to receive a periarticular intraoperative multimodal drug injection or to receive no injection . All patients received patient-controlled analgesia for 24 hours after surgery . The final assessment was at 6 weeks . Results Patients receiving the periarticular injection used less patient-controlled analgesia 6 hours postoperatively . The 24-hour patient-controlled analgesia requirement postsurgery also was less . The visual analog scale score for pain on activity in the postanesthetic care unit was less for patients who received an injection . The visual analog scale satisfaction score was similar in the two groups throughout the followup period . Recorded unbound ropivacaine levels were 2.5 times lower than toxic levels . Conclusions Periarticular intraoperative injection with multimodal drugs can reduce postoperative patient-controlled analgesia requirements and pain on activity in patients undergoing THA with no apparent increase in risk . Level of Evidence Level I , therapeutic study . See the guidelines online for a complete description of level of evidence OBJECTIVE Postoperative pain after total hip arthroplasty ( THA ) is not well tolerated . We assessed postoperative pain relief and the need for opioid use after using a cocktail of local and intraarticular analgesic injection ( LIA ) after THA . METHODS Eighty patients undergoing THA under spinal anesthesia were r and omly assigned to receive either LIA or placebo . The LIA was composed of 5 mg morphine , 30 mg bupivacaine ( 15 mg/1.5 mL ) , 1 mL betamethasone , and 0.5 mL epinephrine ( 1:1,000 ) intraoperatively . We compared three outcomes total morphine consumption , visual analog scale ( VAS ) at rest and during activity , and hip flexion angle while st and ing . RESULTS When compared with placebo , opioid consumption was significantly reduced in the trial group , as well as VAS at rest and during mobilization . Earlier rehabilitation and better range of motion ( ROM ) were achieved in the trial group . There were no significant differences in side effects or postoperative wound healing between groups . CONCLUSION In patients undergoing THA , LIA may reduce postoperative systemic opioid use and offer better pain control and earlier rehabilitation , without observable risks Background : Combined analgesic regimens have been suggested to improve the treatment of postoperative pain . The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol , in combination with morphine Purpose To evaluate the efficacy of a single shot “ 3-in-1 ” femoral nerve block for prosthetic hip surgery in association with general anaesthesia on post-operative analgesia . Methods Forty patients , ASA 1 to 3 , received sham block or “ 3-in-1 ” femoral nerve block , following Winnie ’s l and marks with a nerve stimulator , and 40 ml bupivacaine 0.5 % with epinephrine were injected after induction of anaesthesia . Vecuronium , 0.1 mg · kg−1 , was added after performing the block and anaesthesia was maintained with isoflurane , oxygen 40 % and nitrous oxide 60 % . Fentanyl , 1.5 μg · kg−1 , was administered before incision to all patients . Heart rate , blood pressure , fentanyl requirements and FETiso were measured throughout surgery . During the post-operative period , 75 mg diclofenacim and /or 0.1 mg · kg−1 morphine sc were administered when pain score was > 3/10 and repeated when necessary . Pain scores at first analgesic intervention , at 24 hr and 48 hr as well as diclofenac and morphine requirements after surgery were recorded . Results There was no difference in anaesthetic requirements during surgery . The time from performance of sham or “ 3-in-1 ” femoral nerve block to the first analgesic intervention ( 261 ± 49 min versus 492 ± 40 min , P < 0.05 ) and time from extubation to the first analgesic intervention ( 61 ± 44 minvs 298 ± 39 min , P < 0.05 ) were prolonged in the study group . However , pain scores and the analgesic requirements in the postoperative periods ( 24 and 48 hr ) were similar . Conclusion There is a short-term benefit during the first few postoperative hours in using a single shot “ 3-in-1 ” femoral nerve block to complement general anaesthesia for elective hip surgery . RésuméObjectifÉvaluer l’efficacité du bloc fémoral « 3-dans-1 » en une injection pour la chirurgie prosthétique de la hanche associé à une anesthésie générale pour procurer l’analgésie postopératoire . MéthodesQuarante patients , ASA 1 à 3 , ont reçu un bloc factice ou un bloc fémoral « 3-dans-1 » avec repérage des points de Winnie par stimulateur nerveux et réalisé avec de la bupivacaïne 0,5 % adrénalinée 40 ml injectée après l’induction de l’anesthésie . Du vécuronium , 0,1 mg · kg−1 , était ajouté après la réalisation du bloc et d’une anesthésie maintenue à l’isoflurane , oxygène 40 % et protoxyde d’azote 60 % . On administrait 1,5 μg·kg−1 de fentanyl à tous les patients avant l’incision . La fréquence cardiaque , la pression artérielle , les besoins en fentanyl et la PETiso étaient mesurés pendant la chirurgie . À la période postopératoire , les patients recevaient 75 mg de diclofénacim et/ou 0,1 mg · kg−1 de morphine sc lorsque le score dépassait 3 sur l’échelle de 10 , au besoin . On enregistrait les scores de douleurs au moment de la première administration d’analgésique , à 24 h et 48 h de même que les doses de diclofénac et de morphine après la chirurgie . RésultatsLes besoins d’anesthésie étaient les mêmes pendant la chirurgie . L’intervalle entre le bloc factice ou le bloc « 3-dans-1 » et la première administration d’analgésique ( 261 ± 49 min vs 492 ± 40 min , P < 0,05 ) et l’intervalle entre l’extubation et la première administration analgésique ( 61 ±44 minvs 298 ± 39 min , P < 0,05 ) se prolongeaient dans le groupe d’étude . Cependant , les scores de douleur et les besoins analgésiques de la période postopératoire ( à 24 et 48 h ) étaient semblables . Conclusion Le bloc fémoral en une injection « 3-dans-1 » administré comme complément à l’anesthésie générale procure un avantage à court terme au cours des premières heures qui suivent une intervention chirurgicale non urgente de la hanche Postoperative pain relief immediately after major surgery can not be achieved with opioids alone in all patients without respiratory depression or other significant side effects . This investigation was conducted to determine whether the need for opioids and the incidence of side effects can be reduced while maintaining the quality of pain relief using a nonsteroidal antiinflammatory drug as an adjuvant to an opioid . The analgesic efficacy and safety of patient-controlled analgesia using fentanyl with and without intravenous diclofenac were compared after total hip replacement . Forty patients were r and omly assigned to receive either diclofenac 75 mg as an initial intravenous loading dose followed by an infusion of 5 mg per hour or saline in a double-blind fashion . The amount of fentanyl administered was recorded . The patients assessed their pain intensity verbally and on a visual analogue scale at intervals of 4 h. The diclofenac group showed a significant reduction in the amount of fentanyl administered during the first 16 h postoperatively as compared to the placebo group ( 0.65 mg + /- 0.2 vs. 1.08 mg + /- 0.4 respectively , P less than 0.01 ) , and also reported less pain at 16 h ( median score on visual analogue scale 0.75 vs. 2.4 respectively , P less than 0.05 ) ) . There were no differences in side effects , postoperative blood loss , plasma activated partial thromboplastin time , or Ivy bleeding time between the groups . In conclusion , the addition of diclofenac led to a reduction in fentanyl requirement but did not have any other significant advantages in the treatment of pain following major orthopedic surgery Background and objective : Oral morphine may be useful for postoperative pain relief , but few studies have tested its use after in‐hospital surgery . Methods : We evaluated clinical efficacy and the pharmacokinetic parameters of oral morphine after total hip arthroplasty . We recruited 60 patients who had total hip arthroplasty under general anaesthesia . The patients were r and omized to receive placebo , 10 mg morphine sulphate or 20 mg morphine sulphate orally every 4 h for 24 h. The oral administration was started 3 h after the morphine‐loading dose in the Post Anaesthesia Care Unit and then patients used intravenous morphine patient‐controlled analgesia for 24 h. Pain score at rest ( scored by patients on a visual analogue scale ) , sedation , nausea , vomiting and urinary retention were monitored . In 11 additional total hip arthroplasty patients , we determined the pharmacokinetics of morphine and its metabolites after oral administration of 20 mg morphine sulphate every 4 h for 16 h. Results : The amount of morphine administered via patient‐controlled analgesia over 24 h was reduced in the 20‐mg group compared with that in the placebo group ( 19.0 ± 2.7 mg vs. 33.0 ± 5.5 mg ; P = 0.03 ) . No significant morphine‐sparing effect was observed in the 10‐mg group . Pain scores and side‐effects were similar in all groups . The pharmacokinetic study revealed a limited and slow absorption of morphine . Conclusion : Despite a limited absorption of oral morphine postoperatively , high doses of oral morphine have a significant analgesic effect after total hip arthroplasty BACKGROUND : Preoperative glucocorticoids reduce postoperative nausea but may also improve analgesia and decrease opioid consumption . METHODS : Fifty consecutive patients undergoing elective , unilateral , primary total hip arthroplasty under spinal anesthesia with propofol sedation received in a r and omized , double-blind , placebo-controlled manner either 40 mg of dexamethasone or saline placebo IV before the start of surgery . IV patient-controlled analgesia morphine , ibuprofen 400 mg po q6 h and acetaminophen 650 mg po q6 h were given for 48 h. Pain ( 0–10 numeric rating scale , NRS ) at rest , side effects , and total cumulative patient-controlled analgesia morphine consumption were recorded q4 h for 48 h. Dynamic pain NRS score was recorded at 24 h. C-reactive protein levels were measured in a subgroup of 25 patients at 48 h. RESULTS : The intraoperative sedation requirement with propofol was significantly increased in the dexamethasone group ( 234.6 ± 160.1 vs 138.8 ± 122.7 mg , P = 0.02 ) . Dynamic pain was greatly reduced in the dexamethasone group ( NRS score : 2.7 , 95 % CI : 2.2–3.1 vs 6.8 , 6.4–7.2 ; P < 0.0001 ) . There was no significant effect on pain at rest or cumulative morphine consumption at any time . C-reactive protein levels at 48 h were markedly reduced by dexamethasone ( 52.4 mg/mL , 28.2–76.6 vs 194.2 , 168.9–219.4 ; P < 0.0001 ) . Seven patients in the control group , but only one in the dexamethasone group , were treated for nausea ( P = 0.05 ) . CONCLUSIONS : A single , preoperative IV dose of dexamethasone 40 mg has a prolonged suppressive effect on the inflammatory response and decreases dynamic pain 24 h after total hip arthroplasty Purpose Epidural and intravenous patient-controlled analgesia ( PCA ) are established methods for pain relief after total hip arthroplasty ( THA ) . Periarticular infiltration is an alternative method that is gaining ground due to its simplicity and safety . Our study aims to assess the efficacy of periarticular infiltration in pain relief after THA . Methods Sixty-three patients undergoing THA under spinal anaesthesia were r and omly assigned to receive postoperative analgesia with continuous epidural infusion with ropivacaine ( epidural group ) , intraoperative periarticular infiltration with ropivacaine , clonidine , morphine , epinephrine and corticosteroids ( infiltration group ) or PCA with morphine ( PCA group ) . PCA morphine provided rescue analgesia in all groups . We recorded morphine consumption , visual analog scale ( VAS ) scores at rest and movement , blood loss from wound drainage , mean arterial pressure ( MAP ) and adverse effects at 1 , 6 , 12 , 24 h postoperatively . Results Morphine consumption at all time points , VAS scores at rest , 6 , 12 and 24 h and at movement , 6 and 12 h postoperatively were lower in infiltration group compared to PCA group ( p < 0.05 ) , but did not differ between infiltration and epidural group . There was no difference in adverse events in all groups . At 24 h , MAP was higher in the PCA group ( p < 0.05 ) and blood loss was lower in the infiltration group ( p < 0.05 ) . Conclusions In our study periarticular infiltration was clearly superior to PCA with morphine after THA , providing better pain relief and lower opioid consumption postoperatively . Infiltration seems to be equally effective to epidural analgesia without having the potential side effects of the latter BACKGROUND Instillation of local anesthetics into a surgical site has been gaining popularity in post-operative pain management . AIM To determine whether continuous intra-articular infusion of bupivacaine via pain-control infusion pumps ( PCIP ) enhances and sustains analgesia after total hip arthroplasty ( THA ) . METHODS Ninety-two patients undergoing THA were r and omized to receive continuous intra-articular infusion of either 0.5 % bupivacaine or 0.9 % normal saline at a flow rate of 2 mL/h via a PCIP for 48 h. The primary outcome measure was pain intensity on Visual Analogue Scale ( VAS ) scores in the first 72 h. Other measures included time to first rescue dose of narcotics , amount of narcotic use , presence of adverse events , length of hospital stay , and hip function evaluated with the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index . RESULTS Despite a longer time to first narcotic rescue ( 56 versus 21 min , p<0.0001 ) in patients receiving bupivacaine , the two groups did not differ significantly in overall pain relief ( p=0.54 ) . A lower VAS score was found only at time 0 and 2 h ; no difference in VAS score was noted at any other time point . Additionally , no difference was found in terms of amount of narcotic use , incidence of adverse events , hospitalization days , and the WOMAC score . CONCLUSION Continuous intra-articular infusion of 0.5 % bupivacaine at 2 mL/h via a PCIP does not provide sustained post-operative pain relief in patients undergoing THA BACKGROUND Optimal pain treatment with minimal side-effects is essential for early mobility and recovery in patients undergoing total hip arthroplasty . We investigated the analgesic effect of pregabalin and dexamethasone in this surgical procedure . METHODS One hundred and twenty patients were r and omly allocated to either Group A ( placebo ) , Group B ( pregabalin 300 mg ) , or Group C ( pregabalin 300 mg+dexamethasone 8 mg ) . The medication and acetaminophen 1 g were given before operation . Spinal anaesthesia was performed . Postoperative pain treatment was with acetaminophen 1 g three times daily and patient-controlled i.v morphine , 2.5 mg bolus . Nausea was treated with ondansetron . Morphine consumption , pain intensity at rest and during mobilization , nausea and vomiting , sedation , dizziness , and consumption of ondansetron were recorded 2 , 4 , and 24 h after operation . P<0.05 was considered statistically significant . RESULTS Twenty-four hour morphine consumption was significantly reduced in Groups B [ mean ( SD ) 24 ( 14 ) mg ] and C [ 25 ( 19 ) mg ] compared with Group A [ 47 ( 28 ) mg ] . Vomiting was reduced in Group C compared with Group B ( P=0.03 ) . Sedation was significantly increased in Group B compared with the other groups . CONCLUSIONS Pregabalin result ed in a 50 % reduction in 24 h postoperative morphine requirements . This was not associated with a reduced incidence of nausea or vomiting . Pregabalin result ed in increased levels of sedation . Combining pregabalin and dexamethasone provided no additional effects on pain or opioid requirements Ketamine and pregabalin each provide postoperative analgesia , although the combination has yet to be evaluated . One hundred and forty‐two patients undergoing total hip arthroplasty were r and omly assigned to receive ketamine alone , pregabalin alone , ketamine and pregabalin combined , or placebo . Pain scores at rest and on movement , morphine consumption , side‐effects , pressure pain thresholds and secondary hyperalgesia were evaluated . Mean ( SD ) total 48‐h morphine use was reduced in patients given ketamine alone ( 52 ( 22 ) mg ) and pregabalin alone ( 44 ( 20 ) mg ) compared with placebo ( 77 ( 36 ) mg ) p < 0.001 . Morphine use was further reduced in patients given both ketamine and pregabalin ( 38 ( 19 ) mg ) with an interaction between ketamine and pregabalin ( ANOVA factorial ; p = 0.028 ) . Secondary hyperalgesia was reduced by ketamine . There were no differences between groups in pain scores after surgery , pressure pain thresholds or side‐effects . The combination of pregabalin and ketamine has a small , beneficial clinical effect UNLABELLED We assessed the analgesic efficacy of postoperative epidural ropivacaine 0.1 % with and without sufentanil 1 microgram/mL in this prospect i ve , r and omized , single-blinded study of 30 ASA physical status I-III patients undergoing elective total hip replacement . Lumbar epidural block using 0.75 % ropivacaine was combined with either propofol sedation or general anesthesia for surgery . After surgery , the epidural infusion was commenced . Fifteen patients in each group received either an epidural infusion of 0.1 % ropivacaine with 1 microgram/mL sufentanil ( R + S ) or 0.1 % ropivacaine without sufentanil ( R ) at a rate of 5 - 9 mL/h . All patients had access to i.v . piritramide via a patient-controlled analgesia device . The R + S group consumed six times less piritramide over a 48-h infusion period than the R group ( median 12.7 vs 73.0 mg ; P < 0.001 ) . Motor block was negligible for the study duration in both groups . Patient satisfaction was excellent . The incidence of adverse events , such as nausea , was similar . We conclude that a continuous epidural infusion of 0.1 % ropivacaine with 1 microgram/mL sufentanil is more effective than ropivacaine alone in treating pain after elective hip replacement without motor block . IMPLICATION S This is the first r and omized study comparing the efficacy of the epidural combination of ropivacaine 0.1 % and sufentanil 1 microgram/mL versus plain ropivacaine 0.1 % in treating pain after hip replacement . We found that ropivacaine 0.1 % and sufentanil 1 microgram/mL led to a sixfold reduction in opioid requirements after total hip replacement by producing a negligible motor block Background The usefulness of peripheral nerve blockade in the anesthetic management of hip surgery has not been clearly established . Because sensory afferents from the hip include several branches of the lumbar plexus , the authors hypothesized that a lumbar plexus block could reduce pain from a major hip procedure . Methods In a double-blind prospect i ve trial , 60 patients undergoing total hip arthroplasty were r and omized to receive general anesthesia with ( plexus group , n = 30 ) or without ( control group , n = 30 ) a posterior lumbar plexus block . The block was performed after induction using a nerve stimulator , and 0.4 ml/kg bupivacaine , 0.5 % , with epinephrine was injected . General anesthesia was st and ardized , and supplemental fentanyl was administered per hemodynamic guidelines . Postoperative pain and patient-controlled intravenous morphine use were serially assessed for 48 h. Results The proportion of patients receiving supplemental fentanyl intraoperatively was more than 3 times greater in the control group ( 20 of 30 vs. 6 of 29 , P = 0.001 ) . In the postanesthesia care unit , a greater than fourfold reduction in pain scores was observed in the plexus group ( visual analogue scale [ VAS ] pain score at arrival 1.3 ± 2 vs. 5.6 ± 3 , P < 0.001 ) , and “ rescue ” morphine boluses ( administered if VAS > 3 ) were administered 10 times less frequently ( in 2 of 28 vs. in 22 of 29 patients , P < 0.0001 ) . Pain scores and morphine consumption remained significantly lower in the plexus group until 6 h after r and omization ( VAS at 6 h , 1.4 ± 1.3 vs. 2.4 ± 1.4 , P = 0.007 ; cumulative morphine at 6 h , 5.6 ± 4.7 vs. 12.6 ± 7.5 mg , P < 0.0001 ) . Operative and postoperative ( 48 h ) blood loss was modestly decreased in the treated group . Epidural-like distribution of anesthesia occurred in 3 of 28 plexus group patients , but no other side-effects were noted . Conclusions Posterior lumbar plexus block provides effective analgesia for total hip arthroplasty , reducing intra- and postoperative opioid requirements . Moreover , blood loss during and after the procedure is diminished . Epidural anesthetic distribution should be anticipated in a minority of cases Objective : Magnesium has been used as an adjuvant by various routes , including intravenous , intrathecal , and epidural in different dosage regimens . The effect of single bolus dose of magnesium as an adjuvant to fentanyl for postoperative analgesia has not been studied . This prospect i ve r and omized controlled trial was done to evaluate the efficacy of single bolus administration of magnesium epidurally as an adjuvant to epidural fentanyl for postoperative analgesia in patients undergoing total hip replacement under combined spinal epidural anesthesia . Methods : Sixty patients received combined spinal – epidural anesthesia with 2 mL of 0.5 % hyperbaric bupivacaine intrathecally . After the surgery , patients were r and omized into Group F [ epidural fentanyl ( 1 μg/kg ) in 10 mL saline ] and Group FM [ epidural magnesium ( 75 mg ) along with fentanyl ( 1 μg/kg ) in 10 mL saline ] . Supplementary analgesia was provided by 50 mg intravenous tramadol if Verbal Rating Score ( VRS ) > 4 . Patient 's first analgesic requirement and duration of analgesia were recorded . Results : The duration of analgesia was significantly longer for Group FM , 340±28.8 min , compared with Group F , 164±17.1 min ( P=0.001 ) . The frequency of rescue analgesics required in 24-h postoperative period in Group FM ( 2.3±0.5 ) was significantly less than that in Group F ( 4.3±0.5 ) ( P=0.001 ) . VRS was significantly lower in Group FM up to 4 h in the postoperative period ( P=0.001 ) . Bromage scale was statistically insignificant at all points of time . Conclusions : The administration of magnesium ( 75 mg ) as an adjuvant to epidural fentanyl ( 1 μg/ kg ) for postoperative analgesia results in significantly lower VRS with prolonged duration of analgesia as compared with epidural fentanyl ( 1 μg/kg ) alone . Concomitant administration of magnesium also reduces the requirement of breakthrough analgesics with no increased incidence of side effects AIM Over the last several years , significant efforts have been directed towards improving the quality of postoperative pain management . As data are lacking on the organization and quality of these services in Italy , we surveyed current Italian practice s. METHODS A 16-item question naire was r and omly supplied to 650 anesthesiologists attending the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care Medicine ( SIAARTI ) National Congress in 2006 . The survey requested information concerning their current practice s in analgesic techniques , use of guidelines , educational programs , availability of an Acute Pain Service ( APS ) , and existing barriers to optimal postoperative pain management . RESULTS Based on 588 respondents , a sample of 163 hospitals was analyzed ( 24.4 % of Italian public hospitals ) ; 41.7 % of the surveyed hospitals had an organized APS . University and teaching hospitals had an organized APS more frequently than did other hospitals ( P<0.02 ) . Continuous intravenous analgesia using elastomeric infusion systems was the most commonly used analgesic technique , performed in 44 % of the treated patients . The frequency of both intravenous patient-controlled analgesia and epidural techniques was extremely low ( 5 % and 13 % , respectively ) . The main reasons given for suboptimal pain relief were inadequate training of surgeons and nurses ( 44.3 % ) , poor organization ( 29.9 % ) , and lack of equipment ( 21.5 % ) . A total of 51.2 % of the respondents would like to have a dedicated anesthesiologist assigned on a daily rotational basis to postoperative pain management . CONCLUSIONS A comparison to international survey data showed that postoperative pain management in Italy is still below the European st and ards . Additional efforts to overcome these hurdles and to reach an acceptable level of quality are required & NA ; Surveys evaluating pain in hospitals keep on showing that postoperative pain ( POP ) remains undertreated . At the time when guidelines are edited and organisational changes are implemented , more recent data are necessary to check the impact of these measures on daily practice and needs for improvement . This prospect i ve , cross‐sectional , observational , multi‐centre practice survey was performed in 2004–2005 in 7 European countries . It was conducted in surgical wards of a r and omised sample of hospitals . Data on POP management practice s following surgery in adult in‐ patients were collected anonymously via a st and ardised multiple choice question naire . Among 1558 question naires received from 746 European hospitals , 59 % were provided by anaesthetists and 41 % by surgeons . There are no regular on‐site staff training programmes on POP management in the institution for 34 % of the respondents , patients are systematic ally provided with POP information before surgery for 48 % of respondents ; balanced analgesia following major surgery and regular administration of analgesics are largely used ; 25 % of respondents have specific written POP management protocol s for all patients in their ward ; 34 % of respondents say that pain is not assessed and 44 % say that pain scores are documented in the patient ’s chart . This largest ever performed survey confirms the extensive body of evidence that current POP management remains suboptimal and identifies needs for improvement on European surgical wards . However , the wide use of balanced analgesia and the regular administration of analgesics are indicators of ongoing change BACKGROUND Continuous femoral or lumbar plexus blocks have been demonstrated to provide effective postoperative analgesia of the lower extremity following total joint arthroplasty . The purpose of this study was to compare these two techniques when used with intravenous patient-controlled analgesia and the use of patient-controlled analgesia alone for postoperative pain management following unilateral primary hip arthroplasty . METHODS Two hundred and twenty-five patients undergoing unilateral total hip arthroplasty for a diagnosis of osteoarthritis were r and omly allocated into one of three postoperative treatment groups : continuous lumbar plexus block with patient-controlled analgesia , continuous femoral block with patient-controlled analgesia , and patient-controlled analgesia alone . Scores on a visual analog pain scale administered during physiotherapy twenty-four hours postoperatively were used as the primary outcome measured . Secondary outcomes included scores on a visual analog pain scale at rest , hydromorphone consumption , opioid-related side effects , complications , sensory and motor blockade , and patient satisfaction . RESULTS Continuous lumbar plexus block significantly reduced pain scores during physiotherapy on postoperative day 1 ( p < 0.0001 ) and day 2 ( p < 0.0001 ) compared with either continuous femoral block or patient-controlled analgesia alone . There were no significant differences for pain at rest between the two regional analgesic techniques . Both regional anesthesia techniques significantly reduced total hydromorphone consumption ( p < 0.05 ) and delirium ( disorientation to time and /or place ) compared with patient-controlled analgesia alone ( p < 0.023 ) . In addition , the use of continuous lumbar plexus block was associated with fewer patients with opioid-related side effects ( p < 0.05 ) , greater distances walked ( p < 0.05 ) , and enhanced patient satisfaction ( p < 0.05 ) compared with the use of a continuous femoral nerve block with patient-controlled analgesia or with patient-controlled analgesia alone . CONCLUSIONS Continuous lumbar plexus and femoral blocks significantly reduce the need for opioids and decrease related side effects . Continuous lumbar plexus block is a more effective analgesic modality than is a continuous femoral block or patient-controlled intravenous administration of hydromorphone alone during physical therapy following primary unilateral total hip arthroplasty Background : The perioperative effects of intrathecal and epidural clonidine combined with local anesthetic were evaluated in 60 patients undergoing hip arthroplasty OBJECTIVES To analyze the analgesic efficacy , safety and side effects of subarachnoid morphine ( 0.1 mg ) with bupivacaine in patients undergoing total hip arthroplasty . PATIENTS AND METHODS Thirty patients scheduled for total hip replacement under spinal anesthesia with bupivacaine were r and omly assigned to two groups according to whether local anesthetic with 0.1 mg subarachnoid morphine was also provided or not ( group M [ n = 15 ] and group S ņ = 15 [ , respectively ) . Top-up analgesia with morphine was available through a patient-controlled device . Postoperative pain was assessed on a visual analogue scale ( VAS ) and consumption of intravenous morphine in the first 48 hours after surgery was recorded . RESULTS VAS scores ( mean + /- SD ) were significantly lower in the first six hours in group M , but no differences between the two groups were observed thereafter . Total consumption of morphine at 48 hours was much lower in group M ( 6.80 + /- 7.74 mg ) than in group S ( 31.38 + /- 13.17 mg ) . The incidence of nausea was high in both groups ( 46 % ) . Slight pruritus affected 26.6 % of patients in group M. Urinary retention necessitating temporary placement of a catheter was observed only in group M , where the incidence was 35.7 % . No cases of respiratory depression occurred . Drowsiness was observed in 26.6 % of patients in group S in comparison with 6.6 % in group M. CONCLUSIONS Combining 0.1 mg morphine and bupivacaine for total spinal anesthesia during hip arthroplasty significantly decreased the consumption of intravenous morphine during the first 48 hours after surgery . No respiratory depression occurred and the only side effects were urinary retention and mild pruritus and drowsiness A r and omized double-blind controlled study was undertaken to assess the analgesic efficacy of piroxicam . Twenty-four patients underwent total hip replacement under spinal anaesthetic ; after operation , they received a 3-day course of either placebo ( n = 12 ) or piroxicam ( n = 12 ) . Adequate analgesia was provided for 48 h by a patient-controlled analgesia system delivering morphine . Patients receiving piroxicam required 50 % less morphine than the control group ( 38 mg compared with 76 mg ( P less than 0.002 ] . This technique was tolerated well and there were no significant side effects Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride ( 75 micro gram ) and morphine sulfate ( 0.5 mg ) was compared with analgesia produced after either intrathecal morphine ( 0.5 mg ) or 0.9 % sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia . Patient-controlled morphine requirements were significantly reduced ( P < 0.001 ) postoperation by both clonidine/morphine ( median 5 mg/24 h ) and morphine ( median 7 mg/24 h ) compared with control ( saline ) ( median 28 mg/24 h ) . However , no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone . Visual analog pain scores , although good in all groups at all times , were significantly poorer in the control group at 2 h ( P < 0.04 ) and 4 h ( P < 0.001 ) after operation compared with both treatment groups , and significantly poorer than the clonidine/morphine group at 6 h ( P < 0.002 ) and 24 h ( P < 0.009 ) postoperation . Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups ( P < 0.001 ) between 2 and 5 h after operation . The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group . ( Anesth Analg 1995;80:86 - 91 Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale BACKGROUND : Parecoxib , a selective cyclooxygenase-2 inhibitor , may reduce postoperative pain without increasing bleeding when administered before surgery . METHODS : We r and omly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule : 1 ) placebo at induction , at wound closure , and 12 h after induction ( control ) ; 2 ) parecoxib 40 mg at induction , placebo at wound closure , and parecoxib 40 mg 12 h after induction ( pre ) ; or , 3 ) placebo at induction , parecoxib 40 mg at wound closure , and parecoxib 40 mg 12 h after induction ( post ) . Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale . Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated . RESULTS : Postoperative pain scores were less in the pre and post groups than in the control group . Postoperative bleeding was similar in the three groups . There were no significant differences between the pre and post groups , nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib . Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group ( 14.2 ± 2.0 , and 15.7 ± 2.0 , vs 20.4 ± 2.3 mg ) , although the trend was only significant ( P < 0.05 ) in the pre group . The first pain score was also reduced in the pre and post groups compared to the control group ( 56.1 ± 7.5 and 64.2 ± 7.0 vs 78.3 ± 5 ) , but this was also only significant for the pre group ( P = 0.001 ) . The delay for first analgesic dem and was increased for both the pre and post group compared to the control group ( 38 ± 9 and 28.2 ± 6.6 vs 18 ± 6 min ) but , again , this was only significant for the pre group ( P = 0.05 ) . Twenty-four hour consumption of morphine was similar in the pre ( 26 ± 12 mg ) and post groups ( 25 ± 13 mg ) ; both were significantly less than in the control group ( 47 ± 27 mg , P < 0.001 ) . CONCLUSIONS : Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia . There was a trend towards improved analgesia immediately after surgery with preincision administration , consistent with the expected time course of nonsteroidal antiinflammatory drug ’s effect . Perioperative parecoxib administration , consisting of two injections spaced 12 h apart , improved postoperative analgesia over the first 24 h without increasing bleeding Clinical studies on pre‐emptive analgesia have produced inconsistent results . We conducted a clinical study investigating the effect of long‐lasting pre‐emptive epidural analgesia on consumption of analgesics and acute pain . Forty‐two patients scheduled for elective hip replacement for osteo‐arthritis were r and omly assigned to receive , on the day before operation , either 5 ml.h−1 ropivacaine 0.2 % ( study group , n = 21 ) or 5 ml.h−1 saline ( control group , n = 21 ) . Postoperative analgesia was achieved in both groups by patient‐controlled epidural analgesia ( PCEA ) with ropivacaine 0.2 % . The main outcome measure was consumption of local anaesthetics . Additional parameters included visual analogue pain scale ( VAS ) scores , consumption of rescue analgesics , requests for PCEA boluses , and side‐effects . The pre‐operative parameters and pain scores were similar in the two groups . Epidural blocks provided sufficient operative analgesia in all patients . Pre‐emptive analgesia was continued for 11–20 h and led to significantly decreased pain scores before surgery . The consumption of local anaesthetics was decreased postoperatively in the study group ( 194 mg vs. 284 mg in the postoperative period ) . Furthermore , bolus requests occurred more frequently in the control group . VAS scores did not differ significantly between groups . Long‐lasting ‘ pre‐emptive ’ epidural analgesia decreases postoperative pain with improved pain control We assessed whether a modified fascia iliaca compartment block in unilateral total hip arthroplasty provides a morphine-sparing effect in the first 24 hours . This involved a r and omised , double blind study of 44 patients . Both groups received a modified fascia iliaca block with the trial group receiving 30 ml 0.5 % bupivacaine with 1:200,000 adrenaline , 150 μg clonidine and 9 ml 0.9 % > saline and the control group receiving 40 ml 0.9 % saline . Otherwise both groups received identical care with a subarachnoid block for operative anaesthesia . Patient-controlled morphine analgesia was commenced postoperatively and data were collected at three , six , 12 and 24 hours post commencement of surgery . We found that the trial group used less morphine at 12 and 24 hours ( P < 0.001 ) . The median morphine usage at 24 hours was 37.5 mg in the control patients and 22 mg in the trial patients . Pain scores were similar between groups . We conclude that a modified fascia iliaca compartment block has a significant morphine-sparing effect in unilateral total hip arthroplasty We have studied the anaesthetic and analgesic properties of intrathecal clonidine and intrathecal morphine in patients undergoing total hip replacement under spinal anaesthesia . After routine spinal anaesthesia with 0.5 % plain bupivacaine 2.75 ml , patients were allocated r and omly to receive intrathecal clonidine , morphine or saline ( control ) as adjuvant to the bupivacaine . Postoperative analgesic effects were measured by consumption of morphine via patient-controlled analgesia and visual analogue pain scores . Both intrathecal clonidine and intrathecal morphine prolonged the time to first analgesia compared with saline ( mean 278 ( SD 93.2 ) min , 498 ( 282.4 ) min and 54 ( 61.9 ) min , respectively ) ( P < 0.001 ) . Total morphine consumption on the first night after operation was significantly less in the intrathecal morphine group . There were no differences between the clonidine and the control group . Intrathecal clonidine prolonged the duration of spinal analgesia , but was markedly inferior to the intrathecal morphine in providing subsequent postoperative analgesia & NA ; This study evaluated the pre‐emptive analgesic effect of intravenous ( i.v . ) ketorolac ( KET ) for total hip replacement ( THR ) . Sixty patients who underwent surgery for THR under general anesthesia were r and omly allocated to 3 groups . Two i.v . injections were administered : one before induction and one after surgery . The patients were studied prospect ively in a double‐blind manner . The control group ( CONT ; n = 20 ) received 2 ml of normal saline ( NS ) for both injections . The pre‐operative KET group ( PRE ; n = 20 ) received 60 mg of KET and then 2 ml of NS . The postoperative KET group ( POST ; n = 20 ) received 2 ml of NS and then 60 mg Of KET . General anesthesia was st and ardized with a intra‐operative cumulated dose of fentanyl limited to 4&mgr;g/kg . In the recovery room ( RR ) , pain was controlled with an i.v . titration of morphine ; thereafter , on the surgical ward , patients used a patient‐controlled analgesia ( PCA ) pump ( Abbott ) . Pain was evaluated with a visual analogue scale ( VAS ) at rest and movement in the RR , then every hour for 6 h and every 6 h for 2 days . The side effects monitored were : sedation , respiratory depression , nausea , perioperative bleeding . The patients and surgery were similar for the 3 groups . Upon arrival in the RR , VAS scores taken at rest and at movement were lower for the PRE group than for the CONT and POST groups . Otherwise , VAS scores were similar in all 3 groups . The cumulative dose of morphine in the PRE group was lower than that for the CONT and POST groups from 0 to 6 h. However , the hourly consumption of morphine after titration was similar in all 3 groups for the entire study . Four patients , 2 in the PRE and 2 in the POST group had abnormal bleeding . In this study 60 mg of pre‐operative KET had greater analgesic effect than the same dose administered at skin closure . This beneficial effect was important in the immediate postoperative period but was not sustained with time STUDY OBJECTIVE To determine the amount of change in pain severity , as measured by a visual analog scale , that constitutes a minimum clinical ly significant difference . METHODS Patients 18 years of age or older who presented with acute pain result ing from trauma were enrolled in this prospect i ve , descriptive study . The setting was an urban county hospital emergency department with a Level 1 trauma center . In the course of a brief interview , patients were asked to indicate their current pain severity with a single mark through a st and ard 100-mm visual analog scale . At intervals of 20 minutes for the next 2 hours , patients were asked to repeat this measurement and , in addition , to contrast their present pain severity with that at the time of the previous measurement . They were to indicate whether they had " much less , " " a little less , " " about the same , " " a little more , " or " much more " pain . All contrasts were made without reference to prior visual analog scale measurements . A maximum of six measurements of pain change were recorded per patient . Measurements ended when the patient left the ED or when the patient reported a pain score of zero . The minimum clinical ly significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain . RESULTS Forty-eight subjects were enrolled , and 248 pain contrasts were recorded . Of these contrasts , 41 were rated as a little less and 39 as a little more pain . The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm ( 95 % confidence interval , 10 to 17 mm ) . CONCLUSION The minimum clinical ly significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm . Studies of pain experience that report less than a 13-mm change in pain severity , although statistically significant , may have no clinical importance |
2,633 | 28,912,963 | O-6-methylguanine-DNA methyltransferase status predicts a more favourable response to treatment and is thus a predictive marker .
Based on genomic aberrations , Verhaak et al have suggested a division of GBM into three subgroups , namely , proneural , classical and mesenchymal , which could be meaningful in the clinic and could help guide and differentiate treatment decisions according to the specific subgroup . | Despite decades of intense research , the complex biology of glioblastoma ( GBM ) is not completely understood .
Progression-free survival and overall survival have remained unchanged since the implementation of the STUPP regimen in 2005 with concomitant radio-/chemotherapy and adjuvant chemotherapy with temozolomide .
In the context of Hanahan and Weinberg 's six hallmarks and two emerging hallmarks of cancer , we discuss up-to- date status and recent research in the biology of GBM . | PURPOSE A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells ( αDC1 ) loaded with synthetic peptides for glioma-associated antigen ( GAA ) epitopes and administration of polyinosinic-polycytidylic acid [ poly(I : C ) ] stabilized by lysine and carboxymethylcellulose ( poly-ICLC ) in HLA-A2(+ ) patients with recurrent malignant gliomas . GAAs for these peptides are EphA2 , interleukin (IL)-13 receptor-α2 , YKL-40 , and gp100 . PATIENTS AND METHODS Twenty-two patients ( 13 with glioblastoma multiforme [ GBM ] , five with anaplastic astrocytoma [ AA ] , three with anaplastic oligodendroglioma [ AO ] , and one with anaplastic oligoastrocytoma [ AOA ] ) received at least one vaccination , and 19 patients received at least four vaccinations at two αDC1 dose levels ( 1 × or 3 × 10(7)/dose ) at 2-week intervals intranodally . Patients also received twice weekly intramuscular injections of 20 μg/kg poly-ICLC . Patients who demonstrated positive radiologic response or stable disease without major adverse events were allowed to receive booster vaccines . T-lymphocyte responses against GAA epitopes were assessed by enzyme-linked immunosorbent spot and HLA-tetramer assays . RESULTS The regimen was well-tolerated . The first four vaccines induced positive immune responses against at least one of the vaccination-targeted GAAs in peripheral blood mononuclear cells in 58 % of patients . Peripheral blood sample s demonstrated significant upregulation of type 1 cytokines and chemokines , including interferon-α and CXCL10 . Nine ( four GBM , two AA , two AO , and one AOA ) achieved progression-free status lasting at least 12 months . One patient with recurrent GBM demonstrated sustained complete response . IL-12 production levels by αDC1 positively correlated with time to progression . CONCLUSION These data support safety , immunogenicity , and preliminary clinical activity of poly-ICLC-boosted αDC1-based vaccines PURPOSE Glioblastomas are notorious for resistance to therapy , which has been attributed to DNA-repair proficiency , a multitude of deregulated molecular pathways , and , more recently , to the particular biologic behavior of tumor stem-like cells . Here , we aim ed to identify molecular profiles specific for treatment resistance to the current st and ard of care of concomitant chemoradiotherapy with the alkylating agent temozolomide . PATIENTS AND METHODS Gene expression profiles of 80 glioblastomas were interrogated for associations with resistance to therapy . Patients were treated within clinical trials testing the addition of concomitant and adjuvant temozolomide to radiotherapy . RESULTS An expression signature dominated by HOX genes , which comprises Prominin-1 ( CD133 ) , emerged as a predictor for poor survival in patients treated with concomitant chemoradiotherapy ( n = 42 ; hazard ratio = 2.69 ; 95 % CI , 1.38 to 5.26 ; P = .004 ) . This association could be vali date d in an independent data set . Provocatively , the HOX cluster was reminiscent of a " self-renewal " signature ( P = .008 ; Gene Set Enrichment Analysis ) recently characterized in a mouse leukemia model . The HOX signature and EGFR expression were independent prognostic factors in multivariate analysis , adjusted for the O-6-methylguanine-DNA methyltransferase ( MGMT ) methylation status , a known predictive factor for benefit from temozolomide , and age . Better outcome was associated with gene clusters characterizing features of tumor-host interaction including tumor vascularization and cell adhesion , and innate immune response . CONCLUSION This study provides first clinical evidence for the implication of a " glioma stem cell " or " self-renewal " phenotype in treatment resistance of glioblastoma . Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection BACKGROUND Concurrent treatment with temozolomide and radiotherapy followed by maintenance temozolomide is the st and ard of care for patients with newly diagnosed glioblastoma . Bevacizumab , a humanized monoclonal antibody against vascular endothelial growth factor A , is currently approved for recurrent glioblastoma . Whether the addition of bevacizumab would improve survival among patients with newly diagnosed glioblastoma is not known . METHODS In this r and omized , double-blind , placebo-controlled trial , we treated adults who had central ly confirmed glioblastoma with radiotherapy ( 60 Gy ) and daily temozolomide . Treatment with bevacizumab or placebo began during week 4 of radiotherapy and was continued for up to 12 cycles of maintenance chemotherapy . At disease progression , the assigned treatment was revealed , and bevacizumab therapy could be initiated or continued . The trial was design ed to detect a 25 % reduction in the risk of death and a 30 % reduction in the risk of progression or death , the two co primary end points , with the addition of bevacizumab . RESULTS A total of 978 patients were registered , and 637 underwent r and omization . There was no significant difference in the duration of overall survival between the bevacizumab group and the placebo group ( median , 15.7 and 16.1 months , respectively ; hazard ratio for death in the bevacizumab group , 1.13 ) . Progression-free survival was longer in the bevacizumab group ( 10.7 months vs. 7.3 months ; hazard ratio for progression or death , 0.79 ) . There were modest increases in rates of hypertension , thromboembolic events , intestinal perforation , and neutropenia in the bevacizumab group . Over time , an increased symptom burden , a worse quality of life , and a decline in neurocognitive function were more frequent in the bevacizumab group . CONCLUSIONS First-line use of bevacizumab did not improve overall survival in patients with newly diagnosed glioblastoma . Progression-free survival was prolonged but did not reach the prespecified improvement target . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00884741 . ) The objective of the study was to investigate the predictive value of various clinical , biochemical , and histopathological parameters , with special emphasis on the expression of the retinoblastoma protein ( pRB ) , on the radiation response in bladder cancer . In order to obtain a truly objective response measure , patients receiving preoperative radiotherapy followed by cystectomy were studied . Pretreatment tumour sample s and clinical data from 108 consecutive patients were collected . End points were complete response ( CR ) to radiotherapy , relapse-free survival time and overall survival time . Expression of pRB was assessed by immunohistochemical staining as present or absent . Complete response to radiotherapy was obtained in 42 of 106 evaluable patients ( 40 % ) . Predictive for CR to radiotherapy , in univariate analysis , was transurethral resection ( as opposed to biopsy ) , B-haemoglobin , no upper urinary retention , and loss of pRB staining . Loss of pRB staining was the strongest independent predictor of radiation response in multivariate logistic regression analysis and absence of upper urinary retention was the only other significant factor . Loss of pRB was the only parameter showing statistically significant , independent association with relapse-free survival , whereas B-haemoglobin was also independently associated with overall survival . Loss of pRB expression seems to indicate a phenotype displaying enhanced radiosensivity and may be of benefit by denoting patients who would selectively benefit from a treatment schedule containing radiotherapy BACKGROUND In 2004 , a r and omised phase III trial by the European Organisation for Research and Treatment of Cancer ( EORTC ) and National Cancer Institute of Canada Clinical Trials Group ( NCIC ) reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy . We report the final results with a median follow-up of more than 5 years . METHODS Adult patients with newly diagnosed glioblastoma were r and omly assigned to receive either st and ard radiotherapy or identical radiotherapy with concomitant temozolomide followed by up to six cycles of adjuvant temozolomide . The methylation status of the methyl-guanine methyl transferase gene , MGMT , was determined retrospectively from the tumour tissue of 206 patients . The primary endpoint was overall survival . Analyses were by intention to treat . This trial is registered with Clinical trials.gov , number NCT00006353 . FINDINGS Between Aug 17 , 2000 , and March 22 , 2002 , 573 patients were assigned to treatment . 278 ( 97 % ) of 286 patients in the radiotherapy alone group and 254 ( 89 % ) of 287 in the combined-treatment group died during 5 years of follow-up . Overall survival was 27.2 % ( 95 % CI 22.2 - 32.5 ) at 2 years , 16.0 % ( 12.0 - 20.6 ) at 3 years , 12.1 % ( 8.5 - 16.4 ) at 4 years , and 9.8 % ( 6.4 - 14.0 ) at 5 years with temozolomide , versus 10.9 % ( 7.6 - 14.8 ) , 4.4 % ( 2.4 - 7.2 ) , 3.0 % ( 1.4 - 5.7 ) , and 1.9 % ( 0.6 - 4.4 ) with radiotherapy alone ( hazard ratio 0.6 , 95 % CI 0.5 - 0.7 ; p<0.0001 ) . A benefit of combined therapy was recorded in all clinical prognostic subgroups , including patients aged 60 - 70 years . Methylation of the MGMT promoter was the strongest predictor for outcome and benefit from temozolomide chemotherapy . INTERPRETATION Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up . A few patients in favourable prognostic categories survive longer than 5 years . MGMT methylation status identifies patients most likely to benefit from the addition of temozolomide . FUNDING EORTC , NCIC , Nélia and Amadeo Barletta Foundation , Schering-Plough BACKGROUND Epigenetic silencing of the MGMT ( O6-methylguanine-DNA methyltransferase ) DNA-repair gene by promoter methylation compromises DNA repair and has been associated with longer survival in patients with glioblastoma who receive alkylating agents . METHODS We tested the relationship between MGMT silencing in the tumor and the survival of patients who were enrolled in a r and omized trial comparing radiotherapy alone with radiotherapy combined with concomitant and adjuvant treatment with temozolomide . The methylation status of the MGMT promoter was determined by methylation-specific polymerase-chain-reaction analysis . RESULTS The MGMT promoter was methylated in 45 percent of 206 assessable cases . Irrespective of treatment , MGMT promoter methylation was an independent favorable prognostic factor ( P<0.001 by the log-rank test ; hazard ratio , 0.45 ; 95 percent confidence interval , 0.32 to 0.61 ) . Among patients whose tumor contained a methylated MGMT promoter , a survival benefit was observed in patients treated with temozolomide and radiotherapy ; their median survival was 21.7 months ( 95 percent confidence interval , 17.4 to 30.4 ) , as compared with 15.3 months ( 95 percent confidence interval , 13.0 to 20.9 ) among those who were assigned to only radiotherapy ( P=0.007 by the log-rank test ) . In the absence of methylation of the MGMT promoter , there was a smaller and statistically insignificant difference in survival between the treatment groups . CONCLUSIONS Patients with glioblastoma containing a methylated MGMT promoter benefited from temozolomide , whereas those who did not have a methylated MGMT promoter did not have such a benefit BACKGROUND The epidermal growth factor receptor variant III deletion mutation , EGFRvIII , is expressed in ∼30 % of primary glioblastoma and linked to poor long-term survival . Rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin . In previous phase II trials ( ACTIVATE/ACT II ) , rindopepimut was well tolerated with robust EGFRvIII-specific immune responses and promising progression-free and overall survival . This multicenter , single-arm phase II clinical trial ( ACT III ) was performed to confirm these results . METHODS Rindopepimut and st and ard adjuvant temozolomide chemotherapy were administered to 65 patients with newly diagnosed EGFRvIII-expressing ( EGFRvIII+ ) glioblastoma after gross total resection and chemoradiation . RESULTS Progression-free survival at 5.5 months ( ∼8.5 mo from diagnosis ) was 66 % . Relative to study entry , median overall survival was 21.8 months , and 36-month overall survival was 26 % . Extended rindopepimut vaccination ( up to 3.5 + years ) was well tolerated . Grade s 1 - 2 injection site reactions were frequent . Anti-EGFRvIII antibody titers increased ≥4-fold in 85 % of patients , and increased with duration of treatment . EGFRvIII was eliminated in 4/6 ( 67 % ) tumor sample s obtained after > 3 months of therapy . CONCLUSIONS This study confirms , in a multicenter setting , the preliminary results seen in previous phase II trials of rindopepimut . A pivotal , double-blind , r and omized , phase III trial ( " ACT IV " ) is under way |
2,634 | 28,349,514 | Due to the limited number of included trials , short-term treatment , and inadequate reporting , we were unable to draw any conclusions about the efficacy or safety of L-carnitine for cognitive enhancement in healthy adults . | BACKGROUND Safe interventions to enhance cognitive function in cognitively healthy people would be very valuable for several reasons , including a better quality of life and professional success .
While L-carnitine has been reported to enhance cognitive function in some conditions , its efficacy is disputed .
The evidence of its efficacy for cognitively healthy people has not previously been systematic ally review ed .
OBJECTIVES To assess the efficacy and safety of L-carnitine for the enhancement of cognitive function in people without cognitive impairment .
We used the search terms ' L-carnitine ' or ' acetyl-L-carnitine ' or ' propionyl-L-carnitine ' or ' ALC ' or ' PLC ' or ' ALCAR ' or ' ALPAR ' . | We examined the effects of citric acid and l-carnitine administration on physical fatigue . In a double-blind , placebo-controlled , 3-way crossover study , 18 healthy volunteers were r and omized to oral citric acid ( 2,700 mg/day ) , l-carnitine ( 1,000 mg/day ) , or placebo for 8 days . The fatigue-inducing physical task consisted of workload trials on a cycle ergometer at fixed workloads for 2 h on 2 occasions . Before the physical load , salivary chromogranin A , measured as a physiological stress marker , was lower in the group given citric acid than in the group given placebo . Also , after the physical load , the subjective feeling of fatigue assessed with a visual analogue scale was lower in the citric acid group than in the placebo group . In contrast , l-carnitine had no effect on chromogranin A or subjective fatigue . These results suggest that citric acid reduces physiological stress and attenuates physical fatigue , whereas l-carnitine does not Background The purpose of this study was to examine the effect of acute and prolonged ( 4-weeks ) ingestion of a supplement design ed to improve reaction time and subjective measures of alertness , energy , fatigue , and focus compared to placebo . Methods Nineteen physically-active subjects ( 17 men and 2 women ) were r and omly assigned to a group that either consumed a supplement ( 21.1 ± 0.6 years ; body mass : 80.6 ± 9.4 kg ) or placebo ( 21.3 ± 0.8 years ; body mass : 83.4 ± 18.5 kg ) . During the initial testing session ( T1 ) , subjects were provided 1.5 g of the supplement ( CRAM ; α-glycerophosphocholine , choline bitartrate , phosphatidylserine , vitamins B3 , B6 , and B12 , folic acid , L-tyrosine , anhydrous caffeine , acetyl-L-carnitine , and naringin ) or a placebo ( PL ) , and rested quietly for 10-minutes before completing a question naire on subjective feelings of energy , fatigue , alertness and focus ( PRE ) . Subjects then performed a 4-minute quickness and reaction test followed by a 10-min bout of exhaustive exercise . The question naire and reaction testing sequence was then repeated ( POST ) . Subjects reported back to the lab ( T2 ) following 4-weeks of supplementation and repeated the testing sequence . Results Reaction time significantly declined ( p = 0.050 ) between PRE and POST at T1 in subjects consuming PL , while subjects under CRAM supplementation were able to maintain ( p = 0.114 ) their performance . Significant performance declines were seen in both groups from PRE to POST at T2 . Elevations in fatigue were seen for CRAM at both T1 and T2 ( p = 0.001 and p = 0.000 , respectively ) , but only at T2 for PL ( p = 0.029 ) . Subjects in CRAM maintained focus between PRE and POST during both T1 and T2 trials ( p = 0.152 and p = 0.082 , respectively ) , whereas significant declines in focus were observed between PRE and POST in PL at both trials ( p = 0.037 and p = 0.014 , respectively ) . No difference in alertness was seen at T1 between PRE and POST for CRAM ( p = 0.083 ) , but a significant decline was recorded at T2 ( p = 0.005 ) . Alertness was significantly lower at POST at both T1 and T2 for PL ( p = 0.040 and p = 0.33 , respectively ) . No differences in any of these subjective measures were seen between the groups at any time point . Conclusion Results indicate that acute ingestion of CRAM can maintain reaction time , and subjective feelings of focus and alertness to both visual and auditory stimuli in healthy college students following exhaustive exercise . However , some habituation may occur following 4-weeks of supplementation BACKGROUND Centenarians are characterized by weakness , decreasing mental health , impaired mobility , and poor endurance . L-Carnitine is an important contributor to cellular energy metabolism . OBJECTIVE This study evaluated the efficacy of L-carnitine on physical and mental fatigue and on cognitive functions of centenarians . DESIGN This was a placebo-controlled , r and omized , double-blind , 2-phase study . Sixty-six centenarians with onset of fatigue after even slight physical activity were recruited to the study . The 2 groups received either 2 g levocarnitine once daily ( n = 32 ) or placebo ( n = 34 ) . Efficacy measures included changes in total fat mass , total muscle mass , serum triacylglycerol , total cholesterol , HDL cholesterol , LDL cholesterol , Mini-Mental State Examination ( MMSE ) , Activities of Daily Living , and a 6-min walking corridor test . RESULTS At the end of the study period , the levocarnitine-treated centenarians , compared with the placebo group , showed significant improvements in the following markers : total fat mass ( -1.80 compared with 0.6 kg ; P < 0.01 ) , total muscle mass ( 3.80 compared with 0.8 kg ; P < 0.01 ) , plasma concentrations of total carnitine ( 12.60 compared with -1.70 mumol ; P < 0.05 ) , plasma long-chain acylcarnitine ( 1.50 compared with -0.1 micromol ; P < 0.001 ) , and plasma short-chain acylcarnitine ( 6.0 compared with -1.50 micromol ; P < 0.001 ) . Significant differences were also found in physical fatigue ( -4.10 compared with -1.10 ; P < 0.01 ) , mental fatigue ( -2.70 compared with 0.30 ; P < 0.001 ) , fatigue severity ( -23.60 compared with 1.90 ; P < 0.001 ) , and MMSE ( 4.1 compared with 0.6 ; P < 0.001 ) . CONCLUSIONS Our study indicates that oral administration of levocarnitine produces a reduction of total fat mass , increases total muscular mass , and facilitates an increased capacity for physical and cognitive activity by reducing fatigue and improving cognitive functions Objective : To determine the efficacy of acetyl-l-carnitine ( ALCAR ) on the rate of decline in early-onset AD patients . Methods : A 1-year , multicenter , double-blind , placebo-controlled , r and omized trial was conducted . Subjects were 45 to 65 years old , with a diagnosis of probable AD according to National Institute of Neurological Communicative Disorders – Alzheimer ’s Disease and Related Disorders Association criteria and had a Mini-Mental State Examination ( MMSE ) score between 12 and 26 . They were treated with ALCAR ( 1 g tid ) or placebo . Primary outcome measures were the Alzheimer ’s Disease Assessment Scale – Cognitive Component and the Clinical Dementia Rating Scale . Secondary measures included the ADAS Non-Cognitive Subscale , the MMSE , an Activities of Daily Living Scale ( ADL ) , and a Clinician-Based Impression of Change ( CIBIC ) . Results : Two-hundred twenty-nine patients were enrolled and r and omized to drug treatment , with 117 taking placebo and 112 taking ALCAR . There were no significant differences between the two groups at baseline . For the primary outcome measures , there were no significant differences between the treatment groups on the change from baseline to endpoint in the intent-to-treat analysis . In the completer sample only , there was less deterioration in the MMSE for the ALCAR-treated subjects . There was no difference in rate of decline on the CIBIC and the ADL scale . There were no significant differences in the incidence of adverse events by treatment arm . Conclusion : Overall , in a prospect ively performed study in young-onset AD patients , ALCAR failed to slow decline . Less decline was seen on the MMSE in the completer sample only , with the difference being mediated by reducing decline in attention . A combination of ALCAR and a cholinesterase inhibitor should be tested for additivity A single-blind clinical trial was carried out on 481 subjects enrolled in 44 geriatric and neurologic units following a strict selection criteria : age , Mini Mental State Examination ( MMSE ) Global Deterioration Scale and Geriatric Depression Scale ( GDS ) . After the initial screening and enrollment , the trial was run for 150 days in four phases : phase T0 ( placebo treatment for 30 days ) , phases T1 and T2 ( L-acetylcarnitine ( LAC ) 1500 mg/day for 90 days ) , phase T3 ( further 30 days of placebo treatment ) . Drug efficacy was evaluated according to changes occurring from the beginning to the end of the tests which evaluate either whole and specific cognitive performances , or emotional-affective and relational behaviour . The outcome of phase T3 enabled the authors to estimate the possible favourable effects persisting after termination of L-acetylcarnitine therapy . The cognitive sphere evaluated by MMSE showed a significant increase in the total score at the end of LAC treatment ( p < 0.0001 ) . The R and t Memory Test also revealed that LAC treatment improved the items tested : the total score and the memory index increased significantly and the favourable effect persisted after LAC was discontinued . The emotional-affective area showed a significant improvement in the total score of the GDS after LAC therapy , and the positive results were confirmed by the Hamilton Rating Scale ( p < 0.0001 ) . The behavioural-relational aspects evaluated by the Family Stress Scale showed a significant decrease in the total score after treatment ( p < 0.0004 ) ; the same trend was observed in the scores for instability and negative feeling . No significant adverse drug reaction occurred during the trial . In conclusion , the statistical analysis of the data from this single-blind , multicentre trial of mild mental impairment in the elderly showed a significant improvement of several performances during and after LAC treatment . Other reports indicate that this drug may be effective in the treatment of dementia Twelve students with in apparent good health and fasting since the previous evening ingested 2 g of L-carnitine on one day and a placebo on another day in a single-blind trial . Six blood sample s were taken during the 24 h following the ingestion . Their blood carnitine levels increased ( the free form by 81 % , and the total by 57 % ) to a maximum at about 3.5 h and then slowly decreased . Twenty-four hours after ingestion , blood carnitine concentrations had still not returned to their initial levels . In the time interval where the decay curve approximated a single exponential , the half-life of the carnitine appeared to be of the order of 15 h. During the 24 h after the administration of the 2 g of L-carnitine , 7 % + /- 1 % of it was eliminated in the urine . This work suggest that the daily administration during a long period , of 2 g of L-carnitine guarantee in a healthy subject blood carnitine concentrations superior to the normal levels . Its remains to determine if the dose is sufficient in the case where L-carnitine is given to ameliorate a primary or secondary lack of carnitine , or to lower a high level of lipids in blood Abstract Objectives : To determine the efficacy of L-carnitine in reducing hyperammonaemia and improving neuropsychological performance in patients with hepatic cirrhosis and sub clinical hepatic encephalopathy ( SHE ) . Design : R and omised , parallel group , controlled trial . Patients and Methods : The study enrolled 31 patients with hepatic cirrhosis result ing from hepatitis C and /or hepatitis B , alcohol abuse and other causes . Patients r and omised to active treatment , received oral L-carnitine 6 g/day in two divided doses for 4 weeks . Diagnosis of SHE was based on psychometric tests ( subtests of the Wechsler Adult Intelligence Scale-Revised and the Halstead-Reitan Neuropsychological Test Battery ) carried out at beginning and end of study . Serum ammonia levels were measured before treatment and weekly thereafter . Results : A total of 27 patients completed the study . Sixteen patients received L-carnitine and 11 served as controls ( no treatment ) . L-carnitine caused rapid and significant reductions in ammonia levels , sustained over the 4-week treatment period ( mean reductions 60.1 and 1.4 ( μmol/L in the treated and control groups , respectively ) . Normal ammonia levels were attained in 14 of 16 patients receiving L-carnitine . Based on psychometric test results , seven patients ( 43.7 % ) in the L-carnitine group and five ( 45.5 % ) in the control group had SHE at baseline . L-carnitine treatment for 4 weeks caused a net overall improvement in psychometric test results compared with controls . No clinical ly significant adverse events were reported and all patients receiving L-carnitine reported subjective improvements in their condition . Conclusions : Results of this preliminary study indicate that L-carnitine reduces hyperammonaemia and improves the clinical symptoms of SHE in patients with hepatic cirrhosis Background : The health status of employees with chronic hepatitis C has major implication s for organizations and labour market . Objectives : To assess the effects of Acetyl-L-Carnitine administration on work productivity , daily activity , and fatigue in subjects with chronic hepatitis C treated with Pegylated-Interferon-α2b and Ribavirin . Patients and Methods : In this prospect i ve , r and omized , placebo controlled , double blind clinical trial , 30 subjects ( Group A ) with chronic hepatitis , received Pegylated-Interferon-α2b ( 1.5 mg/kg per week ) plus Ribavirin and placebo , while 32 subjects ( Group B ) received the same dosage of Pegylated-Interferon-α2b plus Ribavirin plus 2 g Acetyl-L-Carnitine twice per day , for 12 months . Work productivity loss , impairment in daily activities , presenteeism , absenteeism , have been assessed using the Work Productivity and Activity Impairment question naire . We also evaluated severity of fatigue , mental fatigue and physical fatigue . Results : Significant difference were observed in physical fatigue , mental fatigue and severity of fatigue , aspartate aminotransferase , alanine aminotransferase , and viremia after 12 months treatment . In Group B we observed a significant decrease of presenteeism and daily activity impairment after 6 months , 12 months and at follow up . A significant increase of work productivity was observed after 12 months and at follow up . Conclusions : Office workers with chronic hepatitis C , treated with Pegylated-Interferon-α2b plus Ribavirin , had work performance loss . In subjects treated with Acetyl-L-Carnitine supplementation we observed increased daily activity and reduced presenteeism and fatigue . Acetyl-L-Carnitinegroup had a smaller reduction of productivity comparing to placebo group This study was performed in order to investigate the extent and severity of cyproheptadine effects on psychomotor performance , mood and memory functions and to compare them to the effects of DL carnitine , another appetite stimulant . Twelve healthy volunteers received 2 doses ( at 800 am and 1200 am ) of 6 mg cyproheptadine , 1600 mg DL carnitine and placebo on separate days at a weekly intervals . The study followed a double-blind , latin-square design . Assessment of dependent variables was performed 1 h after the first and 1 h and 5 h after the second administration of the drug . On each of these occasions , the following measurements were performed : choice reaction time ( CRT ) , critical flicker fusion ( CFF ) , digit symbol substitution test ( DSST ) , short-term memory ( paired words association test ) , long-term memory ( picture test ) and 100 mm visual analogue scales of subjective ratings ( VAS ) . Cyproheptadine significantly impaired objective measures ( CFF ) and subjective ratings both at 1 h and 5 h after the second dosage . Compared with cyproheptadine , DL carnitine induced a slight improvement in psychomotor performance as assessed by CRT . None of the drugs had any effect on memory and on appetite at the doses studied . In conclusion , cyproheptadine at usual doses had a sedative effect , the intensity and duration of which implied a certain risk in performing daytime functions eg when driving , or manipulating machines . DL carnitine had no effect on vigilance OBJECTIVES To To compare testosterone undecanoate versus propionyl-L-carnitine plus acetyl-L-carnitine and placebo in the treatment of male aging symptoms . METHODS A total of 120 patients were r and omized into three groups . The mean patient age was 66 years ( range 60 to 74 ) . Group 1 was given testosterone undecanoate 160 mg/day , the second group was given propionyl-L-carnitine 2 g/day plus acetyl-L-carnitine 2 g/day . The third group was given a placebo ( starch ) . Drugs and placebo were given for 6 months . The assessed variables were total prostate-specific antigen , prostate volume , peak systolic velocity , end-diastolic velocity , resistive index of cavernosal penile arteries , nocturnal penile tumescence , total and free testosterone , prolactin , luteinizing hormone , International Index of Erectile Function score , Depression Melancholia Scale score , fatigue scale score , and incidence of side effects . The assessment was performed at intervals before , during , and after therapy . RESULTS Testosterone and carnitines significantly improved the peak systolic velocity , end-diastolic velocity , resistive index , nocturnal penile tumescence , International Index of Erectile Function score , Depression Melancholia Scale score , and fatigue scale score . Carnitines proved significantly more active than testosterone in improving nocturnal penile tumescence and International Index of Erectile Function score . Testosterone significantly increased the prostate volume and free and total testosterone levels and significantly lowered serum luteinizing hormone ; carnitines did not . No drug significantly modified prostate-specific antigen or prolactin . Carnitines and testosterone proved effective for as long as they were administered , with suspension provoking a reversal to baseline values . Only the group 1 prostate volume proved significantly greater than baseline 6 months after testosterone suspension . Placebo administration proved ineffective . Negligible side effects emerged . CONCLUSIONS Testosterone and , especially , carnitines proved to be active drugs for the therapy of symptoms associated with male aging A 1-year , double-blind , placebo-controlled , r and omized , parallel-group study compared the efficacy and safety of acetyl-L-carnitine hydrochloride ( ALCAR ) with placebo in patients with probable Alzheimer 's disease ( AD ) . Subjects with mild to moderate probable AD , aged 50 or older , were treated with 3 g/day of ALCAR or placebo ( 1 g tid ) for 12 months . Four hundred thirty-one patients entered the study , and 83 % completed 1 year of treatment . The Alzheimer 's Disease Assessment Scale cognitive component and the Clinical Dementia Rating Scale were the primary outcome measures .Overall , both ALCAR- and placebo-treated patients declined at the same rate on all primary and most secondary measures during the trial . In a sub analysis by age that compared early-onset patients ( aged 65 years or younger at study entry ) with late-onset patients ( older than 66 at study entry ) , we found a trend for early-onset patients on ALCAR to decline more slowly than early-onset AD patients on placebo on both primary endpoints . In addition , early-onset patients tended to decline more rapidly than older patients in the placebo groups . Conversely , late-onset AD patients on ALCAR tended to progress more rapidly than similarly treated early-onset patients . The drug was very well tolerated during the trial . The study suggests that a subgroup of AD patients aged 65 or younger may benefit from treatment with ALCAR whereas older individuals might do more poorly . However , these preliminary findings are based on post hoc analyses . A prospect i ve trial of ALCAR in younger patients is underway to test the hypothesis that young , rapidly progressing subjects will benefit from ALCAR treatment . NEUROLOGY 1996;47 : 705 - In this paper the preliminary findings of a multicentre study on the effects of Acetyl-L-Carnitine on mildly impaired elderly are reported . Statistical analysis was carried out on 236 out of 469 subjects sample d in 42 different Italian geriatric or hospital units . Each subject was treated over 150 days , and a battery of tests ( investigating cognitive functioning , emotional-affective state and relational behavior ) was administered at the beginning on the treatment and the conclusion of each of its four phases . In the first and the last phases there was a 30 days placebo treatment ( aim ed respectively to wash-out the effects of previous drug and to assess the residual effects of the treatment ) , while in the second and the third ones ( both 45 days long ) the subjects took 1500 mg/day of Acetyl-L-carnitine . Repeated multivariate analysis of variance and of covariance ( taking as independent variables phases of treatment , age , gender , etiology and severity of mental impairment , as dependent variables the scores either of each test administered or of groups of items and as covariants the level of depression and the sensitivity to placebo effect ) showed that drug treatment significantly increased the effectiveness of performance on all the measures of cognitive functioning and of emotional-affective state and on some scores of the relational behavior . Age result ed significantly influential on cognitive functioning and relational behavior , but not on emotional-affective state . Severity of mental impairment significantly influenced also several measures of cognitive functioning and relational behavior , while less consistent results were shown for gender and etiology of mental impairment . The placebo effect , although significant for some cognitive processes , was lower than that of treatment . There findings suggest that Acetyl-L-carnitine treatment is effective against the outcomes of mental impairment in the cognitive ( in particular , for memory functioning and constructional thinking ) and emotional-affective domains , while its effects on relational behaviour are less consistent , probably because they are partly biased in the subjective evaluation of caregivers and relatives by factors such as age and levels of mental impairment and depression Preliminary data are reported from a multicentred double-blind placebo-controlled study concerned with the effects of acetyl-L-carnitine ( LAC ) on some cognitive deficits of at least one month-abstinent alcoholics . Fifty-five patients , showing impaired performance in at least two out of six mnemonic , praxic and verbal tasks , were r and omly assigned to either LAC 2 g/day or a placebo group . They were tested by means of a neuropsychological battery exploring the areas of memory , constructional praxia , deductive-logical functions and language . Testing time was on baseline ( T0 ) , after 45 ( T45 ) and 90 ( T90 ) days . On the Rey 's 15 word memory test ( long-term ) , the Wechsler memory scale ( logical memory ) , and the Similarities WAIS subtest , the T90 difference between LAC and the placebo was significant in favour of the former treatment . On the copying drawing test ( simple copy ) , the placebo group did not show any T0-T90 variation , while significant improvement in the LAC group was greater than in the placebo group . As LAC has proved to ameliorate the performance or to accelerate the recovery on tests representative of all cognitive areas explored , it is conceivable that the drug acts diffusely , either at the cholinergic transmission or at the neuronal metabolism level . It is concluded that acetyl-L-carnitine can be a useful and safe therapeutic agent in the subtle cognitive disturbances of chronic alcoholics OBJECTIVE Aim of this r and omized , double-blind , placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine ( ALC ) , at different dosages , on specific anhedonic symptoms in detoxified alcohol dependent subjects . Secondary endpoints were the effect of ALC on melancholic and negative symptoms . METHOD Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were r and omized : 23 received ALC at a dosage of 3g/day , 21 received ALC at a dosage of 1g/day , and 20 were given placebo . ALC was given intravenously for 10days , followed by 80days of oral treatment plus a follow-up period of 45days . The presence of anhedonic symptoms was determined by the SHAPS ( Snaith-Hamilton Pleasure Scale ) and the VASa ( Visual Analogue Scale for Anhedonia ) ; negative and melancholic symptoms were evaluated by the SANS ( Scale for the Assessment of Negative Symptoms ) , and the BRMS ( Bech-Rafaelsen Melancholia Scale ) . RESULTS The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study . Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early , on day 10 . At this step levels of anhedonia ( SHAPS , VASa ) and melancholic symptoms ( BRMES ) result ed significantly reduced ( p<0.05 ) in both the ALC 3 g and ALC 1 g groups with respect to placebo ; SANS scores significantly reduced only in the ALC 1 g respect to placebo ( p=0.014 ) . During oral treatment with ALC , anhedonia scores did not differ from placebo . CONCLUSION Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia , melancholic and negative symptoms , whereas oral ALC treatment starting on day 10 showed no further improvements . Accordingly , in alcohol dependent subjects , ALC may be considered as a new potentially useful drug for the treatment of anhedonia It is accepted that acetylcholine-mediated neurones modulate memory . As lecithin , carnitine and glucose all influence acetylcholine metabolism , the possibility of synergistic interactions was considered . Four hundred young adult females r and omly , and under a double-blind procedure , received capsules for 3 days that contained a placebo , lecithin ( 1.6 g/day ) , carnitine ( 500 mg/day ) or carnitine plus lecithin . A battery of cognitive tests was administered prior to taking the capsules , after 3 days of taking the supplements , and for a third time after consuming either a glucose drink or a placebo . Reaction times were more rapid when carnitine and a glucose drink were taken together . Memory was enhanced in those taking a glucose rather than placebo drink . Neither mood nor the ability to sustain attention were influenced by these procedures . The hypothesis that memory would be facilitated by offering supplements of lecithin , carnitine and glucose was not supported A multicentre study was planned and executed to evaluate the effect of psychopharmacological treatment in cognitive decline , while also monitoring the influence of pivotal variables . Using 42 health centres , whose comparability of methodology was ensured through a training seminar and an instructional booklet on the psychometric battery of tests employed , 469 Ss ( 60 years and over older ) were enrolled using strict selection criteria . The treatment was run in four phases over 150 days . The first and the last phases consisted of 30-days placebo treatment , whereas the second and third consisted of 45-days treatment with 1,500 mg of acetyl-L-carnitine . A psychometric evaluation followed each phase . Using this plan it was possible to evaluate the placebo effects , make cross- study comparisons and isolate the effects of the drug treatment The aim of this study was to evaluate the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain . The trial was conducted on a double-blind basis , with a total of 40 patients divided into two groups of 20 , treated for 40 days with L-acetylcarnitine and placebo , respectively -- the therapeutic regimen being two 500 mg tablets t.i.d . Mental parameters of the senile brain were assessed at 0 , 20 and 40 days of treatment , while basal and final values were recorded for a number of laboratory tests . Statistical analysis of results confirmed that short-term , intensive L-acetylcarnitine treatment can determine a significant improvement of the main mental parameters of the senile brain , without incidence of significant side effects In a double-blind , placebo-controlled , parallel-group , r and omized clinical trial , we studied the efficacy of long-term ( 1-year ) oral treatment with acetyl-L-carnitine in 130 patients with a clinical diagnosis of Alzheimer 's disease . We employed 14 outcome measures to assess functional and cognitive impairment . After 1 year , both the treated and placebo groups worsened , but the treated group showed a slower rate of deterioration in 13 of the 14 outcome measures , reaching statistical significance for the Blessed Dementia Scale , logical intelligence , ideomotor and buccofacial apraxia , and selective attention . Adjusting for initial scores with analysis of covariance , the treated group showed better scores on all outcome measures , reaching statistical significance for the Blessed Dementia Scale , logical intelligence , verbal critical abilities , long-term verbal memory , and selective attention . The analysis for patients with good treatment compliance showed a greater drug benefit than for the overall sample . Reported adverse events were relatively mild , and there was no significant difference between the treated and placebo groups either in incidence or severity A multicentre study was planned and executed to evaluate the effect of acetyl-L-carnitine in the treatment of cerebral aging . Using 42 health centres , whose comparability of methodology was ensured through a training seminar and an instructional booklet on the psychometric battery of tests employed , some 400 elderly patients aged 60 - 80 years were enrolled using strict selection criteria . Treatment was run in four phases over 150 days . The first phase , serving as the baseline evaluation , defined through a battery of tests , consisted of 30-day placebo treatment . In the second phase of 45 days , daily treatment with 1500 mg acetyl-L-carnitine was given followed by a psychometric evaluation . For the next 45 days the same drug therapy was employed with a complete psychometric evaluation on the final day . In the last phase of 30 days the placebo was again administered and a final assessment made of the residual benefits of the 90-day treatment with acetyl-L-carnitine . Using this plan made it possible to evaluate the placebo effects , perform cross- study comparisons and demonstrate the effectiveness of the drug treatment Carnitine deficiency is prevalent in population s with chronic illness , including cancer . In a recent open-label study , L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients . To further evaluate this finding , adult patients with advanced cancer , carnitine deficiency ( free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females , or acyl/free carnitine ratio of more than 0.4 ) , moderate to severe fatigue , and a Karnofsky Performance Status ( KPS ) score of 50 or more , were r and omly assigned to receive either L-carnitine ( 0.5 g/day for two days , followed by 1g/day for two days , and then 2g/day for 10 days ) or placebo . This double-blind phase was followed by an open-label phase , during which all patients received L-carnitine supplementation for two weeks . Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) , the Linear Analog Scale Assessment s ( LASA ) , the Mini-Mental State Exam ( MMSE ) , and the KPS . Twenty-nine patients ( 12 placebo , 17 L-carnitine ) were included in the intent-to-treat ( ITT ) analysis . From baseline to the end of the double-blind phase , serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 ( P=0.004 ) , and from 22.9+/-19.4 to 45.3+/-17.2 ( P=0.004 ) , respectively , in the L-carnitine-treated group , and from 28.2+/-10.2 to 36.2+/-8.7 ( P = ns ) , and from 22.6+/-7.9 to 28.7+/-8.6 ( P = ns ) in the placebo group , respectively . The planned ITT analysis revealed no significant improvement in any of the study 's endpoints , and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated . However , an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale ( P<0.03 ) , and significantly improved FACT-An functional well-being subscale ( P<0.03 ) , and KPS ( P<0.003 ) , in the group that started with L-carnitine during the double-blind phase . These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients . However , L-carnitine supplementation does increase L-carnitine serum levels , and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a sub population of cancer patients |
2,635 | 17,699,539 | The prospect i ve studies provided no strong evidence for a causal role of CRP in cancer . | The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein ( CRP ) and cancer through a systematic review . | Objective —C-reactive protein ( CRP ) concentrations are predictive of cardiovascular disease , and levels are heritable , in part . We identified novel polymorphisms in the CRP gene and assessed their influence on CRP level . Methods and Results —CRP was measured in 250 male army recruits before and after strenuous exercise and perioperatively in 193 coronary artery bypass graft ( CABG ) patients . Two novel polymorphisms were identified in the CRP gene , −717G > A in the promoter and + 1444C > T in the 3′UTR . Among army recruits , CRP was higher in + 1444TT homozygotes than + 1444 C-allele carriers at baseline ( 1.04±0.38 versus 0.55±0.06 , P = 0.014 ) and at all time points after exercise ( 2.35±0.68 versus 1.07±0.12 , 2.11±0.53 versus 0.88±0.09 , and 1.77±0.44 versus 0.71±0.09 , P = 0.034 , P = 0.007 , and P = 0.013 , at 2 , 48 , and 96 hours after exercise , respectively ) . In the CABG patients , mean CRP ( mg/L ) rose from 1.97±0.36 at baseline to 167.2±5.0 72 hours postoperatively . Genotype did not influence CRP at baseline ; however , peak post-CABG CRP levels were higher in + 1444TT homozygotes compared with + 1444C-allele carriers ( 198±17 versus 164±5 , P = 0.03 ) . Conclusions —The CRP gene + 1444C > T variant influences basal and stimulated CRP level . These findings have implication s both for the prediction and pathogenesis of coronary heart disease Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading , despite our best efforts to improve the design and analysis of studies . Mendelian r and omization-the r and om assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures . The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies . Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian r and omization and are described . The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study , that polymorphisms may have several phenotypic effects associated with disease , the lack of suitable polymorphisms for study ing modifiable exposures of interest , and canalization-the buffering of the effects of genetic variation during development . Nevertheless , Mendelian r and omization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to underst and ing and preventing the adverse effects on human health of modifiable exposures Abstract The goals of our work were to study prospect ively the possibility of differentiating between infections and neoplastic fever in adult cancer patients on admission , by means of C-reactive protein ( CRP ) and erythrocyte sedimentation rate ( ESR ) or of follow-up CRP values . Patients and methods were as follows : the final infection group consisted of 56 patients and the noninfection group of 10 patients with neoplastic fever ; CRP was measured on days 0 , 3 and 5 and ESR at entry . The main results showed that the median CRP did not differ between the groups ( 91 mg/l vs 102 mg/l ) on entry , while the ESR level was higher in the neoplastic fever group ( 50 mm/H vs 89 mm/H , P=0.023 ) . On admission , both markers had low area under receiver operating characteristic curves for the demonstration of infection ( CRP 0.42 ; ESR 0.27 ) . The CRP level dropped significantly in the infection group within 5 days ( P=0.009 ) . We conclude that neither of the markers was useful in differentiating between infections and neoplastic fever on admission , but that the follow-up CRP values were advantageous in this respect Background —C-reactive protein ( CRP ) values predict atherothrombotic cardiovascular disease and type 2 diabetes mellitus . Associations between CRP and obesity , predominantly assessed anthropometrically , may partly explain these observations . Previous studies have been unable to control for genetic influences on CRP and obesity . The aim of this study was to examine the relationship between CRP and accurately measured body fat , lipids , apolipoproteins , blood pressure , and environmental and behavioral factors , independent of genetic influences . Methods and Results —One hundred ninety-four healthy female twins ( age 57.2±7 years ) were studied after excluding pairs with CRP values > 10 mg/L. Total body fat and central abdominal fat ( CAF ) were measured by dual-energy x-ray absorptiometry . CRP concentration was strongly related to surrogate and direct measures of body fat ( r = 0.31 to 0.54 , P < 0.001 ) , diastolic blood pressure ( r = 0.20 , P = 0.003 ) , and lipid and apolipoprotein levels ( r = 0.21 to 0.51 , P < 0.008 ) . Light-to-moderate alcohol consumers and nonusers of hormone replacement therapy ( HRT ) had lower CRP levels than abstainers and HRT users , respectively . In stepwise multiple regression analysis , CAF , triglycerides , apolipoprotein B , and HRT use explained 46 % of the variance in circulating CRP . In analyses controlling for genetic influences in monozygotic twins , within-pair differences in CRP were associated with within-pair differences in total body fat ( r = 0.39 , P < 0.001 ) , CAF ( r = 0.34 , P = 0.002 ) , diastolic blood pressure ( r = 0.24 , P = 0.03 ) , apolipoprotein AI ( r = −0.33 , P = 0.01 ) , HDL cholesterol ( r = −0.42 , P = 0.001 ) , and triglycerides ( r = 0.35 , P = 0.007 ) . Conclusions —CRP was strongly related to total and central abdominal obesity , blood pressure , and lipid levels , independent of genetic influences . These relationships are likely to contribute significantly to prospect i ve associations between CRP and type 2 diabetes and coronary events Summary Retrospective analysis previously identified significant elevation of five tumour markers , carcinoembryonic antigen ( CEA ) , ferritin , orosomucoid , C-reactive protein and erythrocyte sedimentation rate ( ESR ) , in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response . In this study we have prospect ively tested these findings . None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups . They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer . There was a significant elevation of all five markers in patients with systemic breast cancer ( P < 0.0001 ; analysis of variance ) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response . Prospect i ve confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice . We conducted a prospect i ve longitudinal , before-after trial in our 600-bed teaching hospital . Twenty-four patients with obstructive jaundice were investigated , 11 with benign obstruction and 13 with malignant disease . Endoscopic internal biliary drainage was performed in all patients ( 7 by papillotomy and 17 by endoprostheses ) . Endotoxin , tumor necrosis factor alpha ( TNF-α ) , interIeukin-6 ( IL-6 ) , nitric oxide production , and C-reactive protein ( CRP ) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished . Bile cultures were obtained before and at the time of drainage . Endotoxin , IL-6 , TNF-α , and CRP were significantly higher in patients with cancer . After internal drainage , endotoxin ( 11.4 vs. 2 EU/L ; p<0.05 ) , TNF-α ( 87.5 vs. 48 pg/ml ; p=0.03 ) , and IL-6 ( 324 vs. 232 pg/ml;/ p<0.05 ) plasma levels decreased significantly in the early postdrainage period in patients with cancer . Endotoxin , cytokines , as well as the CRP plasma values , however , increased again on day 7 after drainage . This trend was less marked in patients with benign obstruction . Patients with positive bile cultures after drainage displayed higher levels of CRP ( 115 vs. 62 mg/L ; p=0.03 ) , IL-6 ( 598 vs. 330 pg/ml ; p=0.04 ) , and endotoxin ( 10.6 vs. 4.8 EU/L ; p=0.02 ) than those with negative bile cultures . Biliary tract obstruction is associated with an increase in endotoxin levels , a positive acute-phase response , and plasma cytokine elevation . After biliary drainage a transitory improvement of these alterations was observed , although values remained high 1 week postdrainage . These findings were associated with positive bile cultures . RésuméLe drainage biliaire préopératoire peut améliorer les perturbations des cytokines et celles observées dans la réponse de la phase aiguë chez les patients atteints d’ictère obstructif . Cette étude , prospect i ve , longitudinale , a consisté à étudier 24 patients atteints d’ictère obstructif , 11 d’origine bénigne , 13 d’origine maligne , avant et après traitement dans un Hôpital Universitaire de 600 lits . Les interventions comportaient toujours un drainage endoscopique interne ( 7 papillotomies et 17 endoprothèses ) . On a mesuré l’endotoxine , le facteur TNF-α , l’IL-6 , la production en oxyde nitrique et la C-réactive protéine ( CRP ) au moment de l’admission et aux jours 2 et 7 après drainage biliaire interne . Des cultures ont été obtenues avant et au moment du drainage . Les taux d’endotoxine , de l’IL-6 , du TNF-α et de la CRP étaient significativement plus élevés chez les patients atteints de cancer . Après drainage interne , les taux plasmatiques de l’endotoxine ( 11.4 vs. 2 EU/L ; p<0.05 ) , de TNF-α ( 87.5 vs. 48 pg/ml ; p=0.03 ) et d’IL-6 ( 324 vs. 232 pg/ml ; p<0.05 ) ont diminué de façon significative après drainage chez les patients atteints de cancer . Les taux d’endotoxine et des cytokines tout comme les taux plasmatiques de la CRP ont cependant augmenté au jour sept . Cette tendance a été moins marquée chez les patients porteurs d’obstruction bénigne . Les patients ayant des cultures de bile positives après drainage avaient un taux postdrainage plus élevé de CRP ( 115 vs. 62 mg/L ; p=0.03 ) , d’IL-6 ( 598 vs. 330 pg/ml ; p=0.04 ) et d’endotoxine ( 10.6 vs. 4.8 EU/L ; p=0.02 ) que ceux ayant des cultures de bile négatives . L’obstruction biliaire est associée à une augmentation des taux d’endotoxines , à une réponse de phase aiguë positive et à une élévation des cytokines plasmatiques . Après drainage biliaire , on observe une amélioration transitoire de ces altérations , même si les valeurs restaient élevées une semaine après le drainage , surtout en cas de cultures de bile positives . ResumenEn pacientes ictéricos , el drenaje biliar preoperatorio parece mejorar las atocinas y las alteraciones de respuesta de la fase aguda . En un Hospital Universitario de 600 camas , se diseñó un estudio clínico prospect ivo longitudinal . Se estudiaron 24 pacientes con ictericia obstructiva : La obstrucción era benigna en 11 y maligna en 13 . El drenaje biliar interno se realizó por vía endoscópica ( 7 papilotomías y 17 endoprótesis ) . El día del ingreso y a los 2 y 7 días del drenaje biliar interno se determinaron : endotoxina , TNF-α , IL-6 , producción de óxido nítrico y proteína C reactiva ( CRP ) . Las endotoxina , IL-6 , TNF-α y CRP estaban significativamente más elevadas en pacientes con cáncer . En pacientes cancerosos , tras drenaje interno , los niveles plasmáticos descendieron inmediata y significativamente : endotoxina ( 11.4 vs. 2 EU/L ; p<0.05 ) TNF-α ( 87.5 vs. pg/ml ; p=0.03 ) , y IL-6 ( 324 vs. 232 pg/ml ; p<0.05 ) . Sin embargo , la citocina , endotoxina y los valores plasmáticos de la CRP volvieron ha elevarse al 7 ° día post-drenaje . Estas modificaciones fueron menores en pacientes con ictericia obstructiva benigna . Tras el drenaje , los pacientes con cultivos biliares positivos , mostraron mayores elevaciones de la CRP ( 115 vs. 62 mg/L ; p=0.03 ) , IL-6 ( 598 vs. 330 pg/ml ; p=0.04 ) y de la endotoxina ( 10.6 vs. 4.8 EU/L ; p=0.02 ) , que aquellos cuyos cultivos fueron negativos . La obstrucción del colédoco se acompaña de : un incremento de los niveles de endotoxina , respuesta positiva de la fase aguda y elevación de las citocinas plasmáticas . Tras drenaje biliar se produce una mejora transitoria de las alteraciones observadas , aunque los parámetros persisten elevados transcurrida una semana del drenaje biliar . Este hecho se observó en pacientes con cultivos positivos en la bilis Background —C-reactive protein ( CRP ) has repeatedly been associated with blood pressure and prevalent and incident hypertension , but whether a causal link exists is uncertain . Methods and Results —We assessed the cross-sectional relations of CRP to systolic blood pressure , pulse pressure , and prevalent hypertension in a representative sample of > 3500 British women aged 60 to 79 years . For both outcomes , substantial associations were observed . However , these associations were greatly attenuated by adjustment for a wide range of confounding factors acting over the life course . We further investigated causality using a Mendelian r and omization approach by examining the association of the 1059G/C polymorphism in the human CRP gene with CRP and with blood pressure , pulse pressure , and hypertension . The polymorphism was associated with a robust difference in CRP , and the expectation would be for higher blood pressure and pulse pressure and greater prevalence of hypertension among those carrying the genetic variant associated with higher CRP levels . This was not observed , and the predicted causal effects of CRP on blood pressure , pulse pressure , and hypertension using instrumental variables methods were close to 0 , although with wide CIs . Conclusions —CRP levels are associated with blood pressure , pulse pressure , and hypertension , but adjustment for life course confounding and a Mendelian r and omization approach suggest the elevated CRP levels do not lead to elevated blood pressure Serum neural cell adhesion molecule ( NCAM ) has been described as a prognostic marker in multiple myeloma ( MM ) . Both C-reactive protein ( CRP ) and beta 2-microglobulin ( beta 2 M ) are established prognostic markers in MM . We tested the diagnostic value of these markers in 212 serum sample s of patients with paraproteinemia registered prospect ively in a population -based registry . Sixty patients had MM and 152 had other monoclonal gammopathies ( hematologic diseases [ 48 ] , paraneoplastic disease [ 35 ] , autoimmune disease [ 15 ] , and monoclonal gammopathy of undetermined significance [ 56 ] ) . CRP and beta 2 M had wide and overlapping ranges in all diagnostic categories . However , serum neural cell adhesion molecule ( NCAM ) was low ( < 20 U/mL ) in all but 4 of 152 nonmyeloma cases and high ( > or = 20 U/mL ) in 31 ( 52 % ) of the 60 MM cases . Two patients with non-Hodgkin 's lymphoma , 1 with chronic lymphatic leukemia , and 1 with autoimmune disease had serum NCAM values between 20 and 30 U/mL. In a discriminant analysis in which serum NCAM , CRP , beta 2 M , paraprotein type and concentration , hemoglobin , leukocyte and thrombocyte counts , creatinine , corrected calcium , lactate dehydrogenase , and alkaline phosphatase were included , paraprotein type and concentration and serum NCAM turned out to be the best combination of parameters predicting whether a patient had MM , with 89 % of cases being correctly classified . Even without bone marrow and x-ray examinations , serum NCAM , in combination with paraprotein type and concentration , can differentiate between MM and nonmyeloma patients Altered immune , inflammatory , and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma ( HNSCC ) , and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis . In this study , we examined the hypothesis that HNSCC cells produce cytokines that regulate immune , inflammatory , and angiogenesis responses . We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry . The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses ( i.e. , fibrinogen , C-reactive protein , and erythrocyte sedimentation rate ) from patients with HNSCC was determined , and the potential relationship of serum cytokine levels to tumor volume was analyzed . Cytokines interleukin (IL)-1alpha , IL-6 , IL-8 , granulocyte-macrophage colony-stimulating factor ( GM-CSF ) , vascular endothelial growth factor ( VEGF ) , and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma ( UM-SCC ) cell lines and supernatants of freshly isolated primary HNSCC cultures . Evidence for the expression of IL-1alpha , IL-6 , IL-8 , granulocyte-macrophage colony-stimulating factor , and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry . In a prospect i ve comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum , we report that cytokines IL-6 , IL-8 , and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects ( at P < 0.05 ) . The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume ( R2 = 0.2 and 0.4 , respectively ) . Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects ( at P < 0.05 ) . We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines , tissue specimens , and serum from patients with HNSCC . These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy Background : Inflammation is an important component of carcinogenesis but little research has been conducted on whether inflammation markers can be predictive of cancer risk in humans . Methods : We analyzed C-reactive protein ( CRP ) , a marker of inflammation , in plasma sample s of 496 cases of cancer and 996 controls selected among participants in a prospect i ve study from Greece . Results : Plasma CRP level was higher in cancer cases than controls ( odds ratio for increase in CRP level of 3.2 mg/L , 1.20 ; 95 % confidence interval , 1.10 - 1.32 ) : The corresponding odds ratio after exclusion of the first year of follow-up and of individuals with CRP level above 20 mg/L was 1.32 ( 95 % confidence interval , 1.15 - 1.52 ) . Although based on small number of cases , the association between elevated plasma CRP level and risk was stronger for cancers of the liver , lung , skin , kidney , and bladder , as well as for lymphoma and leukemia than for other neoplasms . Conclusions : Our results confirm the important role of inflammation in human cancer and suggest that plasma CRP level is a potential marker of increased cancer risk . ( Cancer Epidemiol Biomarkers Prev 2006;15(2):381–4 We investigated whether , in Italian patients , C-reactive protein ( CRP ) determination could be considered a useful adjunct , complementary to α1-fetoprotein , in the detection of liver cancer . CRP was determined by particle-enhanced nephelometry in 171 subjects ( 102 male , 69 female ) . Fifty-five patients had mild chronic liver disease ( CLD ) , 45 cirrhosis ( CIR ) , 38 hepatocellular carcinoma ( HCC ) ; 33 subjects were healthy controls . Patients with HCC and CIR had higher CRP levels ( P<0.05 ) than those found in patients with CLD and controls . CRP higher than 5 mg/l was found in 30/38 ( 78.9 % ) patients with HCC , 28/45 ( 62.2 % ) patients with CIR , 16/55 ( 29.1 % ) patients with CLD ( χ2 56.0,P<0.0001 ) . Sensitivity , specificity and diagnostic accuracy of CRP in diagnosing HCC with respect to CLD+CIR were : 78.9 % , 56.0 % and 34.9 % . However , when considered only in the subgroup of patients with α1-fetoprotein below or equalling 30 ng/ml , they were 50.0 % , 54.3 % and 4.3 % respectively . In conclusion , CRP concentration is frequently elevated in patients with HCC , however , it does not seem to improve the ability of α1-fetoprotein to discriminate HCC from CIR Context Inflammatory markers , such as C-reactive protein ( CRP ) , independently predict future coronary artery disease in patients without known disease at baseline . However , an elevated CRP level also predicts all-cause mortality ; therefore , it may not be specific for cardiovascular disease . Contribution This prospect i ve casecontrol study showed that CRP level predicted the development of acute cardiovascular events but not cancer among 28 345 women followed for a mean of 58 months . Clinical Implication s parental history of coronary heart disease . In women , CRP level appears specifically predictive of car-diovascular disease but not cancer . This study adds further evidence that CRP levels may be useful in the clinical prediction of cardiovascular risk , at least in population s. The Editors Recent evidence suggests that atherosclerosis is in part a chronic low- grade inflammatory condition ( 1 ) , and prospect i ve epidemiologic studies have demonstrated that plasma markers of inflammation , such as C-reactive protein ( CRP ) , are strong independent predictors of future coronary events in apparently healthy persons ( 2 - 6 ) . However , as an acute-phase reactant , CRP increases dramatically in various pathologic conditions . Moreover , CRP has been shown to predict all-cause mortality ( 7 , 8) , an observation that raises the possibility that CRP may not be specific for vascular disease . To evaluate this hypothesis , we directly compared the predictive value of CRP for incident cancer and cardiovascular disease , the two most important determinants of all-cause mortality in the western world . Methods We performed a prospect i ve , nested casecontrol analysis within the Women 's Health Study , an ongoing r and omized , double-blind , placebo-controlled trial of aspirin and vitamin E for primary prevention of heart disease and cancer , which involves 39 876 U.S. women 45 years of age and older . Of these study participants , 28 345 ( 71 % ) provided baseline blood sample s , which were stored at 70 C until the time of laboratory analysis . In the Women 's Health Study , all participants are followed prospect ively for incident health events , including cancer and cardiovascular events . The methods used for cohort follow-up , end-point ascertainment , and adjudication for both cancer and cardiovascular events are described in detail elsewhere ( 5 , 9 ) . For this study , we defined case- patients as apparently healthy women who provided an adequate baseline plasma sample and who subsequently developed cancer ( n = 513 ) or an acute cardiovascular event ( myocardial infa rct ion , stroke , or cardiovascular death ) ( n = 130 ) over a mean follow-up period of 58 months . For each woman who had confirmed cancer or cardiovascular event during follow-up , one control of the same age ( 1 year ) and smoking habit ( former smoker , current smoker , or nonsmoker ) was selected from among participants who provided baseline plasma sample s and remained free of reported disease during the same follow-up period . Using these criteria , we evaluated 643 case- patients and an equal number of controls in two separate matched pairs , one for cancer ( n = 513 ) and another for cardiovascular events ( n = 130 ) . The Institutional Review Board of the Brigham and Women 's Hospital approved this study . For each case-patient and control , plasma stored since the baseline examination was thawed and assayed for CRP levels by using a high-sensitivity assay ( Dade Behring , Newark , Delaware ) ( 10 ) . Blood specimens were analyzed in blinded pairs with the position of the patient 's specimen varied at r and om to reduce the possibility of systematic bias and to decrease interassay variability . The day-to-day precision values , at CRP concentrations of 0.15 mg/L and 0.49 mg/L , were 4.9 % and 6.4 % , respectively . Because CRP values are skewed rightward , median plasma concentrations were computed , and the significance of any difference in the distributions between the case- patients and controls was assessed by performing the Wilcoxon rank-sum test . We then used conditional logistic regression models to determine the risk for developing cancer or cardiovascular end points after dividing the study sample into quartiles on the basis of the distribution of the control group . Adjusted estimates of risk were obtained by use of similar models that accounted for the matching variables and that controlled for r and omized treatment assignment ( for vitamin E , aspirin , or both ) , body mass index , diabetes mellitus , history of hyperlipidemia , history of hypertension , and parental history of coronary heart disease . All analyses were performed by using SAS software , release 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) . All P values were two tailed , and CIs were computed at the 95 % level . The funding sources played no role in the design , conduct , or reporting of the study . Results Table 1 shows the baseline characteristics of the study participants . We noted no significant differences at baseline between women who subsequently developed cancer and those who did not . As expected , women who subsequently developed cardiovascular events had an increased baseline prevalence of hyperlipidemia , hypertension , diabetes , and obesity compared with controls who did not develop vascular events during follow-up . Table 1 . Baseline Clinical Characteristics of the Study Participants Overall , median levels of CRP at baseline among women who subsequently developed cancer ( 2.6 mg/L [ interquartile range , 1.1 to 5.9 mg/L ] ) were not significantly different from those of the control group ( 2.5 mg/L [ interquartile range , 0.9 to 5.5 mg/L ] ) ( P > 0.2 ) . Furthermore , we observed no evidence of an association between baseline CRP level and the development of cancer in site-specific analyses evaluating carcinoma of the breast ( n = 223 ) , ovary or uterus ( n = 75 ) , colon ( n = 44 ) , lung ( n = 32 ) , hematopoietic system ( n = 31 ) , thyroid ( n = 14 ) , bladder ( n = 9 ) , brain ( n = 8) , or pancreas ( n = 8) ; melanoma ( n = 31 ) ; or other types of cancer ( n = 38 ) . In contrast , and consistent with previous work in this cohort for the end point of any vascular event ( 5 ) , median CRP levels at baseline among women who subsequently developed cardiovascular disease ( 5.1 mg/L [ interquartile range , 2.6 to 8.5 mg/L ] ) were significantly higher than those of the control group ( P < 0.001 ) . Table 2 presents relative risks for developing either cancer or cardiovascular disease according to increasing quartiles of CRP levels obtained at study entry . As Table 2 shows , there was little evidence that baseline levels of CRP predicted incident cancer in either crude or adjusted analyses . We found similar results after additional correction for alcohol use and age at menarche ( data not shown ) . In contrast , increasing quartiles of baseline CRP level were a strong marker of risk for incident cardiovascular disease in crude and adjusted analyses . For example , the adjusted relative risks from the lowest to the highest quartiles of baseline CRP levels were 1.0 , 2.9 , 3.4 , and 5.6 , respectively ( P for trend < 0.001 ) . Table 2 . Relative Risk for Future Cancer and Cardiovascular Events , according to Baseline Plasma C-Reactive Protein Level Discussion In this prospect i ve study of apparently healthy middle-aged and older women , baseline plasma CRP concentrations were not significantly related to the incidence of future cancer but were a strong independent predictor of future myocardial infa rct ion , stroke , and cardiovascular death . We believe these data have importance for general medical practice for several reasons . First , our data corroborate the findings in several previous reports ( 2 - 6 ) that baseline levels of CRP predict future vascular events among apparently healthy men and women ( 2 - 6 ) and that CRP level adds to the predictive value of total and high-density lipoprotein cholesterol levels ( 5 , 11 ) . As a result of these earlier findings , outpatient screening for CRP has recently become available . However , if CRP is clinical ly nonspecific , as two recent studies evaluating all-cause mortality suggest ( 7 , 8) , then screening for this inflammatory marker might have reduced diagnostic utility . Thus , our finding that CRP appears to be specific for incident vascular disease but not for incident cancer has substantial clinical importance and suggests that data linking CRP level to overall death rates may have been due to the large contribution that vascular disorders make to all-cause mortality , particularly in the western world . Second , the relative risks for future myocardial infa rct ion or stroke observed among women in the top versus bottom quartile of baseline CRP in this analysis are somewhat greater than those previously reported from this cohort for the end point of any vascular eventan end point that included not only myocardial infa rct ion , stroke , and cardiovascular disease mortality , but also coronary revascularization ( 5 ) . Thus , these data also suggest that CRP level may be a stronger marker for events involving atherosclerotic plaque rupture and acute thrombosis than for events primarily involving progression of lesional stenosis . These epidemiologic data are thus consistent with the hypothesis that inflammation is an important determinant of plaque vulnerability ( 12 ) . Finally , we believe that our observation that CRP levels do not strongly predict future cancers is itself of pathophysiologic interest ; this is of particular interest because levels of CRP and other inflammatory biomarkers are known to increase after development of certain malignancies ( 13 , 14 ) . As such , our data also suggest that the systemic inflammatory component of cancer previously reported in cross-sectional studies may be a late development in the genesis of that disease but is not likely to prove useful in determining risk among healthy persons . Several limitations of our study deserve attention . Plasma CRP levels increase acutely in a wide variety of pathologic conditions , including febrile illness , various inflammatory states , and trauma ( 15 ) . In A cross sectional and prospect i ve analysis of 3,745 British women aged 60 - 79 years at baseline was undertaken . Among these women there were 570 prevalent cases of coronary heart disease ( CHD ) and 151 new cases among 12,641 person-years of follow up of women who were free of CHD at baseline . Both fibrinogen and CRP were associated with indicators of socioeconomic position in childhood and adulthood and there was a cumulative effect of socioeconomic position from across the life course . The age-adjusted odds ratio ( 95 % confidence interval ) of prevalent CHD for a 1 unit ( 1 g/L ) increase in fibrinogen was 1.29 ( 1.12 , 1.49 ) ; with full adjustment for all potential confounding factors this attenuated to 1.09 ( 0.93 , 1.28 ) . The hazards ratio for incident CHD among those free of disease at baseline was 1.28 ( 1.00 , 1.64 ) ; with full adjustment for all potential confounding factors this attenuated to 1.09 ( 0.84 , 1.44 ) . Similar effects of adjustment for confounding factors were seen for the associations between CRP and both prevalent and incident CHD . By contrast , the strong positive association between smoking ( an established causal risk factor for CHD ) and CHD was not attenuated by adjustment for life course socioeconomic position or other risk factors . We conclude that fibrinogen and CRP predict CHD but may not be causally related to it Context Some data suggest that low- grade inflammation may play a role in the development of colorectal cancer . Contribution In this 10-year prospect i ve study involving 27913 healthy women age 45 years or older , elevated C-reactive protein ( CRP ) levels at baseline were not associated with a higher likelihood of colorectal cancer . Caution s A single baseline CRP measurement may be an imperfect marker of inflammation . The investigators relied on a woman 's report of cancer rather than an ongoing surveillance protocol for colorectal lesions . Implication s Low- grade inflammation may not be associated with in-creased colorectal cancer risk . The Editors C-reactive protein ( CRP ) , a marker of inflammation , is consistently associated with increased risk for cardiovascular disease ( 1 ) . A recent epidemiologic study has raised the hypothesis that CRP levels might also be associated with incident colon cancer ( 2 ) . This latter hypothesis is supported by clinical observations of an increased risk for colorectal cancer in patients with chronic , relapsing and remitting inflammatory disordersulcerative colitis and Crohn diseasecollectively known as inflammatory bowel diseases ( 3 , 4 ) . Reduced risk for colorectal adenomas and cancer associated with long-term use of aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) in observational studies and some clinical trials also supports this hypothesis ( 5 ) . Moreover , CRP levels in patients with colorectal cancer are correlated with tumor stage ( 6 - 10 ) . However , colorectal cancer associated with inflammatory bowel diseases accounts for only 1 % to 2 % of all cases of colorectal cancer in the general population ( 3 ) . In addition , the mechanisms by which NSAIDs may reduce the risk for colorectal neoplasia are still under debate and may not necessarily reflect disease inflammatory pathways ( 11 ) . Furthermore , abundant evidence suggests that inflammation is part of the host response to cancer ( 12 , 13 ) ; thus , the elevations in CRP levels observed in patients with colorectal cancer may be a result rather than a cause of disease . Because of the public health importance of this issue , we evaluated whether CRP levels predict colorectal cancer risk among 27913 participants in the Women 's Health Study for whom CRP was measured at baseline ; the maximum duration of follow-up was 10.8 years . Methods Study Cohort Beginning in 1993 , 39876 female U.S. health professionals age 45 years or older who were free of cancer and cardiovascular disease were enrolled into the Women 's Health Study , a r and omized , double-blind , placebo-controlled , 22 factorial trial evaluating the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cancer and cardiovascular disease ( 14 ) . Upon study enrollment , all participants completed a baseline question naire about their medical history and lifestyle characteristics , including potential risk factors for colorectal cancer . Before r and omization , 28345 women ( 71 % of those r and omly assigned ) also provided baseline blood specimens , sent via overnight courier , using a kit that contained a gel-filled freezer pack as a coolant . Upon arrival at our laboratory , the sample s were subjected to centrifugation ; separated into plasma , leukocytes , and erythrocytes ; and stored in liquid nitrogen . Baseline characteristics among women who did and did not provide blood specimens were largely similar ( mean age , 54.7 years vs. 54.4 years ; body mass index 25 kg/m2 , 48.4 % vs. 51.1 % ; family history of colorectal cancer , 10.6 % vs. 10.5 % ; current use of postmenopausal hormones , 43.5 % vs. 37.5 % ; ever use of oral contraceptives , 69.6 % vs. 69.4 % ; aspirin use before the trial , 11.7 % vs. 10.8 % ; current use of multivitamin supplements , 29.4 % vs. 28.6 % ; history of benign colon polyps , 2.5 % vs. 2.5 % ; and median alcohol intake , 1.1 g/d vs. 0.9 g/d ) . The following were the exceptions : Women who provided blood specimens were more physically active ( median , 598.6 kcal/wk vs. 526.0 kcal/wk ) but were less likely to be current smokers ( 11.7 % vs. 16.8 % ) . Of the 28345 sample s received , 27939 usable sample s were measured for plasma CRP by a vali date d high-sensitivity assay ( Denka Seiken Co. , Tokyo , Japan ) in a core laboratory facility for ongoing st and ardization programs on the CRP measurement ( 15 ) . The current analysis was restricted to 27913 women after the additional exclusion of 21 women with prer and omization cancer reported after r and omization and confirmed by medical record review and 5 women with newly diagnosed nonadenocarcinoma colorectal cancer during follow-up . Ascertainment of Cases of Colorectal Cancer Every 6 months during the first year of follow-up and then annually thereafter , participants were sent question naires asking about newly diagnosed end points , including colon or rectal cancer . Family members or postal authorities reported deaths of participants . Within the past 2 years , morbidity follow-up is 97 % , and mortality follow-up is nearly 100 % . For those who reported a diagnosis of colorectal cancer and for those who are deceased , we sought medical records and other relevant information , which were review ed by an Endpoints Committee consisting of physicians to confirm medical diagnoses . Of the self-reports , medical record review confirmed 96 % . The review ers additionally extracted information on anatomic location and tumor stage at diagnosis ( Duke 's A , spread to submucosa or muscle only ; Duke 's B , spread to pericolic or perirectal tissues , but no lymphatic involvement ; Duke 's C , lymph node involvement or metastasis ) . The current analysis included only confirmed incident cases of colorectal adenocarcinoma . Statistical Analysis We first compared the distribution of baseline risk factors for colorectal cancer by category of plasma CRP level to assess their potential for confounding . Participants were categorized into CRP levels of less than 1 , 1 to 3 , and greater than 3 mg/L , the cutoff points proposed in clinical guidelines for cardiovascular disease ( 16 ) and previously used in this cohort to define cardiovascular disease risk ( 15 ) . For the analysis of total cancer of the colon and rectum , we also categorized women into quartiles of CRP based on the CRP distribution among never users or among ever users of postmenopausal hormones at baseline ( postmenopausal hormone use elevates CRP level [ 17 - 19 ] ) . We calculated person-years for each participant from the date of r and omization to the date of diagnosis of confirmed cancer , death , or 20 February 2004 , whichever occurred first . A Cox proportional hazards regression model , which treats disease outcome as a r and om variable that would change over time , was used to calculate the hazard ratios and 95 % CIs . We first estimated the crude hazard ratios according to category of CRP and then additionally adjusted for age ( in years ) or age and r and omized treatment assignment ( aspirin vs. placebo , vitamin E vs. placebo ) to control for potential confounding by the effects of these treatments . We further performed a multivariate analysis that additionally adjusted for postmenopausal hormone use ( never , past , current ) ; body mass index ( < 23 , 23 to < 25 , 25 to < 27 , 27 to < 30 , 30 kg/m2 ) ; family history of colorectal cancer in first-degree relatives ( yes or no ) ; physical activity ( total kcal/wk in quartiles ) ; smoking status ( never , past , current ) ; aspirin use before the trial ( yes or no ) ; alcohol consumption ( 0 , > 0 to < 15 , 15 g/d ) ; oral contraceptive use ( never or ever ) ; menopausal status ( premenopausal , postmenopausal , uncertain/unknown ) ; and multivitamin supplement use ( never , past , current ) at baseline . We also conducted an analysis that additionally adjusted for history of self-reported colon polyps at baseline ( yes or no ) . Of the 27913 women in the current analysis , 1817 participants who had missing values for 1 or more covariates were dropped from multivariate analyses . Furthermore , we performed an analysis according to tumor location ( proximal colon , distal colon , and rectum ) and tumor stage at diagnosis ( Duke 's A , B , and C ) . Tests for trend were performed by using the median value for each CRP category as a continuous variable . The assumption of proportional hazards over time was tested by using log likelihood ratio tests to compare models with or without interaction terms between CRP and the logarithm of follow-up time in regression models . There was no indication that the proportionality assumption was violated . Additional analyses excluded incident cases diagnosed within 1 , 2 , and 5 years of follow-up , with further adjustment for symptomatic examination ( yes or no ) and regular screening ( yes or no ) by colonoscopy or sigmoidoscopy , which were asked on the 12-month follow-up question naire to address the potential effect of screening . We conducted analyses stratified by level of other risk factors for colorectal cancer to evaluate whether the association between baseline plasma CRP level and colon cancer risk may exist in subgroups . Tests for interaction between CRP and level of other risk factors in relation to colorectal cancer risk were carried out by using the median value for each CRP category as a continuous variable , an indicator variable for risk factor , and a product term of these 2 variables . The Wald test was used to assess the statistical significance of the interaction term . All P values were 2-sided . All analyses were performed by using SAS software , version 8 ( SAS Institute , Inc. , Cary , North Carolina ) . Role of the Funding Source The National Institutes of Health , the Doris Duke Foundation , and the Donald W. Reynolds Foundation sponsored the study . The sponsors did not participate in the design and conduct of the study ; in the collection , analysis , and interpretation of the data ; or in the preparation , review , or approval of the manuscript . The authors had full access to the data files of the study . Results Through 20 February 2004 , 169 incident cases of invasive colorectal adenocarcinoma were confirmed : 70 cases of This prospect i ve study was carried out to explore cytokine-related immune alterations in 69 renal cell carcinoma patients ( RCC ) and to look for changes which might potentially serve as a reliable predictors of response to cytokine-based therapy . Interleukin-2 ( IL-2 ) , its soluble receptor ( sIL-2R ) and tumor necrosis factor ( TNF-alpha ) levels produced in vitro by PHA activated and intact mononuclear cells ( P BMC ) were determined . Concentrations of IL-2 , IL-4 , IL-6 , sIL-2R , TNF-alpha and CRP were measured in sera . Cytokine level was evaluated by enzyme-linked immunoadsorbent assay ( ELISA ) and CRP was determined by means of turbidimetric method . All measurements were performed in patients without any prior treatment . PHA activated P BMC of RCC patients were significantly defective in producing IL-2 and TNF-alpha comparing to controls ( p < 0.03 and p < 0.001 ) . The difference of sIL-2R was noted in metastatic stage only ( p < 0.03 ) . Unstimulated P BMC manifested decrease in IL-2 ( p < 0.03 ) and increased level of TNF-alpha in advanced disease ( p < 0.02 ) . This impairment reflected tumor size and differentiation stage . Serum concentrations of IL-2 , sIL-2R and TNF-alpha were within normal range . However , in relation to the clinical stage , significantly increased serum IL-2 was noted in combined Stage I and II as compared to controls ( p = 0.012 ) . IL-6 and CRP showed markedly elevated levels with a significancy which allowed to distinguish sample s from metastatic patients . In conclusion careful comparisons of these data with clinical course of cytokine treated patients will disclose which of those tests may possess predictive power in the individual patients who are likely to respond to cytokine-based treatment C-reactive protein is a biomarker indicating inflammation in the body . We measured plasma C-reactive protein to assess whether this biomarker could predict subsequent colorectal cancer incidence . A nested case-control study was conducted within a Japan Public Health Center – based prospect i ve study . During a 11.5-year follow-up , 375 newly diagnosed colorectal cancers were identified in a cohort of 38,373 adults who had returned the baseline question naire and provided blood sample s. Two controls were selected from the cohort for each case matched by age , sex , study area , date of blood drawn , and fasting time at blood donation . The odds ratio of colorectal cancer for plasma C-reactive protein was estimated using a conditional logistic regression model adjusted for pack-years of smoking , body mass index , alcohol consumption , physical exercise , and family history of colorectal cancer . The highest quartile group of plasma C-reactive protein was significantly associated with colorectal cancer compared with the lowest group ( odds ratio , 1.6 ; 95 % confidence interval , 1.1 - 2.5 ; Ptrend = 0.053 ) . The association became clearer after excluding cases of rectal cancer ( Ptrend = 0.041 ) and limiting colorectal cancer to the intramucosal type ( Ptrend = 0.017 ) . This association was unchanged after deletion of the first 2-year cases . In conclusion , plasma levels of C-reactive protein were associated with a subsequent risk of colon cancer . Inflammation may be involved at the early stage of colon tumor growth . ( Cancer Epidemiol Biomarkers Prev 2006;15(4):690–5 CONTEXT Inflammation may play a role in the pathogenesis of colorectal cancer ; however , epidemiological evidence supporting this hypothesis in average-risk persons is sparse . OBJECTIVE To determine the risk of incident colon and rectal cancer associated with elevated baseline plasma concentrations of C-reactive protein ( CRP ) . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve , nested case-control study of a cohort of 22 887 adults ( > 18 years and Washington County , Maryl and , residents ) enrolled between May and October 1989 and followed up through December 2000 . A total of 172 colorectal cancer cases were identified through linkage with the Washington County and Maryl and State Cancer registries . Up to 2 controls ( n = 342 ) were selected from the cohort for each case and matched by age , sex , race , and date of blood draw . MAIN OUTCOME MEASURE Odds ratio ( OR ) of incident colon and rectal cancer . RESULTS Plasma CRP concentrations were higher among all colorectal cases combined than controls ( median CRP , 2.44 vs 1.94 mg/L ; P = .01 ) . The highest concentration was found in persons who subsequently developed colon cancer vs matched controls ( median CRP , 2.69 vs 1.97 mg/L ; P<.001 ) . Among rectal cancer cases , CRP concentrations were not significantly different from controls ( median CRP , 1.79 vs 1.81 mg/L ; P = .32 ) . The risk of colon cancer was higher in persons in the highest vs lowest quartile of CRP ( OR , 2.55 ; 95 % confidence interval [ CI ] , 1.34 - 4.88 ; P for trend = .002 ) . In nonsmokers , the corresponding association was stronger ( OR , 3.51 ; 95 % CI , 1.64 - 7.51 ; P for trend<.001 ) . A 1-SD increase in log CRP ( 1.02 mg/L ) was associated with an increased risk of colon cancer after adjusting for potential confounders and excluding cases occurring within 2 years of baseline ( OR , 1.35 ; 95 % CI , 1.05 - 1.74 ) or excluding those with late-stage colon cancer at the time of diagnosis ( OR , 1.38 ; 95 % CI , 0.99 - 1.91 ) . CONCLUSIONS Plasma CRP concentrations are elevated among persons who subsequently develop colon cancer . These data support the hypothesis that inflammation is a risk factor for the development of colon cancer in average-risk individuals Anti-angiogenic therapies are currently in cancer clinical trials , but to date there are no established tests for evaluating the angiogenic status of a patient . We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment . The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden . We measured VEGF-A , PlGF , SCF , MMP-9 , EDB+ -fibronectin , sVEGFR-2 , sVEGFR-1 , salphaVbeta3 , sTie-2 , IL-8 and CRP in the blood of 22 healthy volunteers , 17 early breast , 17 early colorectal , and 8 advanced sarcoma/melanoma cancer patients . Breast cancer patients had elevated levels of VEGF-A and sTie-2 , colorectal cancer patients of VEGF-A , MMP-9 , sTie-2 , IL-8 and CRP , and melanoma/sarcoma patients of sVEGFR-1 . salphaVbeta3 was decreased in colorectal cancer patients . A correlation between VEGF-A and MMP-9 was found . After tumor removal , MMP-9 and salphaVbeta3 significantly decreased in breast and CRP in colorectal cancer , whereas sVEGFR-1 increased in colorectal cancer patients . In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A , SCF , VEGFR-2 , MMP-9 , Tie-2 and CRP , a correlation between CRP and IL-8 , and a decreased in sVEGFR-1 levels . In conclusion , among all factors measured , only VEGF-A and MMP-9 consistently correlated to each other , elevated CRP levels were associated with tumor burden , whereas sVEGF-R1 increased after tumor removal in colorectal cancer . Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch . These results warrant a prospect i ve study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value Interleukin‐16 ( IL‐16 ) is a chemoattractant of CD4(+ ) lymphocytes , and it has been implicated in the pathogenesis of various inflammatory diseases . There is evidence that it may have a role in multiple myeloma ( MM ) . In the present study , we determined the serum level of IL‐16 both before and after treatment of MM and related it to inflammatory markers and survival . Forty‐eight newly diagnosed MM patients were included in the study . Disease stage was defined using the Durie – Salmon classification system ( 10 patients were in stage I , 19 in stage II , and 19 in stage III ) . After st and ard treatment , 22 patients reached the plateau phase and were re‐evaluated . The following serum parameters were measured : IL‐16 , IL‐6 , α‐1 antitrypsin ( α1AT ) , and C‐reactive protein ( CRP ) . Survival was determined as the number of months elapsed since original diagnosis . The mean ± SD of serum IL‐16 was 343 ± 195 pg/ml in the pre‐treatment MM group and 101 ± 30 pg/ml in the control group . All measured parameters were higher in the patient group compared to healthy controls . Furthermore , IL‐16 , IL‐6 , α1AT , and CRP were significantly increased with increasing stage of disease , from stage I to stage III ( P < 0.01 ) . All parameters decreased significantly following effective chemotherapy ( P < 0.002 ) . Patients with a high level of IL‐16 ( > 430 pg/ml ) displayed an inferior survival time in comparison to those with lower levels of IL‐16 . In the pre‐treatment group , IL‐16 correlated with α1AT and IL‐6 ( r = 0.374 , P < 0.01 and r = 0.454 , P < 0.002 , respectively ) . IL‐16 may play a role in multiple myeloma ; however , further functional studies are required . Am . J. Hematol . 75:101–106 , 2004 . © 2004 Wiley‐Liss , Erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) and serum lactate dehydrogenase ( LDH ) are non-specific biochemical markers , accompanying the growth of some neoplasms , both in adults and in children . The aim of this study was to determine the clinical value of ESR , CRP and LDH evaluation in the diagnosis , prognosis and monitoring of treatment among children suffering from cancer . 100 children patients with acute leukaemia , Hodgkin 's and non-Hodgkin 's lymphoma , nephroblastoma and soft tissue sarcoma were included in the study , being compared to 30 healthy children of the control group . In oncological patients all the markers were estimated prospect ively at 5 stages or the disease , i.e. : before treatment , during treatment -- in partial remission ( PR ) and after complete clinical remission was achieved ( CR ) , after therapy and during the relapse or progression of cancer ( PROG ) . The mean pre-treatment levels of analysed markers in cancer patients were significantly higher than in healthy children ( p<0.001 ) . The elevation of ESR , CRP and LDH was observed in 78.7 , 50.8 and 72.1 % of cases respectively . Good clinical response to antitumour therapy was paralleled with the significant decrease of pre-treatment ESR , CRP and LDH levels , but the values observed in CR , both while treatment and after therapy , did not return towards normal range . The progression of disease was accompanied by the increase of ESR , CRP and LDH levels , however only ESR and CRP values differed significantly in PROG as compared to the CR phase . Among analysed markers , only LDH level at diagnosis proved to be an independent prognostic factor for the overall survival rate . Three-year overall survival rate for patients with pre-treatment LDH level < 1.5 x normal value ( N ) was 94 % while for those with LDH > 1.5 x N -- 67 % . It has been demonstrated that ESR , CRP and LDH determinations in children suffering from cancer may serve as useful markers both in diagnostics and monitoring of the disease course . Moreover , the pre-treatment LDH level appeared to have an important role in prognosis of the overall survival rate Testicular cancer patients have an increased risk for coronary artery disease more than ten years after cisplatin-based chemotherapy . We investigated whether vascular changes , including endothelial dysfunction , are present earlier . Ninety chemotherapy-treated testicular cancer patients ( median follow-up of seven years ) were compared with 44 patients after orchidectomy only and 47 healthy men . Microalbuminuria was present in 10 ( 12 % ) chemotherapy patients , one stage I patient and none of the controls . Chemotherapy patients had higher levels of fibrinogen , C-reactive protein ( hs-CRP ) , von Willebr and factor ( vWF ) , plasminogen activator inhibitor ( PAI-1 ) , and tissue-type plasminogen activator ( t-PA ) . Chemotherapy patients with elevated PAI-1 ( 25/90 ) showed clustering of cardiovascular risk factors resembling the metabolic syndrome . In conclusion , cured testicular cancer patients showed a high prevalence of microalbuminuria and increased plasma levels of endothelial and inflammatory marker proteins , which might progress to more severe endothelial dysfunction and overt atherosclerosis |
2,636 | 30,043,270 | Although pharmacotherapy and psychological interventions are helpful for many , these treatment approaches are not effective for everyone and are insufficient to address common physical health complications , such as the elevated risk of cardiovascular disease .
Given the combined anxiolytic and physical health benefits of increased activity , PA presents a promising additional treatment option for people with anxiety disorders . | Purpose of Review The purpose of this paper was to provide a comprehensive narrative review of the relationship between physical activity ( PA ) and anxiety and the rationale for including it as a treatment option for anxiety disorders .
Several gaps in the literature are highlighted alongside recommendations for future research .Recent Findings PA in the general population has established efficacy in preventing and managing cardiovascular disease and improving wellbeing .
Recent epidemiological data further suggests that people who are more active may be less likely to have anxiety disorders .
In addition , evidence from systematic review s of r and omised control trials suggests that exercise training , a subset of PA , can reduce symptoms in anxiety and stress-related disorders , such as post-traumatic stress disorder , agoraphobia and panic disorder .
Summary Anxiety disorders are common , burdensome and costly to individuals and wider society .
In addition to the profound negative impact on individuals ’ wellbeing and functioning , they are associated with worsened physical health , including a higher risk for cardiovascular diseases and premature mortality . | The purpose of this study was to compare the relative effects of a single bout of aerobic exercise versus resistance training on cognitive vulnerabilities for anxiety disorders . Seventy-seven participants ( 60 % female ; 84 % Caucasian ) were r and omized to complete 20 min of moderate-intensity aerobic exercise , resistance training , or rest , followed by a 35 % CO2/65 % O2 inhalation challenge task . Results indicated that aerobic exercise and resistance training were significantly and equally effective in reducing anxiety sensitivity ( AS ) compared with rest ( ) , though only aerobic exercise significantly attenuated reactivity to the CO2 challenge task . Neither form of exercise generated observable effects on distress tolerance , discomfort intolerance , or state anxiety ( all ps>.10 ) . The results of this study are discussed with regard to their implication s for the use of exercise interventions for anxiety and related forms of psychopathology , and potential directions for future research are discussed Regular physical activity is anxiolytic in both healthy subjects and patients with panic disorder . In contrast , acute exercise may induce acute panic attacks or increase subjective anxiety in patients with panic disorder more than in other people . The effects of quiet rest or an aerobic treadmill exercise ( 30 min at an intensity of 70 % of the maximal oxygen uptake , VO2max ) on cholecystokinin tetrapeptide ( CCK-4 ) induced panic attacks were studied in a crossover design in 12 patients with panic disorder and 12 matched healthy subjects . The effects of CCK-4 ( 25 microg in patients and 50 microg in control subjects ) were measured with the Acute Panic Inventory ( API ) score , comparing panic attack frequencies , total score , and subscores for anxiety and somatic symptoms . CCK-4-induced panic attacks were less frequent after prior exercise : they occurred in 15 ( 62.5 % ) subjects after rest ( 9 patients and 6 control subjects ) , but only 5 ( 20.8 % ) subjects after exercise ( 4 patients and 1 control subject ) . In both conditions , CCK-4 administration induced a significant increase in the total API score and the anxiety and somatic symptoms subsores . However , compared to prior rest , exercise result ed in a significantly reduced CCK-4-induced increase of the total API score and the anxiety subscore . In patients with panic disorder exercise increased the total API score and the somatic symptoms subscale but not the anxiety subscore . Patients with panic disorder showed increased somatic but not anxiety symptoms after an acute bout of exercise . Severity of CCK-4-induced panic and anxiety , on the other h and was reduced by exercise . These findings suggest that in addition to exercise training an acute bout of exercise may be used to reduce anxiety and panic attack frequency and intensity in panic disorder patients Cognitive dysfunction has been repeatedly observed in major depressive disorder ( MDD ) , particularly in areas of attention , verbal and nonverbal learning and memory , and executive functioning . Exercise has been shown to improve cognitive outcomes in other population s , including age-associated cognitive decline , but has not to our knowledge been investigated as an augmentation strategy in depression . This study evaluated the effectiveness of exercise augmentation on cognitive performance in persons with MDD and residual symptoms that included cognitive complaints following initial treatment with a selective serotonin reuptake inhibitor ( SSRI ) . Participants enrolled in the Treatment with Exercise Augmentation for Depression ( TREAD ) study were r and omized to receive either a low or high dose exercise regimen . TREAD participants who provided informed consent for the current study completed Cambridge Neuropsychological Test Automated Battery measures assessing Attention , Visual Memory , Executive Function/Set-shifting and Working Memory , and Executive Function/Spatial Planning domains . Data were analyzed for 39 participants completing both baseline and Week 12 cognitive testing . Overall tests indicated a significant task × group × time interaction for the Executive Function/Set-shifting and Working Memory domain . Post-hoc tests indicated improvements in high dose exercisers ' spatial working memory , but decreases in spatial working memory and set-shifting outcomes in low dose exercisers . Both groups improved on measures of psychomotor speed , attention , visual memory and spatial planning . This study suggests a dose-response effect of exercise in specific executive function and working memory tasks among depressed persons with a partial response to SSRI and cognitive complaints , with some cognitive functions improving regardless of exercise dose OBJECTIVE Physical activity and cardiorespiratory fitness may help prevent depression and anxiety . Previous studies have been limited by error-prone measurements . We examined whether self-reported physical activity domains and peak exercise capacity ( peakVO₂ ) are associated with incident and recurrent major depressive disorder ( MDD ) , depressive symptoms , and anxiety disorders . METHODS This was a prospect i ve population -based study of 1,080 adult men and women ( 25 - 83 years ) with a median follow-up of 4.5 years and measures of physical activity during leisure time , sports , and work ( Baecke question naire ) ; a measure of depressive symptoms ( Beck Depression Inventory II ) ; symptom-limited cycle ergometer testing ( peakVO₂ , oxygen uptake at anaerobic threshold [ VO₂@AT ] , maximum power output at peak exertion ) ; and a structured psychiatric interview ( Munich Composite International Diagnostic Interview ) . Baseline data were collected between 2002 and 2006 , and follow-up data , between 2007 and 2010 . RESULTS After adjustment for age , sex , education , smoking , alcohol consumption , and waist circumference , the relative risks for incident MDD per st and ard deviation ( SD ) increase in leisure-time physical activity , physical activity during sport , physical activity at work , peakVO₂ , VO₂@AT , and maximum power output were 1.002 ( 95 % confidence interval , 0.90 to 1.12 ) , 1.02 ( 0.90 to 1.15 ) , 0.94 ( 0.80 to 1.10 ) , 0.71 ( 0.52 to 0.98 ) , 0.83 ( 0.66 to 1.04 ) , and 0.71 ( 0.52 to 0.96 ) , respectively . PeakVO₂ , VO₂@AT , and maximum power output were associated with recurrent MDD , depressive symptoms , and anxiety . PeakVO₂ was more strongly related to the co-occurrence of MDD and anxiety ( adjusted odds ratio [ OR ] = 0.45 [ 0.24 to 0.84 ] ) than depression or anxiety alone ( OR = 0.71 [ 0.53 to 0.94 ] ) . CONCLUSIONS Greater cardiorespiratory fitness but not domain-specific physical activity was associated with a lower incidence of MDD and clinical anxiety BACKGROUND Although generalized anxiety disorder ( GAD ) and major depressive episode ( MDE ) are known to be highly co-morbid , little prospect i ve research has examined whether these two disorders predict the subsequent first onset or persistence of the other or the extent to which other predictors explain the time-lagged associations between GAD and MDE . METHOD Data were analyzed from the nationally representative two-wave panel sample of 5001 respondents who participated in the 1990 - 1992 National Comorbidity Survey ( NCS ) and the 2001 - 2003 NCS follow-up survey . Both surveys assessed GAD and MDE . The baseline NCS also assessed three sets of risk factors that are considered here : childhood adversities , parental history of mental-substance disorders , and respondent personality . RESULTS Baseline MDE significantly predicted subsequent GAD onset but not persistence . Baseline GAD significantly predicted subsequent MDE onset and persistence . The associations of each disorder with the subsequent onset of the other attenuated with time since onset of the temporally primary disorder , but remained significant for over a decade after this onset . The risk factors predicted onset more than persistence . Meaningful variation was found in the strength and consistency of associations between risk factors and the two disorders . Controls for risk factors did not substantially reduce the net cross-lagged associations of the disorders with each other . CONCLUSIONS The existence of differences in risk factors for GAD and MDE argues against the view that the two disorders are merely different manifestations of a single underlying internalizing syndrome or that GAD is merely a prodrome , residual , or severity marker of MDE Objective : To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to st and ard antidepressant medication ( sertraline ) and greater reductions in depression compared to placebo controls . Methods : Between October 2000 and November 2005 , we performed a prospect i ve , r and omized controlled trial ( SMILE study ) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital . A total of 202 adults ( 153 women ; 49 men ) diagnosed with major depression were assigned r and omly to one of four conditions : supervised exercise in a group setting ; home-based exercise ; antidepressant medication ( sertraline , 50–200 mg daily ) ; or placebo pill for 16 weeks . Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale ( HAM-D ) . Results : After 4 months of treatment , 41 % of the participants achieved remission , defined as no longer meeting the criteria for major depressive disorder ( MDD ) and a HAM-D score of < 8 . Patients receiving active treatments tended to have higher remission rates than the placebo controls : supervised exercise = 45 % ; home-based exercise = 40 % ; medication = 47 % ; placebo = 31 % ( p = .057 ) . All treatment groups had lower HAM-D scores after treatment ; scores for the active treatment groups were not significantly different from the placebo group ( p = .23 ) . Conclusions : The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD . Placebo response rates were high , suggesting that a considerable portion of the therapeutic response is determined by patient expectations , ongoing symptom monitoring , attention , and other nonspecific factors . BDI = Beck Depression Inventory ; CI = confidence interval ; HAM-D = Hamilton Depression Rating Scale ; ITT = intention-to-treat ; MDD = major depressive disorder ; SD = st and ard deviation ; SSRIs = selective serotonin reuptake inhibitors ; TSH = thyroid stimulating hormone Evidence supports exercise as an intervention for many mental health concerns ; however , r and omized controlled investigations of the efficacy of different exercise modalities and predictors of change are lacking . The purpose s of the current trial were to : ( 1 ) quantify the effects of aerobic exercise and resistance training on anxiety-related disorder ( including anxiety disorders , obsessive-compulsive disorder , and posttraumatic stress disorder ) status , symptoms , and constructs , ( 2 ) evaluate whether both modalities of exercise were equivalent , and ( 3 ) to determine whether exercise enjoyment and physical fitness are associated with symptom reduction . A total of 48 individuals with anxiety-related disorders were r and omized to aerobic exercise , resistance training , or a waitlist . Symptoms of anxiety-related disorders , related constructs , and exercise enjoyment were assessed at pre-intervention and weekly during the 4-week intervention . Participants were further assessed 1-week and 1-month post-intervention . Both exercise modalities were efficacious in improving disorder status . As well , aerobic exercise improved general psychological distress and anxiety , while resistance training improved disorder-specific symptoms , anxiety sensitivity , distress tolerance , and intolerance of uncertainty . Physical fitness predicted reductions in general psychological distress for both types of exercise and reductions in stress for aerobic exercise . Results highlight the efficacy of different exercise modalities in uniquely addressing anxiety-related disorder symptoms and constructs BACKGROUND Exercise is a potential treatment for depression . However , few studies have evaluated the role of adjunct exercise in the treatment of severely major depressed in patients . The goal of this study was to evaluate the effects of add-on exercise on the usual treatment of severely depressed in patients . METHODS Fifty participants were r and omized to an exercise ( exercise + usual treatment ) or a control ( usual treatment ) group . Twenty-five patients were r and omly allocated to each group . The participants in the exercise group performed three sessions per week throughout the hospitalization period , with a goal dose of 16.5 kcal/kg/week plus the usual pharmacological treatment . Depressive symptoms and the Quality of Life ( QoL ) of the participants were assessed at the baseline , the second week , and discharge . RESULTS A significant group × time interaction was found for depressive symptoms and the physical and psychological domains of QoL. Differences between groups occurred at the second week and discharge with respect to depressive symptoms and the physical and psychological domains of QoL. There was no difference in the remission rate at discharge ( 48 % and 32 % for the exercise and control group , respectively ) . An NNT of 6.25 was found . No significant baseline characteristics predict remission at discharge . CONCLUSION Add-on exercise is an efficacious treatment for severely depressed in patients , improving their depressive symptoms and QoL. Initial acceptance of exercise remains a challenge BACKGROUND Chronic exercise has been shown to have therapeutic effects in panic disorder ( PD ) . The mechanism of these effects is unknown . Acute exercise reduces the effect of a panic challenge in healthy volunteers . Such an effect has not yet been demonstrated in PD patients . The present study aim ed at exploring the antipanic effects of acute exercise on a 35 % CO2 panic provocation in treatment-naïve PD patients to further eluci date the mechanisms of the beneficial effects of exercise on panic . METHODS Eighteen PD patients performed either moderate/hard exercise or very-light exercise before a 35 % CO2 challenge in a r and omized , between-group design . The reactivity to CO2 was assessed with the Visual Analogue Anxiety Scale and the DSM-IV Panic Symptom List . RESULTS Panic reactions to CO2 were smaller in patients that performed moderate/hard exercise in contrast to those that performed very-light exercise . Increments in both measurements and panic rates were consistently reduced by intense exercise . LIMITATIONS Since this study focuses on the acute effects of exercise on CO2 sensitivity in patients with PD , the results of repetitive exercise sessions on the rate of spontaneous panic attacks and overall symptoms are warranted . The small sample size and other limitations are addressed . CONCLUSIONS Exercise reduced the panicogenic effects of a CO2 challenge . In addition to its therapeutic potential , exercise may also be useful as a laboratory maneuver with heuristic value in experimental research into the mechanisms of antipanic treatment Background . Low and middle income countries ( LMICs ) are facing an increase of the impact of mental health problems while confronted with limited re sources and limited access to mental health care , known as the ‘ mental health gap ’ . One strategy to reduce the mental health gap would be to utilize the internet to provide more widely-distributed and low cost mental health care . We undertook this systematic review to investigate the effectiveness and efficacy of online interventions in LMICs . Methods . We systematic ally search ed the data -bases PubMed , PsycINFO , JMIR , and additional sources . MeSH terms , Thesaurus , and free text keywords were used . We included all r and omized controlled trials ( RCTs ) of online interventions in LMICs . Results . We found only three articles reported results of RCTs on online interventions for mental health conditions in LMICs , but none of these interventions was compared with an active control condition . Also , the mental health conditions were diverse across the three studies . Conclusions . There is a dearth of studies examining the effect of online interventions in LMICs , so we can not draw a firm conclusion on its effectiveness . However , given the effectiveness of online interventions in high income countries and sharp increase of internet access in LMICs , online interventions may offer a potential to help reduce the ‘ mental health gap ’ . More studies are urgently needed in LMICs Although it has been hypothesized that the association of physical activity with depressive and anxiety symptoms is bidirectional , few studies have examined this issue in a prospect i ve setting . We studied this bidirectional association using data on physical activity and symptoms of anxiety and depression at three points in time over 8 years . A total of 9,309 participants of the British Whitehall II prospect i ve cohort study provided data on physical activity , anxiety and depression symptoms and 10 covariates at baseline in 1985 . We analysed the associations of physical activity with anxiety and /or depression symptoms using multinomial logistic regression ( with anxiety and depression symptoms as dependent variables ) and binary logistic regression ( with physical activity as the dependent variable ) . There was a cross-sectional inverse association between physical activity and anxiety and /or depressive symptoms at baseline ( ORs between 0.63 and 0.72 ) . In cumulative analyses , regular physical activity across all three data waves , but not irregular physical activity , was associated with reduced likelihood of depressive symptoms at follow-up ( OR = 0.71 , 95 % CI 0.54 , 0.99 ) . In a converse analysis , participants with anxiety and depression symptoms at baseline had higher odds of not meeting the recommended levels of physical activity at follow-up ( OR = 1.79 , 95 % CI 1.17 , 2.74 ) . This was also the case in individuals with anxiety and /or depression symptoms at both baseline and follow-up ( OR = 1.70 , 95 % CI 1.10 , 2.63 ) . The association between physical activity and symptoms of anxiety and /or depression appears to be bidirectional BACKGROUND Exercise interventions repeatedly have been shown to be efficacious for the treatment of depression , and initial studies indicate similar efficacy for the treatment of anxiety conditions . To further study the potential beneficial role of prescriptive exercise for anxiety-related conditions , we examined the role of exercise in reducing fears of anxiety-related sensations ( anxiety sensitivity ) . METHODS We r and omly assigned 60 participants with elevated levels of anxiety sensitivity to a 2-week exercise intervention , a 2-week exercise plus cognitive restructuring intervention , or a waitlist control condition . Assessment of outcome was completed at pretreatment , midtreatment , 1-week posttreatment , and 3-week follow-up . RESULTS We found that both exercise conditions led to clinical ly significant changes in anxiety sensitivity that were superior to the waitlist condition , representing a large controlled effect size ( d=2.15 ) . Adding a cognitive component did not facilitate the effects of the exercise intervention . Consistent with hypotheses , changes in anxiety sensitivity mediated the beneficial effects of exercise on anxious and depressed mood . CONCLUSIONS We discuss these findings in terms of the potential role of exercise as an additional psychosocial intervention for conditions such as panic disorder , where anxiety sensitivity is a prominent component of pathology OBJECTIVE This study examined the unadjusted and adjusted prevalence estimates of depression and anxiety at the state level and examined the odds ratios of depression and anxiety for selected risk behaviors , obesity , and chronic diseases . METHODS The 2006 Behavioral Risk Factor Surveillance Survey , a r and om-digit-dialed telephone survey , collected depression and anxiety data from 217,379 participants in 38 states , the District of Columbia , Puerto Rico , and the U.S. Virgin Isl and s. Current depressive symptoms were assessed with the st and ardized and vali date d eight-item Patient Health Question naire , and lifetime diagnosis of depression and anxiety was assessed by two additional questions ( one question for each diagnosis ) . RESULTS The overall prevalence of current depressive symptoms was 8.7 % ( range by state and territory , 5.3%-13.7 % ) ; of a lifetime diagnosis of depression , 15.7 % ( range , 6.8%-21.3 % ) ; and of a lifetime diagnosis of anxiety , 11.3 % ( range , 5.4%-17.2 % ) . After sociodemographic characteristics , adverse health behaviors , and chronic illnesses were adjusted for , cardiovascular disease , diabetes , asthma , smoking , and obesity were all significantly associated with current depressive symptoms , a lifetime diagnosis of anxiety , and a lifetime diagnosis of depression . Physically inactive adults were significantly more likely than those who were physically active to have current depressive symptoms or a lifetime diagnosis of depression , whereas those who drank heavily were significantly more likely than those who did not to have current depressive symptoms or a lifetime diagnosis of anxiety . CONCLUSIONS Depression and anxiety were strongly associated with common chronic medical disorders and adverse health behaviors . Examination of mental health should therefore be an integral component of overall health care OBJECTIVE The purpose of the present study was to address 1 ) whether exercise provides protection against new-onset depression and anxiety and 2 ) if so , the intensity and amount of exercise required to gain protection and , lastly , 3 ) the mechanisms that underlie any association . METHOD A " healthy " cohort of 33,908 adults , selected on the basis of having no symptoms of common mental disorder or limiting physical health conditions , was prospect ively followed for 11 years . Vali date d measures of exercise , depression , anxiety , and a range of potential confounding and mediating factors were collected . RESULTS Undertaking regular leisure-time exercise was associated with reduced incidence of future depression but not anxiety . The majority of this protective effect occurred at low levels of exercise and was observed regardless of intensity . After adjustment for confounders , the population attributable fraction suggests that , assuming the relationship is causal , 12 % of future cases of depression could have been prevented if all participants had engaged in at least 1 hour of physical activity each week . The social and physical health benefits of exercise explained a small proportion of the protective effect . Previously proposed biological mechanisms , such as alterations in parasympathetic vagal tone , did not appear to have a role in explaining the protection against depression . CONCLUSIONS Regular leisure-time exercise of any intensity provides protection against future depression but not anxiety . Relatively modest changes in population levels of exercise may have important public mental health benefits and prevent a substantial number of new cases of depression BACKGROUND The present review systematic ally evaluates correlates of physical activity across the socio-ecological model for people with depression . SUBJECTS AND METHODS Two independent review ers search ed Embase , PubMed , and CINAHL from their inception until May 2015 , combining the medical subject heading ' depression ' or ' depressive ' with ' physical activity ' or ' exercise ' . Data were extracted by the same independent research ers and summarized according to the socio-ecological model . RESULTS Fifty-nine papers involving 101,539 persons with depression were eligible and enabled us to evaluate 42 correlates . Correlates that were consistently ( n ≥ 4 ) associated with lower physical activity participation in depressed persons were a higher level of depressive symptoms , a higher body mass index , the presence of physical co-morbidity and a lower self-efficacy . The role of social , environmental and policy factors on physical activity participation is unknown and should be addressed in future research . CONCLUSION In persons with depression physical activity participation is a complex behavior that is influenced by many different factors . Significant correlates should be confirmed in prospect i ve studies . Interventions to improve modifiable physical and mental health variables in people with depression should be developed and evaluated OBJECTIVES The purpose of this study was to investigate the long-term cardiac effects of depression and anxiety assessed at a young age , when reverse causation is not feasible . BACKGROUND Most prospect i ve studies found a relatively strong association between depression and subsequent coronary heart disease ( CHD ) . However , almost exclusively , only middle-age or older participants were examined , and sub clinical atherosclerosis might contribute to the observed association . The prospect i ve association between anxiety and CHD was less evident in previous studies and has been subjected to similar method ological concerns on the possibility for a reverse causation . METHODS In a nationwide survey , 49,321 young Swedish men , 18 to 20 years of age , were medically examined for military service in 1969 and 1970 . All the conscripts were seen by a psychologist for a structured interview . Conscripts reporting or presenting any psychiatric symptoms were seen by psychiatrists . Depression and anxiety was diagnosed according to International Classification of Diseases-8th Revision ( ICD-8 ) . Data on well-established CHD risk factors and potential confounders were also collected ( i.e. , anthropometrics , diabetes , blood pressure , smoking , alcohol consumption , physical activity , socioeconomic position , family history of CHD , and geographic area ) . Participants were followed for CHD and for acute myocardial infa rct ion for 37 years . RESULTS Multiadjusted hazard ratios associated with depression were 1.04 ( 95 % confidence interval [ CI ] : 0.70 to 1.54 ) , 1.03 ( 95 % CI : 0.65 to 1.65 ) , for CHD and for acute myocardial infa rct ion , respectively . The corresponding multiadjusted hazard ratios for anxiety were 2.17 ( 95 % CI : 1.28 to 3.67 ) and 2.51 ( 95 % CI : 1.38 to 4.55 ) . CONCLUSIONS In men , aged 18 to 20 years , anxiety as diagnosed by experts according to ICD-8 criteria independently predicted subsequent CHD events . In contrast , we found no support for such an effect concerning early-onset depression in men |
2,637 | 30,702,552 | In term of sexual dysfunction , urinary retention , the number of apical lymph nodes , and long-term oncologic outcomes , there were no significant differences between the LCA non-preservation and LCA preservation group .
Conclusions : The pooled data provided evidence to support the LCA preservation preferred over LCA non-preservation in anastomotic leakage . | Background : It remains unclear whether or not preservation of the left colic artery ( LCA ) for colorectal cancer surgery .
The objective of this up date d systematic review and meta- analysis is to evaluate the current scientific evidence of LCA non-preservation versus LCA preservation in colorectal cancer surgery . | Background High morbidity rates related to anastomotic leakage and other factors restrict the application of laparoscopic rectal excision . The aim of the present study was to assess the effect of left colonic artery ( LCA ) preservation on postoperative complications after laparoscopic rectal excision . Methods Data from 888 patients from 28 leading hospitals in Japan who underwent laparoscopic-assisted sphincter-preserving resection of middle and low rectal cancers between 1994 and 2006 were analyzed . The effects of LCA preservation were analyzed among all anterior resection ( AR ) cases ( n = 888 ) and among AR cases with radical lymph node excision ( n = 411 ) . Results Among all AR cases , the tumor size , number of lymph nodes collected with evidence of metastasis , TNM factor , and TNM staging were smaller in the LCA preservation group . Regarding complications , the rate of anastomotic leak was significantly higher in the LCA non-preservation group among all AR cases , as well as among AR cases with radical lymph node excision . Nevertheless , there was no difference in survival rate between LCA preservation group and non-preservation group , as measured by the Kaplan – Meier method . Conclusions Our data suggest that the preservation of the LCA in laparoscopic AR for middle and low rectal cancer is associated with lower anastomotic leak rates OBJECTIVE To investigate the effect of ligation level of inferior mesenteric artery ( IMA ) on postoperative defecation function in patients with rectal cancer . METHODS A total of 128 rectal cancer patients who were planned to undergo low anterior resection in the First Hospital of Zibo City between January 1 , 2012 and December 31 , 2013 were prospect ively enrolled and r and omly divided into IMA high ligation group(63 cases , cutting distance of 1.0 to 1.5 cm to the root of IMA ) and low ligation group(65 cases , cutting distance of 0.5 to 1.0 cm to the root of left colic artery originated from IMA ) . The efficacy , especially the defecation function , was observed and compared 3 months and 1 year after surgery between the two groups . RESULTS No significant difference was found in the number of harvested lymph nodes between two groups[8(1 - 30 ) vs. 7(2 - 28 ) , P=0.125 ] , but high ligation group had greater number of metastatic lymph nodes[1(0 - 9 ) vs. 0(0 - 8 ) , P=0.041 ] . Frequency of defecation in high ligation group was significantly higher than that in low ligation group during postoperative 3-month follow-up[5(2 - 10)/d vs. 3(1 - 8)/d , P=0.035 ] , whereas other indexes of defecation function were not significantly different(all P>0.05 ) . The proportion of patients needing laxatives in high ligation group was higher than that in low ligation group during postoperative 1-year follow-up [ 11.3%(6/53 ) vs. 1.7%(1/58 ) , P=0.038 ] , whereas other indexes of defecation function were not significantly different as well ( all P>0.05 ) . Three cases and 2 cases showed recurrence in high ligation group and low ligation group respectively during postoperative 1-year follow-up without significant difference(P=0.623 ) . CONCLUSION Low ligation of IMA in low anterior resection for rectal cancer is beneficial to the protection against defecation function Purpose Both “ high tie ” ( HT ) and “ low tie ” ( LT ) are well-known strategies in rectal surgery . The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT . Methods Patients undergoing rectal resection for malignancy were included . Colonic perfusion was measured with laser Doppler flowmetry , immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop ( measurement A ) . This measurement was repeated after rectal resection ( measurement B ) . The blood flow ratios ( B/A ) were compared between the HT group and the LT group . Results Blood flow was measured in 33 patients , 16 undergoing HT and 17 undergoing LT . Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group . The blood flow ratio was significantly higher in the LT group ( 1.48 vs. 0.91 ; p = 0.04 ) , independent of the blood pressure . Conclusion This study shows the blood flow ratio to be higher in the LT group . This suggests that anastomoses may benefit from better perfusion when LT is performed Background Many Japanese surgeons routinely perform extended D3 lymph node dissection for the treatment of advanced rectosigmoid cancer with a view to achieving better tumor control . However , the application of a laparoscopic approach to perform D3 lymphadenectomy has been challenging . This phase 2 prospect i ve study aim ed to explore the oncologic results of this surgical approach . Methods The study was conducted during a 6-year period , in consideration of median follow-up time being > 3 years . The study subjects were tumor , node , metastasis system stage III rectosigmoid cancer staged by clinical images . The extent of D3 dissection and the postoperative lymph node mapping were according to the guidelines of the Japanese Society for Cancer of the Colon and Rectum . Patients were stratified according to the histopathologically proved highest level of involved lymph nodes and placed into N0 , N1 , N2 , and N3 groups . The primary end points of the study were the estimated time to recurrence and 5-year recurrence rate of cancer after laparoscopic D3 dissection . Results The estimated 5-year recurrence rate ( 20 % in the N0 group [ n = 10 ] ; 25 % in N1 [ n = 44 ] ; 33.3 % in N2 [ n = 30 ] ; and 42.8 % in N3 [ n = 14 ] ) , time to recurrence ( mean [ 95 % confidence interval ] 59.8 [ 42.6–76.9 ] months in the N0 group ; 56.8 [ 48.3–65.2 ] months in N1 ; 46.8 [ 37.5–56.1 ] months in N2 ; and 43.9 [ 28.3–59.4 ] months in N3 ) , and recurrence patterns were without significant difference ( all P values > .05 ) among N0 , N1 , N2 , and N3 groups . Therefore , by laparoscopic wide anatomic dissection , patients with lymph node involvement could be treated as well as those without lymph node metastasis . Laparoscopic D3 dissection facilitated the collection of more lymph nodes ( mean ± st and ard deviation , 27.4 ± 4.2 ) for histopathologic examination . Mapping of dissected lymph nodes showed that 18.2 % ( 16 of 88 ) patients had skip lymph node metastasis . D3 dissection facilitated upstaging of cancer ( from N0 to N3 ) in five patients ( 5.1 % ) . However , this procedure result ed in transient voiding dysfunction in 77.5 % patients and loss of ejaculatory function in 91.7 % . By laparoscopic approach , the D3 lymph node dissection was safely performed through small wounds , result ing in quick functional recovery and only moderate blood loss ( 324.8 ± 44.5 mL ) , but at the expense of a long operation time ( 294.4 ± 34.8 minutes ) . Conclusions The good short-term oncologic results and quick convalescence mean that the laparoscopic D3 dissection may be recommended for patients with stage III rectosigmoid cancer who could accept the genitourinary dysfunction Background : The level of inferior mesenteric artery ( IMA ) ligation for anterior resection of rectal cancer has several considerations concerning oncological outcomes . The primary endpoint of this r and omized controlled trial ( RCT ) was to assess bowel function between high and low ligation . This study was intended to clarify oncological outcome as the secondary endpoint . Objective : The aim of this study was to assess in a prospect i ve RCT whether the ligation level of the IMA in rectal cancer influences oncological outcomes . Methods : Between February 2008 and December 2011 , 100 patients who underwent anterior resection for rectal cancer were r and omized to perform either high or low ligation of the IMA . Oncological outcomes was the secondary endpoint of this RCT , whereas assessing bowel function was the primary endpoint . This RCT was registered at clinical trials.gov ( NCT00701012 ) . Results : There were no differences between the groups in terms of clinical data except for tumor stage . There were more advanced-stage patients in the high ligation group ( p = 0.046 ) . There were no lymph node ( LN ) metastases in the root of the IMA in the high ligation group . The average number of harvested LNs for the high and low ligation groups was 16.7 and 14.9 , respectively . There was no difference in disease-free survival ( DFS ) , site of first recurrence , and overall survival ( OS ) . When patients were in stage III , there was also no difference in DFS and OS . Conclusions : The ligation level of the IMA in rectal cancer may not influence oncological outcomes . However , further large-scale RCTs are needed to conclude this issue Aims The aim of this study is to evaluate the influence of dividing the inferior mesenteric artery ( IMA ) and preserving the left colic artery ( LCA ) on rectosigmoid cancer surgery . Patients and methods Colonic blood flow at the proximal site of the anastomosis was measured by laser Doppler flowmetry in 96 patients with cancer of the rectum and sigmoid colon while clamping IMA or LCA . Results were analyzed with patient characteristics and postoperative complications . Results Blood flow was significantly decreased by either IMA or LCA clamping , and its reduction rate was 38.5 ± 1.8 % , ranged from 0 to 82.8 % , or 16.4 ± 1.8 % , ranged from 0 to 66.2 % , respectively . For multivariate analyses , aging and male gender were predictive factors of high blood flow reduction by IMA clamping . The reduction rate was significantly correlated with aging in male patients , while no such correlation was observed in women . Aging correlation in men was more significant in ultralow anterior resection cases . Three elderly male patients received IMA high ligation among 19 patients who demonstrated more than 50 % blood flow reduction by IMA clamping . Among these , two patients , those who underwent ultralow anterior resection , suffered severe anastomotic ischemia . Conclusions Colonic blood flow at the proximal site of the anastomosis was significantly decreased by either IMA or LCA clamping . Patients with high reduction by IMA clamping need intraoperative efforts to prevent anastomotic ischemia , particularly in elderly male patients who undergo ultralow anterior resection Background and Aims : Impaired blood perfusion may be implicated in anastomotic leakage after anterior resection for rectal cancer . We investigated whether high ligation of the inferior mesenteric artery or total mesorectal excision compromises visceral blood flow in the colonic limb and the rectal stump , respectively . Material and Methods : A prospect i ve cohort study was conducted in a university hospital setting . We used Laser Doppler flowmetry to evaluate the impact of level of tie on colonic limb perfusion and the extent of the mesorectal excision on the rectal blood flow . In the rectum , different quadrants were also assessed . The Mann – Whitney U test was used to compare mean blood flow ratios between groups . Results : Some 23 patients were recruited in a convenience sample during a period in 2012–2013 . The mean blood flow ratio was not decreased after high tie compared to low tie surgery ( 1.71 vs 1.19 ; p = 0.28 ) . Total mesorectal excision reduced the mean blood flow ratio in the rectum , as compared with partial mesorectal excision ( 0.76 vs 1.28 ; p = 0.14 ) . This was especially pronounced in the posterior aspect of the rectum ( 0.66 vs 1.68 ; p = 0.02 ) . Conclusion : High tie ligation did not seem to decrease colonic limb perfusion , while total mesorectal excision may decrease rectal blood flow . The posterior quadrant of the rectum might be particularly vulnerable to the dissection involved in total mesorectal excision |
2,638 | 31,540,240 | No specific adjustments to exercise prescription were described .
There was a lack of tailoring of exercise programmes and limited effects were found . | Patients with chronic obstructive pulmonary disease ( COPD ) , asthma and interstitial lung diseases ( ILD ) frequently suffer from cardiovascular comorbidities ( CVC ) .
Exercise training is a cornerstone intervention for the management of these conditions , however recommendations on tailoring programmes to patients suffering from respiratory diseases and CVC are scarce .
This systematic review aim ed to identify the eligibility criteria used to select patients with COPD , asthma or ILD and CVC to exercise programmes ; assess the impact of exercise on cardiovascular outcomes ; and identify how exercise programmes were tailored to CVC . | The clinical and physiological effects of a medically supervised , indoor physical training programme were investigated in 36 asthmatic subjects aged 16 - 40 years . After clinical evaluation , lung function assessment , and progressive incremental exercise testing subjects were r and omly allocated to control and training groups . The measurements were repeated after a six week run in period and after a further three months in which those in the training group underwent an indoor training programme . The measurements made at three months were compared with those at the end of the run in period . There was no significant change in anthropometric characteristics , blood lipid profiles , or the provocative concentration of histamine causing a 20 % fall in FEV1 ( histamine PC20 ) in the group who underwent training . After training there were significant increases in mean maximal oxygen uptake ( ml kg-1 min-1 ) from 23 ( 5 ) to 28 ( 6 ) , oxygen pulse ( ml/beat ) from 8.8 ( 2.3 ) to 10.8 ( 2.4 ) , and anaerobic threshold ( 1/min ) from 1.11 ( 0.27 ) to 1.38 ( 0.33 ) . These changes were significantly greater in the group undergoing training than in the control group . There was also a significant fall in breathlessness scores ( Borg ratings ) , blood lactate , carbon dioxide output , and minute ventilation during submaximal exercise in the training group , with no change in the control group . The subject 's motivation , the initial level of fitness , and the symptom score at the time of training were the most important factors influencing improvements in cardiorespiratory fitness . Thus submaximal physical exercise of controlled intensity , sustained for three months , produced significant improvements in fitness and cardiorespiratory performance that should be advantageous to the exercising asthmatic patient . The availability of medical supervision throughout the exercise programme appears to have contributed to the successful outcome Introduction Patients with chronic obstructive pulmonary disease ( COPD ) exhibit aerobic function , autonomic nervous system , and mucociliary clearance alterations . These parameters can be attenuated by aerobic training , which can be applied with continuous or interval efforts . However , the possible effects of aerobic training , using progressively both continuous and interval sessions ( ie , linear periodization ) , require further investigation . Aim To analyze the effects of 12-week aerobic training using continuous and interval sessions on autonomic modulation , mucociliary clearance , and aerobic function in patients with COPD . Methods Sixteen patients with COPD were divided into an aerobic ( continuous and interval ) training group ( AT ) ( n=10 ) and a control group ( CG ) ( n=6 ) . An incremental test ( initial speed of 2.0 km·h−1 , constant slope of 3 % , and increments of 0.5 km·h−1 every 2 minutes ) was performed . The training group underwent training for 4 weeks at 60 % of the peak velocity reached in the incremental test ( vVO2peak ) ( 50 minutes of continuous effort ) , followed by 4 weeks of sessions at 75 % of vVO2peak ( 30 minutes of continuous effort ) , and 4 weeks of interval training ( 5 × 3-minute effort at vVO2peak , separated by 1 minute of passive recovery ) . Intensities were adjusted through an incremental test performed at the end of each period . Results The AT presented an increase in the high frequency index ( ms2 ) ( P=0.04 ) , peak oxygen uptake ( VO2peak ) ( P=0.01 ) , vVO2peak ( P=0.04 ) , and anaerobic threshold ( P=0.02 ) . No significant changes were observed in the CG ( P>0.21 ) group . Neither of the groups presented changes in mucociliary clearance after 12 weeks ( AT : P=0.94 and CG : P=0.69 ) . Conclusion Twelve weeks of aerobic training ( continuous and interval sessions ) positively influenced the autonomic modulation and aerobic parameters in patients with COPD . However , mucociliary clearance was not affected by aerobic training Objective To evaluate an entirely outpatient-based program of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease COPD , using St . George ’s Respiratory question naire ( SGRQ ) , the 6-minutes walking test ( 6-MWT ) and BODE index as the primary outcome measures . Methods A prospect i ve , parallel-group controlled study of an outpatient rehabilitation program in 80 patients with COPD ( 67 men and 13 women ; mean age 64.8 ± 10.6 years ; FEV1 , 42.8 % ± 7.6 % of the predicted value . The active group ( n = 40 ) took part in a 14-week rehabilitation program [ 3 h/wk , 1.5 h of education and exercise and 1.5 h of cycling ] . The control group ( n = 40 ) was review ed routinely as medical out patients . The following evaluations were carried out at study entry and after14 weeks : ( 1 ) pulmonary function studies ; ( 2 ) 6-minutes walking test 6MWT ; ( 3 ) quality of life ; and ( 4 ) BODE index . Results The following patients completed the study : 35 patients ( 87.5 % ) from the active group ( mean age , 63.7 ± 11.9 years ; mean forced expiratory volume in one second ( FEV1 ) , 41.9 ± 2.6 % of the predicted value ) ; and 36 patients ( 88 % ) from the control group ( mean age , 65.9 ± 10.3 years ; mean FEV1 , 43.33 ± 3.6 % of the predicted value ) . We found no changes in pulmonary function parameters in the active group and the control one at 14weeks . On the other h and , there were significant changes within the components of the SGRQ ( 12.3 for the score total ) for the patients of the active group but not for the patients of the control one ( only 1.5 for the score total ) , we observed also a significant increase in the distance of the 6-MWT in the patients of the active group but not for the patients of the control one , and finally a decrease of two points ( from 6 to 4 ) was noted in the score of the active group ’s BODE index without any change in the control group ’s one . Conclusion An outpatient-based of 14-week rehabilitation program significantly improved the quality of life and exercise tolerance without any change in the pulmonary function in patients with moderate COPD , and there was also a large decrease in the risk of death in rehabilitated patients as measured using the BODE index Background Chronic obstructive pulmonary disease ( COPD ) is a common cause of morbidity and mortality affecting a large number of individuals in both developed and developing countries and it represents a significant financial burden for patients , families and society . Pulmonary rehabilitation ( PR ) is a multidisciplinary program that integrates components of exercise training , education , nutritional support , psychological support and self-care , result ing in an improvement in dyspnea , fatigue and quality of life . Despite its proven effectiveness and the strong scientific recommendations for its routine use in the care of COPD , PR is generally underutilized and strategies for increasing access to PR are needed . Home-based self-monitored pulmonary rehabilitation is an alternative to outpatient rehabilitation . In the present study , patients with mild , moderate and severe COPD su bmi tted to either an outpatient or at-home PR program for 12 weeks were analyzed . Methods Patients who fulfilled the inclusion criteria were r and omized into three distinct groups : an outpatient group who performed all activities at the clinic , a home-based group who performed the activities at home and a control group . PR consisted of a combination of aerobic exercises and strengthening of upper and lower limbs 3 times a week for 12 weeks . Results There was a significant difference in the distance covered on the six-minute walk test ( p < 0.05 ) and BODE index ( p < 0.001 ) in the outpatient and at-home groups after participating in the rehabilitation program compared to baseline . Conclusion A home-based self-monitoring pulmonary rehabilitation program is as effective as outpatient pulmonary rehabilitation and is a valid alternative for the management of patients with COPD .RiassuntoRazionaleLa broncopneumopatia cronica ostruttiva ( BPCO ) è una causa frequente di morbilità e mortalità che colpisce un’ampia quota di popolazione sia nel mondo industrializzato che nei Paesi in via di sviluppo e rappresenta un peso economico di rilievo per pazienti , familiari e collettività . La riabilitazione respiratoria ( PR ) è un programma multidisciplinare che inegra componenti di riallenamento all’esercizio fisico , educazionale , supporto nutrizionale , supporto psicologico ed autoaiuto , che porta ad un miglioramento della dispnea , della affaticabilità e della qualità della vita . Nonostante la provata efficacia e le forti raccom and azioni delle società scientifiche al suo impiego routinario nel trattamento della BPCO , la PR è generalmente sottoutilizzata e si rendono perciò necessarie strategie per aumentarne l’utilizzo . La PR effettuata a domicilio ed auto-monitorata dal paziente stesso è un’alternativa alla classica riabilitazione ambulatoriale . In questo studio sono stati valuati pazienti con BPCO di grado lieve , moderato e grave sottoposti a un programma di PR ambulatoriale o domiciliare . MetodiI pazienti eligibili allo studio sono stati r and omizzati in tre gruppi : un gruppo ambulatoriale che effettuava tutte le attività in ospedale , un gruppo domiciliare che effettuava il programma a domicilio ed un gruppo di controllo . Il programma di PR consisteva in una combinazione di esercizi aerobici e di rafforzamento della muscolatura degli arti superiori e inferiori per 3 volte la settimana per 12 settimane . RisultatiSia nel gruppo che ha partecipato al PR ambulatoriale che in quello domiciliare si sono rilevate differenze significative rispetto alle misure di base nella distanza coperta con il test del cammino di 6 minuti ( p < 0.05 ) che nell’indice BODE ( p < 0.001 ) . Conclusion iUn programma di riabilitazione respiratoria automonitorato eseguito a domicilio ha efficacia sovrapponibile ad un programma ambulatoriale e può perciò essere considerato una valida alternativa nella gestione del paziente con BPCO This study poses two questions : 1 ) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease ( COPD ) ? and 2 ) what is the effect of a r and omized , controlled , 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance ? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients ( age 49+/-11 yrs ) , mean forced expiratory volume in one second ( FEV1 ) 77+/-23 % pred and 52 healthy , sedentary subjects ( age 51 ( 10 ) yrs ) , mean FEV1 109+/-16 % pred . The 43 COPD patients were r and omly allocated into training ( n=26 ) and control ( n=17 ) groups . Isokinetic and isotonic muscle function , whole body endurance , maximal exercise capacity and lung function were measured . The COPD patients had reduced isokinetic muscle function ( with the exception of sustained upper limb strength ) as compared with healthy sedentary subjects . Muscle function improved after weight training in the COPD patients . Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption . A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which can not be explained by factors such as hypoxaemia and malnutrition . Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning Global asthma control levels are suboptimal . The influence of regular exercise on asthma control is unclear . We assessed the effects of a 12-week supervised exercise intervention followed by 12 weeks of self-administered exercise on adults with partially controlled asthma ( n = 21 ) and matched controls ( n = 15 ) . Assessment s were conducted at baseline and week 12 for both the exercise and control group , and again at week 24 for the exercise group . There was a significant treatment effect on asthma control in the exercise group , as measured by the Asthma Control Question naire ( ACQ ) , from baseline to week 12 , compared with the control group . A clinical ly significant improvement ( 0.5 increase in ACQ score ) was observed for asthma quality of life and ACQ in the exercise group from baseline to week 12 . There was a significant improvement in aerobic fitness from baseline to week 24 in the exercise group . In conclusion , a 12-week supervised exercise intervention led to improvements in asthma control and quality of life in partially controlled asthmatics motivated to exercise . These improvements were maintained , while aerobic fitness and perceived asthma control significantly improved over an additional 12 weeks of self-administered exercise . These findings indicate that a structured exercise intervention can improve asthma control Most pulmonary rehabilitation ( PR ) programs do not currently incorporate IMT in their PR programs for COPD patients . The aim of the present study was to assess the influence of adding IMT to the patients already involved in a rehabilitation program . Thirty-four patients with significant COPD were recruited for the study . All patients participated in a general exercise reconditioning ( GER ) program for 12 weeks . The patients were then r and omized to receive IMT or sham IMT , in addition to GER for the next 6 months . Following three months of GER training there was a significant increase in the 6-min walk test ( 6MWT ) ( from mean+/-SEM 254+/-38 to 322+/-42 m , p<0.01 ) , and small but non-significant decreases in the perception of dyspnea ( POD ) , and in the St. George Respiratory Question naire score ( SGRQ ) . Following the addition of IMT to the GER program there was a significant increase in the PI(max ) in the GER+IMT group ( from 66+/-4.7 to 78+/-4.5 cm H(2)O , p<0.01 ) . This was accompanied by a significant improvement in the POD and a further significant improvement in the SGRQ score . IMT provides additional benefits to patients undergoing PR program and is worthwhile even in patients who have already undergone a GER program The main objective of this study is to investigate the long-term effects , 3 years after the end of a 2-year pulmonary rehabilitation program with three weekly 1-h exercise sessions and 32 h of education in patients with chronic obstructive pulmonary disease . The method consists of open prospect i ve observational study with 30 patients . Outcome measures were quality of life ( QoL ) ( St George 's Respiratory Question naire , SGRQ ) , physical exercise performance ( 6-min walking test , 6MWT ) , self-management abilities , lung function , hospitalization , and self-reported exercise . FEV(1 ) at baseline was 40.1 % of predicted . The participants had statistical and clinical significant decrease in SGRQ ( improved QoL ) and increase in 6MWT during the program . They maintained the level of health they achieved during the program in the next 3 years , with a stable SGRQ score ( -0.5 points , 95 % CI -3.8 to 2.6 P=1.000 ) and 6MWT ( + 10 m 95 % CI 28 to -4 , P=0.273 ) . Eighty percent of the participants had exercised at least 30 min three times a week from the end of the program to year 5 . In conclusion , the participants had maintained their achieved level of health , improved their lung function slightly , and continued to exercise regularly 3 years after the end of the program STUDY OBJECTIVES To determine whether long-term treatment with exercise therapy results in more favorable , disease-specific , health-related quality of life ( HRQL ) compared with short-term treatment with exercise therapy ; and to determine whether there are gender differences in disease-specific HRQL among individuals r and omized into the two treatment groups . DESIGN R and omized clinical trial . SETTING Center-based exercise therapy unit at a university . PARTICIPANTS One hundred forty patients with COPD ; 118 completed trial . INTERVENTIONS Short-term exercise therapy ( 3 months ) ; long-term exercise therapy ( 18 months ) . MEASUREMENTS Chronic Disease Respiratory Question naire ( CRQ ) . RESULTS After 3 months of treatment , there were significant improvements in all CRQ scores for men and women ( p < 0.01 ) , and for the total sample ( p < 0.01 ) . At 18 months , individuals r and omized into the long-term group had significantly more favorable scores than the short-term group for dyspnea ( p = 0.03 ) , fatigue ( p < 0.01 ) , emotional function ( p = 0.04 ) , and mastery ( p = 0.04 ) . However , these effects were moderated by gender . That is , men in the long-term group reported significantly more favorable scores than men in the short-term group for dyspnea ( 0.04 ) , fatigue ( p < 0.001 ) , emotional function ( p = 0.02 ) , and mastery ( p = 0.02 ) . At the 18-month assessment , there were no differences between long-term and short-term exercise therapy for women on any of the subscales of the CRQ . CONCLUSIONS Taken collectively , the CRQ data demonstrate that long-term exercise therapy has little added benefit for women over short-term exercise therapy ; however , men derive significant benefits from extended training Background The effectiveness of clinic-based pulmonary rehabilitation in advanced COPD is well established , but few data exist for less severe patients treated in alternative setting s. The purpose of this study was to investigate whether a novel , community-based exercise program ( CBE ) was feasible and effective for patients with moderate COPD . Methods Nineteen patients with moderate COPD ( mean FEV1 62 % ) and self-reported exercise impairment were r and omized to 12-weeks of progressive endurance and strength training at a local health club under the guidance of a certified personal trainer , or to continuation of unsupervised habitual physical activity . Outcomes assessed at baseline and 12 weeks included session compliance , intensity adherence , treadmill endurance time , muscle strength , dyspnea , and health status . Results Compliance was 94 % and adherence was 83 % . Comparisons between CBE and control groups yielded the following mean ( SEM ) differences in favor of CBE : endurance time 134 ( 74 ) seconds versus -59 ( 49 ) seconds ( P = 0.041 ) and TDI 5.1 ( 0.8 ) versus -0.2 ( 0.5 ) ( P < 0.001 ) . The CBE group increased muscle strength ( weight lifted ) by 11.8 kilograms per subject per week of training ( P < 0.001 ) . SGRQ was not significantly changed . Conclusions We demonstrated the feasibility and effectiveness of a novel community-based exercise program involving health clubs and personal trainers for patients with moderate COPD .Trial registration Clinical Trials.gov Identifier NCT01985529 Pulmonary rehabilitation ( PR ) remains grossly underutilised by suitable patients worldwide . We investigated whether home-based maintenance tele-rehabilitation will be as effective as hospital-based maintenance rehabilitation and superior to usual care in reducing the risk for acute chronic obstructive pulmonary disease ( COPD ) exacerbations , hospitalisations and emergency department ( ED ) visits . Following completion of an initial 2-month PR programme this prospect i ve , r and omised controlled trial ( between December 2013 and July 2015 ) compared 12 months of home-based maintenance tele-rehabilitation ( n=47 ) with 12 months of hospital-based , outpatient , maintenance rehabilitation ( n=50 ) and also to 12 months of usual care treatment ( n=50 ) without initial PR . In a multivariate analysis during the 12-month follow-up , both home-based tele-rehabilitation and hospital-based PR remained independent predictors of a lower risk for 1 ) acute COPD exacerbation ( incidence rate ratio ( IRR ) 0.517 , 95 % CI 0.389–0.687 , and IRR 0.635 , 95 % CI 0.473–0.853 ) , respectively , and 2 ) hospitalisations for acute COPD exacerbation ( IRR 0.189 , 95 % CI 0.100–0.358 , and IRR 0.375 , 95 % CI 0.207–0.681 ) , respectively . However , only home-based maintenance tele-rehabilitation and not hospital-based , outpatient , maintenance PR was an independent predictor of ED visits ( IRR 0.116 , 95 % CI 0.072–0.185 ) . Home-based maintenance tele-rehabilitation is equally effective as hospital-based , outpatient , maintenance PR in reducing the risk for acute COPD exacerbation and hospitalisations . In addition , it encounters a lower risk for ED visits , thereby constituting a potentially effective alternative strategy to hospital-based , outpatient , maintenance PR . Home tele-rehabilitation reduces risk of COPD exacerbation ; is effective alternative to in-hospital rehabilitation Purpose : The aim of this study was to investigate the effect of outpatient pulmonary rehabilitation ( PR ) program and the use of 6-min walk distance ( 6MWD ) , expressed as a percentage of the predicted value ( % 6MWD ) , to quantify response to PR in elderly patients with interstitial lung disease ( ILD ) . Methods : This was a prospect i ve , nonr and omized controlled study . Forty eligible patients with stable ILD ( ≥65 y old ) were advised to attend an outpatient PR program for 3 mo . Thirteen patients completed the PR program and formed the PR group . Ten patients who did not attend the PR program were evaluated after 3 mo and formed the control group . Patients in the PR group underwent a comprehensive 3-mo hospital-based outpatient PR program , consisting of educational support and supervised exercise training , and attended the rehabilitation unit weekly . Results : Change in the absolute 6MWD ( & Dgr;6MWD ) in the PR group was not significantly different compared with the control group ( P = .062 ) . Change in % 6MWD ( & Dgr;%6MWD ) was greater in the PR group than in the control group . Baseline 6MWD was not correlated with & Dgr;6MWD , but baseline % 6MWD was significantly correlated with & Dgr;6MWD and & Dgr;%6MWD . Conclusion : PR had a beneficial effect on elderly patients with ILD in terms of exercise endurance . % 6MWD might be more useful than the absolute 6MWD as an outcome measure of PR and as a predictor of response to PR in elderly patients with ILD Background Religious coping ( RC ) is defined as the use of behavioral and cognitive techniques in stressful life events in a multidimensional construct with positive and negative effects on outcomes , while religiosity is considered a use of individual beliefs , values , practice s , and rituals related to faith . There is no evidence for the effects of pulmonary rehabilitation ( PR ) in RC and religiosity in patients with COPD . The aims of this study were 1 ) to compare RC and religiosity in patients with COPD following PR and 2 ) to investigate associations between changes in RC , religiosity and exercise capacity , quality of life ( QoL ) , anxiety , depression , and dyspnea . Methods Seventy-four patients were enrolled in this study including 38 patients in the PR group and 36 patients in the control group . PR protocol was composed of a 12-week ( three sessions per week , 60 min per day ) outpatient comprehensive program , and the control group was composed of patients in a waiting list for admission to PR program . RC , religiosity , exercise capacity , QoL , anxiety , depression , and dyspnea were measured before and after the study protocol . Results Positive religious coping and organizational religious activities increased ( p=0.01 ; p<0.001 , respectively ) , while negative religious coping decreased ( p=0.03 ) after 12 weeks in the PR group ( p<0.001 ) . Significant associations were observed between changes in RC , organizational religiosity with exercise capacity , and QoL following PR . No differences were found in the control group . Conclusion PR improves RC and organizational religiosity in patients with COPD , and these improvements are related to increases in exercise capacity and BACKGROUND Idiopathic pulmonary fibrosis ( IPF ) is a chronic , progressive and fatal interstitial lung disease associated with cardiovascular impairments which compromise exercise tolerance and worsen prognosis . AIM To examine the effect of participating in supervised exercise training ( ET ) program on cardiovascular function in patients with IPF . DESIGN A r and omized controlled study . SETTING Outpatient hospital . POPULATION Thirty-two IPF patients ( 68±8 years ) . METHODS An ET group ( N.=15 ) participated in a 12-week twice a week 60-minute supervised exercise program while a control group ( N.=17 ) received usual care . At baseline and after the 12-week intervention all patients underwent resting echocardiography , cardiopulmonary exercise testing and N-terminal pro-brain natriuretic peptide ( NT-proBNP ) assessment s. RESULTS The ET group significantly improved peak values of exercise cardiovascular indexes while the control group showed a trend of deterioration in the outcomes . The mean difference between the groups ( 95 % CI ) for circulatory power was 638 mLO2/kg/min/mmHg ( 95 % CI : 197 - 1080 ) ( P=0.006 ) , cardiac power output 0.3 W ( 95 % CI : 0.1 to 0.6 ) ( P=0.041 ) , and stroke work 312 mL/beat/mmHg ( 95 % CI : 52 - 573 ) ( P=0.02 ) . No significant differences between groups were detected in most echocardiography measures and NT-proBNP . Changes in exercise cardiovascular indexes showed significant correlation with improvements in functional capacity , dyspnea and quality of life among ET group . CONCLUSIONS Participation in supervised ET program can improve exercise cardiovascular function in patients with IPF , however resting cardiac evaluations seem to be less sensitive to detect such changes . CLINICAL REHABILITATION IMPACT These findings underscore the utility of supervised ET for cardiovascular enhancement which may also be clinical ly beneficial in reducing the cardiovascular morbidity and mortality in IPF patients Background In COPD , functional status is improved by pulmonary rehabilitation ( PR ) but requires specific facilities . Tai Chi , which combines psychological treatment and physical exercise and requires no special equipment , is widely practice d in China and is becoming increasingly popular in the rest of the world . We hypothesized that Tai Chi is equivalent ( ie , difference less than ±4 St. George ’s Respiratory Question naire [ SGRQ ] points ) to PR . Methods A total of 120 patients ( mean FEV1 , 1.11 ± 0.42 L ; 43.6 % predicted ) bronchodilator‐naive patients were studied . Two weeks after starting indacaterol 150 & mgr;g once daily , they r and omly received either st and ard PR thrice weekly or group Tai Chi five times weekly , for 12 weeks . The primary end point was change in SGRQ prior to and following the exercise intervention ; measurements were also made 12 weeks after the end of the intervention . Results The between‐group difference for SGRQ at the end of the exercise interventions was –0.48 ( 95 % CI PR vs Tai Chi , –3.6 to 2.6 ; P = .76 ) , excluding a difference exceeding the minimal clinical ly important difference . Twelve weeks later , the between‐group difference for SGRQ was 4.5 ( 95 % CI , 1.9 to 7.0 ; P < .001 ) , favoring Tai Chi . Similar trends were observed for 6‐min walk distance ; no change in FEV1 was observed . Conclusions Tai Chi is equivalent to PR for improving SGRQ in COPD . Twelve weeks after exercise cessation , a clinical ly significant difference in SGRQ emerged favoring Tai Chi . Tai Chi is an appropriate substitute for PR . Trial Registry Clinical Trials.gov ; No. : NCT02665130 ; URL : www . clinical trials.gov BACKGROUND Supplemental oxygen therapy has been shown to improve exercise performance in patients with chronic obstructive pulmonary disease ( COPD ) . It is unknown whether the magnitude of this benefit would be affected by participation in a pulmonary rehabilitation program . OBJECTIVE To compare the effects of supplemental oxygen on exercise capacity in nonhypoxemic COPD patients before and after participation in a pulmonary rehabilitation program . METHODS Sixteen patients with COPD underwent two pairs of constant-load exercise tests before and after participation in a three-month outpatient pulmonary rehabilitation program . Each pair of exercise tests consisted of a test performed with room air and a second test performed with 50 % supplemental oxygen , in r and om order . The primary outcome was the difference in exercise duration between tests performed with supplemental oxygen and with room air . This difference was compared before and after participation in a pulmonary rehabilitation program . RESULTS Supplemental oxygen therapy improved exercise duration by 75 s before participation in a pulmonary rehabilitation program and by 153 s following pulmonary rehabilitation . Rehabilitation alone improved exercise duration by 28 s , but rehabilitation appeared to augment the exercise benefits of supplemental oxygen therapy by a mean of 78 s ( 95 % CI 11 s to 145 s ; P = 0.03 ) . CONCLUSION The effects of supplemental oxygen therapy were augmented after pulmonary rehabilitation . The improvement in exercise duration with supplemental oxygen following rehabilitation was greater than either supplemental oxygen or pulmonary rehabilitation alone Background Although the endurance shuttle walk test ( ESWT ) has proven to be responsive to change in exercise capacity after pulmonary rehabilitation ( PR ) for COPD , the minimally important difference ( MID ) has not yet been established . We aim ed to establish the MID of the ESWT in patients with severe COPD and chronic hypercapnic respiratory failure following PR . Methods Data were derived from a r and omized controlled trial , investigating the value of noninvasive positive pressure ventilation added to PR . Fifty-five patients with stable COPD , GOLD stage IV , with chronic respiratory failure were included ( mean ( SD ) FEV1 31.1 ( 12.0 ) % pred , age 62 ( 9 ) y ) . MID estimates of the ESWT in seconds , percentage and meters change were calculated with anchor based and distribution based methods . Six minute walking distance ( 6MWD ) , peak work rate on bicycle ergometry ( Wpeak ) and Chronic Respiratory Question naire ( CRQ ) were used as anchors and Cohen ’s effect size was used as distribution based method . Results The estimated MID of the ESWT with the different anchors ranged from 186–199 s , 76–82 % and 154–164 m. Using the distribution based method the MID was 144 s , 61 % and 137 m. Conclusions Estimates of the MID for the ESWT after PR showed only small differences using different anchors in patients with COPD and chronic respiratory failure . Therefore we recommend using a range of 186–199 s , 76–82 % or 154–164 m as MID of the ESWT in COPD patients with chronic respiratory failure . Further research in larger population s should eluci date whether this cut-off value is also valid in other COPD population s and with other interventions .Trial registration Clinical Trials . Gov ( ID NCT00135538 ) Abstract Background Evidence regarding the efficacy of nutritional supplementation to enhance exercise training responses in COPD patients with low muscle mass is limited . The objective was to study if nutritional supplementation targeting muscle derangements enhances outcome of exercise training in COPD patients with low muscle mass . Methods Eighty‐one COPD patients with low muscle mass , admitted to out‐patient pulmonary rehabilitation , r and omly received oral nutritional supplementation , enriched with leucine , vitamin D , and omega‐3 fatty acids ( NUTRITION ) or PLACEBO as adjunct to 4 months supervised high intensity exercise training . Results The study population ( 51 % males , aged 43–80 ) showed moderate airflow limitation , low diffusion capacity , normal protein intake , low plasma vitamin D , and docosahexaenoic acid . Intention‐to‐treat analysis revealed significant differences after 4 months favouring NUTRITION for body mass ( mean difference ± SEM ) ( + 1.5 ± 0.6 kg , P = 0.01 ) , plasma vitamin D ( + 24 % , P = 0.004 ) , eicosapentaenoic acid ( + 91%,P < 0.001 ) , docosahexaenoic acid ( + 31 % , P < 0.001 ) , and steps/day ( + 24 % , P = 0.048 ) . After 4 months , both groups improved skeletal muscle mass ( + 0.4 ± 0.1 kg , P < 0.001 ) , quadriceps muscle strength ( + 12.3 ± 2.3 Nm , P < 0.001 ) , and cycle endurance time ( + 191.4 ± 34.3 s , P < 0.001 ) . Inspiratory muscle strength only improved in NUTRITION ( + 0.5 ± 0.1 kPa , P = 0.001 ) and steps/day declined in PLACEBO ( −18%,P = 0.005 ) . Conclusions High intensity exercise training is effective in improving lower limb muscle strength and exercise performance in COPD patients with low muscle mass and moderate airflow obstruction . Specific nutritional supplementation had additional effects on nutritional status , inspiratory muscle strength , and physical activity compared with placebo The aim of this study was to examine the effect of high intensity physical group training in water and on l and for patients with COPD with regard to physical capacity and health related quality of life ( HRQoL ) . A controlled , semi-r and omised study was conducted where 30 patients were r and omised to training either in water or on l and . Thirteen patients constituted a control group . Forty-three out patients , with moderate to severe COPD ( 27w/16 m ) , from two local hospitals in northern Sweden , were included in the study . High intensity physical group training in water ( water group ) or on l and ( l and group ) was performed for 12weeks , three times per week , 45min per session . The control group received no intervention . Pre- and post-intervention , all patients performed incremental and endurance shuttle walking tests ( ISWT and ESWT ) , cycle ergometer tests and responded question naires about HRQoL ( St. Georges Respiratory Question naire -- SGRQ and SF-36 ) . The patients trained with a mean heart rate of 80 - 90 % of peak heart rate . Both training groups increased the distance walked , i.e. l and group in ISWT ( 25 m ) and water group in ESWT ( 179 m ) . The water group increased the distance in ESWT significantly more that both the l and and the control groups . Both training groups increased the time cycled ( 40 - 85s ) and work load ( 10 - 20W ) in the cycle ergometer test . The control group deteriorated in HRQoL according to total score in SGRQ while the training groups remained constant . The water group improved their activity score in SGRQ and their physical health score in SF-36 and those improvements were significant as compared to the l and and the control groups . In conclusion , high intensity physical group training in water is of benefit for patients with COPD . It was in some areas found to be even more effective regarding improvements in physical capacity and experienced physical health compared to the same kind of training on l and Purpose : To determine the opinions and attitudes toward exercise in people with chronic obstructive pulmonary disease ( COPD ) who had completed a r and omised controlled trial of 12‐months maintenance exercise . Methods : Participants were eligible for recruitment to the maintenance exercise study if they had COPD and had completed an 8‐week pulmonary rehabilitation program . They were r and omized into an Intervention Group ( IG ) that consisted of once weekly , supervised hospital‐based maintenance exercise plus home exercise for 12 months or a Control Group that undertook unsupervised home maintenance exercise for 12 months . At the end of the 12 months , participants completed a survey consisting of 23 questions using a visual analogue scale ( VAS ) of 100 mm . Results : Forty‐eight participants completed the 12 month study and 36 participants ( 75 % ) completed the survey [ IG mean ( SD ) : age 65 ( 8) years , FEV1 58 ( 20 ) % predicted ; CG : age 66 ( 8) years , FEV1 67 ( 17 ) % predicted ] . No between group difference was found for the importance of exercise , the benefits of the program or the importance of support from the physiotherapist . However , the IG reported exercising more regularly , having more enjoyment of being involved in the maintenance exercise program , greater benefit in general well‐being , and better physical fitness . Conclusions : At the completion of the 12 month exercise study , the survey results showed that all participants reported positive attitudes towards both supervised and unsupervised maintenance exercise programs , with the IG reporting greater benefits Purpose Loss of skeletal muscle strength is commonly seen with chronic obstructive pulmonary disease ( COPD ) . The study aim was to determine the effects of comprehensive upper-body resistance training ( 8 different lifts ) and a self-efficacy enhancing intervention in COPD with respect to muscle strength , symptoms , functional status and exercise adherence . Methods This r and omized trial had 3 groups : upper-body resistance training with an intervention to enhance self-efficacy ( UBR + SE ) , upper-body resistance training and health education ( UBR + HE ) , gentle chair exercises and health education ( CE + HE ) . Subjects performed 16 weeks of supervised training , then 12 months of long-term maintenance at home . Outcomes were : muscle strength , dyspnea , functional status , self-efficacy , and adherence . Results Sixty-four subjects completed 16 wks of training : age 71 ± 8 yr , fat-free mass index 19 ± 3 kg/m2 , forced expiratory volume in one second 58 ± 18 percent predicted . The UBR + SE intervention produced a 46 % increase in strength compared to a 36 % increase in the UBR + HE group ( P = 0.054 ) . The combined UBR + SE and UBR + HE groups produced a 41 % increase in strength compared to an 11 % increase in the CE+HE ( P < 0.001 ) . The combined UBR groups also demonstrated increases in lean arm mass ( P = 0.003 ) and a trend toward decreased dyspnea ( P = 0.053 ) . There were no group differences in attrition , attendance and training progression . Fifty subjects completed long-term maintenance and the UBR + SE and UBR + HE groups retained some gains in muscle strength , 24 % and 21 % respectively , and the CE + HE group lost 3 % of muscle strength from baseline . Conclusion The study provides strong evidence that comprehensive resistance training increased strength and lean arm mass and that strength can be partially maintained through a simple home program using h and weights . It provides limited evidence that upper-body resistance training improved dyspnea and that the exercise-specific self-efficacy enhancing intervention was beneficial BACKGROUND Physical exercise training is an evidence -based treatment in chronic obstructive pulmonary disease , and patients ' peak work rate is associated with reduced chronic obstructive pulmonary disease mortality . We assessed whether supplemental oxygen during exercise training in nonhypoxemic patients with chronic obstructive pulmonary disease might lead to superior training outcomes , including improved peak work rate . METHODS This was a r and omized , double-blind , controlled , crossover trial . Twenty-nine patients with chronic obstructive pulmonary disease ( aged 63.5 ± 5.9 years ; forced expiratory volume in 1 second percent predicted , 46.4 ± 8.6 ) completed 2 consecutive 6-week periods of endurance and strength training with progressive intensity , which was performed 3 times per week with supplemental oxygen or compressed medical air ( flow via nasal cannula : 10 L/min ) . Each session of electrocardiography-controlled interval cycling lasted 31 minutes and consisted of a warm-up , 7 cycles of 1-minute intervals at 70 % to 80 % of peak work rate alternating with 2 minutes of active recovery , and final cooldown . Thereafter , patients completed 8 strength-training exercises of 1 set each with 8 to 15 repetitions to failure . Change in peak work rate was the primary study end point . RESULTS The increase in peak work rate was more than twice as high when patients exercised with supplemental oxygen compared with medical air ( 0.16 ± 0.02 W/kg vs 0.07 ± 0.02 W/kg ; P < .001 ) , which was consistent with all other secondary study end points related to exercise capacity . The impact of oxygen on peak work rate was 39.1 % of the overall training effect , whereas it had no influence on strength gain ( P > .1 for all exercises ) . CONCLUSIONS We report that supplemental oxygen in nonhypoxemic chronic obstructive pulmonary disease doubled the effect of endurance training but had no effect on strength gain AIM In this study , the effects of a 12-week hospital-based outpatient pulmonary rehabilitation program ( HRP ) are compared with those of a 12-week home-care rehabilitation program ( HCRP ) in COPD patients . A control group received no rehabilitation therapy . METHODS After r and omization and stratification , effects on lung function , exercise performance ( 4-min walking test and cycle ergometer test ) , dyspnea , and leg effort during exercise , and well-being were assessed in 45 COPD patients with moderate to severe airflow limitation ( mean [ SD ] FEV1 percent predicted , 42.8 [ 8.4 ] ) . RESULTS After HRP and HCRP , at 3 to 6 months after the start of the study , equal improvements were detected in exercise capacity and in Borg dyspnea and leg effort scores at similar work levels during the cycle test . However , whereas after HRP at longer term values tended to return to baseline outcome , after HCRP a further ongoing significant improvement in exercise capacity was observed , while Borg dyspnea scores remained significantly improved over 18 months . Improvements in cycle workload and dyspnea score were significantly better maintained after HCRP as compared with HRP . Lung function , arterial oxygen saturation , and heart frequency during exercise did not change . A significant improvement in well-being was maintained over 18 months in both rehabilitation groups . CONCLUSION Beneficial effects are achieved both after a HRP and a HCRP in COPD patients with moderate to severe airflow limitation . Yet we recommend to initiate HCRPs as improvements are maintained longer and are even further strengthened in this setting PURPOSE Research supports an association between aerobic fitness and cognitive functioning in chronic obstructive pulmonary disease ( COPD ) patients . However , the impact of exercise intervention duration has not been satisfactorily examined . Therefore , the purpose of this study was to examine the effects of a 3-month and an 18-month exercise intervention on the cognitive functioning of an older COPD sample . METHODS COPD patients ( 56 - 80 yr ) were given a 3-month exercise program and then were r and omly assigned to continue for an additional 15 months ( long-term group ) or to leave the exercise program ( short-term group ) . Age and education were assessed before involvement in the exercise intervention ( baseline ) . Fluid intelligence , pulmonary function , aerobic fitness , and depression were assessed at baseline , at 3 months , and at 18 months . RESULTS After 3 months of exercise , results indicated that cognitive function and walk distance improved significantly . Results also indicated that the gain in cognitive function was reliably predicted by the decrease in VE at VO2peak . At 18 months , results indicated that cognitive performance did not differ between the short- and long-term exercise groups , but that walk distance improved significantly for the long-term group , but not for the short-term group . Results of a regression analysis showed that the cognitive performance improvement from 3 months to 18 months was predicted by the gain in walk distance and by the decrease in VE at VO2peak . CONCLUSION It is concluded that improvements in aerobic fitness are associated with gains in fluid intelligence after 3 and 18 months of exercise training in COPD patients . However , at 18 months , exercise group was not predictive of the gains in cognitive performance . Therefore , a 3-month exercise program may be a sufficient impetus to foster these cognitive gains in COPD patients INTRODUCTION : Pulmonary rehabilitation is effective for patients with COPD , but its benefit is less clearly established in idiopathic pulmonary fibrosis ( IPF ) , especially in regard to levels of physical activity and health-related quality of life . The objectives were to determine whether pulmonary rehabilitation increased physical activity as assessed by the International Physical Activity Question naire ( IPAQ ) , and improved quality of life and symptoms as assessed by the St George respiratory question naire for IPF ( SGRQ-I ) and the Borg dyspnea index ( BDI ) . METHODS : Subjects who met current criteria for IPF were r and omized to a 3-month pulmonary rehabilitation program ( n = 11 ) or to a control group ( n = 10 ) . The rehabilitation group participated in twice-weekly , 90-min exercise sessions ( 24 total sessions ) . The control group maintained its preceding , normal physical activity . All subjects underwent 6-min walk tests to assess the postexertion BDI . The SGRQ-I and a 5-point self- assessment of health were completed at baseline , after 3 months of intervention or observation , and after 3-month follow-up . All subjects completed the IPAQ weekly . RESULTS : Subjects in the rehabilitation group maintained significantly higher levels of physical activity throughout the 3-month rehabilitation program ( rehabilitation : 51,364 ± 57,713 [ mean ± SD ] metabolic equivalent of task-minutes ; control : 20,832 ± 37,155 , P = .027 by 2-tailed Mann-Whitney test ) . SGRQ-I symptom domain scores improved considerably by −9 ± 22 in the rehabilitation group , whereas in the control group they worsened ( 16 ± 12 rehabilitation compared with control , P = .013 by 2-tailed Mann-Whitney test ) . During the 3-month follow-up , self-reported physical activity levels in the rehabilitation group were 14,428 ± 8,884 metabolic equivalent of task-minutes and in the control group 16,923 ± 32,620 ( P = .17 by 2-tailed Mann-Whitney test ) , demonstrating substantial reversal of activity in the rehabilitation group . BDI scores after 6-min walk tests did not change significantly . CONCLUSIONS : A 3-month rehabilitation program significantly improved symptoms ( SGRQ-I ) and physical activity levels ( IPAQ ) in subjects with IPF while they participated actively in the program . ( Clinical Trials.gov registration NCT01118221 . OBJECTIVE To evaluate the influence of physical training with or without noninvasive ventilation at 2 levels of pressure in the airways ( BiPAP ) in patients with chronic obstructive pulmonary disease . METHODS Eighteen patients with FEV(1 ) = 34 + /- 8 % of predicted values , mean age of 68 + /- 9 years were r and omly distributed into 2 groups , one group performing physical training on a treadmill and the other group performing physical training associated with BiPAP ( physical training+B ) , for 30 minutes , 3 times a week for 12 weeks . The training velocity was based on a test of cardiopulmonary force performed pre- and postintervention , which registered the values for heart rate , systolic blood pressure , diastolic blood pressure , peripheral oxygen saturation , blood lactate , sensation of dyspnea , respiratory muscle strength , and analysis of gases expired such as oxygen consumption and the production of carbon dioxide . RESULTS For both groups , there was a significant improvement in dyspnea and peripheral oxygen saturation at identical levels of physical exercise , in distance walked during the physical training , and in respiratory muscle strength ( P < 0.05 ) . Only the physical training+B group had a significant improvement in heart rate , systolic blood pressure , and oxygen consumption after training ( P < 0.05 ) . Significant reductions of blood lactate were observed at identical levels of exercise in physical training+B when compared to isolated physical training ( from 1.3 + /- 0.7 mMol/L versus 2.5 + /- 0.9 mMol/L , ( P < 0.05 ) , respectively ) . CONCLUSION Physical training associated with BiPAP enhanced the oxidative muscular capacity and could be an adjunctive recourse for physical rehabilitation in patients with chronic obstructive pulmonary disease STUDY OBJECTIVES The purpose s of this study were as follows : ( 1 ) to determine whether physical performance , quality of life , and dyspnea with activities of daily living improved following both short-term and long-term pulmonary rehabilitation ( PR ) across multiple hospital outpatient programs ; ( 2 ) to examine the differences in these parameters between men and women ; and ( 3 ) to determine what relationships existed between the psychosocial parameters and the results of the 6-min walk ( 6MW ) test performance across programs . DESIGN Non-experimental , prospect i ve , and comparative . SETTING Seven outpatient hospital PR programs from urban and rural setting s across North Carolina . PARTICIPANTS Three hundred nine women and 281 men who were 20 to 93 years of age ( mean [ + /- SD ] age , 66.7 + /- 11.1 years ) with chronic lung disease . INTERVENTIONS All 6MW tests and health surveys were administered prior to and immediately following 12 and 24 weeks of supervised PR participation . Scores from the 6MW tests , the Ferrans and Powers quality of life index-pulmonary version III ( QLI ) , the Medical Outcomes Study 36-item short form ( SF-36 ) , and the University of California at San Diego shortness of breath question naire ( SOBQ ) were compared at PR entry , at 12 weeks , and at 24 weeks for differences by gender with repeated- measures analysis of variance . The study entry and follow-up SF-36 physical and mental component summary scores , the QLI health/function and overall scores , and the SOBQ scores were also compared to the 6MW test scores with Pearson correlation coefficient analysis . RESULTS The mean summary scores on the SF-36 and the QLI increased after 12 weeks of PR ( p < 0.05 ) , and improvements were maintained by 24 weeks of PR participation ( p < 0.05 ) . Scores on the SOBQ improved after 12 weeks ( p < 0.001 ) among the short-term participants , but not until after 24 weeks among the long-term participants ( p = 0.009 ) . The 6MW test performance improved after 12 weeks ( p < 0.001 ) and again from 12 to 24 weeks ( p = 0.002 ) in the long-term participants . No relevant correlational relationships were found between 6MW scores and the summary scores of the administered surveys ( r = -0.43 to 0.36 ) . CONCLUSIONS Physical performance , as measured by the 6MW test , continued to improve with up to 24 weeks of PR participation . Quality -of-life measures and the perception of dyspnea improved after 12 weeks of PR participation , with improvements maintained by 24 weeks of PR participation . It is recommended that PR patients participate in supervised PR for at least 24 weeks to gain and maintain optimal health benefits We have developed a rehabilitation programme at home and have investigated its effects on quality of life ( QOL ) , lung function , and exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . We studied 43 patients with severe airflow obstruction : forced expiratory volume in one second ( FEV1 ) 1.3 + /- 0.4 l ( mean + /- SD ) , FEV1/inspiratory vital capacity ( IVC ) 37 + /- 7.9 % . After stratification , 28 patients were r and omly allocated in a home rehabilitation programme for 12 weeks . Fifteen patients in a control group received no rehabilitation . The rehabilitation group received physiotherapy by the local physiotherapist , and supervision by a nurse and a general practitioner . Quality of life was assessed by the four dimensions of the Chronic Respiratory Question naire ( CRQ ) . We found a highly significant improvement in the rehabilitation group compared to the control group for the dimensions dyspnoea , emotion , and mastery . Lung function showed no changes in the rehabilitation group . The exercise tolerance improved significantly in the rehabilitation group compared to the control group . The improvement in quality of life was not correlated with the improvement in exercise tolerance . Rehabilitation of COPD patients at home may improve quality of life ; this improvement is not correlated with an improvement in lung function and exercise tolerance Background Patients with COPD present a major recruitment of the inspiratory muscles , predisposing to chest incoordination , increasing the degree of dyspnea and impairing their exercise capacity . Stretching techniques could decrease the respiratory muscle activity and improve their contractile capacity ; however , the systemic effects of stretching remain unknown . Objective The aim of this study was to evaluate the effects of aerobic training combined with respiratory muscle stretching on functional exercise capacity and thoracoabdominal kinematics in patients with COPD . Design This study was a r and omized and controlled trial . Participants A total of 30 patients were allocated to a treatment group ( TG ) or a control group ( CG ; n=15 , each group ) . Intervention The TG was engaged in respiratory muscle stretching and the CG in upper and lower limb muscle stretching . Both groups performed 24 sessions ( twice a week , 12 weeks ) of aerobic training . Evaluations Functional exercise capacity ( 6-minute walk test ) , thoracoabdominal kinematics ( optoelectronic plethysmography ) , and respiratory muscle activity ( surface electromyography ) were evaluated during exercise . Analysis of covariance was used to compare the groups at a significance level of 5 % . Results After the intervention , the TG showed improved abdominal ( ABD ) contribution , compartmental volume , mobility , and functional exercise capacity with decreased dyspnea when compared with the CG ( P<0.01 ) . The TG also showed a decreased respiratory muscle effort required to obtain the same pulmonary volume compared to the CG ( P<0.001 ) . Conclusion Our results suggest that aerobic training combined with respiratory muscle stretching increases the functional exercise capacity with decreased dyspnea in patients with COPD . These effects are associated with an increased efficacy of the respiratory muscles and participation of the ABD compartment Background : Idiopathic pulmonary fibrosis ( IPF ) is a chronic , devastating , interstitial lung disease , with few therapeutic options . IPF is characterized by pulmonary restriction , dyspnea , hypoxemia , exercise intolerance and poor quality of life ( QOL ) . Objectives : We aim ed to examine the effect of exercise training ( ET ) on clinical outcomes in IPF patients . Methods : A r and omized controlled study included thirty-two IPF patients ( aged 68 ± 8 years ) who were allocated either to the ET group ( n = 15 ) , participating in a 12-week , twice-weekly 60-min supervised ET-based pulmonary rehabilitation program , or to a control group ( n = 17 ) continuing with regular medical treatment alone . Cardiopulmonary exercise test , 6-min walking distance ( 6MWD ) test , 30-second chair-st and test , pulmonary function tests , dyspnea and QOL were assessed at baseline and at the end of the 12-week intervention . Results : Significant differences were observed between the ET and the control groups in raw mean deltas ( Δ = post- - pre-intervention ) : Δ6MWD , 81 m , p < 0.001 ; ΔVO2 peak , 2.6 ml/kg/min , p = 0.002 ; Δwork rate , 22 W , p < 0.001 ; Δanaerobic threshold , 3.1 ml/kg/min , p < 0.001 , and ΔFVC % predicted , 6 % , p = 0.038 . Dyspnea , QOL and 30-second chair-st and were also improved significantly following the program . Conclusions : ET improves exercise tolerance , functional capacity , pulmonary function , dyspnea and QOL in patients with IPF , suggesting a short-term treatment efficacy for clinical improvement , and should be considered the st and ard care for IPF Background The benefits of aerobic training for the main features of asthma , such as bronchial hyperresponsiveness ( BHR ) and inflammation , are poorly understood . We investigated the effects of aerobic training on BHR ( primary outcome ) , serum inflammatory cytokines ( secondary outcome ) , clinical control and asthma quality of life ( Asthma Quality of Life Question naire ( AQLQ ) ) ( tertiary outcomes ) . Methods Fifty-eight patients were r and omly assigned to either the control group ( CG ) or the aerobic training group ( TG ) . Patients in the CG ( educational programme+breathing exercises ( sham ) ) and the TG ( same as the CG+aerobic training ) were followed for 3 months . BHR , serum cytokine , clinical control , AQLQ , induced sputum and fractional exhaled nitric oxide ( FeNO ) were evaluated before and after the intervention . Results After 12 weeks , 43 patients ( 21 CG/22 TG ) completed the study and were analysed . The TG improved in BHR by 1 doubling dose ( dd ) ( 95 % CI 0.3 to 1.7 dd ) , and they experienced reduced interleukin 6 ( IL-6 ) and monocyte chemoattractant protein 1 ( MCP-1 ) and improved AQLQ and asthma exacerbation ( p<0.05 ) . No effects were seen for IL-5 , IL-8 , IL-10 , sputum cellularity , FeNO or Asthma Control Question naire 7 ( ACQ-7 ; p>0.05 ) . A within-group difference was found in the ACQ-6 for patients with non-well-controlled asthma and in sputum eosinophil and FeNO in patients in the TG who had worse airway inflammation . Conclusions Aerobic training reduced BHR and serum proinflammatory cytokines and improved quality of life and asthma exacerbation in patients with moderate or severe asthma . These results suggest that adding exercise as an adjunct therapy to pharmacological treatment could improve the main features of asthma . Trial registration number NCT02033122 Background Pulmonary Rehabilitation for moderate Chronic Obstructive Pulmonary Disease in primary care could improve patients ’ quality of life . Methods This study aim ed to assess the efficacy of a 3-month Pulmonary Rehabilitation ( PR ) program with a further 9 months of maintenance ( RHBM group ) compared with both PR for 3 months without further maintenance ( RHB group ) and usual care in improving the quality of life of patients with moderate COPD .We conducted a parallel-group , r and omized clinical trial in Majorca primary health care in which 97 patients with moderate COPD were assigned to the 3 groups . Health outcomes were quality of life , exercise capacity , pulmonary function and exacerbations . Results We found statistically and clinical ly significant differences in the three groups at 3 months in the emotion dimension ( 0.53 ; 95%CI0.06 - 1.01 ) in the usual care group , ( 0.72 ; 95%CI0.26 - 1.18 ) the RHB group ( 0.87 ; 95%CI 0.44 - 1.30 ) and the RHBM group as well as in fatigue ( 0.47 ; 95%CI 0.17 - 0.78 ) in the RHBM group . After 1 year , these differences favored the long-term rehabilitation group in the domains of fatigue ( 0.56 ; 95%CI 0.22 - 0.91 ) , mastery ( 0.79 ; 95%CI 0.03 - 1.55 ) and emotion ( 0.75 ; 95%CI 0.17 - 1.33 ) . Between-group analysis only showed statistically and clinical ly significant differences between the RHB group and control group in the dyspnea dimension ( 0.79 95%CI 0.05 - 1.52 ) . No differences were found for exacerbations , pulmonary function or exercise capacity . Conclusions We found that patients with moderate COPD and low level of impairment did not show meaningful changes in QoL , exercise tolerance , pulmonary function or exacerbation after a one-year , community based rehabilitation program . However , long-term improvements in the emotional , fatigue and mastery dimensions ( within intervention groups ) were identified . Trial registration IS RCT Rationale Pulmonary rehabilitation is an important treatment for patients with Chronic Obstructive Pulmonary Disease , who are often vitamin D deficient . As vitamin D status is linked to skeletal muscle function , we aim ed to explore if high dose vitamin D supplementation can improve the outcomes of rehabilitation in Chronic Obstructive Pulmonary Disease . Material and methods This study is a post-hoc subgroup analysis of a larger r and omized trial comparing a monthly dose of 100.000 IU of vitamin D with placebo to reduce exacerbations . 50 Subjects who followed a rehabilitation program during the trial are included in this analysis . We report changes from baseline in muscle strength and exercise performance between both study arms after 3 months of rehabilitation . Results Vitamin D intervention result ed in significantly higher median vitamin D levels compared to placebo ( 51 [ 44 - 62 ] ng/ml vs 15 [ 13 - 30 ] ng/ml ; p < 0.001 ) . Patients receiving vitamin D had significantly larger improvements in inspiratory muscle strength ( -11±12 cmH2O vs 0±14 cmH2O ; p = 0.004 ) and maximal oxygen uptake ( 110±211 ml/min vs -20±187 ml/min ; p = 0.029 ) . Improvements in quadriceps strength ( 15±16 Nm ) or six minutes walking distance ( 40±55 meter ) were not significantly different from the effects in the placebo group ( 7±19 Nm and 11±74 meter ; p>0.050 ) . Conclusion High dose vitamin D supplementation during rehabilitation may have mild additional benefits to training The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment , and a 3 month control period of drug treatment only , for asthmatic patients and patients with chronic obstructive pulmonary disease ( COPD ) . The programme was run by physiotherapists in eight local practice s , and included exercise training , patient education , breathing retraining , evacuation of mucus , relaxation techniques , and recreational activities . In a r and omized controlled trial with a cross-over design , the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life ( QOL ) . Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests . QOL was evaluated by means of the Chronic Respiratory Disease Question naire ( CRDQ ) . After 3 months , the patients who started with rehabilitation showed significant improvements in endurance time ( 421 s ) and cardiac frequency ( 6 beats.min-1 ) during cycling , walking distance ( 39 m ) , and total CRDQ score ( 17 points ) compared to the control group . These improvements were still significant after 6 months . Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way , with the exception that there was a greater improvement in walking distance for asthmatics . Improvements in exercise tolerance were not significantly correlated with improvements in QOL . Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practice s improves exercise tolerance and quality of life Little is known about effects of community-based physiotherapeutic exercise programmes incorporated in COPD self-management programmes . In a r and omised trial , the effect of such a programme ( COPE-active ) on exercise capacity and various secondary outcomes including daily activity as a marker of behaviour change was evaluated . All patients attended four 2-h self-management sessions . In addition the intervention group participated in the COPE-active programme offered by physiotherapists of private practice s , consisting of a 6-month " compulsory " period ( 3 sessions/week ) and subsequently a 5-month " optional " period ( 2 sessions/week ) . Because COPE-active was intended to change behaviour with regard to exercise , one session/week in both periods consisted of unsupervised home-based exercise training . Of 153 patients , 74 intervention and 68 control patients completed the one-year follow-up . Statistically significant between-group differences in incremental shuttle walk test-distance ( 35.1 m ; 95 % CI ( 8.4 ; 61.8 ) ) and daily activity ( 1190 steps/day ; 95 % CI ( 256 ; 2125 ) ) were found in favour of the intervention group . Over the 12-month period a significant difference of the chronic respiratory question naire ( CRQ ) dyspnoea-score ( 0.33 points ; 95 % CI ( 0.01 ; 0.64 ) ) and a non-significant difference of the endurance shuttle walk test ( 135 m ( 95 % CI ( -29 ; 298 ) ) was found . No differences were found in the other CRQ-components , anxiety and depression scores and percentage of fat free mass . This study demonstrates that a community-based reactivation programme improves exercise capacity in patients with moderately to severe COPD . Even more important , the programme improves actual daily activity after one-year which indicates behaviour change with regard to daily exercise . Registered trail number : IS RCT N81447311 PURPOSE Pulmonary rehabilitation programs are effective in patients with severe chronic obstructive pulmonary disease ( COPD ) in the short term , but their long-term effects are not known . We investigated the short- and long-term effects of a 6-month outpatient rehabilitation program in patients with severe COPD . SUBJECTS AND METHODS One hundred patients were r and omly assigned to receive either an exercise training program that included cycling , walking , and strength training ( n = 50 ) or usual medical care ( n = 50 ) . Thirty-four patients in the training group were evaluated after 6 months ( end of training ) , and 26 were evaluated after 18 months of follow-up . In the control group , 28 patients were evaluated at 6 months and 23 after 18 months . We measured pulmonary function , 6-minute walking distance , maximal exercise capacity , peripheral and respiratory muscle strength , and quality of life ( on a 20 to 140-point scale ) , and estimated the cost-effectiveness of the program . RESULTS At 6 months , the training group showed improvement in 6-minute walking distance [ mean difference ( training - control ) of 52 m ; 95 % confidence interval ( CI ) , 15 to 89 m ] , maximal work load ( 12 W ; 95 % CI , 6 to 19 W ) , maximal oxygen uptake ( 0.26 liters/min ; 95 % CI , 0.07 to 0.45 liters/min ) , quadriceps force ( 18 Nm ; 95 % CI , 7 to 29 Nm ) , inspiratory muscle force ( 11 cm H(2)O ; 95 % CI , 3 to 20 cm H(2)O ) , and quality of life ( 14 points ; 95 % CI , 6 to 21 points ; all P < 0.05 ) . At 18 months all these differences persisted ( P < 0.05 ) , except for inspiratory muscle strength . For 6-minute walking distance and quality of life , the differences between the training group and controls at 18 months exceeded the minimal clinical ly-important difference . CONCLUSION Among patients who completed the 6-month program , outpatient training result ed in significant and clinical ly relevant changes in 6-minute walking distance , maximal exercise performance , peripheral and respiratory muscle strength , and quality of life . Most of these effects persisted 18 months after starting the program Background Pulmonary rehabilitation programs only modestly enhance daily physical activity levels in patients with chronic obstructive pulmonary disease ( COPD ) . This r and omised controlled trial investigates the additional effect of an individual activity counselling program during pulmonary rehabilitation on physical activity levels in patients with moderate to very severe COPD . Methods Eighty patients ( 66±7 years , 81 % male , forced expiratory volume in 1 second 45±16 % of predicted ) referred for a six‐month multidisciplinary pulmonary rehabilitation program were r and omised . The intervention group was offered an additional eight-session activity counselling program . The primary outcomes were daily walking time and time spent in at least moderate intense activities . Results Baseline daily walking time was similar in the intervention and control group ( median 33 [ interquartile range 16–47 ] vs 29 [ 17–44 ] ) whereas daily time spent in at least moderate intensity was somewhat higher in the intervention group ( 17[4–50 ] vs 12[2–26 ] min ) . No significant intervention*time interaction effects were observed in daily physical activity levels . In the whole group , daily walking time and time spent in at least moderate intense activities did not significantly change over time . Conclusions The present study identified no additional effect of eight individual activity counselling sessions during pulmonary rehabilitation to enhance physical activity levels in patients with COPD . Trial Registration clinical trials.gov Underst and ing of what constitutes a training load adequate to induce training effects in patients with chronic obstructive pulmonary disease ( COPD ) is still evolving . The present study investigated whether interval training ( IT ) is effective in terms of inducing measurable improvements in physiological response and compared its effects on exercise tolerance ( ET ) and quality of life to those of continuous training ( CT ) . Thirty-six COPD patients , with a forced expiratory volume in one second of 45±4 % of the predicted value ( mean±sem ) , were r and omly assigned to CT ( exercise at 50 % of baseline peak work-rate ) or IT ( work for 30 s at 100 % of peak work-rate alternating with 30‐s rest intervals ) groups that cycled 40 min·day−1 and 2 days·week−1 for 12 weeks . After training , both groups showed significantly improved ET ( IT , 57±6 to 71±8 W ; CT , 57±5 to 70±6 W ) and total quality -of-life score of the Chronic Respiratory Disease Question naire ( IT , 77±3 to 88±2 ; CT , 78±3 to 93±2 ) . At identical levels of exercise , minute ventilation was significantly reduced ( IT , 35.8±2.5 to 31.7±2.5 L·min−1 ; CT , 36.4±2.7 to 32.5±2.7 L·min−1 ) . The magnitude of improvement in these variables was not significantly different among groups . The present data exp and on the principles of exercise prescription for chronic obstructive pulmonary disease patients by demonstrating that interval training elicits substantial training effects , which are similar in magnitude to those produced by continuous training at half the exercise intensity but double the exercise time The effects of endurance training on exercise capacity and health-related quality of life ( HRQL ) in chronic obstructive pulmonary disease ( COPD ) patients have been studied thoroughly , while resistance training has been rarely evaluated . This study investigated the effects of resistance training in comparison with endurance training in patients with moderate to severe COPD and peripheral muscle weakness ( isometric knee extension peak torque < 75 % predicted ) . Forty-eight patients ( age 64±8 yrs , forced expiratory volume in one second 38±17 % pred ) were r and omly assigned to resistance training ( RT , n=24 ) or endurance training ( ET , n=24 ) . The former consisted of dynamic strengthening exercises . The latter consisted of walking , cycling and arm cranking . Respiratory and peripheral muscle force , exercise capacity , and HRQL were re-evaluated in all patients who completed the 12-week rehabilitation ( RT n=14 , ET n=16 ) . Statistically significant increases in knee extension peak torque ( RT 20±21 % , ET 42±21 % ) , maximal knee flexion force ( RT 31±39 % , ET 28±37 % ) , elbow flexion force ( RT 24±19 % , ET 33±25 % ) , 6-min walking distance ( 6MWD ) ( RT 79±74 m , ET 95±57 m ) , maximum workload ( RT 15±16 Watt , ET 14±13 Watt ) and HRQL ( RT 16±25 points , ET 16±15 points ) were observed . No significant differences in changes in HRQL and 6MWD were seen between the two treatments . Resistance training and endurance training have similar effects on peripheral muscle force , exercise capacity and health-related quality of life in chronic obstructive pulmonary disease patients with peripheral muscle weakness The purpose of this study was to investigate the effects on activities of daily living , quality of life , and exercise tolerance of a comprehensive out-patient rehabilitation programme for patients with moderate-to-severe chronic obstructive pulmonary disease . In this r and omized and controlled trial , the main outcome measures were Activities of Daily Living ( ADL ) score , York Quality of Life Question naire ( YQLQ ) score , Chronic Respiratory Disease Question naire ( CRDQ ) score , 6 min walking distance ( 6MWD ) , forced expiratory volume in one second ( FEV1 ) , and forced vital capacity ( FVC ) . The rehabilitation programme included physical training , occupational therapy , education , and smoking cessation therapy , and lasted for 12 weeks . The patients were evaluated at entry , halfway through , and at the end of the programme . Follow-up was at 24 weeks . Forty seven patients were recruited , and 16 in each group completed the trial . There were significant differences in the improvements in ADL and CRDQ between the control and the treatment groups at 12 and 24 weeks , and at 24 weeks , respectively . At 6 , 12 and 24 weeks , improvements in the 6MWD were 21.6 versus 79.8 , 36.1 versus 113.1 and 21.4 versus 96.2 for control and treatment groups , respectively ( p<0.004 ) . A correlation matrix showed only ADL and 6MWD to be significantly correlated ; the matrix was also used to vali date the translated question naires . The programme required 124 staff-hours in total . An inexpensive , comprehensive out-patient rehabilitation programme can produce long-term improvement in activities of daily living , quality of life , and exercise tolerance in patients with moderate-to-severe chronic obstructive pulmonary disease Background Pulmonary rehabilitation is known to be a beneficial treatment for COPD patients . To date , however , there is no agreement for how long a rehabilitation program should be implemented . In addition , current views are that pulmonary rehabilitation does not improve FEV1 or even slow its decline in COPD patients . The aim of the study was to examine the efficacy of a 3 year outpatient pulmonary rehabilitation ( PR ) program for COPD patients on pulmonary function , exercise capability , and body mass index ( BMI ) . Methods A matched controlled trial was performed with outcome assessment s evaluated at 6 , 12 , 18 , 24 , 30 , and 36 months . Eighty patients with moderate to severe COPD ( age 63 ± 7 years ; FEV1 48 % ± 14 ) were recruited . The control group received st and ard care only , while in addition , the case study group received PR for duration of three years . These groups were matched for age , sex , BMI , FEV1 % and number of pack-years smoked . Results The decline in FEV1 after the three years was significantly lower in the PR group compared to control , 74 ml versus 149 ml , respectively ( p < 0.001 ) . Maximal sustained work and endurance time improved after a short period of PR and was maintained throughout the study , in contrast to the control group ( p < 0.01 ) . A decreased BMI was noted in the control group after three years , while in the PR group a mild improvement was seen ( p < 0.05 ) . Conclusion Three years of outpatient pulmonary rehabilitation result ed in modifying the disease progression of COPD , as well as improving physical performance in these patients The study aim ed to estimate the cost-effectiveness of interdisciplinary community-based chronic obstructive pulmonary disease ( COPD ) management in patients with COPD . We conducted a cost-effectiveness analysis alongside a 2-yr r and omised controlled trial , in which 199 patients with less advanced airflow obstruction and impaired exercise capacity were assigned to the INTERCOM programme or usual care . The INTERCOM programme consisted of exercise training , education , nutritional therapy and smoking cessation counselling offered by community-based physiotherapists and dieticians and hospital-based respiratory nurses . All-cause re source use during 2 yrs was obtained by self-report and from hospital and pharmacy records . Health outcomes were the St George 's Respiratory Question naire ( SGRQ ) , exacerbations and quality -adjusted life years ( QALYs ) . The INTERCOM group had 30 % ( 95 % CI 3–56 % ) more patients with a clinical ly relevant improvement in SGRQ total score , 0.08 ( 95 % CI -0.01–0.18 ) more QALYs per patient , but a higher mean number of exacerbations , 0.84 ( 95 % CI -0.07–1.78 ) . Mean total 2-yr costs were € 2,751 ( 95 % CI -€632–€6,372 ) higher for INTERCOM than for usual care , which result ed in an incremental cost-effectiveness ratio of € 9,078 per additional patient with a relevant improvement in SGRQ or € 32,425 per QALY . INTERCOM significantly improved disease-specific quality of life , but did not affect exacerbation rate . The cost per QALY ratio was moderate , but within the range of that generally considered to be acceptable BACKGROUND The natural history of disease in patients with stage IV ( fibrotic ) sarcoidosis may mirror that of patients with idiopathic pulmonary fibrosis ( IPF ) . Both are bothered by progressive dyspnea , exercise limitation and fatigue . OBJECTIVE To establish whether patients suffering from pulmonary fibrosis might benefit from a physical training program . STUDY DESIGN Twenty-four eligible patients referred to the out-patient clinic of the ild care expertise team of Hospital Gelderse Vallei , Ede , The Netherl and s between November 2012 and November 2013 were included in this observational pilot study of a 12-week physical training program . Outcomes , including exercise capacity , skeletal muscle strength , lung function and fatigue were assessed at two time points : 1 ) baseline ; and 2 ) after completion of a 12-week physical training program . RESULTS At baseline , the percentage predicted DLCO , FVC , FEV1 and exercise capacity ( assessed by six-minute walking distance ( 6MWD ) or maximal oxygen uptake ) was reduced in both groups . After program completion , exercise capacity improved ( > 10 % improvement 6MWD ) in 13 subjects ( 54.2 % ) : 7 with IPF and 6 with sarcoidosis subjects . Other secondary endpoints , including pulmonary function tests and patient-reported outcome measures improved in some subjects . CONCLUSION A 12-week physical training program improved or maintained exercise capacity in patients with IPF ( despite disease progression ) or fibrotic sarcoidosis . The results from this pilot study could be used to design prospect i ve studies aim ed at answering lingering questions about exercise training in patients with these progressive , incurable conditions Background Aerobic exercise appears to have clinical benefits for many asthmatics , yet a complete underst and ing of the mechanisms underlying these benefits has not been eluci date d at this time . Purpose The objective of this study was to determine feasibility for a larger , future study that will define the effect of aerobic exercise on cellular , molecular , and functional measures in adults with mild-moderate asthma . Design Recruited subjects were r and omized into usual care ( sedentary ) or usual care with moderate intensity aerobic exercise treatment groups . Setting / Participants Nineteen adults with mild-moderate asthma but without a recent history of exercise were recruited at the UAB Lung Health Center , Birmingham , AL.InterventionThe exercise group underwent a 12 week walking program exercising at 60 – 75 % of maximum heart rate ( HRmax ) . Subjects self-monitored HRmax levels using heart rate monitors ; exercise diaries and recreation center sign-in logs were also used . Main outcome measures Functional measures , including lung function and asthma control scores , were evaluated for all subjects at pre- and post- study time-points ; fitness measures were also assessed for subjects in the exercise group . Peripheral blood and nasal lavage fluid were collected from all subjects at pre- and post- study visits in order to evaluate cellular and molecular measures , including cell differentials and eosinophilic cationic protein ( ECP ) . Results Sixteen subjects completed the prescribed protocol . Results show that subjects r and omized to the exercise group adhered well ( 80 % ) to the exercise prescription and exhibited a trend toward improved fitness levels upon study completion . Both groups exhibited improvements in ACQ scores . No changes were observed in lung function ( FEV1 , FEV1/FVC ) , cell differentials , or ECP between groups . Conclusions Results indicate that a moderate intensity aerobic exercise training program may improve asthma control and fitness levels without causing asthma deterioration in adult asthmatics . As such , these findings demonstrate the feasibility of the study protocol in preparation for a larger , clinical trial that will eluci date the functional consequences of aerobic exercise on asthmatic cellular and molecular responses We evaluated comorbidity , hospitalization , and mortality in chronic obstructive pulmonary disease ( COPD ) , with special attention to risk factors for frequent hospitalizations ( more than three during the follow-up period ) , and prognostic factors for death . Two hundred eighty-eight consecutive COPD patients admitted to respiratory medicine wards in four hospitals for acute exacerbation were enrolled from 1999 to 2000 in a prospect i ve longitudinal study , and followed up until December 2007 . The Charlson index without age was used to quantify comorbidity . Clinical and biochemical parameters and pulmonary function data were evaluated as potential predictive factors of mortality and hospitalization . FEV1 , RV , PaO2 , and PaCO2 were used to develop an index of respiratory functional impairment ( REFI index ) . Hypertension was the most common comorbidity ( 64.2 % ) , followed by chronic renal failure ( 26.3 % ) , diabetes mellitus ( 25.3 % ) , and cardiac diseases ( 22.1 % ) . Main causes of hospitalization were exacerbation of COPD ( 41.2 % ) and cardiovascular disease ( 34.4 % ) . Most of the 56 deaths ( 19.4 % ) were due to cardiovascular disease ( 67.8 % ) . Mortality risk depended on age , current smoking , FEV1 , PaO2 , the REFI index , the presence of cor pulmonale , ischemic heart disease , and lung cancer . Number and length of hospital admissions depended on the degree of dyspnea and REFI index . The correct management of respiratory disease and the implementation of aggressive strategies to prevent or treat comorbidities are necessary for better care of COPD patients BACKGROUND Non-invasive ventilation and exercise training might prove beneficial in the management of COPD patients . OBJETIVE to compare the combined use of exercise training and non-invasive ventilation with the two interventions separately in chronic respiratory failure due to chronic obstructive pulmonary disease . As primary objective exercise capacity and secondary objectives gas exchange , peripheral muscle strength , BODE index , quality of life and systemic inflammatory response . METHODS Forty-five patients with severe chronic obstructive pulmonary disease were r and omized into three groups for an intervention of 12 weeks : exercise training alone , ventilation alone and combined treatment . We assessed exercise capacity , pulmonary function , BODE index , perception of dyspnoea , quality of life and several biomarkers . RESULTS All exercise capacity parameters improved after training and the combined treatment . In addition , peripheral muscle strength and six-minute walk distance increased after ventilation . We found differences between the combined group and the ventilation group in submaximal effort and in oxygen consumption . Changes in respiratory function were observed in blood gases that improved after ventilation and the combined treatment , with differences between these groups . BODE index , perception of dyspnoea and quality of life improved in all three groups without differences between groups . Levels of interleukin 8 and tumour necrosis factor α decreased after ventilation , and interleukin 8 , C-reactive protein and surfactant protein D decreased after training , while all four of these markers fell after the combined treatment . No differences between groups were found . CONCLUSIONS The combination of ventilation and exercise training had greater benefits than the separate treatments : improvements were observed in both blood gases and the levels of more biomarkers decreased . In addition , submaximal exercise capacity increased in all groups . The improvements seen in BODE index , perception of dyspnoea and quality of life were similar in all groups PURPOSE To compare the effects of short-term ( 3 months ) and long-term ( 18 months ) involvement in an exercise program on self-reported disability and physical function in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A total of 140 patients with COPD were studied in a r and omized , single-blinded clinical trial . Self-reported disability and physical function were assessed using a 21-item question naire , a 6-minute walk , timed stair climb , and an overhead task . RESULTS At the completion of the trial , participants in the long-term intervention reported 12 % less disability than those in the short-term intervention ( adjusted mean with 95 % confidence interval , 1.53 ( 1.43 - 1.63 ) versus 1.71 ( 1.61 to 1.81 ) units , respectively ; P=.016 ) , walked 6 % farther during 6-minutes ( 1,815.0 [ 1,750.4 - 1,879.6 ] vs 1,711.5 [ 1,640.7 - 1,782.3 ] feet , respectively ) , climbed steps 11 % faster ( 11.6 [ 11.0 - 12.2 ] vs 12.9 [ 12.3 - 13.5 ] seconds , respectively ) , and completed an overhead task 8 % faster ( 46.8 [ 44.4 - 49.2 ] vs 50.4 [ 47.8 - 53.0 ] seconds , respectively ) than those in the short-term intervention . CONCLUSION An 18 month exercise program results in greater improvements in self-reported disability and physical function in patients with COPD when compared with a 3-month exercise program . As such , long-term exercise should be recommended for all patients with COPD This study aim ed at investigating whether providing feedback on physical activity ( PA ) levels to patients with chronic obstructive pulmonary disease ( COPD ) is feasible and enhances daily PA during pulmonary rehabilitation ( PR ) . Patients with COPD participated in a 12-week PR program . Daily PA was measured using activity monitors on weeks 1 , 7 , and 12 , and feedback was given in the following weeks on the number of steps , time spent in sedentary , light , and moderate-to-vigorous intensity activities , and time spent st and ing , sitting , and lying . Compliance with PA monitoring was collected . Two focus groups were conducted to obtain patients ’ perspectives on the use of activity monitors and on the feedback given . Differences in PA data were also assessed . Sixteen patients ( 65.63 ± 10.57 years ; forced expiratory volume in one second ( FEV1 ) 70.31 ± 22.74 % predicted ) completed the study . From those , only eleven participants used the activity monitors during all monitoring days . Participants identified several problems regarding the use of activity monitors and monitoring duration . Daily steps ( p = 0.026 ) and st and ing time ( p = 0.030 ) were improved from week 1 to week 7 ; however , the former declined from week 7 to week 12 . Findings suggest that using feedback to improve PA during PR is feasible and results in improved daily steps and st and ing time on week 7 . The subsequent decline suggests that additional strategies may be needed to stimulate/maintain PA improvements . Further research with more robust design s is needed to investigate the impact of feedback on patients ’ daily PA Background : Skeletal muscle wasting and dysfunction are strong independent predictors of mortality in patients with chronic obstructive pulmonary disease ( COPD ) . Creatine nutritional supplementation produces increased muscle mass and exercise performance in health . A controlled study was performed to look for similar effects in 38 patients with COPD . Methods : Thirty eight patients with COPD ( mean ( SD ) forced expiratory volume in 1 second ( FEV1 ) 46 (15)% predicted ) were r and omised to receive placebo ( glucose polymer 40.7 g ) or creatine ( creatine monohydrate 5.7 g , glucose 35 g ) supplements in a double blind trial . After 2 weeks loading ( one dose three times daily ) , patients participated in an outpatient pulmonary rehabilitation programme combined with maintenance ( once daily ) supplementation . Pulmonary function , body composition , and exercise performance ( peripheral muscle strength and endurance , shuttle walking , cycle ergometry ) took place at baseline ( n = 38 ) , post loading ( n = 36 ) , and post rehabilitation ( n = 25 ) . Results : No difference was found in whole body exercise performance between the groups : for example , incremental shuttle walk distance mean −23.1 m ( 95 % CI −71.7 to 25.5 ) post loading and −21.5 m ( 95 % CI −90.6 to 47.7 ) post rehabilitation . Creatine increased fat-free mass by 1.09 kg ( 95 % CI 0.43 to 1.74 ) post loading and 1.62 kg ( 95 % CI 0.47 to 2.77 ) post rehabilitation . Peripheral muscle performance improved : knee extensor strength 4.2 N.m ( 95 % CI 1.4 to 7.1 ) and endurance 411.1 J ( 95 % CI 129.9 to 692.4 ) post loading , knee extensor strength 7.3 N.m ( 95 % CI 0.69 to 13.92 ) and endurance 854.3 J ( 95 % CI 131.3 to 1577.4 ) post rehabilitation . Creatine improved health status between baseline and post rehabilitation ( St George ’s Respiratory Question naire total score −7.7 ( 95 % CI −14.9 to −0.5 ) ) . Conclusions : Creatine supplementation led to increases in fat-free mass , peripheral muscle strength and endurance , health status , but not exercise capacity . Creatine may constitute a new ergogenic treatment in COPD Purpose . To investigate effects of decreased training frequency in patients with COPD . Methods . Forty-three COPD patients participated in a controlled study . The intervention group ( 30 patients ) trained 3 times a week during 3 months and once a week during 6 months . Before , after 3 and 9 months all patients performed walking tests , cycle ergometer tests and responded question naires on health-related quality of life ( HRQoL ) ( SGRQ , SF-36 ) . Results . At 9 months compared to 3 months there were no changes in distance walked in the groups . Both groups decreased their VO2peak and the training group deteriorated in HRQoL. At 9 months compared to baseline the training group showed increased distance walked compared to the control group . In the disease-specific SGRQ the training group tended to improve their activity score while the control group tended to deteriorate in total score . In SF-36 the control group decreased their physical component score . Conclusion . Training once a week does not seem to be sufficient to maintain the level achieved after the 3-month period of training in COPD patients . However , training once a week during 6 months preceded by 3 months of high frequency training seems to prevent deterioration in physical capacity and HRQoL compared to baseline . Further studies are needed to investigate how to best sustain the benefits gained after physical training OBJECTIVE To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age . DESIGN Prospect i ve cohort study . PATIENTS A total of 140 patients with chronic obstructive pulmonary disease ( Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) 3 - 4 ) admitted to our centre for pulmonary rehabilitation . METHODS Patients were divided into 3 groups : group A ( < 65 years ) , group B ( 65 - 74 years ) and group C ( ≥ 75 years ) . All the patients received an education and individualized training programme . Pulmonary rehabilitation efficacy was evaluated at 6 months of treatment and 12 months post-treatment . RESULTS A total of 116 patients completed the pulmonary rehabilitation programme : 59 in group A ( 85.5 % ) , 40 in group B ( 80 % ) and 17 in group C ( 80.9 % ) . All the parameters studied ( number of sessions , 6-min walking distance , isometric quadriceps strength , health-related quality of life , maximal load , peak oxygen uptake , maximal inspiratory and expiratory pressures ) were significantly improved in each of the groups at 3 and 6 months compared with baseline . Moreover , percentage changes from baseline at 6 months for all of the parameters studied were not significantly different between age-groups . CONCLUSION Pulmonary rehabilitation is efficient in elderly patients with severe and very severe chronic obstructive pulmonary disease , and their compliance with pulmonary rehabilitation was similar to that seen in younger groups . Therefore , elderly patients with chronic obstructive pulmonary disease should not be denied pulmonary rehabilitation BACKGROUND Current literature lacks solid evidence on the improvement of heart rate variability ( HRV ) after exercise training in patients with COPD . OBJECTIVES We aim ed to investigate changes in HRV after two exercise training programs in patients with COPD and to investigate the determinants of these eventual changes . METHODS Forty patients with COPD ( FEV(1 ) 39 ± 13%pred ) were r and omized into high ( n = 20 ) or low ( n = 20 ) intensity exercise training ( 3-month duration ) , and had their HRV assessed by the head-up tilt test before and after either protocol s. Baseline spirometry , level of daily physical activity , exercise capacity , body composition , functional status , health-related quality of life and muscle force were also assessed to investigate the determinants of improvement in HRV after the training program . RESULTS There was a significant improvement in HRV only after the high-intensity protocol ( pre versus post ; SDNN 29 ± 15 ms versus 36 ± 19 ms ; rMSSD 22 ± 14 ms versus 28 ± 22 ms ; p < 0.05 for both ) . Higher values of biceps brachialis strength , time spent walking in daily life and SDNN at baseline were determinants of improvement in HRV after the training program . CONCLUSIONS High-intensity exercise training improves HRV at rest and during orthostatic stimulus in patients with COPD . Better baseline total HRV , muscle force and daily physical activity level are predictors of HRV improvements after the training program PURPOSE Pulmonary rehabilitation programs often show beneficial effects in patients with chronic obstructive pulmonary disease ( COPD ) . These programs are usually hospital-based . This study assesses the feasibility and application of a 12-week Home-Care Rehabilitation Program ( HCRP ) , carried out by general practitioners , physiotherapists , and home-care nurses . METHODS Effects of the HCRP are assessed in 15 COPD patients with moderate to severe airflow limitation ( inspiratory vital capacity [ IVC ] : mean , 75.4 [ SD , 13.7 ] percent predicted , mean FEV1 : 45.5 [ 6.9 ] percent predicted ) and are compared with a stratified and r and omized control group ( n = 15 ) . RESULTS All participating disciplines judged the program to be useful and feasible . Patient compliance with the rehabilitation exercises was high . No major problems concerning the rehabilitation program were reported . After the HCRP , 4-minute walking distance improved significantly from 274 m [ 61 ] to 301 m [ 72 ] and maximal work load ( W max ) , as measured during an incremental cycle test , increased from 75.3 W [ 24 ] to 85.3 W [ 28 ] . At equal work levels ( W submax ) during the cycle test both Borg dyspnea and leg effort scores decreased significantly after the HCRP ( 6.7 [ 1.3 ] versus 4.9 [ 1.7 ] and 4.2 [ 2.0 ] versus 1.7 [ 2.5 ] , respectively ) . Changes in walking distance , dyspnea , and leg effort scores at W submax were significantly different between the two groups . IVC and FEV1 did not change significantly . In the control group , no significant changes in any parameter were observed . CONCLUSION It was possible to design and perform successfully a home-care rehabilitation program , providing both objective and subjective improvements in a group of patients with COPD . A home-care rehabilitation program appears to be a valuable component in the management of COPD patients with a moderate to severe airflow limitation BACKGROUND Acupressure is a therapy in which gentle pressure is applied with fingers at specific acupoints on the body . It is reported to relieve pain and have other beneficial effects . This study was design ed to ascertain the value of self-administered acupressure as an adjunct to a pulmonary rehabilitation program ( PRP ) for relief of dyspnea and other symptoms in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS A single-blind pretest-posttest , cross-over design was used . Thirty-one new patients beginning a 12-week PRP at two private hospitals were r and omly assigned to one of two groups . Patients in group 1 were taught acupressure and practice d it daily at home for 6 weeks , then sham acupressure for the following 6 weeks . In group 2 , the order of acupressure and sham acupressure was reversed . During weeks 1 , 6 , and 12 , patient dyspnea , other symptoms associated with COPD , activity tolerance , lung function , and functional exercise capacity were assessed . RESULTS Real acupressure was more effective than sham acupressure for reducing dyspnea as measured by a visual analog scale ( P = .009 , one-tailed ) , and was minimally effective for relieving decathexis ( P = .044 , one-tailed ) . Sham acupressure seemed to be more effective than real acupressure for reducing peripheral sensory symptoms ( P = .002 , two-tailed ) , but the presence of these symptoms may also be an indication that the acupressure is affecting the body . CONCLUSIONS Acupressure seems to be useful to patients with COPD as an adjunct to a PRP in reducing dyspnea . Some persons who are not initially familiar with traditional Chinese medicine can learn and will accept self-administered acupressure as part of their self-care BACKGROUND AND OBJECTIVES The present pilot study was undertaken to evaluate the efficacy of an aerobic exercise training ( AET ) program alone or combined with an antihypertensive agent ( irbesartan ) to reduce blood pressure ( BP ) and enhance heart rate variability ( HRV ) in chronic obstructive pulmonary disease patients . METHODS Twenty-one patients were r and omly assigned to a double-blind treatment with exercise and placebo ( n=11 ) or exercise and irbesartan ( n=10 ) . Subjects underwent 24 h BP monitoring and 24 h electrocardiographic recording before and after the 12-week AET . HRV was investigated using three indexes from the power spectral analysis and three indexes calculated from the time domain . The AET program consisted of exercising on a calibrated ergocycle for 30 min three times per week . Five patients in the placebo group were excluded during follow-up because they were not compliant . RESULTS There was no change in 24 h systolic and diastolic BP before ( 130+/-14 mmHg and 70+/-3 mmHg , respectively ) and after ( 128+/-8 mmHg and 70+/-8 mmHg , respectively ) exercise training in the placebo group , whereas in the irbesartan group systolic and diastolic BP decreased from 135+/-9 mmHg and 76+/-9 mmHg to 126+/-12 mmHg and 72+/-8 mmHg , respectively ( P<0.02 ) . There were no changes in HRV parameters in either group . CONCLUSIONS The present study suggests that a 12-week AET program is not associated with a significant reduction in BP or enhancement in HRV , whereas an AET program combined with irbesartan is associated with a reduction in 24 h BP Background Patients with idiopathic pulmonary fibrosis ( IPF ) have severely limited exercise capacity due to dyspnea , hypoxemia , and abnormal lung mechanics . This pilot study was design ed to determine whether pulmonary rehabilitation were efficacious in improving the 6-min walk test ( 6-MWT ) distance , exercise oxygen uptake , respiratory muscle strength [ maximum inspiratory pressure ( MIP ) ] , and dyspnea in patients with IPF . Underlying physiological mechanisms and effects of the intervention were investigated . Methods Subjects were r and omly assigned to a 3-month pulmonary rehabilitation program ( n = 11 ) or to a control group ( n = 10 ) . All subjects initially underwent the 6-MWT and constant load exercise gas exchange studies . Results Subjects in the rehabilitation group increased treadmill exercise [ metabolic equivalent of task-minutes ] over the first 14 sessions . Beneficial effects on physical function result ed in those who completed rehabilitation . Subjects who completed the program increased cycle ergometer time and maintained exercise oxygen consumption ( exercise VO2 ) at the baseline level over 3 months , while the control group suffered a significant decrease in exercise VO2 . Rehabilitation subjects also increased their MIP . Plasma lactate doubled and brain natriuretic peptide levels increased significantly after exercise , as did the plasma amino acids glutamic acid , arginine , histidine , and methionine . These changes were associated with significant decreases in arterial oxygen saturation and increases in 15-F2t-isoprostanes after exercise . Conclusions Pulmonary rehabilitation effectively maintained exercise oxygen uptake over 3 months and lengthened constant load exercise time in patients with moderately severe IPF . Exercise endurance on cycle ergometry testing was limited by dyspnea and severe hypoxemia associated with systemic oxidant stress The effects of a pulmonary rehabilitation program on 44 patients with chronic obstructive pulmonary disease ( COPD ) were compared to a control group . The treated group was admitted to the program for a period of three months . The program consisted of several parts , such as physical training , health education , and psychological and social matters . Before participation , the patients were thoroughly examined and provided with optimal medical treatment . Both groups were assessed by means of biometrical tests and question naires for a period of 2 years . The rehabilitation group improved significantly in endurance , psychological parameters , and consumption of medical care . Working days increased and their way of life became more active . Smoking habits and body fat percentage decreased . Bronchial hyperreactivity , need for pulmonary drugs , and coughing and sputum production did not improve in the rehabilitation group compared to the control group . Airway obstruction , expressed as forced expiratory volume in one second , and complaints of dyspnea , allergy and hyperreactivity scores on question naires improved only in the short term ( < 1 year ) , but did not improve significantly in the long term . This study shows that pulmonary rehabilitation can result in improvements in patients with asthma or COPD who have many complaints despite the fact that their pulmonary function is not severely disturbed BACKGROUND : The effects of different exercise training programs on the level of physical activity in daily life in patients with COPD remain to be investigated . OBJECTIVE : In patients with COPD we compared the effects of 2 exercise/training regimens ( a high-intensity whole-body endurance- and -strength program , and a low-intensity calisthenics- and -breathing-exercises program ) on physical activity in daily life , exercise capacity , muscle force , health-related quality of life , and functional status . METHODS : We r and omized 40 patients with COPD to perform either endurance- and -strength training ( no. = 20 , mean ± SD FEV1 40 ± 13 % of predicted ) at 60–75 % of maximum capacity , or calisthenics- and -breathing-exercises training ( no. = 20 , mean ± SD FEV1 39 ± 14 % of predicted ) . Both groups underwent 3 sessions per week for 12 weeks . Before and after the training programs the patients underwent activity monitoring with motion sensors , incremental cycle-ergometry , 6-min walk test , and peripheral-muscle-force test , and responded to question naires on health-related quality of life and functional status ( activities of daily living , pulmonary functional status , and dyspnea ) . RESULTS : Time spent active and energy expenditure in daily life were not significantly altered in either group . Exercise capacity and muscle force significantly improved only in the endurance- and -strength group . Health-related quality of life and functional status improved significantly in both groups . CONCLUSIONS : Neither training program significantly improved time spent active or energy expenditure in daily life . The training regimens similarly improved quality of life and functional status . Exercise capacity and muscle force significantly improved only in the high-intensity endurance- and -strength group STUDY OBJECTIVE Low- grade systemic inflammation may cause a chronic catabolic state that may affect trainability in patients with COPD as has been seen previously in healthy elderly . Therefore , the aim of the present study was to study the relationship between baseline circulating levels of inflammatory markers and the response to exercise training in clinical ly stable patients with COPD . DESIGN An open prospect i ve intervention study . SETTING Tertiary care setting , University Hospital Gasthuisberg , Leuven , Belgium . PATIENTS Seventy-eight clinical ly stable out patients with COPD . INTERVENTION A 12-week outpatient exercise-training program consisting of strengthening and endurance types of exercises . MEASUREMENTS AND RESULTS Circulating levels of inflammatory markers were assessed at baseline . Moreover , lung function , quadriceps force ( QF ) , peak and functional exercise capacity , and health-related quality of life were determined at baseline and after the intervention . Sixty-five of the 78 consecutive out patients completed the study protocol . QF , peak and functional exercise capacity and health-related quality of life improved significantly compared to baseline . The absolute changes in health-related quality of life showed weak relationships with baseline circulating levels of interleukin-8 ( CXCL8 ) in the whole group ( n = 65 ; r= -0.26 ; p = 0.04 ) . In addition , soluble tumor necrosis factor receptor p55 was strongly and positively related to the absolute changes in QF in the female patients only ( n = 18 ; r = 0.81 ; p = 0.0001 ) , while CXCL8 was inversely related to the absolute change in the total score of the Chronic Respiratory Disease Question naire ( r= -0.65 ; p = 0.004 ) . CONCLUSION Baseline markers of low- grade systemic inflammation did not clearly explain the variances in absolute changes in QF , the distance walked in 6 min , peak external load , or health-related quality of life following a 12-week exercise-training program . Hence , they seem not very constructive in the characterization of patients with advanced COPD who do or do not respond to exercise training The purpose of this study was to evaluate whether strength training is a useful addition to aerobic training in patients with chronic obstructive pulmonary disease ( COPD ) . Forty-five patients with moderate to severe COPD were r and omized to 12 wk of aerobic training alone ( AERO ) or combined with strength training ( AERO + ST ) . The AERO regimen consisted of three weekly 30-min exercise sessions on a calibrated ergocycle , and the ST regimen included three series of eight to 10 repetitions of four weight lifting exercises . Measurements of peripheral muscle strength , thigh muscle cross-sectional area ( MCSA ) by computed tomographic scanning , maximal exercise capacity , 6-min walking distance ( 6MWD ) , and quality of life with the chronic respiratory question naire were obtained at baseline and after training . Thirty-six patients completed the program and constituted the study group . The strength of the quadriceps femoris increased significantly in both groups ( p < 0.05 ) , but the improvement was greater in the AERO + ST group ( 20 + /- 12 % versus 8 + /- 10 % [ mean + /- SD ] in the AERO group , p < 0.005 ) . The thigh MCSA and strength of the pectoralis major muscle increased in the AERO + ST group by 8 + /- 13 % and 15 + /- 9 % , respectively ( p < 0.001 ) , but not in the AERO group ( 3 + /- 6 % and 2 + /- 10 % , respectively , p > 0.05 ) . These changes were significantly different in the two study groups ( p < 0.01 ) . The increase in strength of the latissimus dorsi muscle after training was modest and of similar magnitude for both groups . The changes in peak exercise work rate , 6MWD , and quality of life were comparable in the two groups . In conclusion , the addition of strength training to aerobic training in patients with COPD is associated with significantly greater increases in muscle strength and mass , but does not provide additional improvement in exercise capacity or quality of life OBJECTIVE To determine the effect of attendance at an outpatient pulmonary rehabilitation ( OPR ) program on changes in self-efficacy , perception of dyspnea , and exercise endurance in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Single-group , pretest and posttest design . SETTING A moderate sized , urban private hospital in western New York . PATIENTS Sixty patients with a diagnosis of COPD . Their ages ranged from 35 to 82 years ( mean + /- SD = 65 + /- 0.75 years ) . OUTCOME MEASURES Scores on the COPD Self-Efficacy Scale ( CSES ) and the Dyspnea Scale and distance walked ( feet ) on the 12-minute walking-distance test ( 12 MD ) . INTERVENTION The OPR consisted of an educational component and exercise training . Methods to increase self-efficacy were integrated into the rehabilitation program . Preprogram and postprogram measurements were obtained on the CSES , the Dyspnea Scale , and the 12 MD . RESULTS Paired t tests were used to examine the differences in mean scores between preprogram and postprogram results on the CSES , the Dyspnea Scale , and the 12 MD . There was a significant difference between preprogram and postprogram scores on the CSES ( p < 0.01 ) , the Dyspnea Scale ( p = 0.01 ) , and the 12 MD ( p = 0.04 ) . Pearson product moment correlations showed a significant negative correlation between scores on the CSES and scores on the Dyspnea Scale ( r = -0.5566 , p = 0.01 ) and a positive correlation between scores on the CSES and the 12 MD ( r = 0.4293 , p = 0.05 ) . These results indicated that higher self-efficacy scores on the CSES were correlated with lowered perception of dyspnea and greater distances walked in 12 minutes . CONCLUSIONS An OPR can improve self-efficacy or confidence in participants ' ability to manage or avoid breathing difficulty . Improvement in self-efficacy also may be a factor in decreased perception of dyspnea and increased exercise endurance . Methods to increase self-efficacy expectations with education and exercise training provide an approach to assist persons with COPD to manage their breathing difficulty more effectively . Further studies using a r and omized experimental , control design are needed to provide more conclusive direction with regard to effective methods in pulmonary rehabilitation Disability associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and improve quality of life . Many reports of the benefits of rehabilitation have been from uncontrolled trials and unsupervised programmes . In view of the commitment asked of patients , their families , and health-care professionals , rehabilitation should be justified by a demonstration of sustained improvement over conventional treatment . We undertook a prospect i ve r and omised controlled trial of respiratory rehabilitation in 89 subjects ( 44 men , 45 women ) aged 66 ( SD 7 ) years with severe but stable chronic obstructive pulmonary disease who received rehabilitation or conventional community care . The treatment group were rehabilitated as in patients for 8 weeks and supervised as out patients for 16 weeks . Primary outcome measures of exercise tolerance and quality of life were made at baseline and repeated at 12 , 18 , and 24 weeks . The difference between baseline and last follow-up was significant for 6 min walk distance ( 37.9 m [ 95 % CI 10.8 - 65.0 ] , p = 0.0067 ) and submaximal cycle time ( 4.7 min [ 2.1 - 7.3 ] ) . There were also significant differences in question naire assessment of dyspnoea ( p = 0.0061 ) , emotional function ( p = 0.0150 ) , mastery ( p = 0.0002 ) , and dyspnoea index ( p = 0.0053 ) . Improvements in exercise tolerance and quality of life can be achieved and sustained for 6 months in patients undergoing respiratory rehabilitation compared with those receiving conventional care OBJECTIVE To investigate the modulating effects of current smoking on adherence and responses to pulmonary rehabilitation ( PR ) in patients with chronic obstructive pulmonary disease ( COPD ) . METHODS In a prospect i ve study , 18 ex-smokers and 23 current smokers ( GOLD stages II-III ) were enrolled in a 12-week multidisciplinary , supervised PR program . The patients were assessed clinical ly and as to subjective variables ( dyspnea and health-related quality of life ) and objective variables ( body composition , pulmonary function and 6-min walking distance ) . The degree of nicotine dependence in current smokers was assessed by the Fagerström test . Program completion defined PR ' adherence ' . RESULTS There was a significant association between current smoking and non-adherence to PR with 30.4 % vs. 11.1 % and odds ratio=2.9 ( 1.6 - 4.1 ; p<0.01 ) . However , the current smokers who completed the program ( n=16 ) had a similar absentee rate to the ex-smokers , as well as similar gains in the subjective ( quality of life ) and objective ( walked distance ) items . Additionally , there was a significant reduction in daily cigarette consumption and in the degree of nicotine dependence in current smokers ( p<0.05 ) . CONCLUSIONS Although current smoking is negatively related to PR adherence , COPD smokers who complete the PR can have similar gains in functionality and quality of life compared to ex-smokers . Moreover , PR may be related to decreased nicotine dependence , even without a formal smoking withdrawal program This study compared the effects on self-efficacy of participation by patients with chronic obstructive pulmonary disease ( COPD ) in a pulmonary rehabilitation program that combined education and supervised exercise training with the results demonstrated by participation in a program that provided education alone . Thirty-seven patients participated in the pulmonary rehabilitation program , and 22 patients participated in the education-only program . Self-efficacy , as it effects managing or avoiding breathing difficulty , was measured before and after the programs . Patients ' self-efficacy scores significantly improved after the pulmonary rehabilitation program and remained significantly improved 6 months later . Education alone was also effective in significantly improving self-efficacy scores , but patients ' scores 6 months later were not significantly better than preprogram scores . This study indicates that a rehabilitation program that combines education and exercise training is more effective in improving long-term self-efficacy in patients with COPD BACKGROUND Chronic obstructive pulmonary disease ( COPD ) patients have lower levels of physical activity compared to age-matched controls , and they limit physical activities requiring normal exertion . Our purpose was to compare the effectiveness of a traditional exercise therapy ( TET ) program with a behavioral lifestyle activity program ( LAP ) in promoting physical activity . METHODS Moderate physical activity ( kcal/week ) was assessed in 176 COPD patients using the Community Health Activities Model for Seniors question naire . Patients were r and omized to either a three month TET program that meet thrice weekly or a LAP . The LAP was design ed to teach behavioral skills that encouraged the daily accumulation of self-selected physical activities of at least moderate intensity . Interventionist contact was similar ( 36 h ) between the two groups . Patients were assessed at baseline and 3 , 6 and 12 months . RESULTS Compared to baseline values , self-reported moderate physical activity increased three months post-r and omization with no significant difference ( p = 0.99 ) found between the TET ( 2501 + /- 197 kcal/week ) and the LAP ( 2498 + /- 211 kcal/week ) . At 6 and 12 months post-r and omization , there were no significant differences ( p = 0.37 and 0.69 , respectively ) in self-reported levels of moderate physical activity between the TET ( 2210 + /- 187 and 2213 + /- 218 kcal/week , respectively ) and the LAP ( 2456 + /- 198 and 2342 + /- 232 kcal/week , respectively ) . CONCLUSION Although there was no difference between treatment groups , the TET and the LAP were both effective at in increasing moderate levels of physical activity at 3 months and maintaining moderate physical activity levels 12 months post-r and omization . This clinical trial is registered with Clinical Trials.gov . Its identifier is NCT00328484 BACKGROUND Involving family as part of the patient 's rehabilitation plan of care might enhance the management of COPD . The primary aim of this study was to investigate the impact of a family-based pulmonary rehabilitation ( PR ) program on patients and family members ' coping strategies to manage COPD . METHODS Family dyads ( patient and family member ) were r and omly assigned to family-based ( experimental ) or conventional ( control ) PR . Patients from both groups underwent exercise training three times a week and psychosocial support and education once a week , during 12 weeks . Family members of the family-based PR attended the psychosocial support and education sessions together with patients . In the conventional PR , family members did not participate . Family coping and psychosocial adjustment to illness were assessed in patients and family members of both groups . Patients ' exercise tolerance , functional balance , muscle strength , and health-related quality of life were also measured . All measures were collected pre/post-program . RESULTS Forty-two dyads participated ( patients : FEV1 , 70.4 % ± 22.1 % predicted ) . Patients ( P = .048 ) and family members ( P = .004 ) in the family-based PR had significantly greater improvements in family coping than the control group . Family members of the family-based PR had significantly greater changes in sexual relationships ( P = .026 ) and in psychologic distress ( P = .033 ) compared with the control group . Patients from both groups experienced significant improvements in exercise tolerance , functional balance , knee extensors strength , and health-related quality of life after intervention ( P < .001 ) . CONCLUSIONS This research supports family-based PR programs to enhance coping and psychosocial adjustment to illness of the family system . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT02048306 ; URL : www . clinical trials.gov Aerobic exercise training is used for rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) , although it has little effect on muscle weakness and atrophy . Resistance training may be a useful addition to aerobic programs for these patients . The purpose of the present study was to investigate the effects of resistance training in addition to aerobic training on functional outcomes in patients with COPD . Seventeen COPD patients enrolled in an aerobic-based program that met twice a week were assigned to a 12-week control/aerobic [ CON : n=8 ; 63 ( 8) years ; mean ( SD ) ] or a resistance/aerobic group [ RES : n=9 ; 61 ( 7 ) years ] . RES trained an additional twice a week on 12 resistance machines , performing three sets of 8–12 repetitions at 32–64 % of their one-repetition maximum ( 1-RM ) lifts . RES ( P<0.05 ) increased upper ( 36 % ) and lower ( 36 % ) body strength , as well as lean body mass ( 5 % ) , while CON showed little to no change . The 12-min walk distance increased ( P<0.05 ) in only the RES [ 676 ( 219 ) to 875 ( 172 ) m ] . Measurements of three of the eight tasks of activities of daily living improved in RES ( P<0.05 ) compared to CON . This study demonstrated that progressive resistance training was well tolerated and improved functional outcomes in COPD patients that were currently involved in an aerobic training program PURPOSE Aerobic exercise training is a recognized approach for improving functional capacity in COPD . People with greater disease severity often have difficulty achieving higher aerobic exercise training intensity . The effects of resistance training prior to aerobic training were examined to determine if this sequential approach was associated with greater gains in functional status than aerobic training alone or concurrent aerobic and resistance training . METHODS Patients were r and omized to : 1 ) sequential resistance then aerobic training ( RT-then-AT ) ( 8 weeks resistance training followed by 8 weeks aerobic exercise training ) , 2 ) control group ( CE-then-AT + RT ) ( 8 weeks of ' sham ' training followed by 8 weeks concurrent aerobic and resistance training ) , 3 ) control group ( CE-then-AT ) ( 8 weeks ' sham ' training followed by 8 weeks aerobic training ) . Outcomes were assessed at study entry , after week 8 , and after week 16 : aerobic exercise performance ; muscle strength and endurance . RESULTS 75 patients completed training : FEV1 % pred 40 ± 10 , V˙O(2peak ) % predicted , 71 ± 22 , fat-free mass index 19.5 ± 3.1 . RT-then-AT had greater acquisition of peripheral muscle endurance than CE-then-AT + RT and CE-then-AT , but improvements in aerobic exercise performance were similar . Improvements in muscle strength were similar between RT-then-AT and CE-then-AT + RT . Sarcopenia was associated with poorer attendance , and lower aerobic and resistance training volumes . CONCLUSION Although the sequential approach to resistance and aerobic training yielded a greater increase in muscle endurance and higher resistance training volume compared to concurrent resistance and aerobic training , other training outcomes were similar between the two groups , thus the sequential approach is not clearly superior to the concurrent approach in severe COPD . Clinical Trials.gov Identifier : NCT01058213 This study investigated the effects of heavy resistance training in elderly males with chronic obstructive pulmonary disease ( COPD ) . 18 Home-dwelling male patients ( age range : 65 - 80 years ) , with a mean forced expiratory volume in the first second ( FEV1 ) of 46 + /- 3.4 % of predicted value , were recruited . Baseline and post-training assessment s included : Cross-sectional area ( CSA ) of quadriceps assessed by MRI , isometric and isokinetic knee extension strength , isometric trunk strength , leg extension power , normal and maximal gait-speed on a 30 m track , stair climbing time , number of chair st and s in 30 s , lung function ( FEV1 ) and self-reported health . Subjects were r and omized to a resistance training group ( RE , n = 9 ) or a control group conducting breathing exercises ( CON , n = 9 ) . RE performed heavy progressive resistance training twice a week for 12 weeks . 6 RE and 7 CON completed the study . In RE the following improved ( P < 0.05 ) : Quadriceps CSA : 4 % , isometric knee extension strength : 14 % , isokinetic knee extension strength at 60 degrees /s . : 18 % , leg extension power : 19 % , maximal gait speed : 14 % , stair climbing time : 17 % , isometric trunk flexion : 5 % and self-reported health . In CON no changes were found . In conclusion , 12 weeks of heavy resistance training twice a week result ed in significant improvements in muscle size , knee extension strength , leg extension power , functional performance and self-reported health in elderly male COPD patients Objective : To test the effects of pulmonary rehabilitation on fatigue , functional status and health perceptions in patients with chronic obstructive pulmonary disease . Design : R and omized controlled trial . Setting : Pulmonary outpatient department . Subjects : Thirty patients r and omly assigned to a rehabilitation ( 3 men , 9 women , mean age 66 ( ±2 ) years ) or a control group ( 10 men , 4 women , mean age 64 ( ±2 ) years ) . Interventions : The patients in the rehabilitation group participated in a multidisciplinary rehabilitation programme comprising exercise training twice weekly , for a 12-week period , nutritional and self-care advice , and education about disease and energy conservation strategies . Main measures : Fatigue , functional limitations due to fatigue , functional performance and satisfaction , six-minute walking distance , h and grip strength and health perception were assessed at baseline and after 12 weeks . Results : At baseline there were no significant differences between the groups , except for gender . The six-minute walking distance was 312.6 ( ±79.3 ) m for the rehabilitation group and 360.3 ( ±84.7 ) m for the control group . After 12 weeks , the rehabilitation group improved their walking distance by 40.6 ( ±27.2 ) m ( P<0.05 ) . The rehabilitation group improved in performance ( from 4.8 ( ±2.0 ) to 6.0 ( ±1.5 ) scores , P<0.01 ) and satisfaction ( from 4.6 ( ±2.2 ) to 6.0 ( ±2.1 ) scores , P<0.001 ) with regard to own selected daily activities . No statistically significant differences were seen between the changes within the rehabilitation group and changes within the control group at the 12-week follow-up . Conclusions : Although the pulmonary rehabilitation programme had an immediate effect , it was not sustained PURPOSE Pulmonary rehabilitation programs consistently have improved exercise capacity , quality of life , and symptoms over the past decade . Although training has been shown to be an essential component of the rehabilitation program , individual patients do not always benefit to the same extent . The present study was design ed to investigate which patients were achieving significant benefit of exercise training . METHODS Forty-nine stable out patients with moderate to severe COPD ( FEV1 37 (15)%pred ) were evaluated before and after 12 weeks of exercise training ( 3 times per week ) . Responders in exercise capacity were defined as having 15 % increase in maximal workload and /or 25 % increase in walking distance , while responders in quality of life showed an improvement of at least 10 points on the chronic respiratory disease question naire . With multivariate discriminant analysis , responders were distinguished from nonresponders based upon their initial characteristics . RESULTS Thirty-two patients were responders in terms of improved exercise capacity . Ventilatory reserve ( VE/MVV ) , inspiratory muscle strength ( Plmax ) , and peripheral muscle strength ( h and grip force and quadriceps force ) were significant predictors of the training response ( P < 0.05 ) ( accuracy 80 % P < 0.001 ) . Although the explained variance was modest , patients that were clearly ventilatory limited and had normal skeletal muscle strength were not likely to benefit from exercise training in terms of exercise capacity . No physiologic variables predicted whether a patient would increase quality of life after exercise training . CONCLUSION Patients with reduced exercise capacity who experience less ventilatory limitation to exercise and more reduced respiratory and peripheral muscle strength are more likely to improve with exercise training . Improvements in quality of life after exercise training were significant but remained unpredictable with variables included in the present trial BACKGROUND AND OBJECTIVE Skeletal muscle dysfunction contributes to exercise limitation in patients with chronic obstructive pulmonary disease ( COPD ) . Strength training increases muscle strength and muscle mass , but there is an ongoing debate on the additional effect concerning the exercise capacity . The purpose of this study was to compare the effects of three different exercise modalities in patients with COPD including endurance training ( ET ) , progressive strength training ( ST ) and the combination of strength training and endurance training ( CT ) . DESIGN A prospect i ve r and omized trial . METHODS Thirty-six patients with COPD were r and omly allocated either to ET , ST , or CT . Muscle strength , cardiopulmonary exercise testing , lung function testing and quality of life were assessed before and after a 12-week training period . RESULTS Exercise capacity ( Wmax ) increased significantly in all three training groups with increase of peak oxygen uptake ( VO2peak ) in all three groups , reaching statistical significance in the ET group and the CT group . Muscle strength ( leg press , bench press , bench pull ) improved in all three training groups , with a higher improvement in the ST ( + 39.3 % , + 20.9 % , + 20.3 % ) and the CT group ( + 43.3 % , + 18.1 % , + 21.6 % ) compared to the ET group ( + 20.4 % , + 6.4 % , + 12.1 % ) . CONCLUSIONS Progressive strength training alone increases not only muscle strength and quality of life , but also exercise capacity in patients with COPD , which may have implication s in prescription of training modality . CLINICAL TRIALS.GOV IDENTIFIER : NCT01091623 BACKGROUND Optimal strategies to maintain short-term benefits of an initial rehabilitation program ( RP ) are not known . To assess the long-term effects of exercise maintenance ( EM ) after an initial outpatient RP , the authors conducted a prospect i ve study . PATIENTS AND METHODS Fifty-eight patients with moderate to moderately severe chronic obstructive pulmonary disease who completed an initial 7-week outpatient RP were included . They were allocated into four groups according to the conditions of EM they self-selected : 15 patients received a structured EM session supervised by a physiotherapist twice a week ( group A ) ; 14 patients received a structured EM session supervised by a physiotherapist once a week ( group B ) ; 15 patients continued self EM daily at home ( group C ) ; and 14 patients did not continue EM ( group D ) . Patients were evaluated before , immediately after , and 18 months after the initial outpatient RP . Measurements included exercise testing on a cycle ergometer and a visual analog scale to evaluate chronic dyspnea . RESULTS After RP , all patients exhibited improvements in maximal workload ( P < 0.05 ) and in dyspnea ( P < 0.05 ) . Improvements in maximal workload were maintained at 18 months in patients in groups A , B , and C but these only reached significance in groups B and C ( P < 0.05 ) . On the other h and , maximal workload returned to baseline values in group D ( P = 0.01 ) at 18 months . CONCLUSION Our results indicate definite benefits of EM after an initial outpatient RP compared with no EM . Daily EM at home appears to be as efficient as structured EM sessions supervised by a physiotherapist , once or twice a week , in moderate to moderately severe chronic obstructive pulmonary disease OBJECTIVE To examine the short- and long-term effects of an outpatient pulmonary rehabilitation program for COPD patients on dyspnea , exercise , health-related quality of life , and hospitalization rate . SETTING Secondary -care respiratory clinic in Barcelona . METHODS We conducted a r and omized controlled trial with blinding of outcome assessment and follow-up at 3 , 6 , 9 , 12 , 18 , and 24 months . Sixty patients with moderate to severe COPD ( age 65 + /- 7 years ; FEV(1 ) 35 + /- 14 % ) were recruited . Thirty patients r and omized to rehabilitation received 3 months of outpatient breathing retraining and chest physiotherapy , 3 months of daily supervised exercise , and 6 months of weekly supervised breathing exercises . Thirty patients r and omized to the control group received st and ard care . RESULTS We found significant differences between groups in perception of dyspnea ( p < 0.0001 ) , in 6-min walking test distance ( p < 0.0001 ) , and in day-to-day dyspnea , fatigue , and emotional function measured by the Chronic Respiratory Question naire ( p < 0 . 01 ) . The improvements were evident at the third month and continued with somewhat diminished magnitude in the second year of follow-up . The PR group experienced a significant ( p < 0.0001 ) reduction in exacerbations , but not the number of hospitalizations . The number of patients needed to treat to achieve significant benefit in health-related quality of life for a 2-year period was approximately three . CONCLUSION Outpatient rehabilitation programs can achieve worthwhile benefits that persist for a period of 2 years PURPOSE there is evidence suggesting that physical activity has anti-inflammatory effects in many chronic diseases ; however , the role of exercise in airway inflammation in asthma is poorly understood . We aim ed to evaluate the effects of an aerobic training program on eosinophil inflammation ( primary aim ) and nitric oxide ( secondary aim ) in patients with moderate or severe persistent asthma . METHODS sixty-eight patients r and omly assigned to either control ( CG ) or aerobic training ( TG ) groups were studied during the period between medical consultations . Patients in the CG ( educational program + breathing exercises ; N = 34 ) and TG ( educational program + breathing exercises + aerobic training ; N = 34 ) were examined twice a week during a 3-month period . Before and after the intervention , patients underwent induced sputum , fractional exhaled nitric oxide ( FeNO ) , pulmonary function , and cardiopulmonary exercise testing . Asthma symptom-free days were quantified monthly , and asthma exacerbation was monitored during 3 months of intervention . RESULTS at 3 months , decreases in the total and eosinophil cell counts in induced sputum ( P = 0.004 ) and in the levels of FeNO ( P = 0.009 ) were observed after intervention only in the TG . The number of asthma symptom-free days and VO(2max ) also significantly improved ( P < 0.001 ) , and lower asthma exacerbation occurred in the TG ( P < 0.01 ) . In addition , the TG presented a strong positive relationship between baseline FeNO and eosinophil counts as well as their improvement after training ( r = 0.77 and r = 0.9 , respectively ) . CONCLUSIONS aerobic training reduces sputum eosinophil and FeNO in patients with moderate or severe asthma , and these benefits were more significant in subjects with higher levels of inflammation . These results suggest that aerobic training might be useful as an adjuvant therapy in asthmatic patients under optimized medical treatment BACKGROUND Exercise is an important part of chronic obstructive pulmonary disease ( COPD ) treatment . However , it is not know about the minimum effective time of physical training that could beneficially modify the cardiac autonomic modulation ( CAM ) and exercise capacity in these patients . AIM To contrast the potential effects of a physical training program ( PTP ) , for 6 versus 12 weeks , on CAM by linear and nonlinear heart rate variability ( HRV ) indices and exercise capacity in COPD patients . DESIGN Prospect i ve r and omized controlled trial . SETTING Outpatient pulmonary rehabilitation . POPULATION Twenty moderate-to-severe COPD patients were r and omly assigned to either a training group ( N.=10 ) or a control group ( N.=10 ) . METHODS HRV at rest and during submaximal test was determined by linear ( rMSSD and SDNN ) and non-linear indices ( SD1 , SD2 and sample entropy [ SE ] ) . In addition , key responses were obtained during cardiopulmonary exercise testing ( CPET ) , the walking distance ( WD ) during the six minute walking test and submaximal constant speed testing ( CST ) . PTP consisted of 30 minutes of aerobic exercise training on a treadmill , 3 times per week at 70 % of CPET peak speed rate . Patients were evaluated on baseline , 6 and 12 weeks . RESULTS Significant improvements in HRV indices , WD , as well as , other physiological responses were observed after 6 weeks of the PTP and maintained until 12 weeks ( P<0.05 ) . However , after 12 weeks , the SD1 index demonstrated an additional improvement compared with 6 weeks ( P<0.05 ) . Peak oxygen uptake and dioxide carbon production improved only after 12 weeks ( P<0.05 ) . Interestingly , the 6th week-baseline delta ( 6th week-baseline ) of WD , SDNN and SE were significantly higher than 12th week-6th week delta ( P<0.05 ) . CONCLUSION These results indicate that beneficial changes on cardiac autonomic modulation in conjunction with improvement in submaximal functional capacity occur in the first 6 weeks of PTP in moderate to severe COPD . CLINICAL REHABILITATION IMPACT Short-term rehabilitation ( 6 weeks ) is an effective sufficient time to beneficially modify important outcomes as cardiac modulation and exercise capacity in COPD patients BACKGROUND Expiratory flow limitation ( EFL ) is the primary pathophysiological hallmark of chronic obstructive pulmonary disease ( COPD ) . However , the effect of lower-extremity endurance training alone on EFL in patients with COPD remains largely unknown . AIM This study aims to determine the effects of endurance training on EFL and dynamic hyperinflation in patients with stable COPD . METHODS This was a prospect i ve , single-blinded , non-r and omised controlled 12-week study recruiting Chinese patients with stable COPD in an endurance training group ( n = 15 ) or a control group ( n = 13 ) . Before and at the end of the study , we measured the EFL , pulmonary function , peak inspiratory flow ( PIF ) and maximum inspiratory pressure ( MIP ) ; moreover , the patients underwent a constant work rate exercise test in which Borg dyspnoea scale , tidal breathing flow volume curves and inspiratory capacity ( IC ) were determined every other minute . RESULTS Exercise training significantly improved the exercise endurance time ( 7.00 ± 3.05 vs 18.13 ± 6.44 min , P < 0.001 ) , MIP ( 69.49 ± 16.03 vs 80.18 ± 15.97 cmH2 O , P < 0.001 ) and PIF ( 3.96 ± 1.01 vs 4.51 ± 1.13 L/s , P = 0.014 ) , but not EFL ( 3.33 ± 0.49 vs 3.40 ± 0.51 , P = 0.334 ) . Subjects on training had decreased breathing frequency ( 26.26 ± 7.13 vs 23.15 ± 5.34 breaths/min , P = 0.002 ) , minute ventilation ( 30.28 ± 7.52 vs 26.85 ± 4.17 L , P = 0.013 ) , tidal peak expiratory flow ( 1.53 ± 0.22 vs 1.32 ± 0.20 L/s , P = 0.006 ) , mean expiratory flow ( 0.87 ± 0.19 vs 0.68 ± 0.15 L/s , P = 0.011 ) and Borg dyspnoea score ( 7.20 ± 1.15 vs 3.93 ± 1.39 , P < 0.001 ) , as well as increased IC ( 1.50 ± 0.34 vs 1.67 ± 0.45 L , P = 0.002 ) , expiratory time ( 1.47 ± 0.62 vs 1.72 ± 0.62 s , P = 0.004 ) and inspiratory flow reserve ( 2.05 ± 1.10 vs 2.95 ± 1.19 L/s , P = 0.002 ) at isotime . These changes were not observed in the control group . CONCLUSION Endurance training may benefit stable COPD patients in improving exercise endurance , inspiratory muscle strength , ventilatory requirements , exercise-induced hyperinflation and exertional dyspnoea BACKGROUND Asthma symptoms reduce patients ' daily activities , impair their health-related quality of life ( HRQoL ) , and increase their reports of anxiety and depression , all of which seem to be related to a decrease in asthma control . Aerobic exercise training is known to improve aerobic fitness and reduce dyspnea in asthmatics ; however , its effect in reducing psychologic distress and symptoms remains poorly understood . We evaluated the role of an aerobic training program in improving HRQoL ( primary aim ) and reducing psychologic distress and asthma symptoms ( secondary aims ) for patients with moderate or severe persistent asthma . METHODS A total of 101 patients were r and omly assigned to either a control group or an aerobic training group and studied during the period between medical consultations . Control group patients ( educational program plus breathing exercises ) ( n = 51 ) and training group patients ( educational program plus breathing exercises plus aerobic training ) ( n = 50 ) were followed twice a week during a 3-month period . HRQoL and levels of anxiety and depression were quantified before and after treatment . Asthma symptoms were evaluated monthly . RESULTS At 3 months , the domains ( physical limitations , frequency of symptoms , and psychosocial ) and total scores of HRQoL significantly improved only in the training group patients ( P < .001 ) ; the number of asthma-symptom-free days and anxiety and depression levels also significantly improved in this group ( P < .001 ) . In addition , a linear relationship between improvement in aerobic capacity and the days without asthma symptoms was observed ( r = 0.47 ; P < .01 ) . CONCLUSIONS Our results suggest that aerobic training can play an important role in the clinical management of patients with persistent asthma . Further , they may be especially useful for patients with higher degrees of psychosocial distress . TRIAL REGISTRATION clinical trials.gov ; Identifier : NCT-00989365 PURPOSE : Patients with chronic obstructive pulmonary disease ( COPD ) have balance impairments . However , pulmonary rehabilitation ( PR ) is associated with only minor improvements in functional balance . Therefore , there is a need to explore the role of balance training within PR . This study aim ed at assessing the effects of a PR program , with a specific component of balance training , on functional balance of patients with COPD . METHODS : Out patients with COPD ( N = 22 , age = 68.0 ± 11.8 years ; forced expiratory volume in 1 second = 72.2 ± 22.3 % predicted ) participated in a 12-week PR program including exercise training and psychosocial support and education . Exercise training sessions comprised endurance , strength , and a specific component of balance training . The Timed Up and Go ( TUG ) test was used to assess functional balance before and after the PR . Health-related quality of life ( St George 's Respiratory Question naire ) , quadriceps muscle strength ( 10 repetition maximum ) , and exercise tolerance ( 6-minute walk test ) were also assessed . RESULTS : Patients demonstrated significant improvements in TUG scores after PR ( mean change −1.7 ± 1.4 seconds ; P = .001 ; effect size = 1.249 ) . Before PR , 9 ( 41 % ) participants and after PR only 1 ( 4.5 % ) participant had a TUG performance worse than the average performance of age-matched healthy peers ( P = .008 ) . The St George 's Respiratory Question naire symptoms score ( P = .012 ) , quadriceps muscle strength ( P = .001 ) , and exercise tolerance ( P = .001 ) were also improved . CONCLUSIONS : Pulmonary rehabilitation with a specific component of balance training had a large effect on functional balance in patients with COPD . Findings highlight the value of including balance training in PR programs . Further research is needed to determine the optimal intervention to improve balance and its specific components among patients with COPD The aim of this study was to compare the effects of interval training ( 3-min intervals ) with continuous training on peak exercise capacity ( W peak ) , physiological response , functional capacity , dyspnoea , mental health and health-related quality of life ( HRQoL ) in patients with moderate or severe COPD . Sixty patients exercised twice weekly for 16 weeks after r and omisation to interval- or continuous training . Target intensity was 80 % of baseline W peak in the interval group ( I-group ) and 65 % in the continuous group ( C-group ) . Patients were tested by spirometry , ergometer cycle test , cardiopulmonary test and a 12 min walk test . Dyspnoea was measured by the dyspnoea scale from Chronic Obstructive Disease Question naire ( CRDQ ) , mental health by Hospital Anxiety and Depression scale ( HAD ) and HRQoL by the Medical Outcomes Survey Short Form 36 ( SF-36 ) . After training , W peak , peak oxygen uptake ( VO(2 ) peak ) and exhaled carbon dioxide ( VCO(2 ) peak ) increased significantly in both groups , no significant differences between the groups . Minute ventilation ( V(E ) peak ) increased only in the C-group . At identical work rates ( isotime ) VO(2 ) , VCO(2 ) and V(E ) were significantly more decreased in the I-group than in the C-group ( p<0.05 ) . Functional capacity , dyspnoea , mental health , and HRQoL improved significantly in both groups , no difference between the groups . Interval training and continuous training were equally potent in improving peak exercise capacity , functional exercise capacity , dyspnoea , mental health and HRQoL in patients with moderate or severe COPD . At isotime , the physiological response to training differed between the groups , in favour of the interval training Purpose Idiopathic pulmonary fibrosis ( IPF ) is a chronic , devastating , lung disease , with few therapeutic options . Data are limited with respect to the long-term effect of exercise training ( ET ) in IPF . This study sought to evaluate the long-term effects of a 12-week ET program on clinical outcomes in IPF patients . Methods Thirty-four IPF patients were r and omly allocated to ET or control groups . ET group participated in a 12-week supervised exercise program , while the control group continued with regular medical treatment alone . Exercise capacity , 30 s-chair-st and test for leg strength , dyspnea , and Saint George ’s Respiratory Question naire ( SGRQ ) for quality of life ( QOL ) were assessed at baseline and re-evaluated at 11 months from baseline . In addition , at 30-month time point from baseline , the impact of the 12-week intervention was analyzed with respect to survival and cardio-respiratory-related hospitalizations . Results Thirty-two patients completed the 12-week intervention and 28 patients ( 14 in each group ) were re-evaluated . At 11-month follow-up , no significant differences between the groups and time effect were demonstrated for most outcomes . ET group showed preserved values at the baseline level while the control group showed a trend of deterioration . Only the 30 s-chair-st and test ( mean difference 3 st and s , p = 0.01 ) and SGRQ ( mean difference −6 units , p = 0.037 ) were significantly different between the groups . At 30 months , the survival analysis showed three deaths , eight hospitalizations occurred in the control group versus one death , one lung transplantation and seven hospitalizations in the ET group , with no significant differences between groups . Conclusions At 11-month follow-up , the 12-week ET program showed clinical outcomes were preserved at baseline levels with some maintenance of improvements in leg strength and QOL in the ET group . The control group showed a trend of deterioration in the outcomes . At 30 months , the 12-week ET program did not show benefits in prognosis although the study was underpowered to detect such differences . We suggest including ET as a long-term continued treatment and as a core component of pulmonary rehabilitation programs for IPF patients OBJECTIVES To compare conventional exercise-based assessment of pulmonary rehabilitation ( PR ) with improvement in training exercises employed during a PR program , and to describe the cardiopulmonary response of different training exercises during PR of patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Observational study . SETTING Inpatient PR . PARTICIPANTS Patients with moderate to very severe COPD ( N=18 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Cardiopulmonary responses to interval cycling , arm exercise , and a test of functional activities of daily living ( ADLs ) were evaluated during the PR training program using a mobile telemetric breath-by-breath system . The effects of PR were evaluated by comparing pre-PR and post-PR training activities , incremental and constant work-rate cycling , and a 6-minute walk test . RESULTS Interval cycling and the ADLs test were moderate-intensity to heavy-intensity exercises ( 70%-80 % of maximal oxygen consumption ) , while the arm exercise was a low-intensity activity ( 40 % of maximal oxygen consumption ) . After 12 weeks of PR , cycle load , arm weights , and walking distances during training activities had increased alongside increased muscle mass . At iso-intensities , no cardiopulmonary changes in the training exercises were observed . Exercise duration of constant work-rate cycling and 6-minute walk distance increased by 160 % and 14 % , respectively , after PR , with concurrent right-shifts of anaerobic threshold and a decrease in heart rate . CONCLUSIONS Supervised increases in weight , load , and walking distance during training activities were useful clinical outcomes for patients , demonstrating the beneficial effects of progressive training on physical performance . However , for physiologic evaluation of PR , conventional tests , such as maximal incremental cycling , endurance cycling , and a 6-minute walk test , had greater validity . Physiologic evaluation of the training exercises showed that the training program complied with the training recommendations for PR RATIONALE Patients with chronic obstructive pulmonary disease ( COPD ) are afflicted by comorbidities . Few studies have prospect ively evaluated COPD comorbidities and mortality risk . OBJECTIVES To prospect ively evaluate COPD comorbidities and mortality risk . METHODS We followed 1,664 patients with COPD in five centers for a median of 51 months . Systematic ally , 79 comorbidities were recorded . We calculated mortality risk using Cox proportional hazard , and developed a graphic representation of the prevalence and strength of association to mortality in the form of a " comorbidome " . A COPD comorbidity index ( COPD specific comorbidity test [ COTE ] ) was constructed based on the comorbidities that increase mortality risk using a multivariate analysis . We tested the COTE index as predictor of mortality and explored whether the COTE index added predictive information when used with the vali date d BODE index . MEASUREMENTS AND MAIN RESULTS Fifteen of 79 comorbidities differed in prevalence between survivors and nonsurvivors . Of those , 12 predicted mortality and were integrated into the COTE index . Increases in the COTE index were associated with an increased risk of death from COPD -related ( hazard ratio [ HR ] , 1.13 ; 95 % confidence interval , 1.08 - 1.18 ; P < 0.001 ) and non- COPD -related causes ( HR , 1.18 ; 95 % confidence interval , 1.15 - 1.21 ; P < 0.001 ) . Further , increases in the BODE and COTE were independently associated with increased risk of death . A COTE score of greater than or equal to 4 points increased by 2.2-fold the risk of death ( HR , 2.26 - 2.68 ; P < 0.001 ) in all BODE quartile . CONCLUSIONS Comorbidities are frequent in COPD and 12 of them negatively influence survival . A simple disease-specific comorbidities index ( COTE ) helps assess mortality risk in patients with COPD Study design : R and omized clinical trial . Objective : To investigate the effect of including manual therapy ( MT ) in a pulmonary rehabilitation program for patients with chronic obstructive pulmonary disease ( COPD ) . Background : The primary source of exercise limitation in people with COPD is dyspnea . The dyspnea is partly caused by changes in chest wall mechanics , with an increase in chest wall rigidity ( CWR ) contributing to a decrease in lung function . As MT is known to increase joint mobility , administering MT to people with COPD carries with it the potential to influence CWR and lung function . Methods : Thirty-three participants with COPD , aged between 55 and 70 years ( mean = 65·5±4 years ) , were r and omly assigned to three groups : pulmonary rehabilitation ( PR ) only , soft tissue therapy ( ST ) and PR , and ST , spinal manipulative therapy ( SM ) , and PR . Outcome measures including forced expiratory volume in the 1st second ( FEV1 ) , forced vital capacity ( FVC ) , 6-minute walking test ( 6MWT ) , St. George 's respiratory question naire ( SGRQ ) , and the hospital anxiety and depression ( HAD ) scale were recorded at 0 , 8 , 16 , and 24 weeks . Results : There was a significant difference in FVC between the three groups at 24 weeks ( P = 0·04 ) . For the ST+SM+PR group versus PR only the increase was 0·40 l ( CI : 0·02 , 0·79 ; P = 0·03 ) . No major or moderate adverse events ( AE ) were reported following the administration of 131 ST and 272 SM interventions . Discussion : The increase in FVC is a unique finding . Although the underlying mechanisms responsible for this outcome are not yet understood , the most likely explanation is the synergistic effect result ing from the combination of interventions . These results support the call for a larger clinical trial in the use of MT for COPD Background : Various exercise training programs are used for patients with chronic obstructive pulmonary disease ( COPD ) of different severity . Objectives : To investigate the impact of individualized high-intensity training on exercise capacity with COPD . Methods : A total of 49 patients agreed to participate . Of these , 31 were assigned to the training group and 18 served as controls . The training group exercised twice a week for 90 min with consecutively increasing loads . At the time of enrollment ( T0 ) , as well as after 3 ( T1 ) and 6 ( T2 ) months , a 6-min walk test ( 6-MWT ) was performed and data on health-related quality of life , femoral muscle thickness , and various serum markers were obtained . Results : The training group improved in their 6-MWT results ( T0 = 407 ± 152 m vs. T1 = 459 ± 127 m , p = 0.002 , vs. T2 = 483.2 ± 130.1 m , p = 0.004 ) , in their cross-sectional area of the musculus rectus femoris ( T0 = 6.2 ± 1.2 cm2 vs. T1 = 6.9 ± 1.2 cm2 , p = 0.003 , vs. 7.5 ± 1.6 cm2 , p = 0.002 ) , and in their St. George 's Respiratory Question naire ( SGRQ ) score ( T0 = 43.3 ± 18.0 vs. T1 = 36.0 ± 18.4 , p = 0.001 , vs. T2 = 34.7 ± 18 . 0 , p = 0.004 ) . Serum levels of myostatin , irisin , resistin , and α-Klotho did not change significantly within the training period . Of note , the exercise group showed an inverse relationship between serum levels of resistin and those of α-Klotho after 6 months ( r = -0.608 , p = 0.021 ) . Conclusions : COPD patients undergoing an individualized , structured , high-intensity training program improved their exercise capacity , gained muscle mass , and improved their quality of life BACKGROUND : It is well established that physical training enhances functionality and quality of life in patients with COPD . However , little data exist concerning the effects of the usefulness of oxygen supply during exercise training for > 3 months in patients with COPD who are normoxemic at rest and during exercise . We hypothesized that oxygen supply during training sessions enables higher training intensity and thus optimizes training results in patients with COPD . METHODS : In this blinded r and omized controlled study , we carried out a 24-week training program with progressively increasing loads involving large muscle groups . In addition , we compared the influences of oxygen supplementation . Thirty-six subjects with moderate-to-severe COPD who were not dependent on long-term oxygen therapy trained under supervision for 24 weeks ( 3 times/week at 30 min/session ) . Subjects were r and omized into 2 groups : oxygen supply via nasal cannula at a flow of 4 L/min and compressed air at the same flow throughout the training program . Lung function tests at rest ( inspiratory vital capacity , FEV1 , Tiffeneau index ) , cycle spiroergometry ( peak ventilation , peak oxygen uptake , peak respiratory exchange rate , submaximal and peak lactic acid concentrations ) , 6-min walk tests , and quality -of-life assessment s ( Medical Outcomes Study 36-Item Short Form question naire ) were conducted before and after 12 and 24 weeks . RESULTS : Independent of oxygen supplementation , statistically significant improvements occurred in quality of life , maximal tolerated load during cycling , peak oxygen uptake , and 6-min walk test after 12 weeks of training . Notably , there were no further improvements from 12 to 24 weeks despite progressively increased training loads . CONCLUSIONS : Endurance training 3 times/week result ed in significant improvements in quality of life and exercise capacity in subjects with moderate-to-severe COPD within the initial 12 weeks , followed by a stable period over the following 12 weeks with no further benefits of supplemental oxygen PURPOSE : To compare the effects of 12-week training periods ( 2 d·wk−1 ) involving resistance training only with the effects of 12-week training periods involving combined resistance ( once weekly ) and endurance ( once weekly ) training on strength , endurance performance , and quality of life . METHODS : Thirty-six patients with moderate-to-severe chronic obstructive pulmonary disease were r and omized to combined training ( REG ) , resistance training alone ( RG ) , or control ( CG ) groups . Patients were tested for maximal strength of the upper and lower extremities , power output of the lower extremities , maximal ( W max ) and submaximal exercise capacity , performance on a 6-minute walk test ( 6MWT ) , and quality of life . RESULTS : REG and RG induced similar maximal strength gains . Muscle power increased 19 % ( P ⩽ .01 ) and W max improved 13 % ( P < .05 ) in REG . Reductions ( P < .05 ) in the heart rate and blood lactate at a given submaximal workload were observed in REG . Improvements in 6MWT and quality of life were similar in both training groups . CONCLUSIONS : Compared with a twice-weekly resistance training program , the combination of once-weekly resistance and once-weekly endurance training not only produced similar gains in maximal strength , 6MWT performance , and quality of life but also produced improvements in muscle power and endurance performance . These findings may have implication s for the prescription of resistance and endurance exercise for patients with chronic obstructive pulmonary disease BACKGROUND Knowledge of hatha yogic exercises , the most used yoga style , for increasing functional capacity in patients with obstructive pulmonary diseases remains limited . AIM The aim was to evaluate the effects and feasibility of hatha yoga ( HY ) compared to a conventional training program ( CTP ) on functional capacity , lung function and quality of life in patients with obstructive pulmonary diseases . DESIGN R and omized clinical trial . SETTING The study was performed at the Karolinska University Hospital , Stockholm , among out patients . POPULATION Thirty-six patients with obstructive pulmonary disease . METHODS Forty patients were r and omized with 36 ( 24 women , median age = 64 , age range : 40 - 84 years ) participating in HY ( N.=19 ) or CTP ( N.=17 ) . Both HY and CTP involved a 12-week program with a 6-month follow-up . Functional capacity ( using the 6-Minute Walk Test ) , lung function ( spirometry ) , respiratory muscle strength ( respiratory pressure meter ) , oxygen saturation ( SpO2 ) , breathlessness ( Borg ) , respiratory rate ( f ) and disease-specific quality of life ( CRQ ) were measured at baseline , at 12 weeks and at a 6-month follow-up . RESULTS Testing for interactions ( group x time ) with ANOVAs showed significant effects on the CRQ fatigue ( P=0.04 ) and emotional ( P=0.02 ) domains , with improvements in the CTP group after the 12-week intervention ( P=0.02 and 0.01 , respectively ) but not in the HY group . No between group effects emerged , however , within each group , significant improvements emerged for the six-minute walk distance ( 6MWD ) after 12-week intervention ( HY : mean difference 32.6 m ; CI : 10.1 - 55.1 , P=0.014 ; CTP : mean difference 42.4 m ; CI : 17.9 - 67.0 , P=0.006 ) . SECONDARY OUTCOMES within-group improvements in CRQ appeared in both groups . Within the HY group , f decreased and SpO2 increased . Improved effects after follow-up emerged only for the CTP group for diastolic blood pressure ( P=0.05 ) and CRQ emotional and fatigue domain ( P=0.01 ) . CONCLUSIONS There were no between-group differences . After 12 weeks , 6MWD improved significantly within both groups . Within the HY group , improvements in the CRQ mastery domain , f and SpO2 emerged . Within the CTP group , there were improvements in lung function parameter forced vital capacity , respiratory muscle strength and all CRQ-domains . The CTP also exhibited effects on CRQ after the 6months follow-up . CLINICAL REHABILITATION IMPACT Limited effects of HY and CTP emerged . HY seems feasible and safe as a form of physical exercise for pulmonary disease patients . As part of the rehabilitation , HY may constitute an alternative to other physical training activities and may be a useful addition to formal rehabilitation programs The objective of the study was to evaluate the effect of multidisciplinary pulmonary rehabilitation program on cognitive function in COPD patients , adjusting for potential confounders ( gender , age , tobacco consumption , and educational level ) . In this prospect i ve study , 34 COPD patients were su bmi tted to neuropsychological testing before and after a 3-month pulmonary rehabilitation program . A control group with 18 healthy subjects of similar age , sex , and educational status was used to compare the cognitive function of COPD patients and healthy subjects at baseline . The association between the rehabilitation and change on th scores of cognitive variables , adjusted for each covariate , was estimated by means of linear r and om-intercept regression models . At baseline , the COPD patients had worse cognitive function with regard to verbal learning , memory , subjective organization , and verbal processing in comparison to the healthy volunteers . The improvement in cognitive performance by the COPD patients was evidence d even after adjusting for the sociodemographic factors that could potentially interfere on cognitive function . Male gender and age less than 65 years old were associated to higher scores in verbal learning and memory at baseline and after the rehabilitation program . The clinical approach to COPD -induced cognitive dysfunction should include participation in pulmonary rehabilitation programs . There were gender- and age-related differences in cognitive scores that persisted after rehabilitation To examine the efficacy of targeted inspiratory muscle training ( IMT ) , 25 patients with moderate COPD were r and omly assigned to one of three groups . Eight patients received IMT along with general exercise reconditioning , GER+IMT ; nine patients received general exercise reconditioning , GER ; eight patients received sham breathing exercises , CONTROL . All groups used a spring-loaded inspiratory muscle trainer ; however , the GER and CONTROL groups breathed through these devices at only 15 % of their maximal inspiratory pressure . The GER+IMT group increased the load on these devices until at 6 wk the load was equal to 80 % of their maximal inspiratory pressure . All patients exercised three times per week for a 12-wk period in supervised sessions . Analysis of covariance revealed no significant differences in spirometric measurements , maximal inspiratory pressure , or maximal oxygen consumption among any of the three groups after the intervention ( p > 0.05 ) . Twelve-minute walk distance was significantly greater in the GER+IMT and GER groups than in the CONTROL group ( p = 0.03 ) . After the intervention , there was a trend ( p = 0.08 ) for treadmill time to be greater for the GER+IMT and GER groups than for the CONTROL group . Dyspnea ratings at different exercise intensities were not found to be significantly different among the three groups after the intervention . These results demonstrate that GER+IMT and GER alone are equally effective in improving exercise performance in patients with COPD . Additionally , the combination of GER and IMT does not appear to provide any clinical ly significant improvements in exercise performance or perceptions of dyspnea during exercise when compared with GER alone Objectives To study the effects of a one-year physical activity programme on aerobic capacity , physical activity and health-related quality of life ( HRQL ) in patients with systemic lupus erythematosus ( SLE ) by a r and omized control design . Methods Thirty-five women with low or moderate disease activity and organ damage were r and omized to intervention ( I ) or control ( C ) group . The intervention during months 0–3 consisted of education , supervised aerobic exercise at high intensity and individual coaching , as well as self-managed physical activity at low-to-moderate intensity . During months 4–12 , the physical activity was self-managed and the coaching was successively reduced over time . Outcome measures included : maximal oxygen uptake ( VO2 max ) from a bicycle ergometer test , self-reported physical activity and HRQL ( SF-36 ) . Results VO2 at sub-max . and max . increased , independent of group , during the one-year study period ( main effect of time p < 0.0001 ) . VO2 max . increased between baseline and month 3 ( p < 0.0001 ) , between months 3 and 6 ( p = 0.01 ) and the increase was sustained at month 12 ( ns ) . Frequency of physical activity at high intensity also increased , independent of group , during the study period . It was increased at months 3 , 6 and 12 compared to baseline ( p = 0.02 , p < 0.001 , p = 0.03 ) . Improvement in mental health between baseline and month 6 ( p = 0.002 ) was seen for the I-group , not the C-group ( p = 0.03 ) . Disease activity and organ damage did not change . Conclusions Physical activity and aerobic capacity increased after supervised exercise and coaching , and the improvement was sustained during the one-year programme . However , no interactions between the group differences were seen , which suggests that repeated measurements could motivate to increased physical activity and thereby to increased aerobic capacity . As sub-max . VO2 increased over time , training-induced changes in VO2 on-kinetics could be another explanation . Little influence on HRQL was seen after the programme . The study indicates that physical activity at high intensity over one year is tolerated by patients with mild to moderate SLE We compared , in a controlled clinical trial , the effect of specific inspiratory muscle training combined with general exercise reconditioning , for six months , with that of general exercise reconditioning alone on inspiratory muscle strength , endurance , and exercise performance in patients with COPD . Thirty-six patients were recruited into three groups ; 12 patients received specific inspiratory muscle training combined with general exercise reconditioning , 12 patients underwent general exercise reconditioning alone , and the remaining 12 patients received no training . Specific inspiratory muscle training , for six months , improved the inspiratory muscle strength and endurance in patients with COPD . This training combined with general exercise reconditioning also provided improvement in exercise tolerance , and this improvement was significantly greater than that of general exercise reconditioning alone The aim of this study was to investigate the impact of a physical activity (PA)-focused behavioural intervention during and after pulmonary rehabilitation ( PR ) on PA levels ( primary aim ) , health-related outcomes and self-efficacy ( secondary aims ) of patients with COPD . Thirty-two patients were r and omly assigned to an experimental group ( EG ) or control group ( CG ) . The EG received a PA-focused behavioural intervention during PR ( 3 months ) and follow-up support ( 3 months ) . The CG received PR ( 3 months ) . Daily PA was collected : number of steps ; time spent in moderate-to-vigorous PA ( MVPA ) , total PA and sedentary activities ( SA ) . Secondary outcomes comprised exercise capacity , muscle strength , health-related quality of life ( HRQOL ) and self-efficacy . Measures were collected at baseline , 3 and 6 months . Compared with the CG , the EG improved the number of steps ( p = 0.006 ) and time spent in MVPA ( p = 0.007 ) , total PA ( p = 0.014 ) and SA ( p = 0.018 ) at 3 months . Differences were maintained after follow-up support ( 0.025 ≤ p ≤ 0.040 ) , except for SA ( p = 0.781 ) . Exercise capacity , muscle strength and HRQOL were increased at 3 and 6 months ( p ≤ 0.002 ) with no between-group differences ( 0.148 ≤ p ≤ 0.987 ) . No changes were observed in self-efficacy ( p = 0.899 ) . A PA-focused behavioural intervention during and after PR may improve patients ' PA levels . Further research is warranted to assess the sustainability of the findings The objectives of our study were to ( i ) compare , in chronic obstructive pulmonary disease ( COPD ) patients , acute responses to continuous training at high intensity ( CTHI ) , continuous training at ventilatory threshold ( CTVT ) and interval training ( IT ) ; ( ii ) examine associations between acute responses and 12-week adherence ; and ( iii ) investigate whether the relationship between acute responses and adherence is mediated/moderated by affect/vigour . Thirty-five COPD patients ( forced expiratory volume in 1 second = 60.2 ± 15.8 % predicted ) , underwent baseline assessment s , were r and omly assigned to CTHI , CTVT or IT , were monitored throughout about before training , and underwent 12 weeks of exercise training during which adherence was tracked . Compared with CTHI , CTVT was associated with lower respiratory exchange ratio , heart rate and respiratory rate ( RR ) , while IT induced higher V ̇ E , V ̇ E / maximal voluntary ventilation , RR and lower pulse oxygen saturation . From pre- to post-exercise , positive affect increased ( F = 9.74 , p < 0.001 ) and negative affect decreased ( F = 6.43 , p = 0.005 ) across groups . CTVT reported greater end-exercise vigour compared to CTHI ( p = 0.01 ) and IT ( p = 0.02 ) . IT exhibited lowest post-exercise vigour ( p = 0.04 versus CTHI , p = 0.02 versus CTVT ) and adherence rate ( F = 6.69 , p = 0.004 ) . Mean V ̇ O 2 ( r = −0.466 , p = 0.007 ) and end-exercise vigour ( r = 0.420 , p = 0.017 ) were most strongly correlated with adherence . End-exercise vigour moderated the relationship between V ̇ O 2 and adherence ( β = 2.74 , t(32 ) = 2.32 , p = 0.03 ) . In summary , CTHI , CTVT and IT improved affective valence from rest to post-exercise and induced a significant 12-week exercise training effect . However , they elicited different acute physiological responses , which in turn were associated with differences in 12-week adherence to the target training intensity . This association was moderated by acute end-exercise vigour Objects The purpose of this study was to quantitatively assess the effects of water-based Liuzijue exercise on patients with COPD and compare it with l and -based Liuzijue exercise . Material s and methods Participants were r and omly allocated to one of three groups : the water-based Liuzijue exercise group ( WG ) , the l and -based Liuzijue exercise group ( LG ) , and the control group ( CG ) . CG participants accepted no exercise intervention , while training groups performed Liuzijue exercise according to Health Qigong Liuzijue ( People ’s Republic of China ) in different environments for 60-min sessions twice a week for 3 months . Results Of the 50 patients enrolled , 45 ( 90 % ) completed the 3-month intervention . The CG showed decreased expiratory muscle strength , extensor and flexor endurance ratio ( ER ) of the elbow joints and flexor peak torque ( PT ) , total work ( TW ) , and ER of the knee joints ( p<0.05 ) . Both training groups showed improved respiratory muscle strength , which differed from the CG ( p<0.001 ) . In addition , extensor and flexor TW of the elbow joints in the training groups were increased ( p<0.01 ) , and the WG differed from the CG in extensor TW and ER and flexor TW ( p<0.01 ) , while the LG differed from the CG in flexor TW and extensor ER ( p<0.05 ) . PT , PT/body weight ( BW ) , and TW in the knee joint extensor in the training groups were increased as well ( PT and PT/BW : p<0.05 , TW : p<0.01 ) , and the WG differed from the CG in terms of knee joints outcomes , while the LG differed from the CG in flexor TW only ( p<0.05 ) . Conclusion Water-based Liuzijue exercise has beneficial effects on COPD patients ’ respiratory muscle strength and peripheral skeletal muscle function , and additional benefits may exist in endurance of upper limbs and strength and endurance of lower limbs when compared with l and -based Liuzijue exercise Objective : To investigate the effectiveness of neuromuscular electrical stimulation added to pulmonary rehabilitation on walking tolerance and balance in patients with chronic obstructive pulmonary disease ( COPD ) . Design : R and omized clinical trial . Setting : Outpatient , Faculty of Medicine of Sousse , Tunisia . Subjects : A total of 45 patients with COPD were assigned to an intervention group ( n = 25 ) or a control group ( n = 20 ) . Interventions : The intervention group underwent a neuromuscular electrical stimulation added to pulmonary rehabilitation , and the control group underwent only a pulmonary rehabilitation , three times per week during six months . Main Measures : Measures were taken at baseline and after six months of training . A stabilometric platform , time up and go , Berg balance scale tests , 6 minute walking test , and the maximal voluntary contraction were measured . Results : In the intervention group , an increase in an exercise tolerance manifested by a longer distance walked in 6 minute walking test 619.5 ( 39.6 ) m was observed in comparison to the control group 576.3 ( 31.5 ) m. The values of the time up and go , Berg balance scale , and maximal voluntary contraction in the intervention group at follow-up were significantly higher than those in the control group ( P = 0.02 , P = 0.01 , P = 0.0002 , respectively ) . The center of pressure in the mediolateral and in the anteroposterior directions , as well as the center of pressure area was significantly more improved in open eyes and closed eyes in the intervention group compared to the control group ( P < 0.001 ) . Conclusion : The neuromuscular electrical stimulation added to pulmonary rehabilitation group benefited from better walking tolerance and greater balance improvement than the only pulmonary rehabilitation BACKGROUND : Pulmonary rehabilitation programs improve exercise capacity and quality of life in patients with COPD . Domiciliary strategies to maintain these benefits have been proposed . OBJECTIVE : This study aim ed to determine whether a rehabilitation manual would facilitate the maintenance of the benefits acquired during out-patient pulmonary rehabilitation . METHODS : Fifty subjects with stable COPD were included ( 26 women and 24 men ) . All the subjects were evaluated during screening and after 12 wk of out-patient rehabilitation , and then were r and omly divided into 2 groups , with one group that received the rehabilitation manual for home use ( manual group ) and the other group only received verbal recommendations ( control group ) . At this point , the 2 groups were similar . After 12 wk at home , both groups were evaluated a third time . All evaluations included a 6-min walk test ( 6MWT ) , 6-min step test , COPD Assessment Test , and measurement of dyspnea by using the modified Medical Research Council dyspnea scale . RESULTS : When comparing the results of the 6MWT and 6-min step test done at out-patient discharge and after 12 wk at home , the manual group presented no differences ( 6MWT , 0 ± 25 m ; 6-min step test , 1 ± 32 steps ) , whereas the control subjects lost part of the gain obtained during rehabilitation ( 6MWT −46 ± 36 m ; 6-min step test −39 ± 33 steps ) . There was a significant difference between the groups ( P < .05 ) . When comparing the same time points , the change in the COPD Assessment Test score was −1 ± 1 for the manual group and 1 ± 2 for the control group ( P = .01 ) . For the modified Medical Research Council dyspnea scale , the change in score was 0 ± 1 for the manual group and 1 ± 1 for the control group ( P = .01 ) . CONCLUSIONS : The use of a simple , well-illustrated manual facilitated the maintenance of the benefits acquired in out-patient pulmonary rehabilitation over a period of 3 months after study termination Background : Chronic Obstructive Pulmonary Disease ( COPD ) , in addition to its respiratory problems , is accompanied by several musculoskeletal consequences . The aim of this study is to investigate the effectiveness of eccentric exercise in the form of downhill walking ( DW ) on respiratory capacity , physical function and quality of life ( QOL ) in patients with COPD . Methods : The r and omized controlled trial was carried out during 2014 - 2015 in Hazrat-e-Rasool Hospital in Tehran , Iran . The study design was as an assessor blind RCT on 32 patients with COPD that r and omly assigned to the eccentric training ( ET ) and control ( CON ) groups . Patients in ET group received a 12-week DW exercise on the treadmill while the patients in the control group were only treated by COPD conventional medications and walked on paved surfaces . Functional tests , FEV1 , FEV1 to FVC and St. George ’s Respiratory Question naire ( SGRQ ) were used to assess the subject ’s physical status and QOL pre and post-intervention . Results : The FEV1 ( p=0.008 ) , FEV1/FVC ( p=0.002 ) , six-minute walk test ( p=0.029 ) , timed up & go test ( p=0.023 ) , SGRQ symptom ( p=0.022 ) , SGRQ activity ( p=0.007 ) , SGRQ impact ( p=0.033 ) and total score of SGRQ ( p=0.013 ) improved significantly in the ET group compare to the CON group . Conclusion : DW could have positive influence on physical status and QOL of patients with COPD Background Few data are available on the long-term effect of pulmonary rehabilitation ( PR ) and on long PR programs in interstitial lung diseases (ILD).We aim ed to evaluate the effects of PR on exercise capacity ( 6-Minute Walking Distance , 6MWD ; Peak Work Rate , Wmax ) , quality of life ( St George ’s Respiratory Question naire , SGRQ ) , quadriceps force ( QF ) and objective ly measured physical activity in ILD after the 6-month PR-program and after 1 year . Methods 60 patients ( 64 ± 11 years ; 62 % males ; 23 % with IPF ) were r and omly assigned to receive a 6 month-PR program or usual medical care . Results Exercise capacity , quality of life and muscle force increased significantly after the program as compared to control ( mean,95%CI[ll to ul ] ; 6MWD + 72,[36 to 108 ] m ; Wmax 19 , [ 8 to 29]%pred ; SGRQ − 12,[− 19 to − 6 ] points ; QF 10 , [ 1 to 18 ] % pred ) . The gain was sustained after 1 year ( 6MWD 73,[28 to 118 ] m ; Wmax 23 , [ 10 to 35]%pred ; SGRQ − 11,[− 18 to − 4 ] points ; QF 9.5 , [ 1 to 18 ] % pred ) . Physical activity did not change . Conclusions PR improves exercise tolerance , health status and muscle force in ILD . The benefits are maintained at 1-year follow-up . The intervention did not change physical activity . Trial registration Clinical trials.gov NCT00882817 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 OBJECTIVES To compare the effects of two similar 6-month protocol s of high-intensity exercise training , in water and on l and , in patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN R and omised controlled trial . SETTING University-based outpatient clinic . PARTICIPANTS Thirty-six patients with predominantly moderate-to-severe COPD completed the study . INTERVENTION Patients were evaluated at baseline , at 3 months and at the end of the programme ( i.e. 6 months ) . For both groups , the 6-month protocol consisted of high-intensity endurance and strength exercises with gradual increase in time and /or workload , totalling 60 sessions . MAIN OUTCOMES Objective monitoring of physical activity in daily life ( PADL , primary outcome ) , lung function , peripheral and respiratory muscle strength , body composition , maximal and submaximal exercise capacity , functional status , quality of life , and symptoms of anxiety and depression . RESULTS After 6 months of training , a significant improvement in PADL was seen for both groups [ mean difference ( 95 % confidence interval ) : l and group 993 ( 358 to 1628 ) steps/day ; water group 1669 ( 404 to 2934 ) steps/day ] . Significant improvements were also seen in inspiratory , expiratory and peripheral muscle strength ; maximal and submaximal exercise capacity ; quality of life and functional status for both groups . There were no significant improvements in lung function , body composition , and symptoms of anxiety and depression for either group . No difference was found in the magnitude of improvement between the two types of training for any outcome . CONCLUSION High-intensity exercise training in water generates similar effects compared with training on l and in patients with moderate-to-severe COPD , rendering it an equally beneficial therapeutic option for this population . CLINICAL TRIAL REGISTRATION NUMBER NCT01691131 Purpose Pulmonary rehabilitation ( PR ) enhances exercise tolerance in patients with COPD ; however , improvements in physical activity ( PA ) are not guaranteed . This study explored the relationship between baseline exercise tolerance and changes in PA after PR . Material s and methods Patient data from prospect i ve clinical trials in the PR setting s of Athens and Leuven ( 2008–2016 ) were analyzed . Vali date d PA monitors were worn for 1 week before and after a 12-week program . The proportion of patients who improved PA levels ≥1,000 steps/day ( “ PA responders ” ) after PR was compared between those with initial 6-minute walk distance [ 6MWDi ] < 350 m and ≥350 m. Baseline predictors of PA change were evaluated via univariate and multivariate logistic regression analyses . Results Two hundred thirty-six patients with COPD ( median [ IQR ] FEV1 44 [ 33–59 ] % predicted , age 65±8 years , 6MWDi 416 [ 332–486 ] m ) were included . The proportion of “ PA responders ” after PR was significantly greater in those with higher vs lower 6MWDi ( 37.9 % vs 16.4 % , respectively ; P<0.001 ) . 6MWDi group classification was the strongest baseline independent predictor of PA improvement ( univariate OR 3.10 , 95 % CI 1.51–6.36 ) . Conclusion The likelihood of improving PA after PR is increased with greater 6MWDi . Baseline exercise tolerance appears as an important stratification metric for future research in this field BACKGROUND The inclusion of Pulmonary Rehabilitation as part of the management of Interstitial Lung Disease , although being highly recommended in most recent guidelines , still has limited studies exploring the outcomes from such an intervention . The present study aims to contribute to the available literature by investigating the effects of a high intensity , 12 week PR programme on functional and quality of life measures in patients with a diagnosis of Interstitial Lung Disease . METHOD ology : This paper reports outcomes of an observational , prospect i ve , quasi experimental type of study . A total of 120 participants were recruited : 60 patients formed part of the active group , and another 60 patients were enrolled in an inactive group . Each participant was classified according to the modified Medical Research Council dyspnoea scale and placed in one of 5 categories ( 0 - 4 ) according to self-perceived breathlessness during daily activities . The following outcomes were measured : Lung function tests including plethysmography and diffusion capacity of carbon monoxide ( DLCO ) , functional tests ( 6-min walking distance test , Dyspnoea Borg Scale ) and health status measures ( St George 's Respiratory Question naire and Hospital Anxiety and Depression Score ) . RESULTS A 12-week PR programme for patients with Interstitial Lung Disease , led to significant improvements in the active group of patients in the 6 min walking distance test , the modified Borg Scale , mMRC scores and in the health status measures . Lung function measures did not show any significant improvement following this intervention . CONCLUSION This 12week Pulmonary Rehabilitation programme result ed in improvements in functional aspects for patients with Interstitial Lung Disease . Further studies are recommended as Pulmonary Rehabilitation for Interstitial Lung Disease may have an impact at both an individual level and at global organisational/financial levels INTRODUCTION Elastic tubing was recently investigated as an alternative to the conventional resistance training ( RT ) in chronic obstructive pulmonary disease ( COPD ) . The effects of RT on the mucociliary system have not yet been reported in the literature . OBJECTIVE The aim of this study was to evaluate the effects of two RT programs on mucociliary clearance in subjects with COPD . METHODS Twentyeight subjects with COPD were r and omly allocated by strata , according to individual strength of lower limbs , to defined groups : conventional resistance training ( GCT ) or resistance training using elastic tubing ( GET ) . Nineteen subjects ( GET : n=9 ; GCT : n=10 ) completed the study and were included in the analysis . The measurement of vital signs ( blood pressure , heart rate and respiratory rate ) , lung function ( spirometry ) and the primary outcome mucociliary clearance analysis ( saccharin transit time test ( STT ) ) were performed before and after the 12 weeks of RT . RESULTS In relation to the mucociliary transportability analysis , no differences were observed between the baseline evaluations of the training groups ( p=0.05 ) . There was a significant reduction in the STT values in both training groups , GET ( 10.64±5.06 to 6.01±4.91 ) and GCT ( 12.07±5.10 to 7.36±2.54 ) with p=0.03 . However , no differences between groups were observed on the magnitude of SST changes after interventions ( GET : -43.51 % ; GCT : -38.94 % ; p=0.97 ) . CONCLUSION The present study demonstrated that both RT with elastic tubing and conventional training with weights promoted similar gains in the mucociliary transportability of subjects with COPD We compared the effects of a new physical activity education program approach ( EDU ) , based on a periodically supervised protocol of different exercise modalities vs traditionally supervised combined strength-endurance training ( CT ) on health-related factors in patients with stable chronic obstructive pulmonary disease ( COPD ) . Twenty-eight COPD patients without comorbidities were r and omly assigned to receive either EDU or CT . CT was continuously supervised to combine strength-endurance training ; EDU was taught to progressively increase the rate of autonomous physical activity , through different training modalities such as Nordic walking , group classes and circuit training . Body composition , walking capacity , muscle strength , flexibility and balance , total daily energy expenditure and quality of life were evaluated at baseline , after 28 weeks training period ( 3d/week ) and after a 14-week follow-up . No adverse events occurred during the interventions . After training , CT and EDU similarly improved walking capacity , body composition and quality of life . However , after 14 weeks of follow-up , such improvements were not maintained . Only in CT , muscle strength and flexibility improved after training but returned to baseline after follow-up . EDU , similar to CT , can effectively and safely improve health-related parameters in COPD patients . EDU could be an attractive alternative to traditional supervised training for improving quality of life in COPD patients AIM Although the effects of pulmonary rehabilitation ( PR ) have been well defined for chronic obstructive pulmonary disease ( COPD ) , it remains controversial whether PR improves physical activity ( PA ) . The purpose of the present study was to identify factors associated with the effect of PR on PA . METHODS This was a prospect i ve study of 29 patients with COPD . They underwent pulmonary rehabilitation twice weekly for 12 weeks , and were assessed using the hospital anxiety and depression score , 6-min walk distance ( 6MWD ) , and the St. George Respiratory Question naire ( SGRQ ) before and after they underwent PR . The PA of patients was measured by a three-axis accelerometer . Physical activity level ( PAL ) was calculated by dividing each patient 's total energy expenditure by basal metabolic rate . Correlations between changes in PAL after PR and 6MWD , St. George Respiratory Question naire , and hospital anxiety and depression score scores , and clinical parameters , including forced expiratory volume in 1 s were determined . RESULTS 6MWD was significantly increased , but PAL was unchanged after PR . PAL was positively correlated with 6MWD , but not with percent predicted forced expiratory volume in 1 s nor St. George Respiratory Question naire scores before PR . The increase in PAL was negatively correlated with changes in hospital anxiety and depression score anxiety and depression scores , but was not correlated with the change in 6MWD . CONCLUSIONS A PR program for COPD patients improved results of the 6MWD , but not PAL . Increased PAL was associated with improvements in anxiety and depression , but not with increased exercise capacity . Treating the depression and anxiety of patients with COPD might not only reduce emotional distress , but also improve their PAL . Geriatr Gerontol Int 2017 ; 17 : 17 - 23 OBJECTIVE To investigate the effects of a supervised longer- ( 14wk ) versus shorter- duration ( 7wk ) rehabilitation program after lung transplantation ( LTX ) . DESIGN R and omized controlled trial . SETTING Outpatient rehabilitation gym setting . PARTICIPANTS Post-LTX patients aged ≥18 years ( N=66 ; 33 women ; mean age , 51±13y ) who had undergone either single LTX or bilateral LTX . INTERVENTION Outpatient rehabilitation program consisting of thrice-weekly sessions with cardiovascular training on bike ergometer and treadmill plus upper and lower limb strength training . MAIN OUTCOME MEASURES Measures were taken at baseline , 7 weeks , 14 weeks , and 6 months by assessors who were blinded to group allocation . Functional exercise capacity was measured by the 6-minute walk test ( 6MWT ) . Strength of quadriceps and hamstrings was measured on an isokinetic dynamometer and recorded as average peak torque of 6 repetitions for both muscles . Quality of life ( QOL ) was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey . RESULTS Of the participants , 86 % had bilateral LTX and 41 % had primary diagnosis of chronic obstructive pulmonary disease . The 6MWT increased in both groups with no significant difference between groups at any time point ( mean 6mo 6MWD : short , 590±85 m vs long , 568±127 m ; P=0.5 ) . Similarly , at 6 months , there was no difference between groups in quadriceps average peak torque ( mean , 115±38Nm vs 114±40Nm , respectively ; P=.59 ) , hamstring average peak torque ( 57±18Nm vs 52±19Nm , respectively ; P=.36 ) , or mental or physical health domains of quality of life . CONCLUSIONS Shorter duration ( 7wk ) of rehabilitation achieves comparable outcomes with 14 weeks of supervised rehabilitation for functional exercise capacity , lower limb strength , and quality of life at 6 months after LTX PURPOSE : Balance impairment is recognized as an important issue for patients with chronic obstructive pulmonary disease ( COPD ) . The aim of this study was to examine the effect of balance training as part of pulmonary rehabilitation ( PR ) on balance in COPD patients . METHODS : Patients were r and omly assigned to an intervention or usual care group . The intervention group underwent balance training 3 times a week for 6 months in addition to the st and ard PR . The control group received 6 months of the st and ard PR program only . Balance was assessed by the Timed Up and Go ( TUG ) , Tinetti , Berg Balance Scale ( BBS ) , and the Unipodal Stance ( UST ) tests . Balance confidence was rated using the ABC scale . Exercise tolerance was determined using a 6-Minute Walk Test . RESULTS : Following the completion of PR , the intervention group showed improvement in all balance measures . Only TUG , ABC , and UST scores were improved in the usual care group ( P < .05 ) . Results demonstrated significant between-group differences in TUG , Tinetti , BBS , and ABC scores ( P < .01 ) and UST score ( P < .05 ) . CONCLUSIONS : Balance training incorporated into a st and ard PR program significantly improves scores on balance tests in COPD patients |
2,639 | 23,507,014 | The results suggested that CPB may not be associated with cognitive decline that is associated with CABG surgery | OBJECTIVE The aim of this study was to compare cognition following coronary artery bypass grafting ( CABG ) surgery with or without cardiopulmonary bypass ( CPB ) ( on- or off-pump ) . | AIMS Uncertainty persists regarding the impact of the off-pump technique on coronary bypass graft patency . The primary objective of this study was to assess coronary artery bypass graft patency in patients r and omized to off-pump and on-pump multivessel coronary artery bypass grafting ( CABG ) . Secondary objectives were clinical outcomes and neuropsychological functioning . METHODS AND RESULTS One hundred and fifty patients were r and omized to off-pump ( n = 75 ) or on-pump CABG ( n = 75 ) . Graft patency was assessed by multidetector computed tomography 5 weeks after surgery . The two groups were similar regarding patients ' characteristics and logistic Euroscore ( 3.6 vs. 3.7 % ) . Mean number of grafts performed was 3.5 ± 0.6 and 3.5 ± 0.6 in off-pump and on-pump , respectively ( P = 0.7 ) . Raw graft patency rate was 89.9 % in off-pump and 95.0 % in on-pump ( OR 2.2 , 95 % CI 1.07 - 4.44 ; P = 0.03 ) . Nineteen ( 27 % ) off-pump and 9 ( 13 % ) on-pump patients had at least one occluded graft ( P = 0.04 ) and the proportion of patent grafts per patient was 0.91 ± 0.2 in off-pump vs. 0.96 ± 0.1 in on-pump ( P = 0.06 ) . However , after adjusting by heparin dose , graft patency was not statistically different between groups ( OR 0.87 , 95 % CI 0.25 - 2.98 , P = 0.83 ) . At 30 days , there was no statistically significant difference in major adverse events and neuropsychological functioning between off-pump and on-pump groups . One-year follow-up showed similar functional class and positive treadmill exercise tests . CONCLUSIONS Under the conditions this trial was conducted , CABG performed off-pump had lower overall graft patency rate than on-pump , which was not statistically different after controlling for total heparin dose . Thirty-day complications , neuropsychological functioning , and one-year clinical and functional outcomes were not statistically different between the two techniques BACKGROUND Coronary artery bypass surgery with cardiopulmonary bypass carries a significant risk of perioperative brain injury . At least 1 % to 5 % will suffer a stroke , and at 3-months postoperatively approximately 30 % are reported to have cognitive impairment assessed by neuropsychologic testing . In off-pump surgery cardiopulmonary bypass is not used and instrumentation on the ascending aorta is reduced . The main aim of this study was to assess if off-pump surgery reduces intraoperative cerebral embolization . METHODS This was a prospect i ve and r and omized study of two comparable groups with regard to age , sex , years of education , preoperative cognitive functioning , and surgical characteristics . Fifty-two patients ( 29 off-pump ) were monitored by the use of transcranial Doppler ultrasound for cerebral microembolization during surgery . Preoperative and postoperative clinical , cerebral magnetic resonance imaging , and neuropsychologic examinations were also carried out . RESULTS There was a significant reduction in the number of cerebral microemboli during off-pump compared with on-pump surgery ( 16.3 [ range 0 to 131 ] versus 90.0 [ range 15 to 274 ] , p < 0.0001 ) . No significant difference with regard to the incidence of neuropsychologic performance ( decline in 29 % off-pump , 35 % on-pump ) or neuroradiologic findings at 3 months was found , and there was no association between the number of cerebral microemboli and cognitive outcome . CONCLUSIONS This study clearly demonstrates that off-pump surgery leads to a reduction in intraoperative cerebral microembolization . A significant reduction in the number of off-pump patients with cognitive decline or ischemic brain lesions on cerebral magnetic resonance imaging could not be demonstrated in this relatively small patient population OBJECTIVE Age is considered to be the strongest predictive factor of postoperative cognitive dysfunction ( POCD ) after cardiac surgery . Coronary artery bypass grafting ( CABG ) without the use of cardiopulmonary bypass is considered to be less harmful to the patient , especially in terms of neurological complications . METHODS The study was a sub- study of the r and omized best bypass surgery trial that compares off-pump to on-pump treatment , with respect to peri- and postoperative morbidity in patients with a moderate to high-predicted preoperative risk . We investigated cognitive outcomes . A total of 120 elderly patients ( mean age 76 years , SD 4.5 years ) underwent cognitive testing before surgery , of which 90 patients ( 47 vs 43 ) were available for retesting at 1 year ( mean 370 days ) postoperatively , using a neuropsychological test battery that included seven parameters from four tests . POCD was defined as the occurrence of at least two deficits out of the seven possible scores . Secondary analysis was performed based on definition of 20 % decline in cognitive scores compared to baseline , and using z-score analysis . RESULTS The incidence of POCD was 19 % ( 95 % CI 9 - 33 ) in the off-pump group and 9 % ( 95 % CI 3 - 22 ) in the on-pump group ( p=0.18 ) . There were no significant differences in the incidence of cognitive decline between the off-pump and on-pump group regardless of the definition applied . CONCLUSIONS We were unable to detect that CABG surgery without cardiopulmonary bypass was associated with significantly better cognitive outcome in elderly high-risk patients 1 year after the operation CONTEXT Coronary artery bypass graft ( CABG ) surgery is associated with a decline in cognitive function , which has largely been attributed to the use of cardiopulmonary bypass ( on-pump procedures ) . Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass ( off-pump procedures ) and should reduce the cognitive decline associated with on-pump procedures . OBJECTIVE To compare the effect of CABG surgery with ( on-pump ) and without ( off-pump ) cardiopulmonary bypass on cognitive outcome . DESIGN AND SETTING R and omized controlled trial conducted in the Netherl and s of CABG surgery patients enrolled from March 1998 through August 2000 , with 3- and 12-month follow-up . PARTICIPANTS AND INTERVENTION Patients scheduled for their first CABG surgery ( mean age , 61 years ; n = 281 ) were r and omly assigned to off-pump surgery ( n = 142 ) or on-pump surgery ( n = 139 ) . MAIN OUTCOME MEASURES Cognitive outcome at 3 and 12 months , which was determined by psychologists ( blinded for r and omization ) who administered 10 neuropsychological tests before and after surgery . Quality of life , stroke rate , and all-cause mortality at 3 and 12 months were secondary outcome measures . RESULTS Cognitive outcome could be determined at 3 months in 248 patients . Cognitive decline occurred in 21 % in the off-pump group and 29 % in the on-pump group ( relative risk [ RR ] , 0.65 ; 95 % confidence interval [ CI ] , 0.36 - 1.16 ; P = .15 ) . The overall st and ardized change score ( ie , improvement of cognitive performance ) was 0.19 in the off-pump vs 0.13 in the on-pump group ( P = .03 ) . At 12 months , cognitive decline occurred in 30.8 % in the off-pump group and 33.6 % in the on-pump group ( RR , 0.88 ; 95 % CI , 0.52 - 1.49 ; P = .69 ) . The overall st and ardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group ( P = .09 ) . No statistically significant differences were observed between the on-pump and off-pump groups in quality of life , stroke rate , or all-cause mortality at 3 and 12 months . CONCLUSION Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure , but the effects were limited and became negligible at 12 months OBJECTIVE It is unknown whether avoidance of cardiopulmonary bypass during coronary artery bypass grafting affects cerebral injury or long-term neuropsychological function . METHODS Two hundred unselected patients were r and omized to off-pump coronary artery bypass or on-pump coronary artery bypass grafting between March 2000 and August 2001 . One hundred sixty-eight patients had early postoperative brain magnetic resonance imaging . Eighty-seven returned after a mean of 7.5 years of follow-up ; 67 had repeat magnetic resonance imaging , and 76 had neuropsychological testing . RESULTS There were 26 deaths among patients undergoing off-pump coronary artery bypass and 31 among patients undergoing cardiopulmonary bypass as of March 2009 . Seventy-six patients ( 41 undergoing cardiopulmonary bypass and 35 undergoing off-pump coronary artery bypass ) had neuropsychological testing at late follow-up . Groups were similar in age , sex , depression , and IQ . Patients undergoing off-pump coronary artery bypass showed better attention , performing better at tracking and mentally manipulating information ( P = .011 ) . Patients undergoing off-pump coronary artery bypass demonstrated better cognitive reasoning and made fewer errors in reasoning ( P = .05 ) ; they also showed a trend toward better verbal learning ( P = .064 ) . There were no domains in which patients undergoing cardiopulmonary bypass outperformed those undergoing off-pump coronary artery bypass . Early magnetic resonance imaging in 168 patients showed no significant differences between groups in temporal or frontal lobe atrophy , subcortical white matter lesions , or acute infa rct ions . There were no significant differences between groups in atrophy over time or new subcortical white matter lesions or infa rct ions . Acute perioperative cerebral infa rct ions were more common and atrophy more progressive during follow-up among diabetic than nondiabetic patients . CONCLUSIONS After a mean of 7.5 years of follow-up , patients undergoing off-pump coronary artery bypass performed better than those undergoing cardiopulmonary bypass in several neuropsychological domains ; these differences were small and of uncertain clinical importance . Early brain magnetic resonance imaging showed no significant differences in acute cerebral infa rct ions between the off-pump coronary artery bypass and cardiopulmonary bypass groups OBJECTIVE To investigate cognitive outcome after on and off pump coronary artery bypass grafting . METHODS Seventy patients between 50 and 80 years with stable angina pectoris , ejection fraction > 30 % , serum creatinine < 150 micromol/l , and lack of tight main stem stenosis were r and omized to on or off pump coronary artery bypass grafting . St and ardized neuropsychological tests evaluated attention , verbal and visuo-spatial short-term and working memory , verbal learning , delayed recall , visuo-motor speed , and aspects of executive functions . Levels of anxiety and depression were also investigated . Testing was performed before and at 1 week , 1 and 6 months after surgery . RESULTS There was no difference in cognitive impairment ( defined as a 20 % reduction in at least 20 % of the tests ) between groups . The incidence at 1 week post-operatively was 57 % in the on pump group and 58 % in the off pump group , after 1 month 30 % and 12 % and after 6 months 19 % and 15 % , respectively ( p for interaction=0.19 ) . There was no difference between groups in anxiety ( p=0.18 ) or depression ( p=0.48 ) . CONCLUSIONS This prospect i ve , r and omized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients BACKGROUND Neurologic and clinical morbidity after coronary artery bypass grafting ( CABG ) can be significant . By avoiding cardiopulmonary bypass , off-pump CABG ( OPCAB ) may reduce morbidity . METHODS Sixty patients ( 30 CABG and 30 OPCAB ) were prospect ively r and omized . Neurocognitive testing was performed before the operation and 2 weeks and 1 year after the operation . Neurologic testing to detect stroke and (99m)Tc-HMPAO whole-brain single photon emission computed tomography scanning to assess cerebral perfusion were performed before the operation and 3 days afterward . Bilateral middle cerebral artery transcranial Doppler scanning was performed intraoperatively to detect cerebral microemboli . All examiners were blinded to treatment group . Clinical morbidity and costs were compared . RESULTS Coronary artery bypass grafting was associated with more cerebral microemboli ( 575 + /- 278.5 CABG versus 16.0 + /- 19.5 OPCAB ( median + /- semiinterquartile range ) and significantly reduced cerebral perfusion after the operation to the bilateral occipital , cerebellar , precunei , thalami , and left temporal lobes ( p < or = 0.01 ) . Cerebral perfusion with OPCAB was unchanged . Compared with base line , OPCAB patients performed better on the Rey Auditory Verbal Learning Test ( total and recognition scores ) at both 2 weeks and at 1 year ( p < or = 0.05 ) , whereas CABG performance was statistically unchanged for all cognitive measures . Patients who underwent CABG had more chest tube drainage ( 1389 + /- 1256 mL CABG versus 789 + /- 586 mL OPCAB , p = 0.02 ) and required more blood ( 3.9 + /- 5.8 U CABG versus 1.2 + /- 2.2 U OPCAB , p = 0.02 ) , fresh frozen plasma ( 3.0 + /- 6.0 U CABG versus 0.5 + /- 2.2 U OPCAB , p = 0.03 ) , and hours of postoperative use of dopamine ( 16.3 + /- 21.2 hours CABG versus 7.3 + /- 9.7 hours OPCAB , p = 0.04 ) . These differences culminated in higher costs for CABG ( $ 23,053 + /- $ 5,320 CABG versus $ 17,780 + /- $ 4,390 OPCAB , p < 0.0001 ) . One stroke occurred with CABG , compared with none with OPCAB ( p = NS ) . One OPCAB patient died because of a pulmonary embolus ( p = NS ) . CONCLUSIONS Compared with CABG , OPCAB may reduce neurologic and clinical morbidity as well as cost INTRODUCTION The aim of this study was to determine if coronary artery bypass graft ( CABG ) surgery performed utilizing the Octopus II stabilizing system provides myocardial and cerebral protection comparable to traditional CABG surgery utilizing cardiopulmonary bypass ( CPB ) . METHODS Elective patients requiring surgery for double or triple vessel disease were r and omized to receive either conventional CABG with CPB ( n = 14 ) or OPCAB using the Octopus II stabilizing system ( n = 12 ) , after receiving institutional approval and written consent . Exclusion criteria included previous cardiac surgery , recent myocardial infa rct ion , and previous cerebrovascular disease . Troponin T ( TnT ) was measured preoperatively and at 2 , 4 , 6 , 8 , 10 , 12 , 24 , and 72 hours after initiation of grafting . Neuropsychological assessment s ( 10 measures ) were performed in the week prior to surgery , one week , and six months after surgery . RESULTS Troponin T release was reduced in the OPCAB patients at all time points ( repeated measures ANOVA p = 0.043 ) , reaching significance at 8 , 10 and 12 hours ( p = 0.033 , 0.038 , 0.019 ) . Other factors ( composite clinical end point ( prolonged LOS or ICU stay or 30-day mortality ) , infa rct ion , and intubation time ) did not show any significant differences between the two groups . The incidence of neuropsychological deficits was not different between the two groups at both seven-day and six-month follow-up assessment s. CONCLUSIONS Decreased TnT release suggests a myocardial benefit for the OPCAB procedure . A neuropsychological benefit remains to be demonstrated Objective : To describe the association between cognitive outcome in the first postoperative week and that at three months after both off-pump and on-pump coronary bypass surgery , and to make a direct comparison of early cognitive outcome after off-pump versus on-pump surgery . Design : R and omised trial with an additional prediction study within the two r and omised groups . Setting : Three centres for heart surgery in the Netherl and s. Patients : 281 patients , mean age 61 years . Interventions : Participants were r and omly assigned to off-pump or on-pump coronary bypass surgery . Main outcome measures : Cognitive outcome , assessed by psychologists who administered neuropsychological tests one day before and four days and three months after surgery . A logistic regression model was used to study the predictive association between early cognitive outcome , together with eight clinical variables , and cognitive outcome after three months . Results : Cognitive outcome in the first week after surgery was determined for 219 patients and was a predictor of cognitive decline after three months . This association was stronger in on-pump patients ( odds ratio ( OR ) 5.24 , p < 0.01 ) than in off-pump patients ( OR 1.80 , p = 0.23 ) . Early decline was present in 54 patients ( 49 % ) after off-pump surgery and 61 patients ( 57 % ) after on-pump surgery ( OR 0.73 , p = 0.25 ) . Conclusions : In patients undergoing first time coronary bypass surgery , early cognitive decline predicts cognitive outcome after three months . Early cognitive decline is not significantly influenced by the use of cardiopulmonary bypass Background — It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting ( OPCAB ) than with conventional coronary artery bypass grafting ( CCAB ) . However , evidence for this statement is preliminary , and additional insight is needed . Methods and Results — The study was a sub study of the r and omized Best Bypass Surgery trial that compared OPCAB with CCAB treatment with respect to intraoperative and postoperative mortality and morbidity in patients with a moderate to high level of predicted preoperative risk . The outcome was cognitive function . A total of 120 elderly patients ( mean age 76 years , SD 4.5 years ) underwent psychometric testing before surgery and at a mean of 103 ( SD 15 ) days postoperatively with a neuropsychological test battery that included 7 parameters from 4 tests . Cognitive dysfunction was defined as the occurrence of at least 2 of the 7 possible deficits . Secondary analysis was performed on the basis of the definition of a 20 % decline in cognitive scores compared with baseline , and with z score analysis . Cognitive dysfunction was identified in 4 of the 54 patients ( 7.4 % , 95 % confidence interval [ CI ] 2.1 % to 17.9 % ) in the OPCAB group and 5 of the 51 patients ( 9.8 % , 95 % CI 3.3 % to 21.4 % ) in the CCAB group . We found no difference in incidence of cognitive dysfunction between the groups regardless of the definition applied . Conclusions — In elderly high-risk patients , no significant difference was found in the incidence of cognitive dysfunction 3 months after either OPCAB or CCAB CONTEXT Conventional coronary artery bypass graft surgery with use of cardiopulmonary bypass ( on-pump CABG ) is associated with excellent long-term cardiac outcomes but also with a high incidence of cognitive decline . The effect of avoiding cardiopulmonary bypass ( off-pump CABG ) on long-term cognitive and cardiac outcomes is unknown . OBJECTIVE To compare the effect of off-pump CABG and on-pump CABG surgery on long-term cognitive and cardiac outcomes . DESIGN , SETTING , AND PARTICIPANTS The Octopus Study , a multicenter r and omized controlled trial conducted in the Netherl and s , which enrolled 281 low-risk CABG patients between 1998 and 2000 . Five years after their surgery , surviving patients were invited for a follow-up assessment . INTERVENTION Patients were r and omly assigned to receive either off-pump ( n = 142 ) or on-pump ( n = 139 ) CABG surgery . MAIN OUTCOME MEASURE The primary measure was cognitive status 5 years after surgery , which was determined by a psychologist blinded to treatment allocation who administered 10 st and ardized vali date d neuropsychological tests . Secondary measures were occurrence of cardiovascular events ( all-cause mortality , stroke , myocardial infa rct ion , and coronary reintervention ) , anginal status , and quality of life . RESULTS After 5 years , 130 patients were alive in each group . Cognitive outcomes could be determined in 123 and 117 patients in the off-pump and on-pump groups , respectively . When using a st and ard definition of cognitive decline ( 20 % decline in performance in 20 % of the neuropsychological test variables ) , 62 ( 50.4 % ) of 123 in the off-pump group and 59 ( 50.4 % ) of 117 in the on-pump group had cognitive decline ( absolute difference , 0 % ; 95 % confidence interval [ CI ] , -12.7 % to 12.6 % ; P>.99 ) . When a more conservative definition of cognitive decline was used , 41 ( 33.3 % ) in the off-pump group and 41 ( 35.0 % ) in the on-pump group had cognitive decline ( absolute difference , -1.7 % ; 95 % CI , -13.7 % to 10.3 % ; P = .79 ) . Thirty off-pump patients ( 21.1 % ) and 25 on-pump patients ( 18.0 % ) experienced a cardiovascular event ( absolute difference , 3.1 % ; 95 % CI , -6.1 % to 12.4 % ; P = .55 ) . No differences were observed in anginal status or quality of life . CONCLUSION In low-risk patients undergoing CABG surgery , avoiding the use of cardiopulmonary bypass had no effect on 5-year cognitive or cardiac outcomes . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N69438133 Abstract Objective To compare the clinical , angiographic , neurocognitive , and quality of life outcomes of off-pump coronary artery bypass surgery with conventional coronary artery bypass grafting surgery using cardiopulmonary bypass . Design R and omised controlled clinical trial . Setting Tertiary cardiothoracic centre in Middlesex , Engl and . Participants 168 patients ( 27 women ) requiring primary isolated coronary artery bypass grafting surgery . Interventions Patients were r and omised to conventional coronary artery bypass grafting surgery using cardiopulmonary bypass ( n = 84 ) or off-pump coronary artery bypass surgery ( n = 84 ) , carried out by one surgeon . Angiographic examination was carried out at three months postoperatively . Neurocognitive tests were carried out at baseline and at six weeks and six months postoperatively . Main outcome measures Clinical outcome , graft patency at three months , neurocognitive function at six weeks and six months , and health related quality of life . Results Graft patency was evaluated by angiography in 151 ( 89.9 % ) patients and was similar between the cardiopulmonary bypass and off-pump groups ( risk difference − 1 % , 95 % confidence interval − 5 % to 4 % ) , with the off-pump group considered the treatment group . Patients in the off-pump group required fewer blood transfusions ( 1.7 units v 1.0 unit , P = 0.02 ) , shorter duration of mechanical ventilation ( 7.7 hours v 3.9 hours , P = 0.03 ) , and shorter hospital stay ( 10.8 days v 8.9 days ) . Scores for neurocognitive function showed a significant difference in three memory subtests at six weeks and two memory subtests at six months in favour of the off-pump group . Conclusions Patients who underwent off-pump coronary artery bypass surgery showed similar patency of grafts , better clinical outcome , shorter hospital stay , and better neurocognitive function than patients who underwent conventional coronary artery bypass grafting surgery using cardiopulmonary bypass BACKGROUND Preliminary reports have documented the safety of off-pump coronary artery bypass graft compared with conventional coronary artery bypass graft surgery . Whereas off-pump coronary artery bypass graft surgery may be associated with improvement in some short-term outcomes , longer-term outcomes and influence on neurocognitive function have not been fully assessed . We examined short-term and intermediate-term neurocognitive and index admission morbidity and mortality after coronary artery bypass surgery performed with and without the use of extracorporeal circulation . METHODS We prospect ively r and omly assigned 201 patients undergoing nonemergent isolated coronary artery bypass graft surgery to conventional coronary artery bypass graft surgery ( n = 102 ) or off-pump coronary artery bypass graft surgery ( n = 99 ) . The primary end points of the study were neurocognitive function assessed using a 19-test neurocognitive battery at baseline , discharge , and 6 months . Neurocognitive deficit was defined as a 20 % or greater reduction from baseline in at least 20 % of the tests . Secondary end points included index admission mortality , stroke , low-output cardiac failure , return to the operating room for bleeding , and postoperative troponin release . Risk ratios and 95 % confidence intervals were calculated based on intention-to-treat analysis . RESULTS There was no difference in neurocognitive deficit at discharge ( discharge versus preoperative : risk ratio , 0.83 ; 95 % confidence interval , 0.65 to 1.07 ) or at 6 months ( 6 months versus preoperative : risk ratio , 0.94 ; 95 % confidence interval , 0.70 to 1.28 ) . There was no significant difference in mortality or morbidity between the two groups . The off-pump coronary artery bypass graft group had fewer patients with troponin release than the conventional coronary artery bypass graft group . CONCLUSIONS Off-pump coronary artery bypass graft surgery did not result in decreased frequency of neurocognitive deficit . Off-pump coronary artery bypass graft surgery was associated with substantially lower levels of troponin release after surgery BACKGROUND Neurocognitive impairment can be a debilitating complication after coronary artery bypass graft surgery ( CABG ) . Cardiopulmonary bypass , in particular , cerebral emboli , has been implicated . We compared neurocognitive function and cerebral emboli in patients undergoing on-pump and off-pump CABG . METHODS 212 patients admitted for CABG were r and omly assigned to on-pump ( n = 104 ) or off-pump ( n = 108 ) surgery . Embolic signals were detected with bilateral transcranial Doppler ultrasonography of the middle cerebral artery . Neurocognitive tests were administered preoperatively , on discharge from hospital , at 6 weeks , and at 6 months after surgery . Composite neurocognitive scores were derived using principal component analysis and were compared between the two groups , using analysis of covariance to adjust for baseline values . RESULTS At discharge from hospital , the adjusted composite neurocognitive score was 0.25 st and ard deviations greater in the off-pump group compared with the on-pump group ( 95 % confidence interval : 0.05 to 0.45 ; p = 0.01 ) . There was no significant difference at 6 weeks ( 0.09 st and ard deviations , 95 % confidence interval : -0.11 to + 0.30 ; p = 0.4 ) and 6 months ( -0.002 st and ard deviations , 95 % confidence interval : -0.23 to + 0.23 ; p = 1.0 ) . Median number of embolic signals was 1,605 ( 751 to 2,473 ) during on-pump and 9 ( 4 to 27 ) in off-pump CABG ( p < 0.001 ) . Age , length of education , and on-pump status were independent predictors of the predischarge neurocognitive score ( p = 0.02 , 0.03 , and 0.006 , respectively ) . CONCLUSIONS Cerebral emboli are more prevalent during on-pump CABG . At discharge from hospital , neurocognitive function is better after off-pump surgery , possibly as a result of the lower embolic load . However , the difference in neurocognitive function does not persist at 6 weeks and 6 months BACKGROUND Uncertainty remains regarding the benefits and risks of the technique of operating on a beating heart ( off pump ) for coronary artery bypass grafting ( CABG ) surgery versus on-pump CABG . Prior trials had few events and relatively short follow-up . There is a need for a large r and omized , controlled trial with long-term follow-up to inform both the short- and long-term impact of the 2 approaches to CABG . METHODS We plan to r and omize 4,700 patients in whom CABG is planned to undergo the procedure on pump or off pump . The co primary outcomes are a composite of total mortality , myocardial infa rct ion ( MI ) , stroke , and renal failure at 30 days and a composite of total mortality , MI , stroke , renal failure , and repeat revascularization at 5 years . We will also undertake a cost-effectiveness analysis at 30 days and 5 years after CABG surgery . Other outcomes include neurocognitive dysfunction , recurrence of angina , cardiovascular mortality , blood transfusions , and quality of life . RESULTS As of May 3 , 2011 , CORONARY has recruited > 3,884 patients from 79 centers in 19 countries . Currently , patient 's mean age is 67.6 years , 80.7 % are men , 47.0 % have a history of diabetes , 51.4 % have a history of smoking , and 34.4 % had a previous MI . In addition , 20.9 % of patients have a left main disease , and 96.6 % have double or triple vessel disease . CONCLUSIONS CORONARY is the largest trial yet conducted comparing off-pump CABG to on-pump CABG . Its results will lead to a better underst and ing of the safety and efficacy of off-pump CABG Coronary artery bypass graft ( CABG ) surgery with cardiopulmonary bypass ( CPB ) can produce a higher incidence of neuropsychological complications than other types of highly invasive noncardiac vascular surgery . Cognitive complications most likely arise from either embolization or hypoxia . An alternative surgical procedure has been developed that allows CABG to be performed without stopping the heart ( " off-pump " CABG , or OPCABG ) . This study examined the neuropsychological performance of patients undergoing OPCABG , hypothesizing that patients undergoing OPCABG would show fewer cognitive deficits than patients whose hearts were stopped . A 1-hr neuropsychological battery was administered preoperatively to 43 patients before prospect i ve r and omization to either CPB CABG or OPCABG , and again to 34 of those patients 2 to 3 months postoperatively by an examiner blind to surgical condition . Neuropsychological status did not change 2.5 months postsurgically in either OPCABG or CABG groups . However , both groups showed dramatic presurgical cognitive deficits in multiple domains , particularly verbal memory and psychomotor speed . This corroborates previous research suggesting that patients requiring CABG surgery may evidence significant presurgical cognitive deficits as a result of existing vascular disease BACKGROUND Coronary artery bypass grafting ( CABG ) is associated with significant cerebral morbidity . This is usually manifested as cognitive decline and may be caused by cardiopulmonary bypass . The primary objective of this study was to explore whether patients report more cognitive failures 1 year after CABG than preoperatively . Secondary objectives were to evaluate whether there is a difference in reported cognitive failures between patients undergoing on-pump and off-pump CABG and whether a difference between CABG patients and healthy control subjects exists . Finally the relation between objective and subjective cognitive functioning was quantified . METHODS In this prospect i ve study , the Cognitive Failures Question naire ( CFQ ) was assigned preoperatively and 1 year postoperatively to 81 patients who were r and omly assigned to undergo off-pump ( n = 45 ) or on-pump ( n = 36 ) CABG . A control sample of 112 age-matched healthy subjects was included who were administered the CFQ once . RESULTS No difference was found in the total CFQ score ( p = 0.222 ) and CFQ worry score ( p = 0.207 ) between 1 year after CABG and before CABG . There was no difference between on-pump and off-pump CABG ( total score , p = 0.458 ; worry score , p = 0.563 ) . A significant difference was found in CFQ total score between CABG patients and control subjects ( p < 0.001 ) , with control subjects reporting more cognitive failures than CABG patients . Finally , patients who showed cognitive decline in the Octopus trial did not have a higher CFQ total score ( p = 0.671 ) and CFQ worry score ( p = 0.772 ) than patients without cognitive decline 1 year after CABG . CONCLUSIONS The present findings suggest that CABG does not result in a substantial proportion of patients with subjectively experienced cognitive decline 1 year after the procedure , irrespective of the type of surgical technique ( on-pump versus off-pump ) OBJECTIVES The objective of this study was to compare neuropsychologic and quality -of-life outcomes of patients undergoing off-pump coronary artery bypass surgery to those undergoing coronary artery bypass graft surgery using conventional cardiopulmonary bypass . DESIGN A prospect i ve r and omized trial of coronary artery bypass graft surgery with and without the use of cardiopulmonary bypass . SETTING A cardiothoracic surgery unit at a tertiary hospital . PARTICIPANTS Sixty-six patients undergoing coronary artery bypass graft surgery and a control group of 50 participants not undergoing cardiac surgery . INTERVENTIONS Patients were r and omized to receive coronary artery bypass graft surgery with cardiopulmonary bypass or r and omized to coronary artery bypass graft surgery without the use of cardiopulmonary bypass . MEASUREMENTS AND MAIN RESULTS The proportions of neuropsychologic deficits and improvement in quality -of-life were comparable regardless of whether patients were r and omized to receive off-pump coronary artery bypass graft surgery or conventional coronary artery graft surgery with cardiopulmonary bypass . CONCLUSIONS Patients receiving coronary artery bypass grafts without cardiopulmonary bypass did not show fewer cognitive deficits or greater improvement in quality of life BACKGROUND Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion . This study investigates high intensive transient signals ( HITS ) in transcranial Doppler ultrasound ( TCD ) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass ( off-pump CABG ) in comparison with the conventional procedure using cardiopulmonary bypass ( CPB ) . The results are related to the neuropsychologic outcome in both surgical groups . METHODS Forty patients were r and omized in 2 groups ( 20 conventional and 20 off-pump CABG ) . Neurocognitive status was assessed preoperatively and postoperatively . Venous serum levels of S-100 protein were measured before and after coronary operation , HITS were measured in the middle cerebral artery during the operation . RESULTS The median value of HITS was 394.5 ( 0 to 2217 ) in the conventional versus 11 ( 0 to 50 ) in the off-pump group , p less than 0.0001 . Postoperative S-100 serum levels were : 3.76 ( 0.13 to 11.2 ) microg/L ( conventional ) versus 0.13 ( 0.04 to 1.01 ) microg/L ( off-pump ) , p less than 0.0001 . Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90 % of the patients in the conventional group versus no impairment in the off-pump group . CONCLUSIONS Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli . The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation BACKGROUND Risk assessment is integral to patient selection and counseling before coronary artery revascularization . We studied the predictive ability of cerebral magnetic resonance imaging of preoperative and postoperative cerebral ischemic injury on self-reported physical and mental health at 3 months after coronary artery bypass surgery with or without use of cardiopulmonary bypass . METHODS In a prospect i ve clinical trial comparing on-pump and off-pump surgery , 120 patients responded to a question naire for self-report of angina ( Canadian Cardiovascular Society scale ) and physical and mental health status ( Short Form 36 ) at baseline before preoperative cerebral magnetic resonance imaging . Preoperative sets of both magnetic resonance imaging and self- assessment s were available for 103 ( 85.8 % ) patients . These patients were grouped according to classification of preoperative cerebral magnetic resonance imaging findings . Analysis of covariance determined the association of ( 1 ) preoperative magnetic resonance imaging status , ( 2 ) new postoperative cerebral lesions , and ( 3 ) actual use of cardiopulmonary bypass to physical and mental health . RESULTS At 3 months after surgical intervention , 98 of 103 patients completed follow-up . The analysis revealed an interaction effect of preoperative cerebral ischemic injury and use of cardiopulmonary bypass on physical health ( F = 9.07 , P = .003 ) independent of age . No independent effects on health status were found of baseline magnetic resonance imaging or new cerebral lesions at 3 months . CONCLUSIONS This study strongly suggests that the combination of preoperative cerebral ischemic injury and use of cardiopulmonary bypass can predict postoperative health status at 3 months . Cerebral magnetic resonance imaging might be a more specific indicator than age for preoperative assessment of vulnerability or resilience during rehabilitation after on-pump cardiac surgery Abstract Objective : To assess neurocognitive impairment after the off-pump and on-pump techniques for coronary artery bypass graft surgery in patients with triple vessel disease . Design : R and omised controlled trial . Setting : University Hospital of Wales , Cardiff . Participants : 60 patients undergoing coronary artery bypass graft surgery for triple vessel disease prospect ively r and omised to the off-pump or on-pump technique . Main outcome measures : Change in scores in nine st and ard neuropsychometric tests administered preoperatively and at 1 and 10 weeks postoperatively . Results : The on-pump group showed a significantly greater deterioration in scores for two and three tests at 1 week and 10 weeks postoperatively , respectively , than the off-pump group . The on-pump group also showed a significantly higher incidence of major deterioration in one of the tests both 1 week and 10 weeks postoperatively . The incidence of neurocognitive impairment at 1 week postoperatively was 27 % ( 8 out of 30 ) in the off-pump group and 63 % ( 19 out of 30 ) in the on-pump group ( P=0.004 ) ; and at 10 weeks postoperatively was 10 % ( 3 out of 30 ) in the off-pump group and 40 % ( 12 out of 30 ) in the on-pump group ( P=0.017 ) . Conclusion : Off-pump coronary artery bypass graft surgery results in less neurocognitive impairment than the on-pump technique BACKGROUND The R and omized On versus Off Bypass trial found no difference for a global cognitive outcome measure for patients receiving on-pump versus off-pump coronary artery bypass graft surgery ( CABG ) . In this report , we present the baseline patient characteristics that were predictive of post-CABG cognitive decline as well as compare cognitive outcomes between treatment arms . METHODS A neuropsychological battery was administered preoperatively and at 1 year after undergoing CABG . Stepwise regression was used to identify demographic or clinical risk factors associated with cognitive decline . Neuropsychological data were converted to demographically corrected T scores to provide impairment levels . RESULTS Overall 1,156 patients ( 581 on-pump , 575 off-pump ) completed match-paired neuropsychological assessment s at baseline and 1-year follow-up . Baseline cognitive score , age , education level , and ethnicity predicted cognitive decline after CABG . Only 20 % of either group had mild impairment at baseline on three of the test scores , and less than 10 % had severe impairment on individual tests at either time . Few subjects in either group transitioned to clinical ly impaired levels at follow-up on individual tests . CONCLUSIONS At baseline , lower cognitive function , older age , lower education , and ethnicity other than white were predictive of cognitive decline after CABG . Patients in both groups demonstrated low frequencies of cognitive impairment on individual tests at baseline and follow- up , and few patients in either group were classified as impaired at 1-year follow-up on individual tests . In general , the R and omized On versus Off Bypass study documented that neither on-pump nor off-pump CABG adversely impacts long-term brain function BACKGROUND Cognitive difficulties have been reported after coronary artery bypass graft surgery using cardiopulmonary bypass . However , the cognitive benefit of off-pump surgery remains unclear . METHODS Consecutively listed c and i date s for elective bypass were r and omly assigned to either off-pump or on-pump techniques ( n = 107 ) . A battery of 11 st and ardized neuropsychological tests was administered before surgery , and again at 2 and 6 months after surgery . The two groups were compared using a range of statistical procedures , including growth modeling . RESULTS There were no significant differences in cognitive test scores between the off-pump and on-pump groups using t tests at any of the time points . There were no differences between off-pump and on-pump groups in the incidence of cognitive deficits at 2 months or 6 months , with the exception that fewer off-pump patients showed impairment on one test of verbal fluency at 6 months . When the pattern of cognitive change over time between the two groups was compared using sophisticated modeling techniques , the two groups were again comparable , except for results on the test of verbal fluency , in which the off-pump group showed more rapid postsurgical cognitive gains than the on-pump group . CONCLUSIONS The off-pump group appears to be generally comparable to the on-pump group in terms of short-term and long-term postsurgical neurocognitive outcomes Background —Previous r and omized comparisons of off-pump and on-pump coronary artery bypass grafting ( CABG ) have yielded controversial results about the cardiac and neurological events and graft patency . In addition , these r and omized studies were composed of CABG with a few arterial grafts . We performed a prospect i ve r and omized controlled study to compare off-pump and on-pump CABG with multiple arterial grafts . Methods and Results —Between July , 2002 , and September , 2004 , 167 consecutive unselected patients referred for elective primary CABG were r and omly assigned to undergo multiple arterial off-pump CABG ( n=81 ) or on-pump CABG ( n=86 ) . The clinical outcomes and S-100 protein , neuron-specific enolase , and maximum creatine kinase-MB levels were compared . Early graft patency was examined within 3 weeks after the operation by angiography . The number of grafts performed per patient ( 3.5±1.0 for off-pump CABG and 3.6±0.9 for on-pump CABG ) and the number of arterial grafts performed per patient ( 3.3±1.0 for off-pump CABG and 3.4±0.9 for on-pump CABG ) were similar . Completeness of revascularization ( completed grafts/planned grafts ) was 98 % in both procedures . There were no hospital deaths in either group . The operation time was significantly ( P<0.001 ) shorter in the off-pump group than in the on-pump group ( 267±60 minutes versus 307±59 minutes ) . The incidence of perioperative complications was similar . The frequency of no need for transfusion was higher in the off-pump group than in the on-pump group ( 80 % versus 55 % , P<0.001 ) . The S-100 protein levels at the admission into the intensive care unit were significantly ( P<0.001 ) lower in the off-pump group than in the on-pump group ( 0.20±0.11 ng/mL versus 0.34±0.22 ng/mL ) . The neuron-specific enolase levels at the intensive care unit admission were significantly ( P<0.001 ) lower in the off-pump group than in the on-pump group ( 10.4±9.0 ng/mL versus 16.9±6.9 ng/mL ) . Maximum creatine kinase-MB levels were significantly ( P=0.046 ) lower in the off-pump group than in the on-pump group ( 17.1±16.7 IU/L versus 21.5±10.6 IU/L ) . The overall early graft patency rate with or without stenosis was the same ( 98 % ) in both groups , but the rate without stenosis was slightly worse in the off-pump group ( 93 % ) than in the on-pump group ( 96 % ) ( P=0.093 ) . The stenosis-free patency rate in the right coronary area was significantly ( P=0.028 ) worse in the off-pump CABG group ( 90 % ) than in the on-pump group ( 99 % ) . Conclusions —Off-pump CABG with multiple arterial grafts was as safe as the conventional on-pump CABG , with similar completeness of revascularization and early graft patency OBJECTIVES Our purpose was to establish whether coronary revascularization on the beating heart without cardiopulmonary bypass is less harmful to the brain than conventional surgery with cardiopulmonary bypass as indicated by measures of cognitive function or by changes in serum concentrations of S-100 protein , a recognized biochemical marker of cerebral injury . METHODS We conducted a prospect i ve r and omized trial in which the assessors of the outcome measures were blind to the treatment received . Sixty patients without known neurologic abnormality , undergoing coronary revascularization , were prospect ively r and omized to 1 of 2 groups : ( 1 ) cardiopulmonary bypass ( 32 degrees C-34 degrees C ) and cardioplegic arrest ( on pump ) with intermittent ante grade warm blood cardioplegia or ( 2 ) surgery on the beating heart ( off pump ) . Neuropsychologic performance was assessed before and 12 weeks after the operation . Serum S-100 protein concentration was measured at intervals up to 24 hours after the operation . RESULTS The groups had similar preoperative characteristics . There were no deaths or major neurologic complications in either group , nor was there any difference between groups in the chosen index of neurologic deterioration . Serum S-100 protein concentrations were higher in the on-pump group at 30 minutes , but any such difference between groups had disappeared 4 hours later . The extent of the changes in S-100 protein was unrelated to the index of neuropsychologic deterioration . CONCLUSIONS The changes in S-100 protein concentration suggest that the brain and /or blood-brain barrier may be more adversely affected during coronary artery surgery with cardiopulmonary bypass than during surgery on the beating heart , but that this may not be reflected in detectable neuropsychologic deterioration at 12 weeks BACKGROUND Coronary bypass surgery often leads to short-term cognitive dysfunction , whereas coronary angioplasty does not . Perioperative cognitive dysfunction usually resolves , although a subgroup of surgical patients may continue to exhibit long-term cognitive dysfunction . The purpose of this study was to compare cognitive function 5 years after r and omization to a strategy of either initial coronary surgery or initial angioplasty . METHODS AND RESULTS Five centers in the Bypass Angioplasty Revascularization Investigation participated in this ancillary study . Patients with multivessel coronary disease r and omized to angioplasty or surgery were eligible at the time of their 5-year clinic visit . A battery of five measures previously shown to be sensitive to perioperative changes in cognitive function was administered , including the Logical and Figural Memory Scales from the Wechsler Memory Scale , the Digit Symbol and Digit Span subtests from the Wechsler Adult Intelligence Scale , and Part B of the Reitan Trail Making Test . The 125 study patients were generally similar to the 133 patients who were eligible but did not participate , although study participants were significantly younger ( P=.003 ) . The 64 patients r and omly assigned to angioplasty had baseline characteristics similar to those of 61 patients r and omly assigned to surgery . Cognitive function scores were not significantly different between angioplasty or surgery patients in an intention-to-treat analysis ( P=.57 ) . There also was no difference in cognitive function scores when the data were analyzed according to whether the patient had ever undergone bypass surgery ( P=.59 ) . CONCLUSIONS Long-term cognitive function is similar after coronary bypass surgery and coronary angioplasty in the majority of patients OBJECTIVE Coronary artery bypass grafting ( CABG ) with cardiopulmonary bypass is still the gold st and ard for surgical myocardial revascularization . Despite advances in techniques and technologies , documented evidence indicates that cardiopulmonary bypass remains the major source of intraoperative brain injury . This study was set up to test whether offpump coronary artery bypass ( OPCAB ) is superior to CABG regarding postoperative neurologic outcome or neurocognitive function . METHODS Between January 1999 and June 2001 , 251 patients scheduled for coronary revascularization were divided into 2 groups , CABG ( control ) and OPCAB . All patients underwent an extensive neurologic and neurocognitive battery of tests preoperatively and postoperatively at 48 hours , 7 days , and 3 months following surgery . RESULTS There were no statistically significant differences between the 2 groups regarding the preoperative or intraoperative data . The means for patient age , number of grafts , and number of central anastomoses were , respectively , 65.4 years ( CABG ) and 64.6 years ( OPCAB ) , 3.0 ( CABG ) and 2.2 ( OPCAB ) , and 2.0 ( CABG ) and 1.2 ( OPCAB ) . The occurrence of stroke was 2.3 % ( CABG ) and 0 % ( OPCAB ) . CONCLUSION Neurologic complications and postoperative neurocognitive dysfunction remain major concerns in coronary artery surgery . Besides the occurrence of stroke , which dramatically reduces the success of the heart operation , the importance of neurocognitive disorders for postoperative quality of life is not yet well defined . OPCAB significantly improves postoperative neurocognitive function , which may in turn improve the postoperative quality of life BACKGROUND Cardiac operations using extracorporeal circulation bear a risk of cerebral complications . The aim of our study was to investigate if off-pump operations without heart-lung machines can reduce cerebral injury . METHODS S100 , a protein specific for cerebral tissue , was used as a marker for cerebral impairment in 108 r and omized patients undergoing coronary bypass operation : 67 patients ( group A ) were operated on with extracorporeal circulation and cardioplegic cardiac arrest , and 41 patients ( group B ) underwent off-pump beating heart revascularization . Both groups were similar regarding age , sex , ejection fraction , and number of anastomoses . S100 levels were measured from induction of anesthesia until 24 hours after the operation . RESULTS Data collection was 100 % complete . There was no in-hospital death . Nonfatal myocardial infa rct ions occurred in 2 patients in group A , and 1 patient in group B required resternotomy for bleeding . There was no neurologic deficit in either group . S100 levels increased only slightly in the off-pump patients ( group B ) , whereas in group A there was a sharp rise in S100 concentration during extracorporeal circulation , only returning to baseline 6 hours after the end of the operation . Peak S100 levels were four times higher in group A than in group B ( 2.1 microg/L versus 0.5 microg/L ; p < 001 ) . CONCLUSIONS The results of our study suggest that perioperative cerebral impairment is reduced in cardiac operations without the use of extracorporeal circulation . Further large-scale studies are needed to show whether this result is reflected by fewer neurologic deficits Previous research indicates that practice effects are large with repeated versions of memory tests . In contrast , administrations of the same tests using alternate forms typically yield much smaller practice effects . However , most studies do not compare alternate- and same-form conditions directly , and differ widely in terms of test-retest interval , modality of stimuli ( verbal , spatial ) , format of the memory test , and number of examinations . The present study investigated practice effects during repeated administrations of verbal and nonverbal memory tests which have the same administration format . Two groups of healthy participants , matched for age , education , estimated IQ , and baseline memory test performance , were assigned to either a same- or alternate-forms condition . Participants taking the same form every two weeks improved significantly over four sessions . Participants completing alternate forms of the nonverbal memory test produced a small practice gain , but the verbal memory test was resistant to practice effects when alternate forms were used BACKGROUND Off-pump coronary artery bypass grafting surgery reduces the intraoperative cerebral embolic load and may therefore cause less brain injury . The main aim of this study was to compare off-pump and on-pump surgery with regard to the frequency of new postoperative cerebral ischemic lesions and the prevalence of postoperative cognitive impairment . We also assessed whether preoperative cerebral ischemic injury predicts the risk for cognitive dysfunction after surgery . METHODS One hundred twenty patients with ischemic coronary artery disease were prospect ively r and omized to undergo off-pump or on-pump surgery . A detailed neuropsychological assessment and a cerebral magnetic resonance imaging examination were performed on the day before and at 3 months postoperatively . The neuropsychological assessment was repeated at 12 months . RESULTS There was no significant ( p = 0.17 ) difference between off-pump ( 8.2 % ) and on-pump ( 17.3 % ) surgery with regard to new postoperative cerebral lesions . The prevalence of cognitive impairment after surgery was also similar in the two groups ( 3 months : off-pump 20.4 % , on-pump 23.1 % , p = 0.74 ; 12 months : off-pump 24.1 % , on-pump 23.1 % , p = 0.90 ) . The degree of preoperative cerebral ischemic injury was significantly associated with cognitive dysfunction after on-pump ( p = 0.02 ) but not after off-pump ( p = 0.22 ) surgery . None of the patients with normal preoperative radiologic findings were found to have cognitive impairment at 3 months postoperatively ( p = 0.04 ) . CONCLUSIONS Long-term cognitive function and magnetic resonance imaging evidence of brain injury were similar after off-pump and on-pump coronary artery bypass grafting surgery . Preoperative cerebral magnetic resonance imaging can be used to predict the risk for cognitive dysfunction after coronary artery bypass grafting surgery |
2,640 | 19,188,317 | CT colonography with CAD for inexperienced readers was more clinical ly effective and cost-effective than FS .
The addition of CAD to CT colonography screening improves the CRC prevention rate , result ing in advantageous cost-effectiveness for screening . | PURPOSE To analyze the cost-effectiveness of adding computer-aided detection ( CAD ) to a computed tomographic ( CT ) colonography screening program and to compare it with other options of colorectal cancer ( CRC ) prevention . | The disease natural history of colorectal neoplasm regarding two opposing theories , adenoma – carcinoma sequence and de novo carcinoma theory , is controversial and rarely quantified . The aims of this study are therefore to estimate the dwelling times of adenoma – carcinoma sequence by adenoma size and histological type , taking de novo carcinoma into account . The efficacy of polypectomy was therefore estimated making allowance for two pathways . A case – cohort design , underpinning a cohort with 13 908 subjects ( including 10 496 normal subjects , 2652 polyps , 760 colorectal cancers ) who underwent the first examination of colonoscopy between 1979 and 1998 , was devised to estimate parameters associated with two opposing theories by r and omly selecting 305 normal subjects , 300 patients with polyps , and 116 colorectal cancers from the cohort . All the 2652 polyps were linked to national cancer registry to ascertain 25 invasive carcinomas after polypectomy . For the five-state model associated with adenoma size , dwelling times of small ( 0.6–1 cm ) and large adenoma ( > 1 cm ) are 7.75 and 5.27 years for the model without considering de novo , and 17.48 and 15.90 years for the model taking de novo carcinoma into account . Similar findings are observed for the model associated with histological type . The estimated proportions of de novo carcinoma are 31.87 % from the model by adenoma size and 27.81 % from the model by histological type . Compared to size less than 5 mm , patients with adenoma size between 6 and 10 mm and patients with adenoma size larger than 1 cm have 2.17-fold ( 0.67–10.74 ) and 4.25-fold ( 1.23–14.70 ) , respectively , for the risk of malignant transformation . There are similar findings for the model by histological type . The estimates of overall efficacy of colonoscopy in reducing CRC is 73 % for the model allowing for de novo carcinoma and 88 % for the model without considering de novo carcinoma theory . The efficacy of diminutive adenoma and small adenoma increases with follow-up years , whereas the efficacy of large adenoma decreases with follow-up years . In conclusion , about 30 % of cancers arising from de novo sequence are demonstrated . This finding , together with the adenoma – carcinoma sequence associated with adenoma size and histological type , is important for the estimation of dwelling times , the efficacy of colonoscopy , and the surveillance of polyp after polypectomy In a prospect i ve necropsy study of the large bowel in 365 cases , the commonest polyp identified was the hyperplastic ( metaplastic ) variety , of which 86.1 % of the total were located in the rectum . The other main type of polyp found , and of much greater importance because of its malignant potential , was the neoplastic adenoma . These were present , either singly or multiply , in 73 of 198 male cases ( 36.9 % ) and in 48 of 167 female cases ( 28.7 % ) . Their prevalence and their tendency to be multiple rose with increasing age in both sexes . Most adenomas had a tubular growth pattern and 88.8 % of these were under 1 cm in diameter . There was a fairly even distribution of adenomas throughout the large bowel but a higher proportion of adenomas over 1 cm in diameter occurred in the caecum , sigmoid colon , and rectum than at other sites . In the whole series nine adenocarcinomas were present , two of which were arising in adenomas CONTEXT Conventional colonoscopy is the best available method for detection of colorectal cancer ; however , it is invasive and not without risk . Computed tomographic colonography ( CTC ) , also known as virtual colonoscopy , has been reported to be reasonably accurate in the diagnosis of colorectal neoplasia in studies performed at expert centers . OBJECTIVE To assess the accuracy of CTC in a large number of participants across multiple centers . DESIGN , SETTING , AND PARTICIPANTS A nonr and omized , evaluator-blinded , noninferiority study design of 615 participants aged 50 years or older who were referred for routine , clinical ly indicated colonoscopy in 9 major hospital centers between April 17 , 2000 , and October 3 , 2001 . The CTC was performed by using multislice scanners immediately before st and ard colonoscopy ; findings at colonoscopy were reported before and after segmental unblinding to the CTC results . MAIN OUTCOME MEASURES The sensitivity and specificity of CTC and conventional colonoscopy in detecting participants with lesions sized at least 6 mm . Secondary outcomes included detection of all lesions , detection of advanced lesions , possible technical confounders , participant preferences , and evidence for increasing accuracy with experience . RESULTS A total of 827 lesions were detected in 308 of 600 participants who underwent both procedures ; 104 participants had lesions sized at least 6 mm . The sensitivity of CTC for detecting participants with 1 or more lesions sized at least 6 mm was 39.0 % ( 95 % confidence interval [ CI ] , 29.6%-48.4 % ) and for lesions sized at least 10 mm , it was 55.0 % ( 95 % CI , 39.9%-70.0 % ) . These results were significantly lower than those for conventional colonoscopy , with sensitivities of 99.0 % ( 95 % CI , 97.1%->99.9 % ) and 100 % , respectively . A total of 496 participants were without any lesion sized at least 6 mm . The specificity of CTC and conventional colonoscopy for detecting participants without any lesion sized at least 6 mm was 90.5 % ( 95 % CI , 87.9%-93.1 % ) and 100 % , respectively , and without lesions sized at least 10 mm , 96.0 % ( 95 % CI , 94.3%-97.6 % ) and 100 % , respectively . Computed tomographic colonography missed 2 of 8 cancers . The accuracy of CTC varied considerably between centers and did not improve as the study progressed . Participants expressed no clear preference for either technique . CONCLUSIONS Computed tomographic colonography by these methods is not yet ready for widespread clinical application . Techniques and training need to be improved BACKGROUND , AIMS , AND PATIENTS : In a prospect i ve follow up and intervention study of colorectal polyps , leaving all polyps less than 10 mm in situ for three years , analysis of redetection rate , growth , and new polyp formation was carried out in 116 patients undergoing annual colonoscopy . The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo . RESULTS : Redetection rate varied from 75 - 90 % for each year , and was highest in the rectum and sigmoid colon . There was no net change in size of all polyps in the placebo group , however , polyps less than 5 mm showed a tendency to net growth , and polyps 5 - 9 mm a tendency to net regression in size , both for adenomas and hyperplastic polyps . This pattern was verified by computerised image analysis . Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients , and the same was true for those with multiple adenomas ( four to five ) compared with those with a single adenoma . The new adenomas were significantly smaller and 71 % were located in the right side of the colon . Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma . One patient developed an invasive colorectal carcinoma , which may be evolved from a previously overlooked polyp . Two polyps , showing intramucosal carcinoma after follow up for three years , were completely removed , as judged by endoscopy and histological examination . CONCLUSIONS : The results show that follow up of unresected colorectal polyps up to 9 mm is safe . The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations , but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice . The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer BACKGROUND & AIMS The miss rate of colonoscopy for neoplasms is poorly understood . The aim of this study was to determine the miss rate of colonoscopy by same day back-to-back colonoscopy . METHODS Two consecutive same day colonoscopies were performed in 183 patients . The patients were r and omized to undergo the second colonoscopy by the same or a different endoscopist and in the same or different position . RESULTS The overall miss rate for adenomas was 24 % , 27 % for adenomas < or = 5 mm , 13 % for adenomas 6 - 9 mm , and 6 % for adenomas > or = 1 cm . Patients with two or more adenomas at the first examination were more likely than patients with no or one adenoma detected at the first examination to have one or more adenomas at the second examination ( odds ratio , 3.3 ; 95 % confidence interval , 1.69 - 6.46 ) . Right colon adenomas were missed more often ( 27 % ) than left colon adenomas ( 21 % ) , but the difference was not significant . There was evidence of variation in sensitivity between endoscopists , but significant miss rates for small adenomas were found among essentially all endoscopists . CONCLUSIONS Using current colonoscopic technology , there are significant miss rates for adenomas < 1 cm even with meticulous colonoscopy . Miss rates are low for adenomas > or = 1 cm . The results suggest the need for improvements in colonoscopic technology CONTEXT The Framingham Heart Study produced sex-specific coronary heart disease ( CHD ) prediction functions for assessing risk of developing incident CHD in a white middle-class population . Concern exists regarding whether these functions can be generalized to other population s. OBJECTIVE To test the validity and transportability of the Framingham CHD prediction functions per a National Heart , Lung , and Blood Institute workshop organized for this purpose . DESIGN , SETTING , AND SUBJECTS Sex-specific CHD functions were derived from Framingham data for prediction of coronary death and myocardial infa rct ion . These functions were applied to 6 prospect ively studied , ethnically diverse cohorts ( n = 23 424 ) , including whites , blacks , Native Americans , Japanese American men , and Hispanic men : the Atherosclerosis Risk in Communities Study ( 1987 - 1988 ) , Physicians ' Health Study ( 1982 ) , Honolulu Heart Program ( 1980 - 1982 ) , Puerto Rico Heart Health Program ( 1965 - 1968 ) , Strong Heart Study ( 1989 - 1991 ) , and Cardiovascular Health Study ( 1989 - 1990 ) . MAIN OUTCOME MEASURES The performance , or ability to accurately predict CHD risk , of the Framingham functions compared with the performance of risk functions developed specifically from the individual cohorts ' data . Comparisons included evaluation of the e quality of relative risks for st and ard CHD risk factors , discrimination , and calibration . RESULTS For white men and women and for black men and women the Framingham functions performed reasonably well for prediction of CHD events within 5 years of follow-up . Among Japanese American and Hispanic men and Native American women , the Framingham functions systematic ally overestimated the risk of 5-year CHD events . After recalibration , taking into account different prevalences of risk factors and underlying rates of developing CHD , the Framingham functions worked well in these population s. CONCLUSIONS The sex-specific Framingham CHD prediction functions perform well among whites and blacks in different setting s and can be applied to other ethnic groups after recalibration for differing prevalences of risk factors and underlying rates of CHD events The data of the National Polyp Study , a large longitudinal study on surveillance of adenoma patients , is used for testing assumptions on the adenoma‐carcinoma sequence . The observed adenoma and colorectal cancer incidence in the National Polyp Study were compared with the simulated outcomes of the MISCAN‐COLON model of epidemiology and control of colorectal cancer for the U.S. population based on expert opinion . Variants of this model were explored in order to identify assumptions on the adenoma‐carcinoma sequence that are consistent with the study observations . The high observed adenoma detection rates at surveillance and low observed colorectal cancer incidence in the National Polyp Study could only be explained by assuming a high incidence rate of adenomas accompanied by regression of adenomas . The National Polyp Study data suggest that adenoma prevalence results from a dynamic process of both formation as well as regression of adenomas . This lowers the expectations for the effects of colorectal cancer screening strategies that focus on adenoma detection . © 2004 Wiley‐Liss , BACKGROUND & AIMS In a population reflective of a screening setting , our aim was to compare the relative sensitivity and specificity of computed tomography ( CT ) colonography with double-contrast barium enema ( DCBE ) for detection of colorectal polyps and to assess the added value of double reading at CT colonography , using endoscopy as the arbiter . METHODS This prospect i ve , blinded study comprised 837 asymptomatic persons at higher than average risk for colorectal cancer who underwent CT colonography followed by same-day DCBE . Examinations with polyps > or = 5 mm in diameter were referred to colonoscopy . RESULTS CT colonography readers detected 56%-79 % of polyps > or = 10 mm in diameter . In comparison , the sensitivity at DCBE varied between 39 % and 56 % for the 31 polyps > or = 1 cm . All of the readers detected more polyps at CT colonography than DCBE , but the difference was statistically significant for only a single reader ( P = 0.02 ) . Relative specificity for polyps > or = 10 mm on a per-patient basis ranged from 96 % to 99 % at CT colonography , and 99%-100 % at DCBE . Doubly read CT colonography detected significantly more polyps than DCBE ( 81 % vs. 45 % for polyps > or = 1 cm [ P = < 0.01 ] , and 72 % vs. 44 % for polyps 5 - 9 mm [ P < or = 0.01 ] ) . CONCLUSIONS Double-read CT colonography is significantly more sensitive in detecting polyps than single-read double contrast barium enema . DCBE was significantly more specific than CT colonography The natural history of untreated colonic polyps is uncertain . A retrospective review of Mayo Clinic records from a 6-yr period just before the advent of colonoscopy identified 226 patients with colonic polyps greater than or equal to 10 mm in diameter in whom periodic radiographic examination of the colon was elected over excisional therapy . In all patients , follow-up of polyps spanned at least 12 mo ( mean , 68 mo ; range , 12 - 229 mo ) and included at least two barium enema examinations ( mean , 5.2 ; range , 2 - 17 ) . During the follow-up period , 83 polyps ( 37 % ) enlarged . Twenty-one invasive carcinomas were identified at the site of the index polyp at a mean follow-up of 108 mo ( range , 24 - 225 mo ) . Actuarial analysis revealed that the cumulative risk of diagnosis of cancer at the polyp site at 5 , 10 , and 20 yr was 2.5 % , 8 % , and 24 % , respectively . In addition , 11 invasive cancers were found at a site remote from the index polyp during the same follow-up period . These data further support the recommendation for excision of all colonic polyps greater than or equal to 10 mm in diameter . Periodic examination of the entire colon is recommended in this group of patients to identify neoplasms arising at a site remote from the index polyp . Although this study has limitations inherent to any retrospective analysis , comparable prospect i ve data are unlikely to be available in the future because of the current widespread availability of colonoscopy Much clinical and epidemiologic evidence suggests that a timely colonoscopy and removal of colonic polyps may reduce the risk for cancer in the colon and rectum [ 1 - 5 ] . Nevertheless , it has remained unproved that endoscopic procedures other than rigid proctosigmoidoscopy can truly protect against the development of cancer . Besides financial constraints , the lack of unequivocal evidence in favor of endoscopy is the most important reason why colorectal endoscopy with flexible instruments has not been used more widely for the prevention of cancer . Colonoscopy is associated with an overall complication rate of 1 % to 2 % , a perforation rate of 0.1 % , and a death rate of 0.05 % [ 6 ] . Therefore , before a large segment of the population is subjected to endoscopic procedures on a regular basis , it is important to show that these procedures actually do reduce the risk for cancer in the large intestine . We hypothesized that colonoscopy , flexible sigmoidoscopy , and polypectomy protect against the future development of colorectal cancer . We tested this hypothesis among U.S. military veterans , using a casecontrol study design . The study compared the frequency with which flexible endoscopies were done during the period preceding the first diagnosis of cancer among patients with colorectal cancer and among controls without cancer . Methods Data Source The Patient Treatment File consists of many individual data files . The data files are managed by the Department of Veterans Affairs ' Central Automation Center in Austin , Texas . The main files contain records of all inpatient treatments from all Veterans Affairs hospitals throughout the United States . Files are available for each fiscal year since 1970 . Although the contents of the files and their structure have changed over the past two decades , information on essential demographic and health characteristics are available in similar form from all main files . Since 1984 , other files have been added to cover treatment outside Veterans Affairs facilities and in nursing homes . Each patient record contains one primary and up to nine secondary discharge diagnoses . From 1970 to 1980 , the diagnoses were coded according to the 8th revision of the Clinical Modification of the International Classification of Diseases ( ICD-8-CM ) ; since 1981 , the 9th revision of the ICD has been used [ 7 ] . Individual patients can be identified by their social security numbers . Diagnostic procedures and surgical procedures were initially included in the main files . Separate surgical and medical procedure files were initiated in 1984 and 1988 , respectively . Procedures are also coded according to ICD-9-CM , the coding scheme that makes it possible to record in both the medical and surgical procedure files up to five procedures per day of hospitalization . Since 1990 , outpatient procedures have been included in the Patient Treatment File . All outpatient procedures are listed by codes taken from the Current Procedural Terminology ( CPT-code ) [ 8 ] . Identification of Case- Patients and Controls Information on all veterans who were discharged with a diagnosis of colon cancer ( ICD codes 153.0 to 153.9 , except 153.5 ) or rectal cancer ( ICD codes 154.0 to 154.1 ) between 1988 and 1993 was extracted from the Patient Treatment File . Their social security numbers were then used to search all of their previous discharge records since 1970 , and patients with a diagnosis of colon or rectal cancer before 1988 were excluded from the case population . The remaining patients were assumed to represent incident cases with a first diagnosis of colorectal cancer between 1988 and 1993 . Patients who had had a previous diagnosis of Crohn disease ( ICD code 555 ) , ulcerative colitis ( ICD code 556 ) , or familial polyposis ( ICD code 759.6 ) between 1970 and 1993 were also excluded from the case population . Ulcerative colitis and Crohn disease are both associated with an increased risk for colon cancer [ 9 , 10 ] . Patients with inflammatory bowel disease have frequent endoscopies to assess colonic involvement , diagnose complications , and screen for dysplasia . Procedures in these patient population s are determined by considerations other than those in the general population . For each case-patient , one control was selected from among the patients who were discharged during the same fiscal year that the case-patient was first diagnosed with colorectal cancer . Each control was matched to his or her case-patient based on age , sex , and race . Controls who had had any previous discharge diagnosis of colorectal cancer between 1970 and 1993 were excluded from the complete annual files of 1988 through 1993 . Similarly , controls who had had any previous diagnosis of Crohn disease , ulcerative colitis , or familial polyposis were excluded . After the exclusions , the remaining patient records of each year from 1988 to 1993 were r and omized . For each case-patient , the r and omized annual file was scanned sequentially until a control of the same age , race , and sex as the case-patient was identified . Ten-year age categories were used for matchingfor example , less than 25 years , 25 to 34 years , 35 to 44 years , and so on . Extraction of Procedures and Previous Diagnoses Detailed procedural codes based on the ICD-9-CM have been available in the Patient Treatment File since 1981 . Therefore , for case- patients and controls recruited during the last 6 years , we were able to search the procedure files dating from 7 to 13 years before recruitment for a history of previous procedures of the large intestine . The procedure files from 1981 until the date on which cancer was first diagnosed ( or corresponding time of hospitalization in controls ) were search ed for all of the procedural codes shown in Table 1 . The procedure that was used to establish the first diagnosis of cancer was not considered in the analysis . Table 1 . Definition of 9th Revision of the Clinical Modification of the International Classification of Diseases and Current Procedural Terminology Codes In a second search , we followed case- patients and controls backward through the annual files ( all main files since 1970 ) to assess the overall duration of health coverage by the Veterans Affairs system and to determine the number of all hospital discharges before the first diagnosis of colorectal cancer . These two variables were created to adjust for the extent of medical care that an individual veteran received through the Veterans Affairs system . In a third search , we followed case- patients and controls backward through the annual Patient Treatment Files of the 5 years preceding the first diagnosis of colorectal cancer to record all previous discharge diagnoses . Indicator variables were created for the following primary or secondary discharge diagnoses : colorectal polyps ( ICD codes 211.3 , 211.4 , and 569.0 ) , carcinoma in situ ( codes 230.3 and 230.4 ) , any form of anemia ( codes 280 to 285 ) , hemorrhoids and any form of gastrointestinal hemorrhage ( codes 455 , 569.3 , 578.1 , and 578.9 ) , signs and symptoms that suggested intestinal obstruction ( codes 560.0 , 560.3 , 560.9 , 564.0 , and 569.2 ) , diverticulosis and diverticulitis of the colon ( codes 562.10 to 562.13 ) , various types of nonspecific gastrointestinal complaints ( codes 558.9 , 569.4 , 569.8 , 569.9 , 789.0 , and 789.9 ) , abnormal weight loss ( code 783.2 ) , and abdominal or pelvic swelling or mass ( code 789.3 ) . These diagnoses may often be associated with a diagnosis of colorectal cancer , or they may precede its definitive diagnosis ; it is highly unlikely that cancer would be misdiagnosed , for example , as hemorrhoids or bleeding peptic ulcer , for more than 5 years . Arthritis and related disorders ( codes 714 to 716 and 720 to 721 ) were common conditions in the Patient Treatment File that were likely to be treated with nonsteroidal anti-inflammatory drugs . Such drugs have been shown to reduce the risk for death from colorectal cancer [ 11 , 12 ] . Currently , no separate ICD code identifies patients with hereditary nonpolyposis colon cancer ( the Lynch syndrome ) . Statistical Analysis Except for the duration of coverage by the Veterans Affairs system and the number of hospital discharges , all variables were coded as dichotomous variables : Code 1 was used to indicate the attribute of interest , and code 0 was used to indicate its absence . The development of colon or rectal cancer served as the outcome variable . Any type of flexible endoscopy done before the first diagnosis of colorectal cancer served as the main predictor variable . Different types of discharge diagnoses that preceded the diagnosis of colorectal cancer ( for example , polyps or anemia ) represented the other predictor variables . The duration of coverage ( in years ) by the Veterans Affairs system and the number of hospital discharges were transformed into categorical predictor variables according to their quartile ranges . For each pair of predictor variables , the Kendall correlation coefficient or the Spearman correlation coefficient was calculated . The proportional hazards regression procedure of the Statistical Analysis System was used for all types of univariate and multivariate conditional logistic regression analyses [ 13 ] . We did univariate conditional logistic regression analyses in which we considered each predictor variable separately . We also did multivariate conditional logistic regression analyses in which we considered all predictor variables simultaneously [ 14 ] . Besides main-effect models , the possibility of interaction terms among the variables were assessed . We did separate analyses to identify the efficacy of specific procedures . During their follow-up in the Veterans Affairs system , many of the case- patients and controls had the same procedure more than once and different colorectal procedures in varying temporal sequences . Also , the different codes of the ICD-9-CM do not represent completely distinct procedures , whereas some identical procedures , such as colonoscopy or flexible sigmoidoscopy , may be assigned multiple procedural Aim : To study the availability and quality of adult and paediatric colonoscopy in three National Health Service ( NHS ) regions . Method : A prospect i ve four month study of colonoscopies in North East Thames , West Midl and s , and East Anglia . Patients : Subjects undergoing colonoscopy in 68 endoscopy units . Results : A total of 9223 colonoscopies were studied . The mean number of colonoscopies performed over the four month period was 142 in district general hospitals and 213 in teaching hospitals . Intravenous sedation was administered in 94.6 % of procedures , but 2.2 % and 11.4 % of “ at risk ” patients did not have continuous venous access or did not receive supplemental oxygen , respectively . Caecal intubation was recorded in 76.9 % of procedures but the adjusted caecal intubation rate was only 56.9 % . Reasons for failing to reach the caecum included patient discomfort ( 34.7 % ) , looping ( 29.7 % ) , and poor bowel preparation ( 19.6 % ) . A normal colonoscopy was reported in 42.1 % . The most common diagnosis was polyps ( 22.5 % ) followed by diverticular disease ( 14.9 % ) . Inflammatory bowel disease was recorded in 13.9 % and carcinoma in 3.8 % . Only half of the patients remembered being told of possible adverse events prior to the procedure . Rectal bleeding requiring admission following colonoscopy was reported in six patients . The overall perforation rate was 1:769 and colonoscopy was considered a possible factor in six deaths occurring within 30 days of the procedure . Only 17.0 % of colonoscopists had received supervised training for their first 100 colonoscopies and only 39.3 % had attended a training course . Conclusion : There is serious under provision of colonoscopy service in most NHS hospitals . Endoscopy sedation guidelines are not always adhered to and there is a wide variation in practice between units . Colonoscopy is often incomplete and does not achieve the target 90 % caecal intubation rate . Serious complications of colonoscopy were comparable with previous studies . Training in colonoscopy is often inadequate and improved practice should result from better training We prospect ively studied the colonoscopic miss-rate of large colorectal polyps in a blinded trial featuring t and em colonoscopy . Sixty-three lesions greater than or equal to 1 cm in size were discovered and none were missed . Confidence intervals of 95 % are a miss-rate of 0 to 4.6 % . We conclude that less than 5 % of large colorectal polyps are missed during the index colonoscopic examination in a well-prepared colon BACKGROUND & AIMS In isolation , computer-aided detection ( CAD ) for computed tomographic ( CT ) colonography is as effective as optical colonoscopy for detection of significant adenomas . However , the unavoidable interaction between CAD and the reader has not been addressed . METHODS Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients ( 60 with 142 polyps ) , first without CAD and then with CAD after temporal separation of 2 months . Per-patient and per-polyp detection were determined by comparing responses with known patient status . RESULTS With CAD , 41 ( 68 % ; 95 % confidence interval [ CI ] , 55%-80 % ) of the 60 patients with polyps were identified more frequently by readers . Per-patient sensitivity increased significantly in 70 % of readers , while specificity dropped significantly in only one . Polyp detection increased significantly with CAD ; on average , 12 more polyps were detected by each reader ( 9.1 % , 95 % CI , 5.2%-12.8 % ) . Small- ( < or = 5 mm ) and medium-sized ( 6 - 9 mm ) polyps were significantly more likely to be detected when prompted correctly by CAD . However , overall performance was relatively poor ; even with CAD , on average readers detected only 10 polyps ( 51.0 % ) > or = 10 mm and 24 ( 38.2 % ) > or = 6 mm . Interpretation time was shortened significantly with CAD : by 1.9 minutes ( 95 % CI , 1.4 - 2.4 minutes ) for patients with polyps and by 2.9 minutes ( 95 % CI , 2.5 - 3.3 minutes ) for patients without . Overall , 9 readers ( 90 % ) benefited significantly from CAD , either by increased sensitivity and /or by reduced interpretation time . CONCLUSIONS CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but can not substitute for adequate training Colorectal cancer is the second leading cause of cancer-related death in the United States , with 129 400 new cases and 56 600 deaths estimated to have occurred in 1999 ( 1 ) . Most cases of colorectal cancer arise from adenomatous polyps ( 2 ) . Screening has been shown to decrease colorectal cancer incidence and mortality rates ( 3 , 4 ) , and various decision analyses support its cost-effectiveness ( 510 ) . Despite demonstrated clinical and economic benefits , however , use of screening tests is low ( 1113 ) . In a large population -based study , 19.8 % of respondents reported having fecal occult blood testing during the preceding year and 30.4 % reported having sigmoidoscopyproctoscopy during the preceding 5 years ; 9.5 % had had both tests ( 13 ) . In a national strategy to decrease the burden of colorectal cancer , aspirin chemoprevention is a potentially powerful adjunct to screening . Numerous casecontrol ( 1421 ) and cohort studies ( 2226 ) support the hypothesis that aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) decrease the incidence of colorectal adenoma and colorectal cancer and the mortality rate from colorectal cancer by 30 % to 65 % . Many animal models show that NSAIDs have an antitumor effect in the colon ( 27 ) . However , the Physicians ' Health Study , a r and omized study of male physicians that was not design ed to examine colorectal cancer specifically , found no decrease in colorectal cancer incidence when 325 mg of aspirin on alternate days was compared with placebo ( 28 ) . These results may conflict because of the specific dose and duration used and the patients studied . Aspirin is of proven benefit in secondary prevention of cardiovascular morbidity and death ( 29 ) and in primary prevention of myocardial infa rct ion in men ( 30 ) . However , its use for primary cardiovascular prevention remains controversial , in part because mortality prevention is unproven and no r and omized studies in women exist ( 29 ) . Although it is well recognized that aspirin may cause major complications ( 3035 ) , prophylactic aspirin is prescribed on the basis of cardiovascular considerations . In contrast , aspirin is unlikely to be prescribed for colorectal cancer prevention until better estimates of its benefits and risks become available . Since such data are unlikely to be available for the general U.S. population in the near future , we constructed a decision analytic model to explore the incremental clinical and economic effects of aspirin when it is added to an accepted screening program for sporadic colorectal cancer . Accepted screening programs consisted of flexible sigmoidoscopy every 5 years and yearly fecal occult blood testing ( FS/FOBT ) ( 8 , 36 ) or screening colonoscopy every 10 years ( COLO ) , an emerging alternative screening strategy ( 710 , 37 ) . Our primary aim was to clarify whether aspirin chemoprevention might prove to be a cost-effective adjunct to screening . In secondary analyses , we examined the potential role of aspirin chemoprevention in an unscreened population and the effects of screening when added to existing aspirin use . Methods Literature Review We search ed MEDLINE from 1980 to 1999 for English- language literature that provided data on colorectal cancer , screening , aspirin chemoprevention , and aspirin-related complications . Model inputs were based on the literature search and on rigorous literature review s by a multidisciplinary expert panel from the Agency for Health Care Policy and Research ( 8) and by the Office of Technology Assessment ( 7 ) ( Table 1 ) . Table 1 . Inputs in the Cost-Effectiveness Model Decision Analytic Model We created a Markov model using DATA 3.0 ( TreeAge Software Inc. , Williamstown , Massachusetts ) ; Excel 2000 ( Microsoft Corp. , Redmond , Washington ) was used for analysis . The Markov model estimated the clinical and economic consequences of six strategies : natural history ( no aspirin or screening ) , FS/FOBT , COLO , aspirin alone ( ASA ) , FS/FOBT and aspirin ( FS/FOBT/ASA ) , and colonoscopy and aspirin ( COLO/ASA ) . Beginning at 50 years of age , patients progressed through the model for 30 1-year cycles ; principal states were normal , polyp , cancer ( localized , regional , or distant ) , and dead . The Markov model is discussed in detail in the Appendix . To reflect the effect of aspirin in the general population and not in an individual , we varied the percentage of persons in the population who adhered to screening . Using population -based data ( 13 ) , we selected a screening adherence rate of 25 % to reflect current practice . The general population , men , and women were examined separately . Natural History of Sporadic Colorectal Cancer We constructed a model of the natural history of sporadic colorectal cancer in patients at average risk for the disease . Epidemiologic data on colorectal cancer were derived from the Surveillance , Epidemiology , and End Results ( SEER ) program ( 38 ) . According to results of autopsy studies , adenomatous polyp prevalence was assumed to increase from 15 % at 50 years of age to 47 % at 75 years of age ( 16 % to 54 % in men ; 15 % to 40 % in women ) ( 3941 ) . We assumed that 90 % of tumors develop from polyps and that cancer progresses from localized to regional ( 2 years in each state ) to disseminated , with symptomatic presentation by stage as reflected in SEER data . Age-specific transition probabilities were calculated between normal , polyp , and cancer to yield polyp and cancer rates derived from the literature . Age-specific noncolorectal cancer mortality rates were derived from U.S. life tables ( 46 ) . Effect of Colorectal Cancer Screening We selected FS/FOBT as an accepted strategy endorsed by published guidelines ( 8 , 36 ) . In the model , any positive test result was followed by colonoscopy and , if necessary , polypectomy . If the results of colonoscopy were normal , screening resumed in 10 years . After an adenoma was detected , surveillance colonoscopy was performed every 5 years . Although specific patients with high-risk or low-risk adenomas may undergo surveillance at different intervals , we chose 5 years to reflect the average surveillance interval for the population . Colonoscopy was performed at cancer diagnosis and 3 years and every 5 years thereafter ( 8) . As long as results of screening tests remained negative , FS/FOBT was continued . Emerging data from clinical studies and decision analyses suggest that colonoscopy is a cost-effective screening tool ( 710 , 37 ) . Therefore , COLO was examined as an alternative screening strategy . In the model , colonoscopy was performed every 10 years as long as no adenoma or cancer was detected . Surveillance after adenoma detection was the same as that described for FS/FOBT . Effect of Aspirin Aspirin , 325 mg/d , was added to the screening and natural history strategies . In the base case , aspirin was estimated to reduce colorectal cancer risk by 30 % through equal reductions in adenoma incidence and progression to cancer ( 1426 ) . Aspirin may increase occult gastrointestinal blood loss ( 4753 ) , which could affect the FS/FOBT strategy . In the base case , we assumed that aspirin did not affect fecal occult blood testing because increases in blood loss have been reported only with high doses ( 4853 ) and low doses have been reported to have no effect on fecal occult blood testing ( 5456 ) . The protective effect of NSAIDs is not explained by earlier detection of adenomas or cancer ( 19 , 26 ) ; however , increased sensitivity and decreased specificity of FS/FOBT in patients receiving aspirin were assessed in the sensitivity analysis . In the model , aspirin-related complications were followed by aspirin withdrawal and return to baseline risk for colorectal cancer . Using data from trials of low-dose aspirin , we calculated rates of excess serious complications in patients taking aspirin . The rates were 1.4 per 10 000 person-years in patients younger than 65 years of age and 28 to 40 per 10 000 person-years in older patients with cerebrovascular disease ( 30 , 3234 ) . The 1-year prevalence of serious gastrointestinal NSAID-related complications is estimated to increase eightfold after 65 years of age ( 31 ) . Thus , we selected a base-case rate of 2 per 10 000 person-years before 65 years of age and 16 per 10 000 person-years thereafter for serious aspirin-related complications . We modeled mortality rates of 2 % to 8 % after a serious aspirin-related complication ( 4244 ) . We did not include changes in cardiovascular outcomes in the base case for several reasons . First , the role of aspirin in primary cardiovascular prevention is controversial , largely because prevention of death is unproven ( 29 ) . A recent decision analysis suggested that aspirin may be harmful in cohorts at low risk for cardiovascular events and may be only minimally beneficial as risk increases ( 57 ) . Second , aspirin may increase the incidence of hemorrhagic stroke ( 30 ) , and the balance of risks and benefits is unknown , particularly in women ( 29 ) . Third , in patients with cardiovascular indications for aspirin , a potential effect on colon cancer is unlikely to affect prescribing decisions . Thus , we chose to examine the incremental benefit of colorectal cancer screening in a population already receiving aspirin . In the sensitivity analysis , we examined the effect of aspirin by assuming that it reduced cardiovascular mortality . Cardiovascular death accounts for 30 % to 42 % of deaths , depending on age ( 46 ) . Costs Procedure costs were derived from Medicare fee schedules and include professional fees and median procedure reimbursement . We used the wholesale cost of aspirin at the University of Michigan pharmacy , Ann Arbor , Michigan . Complication costs were derived from relevant diagnostic related groups ( 45 ) . Costs for care of stage-specific colon cancer were taken from reports to the National Cancer Institute ( 7 ) . All costs are in 1998 U.S. dollars ( Table 1 ) . Outcomes Colorectal cancer cases by stage , deaths by cause , average life-years after age 50 years , total costs , and itemized costs were determined for each strategy . Costs and life-years were |
2,641 | 28,049,256 | The initial administration of low- versus high-energy supplements did not impact clinical outcomes except for gastrointestinal intolerance in non-malnourished critically ill patients receiving enteral nutrition .
The initial administration of highrather than low-energy may benefit these patients by reducing infections , but this effect might actually be attributable to the concomitant high protein intake | BACKGROUND AND OBJECTIVES Here we systematic ally review ed and quantitatively analyzed r and omized controlled trials ( RCTs ) to compare the important initial outcomes of critically ill adults receiving low- and highenergy enteral nutrition . | BACKGROUND Despite extensive use of enteral ( EN ) and parenteral nutrition ( PN ) in intensive care unit ( ICU ) population s for 4 decades , evidence to support their efficacy is extremely limited . METHODS A prospect i ve r and omized trial was conducted evaluate the impact on outcomes of intensive medical nutrition therapy ( IMNT ; provision of > 75 % of estimated energy and protein needs per day via EN and adequate oral diet ) from diagnosis of acute lung injury ( ALI ) to hospital discharge compared with st and ard nutrition support care ( SNSC ; st and ard EN and ad lib feeding ) . The primary outcome was infections ; secondary outcomes included number of days on mechanical ventilation , in the ICU , and in the hospital and mortality . RESULTS Overall , 78 patients ( 40 IMNT and 38 SNSC ) were recruited . No significant differences between groups for age , body mass index , disease severity , white blood cell count , glucose , C-reactive protein , energy or protein needs occurred . The IMNT group received significantly higher percentage of estimated energy ( 84.7 % vs 55.4 % , P < .0001 ) and protein needs ( 76.1 vs 54.4 % , P < .0001 ) per day compared with SNSC . No differences occurred in length of mechanical ventilation , hospital or ICU stay , or infections . The trial was stopped early because of significantly greater hospital mortality in IMNT vs SNSC ( 40 % vs 16 % , P = .02 ) . Cox proportional hazards models indicated the hazard of death in the IMNT group was 5.67 times higher ( P = .001 ) than in the SNSC group . CONCLUSIONS Provision of IMNT from ALI diagnosis to hospital discharge increases mortality BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management . However , the appropriate caloric intake for critically ill patients remains ill defined . OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy ( IIT ) compared with that of conventional insulin therapy ( CIT ) on the outcomes of critically ill patients . DESIGN This study had a 2 × 2 factorial , r and omized , controlled design . Eligible patients were r and omly assigned to permissive underfeeding or target feeding groups ( caloric goal : 60 - 70 % compared with 90 - 100 % of calculated requirement , respectively ) with either IIT or CIT ( target blood glucose : 4.4 - 6.1 compared with 10 - 11.1 mmol/L , respectively ) . RESULTS Twenty-eight-day all-cause mortality was 18.3 % in the permissive underfeeding group compared with 23.3 % in the target feeding group ( relative risk : 0.79 ; 95 % CI : 0.48 , 1.29 ; P = 0.34 ) . Hospital mortality was lower in the permissive underfeeding group than in the target group ( 30.0 % compared with 42.5 % ; relative risk : 0.71 ; 95 % CI : 0.50 , 0.99 ; P = 0.04 ) . No significant differences in outcomes were observed between the IIT and CIT groups . CONCLUSION In critically ill patients , permissive underfeeding may be associated with lower mortality rates than target feeding . This trial was registered at controlled-trials.com as IS RCT N96294863 Summary Priming of the gastrointestinal ( GI ) tract with low-volume feedings before giving full enteral feedings to very premature , high-risk infants is a controversial practice . We design ed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain , improve tolerance of subsequent feedings , enhance nutritional status , and increase serum concentration of gastrin , a hormone trophic for intestinal growth . Infants were r and omly assigned to receive total parenteral nutrition ( TPN ) alone ( N = 21 ) or GI priming plus TPN ( N = 19 ) for 12 days beginning on day 3 of life . Full-strength premature infant formula was used for priming . Both groups received the same total nutrition . Beginning on day 15 , feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20 , where they were maintained until day 30 . After day 30 , the feedings were modified according to the infants ' condition . The groups did not differ in birth weight , gestational age , or 5-min Apgar scores . GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study . There was no significant difference in weight gain . GI priming improves tolerance of feedings , accelerates rate of rise of serum gastrin during the first weeks of life , and does not increase the risk of feeding complications when compared to TPN alone . This may lead to more rapid maturation of the GI tract in primed infants BACKGROUND Enteral nutrition ( EN ) is recommended for patients in the intensive-care unit ( ICU ) , but it does not consistently achieve nutritional goals . We assessed whether delivery of 100 % of the energy target from days 4 to 8 in the ICU with EN plus supplemental parenteral nutrition ( SPN ) could optimise clinical outcome . METHODS This r and omised controlled trial was undertaken in two centres in Switzerl and . We enrolled patients on day 3 of admission to the ICU who had received less than 60 % of their energy target from EN , were expected to stay for longer than 5 days , and to survive for longer than 7 days . We calculated energy targets with indirect calorimetry on day 3 , or if not possible , set targets as 25 and 30 kcal per kg of ideal bodyweight a day for women and men , respectively . Patients were r and omly assigned ( 1:1 ) by a computer-generated r and omisation sequence to receive EN or SPN . The primary outcome was occurrence of nosocomial infection after cessation of intervention ( day 8) , measured until end of follow-up ( day 28 ) , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00802503 . FINDINGS We r and omly assigned 153 patients to SPN and 152 to EN . 30 patients discontinued before the study end . Mean energy delivery between day 4 and 8 was 28 kcal/kg per day ( SD 5 ) for the SPN group ( 103 % [ SD 18 % ] of energy target ) , compared with 20 kcal/kg per day ( 7 ) for the EN group ( 77 % [ 27 % ] ) . Between days 9 and 28 , 41 ( 27 % ) of 153 patients in the SPN group had a nosocomial infection compared with 58 ( 38 % ) of 152 patients in the EN group ( hazard ratio 0·65 , 95 % CI 0·43 - 0·97 ; p=0·0338 ) , and the SPN group had a lower mean number of nosocomial infections per patient ( -0·42 [ -0·79 to -0·05 ] ; p=0·0248 ) . INTERPRETATION Individually optimised energy supplementation with SPN starting 4 days after ICU admission could reduce nosocomial infections and should be considered as a strategy to improve clinical outcome in patients in the ICU for whom EN is insufficient . FUNDING Foundation Nutrition 2000Plus , ICU Quality Funds , Baxter , and Fresenius Kabi CONTEXT Responses to critical illness , such as excessive inflammation and hyperglycemia , may trigger detrimental chain reactions that damage cellular proteins and organelles . Such responses to illness contribute to the risk of ( nonresolving ) multiple organ dysfunction and adverse outcome . OBJECTIVE We studied autophagy as a bulk degradation pathway able to remove toxic protein aggregates and damaged organelles and how these are affected by preventing hyperglycemia with insulin during critical illness . DESIGN AND SETTING Patients participated in a r and omized study , conducted at a university hospital surgical/medical intensive care unit . PATIENTS We studied adult prolonged critically ill patients vs. controls . INTERVENTIONS Tolerating excessive hyperglycemia was compared with intensive insulin therapy targeting normoglycemia . MAIN OUTCOME MEASURES We quantified (ultra)structural abnormalities and hepatic and skeletal muscle protein levels of key players in autophagy . RESULTS Morphologically , both liver and muscle revealed an autophagy-deficiency phenotype . Proteins involved in initiation and elongation steps of autophagy were induced 1.3- to 6.5-fold by critical illness ( P ≤ 0.01 ) , but mature autophagic vacuole formation was 62 % impaired ( P = 0.05 ) and proteins normally de grade d by autophagy accumulated up to 97-fold ( P ≤ 0.03 ) . Mitophagy markers were unaltered or down-regulated ( P = 0.05 ) . Although insulin preserved hepatocytic mitochondrial integrity ( P = 0.05 ) , it further reduced the number of autophagic vacuoles by 80 % ( P = 0.05 ) . CONCLUSIONS Insufficient autophagy in prolonged critical illness may cause inadequate removal of damaged proteins and mitochondria . Such incomplete clearance of cellular damage , inflicted by illness and aggravated by hyperglycemia , could explain lack of recovery from organ failure in prolonged critically ill patients . These data open perspectives for therapies that activate autophagy during critical illness Objective : To determine whether nutrient intake by early enteral nutrition with parenteral nutrition improves levels of retinol-binding protein and prealbumin ( primary endpoint ) and reduce morbidity and mortality ( secondary endpoint ) in ICU patients . Design : Prospect i ve , double-blind , and r and omized , placebo-controlled study . Setting : Two intensive care units in a tertiary institution . Patients and participants : 120 patients in two groups of 60.¶ Interventions : Patients received either enteral plus parenteral nutrition ( treatment group ) or enteral nutrition plus placebo ( placebo group ) for 4–7 days after initiation of nutritional support . Measurements and results : Retinol-binding protein ( P = 0.0496 ) and prealbumin ( P = 0.0369 ) increased significantly in the treatment group from day 0 to day 7 . There was no reduction in morbidity in ICU . There was no difference in OMEGA score ( 263 vs. 244 ) and length of stay in the ICU ( 16.9 vs. 17.3 ) , but a reduction in length of stay at hospital ( 31.2 ± 18.5 vs. 33.7 ± 27.7 , P = 0.0022 ) . Mortality on day 90 ( 17 vs. 18 ) and after 2 years ( 24 vs. 24 ) was identical . Conclusions : Although it enhances nutrient intake and corrects nutritional parameters such as RBP and prealbumin more rapidly , within 1 week , supplemental parenteral nutrition has no clinical ly relevant effect on outcome in ICU patients at the early phase of nutritional support BACKGROUND Proper caloric intake goals in critically ill surgical patients are unclear . It is possible that overnutrition can lead to hyperglycemia and an increased risk of infection . OBJECTIVE This study was conducted to determine whether surgical infection outcomes in the intensive care unit ( ICU ) could be improved with the use of hypocaloric nutritional support . DESIGN Eighty-three critically ill patients were r and omly allocated to receive either the st and ard calculated daily caloric requirement of 25 - 30 kcal · kg(-1 ) · d(-1 ) ( eucaloric ) or 50 % of that value ( hypocaloric ) via enteral tube feeds or parenteral nutrition , with an equal protein allocation in each group ( 1.5 g · kg(-1 ) · d(-1 ) ) . RESULTS There were 82 infections in the hypocaloric group and 66 in the eucaloric group , with no significant difference in the mean ( ± SE ) number of infections per patient ( 2.0 ± 0.6 and 1.6 ± 0.2 , respectively ; P = 0.50 ) , percentage of patients acquiring infection [ 70.7 % ( 29 of 41 ) and 76.2 % ( 32 of 42 ) , respectively ; P = 0.57 ] , mean ICU length of stay ( 16.7 ± 2.7 and 13.5 ± 1.1 d , respectively ; P = 0.28 ) , mean hospital length of stay ( 35.2 ± 4.9 and 31.0 ± 2.5 d , respectively ; P = 0.45 ) , mean 0600 glucose concentration ( 132 ± 2.9 and 135 ± 3.1 mg/dL , respectively ; P = 0.63 ) , or number of mortalities [ 3 ( 7.3 % ) and 4 ( 9.5 % ) , respectively ; P = 0.72 ] . Further analyses revealed no differences when analyzed by sex , admission diagnosis , site of infection , or causative organism . CONCLUSIONS Among critically ill surgical patients , caloric provision across a wide acceptable range does not appear to be associated with major outcomes , including infectious complications . The optimum target for caloric provision remains elusive AIMS It is unclear whether prescribing a higher amount of calories by enteral nutrition ( EN ) increases actual delivery . This prospect i ve controlled study aim ed at comparing the progression of EN of two study population s with different levels of calorie prescriptions , during the first 5 days of EN . METHODS The daily calorie prescription of group 1 ( n=346 ) was 25 and 20 kcal/kg body weight for women < 60 and > or = 60 years , respectively , and 30 and 25 kcal/kg body weight for men < 60 and > or = 60 years , respectively . The prescription of group 2 ( n=148 ) was 5 kcal/kg body weight higher than in group 1 . Calorie intakes were expressed as percentage of resting energy expenditure ( REE ) and protein intakes as percentage of requirements estimated as 1.2 g/kg body weight/day . Patients were classified as < 60 and > or = 60 years and as medical or surgical patients . Statistical analysis was performed with ANOVA for repeated measures . RESULTS Calorie and protein deliveries increased in both groups independently of age and ward categories ( P < or = 0.0001 ) . Group 2 showed faster progressions of calorie and protein intakes than group 1 in patients altogether ( P < or = 0.002 ) , > or = 60 years ( P < or = 0.01 ) and in surgical patients ( P < or = 0.02 ) . Differences of calorie and protein intakes between day 1 and day 5 were significantly higher in group 2 than group 1 for patients altogether ( 75+/-61 vs. 56+/-54 % of REE ; 41+/-30 vs. 31+/-/-27 % of protein requirements ) , those over 60 years ( 76+/-67 of REE vs. 52+/-59 of protein requirements ) and surgical patients ( 81+/-52 vs. 58+/-57 % of REE ; 44+/-27 vs. 33+/-29 % of protein requirements ) . CONCLUSIONS Increasing the levels of EN prescriptions improved calorie and protein deliveries . While the mean energy delivery over 5 days was sufficient to cover requirements , the protein delivery by EN was insufficient , despite our nutritional support team BACKGROUND AND AIMS Critically ill patients with complicated evolution are frequently hypermetabolic , catabolic , and at risk of underfeeding . The study aim ed at assessing the relationship between energy balance and outcome in critically ill patients . METHODS Prospect i ve observational study conducted in consecutive patients staying > or = 5 days in the surgical ICU of a University hospital . Demographic data , time to feeding , route , energy delivery , and outcome were recorded . Energy balance was calculated as energy delivery minus target . Data in means+/-SD , linear regressions between energy balance and outcome variables . RESULTS Forty eight patients aged 57+/-16 years were investigated ; complete data are available in 669 days . Mechanical ventilation lasted 11+/-8 days , ICU stay 15+/-9 was days , and 30-days mortality was 38 % . Time to feeding was 3.1+/-2.2 days . Enteral nutrition was the most frequent route with 433 days . Mean daily energy delivery was 1090+/-930 kcal . Combining enteral and parenteral nutrition achieved highest energy delivery . Cumulated energy balance was between -12,600+/-10,520 kcal , and correlated with complications ( P < 0.001 ) , already after 1 week . CONCLUSION Negative energy balances were correlated with increasing number of complications , particularly infections . Energy debt appears as a promising tool for nutritional follow-up , which should be further tested . Delaying initiation of nutritional support exposes the patients to energy deficits that can not be compensated later on Objective : Enteral nutrition is provided to mechanically ventilated patients who can not eat normally , yet the amount of support needed is unknown . We conducted this r and omized , open-label study to test the hypothesis that initial low-volume ( i.e. , trophic ) enteral nutrition would decrease episodes of gastrointestinal intolerance/complications and improve outcomes as compared to initial full-energy enteral nutrition in patients with acute respiratory failure . Design : R and omized , open-label study . Patients : A total of 200 patients with acute respiratory failure expected to require mechanical ventilation for at least 72 hrs . Interventions : Patients were r and omized to receive either initial trophic ( 10 mL/hr ) or full-energy enteral nutrition for the initial 6 days of ventilation . Measurements and Main Results : The primary outcome measure was ventilator-free days to day 28 . Baseline characteristics were similar between the 98 patients r and omized to trophic and the 102 patients r and omized to full-energy nutrition . At enrollment , patients had a mean Acute Physiology and Chronic Health Evaluation II score of 26.9 and a Pao2/Fio2 ratio of 182 and 38 % were in shock . Both groups received similar duration s of enteral nutrition ( 5.5 vs. 5.1 days ; p = .51 ) . The trophic group received an average of 15.8 % ± 11 % of goal calories daily through day 6 compared to 74.8 % ± 38.5 % ( p < .001 ) for the full-energy group . Both groups had a median of 23.0 ventilator-free days ( p = .90 ) and a median of 21.0 intensive-care-unit-free days ( p = .64 ) . Mortality to hospital discharge was 22.4 % for the trophic group vs. 19.6 % for the full-energy group ( p = .62 ) . In the first 6 days , the trophic group had trends for less diarrhea ( 19 % vs. 24 % of feeding days ; p = .08 ) and significantly fewer episodes of elevated gastric residual volumes ( 2 % vs. 8 % of feeding days ; p < .001 ) . Conclusion : Initial trophic enteral nutrition result ed in clinical outcomes in mechanically ventilated patients with acute respiratory failure similar to those of early full-energy enteral nutrition but with fewer episodes of gastrointestinal intolerance BACKGROUND Critically ill patients typically receive ∼60 % of estimated calorie requirements . OBJECTIVES We aim ed to determine whether the substitution of a 1.5-kcal/mL enteral nutrition solution for a 1.0-kcal/mL solution result ed in greater calorie delivery to critically ill patients and establish the feasibility of conducting a multicenter , double-blind , r and omized trial to evaluate the effect of an increased calorie delivery on clinical outcomes . DESIGN A prospect i ve , r and omized , double-blind , parallel-group , multicenter study was conducted in 5 Australian intensive care units . One hundred twelve mechanically ventilated patients expected to receive enteral nutrition for ≥2 d were r and omly assigned to receive 1.5 ( n = 57 ) or 1.0 ( n = 55 ) kcal/mL enteral nutrition solution at a rate of 1 mL/kg ideal body weight per hour for 10 d. Protein and fiber contents in the 2 solutions were equivalent . RESULTS The 2 groups had similar baseline characteristics ( 1.5 compared with 1.0 kcal/mL ) . The mean ( ±SD ) age was 56.4 ± 16.8 compared with 56.5 ± 16.1 y , 74 % compared with 75 % were men , and the Acute Physiology and Chronic Health Evaluation II score was 23 ± 9.1 compared with 22 ± 8.9 . The groups received similar volumes of enteral nutrition solution [ 1221 mL/d ( 95 % CI : 1120 , 1322 mL/d ) compared with 1259 mL/d ( 95 % CI : 1143 , 1374 mL/d ) ; P = 0.628 ] , which led to a 46 % increase in daily calories in the group given the 1.5-kcal/mL solution [ 1832 kcal/d ( 95 % CI : 1681 , 1984 kcal/d ) compared with 1259 kcal/d ( 95 % CI : 1143 , 1374 kcal/d ) ; P < 0.001 ] . The 1.5-kcal/mL solution was not associated with larger gastric residual volumes or diarrhea . In this feasibility study , there was a trend to a reduced 90-d mortality in patients given 1.5 kcal/mL [ 11 patients ( 20 % ) compared with 20 patients ( 37 % ) ; P = 0.057 ] . CONCLUSIONS The substitution of a 1.0- with a 1.5-kcal/mL enteral nutrition solution administered at the same rate result ed in a 46 % greater calorie delivery without adverse effects . The results support the conduct of a large-scale trial to evaluate the effect of increased calorie delivery on clinical ly important outcomes in the critically ill OBJECTIVE To determine the effect of early enhanced enteral nutrition ( EN ) on clinical outcome of head-injured patients . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Tertiary neurosurgical and trauma center . PATIENTS Eighty-two patients suffering head injury and requiring mechanical ventilation . INTERVENTIONS Patients were r and omized to receive st and ard EN ( gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements ) or enhanced EN ( started at a feeding rate that met estimated energy and nitrogen requirements ) from day 1 . Good neurologic outcome ( Glasgow Outcome Scale score of 4 or 5 ) was determined at 3 and 6 months after injury , and the incidence of infective and total complications was determined during the hospital stay up to 6 months . MEASUREMENTS AND MAIN RESULTS Disease severity assessed by best preintubation Glasgow Coma Scale score , pupillary responses , Injury Severity Score , Acute Physiology and Chronic Health Evaluation II score , computed tomographic scan categorization , and age was similar in both groups . Intervention patients had a higher percentage of energy ( p = .0008 ) and nitrogen ( p<.0001 ) requirements met by EN in the first week after injury . Neurologic outcome at 6 months was similar between groups , but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients ( 61 % vs. 39 % , p = .08 ) . Fewer intervention patients had an infective complication ( 61 % vs. 85 % , p = .02 ) or more than one total complication ( 37 % vs. 61 % , p = .046 ) compared with control patients . Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury ( p = .004 ) . CONCLUSIONS Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses Objective To compare the initial ( D7 ) calorie intake and tolerability of two early enteral nutrition protocol s in which the optimal flow rate was introduced either immediately or gradually . Design Open , prospect i ve , r and omized study . Setting Two medical-surgical intensive care units . Patients One hundred consecutive intubated and mechanically ventilated patients . Interventions Early enteral nutrition was started within 24 h following intubation , and the optimal flow rate ( 25 Kcal/kg day−1 ) was either introduced immediately or reached in increments . Flow rate of the nutritional solution was adapted to the residual gastric volume , measured every 8 h , and the use of prokinetic agents was encouraged . Vomiting , regurgitation , colectasia , and suspected aspiration were defined as serious adverse events requiring withdrawal of enteral nutrition . Measurements and results When introduced immediately at optimal flow rate , early enteral nutrition led to a significant improvement in actual calorie supply ( p < 0.0001 ) . Although high residual gastric volume ( > 300 ml ) was more frequent when optimal flow rate was introduced immediately ( p = 0.04 ) , frequency of serious adverse events necessitating withdrawal of enteral nutrition was similar in the two groups ( p = 0.64 ) . Conclusions When residual gastric volume is measured regularly and prokinetic agents are used , enteral nutrition can be started early and be introduced at optimal dose regimen , thereby providing better calorie intake . Serious adverse events required early enteral nutrition withdrawal in only 15 patients , with no difference in frequency between the groups STUDY OBJECTIVES To assess the consistency of caloric intake with American College of Chest Physicians ( ACCP ) recommendations for critically ill patients and to evaluate the relationship of caloric intake with clinical outcomes . DESIGN Prospect i ve cohort study . SETTING Adult ICUs at two teaching hospitals . PARTICIPANTS Patients with an ICU length of stay of at least 96 h. MEASUREMENTS AND RESULTS On ICU admission , severity of illness ( ie , simplified acute physiology score II ) and markers of nutritional status ( ie , serum albumin level and body mass index ) were recorded . The route of feeding ( ie , enteral or parenteral ) , actual caloric intake ( ie , percentage of ACCP recommendations : 0 to 32 % [ tertile I ] ; 33 to 65 % [ tertile II ] ; > /== " BORDER="0 " > 66 % [ tertile III ] ) , and evidence of GI intolerance ( ie , gastric aspirate levels , > /== " BORDER="0 " > 100 mL ) were recorded daily . The following outcomes were assessed : status on hospital discharge ( alive vs dead ) ; spontaneous ventilation before ICU discharge ( yes vs no ) ; and ICU discharge without developing nosocomial sepsis ( yes vs no ) . The average caloric intake among 187 participants was 50.6 % of the ACCP targets and was similar in both hospitals . Caloric intake was inversely related to the mean number of gastric aspirates > /== " BORDER="0 " > 100 mL/d ( Spearman rho = -0.04 ; p = 0.06 ) , but not to severity of illness , nutritional status , or route of feeding . After accounting for the number of gastric aspirates > /== " BORDER="0 " > 100 mL , severity of illness , nutritional status , and route of feeding , tertile II of caloric intake ( vs tertile I ) was associated with a significantly greater likelihood of achieving spontaneous ventilation prior to ICU discharge . Tertile III of caloric intake ( vs tertile I ) was associated with a significantly lower likelihood of both hospital discharge alive and spontaneous ventilation prior to ICU discharge . CONCLUSIONS Study participants were underfed relative to ACCP targets . These targets , however , may overestimate needs , since moderate caloric intake ( ie , 33 to 65 % of ACCP targets ; approximately 9 to 18 kcal/kg per day ) was associated with better outcomes than higher levels of caloric intake OBJECTIVE We determined the variability in enteral feeding practice s in mechanically ventilated patients in four adult intensive care units of a tertiary-care , referral hospital . METHODS Patients who had been mechanically ventilated for at least 48 h and received enteral nutrition were prospect ively followed . RESULTS Fifty-five of 101 consecutive mechanically ventilated patients received enteral nutrition ; in 93 % of patients , feedings were infused into the stomach . Patients who were cared for in the medical intensive care unit , where a nutritional protocol was operational , received enteral nutrition earlier in their ventilatory course ( P=0.004 ) and feedings were advanced to target rates faster ( P=0.043 ) than those who received care in other units . The number ( P=0.243 ) and duration ( P=0.668 ) of interruptions in feeding did not differ by patient location . On average , patients received only 50 % to 70 % of their targeted caloric goals during the first 6 days of enteral nutrition . Most feeding discontinuations ( 41 % ) were secondary to procedures . Gastrointestinal intolerances , including vomiting , aspiration , abdominal distention , and increased gastric residuals , were uncommon despite allowing gastric residuals up to 300 mL. CONCLUSIONS The practice of providing enteral feeds to mechanically ventilated patients varies widely , even within one hospital . A protocol enhanced early initiation of enteral feeds and advancement to target feeding rates but did not alter the number or duration of interruptions in enteral feedings . Procedures represented the most common reason for stopping enteral feeds , and gastrointestinal intolerances ( vomiting , aspiration , and increased gastric residuals ) caused few feeding interruptions . The gastric route was safe and well tolerated for early enteral feeding in most mechanically ventilated patients Bacterial translocation from the gut may be the primary event in many disease processes . The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut . Each of 90 female Fischer rats underwent placement of a central venous catheter and was r and omized to one of three groups . Group I ( control ) received food and water ad libitum . Group II received st and ard TPN solution orally from a bottle sipper and drank the solution ad libitum . Group III underwent TPN via the central catheter by pair feeding of the animals with group II . Animals were fed for 2 weeks , and liver , spleen , mesenteric lymph nodes , blood , and cecum were aseptically obtained for culture . A statistically significant difference ( p less than 0.014 ) was found between translocation rates of parenterally fed animals compared with enterally fed animals . Two thirds of the animals ( 18/27 ) fed parenterally had culture-positive mesenteric lymph nodes compared with one third ( 9/27 ) of the enterally fed group and none ( 0/30 ) of the control group . A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution , independent of route . Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense BACKGROUND This study sought to compare 2 strategies for the administration of enteral feeding to mechanically ventilated medical patients . METHODS The prospect i ve , controlled , clinical trial was carried out in a medical intensive care unit ( 19 beds ) in a university-affiliated , urban teaching hospital . Between May 1999 and December 2000 , 150 patients were enrolled . Patients were scheduled to receive their estimated total daily enteral nutritional requirements on either day 1 ( early-feeding group ) or day 5 ( late-feeding group ) of mechanical ventilation . Patients in the late-feeding group were also scheduled to receive 20 % of their estimated daily enteral nutritional requirements during the first 4 days of mechanical ventilation . RESULTS Seventy-five ( 50 % ) consecutive eligible patients were entered into the early-feeding group and 75 ( 50 % ) patients were enrolled in the late-feeding group . During the 5 five days of mechanical ventilation , the total intake of calories ( 2370 + /- 2000 kcal versus 629 + /- 575 kcal ; p < .001 ) and protein ( 93.6 + /- 77.2 g versus 26.7 + /- 26.6 g ; p < .001 ) were statistically greater for patients in the early-feeding group . Patients in the early-feeding group had statistically greater incidences of ventilator-associated pneumonia ( 49.3 % versus 30.7 % ; p = .020 ) and diarrhea associated with Clostridium difficile infection ( 13.3 % versus 4.0 % ; p = .042 ) . The early-feeding group also had statistically longer intensive care unit ( 13.6 + /- 14.2 days versus 9.8 + /- 7.4 days ; p = .043 ) and hospital lengths of stay ( 22.9 + /- 19.7 days versus 16.7 + /- 12.5 days ; p = .023 ) compared with patients in the late-feeding group . No statistical difference in hospital mortality was observed between patients in the early-feeding and late-feeding groups ( 20.0 % versus 26.7 % ; p = .334 ) . CONCLUSIONS The administration of more aggressive early enteral nutrition to mechanically ventilated medical patients is associated with greater infectious complications and prolonged lengths of stay in the hospital . Clinicians must balance the potential for complications result ing from early enteral feeding with the expected benefits of such therapy Purpose The objective of this study was to examine the relationship between the amount of energy and protein administered and clinical outcomes , and the extent to which pre-morbid nutritional status influenced this relationship . Methods We conducted an observational cohort study of nutrition practice s in 167 intensive care units ( ICUs ) across 37 countries . Patient demographics were collected , and the type and amount of nutrition received were recorded daily for a maximum of 12 days . Patients were followed prospect ively to determine 60-day mortality and ventilator-free days ( VFDs ) . We used body mass index ( BMI , kg/m2 ) as a marker of nutritional status prior to ICU admission . Regression models were developed to evaluate the relationship between nutrition received and 60-day mortality and VFDs , and to examine how BMI modifies this relationship . Results Data were collected on 2,772 mechanically ventilated patients who received an average of 1,034 kcal/day and 47 g protein/day . An increase of 1,000 cal per day was associated with reduced mortality [ odds ratio for 60-day mortality 0.76 ; 95 % confidence intervals ( CI ) 0.61–0.95 , p = 0.014 ] and an increased number of VFDs ( 3.5 VFD , 95 % CI 1.2–5.9 , p = 0.003 ) . The effect of increased calories associated with lower mortality was observed in patients with a BMI < 25 and ≥35 with no benefit for patients with a BMI 25 to < 35 . Similar results were observed when comparing increasing protein intake and its effect on mortality . Conclusions Increased intakes of energy and protein appear to be associated with improved clinical outcomes in critically ill patients , particularly when BMI is < 25 or ≥35 OBJECTIVE This study was conducted to develop evidence -based clinical practice guidelines for nutrition support ( ie , enteral and parenteral nutrition ) in mechanically ventilated critically ill adults . OPTIONS The following interventions were systematic ally review ed for inclusion in the guidelines : enteral nutrition ( EN ) versus parenteral nutrition ( PN ) , early versus late EN , dose of EN , composition of EN ( protein , carbohydrates , lipids , immune-enhancing additives ) , strategies to optimize delivery of EN and minimize risks ( ie , rate of advancement , checking residuals , use of bedside algorithms , motility agents , small bowel versus gastric feedings , elevation of the head of the bed , closed delivery systems , probiotics , bolus administration ) , enteral nutrition in combination with supplemental PN , use of PN versus st and ard care in patients with an intact gastrointestinal tract , dose of PN and composition of PN ( protein , carbohydrates , IV lipids , additives , vitamins , trace elements , immune enhancing substances ) , and the use of intensive insulin therapy . OUTCOMES The outcomes considered were mortality ( intensive care unit [ ICU ] , hospital , and long-term ) , length of stay ( ICU and hospital ) , quality of life , and specific complications . EVIDENCE We systematic ally search ed MEDLINE and CINAHL ( cumulative index to nursing and allied health ) , EMBASE , and the Cochrane Library for r and omized controlled trials and meta-analyses of r and omized controlled trials that evaluated any form of nutrition support in critically ill adults . We also search ed reference lists and personal files , considering all articles published or unpublished available by August 2002 . Each included study was critically appraised in duplicate using a st and ard scoring system . VALUES For each intervention , we considered the validity of the r and omized trials or meta-analyses , the effect size and its associated confidence intervals , the homogeneity of trial results , safety , feasibility , and the economic consequences . The context for discussion was mechanically ventilated patients in Canadian ICUs . BENEFITS , HARMS , AND COSTS The major potential benefit from implementing these guidelines is improved clinical outcomes of critically ill patients ( reduced mortality and ICU stay ) . Potential harms of implementing these guidelines include increased complications and costs related to the suggested interventions . SUMMARIES OF EVIDENCE AND RECOMMENDATIONS : When considering nutrition support in critically ill patients , we strongly recommend that EN be used in preference to PN . We recommend the use of a st and ard , polymeric enteral formula that is initiated within 24 to 48 hours after admission to ICU , that patients be cared for in the semirecumbent position , and that arginine-containing enteral products not be used . Strategies to optimize delivery of EN ( starting at the target rate , use of a feeding protocol using a higher threshold of gastric residuals volumes , use of motility agents , and use of small bowel feeding ) and minimize the risks of EN ( elevation of the head of the bed ) should be considered . Use of products with fish oils , borage oils , and antioxidants should be considered for patients with acute respiratory distress syndrome . A glutamine-enriched formula should be considered for patients with severe burns and trauma . When initiating EN , we strongly recommend that PN not be used in combination with EN . When PN is used , we recommend that it be supplemented with glutamine , where available . Strategies that maximize the benefit and minimize the risks of PN ( hypocaloric dose , withholding lipids , and the use of intensive insulin therapy to achieve tight glycemic control ) should be considered . There are insufficient data to generate recommendations in the following areas : use of indirect calorimetry ; optimal pH of EN ; supplementation with trace elements , antioxidants , or fiber ; optimal mix of fats and carbohydrates ; use of closed feeding systems ; continuous versus bolus feedings ; use of probiotics ; type of lipids ; and mode of lipid delivery . VALIDATION This guideline was peer- review ed and endorsed by official representatives of the Canadian Critical Care Society , Canadian Critical Care Trials Group , Dietitians of Canada , Canadian Association of Critical Care Nurses , and the Canadian Society for Clinical Nutrition . SPONSORS This guideline is a joint venture of the Canadian Critical Care Society , the Canadian Critical Trials Group , the Canadian Society for Clinical Nutrition , and Dietitians of Canada . The Canadian Critical Care Society and the Institute of Nutrition , Metabolism , and Diabetes of the Canadian Institutes of Health Research provided funding for development of this guideline BACKGROUND AND AIMS Delivery of enteral nutrition ( EN ) in critical illness is often inadequate . This prospect i ve observational study addresses the implementation of enteral feeding in critically ill medical patients and its relation to energy expenditure . METHODS All admissions to a university medical ICU over a period of one year were screened . Patients receiving EN for at least 7 days were followed up . The caloric target was a minimum of 20 kcal/kg/day . The feeding volume was increased daily by 500 ml and a maximum of 2000 ml/day was targeted to be achieved by day 4 of admission . Energy expenditure was measured with indirect calorimetry on day 3 or 5 . RESULTS Two hundred and thirtyone patients required artificial nutrition , of which 61 patients were enterally fed for 7 days . This group was followed for a total of 750 feeding days . The gastric route was used at the start , with a post-pyloric feeding required during follow-up in 36.1 % of patients due to high gastric residual . EN was interrupted in 32.1 % of the feeding days . The daily administered volume was 86.2 + /- 30.4 % of the prescribed . The mean enteral caloric supply in relation to energy expenditure was between 39.2 + /- 34.6 % on day 1 and 83.1 + /- 31.1 % on day 6 . The targeted maximum feed volume was achieved on day 4 in 75.4 % of the patients . Patients with a delayed target time had a higher mortality rate than those with a target time of < 4 days ( 73.3 % vs. 26.1 % ) , CONCLUSIONS A high delivery-to-prescription rate could be achieved with a st and ardized enteral feeding protocol in critically ill medical patients . However , caloric delivery is much less than measured energy expenditure . Enteral feeding intolerance is associated with a high mortality rate BACKGROUND The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients . METHODS The study was conducted as a nested cohort study within a r and omized controlled trial in a tertiary care intensive care unit ( ICU ) . The main exposure in the study was average caloric intake/target for the first 7 ICU days . The primary outcomes were ICU and hospital mortality . Secondary outcomes included ICU-acquired infections , ventilator-associated pneumonia ( VAP ) , duration of mechanical ventilation days , and ICU and hospital length of stay ( LOS ) . The authors divided patients ( n = 523 ) into 3 tertiles according to the percentage of caloric intake/target : tertile I < 33.4 % , tertile II 33.4%-64.6 % , and tertile III > 64.6 % . To adjust for potentially confounding variables , the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes ( tertile I was used as reference ) and multiple linear regression for continuous outcomes . RESULTS Tertile III was associated with higher adjusted hospital mortality , higher risk of ICU-acquired infections , and a trend toward higher VAP rate . Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation , ICU LOS , and hospital LOS . CONCLUSIONS The data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality , ICU-acquired infections , mechanical ventilation duration , and ICU and hospital LOS . Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients |
2,642 | 28,771,484 | Lack of biological outcomes precludes assessing the link between CDI and HIV incidence | BACKGROUND Despite significant public health implication s , the extent to which community-based condom distribution interventions ( CDI ) prevent HIV infection in the United States is not well understood . | OBJECTIVES We evaluated the efficacy of skills training design ed to increase female condom use among women . METHODS We conducted a r and omized controlled trial of 409 women , recruited from family planning clinics in northern California , who were r and omly assigned to the experimental 4-session female condom skills training intervention or the comparison 4-session women 's general health promotion intervention . Participants received condom use instructions at baseline and male and female condoms during the study . They completed audio computer-assisted self-interviews at baseline and at 3 and 6 months . RESULTS At 3 and 6 months , women in the experimental group were more likely than those in the comparison group to have used the female condom at least once in the prior 3 months . The increase in the percentage of sexual acts protected by female condoms from baseline to the 6-month follow-up was greater for the experimental group . The percentage of sexual acts during which any condom was employed was higher in the experimental group at 6 months . There were no group differences in male condom use . CONCLUSIONS Outcomes suggest that skills training can increase female condom use and protected sexual acts without reducing male condom use among women PURPOSE We conducted an intervention to improve the implementation of a high school condom availability program , and evaluated its effect on students ' awareness of the program and acquisition of condoms . METHODS Twelve public high schools in the Los Angeles , CA area participated , half each in the intervention and control conditions . Project staff facilitated intervention schools ' self- assessment of compliance with the school district 's condom availability policy , creating an action plan by determining which m and atory program elements were lacking and identifying steps to improve compliance . Staff provided technical assistance and follow-up to assist schools in improving program implementation . From 2005 to 2009 ( T1-T5 ) , 29,823 students were r and omly selected by classroom and they completed surveys . We tested for changes in students ' awareness and acquisition of condoms over time between conditions using mixed model logistic regression analyses . Records of condom orders by schools also were review ed . RESULTS Awareness increased significantly among intervention versus control participants from T1 to T3 ( adjusted odds ratio [ AOR ] : 1.28 ; 95 % confidence interval [ CI ] : 1.01 , 1.62 ) , T4 ( AOR : 2.17 ; 95 % CI : 1.70 , 2.76 ) , and T5 ( AOR : 2.78 ; 95 % CI : 2.18 , 3.56 ) . Acquisition of condoms increased significantly among intervention versus control participants from T1 to T4 ( AOR : 1.69 ; 95 % CI : 1.23 , 2.32 ) and T5 ( AOR : 1.81 ; 95 % CI : 1.32 , 2.49 ) . Results were similar across gender and different levels of sexual experience . Orders of condoms increased markedly in intervention schools by T5 . CONCLUSIONS Feasible minor enhancements to condom availability program implementation improved program delivery , result ing in increased student awareness of the program and acquisition of condoms BACKGROUND HIV prevention intervention efficacy is often assessed in the short term . Thus , we conducted a long-term ( mean 4.4 years ) follow-up of a woman-focused HIV intervention for African American crack smokers , for which we had previously observed beneficial short-term gains . METHODS 455 out-of-treatment African American women in central North Carolina participated in a r and omized field experiment and were followed up to determine sustainability of intervention effects across three conditions : the woman-focused intervention , a modified NIDA intervention , and a delayed-treatment control condition . We compared these groups in terms of HIV risk behavior at short-term follow-up ( STFU ; 3 - 6 months ) and long-term follow-up ( LTFU ; average 4 years ) . RESULTS The analyses revealed two distinct groups at STFU : women who either eliminated or greatly reduced their risk behaviors ( low-risk class ) and women who retained high levels of risk across multiple risk domains ( high-risk class ) . At STFU , women in the woman-focused intervention were more likely to be in the low HIV risk group than the women in control conditions , but this effect was not statistically significant at LTFU . However , low-risk participants at STFU were less likely to be retained at LTFU , and this retention rate was lowest among women in the woman-focused intervention . CONCLUSIONS Short-term intervention effects were not observed over 4 years later , possibly due to differential retention across conditions . The retention of the highest risk women presents an opportunity to extend intervention effects through booster sessions for these women As part of the evaluation of a community-level HIV prevention program for women , this study examined predictors of exposure to print media and community outreach and assessed the relationship between exposure to the intervention and condom use behavior . Data from interviews with 479 women r and omly selected from the intervention community in 1995 and 1996 were examined . Analysis of demographic and risk characteristics were conducted to identify predictors of exposure to the project 's HIV prevention messages . Additionally , logistic regression analyses were conducted to examine the effects of intervention exposure on condom use , controlling for factors related to exposure . The results revealed that the print media campaign reached the largest number of women . However , women at highest risk did not have high rates of exposure to print media , but had greater exposure to outreach . Exposure to print media had an effect on increased communication with a main partner about condom use , but was not significantly related to condom use last time had sex . There were no significant main effects for exposure to outreach on condom use behavior . An important finding of this analysis was that each intervention strategy was successful in reaching a different portion of the target population and that exposure had differential effects on the condom use behavior of particular segments of the target population OBJECTIVES To analyze the benefits of a school-based condom availability program relative to the risks that such a program may incur . METHODS A confidentially-administered survey instrument was completed by 152 r and omly selected high-school students ( approximately 14 % of the entire student population ) . RESULTS The respondents had a mean age of 15.9 years ( range : 14 - 19 years ) and a proportionate gender distribution . Ninety-three percent of all respondents had " heard of " the school 's program and knew from whom they could receive condoms . Twenty-six percent of the respondents had received condoms from the program with 67 % using them . Of those receiving condoms but not using them , more than half did not need them , owing to absence of anticipated sexual activity . Of the nonreceivers , 53 % had never had sexual intercourse and 27 % received condoms from other sources . The benefit of the program by aiding a sexually-active student was found to be more than three times as great as the risk of encouraging a nonsexually active student to have sexual intercourse ( RR = 3.2 ; 95 % C.I. = 2.1 , 4.9 ) . The prevalence of sexual activity among all respondents was not significantly higher than the state 's average based on gender and age ( 59.8 % vs. 54.5 % ; z = 1.24 , p > .05 , n.s . ) . CONCLUSION Given the lack of increased sexual activity and the favorable benefit-risk ratio , we conclude that school-based condom availability is successfully utilized by sexually-active adolescents and may be an effective means to reduce potentially harmful outcomes , such as unintended pregnancy and sexually-transmitted diseases Despite strong protests from a minority group of critics , the New York City Board of Education adopted a measure February 27 , 1991 , approving universal availability of condoms in city high schools to students without the need for parental consent . This exp and ed HIV education program allows the system 's 261,000 students in 120 public high schools to procure condoms from any of 17 clinics and any teacher or staff member volunteering for the program . While a few , small U.S. school districts have implemented such programs in efforts to curb the incidence of HIV and other sexually transmitted diseases infections , and unwanted pregnancies , this move by New York city 's enormous school district could set the trend for similar action by other large school systems . The Centers for Disease Control document 691 cases of AIDS in youths aged 13 - 19 , and 7,303 among those aged 20 - 24 . More than 20 % of U.S. AIDS cases are among those aged 20 - 29 . Given the long incubation period for HIV , many if not most of these case probably stem from HIV infection during the teenage years . New York City accounts for 20 % of all reported AIDS cases among youths aged 13 - 21 , placing New York teens at disproportionate risk for infection . The number of infected adolescents doubles every 14 months . More than adults , these youths are likely to have contracted HIV through heterosexual contact instead of through IV-drug use or homosexual intercourse . Making condoms readily and confidentially available to adolescents , youths vulnerable to HIV infection will no longer fail to procure them due to embarrassment , fear of resistance from store clerks , and cost . The Youth News Service reveals youths to have been most supportive of the new program for several months , and anxious for its implementation . A r and om poll of adults found support for condom distribution in high schools and junior high schools to be 64 % and 47 % , respectively |
2,643 | 16,935,735 | Use of clinical practice guidelines , however , has been shown to positively affect clinical practice and patient outcomes across a wide variety of specialties | Clinical practice guidelines are systematic ally developed guidelines or statements design ed to assist the practitioner and /or patient in making appropriate health care decisions in specific clinical circumstances . | Background It is commonly stated that risk factors for postoperative nausea are the same as for vomiting . The authors design ed a prospect i ve study to identify and differentiate the risk factors for postoperative nausea and vomiting in various surgical population s in a clinical audit setting . Methods The study included 671 consecutive surgical in patients , aged 15 yr or more , undergoing various procedures . The study focused on postoperative nausea visual analog scale scores every 4 h and vomiting episodes within 72 h. Both vomiting and retching were considered as emetic events . Patient- , anesthesia- , and surgery-related variables that were considered to have a possible effect on the proportion of patients experiencing postoperative nausea and /or vomiting were examined . The bivariate Dale model for binary correlated outcomes was used to identify selectively the potential risk factors of postoperative nausea and vomiting . Results Among the 671 patients in the study , 126 ( 19 % ) reported one or more episodes of nausea , and 66 patients ( 10 % ) suffered one or more emetic episodes during the studied period . There was a highly significant association between the two outcomes . Some risk factors were predictive of both nausea and vomiting ( female gender , nonsmoking status , and general anesthesia ) . History of migraine and type of surgery were mainly responsible for nausea but not for vomiting . The predictive effect of risk factors was controlled for postoperative pain and analgesic drugs . Conclusion This study shows that differences exist in risk factors of postoperative nausea and vomiting . These could be explained by differences in the physiopathology of the two symptoms Background The safety and antiemetic efficacy of CP-122,721 , a novel neurokinin-1 antagonist , was evaluated when administered alone or in combination with ondansetron . Methods Using a r and omized , double-blind , placebo-controlled study design , CP-122,721 was initially compared with placebo and subsequently to ondansetron alone and in combination for prophylaxis against postoperative nausea and vomiting in 243 women undergoing abdominal hysterectomy . In the dose-ranging studies ( n = 86 ) , patients received either CP-122,721 100 mg ( vs. placebo ) or 200 mg ( vs. placebo ) orally 60–90 min before induction of anesthesia . In the interaction study ( n = 157 ) , patients received CP-122,721 200 mg or placebo 60–90 min before induction of anesthesia , and ondansetron 4 mg or saline 2 ml intravenously 15–30 min before the end of surgery . Patients assessed their level of nausea and pain on arrival in the postanesthesia care unit and at 0.5- , 1- , 1.5- , 2- , 4- , 8- , 12- , and 24-h intervals postoperatively . Emetic episodes , need for rescue antiemetic – antinausea medication , postoperative complications , and patient satisfaction were recorded . Results In the initial dose-ranging study , only 10 % of the patients experienced emesis within the first 8 h after surgery with CP-122,721 200 mg compared with 50 % in the placebo group . CP-122,721 200 mg also decreased the need for rescue medication ( 25%vs . 48 % ) . CP-122,721 100 mg was less effective than 200 mg in decreasing the incidence of repeated episodes of emesis . In the interaction study , 6 % of the patients receiving CP-122,721 200 mg orally experienced emesis less than 2 h after surgery compared with 17 % with ondansetron alone . With combined therapy , only 2 % experienced emesis . In addition , the median times for 75 % of patients to remain free from postoperative nausea and vomiting were 82 , 75 , and 362 min in the ondansetron , CP-122,721 , and combination groups , respectively . Conclusions Oral CP-122,721 200 mg decreased emetic episodes compared with ondansetron ( 4 mg intravenously ) during the first 24 h after gynecologic surgery ; however , there was no difference in patient satisfaction Supplemental 80 % oxygen administration halves the incidence of postoperative nausea and vomiting ( PONV ) in in patients . Whether it prevents PONV after ambulatory surgery is unknown . We tested the efficacy of supplemental 80 % oxygen in decreasing the incidence of PONV after ambulatory gynecologic laparoscopy . One hundred patients were given a st and ardized sevoflurane anesthetic . They were r and omly assigned to two groups : routine oxygen administration with 30 % oxygen , balance nitrogen ( Group A ) ; and supplemental oxygen with 80 % oxygen , balance nitrogen ( Group B ) . Oxygen was administered during surgery and up to 1 h after surgery . The incidence of nausea and vomiting and the need for rescue antiemetics did not differ between the groups in the postanesthesia care unit , in the Phase II unit , or during the 24-h follow-up . The overall incidence of nausea and vomiting during the first postoperative 24 h was 62 % in Group A and 55 % in Group B ( P = 0.486 ) . There were no differences in the recovery profiles and patient satisfaction between the groups . In this study , supplemental oxygen did not prevent PONV in patients undergoing ambulatory gynecologic laparoscopy Postoperative nausea , a common complication in patients receiving general anesthesia , was studied in this r and omized investigation to compare the efficacy of 70 % inhaled isopropyl alcohol and intravenous ondansetron . For the study , 100 healthy women , ASA physical status I or II , scheduled for outpatient gynecologic laparoscopic procedures r and omly received 4 mg of intravenous ondansetron or isopropyl alcohol for the treatment of postoperative nausea . Nausea was measured on arrival to the postanesthesia care unit , at first complaint of nausea , every 5 minutes after initiation of therapy until nausea resolution , and every 15 minutes thereafter using a 0 to 10 verbal numerical rating scale . At 5 , 10 , and 15 minutes , the median verbal numerical rating scores between the ondansetron and alcohol groups were 6.00 and 3.00 , 5.00 and 3.00 , and 5.00 and 2.00 , respectively ( P = .002 , .015 , and .036 , respectively ) . No statistically significant differences were found at any other time interval . Mean times from initiation of therapy to a 50 % reduction in nausea between the ondansetron and alcohol groups were 6.3 minutes and 27.7 minutes , respectively ( P = 0.022 ) . Based on this study , it seems postoperative nausea can be resolved quicker using 70 % inhaled isopropyl alcohol compared with intravenous ondansetron in women undergoing outpatient gynecologic laparoscopic procedures Background : The aim of this study was to identify factors most relevant for postoperative vomiting ( PV ) and to develop a risk score to predict the probability of PV In this double-blind , r and omized , parallel group study , we have investigated the antiemetic activity of the potent and selective NK1 receptor antagonist GR205171 25 mg i.v . compared with placebo in the treatment of established postoperative nausea and vomiting ( PONV ) in patients after major gynaecological surgery performed under general anaesthesia . The incidence of PONV in the study population was 65 % . Thirty-six patients were treated with placebo or GR205171 ( 18 patients per group ) . GR205171 produced greater control of PONV than placebo over the 24-h assessment period . The stimuli for emesis after PONV are multifactorial and the efficacy of GR205171 in this study supports the broad spectrum potential for NK1 receptor antagonists in the management of postoperative emesis . GR205171 was well tolerated and no adverse events were reported that would preclude the further development of this agent BACKGROUND Iletrospective studies fail to identify predictors of postoperative nausea and vomiting ( PONV ) . The authors prospect ively studied 17,638 consecutive out patients who had surgery to identify predictors . METHODS Data on medical conditions , anesthesia , surgery , and PONV were collected in the post-anesthesia care unit , in the ambulatory surgical unit , and in telephone interviews conducted 24 h after surgery . Multiple logistic regression with backward stepwise elimination was used to develop a predictive model An independent set of patients was used to vali date the model RESULTS Age ( younger or older ) , sex ( female or male ) , smoking status ( nonsmokers or smokers ) , previous PONV , type of anesthesia ( general or other ) , duration of anesthesia ( longer or shorter ) , and type of surgery ( plastic , orthopedic shoulder , or other ) were independent predictors of PONV . A 10-yr increase in age decreased the likelihood of PONV by 13 % . The risk for men was one third that for women . A 30-min increase in the duration of anesthesia increased the likelihood of PONV by 59 % . General anesthesia increased the likelihood of PONV 11 times compared with other types of anesthesia . Patients with plastic and orthopedic shoulder surgery had a sixfold increase in the risk for PONV . The model predicted PONV accurately and yielded an area under the receiver operating characteristic curve of 0.785+/-0.011 using an independent validation set . CONCLUSIONS A vali date d mathematical model is provided to calculate the risk of PONV in out patients having surgery . Knowing the factors that predict PONV will help anesthesiologists determine which patients will need antiemetic therapy Background : At dosages above 0.1 mg/kg , droperidol inducesa dose-dependent QTc interval prolongation . Although subject to controversy , low-dose droperidol has recently been suspected to induce cardiac arrhythmias . Hence , 5-hydroxytryptamine type 3 antagonists have become the first-line drug for management of postoperative nausea and vomiting . These drugs are also known to prolong the QTc interval at high dosages . This study describes QTc interval changes associated with postoperative nausea and vomiting treatment by droperidol or ondansetron at low doses . Methods : Eighty-five patients with postoperative nausea and vomiting were included in this prospect i ve , single-blind study . Patients received either 0.75 mg intravenous droperidol ( n = 43 ) or 4 mg intravenous ondansetron ( n = 42 ) . Electrocardiographic recordings were obtained before administration of antiemetic drug and then 1 , 2 , 3 , 5 , 10 , and 15 min after . Electrocardiographic monitoring was maintained for 3 h in eight patients in each group . Results : The QTc interval was prolonged ( > 450 ms in men , > 470 ms in women ) in 21 % of the patients before antiemetic drug administration . This was significantly correlated with lower body temperature and longer duration of anesthesia . Compared with predrug QTc measurement , both antiemetics were associated with a significant QTc interval prolongation ( P < 0.0001 ) . The mean maximal QTc interval prolongation was 17 ± 9 ms after droperidol occurring at the second minute and 20 ± 13 ms after ondansetron at the third minute ( both P < 0.0001 ) . Compared with predrug measurement , the QTc interval was significantly lower after the 90th minute in both groups . Conclusions : Droperidol and ondansetron induced similar clinical ly relevant QTc interval prolongations . When used in treatment of postoperative nausea and vomiting , a situation where prolongation of the QTc interval seems to occur , the safety of 5-hydroxytryptamine type 3 antagonists may not be superior to that of low-dose droperidol BACKGROUND Supplemental intra-operative oxygen 80 % halves the incidence of nausea and vomiting after open and laparoscopic abdominal surgery , perhaps by ameliorating intestinal ischaemia associated with abdominal surgery . It is unlikely that thyroid surgery compromises intestinal perfusion . We therefore tested the hypothesis that supplemental perioperative oxygen does not reduce the risk of postoperative nausea and vomiting ( PONV ) after thyroidectomy . METHODS One hundred and fifty patients undergoing thyroidectomy were given sevoflurane anaesthesia . After induction , patients were r and omly assigned to the following treatments : ( i ) . 30 % oxygen , ( ii ) . 80 % oxygen , or ( iii ) . 30 % oxygen with droperidol 0.625 mg . RESULTS The overall incidence of nausea during the first 24 h after surgery was 48 % in the patients given oxygen 30 % , 46 % in those given oxygen 80 % , and 22 % in those given droperidol ( P=0.004 ) . There were no significant differences between the oxygen 30 % and 80 % groups in incidence or severity of PONV , the need for rescue antiemetics , or patient satisfaction . Droperidol significantly shortened the time to first meal . CONCLUSIONS Supplemental oxygen was ineffective in preventing nausea and vomiting after thyroidectomy , but droperidol reduced the incidence BACKGROUND Despite intensive research , the main causes of postoperative nausea and vomiting ( PONV ) remain unclear . We sought to quantify the relative importance of operative , anaesthetic and patient-specific risk factors to the development of PONV . METHODS We conducted a r and omized controlled trial of 1180 children and adults at high risk for PONV scheduled for elective surgery . Using a five-way factorial design , we r and omly assigned subjects by gender who were undergoing specific operative procedures , to receive various combinations of anaesthetics , opioids , and prophylactic antiemetics . RESULTS Of the 1180 patients , 355 ( 30.1 % 95 % CI ( 27.5 - 32.7 % ) ) had at least one episode of postoperative vomiting ( PV ) within 24 h post-anaesthesia . In the early postoperative period ( 0 - 2 h ) , the leading risk factor for vomiting was the use of volatile anaesthetics , with similar odds ratios ( OR ( 95 % CI ) ) being found for isoflurane ( 19.8 ( 7.7 - 51.2 ) ) , enflurane ( 16.1 ( 6.2 - 41.8 ) ) and sevoflurane ( 14.5 ( 5.6 - 37.4 ) ) . A dose-response relationship was present for the use of volatile anaesthetics . In contrast , no dose response existed for propofol anaesthesia . In the delayed postoperative period ( 2 - 24 h ) , the main predictors were being a child ( 5.7 ( 3.0 - 10.9 ) ) , PONV in the early period ( 3.4 ( 2.4 - 4.7 ) ) and the use of postoperative opioids ( 2.5 ( 1.7 - 3.7 ) ) . The influence of the antiemetics was considerably smaller and did not interact with anaesthetic or surgical variables . CONCLUSION Volatile anaesthetics were the leading cause of early postoperative vomiting . The pro-emetic effect was larger than other risk factors . In patients at high risk for PONV , it would therefore make better sense to avoid inhalational anaesthesia rather than simply to add an antiemetic , which may still be needed to prevent or treat delayed vomiting The authors evaluated the effect of transdermal scopolamine on the incidence of postoperative nausea , retching , and vomiting after outpatient laparoscopy in a double-blind , placebo-controlled study . A B and -Aid-like patch containing either scopolamine or placebo was placed behind the ear the night before surgery . Anesthesia was induced with fentanyl ( 0.5 - 2 micrograms/kg iv ) , thiopental ( 3 - 5 mg/kg iv ) , and succinylcholine ( 1 - 1.5 mg/kg iv ) and maintained with isoflurane ( 0.2 - 2 % ) and nitrous oxide ( 60 % ) in oxygen . Scopolamine-treated patients had less nausea , retching , and vomiting compared with placebo-treated patients ( P = 0.0029 ) . Severe nausea and /or vomiting was present in 62 % of the placebo group but only 37 % of those getting the scopolamine patch . Repeated episodes of retching and vomiting were also less frequent in the scopolamine group compared with the placebo group ( 23 % vs. 41 % ; P = 0.0213 ) as was the need for additional antiemetic therapy ( 13 % vs. 32 % ; P = 0.0013 ) . Patients in the scopolamine group were also discharged from the hospital sooner ( 4 + /- 1.3 vs. 4.5 + /- 1.5 h ; P = 0.0487 ) . Side effects were more frequent among those patients treated with the scopolamine patch ( 91 % vs. 45 % ; P less than 0.05 ) but were not troublesome . The authors conclude that transdermal scopolamine is a safe and effective antiemetic for out patients undergoing laparoscopy A prospect i ve interview‐based survey on the incidence of postoperative nausea and vomiting in 1107 in‐ patients aged 4–86 years was conducted during a 3‐month period . Nausea , emetic episodes and the need for anti‐emetic medication were recorded for 24 h postoperatively . In the recovery room , the incidence of nausea and vomiting was 18 % and 5 % , respectively . Over the whole 24‐h period , these figures were 52 % and 25 % , respectively ; severe nausea was experienced by 8 % . The highest incidence of emetic sequelae was observed in gynaecological patients ; 52 % of the 822 patients who received general anaesthesia and 38 % of the 285 patients who received regional anaesthesia reported nausea . The most important predictive factors associated with an increased risk for nausea and vomiting were female gender , a previous history of postoperative sickness , a longer duration of surgery , nonsmoking and a history of motion sickness . Based on these five items , a simple score predicting the risk of nausea and vomiting was constructed with a moderately good discriminating power In a prospect i ve , double‐blind , r and omised controlled trial , we studied the effects of pre‐operative fluid load on post‐operative nausea and vomiting . Eighty patients attending for laparoscopic cholecystectomy or gynaecological surgery were r and omly allocated to receive 2 ml.kg−1 ( conservative ) or 15 ml.kg−1 ( supplemental ) Hartmann 's solution intravenously , shortly before induction of anaesthesia . During the operation , fluid management was identical in both groups . During the first post‐operative 24 h , post‐operative nausea and vomiting occurred in 29 patients ( 73 % ) in the conservative fluid group and nine patients ( 23 % ) in the supplemental fluid group ( p = 0.01 ) . Supplemental pre‐operative fluid is an inexpensive and safe therapy for reducing post‐operative nausea and vomiting Postoperative nausea and vomiting ( PONV ) is one of the most common postoperative complications . Aside from pharmacological interventions , other complementary healing modalities have been introduced to assist patients in decreasing PONV and improving postoperative outcomes . This study examined acupressure as a potentially holistic and safe complement to the more traditional approach of using drugs to prevent and /or relieve nausea and vomiting in the postoperative patient . Acupressure involves constant pressure ( without puncture of the skin ) on the Nei Guan acupuncture points through the use of a British product called Sea-B and s ( Sea B and UK Ltd , Leics , Engl and ) . These b and s are made of elasticated fabric , with a small round plastic button inside . A quasi-experimental research design was used to examine the effects of unilateral and bilateral application of acupressure on 157 patients who are prone to PONV : postgynecological , postplastic , and posturological surgery patients . The incidence of PONV was determined through retrospective chart review s. The hypothesis was that there would be a difference in the incidence of PONV between 5 groups : group 1 ( Sea-B and s with acupressure on both wrists ) , group 2 ( Sea-B and s with acupressure on one wrist ) , group 3 ( wristb and without acupressure on both wrists ) , group 4 ( wristb and without acupressure on one wrist ) , and group 5 ( no wristb and ) . This hypothesis was examined by using a one-way analysis of variance ( ANOVA ) ; it was not supported . Neither unilateral nor bilateral application of acupressure significantly affected the incidence of nausea and vomiting . These findings must be viewed with caution , however , because power analysis showed low effect sizes and an inadequate sample size . Further research is recommended with a larger sample size . This study has made perianesthesia nurses more aware of other complementary modalities to assist patients with nausea and vomiting We prospect ively studied the relationship between interdisciplinary collaboration and patient outcomes in the medical intensive care unit ( MICU ) using nurses ' and residents ' reports of amount of collaboration involved in making decisions about transferring patients from the MICU to a unit with a less intense level of care . Either readmission to the MICU or death was considered a negative patient outcome . Nurses ' reports of collaboration were significantly ( p = 0.02 ) and positively associated with patient outcome , controlling for severity of illness . Patient predicted risk of negative outcome decreased from 16 % , when the nurse reported no collaboration in decision making , to 5 % when the process was fully collaborative . There was an interaction of collaboration with availability of alternative choices in the transfer decision-making situation . When alternatives were available , collaboration was more strongly associated with patient outcome . There was no significant relationship between residents ' reports of collaboration and patient outcomes . The correlation between amount of collaboration reported by nurses and residents about the same decisions was quite low ( r = 0.10 ) BACKGROUND I.V. fluid administration has been shown to reduce postoperative nausea and vomiting ( PONV ) . The optimum dose is unknown . We tested the hypothesis that administration of i.v . crystalloid of 30 ml kg(-1 ) would reduce the incidence of PONV compared with 10 ml kg(-1 ) of the same fluid . METHODS A total of 141 ASA I female patients undergoing elective gynaecological laparoscopy were r and omized , in double-blind fashion , to receive either 10 ml kg(-1 ) ( n=71 ; CSL-10 group ) or 30 ml kg(-1 ) ( n=70 ; CSL-30 group ) of i.v . compound sodium lactate ( CSL ) . RESULTS In the first 48 h after anaesthesia , the incidence of vomiting was lower in the CSL-30 group than in the CSL-10 group ( 8.6 % vs 25.7 % , P=0.01 ) . Anti-emetic use was less in the CSL-30 group at 0.5 h ( 2.9 % vs 14.3 % , P=0.04 ) . The incidence of severe nausea was significantly reduced in the treatment group at awakening ( 2.9 % vs 15.7 % , P=0.02 ) , 2 h ( 0.0 % vs 8.6 % , P=0.04 ) and cumulatively ( 5.7 % vs 27.1 % , P=0.001 ) . The numbers needed to treat to prevent vomiting , severe nausea and antiemetic use in the first 48 h were 6 , 5 and 6 , respectively . CONCLUSION I.V. administration of CSL 30 ml kg(-1 ) to healthy women undergoing day-case gynaecological laparoscopy reduced the incidence of vomiting , nausea and anti-emetic use when compared with CSL 10 ml kg(-1 ) Background : Postoperative nausea and vomiting ( PONV ) is a distressing problem after strabismus surgery . An inspired oxygen fraction has been reported to decrease PONV in patients after colon resection and to be more effective than ondansetron after gynecologic laparoscopy . Therefore , in a r and omized , prospect i ve , placebo-controlled study , the authors tested whether an inspired oxygen fraction of 0.8 decreases PONV in patients undergoing strabismus surgery and whether oxygen is more effective than ondansetron . Methods : With approval of the authors ’ institutional review board , 210 patients were r and omly assigned to receive one of three treatments : ( 1 ) 30 % inspired oxygen in air plus intravenous administration of saline , ( 2 ) 80 % inspired oxygen in air plus intravenous administration of saline , or ( 3 ) 30 % inspired oxygen in air plus 75 & mgr;g/kg ondansetron intravenously during induction . General anesthesia was st and ardized and included etomi date , alfentanil , and mivacurium for induction and sevoflurane for maintenance . PONV was evaluated 6 and 24 h postoperatively by an investigator unaware of treatment assignment . Results : Overall postoperative incidence of nausea and vomiting was 41 % for inspired oxygen fraction of 0.3 plus placebo , 38 % for inspired oxygen fraction of 0.8 plus placebo , and 28 % for inspired oxygen fraction of 0.3 plus ondansetron , respectively ( P = 0.279 ) . Therefore , there was no statistically significant difference of PONV incidence among groups . Conclusions : An inspired oxygen fraction of 0.8 during general anesthesia with sevoflurane does not decrease PONV in patients undergoing strabismus repair . Ondansetron also did not significantly decrease PONV in our study setting The potential for preoperative IV rehydration to reduce postoperative nausea and vomiting ( PONV ) and pain in patients undergoing ambulatory surgery remains unclear , with conflicting results reported . We sought to determine whether preoperative IV rehydration with a balanced salt solution would decrease the incidence of PONV in patients at increased risk for these symptoms . Eighty ASA grade I – III patients presenting for gynecologic laparoscopy were r and omized to receive large ( 2 mL/kg per hour fasting ) or small ( 3 mL/kg ) volume infusions of compound sodium lactate solution over 20 min preoperatively . A st and ardized balanced anesthetic was used . The incidence and severity of PONV and pain , and need for supplemental antiemetic and analgesic therapy , were assessed by a blinded investigator at 0.5 , 1 , and 4 h postoperatively , and on the first and third postoperative days . The incidence ( control 87 % versus large volume 59 % ) and severity of PONV were significantly reduced in the large volume infusion group at all time intervals . The large volume infusion group also had decreased postoperative pain scores and required less supplemental analgesia . Preoperative correction of intravascular volume deficits effectively reduces PONV and postoperative pain in high risk patients presenting for ambulatory surgery . We recommend the preoperative administration of 2 mL/kg of compound sodium lactate for every hour of fasting to patients with an increased PONV risk presenting for ambulatory surgery OBJECTIVE To investigate the association of collaboration between intensive care unit ( ICU ) physicians and nurses and patient outcome . DESIGN Prospect i ve , descriptive , correlational study using self-report instruments . SETTING S A community teaching hospital medical ICU , a university teaching hospital surgical ICU , and a community non-teaching hospital mixed ICU , all in upstate New York . SUBJECTS Ninety-seven attending physicians , 63 resident physicians , and 162 staff nurses . PROCEDURE When patients were ready for transfer from the ICU to an area of less intensive care , question naires were used to assess care providers ' reports of collaboration in making the transfer decision . After controlling for severity of illness , the association between interprofessional collaboration and patient outcome was assessed . Unit-level organizational collaboration and patient outcomes were ranked . MEASURES Healthcare providers ' reported levels of collaboration , patient severity of illness and individual risk , patient outcomes of death or readmission to the ICU , unit-level collaboration , and unit patient risk of negative outcome . MAIN RESULTS Medical ICU nurses ' reports of collaboration were associated positively with patient outcomes . No other associations between individual reports of collaboration and patient outcome were found . There was a perfect rank order correlation between unit-level organizational collaboration and patient outcomes across the three units . CONCLUSIONS The study offered some support for the importance of physician-nurse collaboration in ICU care delivery , a variable susceptible to intervention and further study To determine whether aromatherapy can reduce postoperative nausea , the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU . After indicating the severity of nausea on a 100-mm visual analogue scale ( VAS ) , subjects received r and omized aromatherapy with isopropyl alcohol , oil of peppermint , or saline ( placebo ) . The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients ' nostrils and exhaled slowly through the mouth . Two and 5 minutes later , the subjects rated their nausea on the VAS . Overall nausea scores decreased from 60.6 + /- 4.3 mm ( mean + /- SE ) before aromatherapy to 43.1 + /- 4.9 mm 2 minutes after aromatherapy ( P < .005 ) , and to 28.0 + /- 4.6 mm 5 minutes after aromatherapy ( P < 10(-6 ) ) . Nausea scores did not differ between the treatments at any time . Only 52 % of the patients required conventional intravenous ( IV ) antiemetic therapy during their PACU stay . Overall satisfaction with postoperative nausea management was 86.9 + /- 4.1 mm and was independent of the treatment group . Aromatherapy effectively reduced the perceived severity of postoperative nausea . The fact that a saline " placebo " was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled STUDY OBJECTIVES To compare repeat intravenous ( i.v . ) dosing of ondansetron 4 mg with placebo for the treatment of postoperative nausea and vomiting ( PONV ) in patients for whom prophylactic , preoperative ondansetron 4 mg i.v . was inadequate DESIGN R and omized , double-blind , placebo-controlled study . SETTING Ten outpatient surgical centers in the United States . PATIENTS 2,199 male and female ASA physical status I , II , and III patients > or = 12 years old scheduled to undergo outpatient surgical procedures and receive nitrous oxide-based general anesthesia . INTERVENTIONS Ondansetron 4 mg i.v . was administered to all patients before induction of general anesthesia . Patients who experienced PONV or requested antiemetic therapy within 2 hours after discontinuation of inhaled anesthesia were r and omized ( 1:1 ) to either a repeat i.v . ondansetron 4 mg dose or placebo . MEASUREMENTS AND MAIN RESULTS Of the 2,199 patients prophylactically treated with ondansetron 4 mg before anesthesia induction , 1,771 ( 80.5 % ) did not experience PONV or request antiemetic therapy during the 2 hours following discontinuation of anesthesia . Of the 428 patients who experienced PONV or requested antiemetic therapy during the same period , and were r and omized to additional treatment ( 214 r and omized to ondansetron , 214 r and omized to placebo ) , the incidence of complete response ( no emesis , no rescue medication , no study withdrawal ) was similar for both ondansetron-r and omized and placebo-r and omized groups for the 2-hour ( 34 % and 43 % , respectively , p = 0.074 ) and 24-hour ( 28 % and 32 % , respectively , p = 0.342 ) postr and omization study periods . Repeat ondansetron dosing was not more effective than placebo in controlling either postoperative emesis or the severity/ duration of postoperative nausea . The administration of an additional dose of ondansetron 4 mg postoperatively did not result in an increased incidence of adverse effects . CONCLUSIONS In patients for whom preoperative prophylaxis with ondansetron 4 mg i.v . is not successful , a repeat dose of ondansetron 4 mg i.v . in the postanesthesia care unit does not appear to offer additional control of PONV We prospect ively examined the incidence of postoperative nausea and vomiting ( PONV ) in a group of 193 elderly surgical in patients receiving no postoperative antiemetic prophylaxis . Risk factors for PONV and detailed data on postoperative opioid use were recorded . The overall postoperative vomiting ( POV ) rate was 23.8 % , whereas postoperative nausea ( PON ) was 51.3 % . Opioid use ( P = 0.025 ) , and female gender ( P = 0.038 ) were identified as significantly influencing POV in this relatively small population . There was a strong logarithmic dose-response relationship between postoperative opioid dose and POV ( r2 = 0.98 , P < 0.01 ) , as well as PON ( r2 = 0.98 , P = 0.01 ) . Use of patient-controlled analgesia or epidural analgesia was a marker for large-dose opioid use ( P < 0.001 ) and was associated with POV in the 24-h postoperative period of 41 % and 31 % respectively , compared with 11 % for other patients ( P < 0.001 ) . Future studies defining risk factors for POV should treat postoperative opioid use as a continuous variable , rather than treat it as a dichotomous variable A carbohydrate‐rich drink ( CHO ) has been shown to reduce preoperative discomfort . It was hypothesized that it may also reduce postoperative nausea and vomiting ( PONV ) One hundred and forty-seven patients undergoing minor orthopaedic surgery were studied prospect ively by logistic regression analysis to determine the association of independent fixed patient factors with the incidence of postoperative sickness ( nausea , retching or vomiting ) . Gender , history of previous postoperative sickness , postoperative opioids and interaction between gender and previous history of sickness were significant independent factors for postoperative sickness ; history of motion sickness was weakly associated . The probability of postoperative sickness in the first 24 h after surgery may be estimated from the equation : logit postoperative sickness = -5.03 + 2.24(postoperative opioids ) + 3.97 ( previous sickness history ) + 2.4 ( gender ) + 0.78 ( motion sickness ) -3.2 ( gender x previous sickness history ) . ( Log likelihood ratio test for 5 degrees of freedom for the coefficients , chi-square = 53.5 ( P < 0.001 ) . ) It is suggested that the calculated probability for sickness may be a useful addition for balancing patient treatment groups and allowing between- study comparisons Background The mechanisms for postoperative nausea and vomiting are numerous and pathways not well eluci date d. Although many medications have been developed to help prevent postoperative nausea and vomiting , the search for better approaches to recovery treatment continues . Objective The purpose of this study was to evaluate the effectiveness of isopropyl alcohol ( IPA ) inhalation for treatment of postoperative nausea and vomiting for patients who have general anesthesia for a surgical procedure . Method Participants were recruited from an urban hospital on the East Coast of the United States . Participants were assigned to an experimental or control group and IPA inhalation was compared to the st and ard anti-emetic treatment for rescue treatment in the immediate postoperative period . Postoperative nausea and vomiting was rated using a descriptive ordinal scale . Results The results of this study show IPA to be effective and that there was no significant difference between the st and ard treatment protocol and treatment with IPA . Treatment with IPA was significantly more cost effective than st and ard drug treatment . Discussion Further research is recommended to evaluate the length of effectiveness , st and ard dose needed , most effective mode of inhalation , and factors blocking IPA effectiveness Objective : The objective of this study was to investigate the effects of 2 levels of intraoperative fluid administration on perioperative physiology and outcome after laparoscopic cholecystectomy . Summary Background Data : Intraoperative fluid administration is variable as a result of limited knowledge of physiological and clinical effects of different fluid substitution regimens . Methods : In a double-blind study , 48 ASA I – II patients undergoing laparoscopic cholecystectomy were r and omized to 15 mL/kg ( group 1 ) or 40 mL/kg ( group 2 ) intraoperative administration of lactated Ringer ’s solution ( LR ) . All other aspects of perioperative management as well as preoperative fluid status were st and ardized . Primary outcome parameters were assessed repeatedly for the first 24 postoperative hours and included pulmonary function ( spirometry ) , exercise capacity ( submaximal treadmill test ) , cardiovascular hormonal responses , balance function , pain , nausea and vomiting , recovery , and hospital stay . Results : Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR led to significant improvements in postoperative pulmonary function and exercise capacity and a reduced stress response ( aldosterone , antidiuretic hormone , and angiotensin II ) . Nausea , general well-being , thirst , dizziness , drowsiness , fatigue , and balance function were also significantly improved , as well as significantly more patients fulfilled discharge criteria and were discharged on the day of surgery with the high-volume fluid substitution . Conclusions : Intraoperative administration of 40 mL/kg compared with 15 mL/kg LR improves postoperative organ functions and recovery and shortens hospital stay after laparoscopic cholecystectomy IMPLICATION S Ondansetron orally disintegrating tablet reduces postdischarge nausea and vomiting and improves patient satisfaction with postoperative nausea and vomiting management BACKGROUND Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied , the authors design ed a r and omized , double-blind , placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol ( 0.625 and 1.25 mg intravenous ) on the QT interval when used for antiemetic prophylaxis during general anesthesia . METHODS One hundred twenty out patients undergoing otolaryngologic procedures with a st and ardized general anesthetic technique were enrolled in this study . After anesthetic induction and before the surgical incision , 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml . A st and ard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period . The QTc ( QT interval corrected for heart rate ) was evaluated from the recorded electrocardiographic strips . In 60 additional patients , a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc . Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted . RESULTS Intravenous droperidol , 0.625 and 1.25 mg , prolonged the QT interval by an average of 15 + /- 40 and 22 + /- 41 ms , respectively , at 3 - 6 min after administration during general anesthesia , but these changes did not differ significantly from that seen with saline ( 12 + /- 35 ms ) ( all values mean + /- SD ) . There were no statistically significant differences among the three study groups in the number of patients with greater than 10 % prolongation in QTc ( vs. baseline ) . Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period , there was no evidence of droperidol-induced QTc prolongation after surgery . Finally , there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period . CONCLUSION Use of a small dose of droperidol ( 0.625 - 1.25 mg intravenous ) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline . More importantly , there was no evidence of any droperidol-induced QTc prolongation immediately after surgery |
2,644 | 20,421,859 | Individual high- quality trials provided moderate evidence that stabilization exercises are more effective than no treatment , that manipulation is more effective than sham manipulation for people with acute symptoms and an intact anulus , and that no difference exists among traction , laser , and ultrasound .
Adverse events were associated with traction ( pain , anxiety , lower limb weakness , and fainting ) and ibuprofen ( gastrointestinal events ) .
Advice is less effective than microdiscectomy in the short term but equally effective in the long term for people who have LDHR .
Moderate evidence favors stabilization exercises over no treatment , manipulation over sham manipulation , and the addition of mechanical traction to medication and electrotherapy .
There was no difference among traction , laser , and ultrasound .
Adverse events were associated with traction and ibuprofen . | OBJECTIVE To determine the efficacy and adverse effects of conservative treatments for people who have lumbar disc herniation with associated radiculopathy ( LDHR ) .
SUMMARY OF BACKGROUND DATA Although conservative management is commonly used for people who have LDHR , the efficacy and adverse effects of conservative treatments for this condition are unclear . | Abstract This single-blind r and omised clinical trial compared osteopathic manipulative treatment with chemonucleolysis ( used as a control of known efficacy ) for symptomatic lumbar disc herniation . Forty patients with sciatica due to this diagnosis ( confirmed by imaging ) were treated either by chemonucleolysis or manipulation . Outcomes ( leg pain , back pain and self-reported disability ) were measured at 2 weeks , 6 weeks and 12 months . The mean values for all outcomes improved in both groups . By 12 months , there was no statistically significant difference in outcome between the treatments , but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks . A similar number from both groups required additional orthopaedic intervention ; there were no serious complications . Crude cost analysis suggested an overall financial advantage from manipulation . Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis , it can be considered as an option for the treatment of symptomatic lumbar disc herniation , at least in the absence of clear indications for surgery . Further study into the value of manipulation at a more acute stage is warranted Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion Objective : To determine the clinical effects of the treatment of lumbar disc herniation with herbal magnetic corsets . Design : A r and omized control trial . Setting : The outpatient and inpatient departments of the Rehabilitation Center of the West China Hospital . Patients : Sixty patients with clinical ly diagnosed lumbar disc herniation were included in the study . Interventions : Both groups received lumbar traction , medium frequency electrotherapy and massage , whereas the experimental group wore herbal magnetic corsets in addition . Main outcome measures : Pain and lumbar function were assessed before treatment and at one week , two weeks and four weeks after intervention . Results : Both groups reported improvements in pain and lumbar function after treatment ( P 0.05 or P 0.001 ) . However , the experimental group reported gradually increasing relief over time leading to a better curative effect than observed in the control group ( P 0.05 for visual analogue scale or P 0.001 for lumbar function ) . Conclusion : Herbal magnetic corsets can facilitate the reduction of pain caused by lumbar disc herniation and can improve lumbar function . This is a safe and effective non-operative therapeutic option for treatment of lumbar disc herniation R and omized controlled clinical trials are conducted to determine whether differences of clinical importance exist between selected treatment regimens . When statistical analysis of the study data finds a P value greater than 5 % , it is convention to deem the assessed difference nonsignificant . Just because convention dictates that such study findings be termed nonsignificant , or negative , however , it does not necessarily follow that the study found nothing of clinical importance . Subject sample s used in controlled trials tend to be too small . The studies therefore lack the necessary power to detect real , and clinical ly worthwhile , differences in treatment . Freiman et al. found that only 30 % of a sample of 71 trials published in the New Engl and Journal of Medicine in 1978 - 79 with a P value greater than 10 % were large enough to have a 90 % chance of detecting even a 50 % difference in the effectiveness of the treatments being compared , and they found no improvement in a similar sample of trials published in 1988 . It is therefore wrong and unwise to interpret so many negative trials as providing evidence of the ineffectiveness of new treatments . One must instead seriously question whether the absence of evidence is a valid justification for inaction . Efforts must be made to look for quantification of an association rather than just a P value , especially when the risks under investigation are small . The authors cite a recent trial comparing octreotide and sclerotherapy in patients with variceal bleeding , as well as the overview of clinical trials evaluating fibrinolytic treatment for preventing reinfa rct ion after acute myocardial infa rct ion as examples 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 ] . ) BACKGROUND Although epidural corticosteroid injections are commonly used for sciatica , their efficacy has not been established . METHODS In a r and omized , double-blind trial , we administered up to three epidural injections of methylprednisolone acetate ( 80 mg in 8 ml of isotonic saline ) or isotonic saline ( 1 ml ) to 158 patients with sciatica due to a herniated nucleus pulposus . All patients had Oswestry disability scores higher than 20 ( on a scale of 1 to 100 , with scores of 20 or less indicating minimal disability , and higher scores greater disability ) . RESULTS At three weeks , the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group ( 95 percent confidence interval for the difference , -7.1 to 2.2 ) . Differences in improvements between the groups were not significant , except for improvements in the finger-to-floor distance ( P=0.006 ) and sensory deficits ( P=0.03 ) , which were greater in the methylprednisolone group . After six weeks , the only significant difference was the improvement in leg pain , which was greater in the methylprednisolone group ( P=0.03 ) . After three months , there were no significant differences between the groups . The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group ( 95 percent confidence interval for the difference , -9.3 to 5.4 ) . At 12 months , the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group ( P=0.90 ) . CONCLUSIONS Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus , this treatment offers no significant functional benefit , nor does it reduce the need for surgery Objectives To evaluate the effects of early lumbar disc surgery compared with prolonged conservative care for patients with sciatica over two years of follow-up . Design R and omised controlled trial . Setting Nine Dutch hospitals . Participants 283 patients with 6 - 12 weeks of sciatica . Interventions Early surgery or an intended six months of continued conservative treatment , with delayed surgery if needed . Main outcome measures Scores from Rol and disability question naire for sciatica , visual analogue scale for leg pain , and Likert self rating scale of global perceived recovery . Results Of the 141 patients assigned to undergo early surgery , 125 ( 89 % ) underwent microdiscectomy . Of the 142 patients assigned to conservative treatment , 62 ( 44 % ) eventually required surgery , seven doing so in the second year of follow-up . There was no significant overall difference between treatment arms in disability scores during the first two years ( P=0.25 ) . Improvement in leg pain was faster for patients r and omised to early surgery , with a significant difference between “ areas under the curves ” over two years ( P=0.05 ) . This short term benefit of early surgery was no longer significant by six months and continued to narrow between six months and 24 months . Patient satisfaction decreased slightly between one and two years for both groups . At two years 20 % of all patients reported an unsatisfactory outcome . Conclusions Early surgery achieved more rapid relief of sciatica than conservative care , but outcomes were similar by one year and these did not change during the second year . Trial Registry IS RCT No 26872154 We analysed 113 reports published in 1980 in a sample of medical journals to relate features of study design to the magnitude of gains attributed to new therapies over old . Overall we rated 87 per cent of new therapies as improvements over st and ard therapies . The mean gain ( measured by the Mann-Whitney statistic ) was relatively constant across study design s , except for non-r and omized controlled trials with sequential assignment to therapy , which showed a significantly higher likelihood that a patient would do better on the innovation than on st and ard therapy ( p = 0.004 ) . R and omized controlled trials that did not use a double-blind design had a higher likelihood of showing a gain for the innovation than did double-blind trials ( p = 0.02 ) . Any evaluation of an innovation may include both bias and the true efficacy of the new therapy , therefore we may consider making adjustments for the average bias associated with a study design . When interpreting an evaluation of a new therapy , readers should consider the impact of the following average adjustments to the Mann-Whitney statistic : for trials with non-r and om sequential assignment a decrease of 0.15 , for non-double-blind r and omized controlled trials a decrease of 0.11 Background The Cochrane Highly Sensitive Search Strategy ( HSSS ) , which contains three phases , is widely used to identify R and omized Controlled Trials ( RCTs ) in MEDLINE . Lefebvre and Clarke suggest that review ers might consider using four revisions of the HSSS . The objective of this study is to vali date these four revisions : combining the free text terms volunteer , crossover , versus , and the Medical Subject Heading CROSS-OVER STUDIES with the top two phases of the HSSS , respectively . Methods We replicated the subject search for 61 Cochrane review s. The included studies of each review that were indexed in MEDLINE were pooled together by review and then combined with the subject search and each of the four proposed search strategies , the top two phases of the HSSS , and all three phases of the HSSS . These retrievals were used to calculate the sensitivity and precision of each of the six search strategies for each review . Results Across the 61 review s , the search term versus combined with the top two phases of the HSSS was able to find 3 more included studies than the top two phases of the HSSS alone , or in combination with any of the other proposed search terms , but at the expense of missing 56 relevant articles that would be found if all three phases of the HSSS were used . The estimated time needed to finish a review is 1086 hours for all three phases of the HSSS , 823 hours for the strategy versus , 818 hours for the first two phases of the HSSS or any of the other three proposed strategies . Conclusion This study shows that compared to the first two phases of the HSSS , adding the term versus to the top two phases of the HSSS balances the sensitivity and precision in the review s studied here to some extent but the differences are very small . It is well known that missing relevant studies may result in bias in systematic review s. Review ers need to weigh the trade-offs when selecting the search strategies for identifying RCTs in MEDLINE QUESTIONS Does the PEDro scale measure only one construct ie , the method ological quality of clinical trials ? What is the hierarchy of items of the PEDro scale from least to most adhered to ? Is there any effect of year of publication of trials on item adherence ? Are PEDro scale ordinal scores equivalent to interval data ? DESIGN Rasch analysis of two independent sample s of 100 clinical trials from the PEDro data base scored using the PEDro scale . RESULTS Both sample s of PEDro data showed fit to the Rasch model with no item misfit . The PEDro scale item hierarchy was the same in both sample s , ranging from the most adhered to item r and om allocation , to the least adhered to item therapist blinding . There was no differential item functioning by year of publication . Original PEDro ordinal scores were highly correlated with transformed PEDro interval scores ( r = 0.99 ) . CONCLUSION The PEDro scale is a valid measure of the method ological quality of clinical trials . It is valid to sum PEDro scale item scores to obtain a total score that can be treated as interval level measurement and subjected to parametric statistical analysis OBJECTIVE Low back pain is a highly common problem and causes much morbidity and socioeconomic loss in the community . Although the use of caudal epidural injections in the management of the low back pain with radicular signs is commonplace , it has not been well investigated . We compare the effectiveness of caudal epidural injection versus non-steroidal anti-inflammatory drugs ( NSAIDs ) in the treatment of low back pain accompanied with radicular pain . METHODS The study was a controlled prospect i ve unblinded trial . A total of consecutive 64 patients with subacute or chronic low back pain accompanied with radicular pain were included . The patients were r and omly allocated to two groups . First group was caudal epidural injection plus therapeutic exercise group , and the second group was NSAIDs plus therapeutic exercise group . Patients were assessed with 10 cm visual analogue scale for pain , straight leg raising test and Oswestry low back pain disability question naire at the beginning and at 15th day , 1st and 3rd month . RESULTS It was seen that both groups ' improvement were good and statistically significant . On the other h and , caudal epidural injection group 's improvement was better and faster than the NSAID group 's , and the differences between assessment scores of the groups were statistically significant , except the 3rd month Oswestry scores . CONCLUSION Finally , caudal epidural injection in the management of the subacute/chronic low back and radicular pain is a preferable choice , if applied by experienced specialists The purpose of this study was to determine if slump stretching results in improvements in pain , central ization of symptoms , and disability in patients with non-radicular low back pain ( LBP ) with likely mild to moderate neural mechanosensitivity . Thirty consecutive patients referred to physical therapy by their primary care physician for LBP who met all eligibility criteria including a positive slump test but who had a negative straight-leg-raise test ( SLR ) agreed to participate in the study . All patients completed several self-report measures including a body diagram , numeric pain rating scale ( NPRS ) , and the modified Oswestry Disability Index ( ODI ) . Patients were r and omized to receive lumbar spine mobilization and exercise ( n = 14 ) or lumbar spine mobilization , exercise , and slump stretching ( n = 16 ) . All patients were treated in physical therapy twice weekly for 3 weeks for a total of 6 visits . Upon discharge , outcome measures were re-assessed . Independent t-tests were used to assess differences between groups at baseline and discharge . No baseline differences existed between the groups ( P > .05 ) . At discharge , patients who received slump stretching demonstrated significantly greater improvements in disability ( 9.7 points on the ODI , P < .001 ) , pain ( .93 points on the NPRS , P = .001 ) , and central ization of symptoms ( P < .01 ) than patients who did not . The results suggest that slump stretching is beneficial for improving short-term disability , pain , and central ization of symptoms . Future studies should examine whether these benefits are maintained at a longer-term follow-up 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 Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results OBJECT Serotonin or 5-hydroxytryptamine ( 5-HT ) is a chemical mediator associated with nucleus pulposus-induced radiculopathy . Inhibition of 5-HT receptors may potentially alleviate symptoms in patients with lumbar disc herniation . This prospect i ve r and omized controlled study was performed to evaluate the efficacy of the 5-HT2A receptor inhibitor in the treatment of symptomatic lumbar disc herniation . METHODS Forty patients with sciatica due to L4 - 5 or L5-S1 disc herniation were r and omly allocated to treatment with the 5-HT2A inhibitor ( sarpogrelate 300 mg/day ) or nonsteroidal antiinflammatory drugs ( NSAIDs ; diclofenac 75 mg/day ) . Low-back pain , leg pain , and numbness were evaluated using a visual analog scale ( VAS ) before and after a 2-week course of treatment . The patients received only allocated medicine during the 2-week regimen and were thereafter allowed to choose any treatment options depending on their residual symptoms . One-year clinical outcomes were assessed based on the rates of additional medical interventions . The mean VAS score improvements in the 5-HT2A and NSAID groups were 33 and 46 % for low-back pain , 32 and 32 % for leg pain , and 35 and 22 % for leg numbness , respectively . After the 2-week regimen , no additional medical interventions were required in 50 % of 5-HT2A-treated patients and 15 % of those receiving NSAIDs . Epidural or nerve root block procedures were performed in 35 % of the 5-HT2A group and 45 % of the NSAID group . Surgery was required in 20 % of the 5-HT2A group and 30 % of the NSAID group patients . CONCLUSIONS The current study provided evidence that the efficacy of the 5-HT2A inhibitor was comparable with that of NSAID therapy for lumbar disc herniation . The 5-HT2A inhibitor has the potential to alleviate symptoms in patients with lumbar disc herniation BACKGROUND CONTEXT Acute back pain and sciatica are major sources of disability . Many medical interventions are available , including manipulations , with conflicting results . PURPOSE To assess the short- and long-term effects of spinal manipulations on acute back pain and sciatica with disc protrusion . STUDY DESIGN / SETTING R and omized double-blind trial comparing active and simulated manipulations in rehabilitation medical centers in Rome and suburbs . PATIENT SAMPLE 102 ambulatory patients with at least moderate pain on a visual analog scale for local pain ( VAS1 ) and /or radiating pain ( VAS2 ) . OUTCOME MEASURES Pain-free patients at end of treatment ; treatment failure ( proportion of patients stopping the assigned treatment for lack of effect on pain ) ; number of days with no , mild , moderate , or severe pain ; quality of life ; number of days on nonsteroidal anti-inflammatory drugs ; number of drug prescriptions ; VAS1 and VAS2 scores ; quality of life and psychosocial findings ; and reduction of disc protrusion on magnetic resonance imaging . METHODS Manipulations or simulated manipulations were done 5 days per week by experienced chiropractors , with a number of sessions which depended on pain relief or up to a maximum of 20 , using a rapid thrust technique . Patients were assessed at admission and at 15 , 30 , 45 , 90 , and 180 days . At each visit , all indicators of pain relief were used . RESULTS A total of 64 men and 38 women aged 19 - 63 years were r and omized to manipulations ( 53 ) or simulated manipulations ( 49 ) . Manipulations appeared more effective on the basis of the percentage of pain-free cases ( local pain 28 vs. 6 % ; p<.005 ; radiating pain 55 vs. 20 % ; p<.0001 ) , number of days with pain ( 23.6 vs. 27.4 ; p<.005 ) , and number of days with moderate or severe pain ( 13.9 vs. 17.9 ; p<.05 ) . Patients receiving manipulations had lower mean VAS1 ( p<.0001 ) and VAS2 scores ( p<.001 ) . A significant interaction was found between therapeutic arm and time . There were no significant differences in quality of life and psychosocial scores . There were only two treatment failures ( manipulation 1 ; simulated manipulation 1 ) and no adverse events . CONCLUSIONS Active manipulations have more effect than simulated manipulations on pain relief for acute back pain and sciatica with disc protrusion Study Design . Assessment of the reliability of st and ardized magnetic resonance imaging ( MRI ) interpretations and measurements . Objective . To determine the intra- and inter-reader reliability of MRI parameters relevant to patients with intervertebral disc herniation ( IDH ) , including disc morphology classification , degree of thecal sac compromise , grading of nerve root impingement , and measurements of cross-sectional area of the spinal canal , thecal sac , and disc fragment . Summary of Background Data . MRI is increasingly used to assess patients with sciatica and IDH , but the relationship between specific imaging characteristics and patient outcomes remains uncertain . Although other studies have evaluated the reliability of certain MRI characteristics , comprehensive evaluation of the reliability of readings of herniated disc features on MRI is lacking . Methods . Sixty r and omly selected MR images from patients with IDH enrolled in the Spine Patient Outcomes Research Trial were each rated according to defined criteria by 4 independent readers ( 3 radiologists and 1 orthopedic surgeon ) . Quantitative measurements were performed separately by 2 other radiologists . A sample of 20 MRIs was re-evaluated by each reader at least 1 month later . Agreement for rating data were assessed with kappa statistics using linear weights . Reliability of the quantitative measurements was assessed using intraclass correlation coefficients ( ICCs ) and summaries of measurement error . Results . Inter-reader reliability was substantial for disc morphology [ overall kappa 0.81 ( 95 % confidence interval ( CI ) : 0.78 , 0.85 ) ] , moderate for thecal sac compression [ overall kappa 0.54 ( 95 % CI : 0.37 , 0.68 ) ] , and moderate for grading nerve root impingement [ overall kappa 0.47 ( 95 % CI : 0.36 , 0.56 ) ] . Quantitative measures showed high ICCs of 0.87 to 0.96 for spinal canal and thecal sac cross-sectional areas . Measures of disc fragment area had moderate ICCs of 0.65 to 0.83 . Mean absolute differences between measurements ranged from approximately 15 % to 20 % . Conclusion . Classification of disc morphology showed substantial intra- and inter-reader agreement , whereas thecal sac and nerve root compression showed more moderate reader reliability . Quantitative measures of canal and thecal sac area showed good reliability , whereas measurement of disc fragment area showed more modest reliability OBJECTIVE This study measures and compares the outcome of traction , ultrasound , and low-power laser ( LPL ) therapies by using magnetic resonance imaging and clinical parameters in patients presenting with acute leg pain and low back pain caused by lumbar disc herniation ( LDH ) . METHODS A total of 60 patients were enrolled in this study and r and omly assigned into 1 of 3 groups equally according to the therapies applied , either with traction , ultrasound , or LPL . Treatment consisted of 15 sessions over a period of 3 weeks . Magnetic resonance imaging examinations were done before and immediately after the treatment . Physical examination of the lumbar spine , severity of pain , functional disability by Rol and Disability Question naire , and Modified Oswestry Disability Question naire were assessed at baseline , immediately after , and at 1 and 3 months after treatment . RESULTS There were significant reductions in pain and disability scores between baseline and follow-up periods , but there was not a significant difference between the 3 treatment groups at any of the 4 interview times . There were significant reductions of size of the herniated mass on magnetic resonance imaging after treatment , but no differences between groups . CONCLUSIONS This study showed that traction , ultrasound , and LPL therapies were all effective in the treatment of this group of patients with acute LDH . These results suggest that conservative measures such as traction , laser , and ultrasound treatments might have an important role in the treatment of acute LDH Background Epidural neuroplasty seems to be one of the promising minimally invasive techniques for adhesiolysis in patients with chronic sciatica with or without low back pain . However , because no data exist from r and omized studies the aim was to investigate whether this procedure is superior to conservative treatment with physiotherapy . Methods A total of 99 patients with chronic low back pain were enrolled in this study and r and omly assigned into either a group with physiotherapy ( n = 52 ) or a second group undergoing epidural neuroplasty ( n = 47 ) . Patients were assessed before and 3 , 6 , and 12 months after treatment by a blinded investigator . Results After 3 months , the visual analog scale ( VAS ) score for back and leg pain was significantly reduced in the epidural neuroplasty group , and the need for pain medication was reduced in both groups . Furthermore , the VAS for back and leg pain as well as the Oswestry disability score were significantly reduced until 12 months after the procedure in contrast to the group that received conservative treatment . Conclusions Epidural neuroplasty results in significant alleviation of pain and functional disability in patients with chronic low back pain and sciatica based on disc protrusion/prolapse or failed back surgery on a short-term basis as well as at 12 months of follow-up 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 . We investigated the effects of continuous lumbar traction in patients with lumbar disc herniation on clinical findings , and size of the herniated disc measured by computed tomography ( CT ) . In this prospect i ve , r and omized , controlled study , 46 patients with lumbar disc herniation were included , and r and omized into two groups as the traction group ( 24 patients ) , and the control group ( 22 patients ) . The traction group was given a physical therapy program and continuous lumbar traction . The control group was given the same physical therapy program without traction , for the same duration of time . Data for the clinical symptoms and signs were collected before and after the treatment together with calculation of a herniation index , from the CT images that showed the size of the herniated disc material . In the traction group , most of the clinical findings significantly improved with treatment . Size of the herniated disc material in CT decreased significantly only in the traction group . In the traction group the herniation index decreased from 276.6±129.6 to 212.5±84.3 with treatment ( p<0.01 ) . In the control group , pretreatment value was 293.4±112.1 , and it decreased to 285.4±115.4 after the treatment ( p>0.05 ) . Patients with greater herniations tended to respond better to traction . In conclusion , lumbar traction is both effective in improving symptoms and clinical findings in patients with lumbar disc herniation and also in decreasing the size of the herniated disc material as measured by CT Study Design . Prospect i ve observational cohorts . Objective . To describe sociodemographic and clinical features , and nonoperative ( medical ) re source utilization before enrollment , in patients who are c and i date s for surgical intervention for intervertebral disc herniation ( IDH ) , spinal stenosis ( SpS ) , and degenerative spondylolisthesis ( DS ) according to SPORT criteria . Summary of Background Data . Intervertebral disc herniation , spinal stenosis , and degenerative spondylolisthesis with stenosis are the three most common diagnoses of low back and leg symptoms for which surgery is performed . There is a paucity of descriptive literature examining large patient cohorts for the relationships among baseline characteristics and medical re source utilization with these three diagnoses . Methods . The Spine Patient Outcomes Research Trial ( SPORT ) conducts three r and omized and three observational cohort studies of surgical and nonsurgical treatments for patients with IDH , SpS , and DS . Baseline data include demographic information , prior treatments received , and functional status measured by SF-36 and the Oswestry Disability Index ( ODI-AAOS/Modems version ) . The data presented represent all 1,411 patients ( 743 IDH , 365 SpS , 303 DS ) enrolled in the SPORT observational cohorts . Multiple logistic regression was used to generate independent predictors of utilization adjusted for sociodemographic variables , diagnosis , and duration of symptoms . Results . The average age was 41 years for the IDH group , 64 years for the SpS group , and 66 years for the DS group . At enrollment , IDH patients presented with the most pain as reported on the SF-36 ( BP 26.3 vs. 33.2 SpS and 33.8 DS ) and were the most impaired ( ODI 51 vs. 42.3 SpS and 41.5 DS ) . IDH patients used more chiropractic treatment ( 42 % vs. 33 % SpS and 26 % DS ) , had more Emergency Department ( ED ) visits ( 21 % vs. 7 % SpS and 4 % DS ) , and used more opiate analgesics ( 49 % vs. 29 % SpS and 27 % DS ) . After adjusting for age , gender , diagnosis , education , race , duration of symptoms , and compensation , Medicaid patients used significantly more opiate analgesics ( 58 % Medicaid vs. 41 % no insurance , 42 % employer , 33 % Medicare , and 32 % private ) and had more ED visits compared with other insurance types ( 31 % Medicaid vs. 22 % no insurance , 16 % employer , 3 % Medicare , and 11 % private ) . Conclusion . IDH patients appear to have differences in sociodemographics , re source utilization , and functional impairment when compared with the SpS/DS patients . In addition , the differences in re source utilization for Medicaid patients may reflect differences in access to care . The data provided from these observational cohorts will serve as an important comparison to the SPORT r and omized cohorts in the future Autotraction ( AT ) is a treatment for low-back pain syndrome of benign etiology that uses a specially design ed traction table divided into two movable sections . While lying on the table , the pelvis secured , the patient controls the traction forces by grasping and pulling the bars at the head of the table . There are controls for the therapist to apply , through movable sections of the table , rotation and bending forces to help restore mobility to the lumbar spine without inducing pain . The present study is based upon a r and omized treatment trial comparing conventional passive traction ( PT ) to AT . The following outcome indicators were used : ( 1 ) subjective response concerning overall improvement , ( 2 ) pain intensity ( visual analog scale , 0 - 100 ) , ( 3 ) qualitative pain severity ( McGill Pain Question naire , short-form , 0 - 45 ) , and ( 4 ) pain related disability ( Oswestry Low Back Pain Disability Score , 0 - 100 ) . The favorable response to AT was 75 % ( 30 of the 40 patients ) versus the 22 % ( 6 of 27 patients ) to PT ( p < 0.001 ) . After 3 months , 19 of the 30 responders to AT ( 63 % ) reported continued improvement . In these patients , pain ratings remained stable and the disability scores decreased to 0 to 23 % of the pretreatment value ( median and mean respectively , p < 0.001 ) 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 In this prospect i ve r and omized clinical trial , the results of epidural corticosteroid injections were evaluated in patients with lumbosciatic pain caused by herniated nucleus pulposus . Thirty-six patients with radicular lumbosciatic pain and positive straight leg raising test because of confirmed prolapsed intervertebral lumbar discs were r and omized into two groups with ( 17 patients ) and without ( 19 patients ) epidural corticosteroid injection . Members of the treatment groups received three injections of 100 mg methylprednisolone in 10 mL bupivacaine 0.25 % each . Additional therapy was st and ardized and identical in both groups . Followup examinations were performed at 2 weeks , 6 weeks , and 6 months . The examinations included pain level ( visual analogue scale ) , straight leg raising test , and functional status ( Hannover Functional Ability Question naire ) . At 2 weeks , patients receiving methylprednisolone injection showed a significant improvement in straight leg raising test results compared with patients in the control group . Results were better in the methylprednisolone group , although not statistically significant for pain relief and mobility . At 6 weeks and 6 months , pain relief , improvement of straight leg raising , and improvement of functional status showed no statistical significance . Epidural corticosteroid injections can be recommended as additional therapy only in the acute phase of the conservative management of lumbosciatic pain A systematic review of r and omised controlled trials was undertaken to evaluate the effectiveness of workplace interventions to prevent low back pain . Potential trials were located by a computerised search supplemented with citation tracking . The method ological quality of the trials was assessed on 11 criteria and the level of evidence for each intervention was determined , based upon the amount , consistency and quality of evidence from the trials . The review located 13 trials that were generally of moderate quality . The trials suggest that work place exercise is effective , braces and education are ineffective , and workplace modification plus education is of unknown value in preventing low back pain Abstract Low back pain is one of the most significant medical and socioeconomic problems in modern society . International guidelines call for evidence -based management for the pain and disability associated with musculoskeletal disorders . The purpose of this r and omized controlled trial is to address the question of efficacy and appropriateness of vertebral axial decompression ( VAX-D ) therapy , a new technology that has been shown in clinical research to create negative intradiscal pressures , and has been shown to be effective in treating patients presenting with chronic low back pain ( > 3 months duration ) with associated leg pain . Successful outcome was defined as a 50 % reduction in pain utilizing a 10 cm Visual Analog Pain Scale and an improvement in the level of functioning as measured by patient-nominated disability ratings . Patients were r and omly assigned to VAX-D or to TENS which was used as a control treatment or placebo . The TENS treatment demonstrated a success rate of 0 % , while VAX-D demonstrated a success rate of 68.4 % ( p < 0.001 ) . A statistically significant reduction in pain and improvement in functional outcome was obtained in patients with chronic low back pain treated with VAX-D. [ Neurol Res 2001 ; 23 : 780 - 784 AIM The aim of this study is to assess the efficacy of a new , simple and cheap device of manual autotraction ( MAT ) , in comparison with Natchev 's autotraction system . METHODS Fifty-four patients , with lumbalgia or sciatalgia for more than 4 months and disc herniation or protrusion at computed tomography ( CT ) or nuclear magnetic resonance ( NRM ) , have been selected , at r and om , in a r and omized control trial . Patients have been treated by MAT or by Natchev 's autotraction . Treatments ' efficacy has been assessed through the differences in visual analogic scale ( VAS ) for pain , and Backill scale for disability , before and after therapy ( diffVAS and diffBi ) . The results of the 2 autotraction 's devices have been compared in order to distinguish their differences . The results have been considered significant if p<0.05 . RESULTS Both treatments proved to be effective ( MAT : diffVAS p<0.0001 , diffBackill p<0.001 ; Natchev 's group : diffVAS p<0.0001 , diffBackill p<0.001 ) . No significant difference of efficacy emerges between the treatments in diffVAS ( p=0.199 ) and diffBi ( p=0.906 ) , and a greater efficacy of both in case of pain with nocturnal aggravation ( MAT group : diffVAS : p=0.001 ; Natchev 's group : p=0.001 ) . CONCLUSIONS The results of this study show an equal efficacy of MAT compared to the known Natchev 's system , so it could be equally proposed like a simple conservative treatment in disc protrusion or herniation without surgery indication |
2,645 | 14,670,218 | Language inclusive/LOE systematic review s were of the highest quality compared with the other types of review s. The CAM review s were of higher quality compared with the CM review s. There were only minor differences in the quality of reports of EL RCTs compared with the eight other language s considered .
However , there are inconsistent differences in the quality of LOE reports depending on the intervention type .
The results , and those reported previously , suggest that excluding reports of RCTs in LOE from the analytical part of a systematic review is reasonable .
This result only applies to review s investigating the benefits of CM interventions .
Language restrictions significantly shift the estimates of an intervention 's effectiveness when the intervention is CAM .
Here , excluding trials reported in LOE , compared with their inclusion , result ed in a reduced intervention effect .
The present results do not appear to be influenced by statistical heterogeneity and publication bias .
Language inclusive/LOE systematic review s appear to be a marker for a better quality systematic review .
Language restrictions do not appear to bias the estimates of a conventional intervention 's effectiveness .
However , there is substantial bias in the results of a CAM systematic review if LOE reports are excluded from it | OBJECTIVE To assemble a large data set of language restricted and language inclusive systematic review s , including both conventional medicinal ( CM ) and complementary and alternative medicine ( CAM ) interventions .
To then assess the quality of these reports by considering and comparing different types of systematic review s and their associated RCTs ; CM and CAM interventions ; the effect of language restrictions compared with language inclusion s , and whether these results are influenced by other issues , including statistical heterogeneity and publication bias , in the systematic review process . | To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient STUDY OBJECTIVE To study the efficacy of intestinal decontamination by oral nonabsorbable antibiotic agents to control a nosocomial outbreak of intestinal colonization and infection with multiresistant Enterobacteriaceae , and to examine its effects on endemic nosocomial infection rates . DESIGN A 10-week prospect i ve incidence study ( group 1 ) , and then an 8-week r and omized , open trial of intestinal decontamination ( groups 2 and 3 ) . SETTING A medical intensive care unit of a tertiary care university hospital . PATIENTS Consecutive patients with unit stay of over 2 days and a severity score at admission of more than 2 ; 124 patients were included in group 1 , 50 in group 2 ( control ) , and 36 in group 3 ( intestinal decontamination ) . INTERVENTIONS Neomycin , polymyxin E , and nalidixic acid were given to group 3 patients throughout their stay in the unit . MEASUREMENTS AND MAIN RESULTS Intestinal colonization with multiresistant strains occurred in 19.6 % of patients in group 1 , at a mean of 16 days after admission , and preceded detection in clinical sample s by a mean of 11 days . During the decontamination trial , intestinal colonization rates decreased to 10 % ( group 2 ) , and 3 % ( group 3 ) ( P = 0.12 and P less than 0.01 , compared with group 1 , respectively ) . Corresponding infection rates were 9 % ( group 1 ) , 3 % ( group 2 ) , and 0 ( group 3 ) . No new cases were detected in the following 4 months . The intestinal colonization rate with gram-positive cocci was higher in group 3 than group 2 ( P less than 0.001 ) . The overall rate of nosocomial infections was at 28 % ( group 1 ) , 33 % ( group 2 ) , and 32 % ( group 3 ) . CONCLUSIONS Intestinal decontamination can help to control an outbreak of intestinal colonization and infection with multiresistant gram-negative bacilli in the intensive care unit , but should not be recommended for routine prevention of endemic nosocomial infections Objective To evaluate the quality of reports of complementary and alternative medicine ( CAM ) r and omized controlled trials ( RCTs ) in the pediatric population . We also examined whether there was a change in the quality of reporting over time . Methods We used a systematic sample of 251 reports of RCTs that used a CAM intervention . The quality of each report was assessed using the number of CONSORT checklist items included , the frequency of unclear allocation concealment , and a 5-point quality assessment instrument . Results Nearly half ( 40 % ) of the CONSORT checklist items were included in the reports , with an increase in the number of items included . The majority ( 81.3 % ) of RCTs reported unclear allocation concealment with no significant change over time . The quality of reports achieved approximately 40 % of their maximum possible total score as assessed with the Jadad scale with no change over time . Information regarding adverse events was reported in less than one quarter of the RCTs ( 22 % ) and information regarding costs was mentioned in only a minority of reports ( 4 % ) . Conclusions RCTs are an important tool for evidence based health care decisions . If these studies are to be relevant in the evaluation of CAM interventions it is important that they are conducted and reported with the highest possible st and ards . There is a need to redouble efforts to ensure that children and their families are participating in RCTs that are conducted and reported with minimal bias . Such studies will increase their usefulness to a board spectrum of interested stakeholders BACKGROUND To investigate the method ological quality of r and omized controlled trials in three areas of complementary medicine . METHODS The method ological quality of 207 r and omized trials collected for five previously published systematic review s on homeopathy , herbal medicine ( Hypericum for depression , Echinacea for common cold ) , and acupuncture ( for asthma and chronic headache ) was assessed using a vali date d scale ( the Jadad scale ) and single quality items . RESULTS While the method ological quality of the trials was highly variable , the majority had important shortcomings in reporting and /or methodology . Major problems in most trials were the description of allocation concealment and the reporting of drop-outs and withdrawals . There were relevant differences in single quality components between the different complementary therapies : For example , acupuncture trials reported adequate allocation concealment less often ( 6 % versus 32 % of homeopathy and 26 % of herb trials ) , and trials on herbal extracts had better summary scores ( mean score 3.12 versus 2.33 for homeopathy and 2.19 for acupuncture trials ) . Larger trials published more recently in journals listed in Medline and in English language scored significantly higher than trials not meeting these criteria . CONCLUSION Trials of complementary therapies often have relevant method ological weaknesses . The type of weaknesses varies considerably across interventions OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries A systematic quantitative and qualitative overview of published r and omized clinical trials was undertaken to assess the yield of medical treatment on the outcome of patients with primary open angle glaucoma . Reports of 102 r and omized clinical trials were published between 1975 and 1991 , totalling about 5000 patients . Only 16 % ( 16/102 ) of the trials were , however , properly design ed ( ie , comparing an active treatment with a placebo-treated or untreated control group ) to answer the question of whether any medical treatment can effectively cure patients with primary open angle glaucoma . Pooled analysis showed a moderate yet statistically significant reduction in mean intraocular pressure ( -4.9 mm Hg ; 95 % confidence interval [ CI ] , -7.3 to -2.5 mm Hg ) ; however , data on long-term visual field changes were available in only three r and omized clinical trials , and their statistical combination failed to show a significant protective effect of active treatment ( odds ratio , 0.75 ; 95 % CI , 0.42 to 1.35 ) . All of the remaining 86 r and omized clinical trials looked at the effectiveness of one drug vs another in lowering intraocular pressure and were thus of no use in the overview . Practicing ophthalmologists should be aware that the effectiveness of pressure-lowering agents in the treatment of primary open angle glaucoma is still to be determined and that the vast majority of published trials are not appropriate to guide clinical practice . It is urgent to plan trials with end-point and follow-up duration that is fully relevant for the health of patients A r and omized controlled trial was initiated in 1972 to compare two chemotherapeutic regimens [ 1 - 3-bis ( 2-chloroethyl ) 1-nitrosourea ( BCNU ) , cyclophosphamide , and prednisone versus melphalan and prednisone ] , to determine whether the two regimens are cross-resistant , and to evaluate the effectiveness of sodium fluoride , vitamin D , calcium gluconate , and fluoxymesterone in the promotion of bone healing . Initial responses ( 50 % ) and survival ( 36 mo median ) for patients treated with the two chemotherapeutic regimens were the same . Patients on either regimen who failed to respond after 6 mo had a very low response rate to the alternative regimen ( approximately 10 % ) . Initially responding patients were r and omly assigned to either an active drug regimen ( sodium fluoride , vitamin D , calcium gluconate , fluoxymesterone ) or placebo tablets . There was no significant difference in the low percentage of patients demonstrating bone improvement . Thus , the BCNU , cyclophosphamide , prednisone regimen is as effective as melphalan and prednisone . Fluoride , calcium , vitamin D , and and rogenic steroids should not be routinely recommended in myeloma , as they seem to add little to effective chemotherapy and may contribute to morbidity Objectives : To review the effectiveness of prayer as an additional intervention for those with health problems already receiving st and ard medical care . Search Strategy : Electronic Search es of Biological Abstract s , CINAHL , The Cochrane Controlled Trials Register , EM-BASE , MEDLINE , PsycLIT , and Sociofile were undertaken . All references of articles selected were search ed for further relevant trials . Selection Criteria : R and omised and quasi-r and omised trials of personal , focused , committed and organised intercessory prayer on behalf of anyone with a health problem were considered . Outcomes such as achievement of desired goals , death , illness , quality of life and well-being for the recipients of prayer , those praying and the caregivers were sought . Data Collection and Analysis : Studies were reliably selected and assessed for method ological quality . Data were extracted by 4 review ers working independently . Dichotomous data were analysed on an intention-to-treat basis , and continuous data with over 50 % completion rate are presented . Main Results : There was no evidence that prayer affected the numbers of people dying from leukaemia or heart disease ( OR 0.64 , CI 0.32–1.27 ) , or that it decreased coronary care complications ( OR 1.05 , CI 0.49–2.26 ) or the time participants stayed in hospital . There were significantly fewer ‘ intermediat//poor outcomes ’ for those with heart disease in the prayed-for group ( OR 0.49 , CI 0.30–0.80 ) , and this finding was robust to some changes in definition . Conclusions : This review provides no guidance for those wishing to uphold or refute the effect of intercessory prayer on the outcomes studied in the available trials . Therefore , in the light of the best available data , there are no grounds to change current practice s. There are very few completed trials of the value of intercessory prayer . The evidence presented so far is interesting enough to justify further study . If prayer is seen as a human endeavour it may or may not be beneficial , and further trials could uncover this . It could be the case that any effects are due to elements beyond present scientific underst and ing that will , in time , be understood . If any benefit derives from God ’s response to prayer it may be beyond any such trials to prove or disprove Many r and omised controlled trials have been conducted in China to evaluate the effectiveness of traditional Chinese medicine , but much of the information is inaccessible to Western doctors . We estimated the total number of r and omised controlled trials published in China and identified problems in applying such methodology to the evaluation of traditional Chinese medicine , which would serve as preparatory work for systematic review and dissemination of the r and omised evidence for such medicine . We r and omly selected 28 journals using stratified sampling from a total of 100 Chinese journals of traditional Chinese medicine ( 4 national , 10 university , 10 provincial or regional , and 4 specialist journals ) . After special training , eight fifth year medical students ( working in pairs ) h and search ed all the issues of the journals published before 1 January 1997 to identify r and omised controlled trials . Discrepancies were settled by one of the principal investigators ( S-YZ ) . Data on method ological quality of r and omised controlled trials were extracted from 414 full length articles This study meta-analysed r and omized , double-blind , placebo controlled trials in patients with intermittent claudication of the lower limbs comparing ticlopidine to placebo in order to test the hypothesis that the drug , a pure antiplatelet agent , is able to reduce the incidence of thrombotic cardio-vascular events on atherosclerotic arteries in these patients . A highly significant reduction , from 9 % to 3 % ( p ranging from 0.006 to 0.002 ) , was observed for fatal or non-fatal cardio-vascular events in a total of 611 patients ( 301 with ticlopidine , 310 with placebo ) . The duration of follow-up ranged from 6 to 12 months . Side-effects , defined as withdrawal from study medication for any reason but death , cardio-vascular events or cancer , were 2.4 times more frequent in the ticlopidine treated patients as compared to placebo . We concluded that in this high risk population , prevention of cardio-vascular events is likely to be effective OBJECTIVE To describe the pattern over time in the level of statistical power and the reporting of sample size calculations in published r and omized controlled trials ( RCTs ) with negative results . DESIGN Our study was a descriptive survey . Power to detect 25 % and 50 % relative differences was calculated for the subset of trials with negative results in which a simple two-group parallel design was used . Criteria were developed both to classify trial results as positive or negative and to identify the primary outcomes . Power calculations were based on results from the primary outcomes reported in the trials . POPULATION We review ed all 383 RCTs published in JAMA , Lancet , and the New Engl and Journal of Medicine in 1975 , 1980 , 1985 , and 1990 . RESULTS Twenty-seven percent of the 383 RCTs ( n = 102 ) were classified as having negative results . The number of published RCTs more than doubled from 1975 to 1990 , with the proportion of trials with negative results remaining fairly stable . Of the simple two-group parallel design trials having negative results with dichotomous or continuous primary outcomes ( n = 70 ) , only 16 % and 36 % had sufficient statistical power ( 80 % ) to detect a 25 % or 50 % relative difference , respectively . These percentages did not consistently increase over time . Overall , only 32 % of the trials with negative results reported sample size calculations , but the percentage doing so has improved over time from 0 % in 1975 to 43 % in 1990 . Only 20 of the 102 reports made any statement related to the clinical significance of the observed differences . CONCLUSIONS Most trials with negative results did not have large enough sample sizes to detect a 25 % or a 50 % relative difference . This result has not changed over time . Few trials discussed whether the observed differences were clinical ly important . There are important reasons to change this practice . The reporting of statistical power and sample size also needs to be improved OBJECTIVE To assess the method ologic quality of approaches used to allocate participants to comparison groups in r and omized controlled trials from one medical specialty . DESIGN Survey of published , parallel group r and omized controlled trials . DATA SOURCES All 206 reports with allocation described as r and omized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology . MAIN OUTCOME MEASURES Direct and indirect measures of the adequacy of r and omization and baseline comparisons . RESULTS Only 32 % of the reports described an adequate method for generating a sequence of r and om numbers , and only 23 % contained information showing that steps had been taken to conceal assignment until the point of treatment allocation . A mere 9 % described both sequence generation and allocation concealment . In reports of trials that had apparently used unrestricted r and omization , the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance . In reports of trials in which hypothesis tests had been used to compare baseline characteristics , only 2 % of reported test results were statistically significant , lower than the expected rate of 5 % . CONCLUSIONS Proper r and omization is required to generate unbiased comparison groups in controlled trials , yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation . Additional analyses suggest that nonr and om manipulation of comparison groups and selective reporting of baseline comparisons may have occurred BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias |
2,646 | 24,995,809 | The results of this study suggest that the differences in occlusal loading between INFL and IFL might not affect the survival of these dental implants and that there is no apparent significant effect on the marginal bone loss . | OBJECTIVES The purpose of the present review was to test the null hypothesis of no difference in the implant failure rates , postoperative infection , and marginal bone loss for patients being rehabilitated using dental implants with immediate nonfunctional loading ( INFL ) compared to immediate functional loading ( IFL ) , against the alternative hypothesis of a difference .
CLINICAL SIGNIFICANCE There has been a controversy concerning whether dental implants should be subjected to immediate functional or nonfunctional loading . | The Cochrane Collaboration should be congratulated for its dedication to documenting continuing clinical trials , teaching critical appraisal , and supporting research into new methods of review ing the literature . However , Cochrane Review s can be created by untrained people who simply follow an algorithmic approach and are unaware of important method ological issues . Therefore , the objective of this article is to highlight important limitations of Cochrane Review s , including the Review Manager software1 that is required,2 the inappropriate use of a summary statistic , and finally the restriction to only r and omised controlled trial ( RCT ) data . To illustrate these points , I have used a 1 % r and om sample of Cochrane Review s — that is , 16 studies numbered 1 , 101 , 201 … 1501 of 1596 of the Cochrane Data base on 3 April 2003.3–18 There are important limitations to the software required by the Cochrane Collaboration ( Review Manager ) . Most important is that Review Manager can not include ( a ) results based on survival analyses — for example , most appropriate analysis for time to next injury— and instead calculates relative risks based on simple proportions ( this leads to inappropriate estimates when patients have different lengths of follow up19 ) and ( b ) analyses adjusted for confounding — that is , multiple regression analysis . Software is available , but requires statistical expertise that would preclude the algorithmic approach . Whereas the Cochrane Collaboration could improve its software , the other two major problems are process oriented . The Cochrane Collaboration promotes wide participation , and this leads to inexperienced authors and peer review ers . For example , it is not always appropriate to pool data into one overall summary statistic,20 and , even when it is , there are different methods —that is , fixed and r and om effects models — to be used depending on the structure of the data .20,21 In the BACKGROUND The aim of this study was the evaluation , from a clinical point of view , of implants subjected to immediate functional loading ( IFL ) and to immediate non-functional loading ( INFL ) in various anatomical configurations . METHODS The study included 152 patients who had given their informed consent . A total of 646 implants were inserted . The implants were placed in 39 totally edentulous m and ibles , 14 edentulous maxillae , 23 edentulous posterior m and ibles , 16 edentulous anterior m and ibles , 16 edentulous anterior maxillae , and 15 edentulous posterior maxillae . Fifty-eight implants were used to replace single missing teeth . In 65 cases , IFL was carried out for 422 implants . INFL was carried out in 116 cases , ( 224 implants ) . RESULTS In the IFL group 6 of 422 implants failed ( 1.4 % ) ; in the INFL group 2 of 224 implants failed ( 0.9 % ) . All the other implants appeared , from clinical and radiographic observations , to have successfully osseointegrated and have been functioning satisfactorily since insertion . All failures were observed in the first few months after implant loading . CONCLUSION Immediate functional and non-functional loading seems to be a technique that gives satisfactory results in selected cases OBJECTIVE The aim of this prospect i ve study was to evaluate the outcome of immediately provisionally restored implants in the posterior m and ible after a minimum of 60 months in function . MATERIAL AND METHODS Twenty-four patients were treated with 40 screw-type implants replacing m and ibular molars and premolars . Implants were provisionalized immediately after placement . Radiographic coronal bone levels , implant survival and success were evaluated 12 , 24 , 36 , 48 and 60 months after the final restoration . RESULTS Measurements of the mean marginal bone levels around immediately loaded implants after 12 months showed a significant bone loss ( P<0.001 ) within the first year after the final restoration . Measurements of coronal bone levels after 24 , 36 , 48 and 60 months , respectively , showed no further significant increase of bone resorption . Two implants were lost within the first year after the final restoration , result ing in an overall survival rate of 95 % ; a total of three implants were recorded as failures ( two implant losses and one excessive bone resorption above 50 % ) , result ing in an overall success rate of 92.5 after an implant observation period of up to 8 years . CONCLUSION The present data revealed results comparable to conventionally loaded implants . Careful patient selection in combination with high primary stability seem to be key factors for immediately loaded implants . Larger long-term r and omized clinical trials are needed to confirm the final evidence of this protocol as the st and ard treatment concept for the partially edentulous m and ible PURPOSE To evaluate whether immediate non-occlusal loading of single zirconia implants could reduce early failures when compared to immediate occlusal loading . MATERIAL S AND METHODS Forty partially edentulous patients who received one single zirconia implant ( Z-Systems ) at least 10 mm long and 3.25 mm wide inserted with a torque of at least 35 Ncm were r and omised to immediate occlusal or non-occlusal loading groups . All patients received provisional acrylic crowns the same day of implant placement . Provisional crowns were replaced after 4 to 5 months by definitive full ceramic crowns . Outcome measures were implant success , any complications and peri-implant marginal bone levels . RESULTS One year after loading , no patients had dropped out . Five implants ( 12.5 % ) failed early : three occlusally loaded and two non-occlusally loaded . Three complications occurred , all after delivery of the definitive crowns : one crown fractured ( occlusal loading ) , one had to be remade after debridement because of hyperplastic tissues ( occlusal loading ) , and one crown decemented ( nonocclusal loading ) . These differences were not statistically significant . Both groups gradually lost periimplant bone in a highly statistically significant way . One year after loading , patients subjected to non-occlusal loading lost an average of 0.7 mm of peri-implant bone versus 0.9 mm in the occlusal group . This difference in bone loss between groups was not statistically significant . There was an association between immediate post-extractive implants and implant failures ( P=0.01 ) . Four of the 10 immediate post-extractive implants ( 40 % ) failed versus one out of 30 delayed implants ( 3 % ) . CONCLUSIONS The results of this study do not provide a conclusive answer to whether immediate non-occlusal loading may decrease implant failures . Immediately loaded zirconia implants placed in post-extractive sites had high failure rates OBJECTIVE The aim of this study was to compare the survival rate , the bone loss and soft-tissue healing patterns of immediately loaded and immediately restored implants in cases of partial posterior m and ibular edentulism . MATERIAL AND METHODS Fifty patients with partial posterior m and ibular edentulism were r and omly selected for two treatments : 25 were included in the immediate loading group ( test ) and 25 in the immediate restoration group ( control ) . All implants were placed in healed sites with a torque of > 25 N cm . The temporary prosthesis of the immediate restoration group was placed so as to avoid occlusal contact in centric and lateral excursions . Both groups received fully occluding final restorations 6 months after surgery . Mean marginal bone loss was assessed at 6- , 12- , 24- and 36-month follow-up examinations by a blinded examiner . RESULTS A total of 100 implants were placed in the period between February 2004 and October 2006 , of which 42 ( 42 % ) were for men and 58 ( 58 % ) for women . Five and 7 weeks after surgery , mobility of one implant was assessed in one ( 4 % ) patient in the test group and one ( 4 % ) patient in the control group , respectively . At the 36-month follow-up , the accumulated mean marginal bone loss was 0.987 mm ( SD=0.375 ) for the immediate restoration group ( n=48 ) and 0.947 mm ( SD=0.323 ) for the immediate loading group ( n=48 ) . There was no statistically significant difference ( P>0.05 ) for the tested outcome measures between the two procedures . CONCLUSIONS This study was unable to detect any statistically significant difference in the survival rate , bone loss and soft tissue healing patterns between the immediately loaded and the immediately restored implants in cases of partial posterior m and ibular edentulism . The immediate temporary rehabilitation of the partially edentulous posterior m and ible is a predictable procedure using both procedures BACKGROUND During the last decade , high success rates have been reported for implants placed with immediate loading procedures , especially when bone quality and quantity provide good implant stability . In many of these studies , straight-walled implants with moderately rough surfaces were employed . Tapered implants are becoming increasingly more popular due to st and ardized drilling protocol s and reports of high initial primary stability . PURPOSE The aim of the present prospect i ve , single center clinical study was to evaluate surface topographical analysis and the clinical and radiographic outcomes of the NanoTite ™ ( BIOMET 3i , Palm Beach Gardens , FL , USA ) Tapered Implant when used for immediate loading of fixed prostheses and single-tooth restorations . MATERIAL S AND METHODS Forty-two patients who needed implant treatment and met admission criteria agreed to participate in the study and were consecutively enrolled . Surgical implant placement requirements consisted of a final torque of a least 30 Ncm prior to final seating and an implant stability quotient above 55 . A total of 139 NanoTite Tapered implants ( 112 maxillary and 27 m and ibular ) were placed by one investigator , and the majority of these implants ( n = 77/55 % ) were placed in posterior regions , and in soft bone ( n = 90/65 % ) . A total of 57 prosthetic constructions were evaluated consisting of 20 single-tooth restorations , 30 fixed partial dentures , and 7 complete , fixed maxillary restorations . Radiographs were taken at baseline and at 12 months of follow-up . RESULTS Of the 139 study implants , one implant failure was declared . The overall cumulative survival rate at 1 year is 99.4 % . Mean marginal bone resorption is 1.01 mm ( SD 0.85 ) during the first year of function . CONCLUSION Although limited to the short follow-up , immediate loading of NanoTite Tapered implants seems to be a viable option in implant rehabilitation , when insertion torque of at least 30 Ncm is achieved . Further studies are needed to authenticate the finding of this study While immediate loading in the edentulous m and ible is a well-documented procedure , there are limited scientific data on immediate loading in the partially edentulous m and ible . Two-year success rates of immediate loading and conventional delayed loading of dental implants in partially dentate m and ibles were compared . Patients were r and omized into three groups : group A ( n = 40 ) , immediate provisionalization with nonocclusal loading ; group B ( n = 40 ) , immediate provisionalization with occlusal loading ; and group C ( n = 37 ) , delayed loading with single-stage surgery . Baseline and 2-year measurements included implant stability quotient , insertion torque , and peri-implant bone crest radiography . Two hundred nine implants were immediately loaded in 80 patients . The 2-year success rates were 93.3 % for group B and 100 % for groups A and C. Immediate provisionalization provided success rates similar to those for delayed loading only when not loaded in occlusion BACKGROUND The aim of this study was to evaluate the survival of dental implants in periodontally susceptible patients using immediate loading/restoration ( ILR ) protocol s and the factors that modulate this response . METHODS Systemically healthy patients who were treated previously for chronic periodontitis and who required implant therapy were recruited . Following data collection , " surgical templates " and provisional fixed restorations were fabricated . Transgingival implants were inserted , and surgical measurements were performed . After abutment connection , the crown/bridge was relined and cemented . Patients were monitored for 12 months , at which time final measurements were performed . RESULTS Twenty patients ( 49 implants ) completed this study ; five implants failed and were removed ( 90 % survival rate ) . All implants were removed during the first 6 months . At 12 months , the mean implants ' probing depth was 2.87 + /- 0.9 mm . The mean electronic mobility testing device value ( -1.3 + /- 0.7 ) was slightly higher than at baseline ( -3.53 + /- 10.7 ) . Radiographic bone loss ranged between -1.24 and 2.77 mm ( mean + /- SD : 0.91 + /- 0.2 mm ) . All of the implants ( 16 ) that were inserted in the premolar region were successful , whereas three of nine implants in the molar region and two of 24 implants in the canine/incisor region failed ( P = 0.0278 ) . Survival in the immediately loaded group ( 83 % ) was slightly lower than in the immediately restored group ( 96 % ) ; however , these differences did not reach statistical significance . None of the other variables ( smoking , arch , stability , implant length and diameter , and bone width ) affected the outcome of this procedure . CONCLUSIONS ILR protocol s are predictable alternatives in periodontally susceptible patients . Results in the molar regions suggested that careful consideration should be given to implants placed in these sites . Long-term success in these patients has not been addressed PURPOSE The aim of this study was to compare implant-supported restorations placed and loaded immediately or with a delay in a longitudinal case control study . MATERIAL S AND METHODS Seventy-six patients with 222 implants were enrolled in this study . One hundred eleven implants ( 45 patients ) were su bmi tted to immediate functional or nonfunctional loading . These were compared to 111 implants ( 51 patients ) that received delayed loading after submerged healing . The mean observation time was 40.3 months ( 3.36 years ) . Implant success was determined , and peri-implant soft tissue parameters and esthetic outcomes for anterior restorations were evaluated . The implants were divided into four groups according to their treatment protocol : immediate ( I ) or delayed ( D ) implant placement ( P ) or function ( F ) , ie : group 1 = IF+IP , group 2 = IF+DP , group 3 = DF+IP , and group 4 = DF+DP . RESULTS Five implants were lost during healing , giving an overall success rate of 97.7 % . Implants with delayed function showed significantly better results ( 100.0 % ) than implants that were immediately loaded ( 95.5 % ) . Four of the five lost implants had been placed immediately post extraction ( success rate for delayed implant placement , 99.4 % , versus 93.1 % for immediate implant placement ) . Regarding the four treatment protocol s , group 1 showed a success rate of 91.3 % ; group 2 achieved 98.5 % ; and both delayed function groups showed 100 % success . No statistically significant difference was seen between the four groups . Esthetically significant advantages were seen for the implants placed into immediate function . Probing depths and bleeding on probing were significantly lower in the group of implants placed into immediate function . CONCLUSIONS Implants that are loaded immediately can achieve good outcomes . However , the risk of implant loss appears to be increased in cases where immediate function is combined with immediate implant placement PURPOSE The aim of this prospect i ve r and omized study was to evaluate the clinical outcome of immediately loaded solid plasma sprayed ( TPS ) BioComp ( BioComp Industries BV , Vught , The Netherl and s ) implants versus immediate provisionalized but non-loaded BioComp implants in the anterior and premolar region of the maxilla . MATERIAL S AND METHODS Forty-eight patients ( 31 females and 17 males ) with a mean age of 42.3+/-13.1 years ( range 19 to 78 years ) were included in the study . Fifty threaded TPS implants were placed and provisionalized within 24 hours after surgery . The patients were r and omly assigned to 2 groups . In the immediate loaded ( IL ) group ( n=24 ) the occlusion of the provisional was design ed with normal contacts in centric relation and at lateral excursions , while in the non-immediate loaded ( IP ) group ( n=24 ) the provisional restoration was adjusted to clear all occlusal contacts or contacts at lateral excursions . Patients were instructed to eat a soft diet and to avoid placing food in the area of the provisional crown during the first 6 weeks . Regular clinical and radiographic controls were performed and the survival rate and implant stability quotient ( ISQ ) values were evaluated at delivery of the definitive restoration at 6 months . At 1 year , radiographic coronal bone defects and gingival esthetics between the 2 groups were assessed . RESULTS Of the IL group , 2 fixtures were lost , while 3 implants were lost in the IP group . The failing implants showed increasing mobility at 2 to 3 weeks after insertion , and were removed . The remaining 45 implants were stable at every subsequent follow-up examination , and 6 months after implant placement , ISQ values were measured . The mean ISQ value in the IL group was 63.7+/-5.8 versus 63.2+/-4.3 for the IP group ( P=.78 ) . The mean mesial marginal bone loss after 12 months in the IL group was 0.27+/-0.2 mm versus 0.28+/-0.22 mm in the IP group ( P=.9 ) . The mean distal marginal bone loss after 12 months in the IL group was 0.19+/-0.15 mm versus 0.2+/-0.11 mm in the IP group ( P=.87 ) . All implants of the IL group had an ideal gingival buccal margin , versus 91 % of the IP group . Full regeneration of the mesial interdental papilla was observed in 70 % of the IL group versus 91 % of the IP group , while full regeneration of the distal papilla was observed in 91 % of both the IL and IP implants . CONCLUSION No significant differences in ISQ mean values in radiographic bone loss and gingival esthetics were found between immediate non-loaded provisionalization and immediately loaded BioComp implants in the maxilla BACKGROUND The original Brånemark protocol for dental implant treatment was based on submerged healing prior to loading . However , immediate loading has been reported possible with high success rates for various indications , provided that good bone quality and quantity are present . In many of these studies , machined-surface implants have been used . Recently , a new surface texture has been developed , based on an oxidation processing , that aims to enhance the early bone response ( Brånemark System Mk IV TiUnite , Nobel Biocare AB , Gothenburg , Sweden ) . It has been documented that this surface texture may help to better maintain primary implant stability during the early healing period and that secondary implant stability can be reached earlier compared with results when using a machined surface . Such a positive influence on implant stability might be an advantage when applying an immediate-loading protocol , especially in soft bone regions where a tendency toward reduced success rates has been reported . PURPOSE The aim of this report was to present the short-term success rates of TiUnite-surfaced immediate occlusally loaded Brånemark System Mk IV implants placed in various regions of the jaws . MATERIAL S AND METHODS Thirty-eight patients received a total of 51 prosthetic reconstructions , all of which were connected on the day the implants were inserted . Of these , 20 were single-tooth restorations , 30 were fixed partial dentures , and 1 was a complete fixed lower jaw restoration . These prostheses were supported by 102 Brånemark System Mk IV TiUnite implants ( 38 maxillary and 64 m and ibular ) , the majority of which were placed in posterior regions ( 88 % ) and mainly in soft bone ( 76 % ) . Cutting resistance measurements were performed during implant insertion , and resonance frequency measurements were conducted during the course of the study . Furthermore , radiographic examinations were performed in connection with the delivery of the prostheses and at the 1- , 6- , and 12-month follow-up visits . This article reports on the results after 1 year of loading . RESULTS Three maxillary implants were removed , although stable , in one patient at the 8-week follow-up because of postoperative infection in the adjacent area of guided bone regeneration ( GBR ) . This result ed in a cumulative success rate of the implants of 97.1 % after 1 year of prosthetic loading . The mean marginal bone resorption after 1 year of loading was 1.2 + /- 0.9 mm ( SD ) . CONCLUSIONS The applied immediate loading protocol in combination with a slightly tapered implant and a modified implant surface texture was shown to be a successful treatment alternative even in regions exhibiting soft bone BACKGROUND Immediate occlusal and non-occlusal loading protocol s have been discussed and , despite varying success rates , are considered viable in selected cases . Preoperative implant planning and intraoperative transfer are essential to the success of implant-supported reconstructions in partially or completely edentulous jaws . PURPOSE This study was performed to compare clinical outcomes of immediate occlusal versus non-occlusal loading of posterior implants . MATERIAL S AND METHODS Of 19 patients with 52 screw-type implants replacing m and ibular molars or premolars , nine patients with 21 implants were r and omized to a study group that received immediate restorations with occlusal loading , whereas 10 patients with 31 implants were r and omized to a control group that received provisional restorations without occlusal loading . Occlusal loading was defined as full loading in maximum intercuspidation . Single-tooth or splinted multiunit restorations were incorporated by screw retention or cementation . Marginal bone defects ( MBD ) , implant survival , and implant success were evaluated 12 months after insertion . RESULTS Both groups revealed similar MBD levels consistent with previous reports . No implants were lost ( overall survival : 100 % ) or found to fail ( overall success : 100 % ) . No significant intergroup differences were noted for any of the evaluated parameters . CONCLUSIONS Immediate restorations in partially edentulous m and ibles demonstrated successful clinical and radiographic 12-month results . Larger long-term prospect i ve studies are needed to confirm the final evidence and predictability of immediate functional loading as a st and ard treatment concept for partially edentulous jaws |
2,647 | 22,258,990 | There is no evidence available from r and omised controlled trials to ascertain whether surgical intervention of humeral shaft fractures gives a better or worse outcome than no surgery . | BACKGROUND Fractures of the shaft of the humerus account for 1 % to 3 % of all fractures in adults .
The management of these fractures , including surgical intervention , varies widely .
OBJECTIVES To assess and compare the effects of surgical versus non-surgical intervention for non-pathological fractures of the humeral shaft in adults . | Summary . A comparison was made between 44 humeral fractures treated conservatively with functional bracing ( Group 1 ) and 45 treated by operation with a locking nail ( Group 2 ) . Thirty-eight of the 44 patients in Group 1 ( 86 % ) and 22 of the 45 patients in Group 2 ( 47 % ) regained full movement of the shoulder joint . The functional end results were somewhat better in Group 1 although over 90 % of patients in both groups were able to clasp their fingers behind their necks and to reach up their backs without restriction . Two patients developed a pseudarthrosis in Group 1 , and 2 patients in Group 2 required operative revision due to a haematoma in 1 case and as a result of an infection in the other . There were 6 cases of primary radial nerve damage in both groups , and 6 had to be decompressed operatively . Residual sensory and motor disturbance remained in 2 patients in Group 1 . Both methods are useful for the treatment of humeral shaft fractures . We advocate functional bracing as the method of choice if no contraindications exist . Résumé . 99 fractures de la diaphyse humérale ont été analysées , do nt 44 ont été traitées par brassard et 45 par clou intramédullaire . 86 % du groupe : traitement conservateur et 47 % du groupe : traitement opératoire présentaient un mouvement illimité de l’épaule , t and is que plus de 90 % des deux groupes arrivaient à toucher la nuque ( rotation externe en abduction ) et la sacrum ( rotation interne en adduction ) avec la main du bras blessé . Il y a eut deux pseudarthroses dans le groupe conservateur . Dans le groupe opératoire deux interventions chirurgicales ont été nécessaires en raison d’une infection et d’une hémorragie . Les deux groupes présentaient chacun 6 cas de paralysie primaire du nerf radial avec une décompression chirurgicale consécutive dans 6 cas . Des déficits moteurs et sensitifs persistaient chez deux malades du groupe conservateur . Les deux méthodes sont efficaces pour le traitement des fractures de la diaphyse de l’humérus . En cas d’absence des contre-indications nous recomm and ons le traitement par brassard comme traitement de premier choix This prospect i ve multicenter study conducted by the German section of the AO International analyzes 302 fractures of the humeral shaft , 170 ( 56 % ) of which were operated upon and 132 ( 44 % ) , treated conservatively . Among those operated upon , 3.5 % developed infections and 10 % showed paresis of the radial nerve . In contrast , the only complication in the group treated conservatively was pseudarthrosis , in 1 case . However , further analysis revealed that complications were distributed unequally among the centers and the most complications were reported from only a few hospitals . We were able to contact 173 ( 57 % ) patients for follow-up . Results of operative and conservative treatment were compared for similar fractures . Both techniques result ed in predominantly good to excellent results . The somewhat inferior results in the group operated upon were explained by the higher percentage of associated local injuries and concomitant injuries to other organs . The results of this study were compared with those of other recent studies , and recommendations were established for the operative and conservative treatment of fractures of the humeral shaft |
2,648 | 29,392,479 | The EORTC QLQ-C30 plus the NMIBC24 module was best aligned to the conceptual model , but failed to represent six outcomes important to NMIBC patients .
Conclusions Currently , some outcomes important in NMIBC are inadequately covered by generic and cancer-specific measures despite similar conceptual models .
This review identified gaps in the literature regarding assessment of symptoms and other PROs considered important by NMIBC patients . | Objective Non-muscle invasive bladder cancer ( NMIBC ) is a chronic condition requiring ongoing treatment and endoscopic examinations that are frequent and can be life-long .
To ensure the comprehensive assessment of the benefits and harms of treatments for NMIBC , the impact on important and relevant patient-reported outcomes ( PROs ) should be determined .
We systematic ally review ed the NMIBC PRO literature to determine the suitability of available PRO measures ( PROMs ) for use in evaluating patient outcomes in NMIBC research . | Abstract Objective : To compare chemotherapy given at home with outpatient treatment in terms of colorectal cancer patients ' safety , compliance , use of health services , quality of life , and satisfaction with treatment . Design : R and omised controlled trial . Setting : Large teaching hospital . Participants : 87 patients receiving adjuvant or palliative chemotherapy for colorectal cancer . Interventions : Treatment with fluorouracil ( with or without folinic acid or levamisole ) at outpatient clinic or at home . Main outcome measures : Treatment toxicity ; patients ' compliance with treatment , quality of life , satisfaction with care , and use of health re sources . Results : 42 patients were treated at outpatient clinic and 45 at home . The two groups were balanced in terms of age , sex , site of cancer , and disease stage . Treatment related toxicity was similar in the two groups ( difference 7 % ( 95 % confidence interval −12 % to 26 % ) ) , but there were more voluntary withdrawals from treatment in the outpatient group than in the home group ( 14 % v 2 % , difference 12 % ( 1 % to 24 % ) ) . There were no differences between groups in terms of quality of life scores during and after treatment . Levels of patient satisfaction were higher in the home treatment group , specifically with regard to information received and nursing care . There were no significant differences in use of health services . Conclusions : Home chemotherapy seemed an acceptable and safe alternative to hospital treatment for patients with colorectal cancer that may improve compliance and satisfaction with treatment . What is already known on this topic Home chemotherapy programmes have been proposed as an alternative to hospital treatment However , they are more costly , and there is little evidence on their impact on outcomes such as compliance , quality of life , or use of other health services What this study adds Home chemotherapy was not associated with an increased use of health services such as primary care or emergency departments Home chemotherapy had no effect on patients ' quality of life but increased their compliance with treatment and satisfaction , particularly with regard to nursing care Home chemotherapy seems an acceptable and safe alternative to outpatient treatment that may improve compliance with Significant morbidity and expense result from frequent recurrences of nonmuscle-invasive bladder cancer ( NMIBC ) after st and ard treatment , and carcinoma in situ ( Tis ) is a poor prognostic factor . Predicated on observational and pre clinical data strongly supporting cyclooxygenase-2 ( COX-2 ) in the pathogenesis , and the activity of COX-2 inhibitors , in bladder cancer , we conducted a r and omized , double-blind , placebo-controlled trial to determine whether celecoxib could reduce the time-to-recurrence ( TTR ) in NMIBC patients at high risk for recurrence . A total of 146 patients were r and omized to celecoxib ( 200 mg ) or placebo orally twice daily for at least 12 months . The average treatment duration was 1.25 years . Primary intent-to-treat analysis revealed celecoxib did not statistically significantly prolong TTR compared with placebo ( P = 0.17 , log rank ) with a median follow-up of 2.49 years . The recurrence-free rate at 12 months with celecoxib was 88 % ( 95 % CI : 0.81–0.96 ) versus 78 % ( 95 % CI : 0.69–0.89 ) with placebo . After controlling for covariates with Cox regression analysis , recurrence rates did not differ between the two study arms ( HR = 0.69 ; 95 % CI : 0.37–1.29 ) . However , celecoxib had a marginally significant effect on reducing metachronous recurrences ( vs. placebo ) with HR of 0.56 ( 95 % CI : 0.3–1.06 ; P = 0.075 ) . Celecoxib was well tolerated , with similar adverse events and quality -of-life in both arms . Our clinical trial results do not show a clinical benefit for celecoxib in preventing NMIBC recurrence but further investigation of COX-2 inhibitors in this setting is warranted . Cancer Prev Res ; 4(10 ) ; 1580–9 . © 2011 AACR PURPOSE Bacillus Calmette-Guérin and intravesical chemotherapy represent viable adjuvant options for intermediate risk nonmuscle invasive bladder cancer . Although bacillus Calmette-Guérin is perceived as less tolerable than intravesical chemotherapy , to our knowledge no comparative studies have addressed quality of life issues . We compared the quality of life of patients with nonmuscle invasive bladder cancer who received adjuvant intravesical gemcitabine or 1/3 dose bacillus Calmette-Guérin . MATERIAL S AND METHODS Our multicenter , prospect i ve , r and omized , phase II study included 120 patients with intermediate risk nonmuscle invasive bladder cancer . Of these patients 88 remained assessable at 1-year followup . Only 1 patient was withdrawn because of adverse events . Overall 61 patients received 2,000 mg/50 cc gemcitabine weekly for 6 weeks ( maintenance monthly for 1 year ) while 59 received 1/3 dose bacillus Calmette-Guérin Connaught weekly for 6 weeks ( maintenance 3 weekly instillations at 3 , 6 and 12 months ) . Quality of life was measured by the EORTC QLQ-C30 ( European Organization for the Research and Treatment of Cancer Quality of Life Question naire Core 30 version 3.0 ) and QLQ-BLS24 ( Quality of Life Superficial Bladder Cancer-Specific 24 ) question naires . Group differences were calculated using ANOVA ( ANOVA/MANOVA ) . RESULTS Treatment was well tolerated in both groups , although local and systemic side effects were more frequently reported in the bacillus Calmette-Guérin arm . Multivariate analyses showed no significant differences between the 2 groups in all quality of life dimensions . No significant changes over time in quality of life domains were detected for patients on bacillus Calmette-Guérin and gemcitabine except for physical functioning , which decreased significantly in both groups ( p = 0.002 ) . No significant differences were detected in terms of recurrence and progression between the 2 groups at 1-year followup . CONCLUSIONS While a higher rate of side effects , albeit mild to moderate , was detected with 1/3 dose bacillus Calmette-Guérin compared to gemcitabine , our study failed to show significant differences between the 2 drugs in terms of quality of life Background Bacillus Calmette-Guérin ( BCG ) is considered the most effective treatment to reduce recurrence and progression of non-muscle invasive bladder cancer ( NMIBC ) but can induce local side effects leading to treatment discontinuation or interruption . Aim of this exploratory study is to investigate if the sequential administration of Hyaluronic acid ( HA ) may reduce local side effects of BCG . Methods 30 consecutive subjects undergoing BCG intravesical administration for high risk NMIBC were r and omized to receive BCG only ( Group A ) or BCG and HA ( Group B ) . A 1 to 10 Visual Analog Scale ( VAS ) for bladder pain , International Prostate Symptom Score ( IPSS ) and number of micturitions per day were evaluated in the two groups before and after six weekly BCG instillations . Patients were also evaluated at 3 and 6 months by means of cystostopy and urine cytology . Results One out of 30 ( 3,3 % ) patients in group A dropped out from the protocol , for local side effects . Mean VAS for pain was significantly lower in group B after BCG treatment ( 4.2 vs. 5.8 , p = 0.04 ) . Post vs. pre treatment differences in VAS for pain , IPSS and number of daily micturitions were all significantly lower in group B. Three patients in group A and 4 in group B presented with recurrent pathology at 6 month follow up . Conclusions These preliminary data suggest a possible role of HA in reducing BCG local side effects and could be used to design larger r and omized controlled trials , assessing safety and efficacy of sequential BCG and HA administration . Trial registration NCT02207608 ( Clinical Trials.gov ) 01/08/2014Policlinico Tor Vergata Ethics Committee , resolution n 69–2011 Abstract Objective The aim of the study was to evaluate the impact of transurethral resection of bladder tumour ( TURBT ) on patients ’ quality of life ( QoL ) and to vali date a tool to quantify problems associated with TURBT in a Danish population . Material s and methods A prospect i ve study was carried out using a combination of question naires and interviews . The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer ( NMIBC ) from 1 May 2011 to 30 April 2012 . Seven patients were selected for interviews . The Danish translation of the QLQ-NMIBC24 Quality of Life Question naire for NMIBC , from the European Organisation for Research and Treatment of Cancer ( EORTC ) , was used . The interviews were semi-structured . The reliability of the subscales quantifying QoL as defined by the EORTC was tested by computing Cronbach ’s coefficient alpha and confirmatory factor analysis . The interviews were analysed using the phenomenological method . Results The question naire was returned by 121 ( 77 % ) patients at a mean of 12 days after hospital discharge . Over half had substantial voiding problems and one-third had emotional concerns . These results were confirmed by the interviews . The mean ± SD score for urinary symptoms was 45.21 ± 23.9 and the mean score for the future worries subscale was 39.9 ± 29.9 . Cronbach ’s coefficient alpha was 0.84 for the urinary symptom subscale and 0.93 for the future worries subscale , which satisfied the reliability criterion for clinical use . Conclusions This first prospect i ve study on QoL following TURBT in patients with NMIBC shows that TURBT has a significant impact on QoL. The Danish version of the EORTC question naire QLQ-NMIBC24 has been vali date d and confirmed in a Danish population OBJECTIVES We carried out a prospect i ve , r and omized , controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette-Guérin ( BCG ) for high-risk non-muscle invasive bladder cancer ( NMIBC ) . METHODS Intravesical instillation of 80 mg Tokyo strain was given to patients with high-risk NMIBC , including carcinoma in situ ( CIS ) , once weekly for eight consecutive weeks as induction therapy . Patients who achieved complete response ( CR ) were r and omly assigned to either the maintenance group or the observation group . RESULTS A total of 90 patients were enrolled . After induction therapy , 75 % of the patients achieved CR and 53 of them were enrolled in the r and omized comparative phase . A total of four maintenance instillations were given . Median follow-up was 26.5 and 28.7 months after r and omization in the maintenance and the observation group , respectively . Although it was not statistically significant , the 2-year recurrence-free survival rate in the maintenance group ( 95.8 % ) was higher than that in the observation group ( 74.1 % , P = 0.078 ) . Univariate analysis identified maintenance therapy as a significant factor influencing recurrence . During induction therapy , 82.2 % of patients experienced urination-related adverse drug reactions , but most events were not serious . There were fewer adverse drug reactions with maintenance therapy than with induction therapy . Neither induction therapy nor maintenance therapy reduced patients ' quality of life ( QOL ) . CONCLUSIONS These findings show high levels of efficacy and safety of BCG induction treatment for high-risk NMIBC , and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL PURPOSE In the treatment of cancer the subjective evaluation of therapy induced side effects and quality of life must be considered . Adjuvant intravesical bacillus Calmette-Guerin ( BCG ) immunotherapy is regarded as highly effective but associated with significant side effects . To clarify whether these side effects significantly impact on patient satisfaction with life , a prospect i ve survey of the health related quality of life and side effects was performed during an intravesical BCG treatment course . MATERIAL S AND METHODS Symptoms and side effects were recorded daily during the 6-week instillation period in 30 patients . The quality of life was determined before , during and after intravesical therapy with the assistance of a self-reported question naire . RESULTS Due to a detailed subjective assessment of side effects , the course of local symptoms could be characterized with great reliability . Although side effects occurred , satisfaction with life in the patients studied was high and was not impaired during the treatment . The incidence of side effects correlated well with patient subjective evaluation of quality of life . CONCLUSIONS Assessment of side effects and quality of life , as presented in this pilot study , can assist in the quantification of localized symptoms in intravesical therapy could contribute to the comparability of clinical studies . With regard to intravesical BCG immunotherapy , our results suggest that the specific side effects do not seriously impair satisfaction with life in these patients PURPOSE We studied the safety , tolerability and pharmacokinetics of a single immediate post-transurethral resection intravesical instillation of apaziquone for patients with nonmuscle invasive bladder cancer . MATERIAL S AND METHODS Patients with cTa-T1 , G1-G2 urothelial cell carcinoma of the bladder underwent transurethral resection of bladder tumor(s ) followed by a single intravesical instillation of apaziquone 4 mg/40 ml for 1 hour within 6 hours of transurethral bladder tumor resection . Adverse events and safety parameters were assessed on days 8 and 15 after transurethral bladder tumor resection . Blood sample s were drawn before and during the instillation for pharmacokinetic analyses . The first 10 patients with pTa-T1 , G1-G2 nonmuscle invasive bladder cancer were also evaluated by cystoscopy 3 months after treatment to determine mucosal healing . RESULTS Of 20 patients receiving apaziquone 13 ( 65 % ) reported 35 adverse events , mostly grade 1 to 2 . Eight patients ( 40 % ) reported 13 adverse events related to treatment , in particular dysuria , hematuria , bladder spasm , abdominal pain , asthenia and postoperative urinary retention . Three grade 3 and 1 grade 4 event(s ) occurred , but these were considered unrelated to treatment . No other significant clinical changes were observed . Apaziquone and the active metabolite EO5a were not detected with pharmacokinetic analyses at any point of time . After 3 months no evidence of impaired mucosal healing was observed . CONCLUSIONS A single immediate post-transurethral bladder tumor resection instillation of apaziquone was well tolerated with an expected good safety profile . Apaziquone and its metabolite EO5a were not detected systemically with pharmacokinetic analyses . These results have lead to further study of a single immediate instillation of apaziquone OBJECTIVE The aim of the study was to investigate the factor of adverse reactions related to compliance with Mycobacterium bovis bacillus Calmette-Guérin maintenance therapy in patients with high-risk non-muscle-invasive bladder cancer . METHODS This study was a post hoc analysis using the data base of a r and omized controlled trial that examined the efficacy of bacillus Calmette-Guérin ( Connaught strain ) maintenance therapy . Among the 42 patients assigned to the bacillus Calmette-Guérin maintenance therapy group , six patients dropped out or withdrew consent before the bacillus Calmette-Guérin maintenance therapy . The adverse reactions and clinical background s of the remaining 36 patients who underwent bacillus Calmette-Guérin maintenance therapy were compared between the two groups : the patients who completed the bacillus Calmette-Guérin maintenance therapy ( the Completed group ) , and those who discontinued the bacillus Calmette-Guérin maintenance therapy ( the Discontinued group ) . RESULTS Of the 36 patients who underwent bacillus Calmette-Guérin maintenance therapy , 15 ( 41.7 % ) were in the Completed group and 21 ( 58.3 % ) were in the Discontinued group . Local adverse reactions ( ≥G2 ) were observed during maintenance therapy in 86.7 % of the Completed group and 95.2 % of the Discontinued group . As for adverse reactions during the induction therapy ( bacillus Calmette-Guérin induction therapy ) , the frequencies of gross hematuria and systemic adverse reactions ( any grade ) tended to be higher in the Discontinued group than in the Completed group , although not significantly so . In the Cochran-Armitage trend test , the linear T trend ( i.e. the trend in the risk of an increased rate of discontinuation according to gross hematuria and systemic adverse reactions with bacillus Calmette-Guérin induction therapy ) was statistically significant ( P = 0.0179 ) . CONCLUSIONS Most patients who completed bacillus Calmette-Guérin maintenance therapy experienced local adverse reactions ( ≥G2 ) during the maintenance therapy . Gross hematuria and systemic adverse reactions during bacillus Calmette-Guérin induction therapy might be related to the discontinuation of bacillus Calmette-Guérin maintenance therapy because of severe adverse reactions PURPOSE The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial . We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of st and ard dose bacillus Calmette-Guérin , with less toxicity and higher quality of life . MATERIAL S AND METHODS After transurethral resection , patients with unresectable multiple nonmuscle invasive bladder cancer and /or carcinoma in situ were r and omized to receive st and ard ( 80 mg ) or low dose ( 40 mg ) bacillus Calmette-Guérin instillation induction therapy ( weekly , 8 times ) . The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15 % decrease in complete response rate . Secondary end points were recurrence-free survival , progression-free survival , overall survival , patient compliance , adverse events and quality of life using the EORTC QLQ-C30 . RESULTS In an intent to treat analysis of 166 patients the complete response rates for low dose and st and ard dose bacillus Calmette-Guérin were 79 % ( 95 % CI 0.70 - 0.88 ) and 85 % ( 95 % CI 0.77 - 0.92 ) , respectively . Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected ( p = 0.119 ) . However , there were no significant differences between the groups in terms of recurrence , progression and overall survival . Low dose bacillus Calmette-Guérin was associated with significantly less fever ( p = 0.001 ) and micturition pain ( p = 0.047 ) , and significantly higher quality of life scores for global quality of life , role functioning and functional impairment . CONCLUSIONS The noninferiority of low dose bacillus Calmette-Guérin was not proven . However , low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to st and ard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer BACKGROUND The schedule for intravesical chemotherapy administration has not been definitively established in patients with low- grade recurrent non-muscle-invasive bladder cancer ( NMIBC ) . OBJECTIVE To assess both the feasibility and the efficacy of a short-term intensive schedule of neoadjuvant intravesical chemotherapy in patients with recurrent NMIBC . DESIGN , SETTING , AND PARTICIPANTS A r and omised phase 2 clinical study included 54 patients with recurrent NMIBC who were su bmi tted to neoadjuvant chemotherapy intravesical instillations according to two different timing schedules . The study was performed at a tertiary care referral centre . INTERVENTION Intravesical mitomycin C ( MMC ) 40 mg/40 ml was administered according to a schedule of either one instillation per week for 6 wk ( group 1 ) or three instillations per week for 2 wk ( group 2 ) prior to transurethral resection ( TUR ) . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Local and systemic toxicity were investigated using the US National Cancer Institute 's ( NCI ) Common Terminology Criteria for Adverse Events ( CTCAE ) v.4.0 question naire at each instillation and the SF-36 question naire at r and omisation and before TUR . A video-recorded cystoscopy and TUR were performed within 14 d after treatment completion . RESULTS AND LIMITATIONS Groups 1 and 2 each were assigned 27 cases . Two patients ( 7.4 % ) in group 2 could not complete the scheduled treatment because of severe lower urinary tract symptoms . No statistically significant difference in SF-36 domain score was documented pre- and post-treatment between groups . Likewise , no statistically significant difference in treatment-related toxicity according to the CTCAE v.4 question naire was registered . Twelve patients ( 44.4 % ) in group 1 and 19 patients ( 70.4 % ) in group 2 ( p=0.054 ) had complete tumour response . The small number of patients included represents the main limitation of the study . CONCLUSIONS The intensive short-term schedule of neoadjuvant chemotherapy is safe and without additional toxicity compared with the weekly regimen . The increased ablative effect may be explained by the improved adherence of the scheduled timing to the duplication rate of tumour cells |
2,649 | 27,436,163 | DISCUSSION DPP-4 inhibitors demonstrated beneficial effects on the glycemic control for diabetic patients with CKD without causing any additional adverse effects . | INTRODUCTION Diabetes mellitus ( DM ) is the leading cause of chronic kidney disease ( CKD ) and the optimal glycemic control is key to delay the progression of the disease and prevent major complications .
Dipeptidyl peptidase-4 ( DPP-4 ) inhibitors have emerged as a promising therapeutic option .
However , the benefits and harms of the treatment have yet to be clarified for diabetic patients with CKD . | Thiazolidinediones ( TZDs ) reduce urinary albumin excretion and proteinuria in diabetic nephropathy . The effect of TZDs on hard renal outcome in diabetic patients with chronic kidney disease ( CKD ) is unknown . We investigate the association of TZDs and risk of long-term dialysis or death in diabetic patients with advanced CKD . The nationwide population -based cohort study was conducted using Taiwan ’s National Health Insurance Research Data base . From January 2000 to June 2009 , 12350 diabetic patients with advanced CKD ( serum creatinine levels greater than 6 mg/dL but not yet receiving renal replacement therapy ) were selected for the study . We used multivariable Cox regression models and a propensity score-based matching technique to estimate hazard ratios ( HRs ) for development of long-term dialysis and the composite outcome of long-term dialysis or death for TZD users ( n=1224 ) as compared to nonusers ( n=11126 ) . During a median follow-up of 6 months , 8270 ( 67.0 % ) patients required long-term dialysis and 2593 ( 21.0 % ) patients died before starting long-term dialysis . Using propensity score matched analysis , we found TZD users were associated with a lower risk for long-term dialysis ( HR , 0.80 ; 95 % confidence interval [ CI ] , 0.74 - 0.86 ) and the composite outcome of long-term dialysis or death ( HR , 0.85 ; 95 % CI , 0.80 - 0.91 ) . The results were consistent across most patient subgroups . Use of TZDs among diabetic patients with advanced CKD was associated with lower risk for progression to end-stage renal disease necessitating long-term dialysis or death . Further r and omized controlled studies are required to vali date this association BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents , including saxagliptin , a dipeptidyl peptidase 4 ( DPP-4 ) inhibitor , are unclear . METHODS We r and omly assigned 16,492 patients with type 2 diabetes who had a history of , or were at risk for , cardiovascular events to receive saxagliptin or placebo and followed them for a median of 2.1 years . Physicians were permitted to adjust other medications , including antihyperglycemic agents . The primary end point was a composite of cardiovascular death , myocardial infa rct ion , or ischemic stroke . RESULTS A primary end-point event occurred in 613 patients in the saxagliptin group and in 609 patients in the placebo group ( 7.3 % and 7.2 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio with saxagliptin , 1.00 ; 95 % confidence interval [ CI ] , 0.89 to 1.12 ; P=0.99 for superiority ; P<0.001 for noninferiority ) ; the results were similar in the " on-treatment " analysis ( hazard ratio , 1.03 ; 95 % CI , 0.91 to 1.17 ) . The major secondary end point of a composite of cardiovascular death , myocardial infa rct ion , stroke , hospitalization for unstable angina , coronary revascularization , or heart failure occurred in 1059 patients in the saxagliptin group and in 1034 patients in the placebo group ( 12.8 % and 12.4 % , respectively , according to 2-year Kaplan-Meier estimates ; hazard ratio , 1.02 ; 95 % CI , 0.94 to 1.11 ; P=0.66 ) . More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure ( 3.5 % vs. 2.8 % ; hazard ratio , 1.27 ; 95 % CI , 1.07 to 1.51 ; P=0.007 ) . Rates of adjudicated cases of acute and chronic pancreatitis were similar in the two groups ( acute pancreatitis , 0.3 % in the saxagliptin group and 0.2 % in the placebo group ; chronic pancreatitis , < 0.1 % and 0.1 % in the two groups , respectively ) . CONCLUSIONS DPP-4 inhibition with saxagliptin did not increase or decrease the rate of ischemic events , though the rate of hospitalization for heart failure was increased . Although saxagliptin improves glycemic control , other approaches are necessary to reduce cardiovascular risk in patients with diabetes . ( Funded by AstraZeneca and Bristol-Myers Squibb ; SAVOR-TIMI 53 Clinical Trials.gov number , NCT01107886 . ) AIM To evaluate the efficacy and safety of saxagliptin vs. placebo in patients with type 2 diabetes mellitus ( T2DM ) and renal impairment . METHODS In this multicentre , r and omized , parallel-group , double-blind , placebo-controlled study , patients with glycated haemoglobin ( HbA1c ) 7 - 11 % and creatinine clearance < 50 ml/min were stratified by baseline renal impairment ( moderate , severe or end-stage on haemodialysis ) , and r and omized ( 1 : 1 ) to saxagliptin 2.5 mg once daily or placebo for 12 weeks . Oral antihyperglycaemic drugs and insulin therapy present at enrolment were continued throughout the study . The absolute change in HbA1c from baseline to week 12 ( primary efficacy end-point ) was analysed using an analysis of covariance model with last observation carried forward methodology . RESULTS A total of 170 patients were r and omized and treated . The adjusted mean decrease from baseline to week 12 in HbA1c was statistically significantly greater in the saxagliptin group than in the placebo group ; the difference between treatments was -0.42 % ( 95 % confidence interval : -0.71 to -0.12 % , p = 0.007 ) . Adjusted mean HbA1c decreases from baseline to week 12 were numerically greater with saxagliptin than with placebo in the subgroups of patients with moderate ( -0.64 vs. -0.05 % ) and severe ( -0.95 vs. -0.50 % ) renal impairment . HbA1c reductions were similar between saxagliptin and placebo in the subgroup with end-stage renal disease on haemodialysis ( -0.84 vs. -0.87 % ) . Saxagliptin was generally well tolerated ; incidences of adverse events and hypoglycaemic events were similar to placebo . CONCLUSIONS Saxagliptin 2.5 mg once daily is a well-tolerated treatment option for patients with inadequately controlled T2DM and renal impairment BACKGROUND Treatment with oral antihyperglycemic agents has not been well characterized in patients with type 2 diabetes and end-stage renal disease ( ESRD ) . The efficacy and safety of sitagliptin and glipizide monotherapy in patients with type 2 diabetes and ESRD on dialysis therapy were assessed in this study . STUDY DESIGN 54-week , r and omized , double-blind , parallel-arm study . SETTING & PARTICIPANTS From 31 clinical sites in 12 countries , 129 patients 30 years or older with type 2 diabetes and ESRD who were on dialysis therapy and had a hemoglobin A1c ( HbA1c ) level of 7%-9 % were r and omly assigned 1:1 to treatment . INTERVENTION Monotherapy with sitagliptin , 25 mg daily or glipizide ( initiated with 2.5 mg daily and titrated up to a potential maximum dose of 10 mg twice daily or down to avoid hypoglycemia ) . OUTCOMES Primary end points were 54-week change in HbA1c level from baseline and tolerability with sitagliptin . A secondary end point was the comparison of sitagliptin versus glipizide on the incidence of symptomatic hypoglycemia . RESULTS Of 129 patients r and omly assigned , 64 were in the sitagliptin group ( mean baseline age , 61 years ; HbA1c , 7.9 % ) and 65 were in the glipizide group ( mean baseline age , 59 years ; HbA1c , 7.8 % ) . After 54 weeks , the least squares mean change from baseline in HbA1c level was -0.72 % ( 95 % CI , -0.95 % to -0.48 % ) with sitagliptin and -0.87 % ( 95 % CI , -1.11 % to -0.63 % ) with glipizide , for a difference of 0.15 % ( 95 % CI , -0.18 % to 0.49 % ) . The incidences of symptomatic hypoglycemia and severe hypoglycemia were 6.3 % versus 10.8 % ( between-group difference , -4.8 % [ 95 % CI , -15.7 % to 5.6 % ] ) and 0 % versus 7.7 % ( between-group difference , -7.8 % [ 95 % CI , -17.1 % to -1.9 % ] ) in the sitagliptin and glipizide groups , respectively . Higher incidences ( ie , 95 % CI around between-treatment difference excluded 0 ) of cellulitis and headache were found with sitagliptin compared to glipizide ( 6.3 % vs 0 % , respectively , for both ) . LIMITATIONS Small sample size limits between-group comparisons . CONCLUSIONS Treatment with sitagliptin or glipizide monotherapy was effective and well tolerated over 54 weeks in patients with type 2 diabetes and ESRD who were receiving dialysis OBJECTIVE Patients with type 2 diabetes mellitus ( T2DM ) and chronic kidney disease have an increased risk of micro- and macrovascular disease , but limited options for antihyperglycemic therapy . We compared the efficacy and safety of sitagliptin with glipizide in patients with T2DM and moderate-to-severe chronic renal insufficiency and inadequate glycemic control . RESEARCH DESIGN AND METHODS Patients ( n = 426 ) were r and omized 1:1 to sitagliptin ( 50 mg every day [ q.d . ] for moderate renal insufficiency and 25 mg q.d . for severe renal insufficiency ) or glipizide ( 2.5 mg q.d . , adjusted based on glycemic control to a 10-mg twice a day maximum dose ) . R and omization was stratified by : 1 ) renal status ( moderate or severe renal insufficiency ) ; 2 ) history of cardiovascular disease ; and 3 ) history of heart failure . RESULTS At week 54 , treatment with sitagliptin was noninferior to treatment with glipizide in A1C change from baseline ( −0.8 vs. −0.6 % ; between-group difference −0.11 % ; 95 % CI −0.29 to 0.06 ) because the upper bound of the 95 % CI was less than the prespecified noninferiority margin of 0.4 % . There was a lower incidence of symptomatic hypoglycemia adverse events ( AEs ) with sitagliptin versus glipizide ( 6.2 and 17.0 % , respectively ; P = 0.001 ) and a decrease in body weight with sitagliptin ( −0.6 kg ) versus an increase ( 1.2 kg ) with glipizide ( difference , −1.8 kg ; P < 0.001 ) . The incidence of gastrointestinal AEs was low with both treatments . CONCLUSIONS In patients with T2DM and chronic renal insufficiency , sitagliptin and glipizide provided similar A1C-lowering efficacy . Sitagliptin was generally well-tolerated , with a lower risk of hypoglycemia and weight loss versus weight gain , relative to glipizide OBJECTIVE To assess the safety of sitagliptin in patients with type 2 diabetes and moderate [ creatinine clearance ( CrCl ) > or = 30 to < 50 ml/min ] or severe renal insufficiency [ CrCl < 30 ml/min including patients with end-stage renal disease ( ESRD ) on dialysis ] . The efficacy of sitagliptin in this patient population was also assessed . METHODS In a 54-week , r and omized , double-blind , parallel-group study , patients with baseline glycosylated haemoglobin A(1c ) ( HbA(1c ) ) values of 6.5 - 10 % were allocated ( 2:1 ) to sitagliptin ( for 54 weeks ) or the sequence of placebo ( for 12 weeks ) followed by active treatment with glipizide ( for 42 weeks ) . To achieve plasma concentrations similar to those observed in patients with normal renal function treated with 100 mg sitagliptin once daily , patients with moderate renal insufficiency were allocated to receive sitagliptin 50 mg once daily and patients with severe renal insufficiency to receive 25 mg once daily . Glipizide treatment was initiated at 2.5 or 5 mg/day and uptitrated to a maximum of 20 mg/day . RESULTS Patients ( N = 91 ) with a mean baseline HbA(1c ) value of 7.7 % ( range : 6.2 - 10.3 % ) were r and omized to sitagliptin ( n = 65 ) or placebo ( n = 26 ) . After 12 weeks , the mean change [ 95 % confidence interval ( CI ) ] from baseline in HbA(1c ) was -0.6 % ( -0.8 , -0.4 ) in the sitagliptin group compared with -0.2 % ( -0.4 , 0.1 ) in the placebo group [ between-group difference ( 95 % CI ) = -0.4 % ( -0.7 , -0.1 ) ] . At 54 weeks , patients continuously treated with sitagliptin had a mean change ( 95 % CI ) from baseline in HbA(1c ) of -0.7 % ( -0.9 , -0.4 ) . The overall incidence of adverse experiences was generally similar between groups . Between-group differences in incidences of specific clinical adverse experiences were generally small ; however , the proportion of patients for whom hypoglycaemia was reported was lower in the sitagliptin group ( 4.6 % ) compared with the placebo/glipizide group ( 23.1 % ) . Consistent with the high mortality risk in this patient population , there were six deaths during this 54-week study [ 5 of 65 patients ( 7.7 % ) in the sitagliptin group and 1 of 26 patients ( 3.8 % ) in the placebo/glipizide group ] ; no death was considered by the investigator to be drug related . The overall incidences of drug-related and serious adverse experiences and discontinuations because of adverse experiences were generally similar between groups . CONCLUSIONS In this study , sitagliptin was generally well tolerated and provided effective glycaemic control in patients with type 2 diabetes and moderate to severe renal insufficiency , including patients with ESRD on dialysis OBJECTIVE Therapeutic options are limited for diabetes patients with renal disease . This report presents 52-week results from a study assessing the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus ( T2DM ) and renal impairment . DESIGN Double-blind study in patients stratified by baseline renal impairment ( moderate , severe or end-stage renal disease [ ESRD ] on haemodialysis ) r and omised to saxagliptin 2.5 mg once daily or placebo added to other antidiabetic drugs in use at baseline , including insulin . PATIENTS A total of 170 adults with glycated haemoglobin ( HbA(1c ) ) 7 - 11 % and creatinine clearance < 50 ml/min or ESRD were r and omised and treated . MEASUREMENTS Absolute changes in HbA(1c ) and fasting plasma glucose ( FPG ) from baseline to week 52 were evaluated using analysis of covariance ( ANCOVA ) with last observation carried forward . Repeated- measures analyses were also performed . RESULTS Adjusted mean decrease in HbA(1c ) was greater with saxagliptin than placebo ( difference , -0.73 % , p < 0.001 [ ANCOVA ] ) . Reductions in adjusted mean HbA(1c ) were numerically greater with saxagliptin than placebo in patients with renal impairment rated as moderate ( -0.94 % vs. 0.19 % respectively ) or severe ( -0.81 % vs. -0.49 % ) , but similar to placebo for those with ESRD ( -1.13 % vs. -0.99 % ) . Reductions in adjusted mean FPG were numerically greater with saxagliptin in patients with moderate or severe renal impairment . Saxagliptin was generally well tolerated ; similar proportions of patients in the saxagliptin and placebo groups reported hypoglycaemic events ( 28 % and 29 % respectively ) . CONCLUSIONS Saxagliptin 2.5 mg once daily offers sustained efficacy and good tolerability for patients with T2DM and renal impairment The potent and selective dipeptidyl peptidase-4 inhibitor vildagliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α- and β-cell responsiveness to glucose . We conducted a prospect i ve , open-label , parallel group , controlled study of 51 patients with type 2 diabetic patients undergoing hemodialysis ( HD ) during the 24-week study period . Patients were assigned to two groups : the vildagliptin group ( n = 30 ) and the control group ( n = 21 ) . Vildagliptin was administered at 50 mg/day for the first 8 weeks . Then doses were titrated by dose-doubling to a maximum of 100 mg/day if hemoglobin A1c ( HbA1c ) or glycated albumin ( GA ) target levels had not been reached . No vildagliptin was administered to the controls . The average final dose of vildagliptin was 80 ± 5 mg daily . After 24 weeks , vildagliptin had decreased average HbA1c levels from 6.7 % baseline to 6.1 % , average GA levels from 24.5 % baseline to 20.5 % and average postpr and ial plasma glucose levels from 186 mg/dL baseline to 140 mg/dL ( all p < 0.0001 ) . In the control group , we observed no such changes . Vildagliptin efficacy did not differ according to age or body mass index , but the GA reduction was significantly greater in the anti-diabetic agents-naïve group . Furthermore , in patients with higher baseline GA levels , a higher vildagliptin dosage was required to produce a noticeable effect . No serious adverse effects such as hypoglycemia or liver impairment were observed in any patient . Vildagliptin was effective as a treatment for diabetic patients undergoing HD OBJECTIVE This placebo-controlled study assessed long-term efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in patients with type 2 diabetes and severe renal impairment ( RI ) . RESEARCH DESIGN AND METHODS In this 1-year , double-blind study , 133 patients with type 2 diabetes ( HbA1c 7.0–10.0 % ) and severe RI ( estimated glomerular filtration rate [ eGFR ] < 30 mL/min/1.73 m2 ) at screening were r and omized to linagliptin 5 mg ( n = 68 ) or placebo ( n = 65 ) once daily , added to existing background therapy . The primary efficacy end point was HbA1c change from baseline to week 12 . Efficacy and safety end points were assessed after 1 year . RESULTS At week 12 , adjusted mean HbA1c decreased by −0.76 % with linagliptin and −0.15 % with placebo ( treatment difference , −0.60 % ; 95 % CI −0.89 to −0.31 ; P < 0.0001 ) . HbA1c improvements were sustained with linagliptin ( −0.71 % ) over placebo ( 0.01 % ) at 1 year ( treatment difference −0.72 % , −1.03 to −0.41 ; P < 0.0001 ) . Mean insulin doses decreased by −6.2 units with linagliptin and −0.3 units with placebo . Overall adverse event incidence was similar over 1 year ( 94.1 vs. 92.3 % ) . Incidence of severe hypoglycemia with linagliptin and placebo was comparably low ( three patients per group ) . Linagliptin and placebo had little effect on renal function ( median change in eGFR , −0.8 vs. −2.2 mL/min/1.73 m2 ) , and no drug-related renal failure occurred . CONCLUSIONS In patients with type 2 diabetes and severe RI , linagliptin provided clinical ly meaningful improvements in glycemic control with very low risk of severe hypoglycemia , stable body weight , and no cases of drug-related renal failure . The potential for linagliptin to spare insulin and provide long-term renal safety warrants further investigations CONTEXT In response to a meal , glucagon-like peptide-1 ( GLP-1 ) and glucose-dependent insulinotropic peptide ( GIP ) are released and modulate glycemic control . Normally these incretins are rapidly de grade d by dipeptidyl peptidase-4 ( DPP-4 ) . DPP-4 inhibitors are a novel class of oral antihyperglycemic agents in development for the treatment of type 2 diabetes . The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test ( OGTT ) were evaluated . OBJECTIVE The objective of the study was to examine the pharmacodynamics , pharmacokinetics , and tolerability of sitagliptin . DESIGN This was a r and omized , double-blind , placebo-controlled , three-period , single-dose crossover study . SETTING The study was conducted at six investigational sites . PATIENTS The study population consisted of 58 patients with type 2 diabetes who were not on antihyperglycemic agents . INTERVENTIONS Interventions included sitagliptin 25 mg , sitagliptin 200 mg , or placebo . MAIN OUTCOME MEASURES Measurements included plasma DPP-4 activity ; post-OGTT glucose excursion ; active and total incretin GIP levels ; insulin , C-peptide , and glucagon concentrations ; and sitagliptin pharmacokinetics . RESULTS Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h , enhanced active GLP-1 and GIP levels , increased insulin/C-peptide , decreased glucagon , and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25- or 200-mg doses of sitagliptin . Sitagliptin was generally well tolerated , with no hypoglycemic events . CONCLUSIONS In this study in patients with type 2 diabetes , near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80 % or greater , corresponding to a plasma sitagliptin concentration of 100 nm or greater , and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT AIM Assess long-term safety and efficacy of the dipeptidlyl peptidase-4 ( DPP-4 ) inhibitor vildagliptin in 369 patients with type 2 diabetes mellitus ( T2DM ) and moderate or severe renal impairment ( RI ) . METHODS Double-blind , r and omized , parallel-group , 52-week clinical trial comparing safety and efficacy of vildagliptin ( 50 mg qd , n = 216 ) and placebo ( n = 153 ) added to ongoing stable antihyperglycaemic treatment , in patients with T2DM and moderate or severe ( glomerular filtration rate [ GFR ] ≥ 30 to < 50 ml/min/1.73 m(2 ) and < 30 ml/min/1.73 m(2 ) ) RI . RESULTS The study population comprised 122 and 89 patients with moderate RI and 94 and 64 patients with severe RI r and omized to vildagliptin and placebo , respectively , with the majority of patients receiving background insulin therapy ( 72 % and 82 % for moderate and severe RI , respectively ) . After 1 year , the between-treatment difference in adjusted mean change in A1C was -0.4 ± 0.2 % ( p = 0.005 ) in moderate RI ( baseline = 7.8 % ) and -0.7 ± 0.2 % ( p < 0.0001 ) in severe RI ( baseline = 7.6 % ) . In patients with moderate RI , similar proportions of patients experienced any adverse event ( AE ) ( 84 vs. 85 % ) , any serious adverse event ( SAE ) ( 21 vs. 19 % ) , any AE leading to discontinuation ( 5 % vs. 6 % ) and death ( 1 % vs. 0 % ) with vildagliptin and placebo , respectively . This was also true for patients with severe RI : AEs ( 85 % vs. 88 % ) , SAEs ( 25 % vs. 25 % ) , AEs leading to discontinuation ( 10 % vs. 6 % ) and death ( 3 % vs. 2 % ) . CONCLUSIONS In patients with T2DM and moderate or severe RI , vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo during 1-year observation . Furthermore , relative to placebo , a clinical ly significant decrease in A1C was maintained throughout 1-year treatment with vildagliptin AIM Assess safety/tolerability and efficacy of the DPP-4 inhibitor vildagliptin in 515 patients with type 2 diabetes mellitus ( T2DM ) and moderate or severe renal impairment ( RI ) . METHODS Double-blind , r and omized , parallel-group , placebo-controlled , 24-week clinical trial assessing safety and efficacy of vildagliptin ( 50 mg qd ) added to current antidiabetic therapy , in patients with T2DM and moderate or severe RI ( GFR ≥ 30 to < 50 or < 30 ml/min/1.73 m(2 ) ) . RESULTS The study population comprised of 165 and 129 patients with moderate RI and 124 and 97 patients with severe RI r and omized to vildagliptin and placebo , respectively , with most patients receiving background insulin therapy ( 68 and 81 % for moderate and severe RI , respectively ) . After 24 weeks , the between-treatment difference in the adjusted mean change in A1C was -0.5 ± 0.1 % ( p < 0.0001 ) in moderate RI ( baseline A1C = 7.9 % ) and -0.6 ± 0.1 % ( p < 0.0001 ) in severe RI ( baseline A1C = 7.7 % ) . In patients with moderate RI , similar proportions of those receiving vildagliptin or placebo experienced any AE ( 68 vs. 73 % ) , any SAE ( 9 vs. 9 % ) , any AE leading to discontinuation ( 3 vs. 5 % ) or death ( 1 vs. 1 % ) . This was also true for patients with severe RI : AEs ( 73 vs. 74 % ) , SAEs ( 19 vs. 21 % ) , AEs leading to discontinuation ( 9 vs. 6 % ) and death ( 2 vs. 4 % ) . CONCLUSIONS In this 24-week study of 515 patients with T2DM and moderate or severe RI , vildagliptin added to ongoing antidiabetic therapy had a safety profile similar to placebo . Further , relative to placebo , vildagliptin elicited a statistically and clinical ly significant decrease in A1C in patients with moderate or severe RI |
2,650 | 29,648,594 | Provider-initiated opt-in testing was the most frequently investigated modality .
Testing at entry and provider-initiated testing were reported to result in comparatively higher uptake ranges .
However , no comparative studies were identified that reported statistically significant differences between testing modalities .
Positivity rates among tested inmates ranged broadly but were generally high for all diseases .
Scale-up of provider-initiated testing in European correctional facilities could substantially reduce the undiagnosed fraction and , hence , prevent additional disease transmission in both prison setting s and the community at large | Prison population s are disproportionally affected by communicable diseases when compared with the general community because of a complex mix of socioeconomic determinants and environmental factors .
Tailored and adequate health care provision in prisons has the potential to reach vulnerable and underserved groups and address their complex needs . | Background Approximately 10 million Americans enter jails annually . The Centers for Disease Control and Prevention now recommends routine opt-out HIV testing in these setting s. The logistics for performing routine opt-out HIV testing within jails , however , remain controversial . The objective of this study was to evaluate the optimal time to routinely HIV test newly incarcerated jail detainees using an opt-out strategy . Methods This prospect i ve , controlled trial of routine opt-out HIV testing was conducted among 298 newly incarcerated male inmates in an urban men 's jail in New Haven , Connecticut . 298 sequential entrants to the men 's jail over a three week period in March and April 2008 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration : immediate ( same day , n = 103 ) , early ( next day , n = 98 ) , or delayed ( 7 days , n = 97 ) . The primary outcome was the proportion of men in each group consenting to testing . Results Routine opt-out HIV testing was significantly higher for the early ( 53 % : AOR = 2.6 ; 95 % CI = 1.5 to 4.7 ) and immediate ( 45 % : AOR = 2.3 ; 95 % CI = 1.3 to 4.0 ) testing groups compared to the delayed ( 33 % ) testing group . The immediate and early testing groups , however , did not significantly differ ( p = 0.67 ) . In multivariate analyses , factors significantly associated with routine opt-out HIV testing were assignment to the ‘ early ’ testing group ( p = 0.0003 ) and low ( bond ≥$5,000 , immigration or federal charges or pre-sentencing > 30 days ) likelihood of early release ( p = 0.04 ) . Two subjects received preliminary positive results and one of them was subsequently confirmed HIV seropositive . Conclusions In this men 's jail where attrition was high , routine opt-out HIV testing was not only feasible , but result ed in the highest rates of HIV testing when performed within 24 hours of incarceration . Trial Registration Clinical Trials.gov Background Ten million Americans enter jails annually . The objective was to evaluate new CDC guidelines for routine opt-out HIV testing and examine the optimal time to implement routine opt-out HIV testing among newly incarcerated jail detainees . Methods This prospect i ve , controlled trial of routine opt-out HIV testing was conducted among 323 newly incarcerated female inmates in Connecticut 's only women 's jail . 323 sequential entrants to the women 's jail over a five week period in August and September 2007 were assigned to be offered routine opt-out HIV testing at one of three points after incarceration : immediate ( same day , n = 108 ) , early ( next day , n = 108 ) , or delayed ( 7 days , n = 107 ) . The primary outcome was the proportion of women in each group consenting to testing . Results Routine opt-out HIV testing was significantly highest ( 73 % ) among the early testing group compared to 55 % for immediate and 50 % for 7 days post-entry groups . Other factors significantly ( p = 0.01 ) associated with being HIV tested were younger age and low likelihood of early release from jail based on bond value or type of charge for which women were arrested . Conclusions In this correctional facility , routine opt-out HIV testing in a jail setting was feasible , with highest rates of testing if performed the day after incarceration . Lower testing rates were seen with immediate testing , where there is a high prevalence of inability or unwillingness to test , and with delayed testing , where attrition from jail increases with each passing day . Trial Registration Clinical Trials.gov Background : The prevalence of hepatitis C ( HCV ) is elevated within prison population s , yet diagnosis in prisons remains low . Dried blood spot testing ( DBST ) is a simple procedure for the detection of HCV antibodies ; its impact on testing in the prison context is unknown . Methods : We carried out a stepped-wedge cluster-r and omized control trial of DBST for HCV among prisoners within five male prisons and one female prison . Each prison was a separate cluster . The order in which the intervention ( training in use of DBST for HCV testing and logistic support ) was introduced was r and omized across clusters . The outcome measure was the HCV testing rate by prison . Imputation analysis was carried out to account for missing data . Planned and actual intervention times differed in some prisons ; data were thus analysed by intention to treat ( ITT ) and by observed step times . Results : There was insufficient evidence of an effect of the intervention on testing rate using either the ITT intervention time ( OR : 0.84 ; 95 % CI : 0.68–1.03 ; P = 0.088 ) or using the actual intervention time ( OR : 0.86 ; 95 % CI : 0.71–1.06 ; P = 0.153 ) . This was confirmed by the pooled results of five imputed data sets . Conclusions : DBST as a st and -alone intervention was insufficient to increase HCV diagnosis within the UK prison setting . Factors such as staff training and allocation of staff time for regular clinics are key to improving service delivery . We demonstrate that prisons can conduct rigorous studies of new interventions , but data collection can be problematic . Trial registration : International St and ard R and omized Controlled Trial Number Register ( IS RCT N number IS RCT N05628482 ) OBJECTIVES We sought to determine the preventive healthcare needs of incarcerated women in the following areas : cervical cancer and breast cancer screening , sexually transmitted infection ( STI ) screening , hepatitis screening and vaccination , and smoking cessation . METHODS A cross-sectional interview survey of a r and om sample of 100 incarcerated women at the Rhode Isl and Department of Corrections ( RIDOC ) in Cranston , Rhode Isl and , was conducted . RESULTS Participants were 62 % white , 11 % African American , 13 % Hispanic , and 14 % of mixed race . Mean age was 35 years . Of those surveyed , 67 % reported having had a Papanicolou ( Pap ) smear in the past year , the strongest predictor of which was having received a Pap smear while incarcerated . Of the inmates > 40 years old , 58 % reported having had a mammogram in the past 2 years . The majority ( 88 % ) reported testing for STIs in the past , and 39 % desired testing during their current incarceration . As for hepatitis C , 70 % had been tested previously and 37 % of those reported testing positive . Hispanics were less likely than whites to have been tested for hepatitis C ( OR 0.1 ) . Over half ( 54 % ) of the women who reported testing positive for hepatitis C also reported having completed the hepatitis A and B vaccine series . Among smokers ( 80 % of all survey participants ) , 61 % were interested in quitting . Those who had been incarcerated multiple times were less likely to want to quit smoking ( OR 0.1 ) . CONCLUSIONS Incarceration presents a unique opportunity to provide preventive healthcare to high-risk , medically underserved women OBJECTIVES In 2010 only 30.9 % , of the Puy-de-Dome prison detainees were screened for human immunodeficiency virus ( HIV ) , hepatitis C virus ( HCV ) and hepatitis B virus ( HBV ) . Our goal was then to promote these assesments , as well as to identify addictive behaviour using FAGERSTROM , Cannabis Abuse Screening Test and CAGE tests , diagnose fibrosis by means of Fibrometer or Fibroscan in hepatic virus carriers and heavy drinkers , and perform HBV vaccinations . SETTING This prospect i ve study of adult detainees in the prisons of Puy-de-Dome , France , took place from June 2012 to December 2013 . RESULTS Of the 702 incarcerated individuals , 396(56.4 % ) were screened and 357(50.9 % ) enrolled . HIV prevalence was 0.3 % , HCV 4.7 % and HBV 0.6 % . While 234/294(79.6 % ) smokers and 115/145(79.3 % ) cannabis users were screened for dependence , excessive alcohol consumption was tested for in 91/179(50.8 % ) cases . Fibrosis was screened for in 75/80(93.7 % ) individuals selected with 16.0 % presenting with moderate to severe fibrosis , 4/9(44.4 % ) HCV carriers and 8/65(12.3 % ) excessive alcohol consumers . HBV vaccination was given to 81/149(54.4 % ) individuals with no serological markers . A total of nine HIV tests were conducted at the 57 discharge consultations , involving 215 detainees being released , all of which were negative . CONCLUSION The promotion of these evaluations proved beneficial , although viral screening could be achieved for only approaching half of the detainees , as could alcohol consumption assessment and HBV vaccination for those concerned . Fibrosis screening revealed lesions in HCV carriers yet also in heavy drinkers , who are typically less likely to be assessed . Consultations and HIV screening on release were found to be rarely possible We sought to determine the prevalence and correlates of self-reported HIV testing among inmates in correctional centers in Ontario , Canada . A cross-sectional survey was conducted with a stratified r and om sample of 597 male and female adult inmates . The participation rate was 89 % . Descriptive statistics and multiple logistic regression were used to analyze HIV testing . Fifty-eight percent had ever been tested , and 21 % had voluntarily tested while incarcerated in the past year . Having ever been tested was more common among those at risk for HIV through injection drug use ( IDU ) or sexual behavior . Testing while incarcerated in the past year was independently associated with being single ( OR = 2.6 ) , frequent IDU ( OR = 4.0 ) , not having casual sex partners prior to incarceration ( OR = 0.53 ) , a history of hepatitis ( OR = 2.4 ) , previous HIV testing ( OR = 3.7 ) , a close relationship with an HIV-positive person in the outside community ( OR = 1.7 ) , knowing an HIV-positive person inside ( OR = 2.7 ) , a perceived chance of being infected during incarceration ( OR = 2.2 ) , and support of m and atory testing ( OR = 2.0 ) . The predominant motivations for testing while incarcerated were IDU or fears of infection inside , possibly through contact with blood , during fights , or even by casual contact . Voluntary HIV testing in prison should be encouraged , and inmates should receive appropriate counseling and information to allow realistic assessment of risk SETTING The correctional system in the United States is large and growing . The Centers for Disease Control and Prevention recommend baseline and annual testing of employees in correctional facilities for latent tuberculosis infection ( LTBI ) . OBJECTIVE To describe the extent of and factors associated with LTBI testing practice s for jail correctional officers . DESIGN A national survey of 1760 r and omly selected jails was conducted . We used multivariable logistic regression models to examine factors associated with testing officers in a guideline -concordant manner and having a written policy . RESULTS A total of 1174 ( 67 % ) surveys were returned . Only 52 % of jails had a written policy on LTBI testing of officers , and 51 % screened officers at least annually ( guideline concordance ) . Large jails ( OR 2.41 , 95%CI 1.67 - 3.49 ) and jails in states with a high tuberculosis incidence ( OR 1.67 , 95%CI 1.17 - 2.38 ) and in the Midwest ( OR 1.58 , 95%CI 1.07 - 2.33 ) were more likely to screen in a guideline -concordant manner . CONCLUSION Screening for LTBI among correctional officers in the United States was inconsistent . Strategies to improve LTBI testing among correctional officers are needed OBJECTIVES To evaluate the effectiveness and cost-effectiveness of testing for hepatitis C ( HCV ) among former injecting drug users ( IDUs ) . DATA SOURCES Electronic data bases 1996-October 2004 . Trent Regional Data base Study . Routine UK mortality data . REVIEW METHODS A decision analytic model was developed to investigate the impact of case-finding and treatment on progression of HCV disease in a hypothetical cohort of 1000 people . This was compared with a cohort in whom no systematic case-finding is implemented but spontaneous presentation for testing is allowed to occur . A group of epidemiological and clinical experts informed the structure of the model , which has three main components : ( 1 ) testing and diagnosis , ( 2 ) treatment , and ( 3 ) long-term consequences of infection . A fourth component , case-finding strategies , examines the potential impact of case-finding in three setting s : prisons , general practice and drug services . RESULTS Case-finding for HCV is likely to prevent , for 1000 people approached , three cases of decompensated cirrhosis , three deaths due to HCV and one case of hepatocellular cancer ( at 30 years ) . Twenty-five additional people are likely to undergo combination therapy as a result of initial case-finding . One liver transplant is likely to be prevented for 10,000 people included in case-finding . Case-finding is likely to cost , in the general case , around pounds sterling 760,000 more than a policy of not case-finding . The total cost of either strategy is high and driven predominantly by the cost of treatment with combination therapy ( the costs of long-term consequences are heavily discounted owing to the duration of the model ) . Systematic ally offering testing to 1000 people would cost around pounds sterling 70,000 . In terms of life-years gained , case-finding is likely to result in an additional life-year gained for an investment of pounds sterling 20,084 . Taking impacts on quality of life into account gives an estimate for the cost-utility of case-finding as pounds sterling 16,514 per QALY . The probabilistic sensitivity analysis shows that , if NHS policy makers view pounds sterling 30,000 per QALY as an acceptable return on investment , there is a 74 % probability that case-finding for HCV would be considered cost-effective . At pounds sterling 20,000 per QALY , the probability that case-finding would be considered cost-effective is 64 % . In all analyses , the probability of case-finding being considered cost-effective at a level of pounds sterling 30,000 per QALY was high . Case-finding in drug services is likely to be the most expensive , owing to the high prevalence of cases in the tested population . Correspondingly , benefits are highest for this strategy and cost-effectiveness is similar , in average terms , to the general case . Case-finding in general practice by offering testing to the whole population aged 30 - 54 years is , paradoxically , estimated to be the least expensive option as only a small number of people accept the offer of testing and HCV prevalence in this group is much higher than would be expected from the general population . Two approaches to case-finding in prison were considered , based on the results of studies in Dartmoor and the Isle of Wight prisons . These differed substantially in the prevalence of cases identified in the tested population s. The analysis based on data from Dartmoor prison had the least favourable average cost-effectiveness of the strategies considered ( pounds sterling 20,000 per QALY ) . Subgroup analyses based on duration of infection show that case-finding is likely to be most cost-effective in people whose infection is more long-st and ing and who are consequently at greater risk of progression . In people who were infected more than 20 years previously , case-finding yields benefits at around pounds sterling 15,000 per QALY . Treatment effectiveness was modelled using estimates from r and omised controlled trials and lower rates of viral response may be seen in practice . However , estimates of cost-effectiveness remained below pounds sterling 30,000 for all levels of treatment effectiveness above 58 % of those shown in the relevant trials . The value of information analysis , based on assumptions that 10,000 people might be eligible for case-finding and that programmes would run for 15 years , suggests that the maximum value of further research into case-finding is in excess of pounds sterling 19 million . Partial expected value of perfect information ( EVPI ) analysis shows that the utility estimates used in the model eclipse all other factors in terms of importance to parameter uncertainty . This is not surprising , since the point estimates for differences in utility between states and across the arms of the model are small . CONCLUSIONS Case-finding for hepatitis C is likely to be considered cost-effective by NHS commissioners . Although there remains considerable uncertainty , it appears unlikely that cost-effectiveness would exceed the levels considered acceptable . Further improvements in the effectiveness of treatments to slow or halt disease progression are likely to improve the cost-effectiveness of case-finding . Case-finding is likely to be most cost-effective if targeted at people whose HCV disease is probably more advanced . Further empirical work is required to specify , in practice , different approaches to case-finding in appropriate setting s and to evaluate their effectiveness and cost-effectiveness directly UNLABELLED Acute hepatitis C virus ( HCV ) infection is underdiagnosed because most patients are asymptomatic . The majority of new infections occur among people who inject drugs ( PWID ) , many of whom have a history of incarceration . In a previous pilot study , we identified symptomatic HCV cases , mainly among Caucasian inmates . We design ed a cross-sectional study to evaluate whether risk factor-based screening of newly incarcerated inmates would enhance identification of asymptomatic acute HCV infection and eluci date any demographic shifts in HCV acquisition . From October 2006 to March 2008 , 6,342 inmates underwent health assessment s and 3,470 inmates ( 55 % ) were screened . The racial distribution was as follows : African American , 24.0 % ; Caucasian , 49.5 % ; Hispanic , 22.2 % . One hundred seventy-one inmates ( 4.9 % ) were classified as high-risk . After further evaluation , 35 ( 20.5 % ) inmates were diagnosed with acute HCV with a mean age of 29 years ; 62.9 % were female and 91 % were Caucasian . No African Americans were diagnosed with acute HCV . Our case-finding rate was 1.9 patients /month nearly a three-fold increase compared with our historical control period with a higher proportion of asymptomatic cases . We estimate a prevalence of ∼1.0 % ( 95 % confidence interval , 0.7%-1.4 % ) of acute HCV infections among newly incarcerated inmates . CONCLUSION Within the correctional system , systematic screening based on risk factors successfully identifies acute HCV infection among PWID , including asymptomatic patients . Our data also reflect changing nationwide patterns of injection drug use that vary by age , ethnicity , and race , leading to a marked reduction of acute HCV infections among African Americans compared with non-Hispanic whites . The nationwide implementation of this simple low-cost strategy in prison-based setting s could identify more than 7,000 acute HCV infections among PWID , provide insight into changing epidemiologic trends , and facilitate appropriate therapeutic and preventive interventions The objective of this study was to assess whether introducing dried blood spot testing can increase hepatitis C virus ( HCV ) diagnostic testing . A cluster r and omized controlled trial was conducted . Sites were matched into pairs , with one site in each pair r and omly allocated to receive the intervention ( training and use of dried blood spot ) . Data were collected from all sites for 6 months before and 6 months after the start of the intervention . The participants were 22 specialist drug clinics and six prisons in Engl and and Wales . The main outcome measure of this study was percentage point difference in individuals tested for HCV ( the difference between the percentage of patients tested 6 months after and 6 months before the introduction of dried blood spot tests ) . Before the trial , 8 % of patients at control and intervention sites had been tested for HCV , with 16 sites testing less than 5 % of their caseload . The average percentage point difference between intervention and control sites was 14.5 % ( 95 % CI 1.3 - 28 % , paired t-test , P = 0.03 ) ; with 13 of the 14 pairs contributing to the positive effect of the intervention ( Wilcoxon matched-pairs signed-rank-test , P = 0.002 ) . The size of the difference between intervention and control sites varied considerably . The study provides preliminary supporting evidence that dried blood spot testing may increase the uptake of HCV diagnostic testing , by increasing the opportunity for patients to be offered testing . Additional trials with a larger number of sites are justified , ideally in the context of drug and treatment policies that gave clearer priority ( and targets ) to infection control and testing OBJECTIVES We tested a modified Network for the Improvement of Addiction Treatment ( NIATx ) process improvement model to implement improved HIV services ( prevention , testing , and linkage to treatment ) for offenders under correctional supervision . METHODS As part of the Criminal Justice Drug Abuse Treatment Studies , Phase 2 , the HIV Services and Treatment Implementation in Corrections study conducted 14 cluster-r and omized trials in 2011 to 2013 at 9 US sites , where one correctional facility received training in HIV services and coaching in a modified NIATx model and the other received only HIV training . The outcome measure was the odds of successful delivery of an HIV service . RESULTS The results were significant at the .05 level , and the point estimate for the odds ratio was 2.14 . Although overall the results were heterogeneous , the experiments that focused on implementing HIV prevention interventions had a 95 % confidence interval that exceeded the no-difference point . CONCLUSIONS Our results demonstrate that a modified NIATx process improvement model can effectively implement improved rates of delivery of some types of HIV services in correctional environments STUDY OBJECTIVES To determine whether short-course treatment of latent tuberculosis infection ( LTBI ) with 2 months of rifampin and pyrazinamide ( 2RZ ) is well tolerated and leads to increased treatment completion among jail inmates , a group who may benefit from targeted testing and treatment for LTBI but for whom completion of > or = 6 months of isoniazid treatment is difficult because of the short duration of incarceration . DESIGN Prospect i ve cohort . SETTING Large , urban county jail . PATIENTS All inmates admitted to the Fulton County Jail who had positive tuberculin skin test results , normal findings on chest radiography , and expected duration of incarceration of at least 60 days . INTERVENTION Inmates were offered 2RZ via daily directly observed therapy for 60 doses as an alternative to isoniazid therapy . MEASUREMENTS AND RESULTS We measured the completion of 2RZ treatment and toxicity due to 2RZ treatment during incarceration . From December 14 , 1998 , through December 13 , 1999 , 1,360 new inmates had positive tuberculin skin test results and normal findings on chest radiography , and 168 new inmates had an expected duration of incarceration of > or = 60 days . One hundred sixty-six inmates ( > 99 % ) were HIV-negative . Eighty-one inmates ( 48 % ) completed 60 doses of 2RZ treatment while incarcerated . Seventy-four inmates ( 44 % ) were released before completion . Treatment was stopped in 1 inmate ( < 1 % ) for asymptomatic elevation of asparginine aminotransferase ( > or = 10 times normal ) and in 12 inmates ( 7 % ) for minor complaints . Twenty-one inmates had completed isoniazid treatment in the year before the availability of 2RZ , and 9 inmates completed isoniazid treatment in the year during the availability of 2RZ . CONCLUSIONS 2RZ was acceptable to and well tolerated by inmates , and led to a marked increase in the number of inmates completing treatment of LTBI during incarceration IMPORTANCE A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy ( ART ) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex . OBJECTIVE To evaluate the rate of within-couple HIV transmission ( heterosexual and men who have sex with men [ MSM ] ) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN , SETTING , AND PARTICIPANTS The prospect i ve , observational PARTNER ( Partners of People on ART-A New Evaluation of the Risks ) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples ( HIV-positive partner taking suppressive ART ) who reported condomless sex ( September 2010 to May 2014 ) . Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples ' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions . EXPOSURES Condomless sexual activity with an HIV-positive partner taking virally suppressive ART . MAIN OUTCOMES AND MEASURES Risk of within-couple HIV transmission to the HIV-negative partner . RESULTS Among 1166 enrolled couples , 888 ( mean age , 42 years [ IQR , 35 - 48 ] ; 548 heterosexual [ 61.7 % ] and 340 MSM [ 38.3 % ] ) provided 1238 eligible couple-years of follow-up ( median follow-up , 1.3 years [ IQR , 0.8 - 2.0 ] ) . At baseline , couples reported condomless sex for a median of 2 years ( IQR , 0.5 - 6.3 ) . Condomless sex with other partners was reported by 108 HIV-negative MSM ( 33 % ) and 21 heterosexuals ( 4 % ) . During follow-up , couples reported condomless sex a median of 37 times per year ( IQR , 15 - 71 ) , with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000 . Although 11 HIV-negative partners became HIV-positive ( 10 MSM ; 1 heterosexual ; 8 reported condomless sex with other partners ) , no phylogenetically linked transmissions occurred over eligible couple-years of follow-up , giving a rate of within-couple HIV transmission of zero , with an upper 95 % confidence limit of 0.30/100 couple-years of follow-up . The upper 95 % confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up . CONCLUSIONS AND RELEVANCE Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex , during median follow-up of 1.3 years per couple , there were no documented cases of within-couple HIV transmission ( upper 95 % confidence limit , 0.30/100 couple-years of follow-up ) . Additional longer-term follow-up is necessary to provide more precise estimates of risk BACKGROUND Data from r and omized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus ( HIV ) infection who have a CD4 + count of more than 350 cells per cubic millimeter . METHODS We r and omly assigned HIV-positive adults who had a CD4 + count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately ( immediate-initiation group ) or to defer it until the CD4 + count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome ( AIDS ) or another condition that dictated the use of antiretroviral therapy ( deferred-initiation group ) . The primary composite end point was any serious AIDS-related event , serious non-AIDS-related event , or death from any cause . RESULTS A total of 4685 patients were followed for a mean of 3.0 years . At study entry , the median HIV viral load was 12,759 copies per milliliter , and the median CD4 + count was 651 cells per cubic millimeter . On May 15 , 2015 , on the basis of an interim analysis , the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy . The primary end point occurred in 42 patients in the immediate-initiation group ( 1.8 % ; 0.60 events per 100 person-years ) , as compared with 96 patients in the deferred-initiation group ( 4.1 % ; 1.38 events per 100 person-years ) , for a hazard ratio of 0.43 ( 95 % confidence interval [ CI ] , 0.30 to 0.62 ; P<0.001 ) . Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 ( 95 % CI , 0.15 to 0.50 ; P<0.001 ) and 0.61 ( 95 % CI , 0.38 to 0.97 ; P=0.04 ) , respectively . More than two thirds of the primary end points ( 68 % ) occurred in patients with a CD4 + count of more than 500 cells per cubic millimeter . The risks of a grade 4 event were similar in the two groups , as were the risks of unscheduled hospital admissions . CONCLUSIONS The initiation of antiretroviral therapy in HIV-positive adults with a CD4 + count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4 + count had declined to 350 cells per cubic millimeter . ( Funded by the National Institute of Allergy and Infectious Diseases and others ; START Clinical Trials.gov number , NCT00867048 . ) BACKGROUND An interim analysis of data from the HIV Prevention Trials Network ( HPTN ) 052 trial showed that antiretroviral therapy ( ART ) prevented more than 96 % of genetically linked infections caused by human immunodeficiency virus type 1 ( HIV-1 ) in serodiscordant couples . ART was then offered to all patients with HIV-1 infection ( index participants ) . The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission . METHODS We r and omly assigned 1763 index participants to receive either early or delayed ART . In the early-ART group , 886 participants started therapy at enrollment ( CD4 + count , 350 to 550 cells per cubic millimeter ) . In the delayed-ART group , 877 participants started therapy after two consecutive CD4 + counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome ( i.e. , an AIDS-defining illness ) developed . The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis . RESULTS Index participants were followed for 10,031 person-years ; partners were followed for 8509 person-years . Among partners , 78 HIV-1 infections were observed during the trial ( annual incidence , 0.9 % ; 95 % confidence interval [ CI ] , 0.7 to 1.1 ) . Viral-linkage status was determined for 72 ( 92 % ) of the partner infections . Of these infections , 46 were linked ( 3 in the early-ART group and 43 in the delayed-ART group ; incidence , 0.5 % ; 95 % CI , 0.4 to 0.7 ) and 26 were unlinked ( 14 in the early-ART group and 12 in the delayed-ART group ; incidence , 0.3 % ; 95 % CI , 0.2 to 0.4 ) . Early ART was associated with a 93 % lower risk of linked partner infection than was delayed ART ( hazard ratio , 0.07 ; 95 % CI , 0.02 to 0.22 ) . No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant . CONCLUSIONS The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners . ( Funded by the National Institute of Allergy and Infectious Diseases ; HPTN 052 Clinical Trials.gov number , NCT00074581 . ) |
2,651 | 19,681,059 | No robust evidence could be found to support this theory .
However , the studies included in the review did support the role of the nocebo effect in triggering acute symptoms in IEI-EMF sufferers .
A narrow focus by clinicians or policy makers on bioelectromagnetic mechanisms is therefore , unlikely to help IEI-EMF patients in the long-term | Idiopathic Environmental Intolerance attributed to electromagnetic fields ( IEI-EMF ; formerly ' electromagetic hypersensitivity ' ) is a medically unexplained illness in which subjective symptoms are reported following exposure to electrical devices .
In an earlier systematic review , we reported data from 31 blind provocation studies which had exposed IEI-EMF volunteers to active or sham electromagnetic fields and assessed whether volunteers could detect these fields or whether they reported worse symptoms when exposed to them .
In this article , we report an up date to that review .
Despite the conviction of IEI-EMF sufferers that their symptoms are triggered by exposure to electromagnetic fields , repeated experiments have been unable to replicate this phenomenon under controlled conditions . | Background Radio-frequency electromagnetic fields ( RF EMF ) of mobile communication systems are widespread in the living environment , yet their effects on humans are uncertain despite a growing body of literature . Objectives We investigated the influence of a Universal Mobile Telecommunications System ( UMTS ) base station-like signal on well-being and cognitive performance in subjects with and without self-reported sensitivity to RF EMF . Methods We performed a controlled exposure experiment ( 45 min at an electric field strength of 0 , 1 , or 10 V/m , incident with a polarization of 45 ° from the left back side of the subject , weekly intervals ) in a r and omized , double-blind crossover design . A total of 117 healthy subjects ( 33 self-reported sensitive , 84 nonsensitive subjects ) participated in the study . We assessed well-being , perceived field strength , and cognitive performance with question naires and cognitive tasks and conducted statistical analyses using linear mixed models . Organ-specific and brain tissue – specific dosimetry including uncertainty and variation analysis was performed . Results In both groups , well-being and perceived field strength were not associated with actual exposure levels . We observed no consistent condition-induced changes in cognitive performance except for two marginal effects . At 10 V/m we observed a slight effect on speed in one of six tasks in the sensitive subjects and an effect on accuracy in another task in nonsensitive subjects . Both effects disappeared after multiple end point adjustment . Conclusions In contrast to a recent Dutch study , we could not confirm a short-term effect of UMTS base station-like exposure on well-being . The reported effects on brain functioning were marginal and may have occurred by chance . Peak spatial absorption in brain tissue was considerably smaller than during use of a mobile phone . No conclusions can be drawn regarding short-term effects of cell phone exposure or the effects of long-term base station-like exposure on human health Abstract Objective To test whether people who report being sensitive to mobile phone signals have more symptoms when exposed to a pulsing mobile signal than when exposed to a sham signal or a non-pulsing signal . Design Double blind , r and omised , within participants provocation study . Setting Dedicated suite of offices at King 's College London , between September 2003 and June 2005 . Participants 60 “ sensitive ” people who reported often getting headache-like symptoms within 20 minutes of using a global system for mobile communication ( GSM ) mobile phone and 60 “ control ” participants who did not report any such symptoms . Intervention Participants were exposed to three conditions : a 900 MHz GSM mobile phone signal , a non-pulsing carrier wave signal , and a sham condition with no signal present . Each exposure lasted for 50 minutes . Main outcome measures The principal outcome measure was headache severity assessed with a 0 - 100 visual analogue scale . Other outcomes included six other subjective symptoms and participants ' ability to judge whether a signal was present . Results Headache severity increased during exposure and decreased immediately afterwards . However , no strong evidence was found of any difference between the conditions in terms of symptom severity . Nor did evidence of any differential effect of condition between the two groups exist . The proportion of sensitive participants who believed a signal was present during GSM exposure ( 60 % ) was similar to the proportion who believed one was present during sham exposure ( 63 % ) . Conclusions No evidence was found to indicate that people with self reported sensitivity to mobile phone signals are able to detect such signals or that they react to them with increased symptom severity . As sham exposure was sufficient to trigger severe symptoms in some participants , psychological factors may have an important role in causing this condition . Trial registration IS RCT N81432775 [ controlled-trials.com ] Transcranial magnetic stimulation of the dorsolateral prefrontal cortex by single pulses of varying field intensities was used to measure thresholds of individual perception and motor response in three groups of subjects : subjectively electrosensitive people , general population controls with a high burden of complaints related to electromagnetic field ( EMF ) exposure in the literature ( highest decile in complaint burden ) , and general population controls with a low burden of complaints ( lowest decile in complaint burden ) . The major study endpoint was the ability of the subjects to differentiate between real magnetic stimulation and a sham condition . There were no significant differences between groups in the thresholds , neither of detecting the real magnetic stimulus nor in motor response . But the three groups differed significantly in differentiating between stimulation and sham condition , with the subjectively electrosensitive people having the lowest ability to differentiate and the control group with high level of EMF-related complaints having the best ability to differentiate . Differences between groups were mostly due to false alarm reactions in the sham condition reported by subjectively electrosensitives ( SES ) . We found no objective correlate of the self perception of being " electrosensitive . " Overall , our experiment does not support the hypothesis that subjectively electrosensitive patients suffer from a physiological hypersensitivity to EMFs or stimuli . Further research should focus on disposing factors explaining the unspecific sensory hyperresponsiveness of subjectively electrosensitive subjects Abstract In modernen Industriegesellschaften sind zunehmend mehr Menschen vom Phänomen der subjektiven Elektrosensibilität betroffen . Als eines der klinischen Symptome werden häufig Dysästhesien in der Haut berichtet , die - physiologischen Überlegungen folgend - hypothetisch auf Änderungen der Mikrozirkulation zurückgeführt werden können . Diese Hypothese wurde in der vorliegenden Studie überprüft durch Messungen der Mikrozirkulation der Haut des rechten Daumens mittels „ Laser-Doppler-Flowmeter “ ( LDF ) an sieben gesunden Proban und an 3 Personen , die überzeugt waren , unter Elektrosensibilität zu leiden mit und ohne den Einfluss eines zirkulär polarisierten magnetischen Wechselfeldes ( 96 μT , 50 Hz ) . Die Feldexposition führte zu keiner signifikanten Änderung der LDF-Werte . Das LDF-Verhältnis ( „ Feld ein“/Kontrollwert ) betrug 1,03 ± 0,03 . I m Gegensatz dazu verursachten physiologische Stimuli signifikante Änderungen der Mikrozirkulation sowohl bei den Prob and en als auch bei den elektrosensiblen Patienten : Während der Phase einer reaktiven Hyperämie nach Blutleere war das LDF-Verhältnis auf 2,02 ± 0,36 erhöht . Nach Simulation einer Hyperventilation ( zehn tiefe Atemzüge ) war das LDF-Verhältnis vermindert auf 0,63 ± 0,18 . Zusammenfassend lässt sich aussagen , dass ein Einfluß des applizierten Magnetfeldes ( 96 μT , 50 Hz ) auf die Mikrozirkulation der Haut weder bei gesunden Prob and en noch bei elektrosensiblen Personen beobachtet werden konnte . Electromagnetic hypersensitivity ( EH ) is an increasing problem in modern industrial societies . As crawling sensations are frequently mentioned by EH patients alterations in cutaneous microcirculation possibly linked to exposure to magnetic fields might be involved in the development of such sensations and further dysesthesias . In seven healthy volunteers and in three persons convinced to suffer from EH the microcirculation of the right thumb was determined by laser-Doppler-flowmetry ( LDF ) during exposure to circularly polarized 50 Hz magnetic flux densities of 96 mT. During field exposure the LDF values remained constant . The LDF ratio „ field on/field off “ was found to be 1.03 ± 0.03 . In contrast , reactive hyperemia and hyperventilation caused significant changes in the LDF values of volunteers as well as of EH patients . Following arterial congestion of the forearm microcirculation of the thumb was clearly increased during reperfusion , and the LDF values were elevated up to 2.02 ± 0.36 . 10 deep breaths caused a significant decrease in the LDF values up to 0.63 ± 0.18 . In conclusion , reactive hyperemia and hyperventilation caused clear alterations of cutaneous microcirculation , whereas , 50 Hz magnetic fields had no influence on cutaneous microcirculation OBJECTIVES The purpose of the study was to see whether the results of an earlier study [ ie , that skin symptoms were reduced by reducing electric fields from visual display units ( VDU ) ] could be reproduced or not . In addition , an attempt was made to determine whether eye symptoms and symptoms from the nervous system could be reduced by reducing VDU electric fields . METHODS The study was design ed as a controlled double-blind intervention . The electric fields were reduced by using electric-conducting screen filters . Forty-two persons completed the study while working at their ordinary job , first 1 week with no filter , then 3 months with an inactive filter and then 3 months with an active filter ( or in reverse order ) . The inactive filters were identical to the active ones , except that their ground cables were replaced by empty plastic insulation . The inactive filters did not reduce the fields from the VDU . The fields were significantly lower with active filters than with inactive filters . RESULTS Most of the symptoms were statistically significantly less pronounced in the periods with the filters when compared with the period with no filter . This finding can be explained by visual effects and psychological effects . No statistically significant difference in symptom severeness was observed between the period with an inactive filter and the one with an active filter . CONCLUSIONS The study does not support the hypothesis that skin , eye , or nervous system symptoms can be reduced by reducing VDU electric fields The objective was to test whether exposure to radio frequency ( RF ) fields from mobile phones may cause head pain or discomfort and whether it may influence physiological variables in individuals attributing symptoms to mobile phones , but not to electromagnetic fields in general . Seventeen eligible individuals , who experienced these symptoms in an open provocation test , took part in a double-blind , r and omized provocation study with cross-over design . Sixty-five pairs of sham and mobile phone RF exposures were conducted . The increase in pain or discomfort ( visual analogue scales ) in RF sessions was 10.1 and in sham sessions 12.6 ( P = 0.30 ) . Changes in heart rate or blood pressure were not related to the type of exposure ( P : 0.30 - 0.88 ) . The study gave no evidence that RF fields from mobile phones may cause head pain or discomfort or influence physiological variables . The most likely reason for the symptoms is a nocebo effect The aim of the present study was to investigate the effect of exposure to a mobile phone-like radiofrequency ( RF ) electromagnetic field on persons experiencing subjective symptoms when using mobile phones ( MP ) . Twenty subjects with MP-related symptoms were recruited and matched with 20 controls without MP-related symptoms . Each subject participated in two experimental sessions , one with true exposure and one with sham exposure , in r and om order . In the true exposure condition , the test subjects were exposed for 30 min to an RF field generating a maximum SAR(1 g ) in the head of 1 W/kg through an indoor base station antenna attached to a 900 MHz GSM MP . The following physiological and cognitive parameters were measured during the experiment : heart rate and heart rate variability ( HRV ) , respiration , local blood flow , electrodermal activity , critical flicker fusion threshold ( CFFT ) , short-term memory , and reaction time . No significant differences related to RF exposure conditions were detected . Also no differences in baseline data were found between subject groups , except for the reaction time , which was significantly longer among the cases than among the controls the first time the test was performed . This difference disappeared when the test was repeated . However , the cases differed significantly from the controls with respect to HRV as measured in the frequency domain . The cases displayed a shift in low/high frequency ratio towards a sympathetic dominance in the autonomous nervous system during the CFFT and memory tests , regardless of exposure condition . This might be interpreted as a sign of differences in the autonomous nervous system regulation between persons with MP related subjective symptoms and persons with no such symptoms The purpose of this study was to examine the effects of short-term GSM ( Global System for Mobile Communications ) cellular phone base station RF-EMF ( radiofrequency electromagnetic fields ) exposure on psychological symptoms ( good mood , alertness , calmness ) as measured by a st and ardized well-being question naire . Fifty-seven participants were selected and r and omly assigned to one of three different exposure scenarios . Each of those scenarios subjected participants to five 50-min exposure sessions , with only the first four relevant for the study of psychological symptoms . Three exposure levels were created by shielding devices in a field laboratory , which could be installed or removed during the breaks between sessions such that double-blinded conditions prevailed . The overall median power flux densities were 5.2 microW/m(2 ) during " low , " 153.6 microW/m(2 ) during " medium , " and 2126.8 microW/m(2 ) during " high " exposure sessions . For scenario HM and MH , the first and third sessions were " low " exposure . The second session was " high " and the fourth was " medium " in scenario HM ; and vice versa for scenario MH . Scenario LL had four successive " low " exposure sessions constituting the reference condition . Participants in scenarios HM and MH ( high and medium exposure ) were significantly calmer during those sessions than participants in scenario LL ( low exposure throughout ) ( P = 0.042 ) . However , no significant differences between exposure scenarios in the " good mood " or " alertness " factors were obtained . We conclude that short-term exposure to GSM base station signals may have an impact on well-being by reducing psychological arousal |
2,652 | 18,632,201 | Tolterodine immediate release ( IR ) had a more favorable profile of adverse events than oxybutynin IR .
Regarding different dosages of IR formulations , dose escalation might yield some limited improvements in the efficacy but at the cost of significant increase in the rate of adverse events .
In the comparisons between IR and extended-release ( ER ) formulations , the latter showed some advantages , both in terms of efficacy and safety .
With regard to the route of administration , use if a transdermal route of administration does not provide significant advantage over an oral one .
With regard to IR formulations , dose escalation might yield some improvements in the efficacy with significant increase in the AE . | CONTEXT Anticholinergic drugs are commonly used in patients with overactive bladder ( OAB ) who do not achieve symptom relief and quality of life improvement with conservative management .
Several drugs , with different doses , formulations , and routes of administration are currently available , making the choice quite difficult .
OBJECTIVE To evaluate efficacy and safety of different doses , formulations , and route of administration of the available anticholinergic drugs . | This study evaluated the efficacy , tolerability , and safety of darifenacin , an M3 selective receptor antagonist ( M3 SRA ) , in patients with overactive bladder ( OAB ) . In a multicenter , double-blind , placebo-controlled dose-ranging study , 439 adult OAB patients ( 85.4 % female ) were r and omized to darifenacin controlled-release tablets 7.5 mg ( n = 108 ) , 15 mg ( n = 107 ) or 30 mg ( n = 115 ) qd , or placebo ( n = 109 ) for 12 weeks . Darifenacin significantly reduced the median number of incontinence episodes/week ( −68.7 , −76.5 , and −77.3 % from baseline at 7.5 , 15 , and 30 mg , respectively , vs −46 % with placebo , all p < 0.01 ) and dose relatedly improved micturition frequency , frequency and severity of urgency , nocturia , and bladder capacity . Darifenacin was well tolerated . Adverse events were commonly mild to moderate dry mouth and constipation . There were no safety concerns . Darifenacin is effective and well tolerated in the treatment of OAB , with 7.5 and 15 mg doses offering flexibility of dosing for optimal treatment outcome Overactive bladder ( OAB ) has a significant impact on a patient ’s health-related quality of life ( HRQoL ) . This study assessed the HRQoL of Japanese OAB patients following 12 weeks ’ treatment with tolterodine extended release ( ER ) or oxybutynin . A total of 293 patients with symptoms of OAB were r and omized for treatment with tolterodine ER 4 mg once daily ( n=114 ) , oxybutynin 3 mg three times daily ( n=122 ) or a placebo ( n=57 ) . Treatment efficacy and safety assessment s were made over the 12-week period . HRQoL was assessed using the King ’s Health Question naire ( KHQ ) . Patients receiving tolterodine ER or oxybutynin showed a significant ( P<0.05 ) improvement in the Incontinence Impact , Role Limitations and most other KHQ domains compared with the placebo . These changes in HRQoL corresponded with significant ( P<0.05 ) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo . Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life The embarrassment and social stigma associated with urinary incontinence ( UI ) in overactive bladder syndrome ( OAB ) sufferers is a major reason for individuals to seek help for their condition . An analysis of 1,873 subjects with OAB with UI was conducted to assess the efficacy of solifenacin in reducing incontinence in a pooled population from four phase III clinical trials , stratified by severity of incontinence , urgency , and other key factors at baseline . Subjects were r and omized to either 5 or 10 mg of solifenacin once daily or placebo for 12 weeks . More than 50 % of the total population became continent at study end , with either dose of solifenacin ( P<0.01 vs placebo ) . Significant reductions in incontinence episodes and higher rates of attainment of continence vs placebo were observed irrespective of age or severity of incontinence or urgency at baseline with solifenacin treatment . Treatment was well tolerated , with the majority of adverse events being mild in nature . Solifenacin is an effective antimuscarinic agent for the treatment of incontinence associated with OAB PURPOSE In this phase 3 trial we assessed the efficacy of solifenacin 5 mg and 10 mg daily in patients with symptoms related to overactive bladder . In addition , we assessed the safety and acceptability of solifenacin . MATERIAL S AND METHODS The study was a multicenter , multinational , r and omized , double-blind , placebo controlled trial . Patients were r and omized to 12-week once daily treatment with solifenacin 5 mg , solifenacin 10 mg or placebo . The primary efficacy variable was changed from baseline to study end point in mean number of micturitions per 24 hours . Secondary efficacy variables included changes from baseline in mean number of urgency , nocturia and incontinence episodes per 24 hours , and mean volume voided per micturition . RESULTS Compared with changes obtained with placebo ( -1.59 ) , micturitions per 24 hours were statistically significantly decreased with solifenacin 5 mg ( -2.37 , p = 0.0018 ) and solifenacin 10 mg ( -2.81 , p = 0.0001 ) . A statistically significant decrease was observed in the number of incontinence episodes with both solifenacin doses ( 5 mg , p = 0.002 and 10 mg , p = 0.016 ) . This effect was also seen for episodes of urge incontinence ( 5 mg , p = 0.014 and 10 mg , p = 0.042 ) . Of patients reporting incontinence at baseline , fully 50 % achieved continence after treatment with solifenacin . Episodes of nocturia were statistically significantly decreased in patients treated with solifenacin 10 mg ( -0.71 , -38.5 % ) versus placebo ( -0.52 , -16.4 % , p = 0.036 ) . Episodes of urgency were statistically significantly reduced with solifenacin 5 mg ( -2.84 , -51 % , p = 0.003 ) and solifenacin 10 mg ( -2.90 , -52 % , p = 0.002 ) . Mean volume voided per micturition was statistically significantly increased with both solifenacin doses ( p = 0.0001 ) . Treatment with solifenacin was well tolerated . Dry mouth , mostly mild in severity , was reported in 7.7 % of patients receiving solifenacin 5 mg and 23 % receiving solifenacin 10 mg ( vs 2.3 % with placebo ) . CONCLUSIONS In this study treatment with solifenacin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including frequency , urgency and incontinence . Solifenacin 10 mg also decreased the frequency of nocturia . Solifenacin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth , especially at the 5 mg starting dose OBJECTIVE To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder . PATIENTS AND METHODS The OPERA ( Overactive bladder : Performance of Extended Release Agents ) trial was a r and omized , double-blind , active-control study performed at 71 US study centers from November 21 , 2000 , to October 18,2001 . Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence ( UUI ) episodes per week and an average of 10 or more voids per 24 hours . Episodes of UUI ( primary end point ) , total ( urge and nonurge ) incontinence , and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2 , 4 , 8 , and 12 and compared . Adverse events were also evaluated . RESULTS Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin ( n = 391 ) or tolterodine ( n = 399 ) . Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency ( P = .003 ) , and 23.0 % of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8 % of women taking tolterodine ( P = .03 ) . Dry mouth , usually mild , was more common with oxybutynin ( P = .02 ) . Adverse events were generally mild and occurred at low rates , with both groups having similar discontinuation of treatment due to adverse events . CONCLUSIONS Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine . In the oxybutynin group , micturition frequency was significantly lower , and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group . Dry mouth was more common with oxybutynin , but tolerability was otherwise comparable , including adverse events involving the central nervous system PURPOSE We evaluated the efficacy , patient acceptability and side effect profile of tolterodine , a new antimuscarinic agent for treating bladder overactivity . MATERIAL S AND METHODS In our r and omized , placebo controlled , parallel group study 123 , 129 and 64 patients 18 years old or older with proved detrusor overactivity ( idiopathic detrusor instability or detrusor hyperreflexia ) were r and omized to receive 1 or 2 mg . tolterodine , or placebo , respectively , twice daily for 12 weeks . Main outcome measures were number of voids per 24 hours , urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects . RESULTS After 12 weeks of treatment mean number of voids per 24 hours plus or minus st and ard deviation decreased from 11.2 + /- 3.1 to 9.0 + /- 2.6 with the 2 mg . dosage ( p = 0.0045 versus placebo ) . At this dose mean urine volume per void increased from 155 + /- 52 to 190 + /- 70 ml . ( p < 0.0001 versus placebo ) , while mean number of incontinence episodes per 24 hours decreased from 3.6 + /- 4.0 to 1.8 + /- 3.1 ( p = 0.19 versus placebo ) . Similar efficacy was observed in patients receiving the 1 mg . dose . Severe dry mouth was reported by only 2 , 1 and 2 % of patients given the 1 and 2 mg . dose , and placebo , respectively . There was no clinical or electrocardiographic evidence of significant cardiac adverse events . CONCLUSIONS Tolterodine administration result ed in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects A r and omized , double-blind , placebo-controlled , four-way crossover , safety study of darifenacin versus oxybutynin was carried out on 76 patients with overactive bladder ( OAB ) . Adults with OAB received 2 weeks each of darifenacin 15 and 30 mg once daily ( q.d . ) , oxybutynin 5 mg three times daily ( t.i.d . ) and placebo , in r and om sequence at 10-day intervals . Darifenacin and oxybutynin significantly reduced incontinence episodes , and the number/severity of urgency episodes ( all P<0.05 versus placebo ) . Improvements in OAB symptoms with darifenacin were dose-dependent . Dry mouth was less common with darifenacin 15 mg than oxybutynin ( 13 % and 36 % ; P<0.05 ) , while constipation was comparable ( 10 % and 8 % , respectively ) . Corresponding rates for darifenacin 30 mg were 34 % and 21 % , respectively . Patients only reported blurred vision or dizziness with oxybutynin ( 3 % and 2 % , respectively ) . Darifenacin ( 15 mg q.d . ) provides comparable efficacy with improved tolerability versus oxybutynin ( 5 mg t.i.d . ) in the treatment of patients with OAB To evaluate urinary symptom relief in women with mixed urinary incontinence ( MUI ) treated for up to 52 weeks with solifenacin succinate for overactive bladder ( OAB ) , as MUI is a complex and distressing condition reported by about a third of incontinent women , and with confirmed efficacy in OAB‐related urge incontinence , anticholinergic agents are a reasonable therapeutic option for such women OBJECTIVE To compare OAB symptom outcomes following initial r and omised treatment with solifenacin 5 mg or tolterodine ER 4 mg at the 4-week clinic-visit and again at 12 weeks for patients choosing to remain on this treatment dose from 4 weeks . METHODS A prospect i ve , double blind , double-dummy , two-arm , parallel-group , 12-week study ( The STAR study ) was conducted to compare the efficacy and safety of solifenacin 5/10 mg and tolterodine extended release ( ER ) 4 mg in OAB patients . RESULTS At 4 weeks mean improvements in OAB symptoms , including urgency , frequency ( primary variable ) , incontinence and nocturia , were larger in patients r and omised to solifenacin 5 mg ; with the difference for incontinence being statistically significant ( mean reduction in incontinence episodes/24 hrs in the solifenacin group of -1.30 vs. -0.90 ( p=0.0181 ) ; the mean result for solifenacin 5 mg amounted to a 44 % additional improvement . ) There was an associated significant reduction in pad use ( reduced by -1.21 vs. -0.80 ; p=0.0089 ) ; the mean result for solifenacin 5 mg amounted to a 51 % additional improvement over that of tolterodine ER 4 mg . For patients choosing to remain on these treatments improvements in favour of solifenacin were maintained at study end ( 12-weeks ) . Treatments were well tolerated . CONCLUSIONS Within 4 weeks solifenacin 5 mg was statistically significantly better than tolterodine ER 4 mg in improving incontinence and reducing incontinence pad use . Differences in efficacy in favour of solifenacin 5 mg were maintained from 4 weeks for the duration of the study for patients choosing to remain on their starting dose Our objectives were to ascertain the tolerability and efficacy of trospium chloride in doses of 20 mg twice daily for long-term therapy ( 52 weeks ) in patients with urge syndrome . The trial comprised a total of 358 patients with urge syndrome or urge incontinence . After r and omisation in the ratio of 3:1 , participants were treated continuously for 52 weeks with either trospium chloride ( 20 mg twice daily ) or oxybutynin ( 5 mg twice daily ) . At intervals of 4–8 weeks , patients were physically examined with measurements of blood pressure and pulse rate , were question ed about any adverse events , checked for compliance and underwent relevant laboratory tests . As an additional safety measure , an ECG was made at 26 and 52 weeks . Urodynamic measurements were performed at the beginning , and at 26 and 52 weeks to determine the maximal cystometric bladder capacity . Among others things , the frequencies of micturition , incontinence and number of urgency events were recorded in patient diary protocol s in weeks 0 , 2 , 26 and 52 . The evaluation of vital parameters , laboratory results and ECGs did not show any relevant changes attributable to the action of the anticholinergics . Analysis of the micturition diary clearly indicated a reduction of the micturition frequency , incontinence frequency , and a reduction of the number of urgencies in both treatment groups . Mean maximum cystometric bladder capacity increased during treatment with trospium chloride by 92 ml after 26 weeks and 115 ml after 52 weeks ( P=0.001 ) . Further comparison with oxybutynin did not reveal any statistically significant differences in urodynamic variables between the drugs . Adverse events occurred in 64.8 % of the patients treated with trospium chloride and 76.7 % of those treated with oxybutynin . The main symptom encountered in both treatment group was dryness of the mouth . For patients on trospium chloride , the estimated risk of an unexpected adverse event was 0.027 per patient per week for all adverse events and 0.009 for dryness of the mouth , result ing in a considerably lower risk during treatment given with trospium chloride than with oxybutynin ( 0.045 and 0.021 , respectively ) . An overall assessment for each of the drugs reveals a comparable efficacy level and a better benefit-risk ratio for trospium chloride than for oxybutynin due to better tolerability An international , multicentre , r and omized double‐blind trial is presented . Patients were r and omized to treatment with tolterodine , placebo , and two doses of solifenacin . The authors concluded that the two doses of solifenacin improved urgency and other symptoms of the overactive bladder , with an acceptable level of side‐effects Abstract : This study compared the clinical efficacy ( determined from micturition diaries ) and safety of 12 weeks ’ treatment with either tolterodine 2 mg twice daily , oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder . A total of 277 patients were r and omized and treated at 25 centers . Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo . Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo ; however , only tolterodine was significantly better than placebo in reducing micturition frequency . Tolterodine and oxybutynin were equivalent in their effectiveness . Tolterodine was significantly better tolerated than oxybutynin when adverse events ( particularly frequency and intensity of dry mouth ) , dose reduction and patient withdrawals were considered . Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness . Tolterodine has equivalent efficacy to oxybutynin , but with less severe adverse effects . This will allow patients to receive more effective treatment for their condition , with better compliance BACKGROUND This double-blind , multicenter study compared the efficacy and tolerability of tolterodine ( Pharmacia , Los Angeles , USA ) with that of oxybutynin ( Alza , Palo Alto , USA ) in Asian patients with overactive bladder . METHODS Two-hundred- and -twenty-eight adults with overactive bladder symptoms were r and omized to receive tolterodine 2 mg twice daily ( bid ) ( n = 112 ) or oxybutynin 5 mg bid ( n = 116 ) . After 8 weeks ' treatment , changes in micturition diary variables , patients ' perception of treatment benefit , and tolerability endpoints were determined . RESULTS The mean ( + /- SD ) number of micturitions/24 h decreased by 2.6 + /- 2.9 ( -21 % ) with tolterodine and 1.8 + /- 4.2 ( -15 % ) with oxybutynin ( both P = 0.0001 vs baseline ) . The mean number of incontinence episodes/24 h decreased by 2.2 + /- 2.3 ( -85 % ) in the tolterodine group and by 1.4 + /- 1.8 ( -58 % ) in the oxybutynin group ( both P = 0.0001 vs baseline ) . Patient perception of treatment benefit was over 70 % in each treatment group . Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients ( 55 % vs 82 % ; P = 0.001 ) . Dry mouth was reported by significantly fewer patients on tolterodine , compared with oxybutynin ( 35 % vs 63 % ; P = 0.001 ) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin ( 10 % vs 16 % ) . There were no safety concerns . CONCLUSIONS Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder , and shows significantly better tolerability . This may enhance compliance during long-term treatment OBJECTIVE To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder . SUBJECTS AND METHODS The OBJECT ( Overactive Bladder : Judging Effective Control and Treatment ) study was a prospect i ve , r and omized , double-blind , parallel-group study conducted between March and October 2000 at 37 US study sites . Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin , 10 mg/d , or tolterodine , 2 mg twice daily . The outcome measures were the number of episodes of urge incontinence , total incontinence , and micturition frequency at 12 weeks adjusted for baseline . RESULTS A total of 315 women and 63 men were r and omized and treated , and 332 participants ( 276 women , 56 men ) completed the study . At the end of the study , extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures : weekly urge incontinence ( P=.03 ) , total incontinence ( P=.02 ) , and micturition frequency episodes ( P=.02 ) adjusted for baseline . Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures ( P<.001 ) . Dry mouth , the most common adverse event , was reported by 28.1 % and 33.2 % of participants taking extended-release oxybutynin and tolterodine , respectively ( P=.32 ) . Rates of central nervous system and other adverse events were low and similar in both groups . CONCLUSIONS Extended-release oxybutynin was more effective than tolterodine as measured by end-of- study urge incontinence , total incontinence , and micturition frequency episodes . Both groups had similar rates of dry mouth and other adverse events OBJECTIVES To compare the efficacy and safety of an oxybutynin transdermal delivery system ( OXY-TDS ) and oral , long-acting tolterodine ( TOL-LA ) with placebo in previously treated patients with urge or mixed urinary incontinence . METHODS After withdrawal of their current antimuscarinic therapy , 361 adult patients were r and omized to 12 weeks of double-blind , double-dummy treatment with twice weekly OXY-TDS 3.9 mg/day , daily TOL-LA 4 mg , or placebo . Evaluations included change from baseline in patient urinary diary symptoms , incontinence-specific quality of life , and safety . RESULTS OXY-TDS 3.9 mg/day and TOL-LA 4 mg/day significantly reduced the number of daily incontinence episodes ( median change -3 OXY-TDS and -3 TOL-LA versus -2 placebo ; P < 0.05 ) , increased the average void volume ( median change 24 and 29 mL versus 5.5 mL , P < 0.01 ) , and improved quality of life ( incontinence impact question naire [ IIQ ] total score , P < 0.05 ; Urogenital Distress Inventory Irritative Symptom subscale , P < 0.05 ) compared with placebo . The most common adverse event for OXY-TDS was localized application site pruritus ( 14 % versus 4 % placebo ) accompanied by a low incidence of systemic side effects ( eg , dry mouth 4.1 % ) . Anticholinergic adverse events occurred with greatest frequency during TOL-LA treatment ( dry mouth 7.3 % versus 1.7 % placebo , P < 0.05 ) . CONCLUSIONS OXY-TDS and TOL-LA are effective and comparable treatments for patients with urge and mixed incontinence . OXY-TDS improves systemic safety with regard to anticholinergic side effects . Local skin irritation occurs in some OXY-TDS patients AIM To evaluate the effects of tolterodine and oxybutynin on visual accommodation , pupillary diameter , intraocular pressure and tear secretion in women with overactive bladder . METHODS One hundred and four eyes from 52 consecutive female patients ( age range : 22 - 60 years ) with a urodynamic diagnosis of overactive bladder were prospect ively investigated . Patients with a history of ocular disease or surgery were excluded . The subjects were r and omly assigned to one of two groups : Group I received 2 mg tolterodine bid and Group II received 5 mg oxybutynin tid . All patients were evaluated at baseline ( day 0 ) and after 1 month of treatment ( day 28 ) by an ophthalmologist who was blinded to the medication . At each time point , a complete ophthalmic examination was performed and accommodation amplitude ( AA ) , and pupillary diameter ( PD ) in dim and bright light were recorded . As well , tear secretion was assessed based on tear film break-up time and Schirmer I-test results . Statistical comparisons were made using the chi-square test , Student 's t-test and Mann-Whitney U-test , as appropriate . RESULTS Twenty-eight patients ( 56 eyes ) received tolterodine and 24 patients ( 48 eyes ) received oxybutynin . The mean ages of the two groups were similar ( P = 0.523 ) . After 4 weeks of treatment , AA was significantly lower in the oxybutynin treated group ( P = 0.003 , 95 % CI 0.15 , 0.62 ) whereas there was no significant change in AA in the tolterodine treated group ( P = 0.155 , 95 % CI -0.042 , 0.86 ) . At day 28 , PD in dim light was significantly larger in the tolterodine treated group ( P = 0.031 , 95 % CI -0.82 , -0.06 ) , whereas no significant change in PD in dim light was noted in the oxybutynin treated group ( P = 0.330 , 95 % CI -0.38 , 0.18 ) . Neither group showed a significant change in PD in bright light values on day 28 ( P > 0.05 for both ) . In each group , the differences from day 0 to day 28 for intraocular pressure , and Schirmer-I results were insignificant ( P > 0.05 for all ) . Both groups had significantly shorter tear film break-up time after 1 month of therapy ( P = 0.014 ( 95 % CI 0.47 , 3.81 ) and P = 0.02 ( 95 % CI 1.14 , 4.61 ) for the tolterodine and oxybutynin treated groups , respectively ) . CONCLUSION Four weeks of st and ard-dose oxybutynin treatment in women with overactive bladder decreases AA significantly , whereas the same duration of st and ard-dose tolterodine does not have this effect . However , tolterodine seemed to affect PD in dim light . One month of treatment with either of these anticholinergic drugs shortens tear film break-up time significantly . Concerning ocular side-effects , tolterodine seems to offer an advantage over oxybutynin because it does not affect AA , however , the shorter tear film break-up time with both agents suggests potential problems for patients who already have dry eye Clinical efficacy and adverse effects of oxybutynin and propantheline in the treatment of symptoms related to detrusor hyperactivity were studied in a r and omized , controlled , double-blind multicenter trial . Of 169 patients entered into the study 154 were evaluable for statistical analysis . Mean grade of improvement ( visual analogue scale ) was significantly higher with oxybutynin ( 58.2 % ) versus propantheline ( 44.7 % ) and placebo ( 43.4 % ) . Mean bladder volume at first involuntary cystometric contraction was significantly increased with oxybutynin ( + 57.0 ml . ) versus placebo ( -9.7 ml . ) . Mean maximum cystometric bladder capacity was also significantly increased with oxybutynin ( + 80.1 ml . ) versus placebo ( + 22.5 ml . ) . Rate of inquired possible adverse effects was significantly higher for oxybutynin ( 63 % ) versus propantheline ( 44 % ) and placebo ( 33 % ) . However , only 5 patients dropped out of the study because of adverse effects ( oxybutynin 2 and propantheline 3 ) . No serious or lasting adverse effects were encountered with dryness of the mouth being the major complaint . Oxybutynin has statistically significant effects on subjective symptoms and objective urodynamic parameters in patients with detrusor hyperactivity compared to propantheline To compare extended‐release ( ER ) tolterodine and immediate‐release ( IR ) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder ( OAB ) OBJECTIVE To determine the efficacy , tolerability , and safety of fesoterodine in subjects with overactive bladder ( OAB ) . METHODS This was a multicentre , r and omised , double-blind , placebo- and active-controlled trial with tolterodine extended release ( ER ) to assess the efficacy and safety of fesoterodine . Eligible subjects ( > or = 18 yr ) with increased micturition frequency and urgency and /or urgency urinary incontinence ( UUI ) were r and omised to placebo , fesoterodine 4 mg , fesoterodine 8 mg , or tolterodine ER 4 mg for 12 wk . The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co- primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response ( " yes " or " no , " based on four-point treatment benefit scale ) . Secondary efficacy variables included mean volume voided per micturition , continent days per week , and number of urgency episodes . RESULTS At the end of treatment , subjects taking fesoterodine 4 and 8 mg had significant ( p<0.05 ) and clinical ly relevant improvements versus placebo in the primary , co- primary , and most secondary efficacy variables . Tolterodine ER ( active control ) also provided significantly greater improvement than placebo for most efficacy variables , confirming the sensitivity of the study design . A more pronounced effect was observed with fesoterodine 8 mg at most end points . CONCLUSIONS Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo . Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments . Active treatments were well tolerated Objective To compare the efficacy of a controlled‐release ( CR ) formulation of oxybutynin with that of conventional oxybutynin in patients with detrusor instability or detrusor hyper‐reflexia whose symptoms were stabilized on conventional oral oxybutynin tablets AIM To compare the effects of propiverine and oxybutynin on ambulatory urodynamic monitoring ( AUM ) parameters , safety , and tolerability in patients with overactive bladder . METHODS This was a r and omized , double-blind , placebo-controlled , multicentre , crossover study . Patients ( n = 77 ) received two of the following treatments during two 2-week periods : propiverine 20 mg once daily , propiverine 15 mg three times daily , oxybutynin 5 mg three times daily , and placebo . AUM parameters , salivary flow , visual near point , and heart rate were assessed . RESULTS A consistent order in the efficacy between active treatment groups was observed for the reduction in mean involuntary detrusor contractions ( IDCs ; oxybutynin 15 mg < /= propiverine 45 mg < /= propiverine 20 mg ) . Differences between the oxybutynin and propiverine 20 mg groups were statistically significant for several AUM endpoints . Statistically significant differences between the oxybutynin and both propiverine groups were also noted in salivary flow rate and heart rate ( oxybutynin 15 mg < both propiverine regimens ) and in heart rate variability ( both propiverine regimens < oxybutynin 15 mg ) . All active treatments lengthened visual near point . The incidence of dry mouth was significantly more pronounced in the oxybutynin group than in either propiverine group . Treatment with propiverine 45 mg result ed in the highest rates of constipation , lengthening of the visual near point , and effects on heart rate . CONCLUSIONS Oxybutynin 15 mg was more effective than propiverine 20 mg in reducing symptomatic and asymptomatic IDCs in ambulatory patients . The primary differences between the two drugs were the incidence and type of adverse events , which varied with the antimuscarinic receptor specificity of each agent OBJECTIVE To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder . DESIGN R and omized , double-blind , placebo-controlled , parallel-group , multinational , phase III study . SETTING Incontinence , older care , urological , and urogynecological clinics in the United Kingdom , France , and the Republic of Irel and . PARTICIPANTS One hundred and seventy-seven older patients ( age > or = 65 years ) with symptoms of urinary urgency , increased frequency of micturition ( > or = 8 micturitions/24 hours ) , and /or urge incontinence ( > or = 1 episode/24 hours ) . INTERVENTION Tolterodine 1 mg or 2 mg twice daily ( bid ) , or placebo , for 4 weeks . MEASUREMENTS Safety and tolerability were evaluated through spontaneously reported adverse events , electrocardiogram , and blood pressure measurements . Efficacy was assessed using micturition diary variables : mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours . RESULTS The mean age of the patient population was 75 years . Overall , > or = 87 % of patients completed the study . Neither dosage of tolterodine was associated with serious drug-related adverse events during the study . No cardiac arrythmogenic events were noted . Dry mouth ( mild to moderate intensity ) was the most common adverse event in both the placebo and tolterodine treatment groups . Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth , compared with 2 % of placebo-treated patients . Compared with placebo , statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups . Furthermore , patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo . CONCLUSION Tolterodine ( taken for 4 weeks ) is safe and shows efficacy , particularly at a dosage of 2 mg bid , in the treatment of older patients with urinary symptoms attributable to overactive bladder OBJECTIVE To evaluate the efficacy , safety and tolerability of tolterodine compared to placebo in patients with an overactive bladder . STUDY DESIGN A double-blind , multi-centre phase III study in France and Belgium 251 patients with overactive bladder symptoms , and urodynamically verified detrusor overactivity , were r and omised to receive 4-week treatment with either placebo or tolterodine 1 or 2 mg twice daily ( bd ) . Efficacy was evaluated from patient micturition diaries . Safety and tolerability endpoints were also evaluated . RESULTS After 4-week treatment , the number of incontinence episodes/24h decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd groups ( P=0.045 and P=0.0089 , respectively ) . Both dosages of tolterodine increased volume voided per micturition compared with placebo ( P=0.055 and P=0.056 , respectively ) , although significant decreases in micturition frequency were not apparent . Tolterodine was safe and well tolerated , few patients were withdrawn due to adverse events . Dry mouth , mainly of mild-to-moderate intensity , was the most common adverse event . No clinical ly relevant changes in blood pressure or laboratory safety variables were reported . CONCLUSION Tolterodine is effective , safe and well tolerated for the treatment of symptoms of an overactive bladder , particularly urge incontinence Objective To compare the efficacy and safety of controlled-release oxybutynin with conventional , immediate-release oxybutynin and determine rates of dry mouth . Methods Patients ( n = 226 ) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were r and omized to receive controlled-release oxybutynin or immediate-release oxybutynin . After an initial placebo run-in period , dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved . Rates of urge incontinence and dry mouth were compared . Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose . Results Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week ( 83 % mean decrease ) and 19.8 to 4.4 per week ( 76 % mean decrease ) in the controlled- and immediate-release oxybutynin groups ( P = .36 ) , respectively . At equal doses , comparable proportions of patients in both groups reported the absence of urge incontinence ( P = .85 ) . The incidence of dry mouth increased with dose in both groups , but there was no difference in dry mouth rates between the groups : 47.7 % and 59.1 % for the controlled- and immediate-release oxybutynin ( P = .09 ) , respectively . However , Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth ( P = .007 ) or any dry mouth ( P = .003 ) compared with those taking immediate-release oxybutynin . Conclusion At the same daily dose , controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes . The incidence of dry mouth was dose dependent but equal in both groups ; first report of moderate to severe dry mouth was significantly lower in the controlled-release group OBJECTIVE Estimate the prevalence of urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) among men and women in five countries using the 2002 International Continence Society ( ICS ) definitions . METHODS This population -based , cross-sectional survey was conducted between April and December 2005 in Canada , Germany , Italy , Sweden , and the United Kingdom using computer-assisted telephone interviews . A r and om sample of men and women aged > /= 18 yr residing in the five countries and who were representative of the general population s in these countries was selected . Using 2002 ICS definitions , the prevalence estimates of storage , voiding , and postmicturition LUTS were calculated . Data were stratified by country , age cohort , and gender . RESULTS A total of 19,165 individuals agreed to participate ; 64.3 % reported at least one LUTS . Nocturia was the most prevalent LUTS ( men , 48.6 % ; women , 54.5 % ) . The prevalence of storage LUTS ( men , 51.3 % ; women , 59.2 % ) was greater than that for voiding ( men , 25.7 % ; women , 19.5 % ) and postmicturition ( men , 16.9 % ; women , 14.2 % ) symptoms combined . The overall prevalence of OAB was 11.8 % ; rates were similar in men and women and increased with age . OAB was more prevalent than all types of UI combined ( 9.4 % ) . CONCLUSIONS The EPIC study is the largest population -based survey to assess prevalence rates of OAB , UI , and other LUTS in five countries . To date , this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions . The results indicate that these symptoms are highly prevalent in the countries surveyed The efficacy and tolerability of propiverine hydrochloride ( 15 , off 45 , 60 mg/d ) were evaluated in the treatment of 185 patients suffering from urgency/urge incontinence in an open , r and omized , multicentre parallel-group trial lasting 21 days . The effects on bladder volume and pressure were assessed on the basis of urodynamics and micturition frequency . Subjective adverse reactions were recorded . The bladder capacity and compliance increased and bladder pressure decreased in a dose dependent manner following therapy with 15 , 30 , 45 and 60 mg/d . In 70 % of the patients a decrease in micturition frequency was observed after 15 mg/d , and in 80 % after 30 to 60 mg/d . Subjective anticholinergic symptoms were reported by 21 , 40 and 28 % of the patients following therapy with 30 , 45 and 60 mg/d . 15 and 30 mg were the daily doses with the most favourable ratio of efficacy in micturition frequency to tolerability . The results suggest that propiverine is a safe and effective drug for the treatment of urgency and urge incontinence . Individual treatment with an initial dosage of 30 mg/d should be recommended OBJECTIVE To compare the efficacy of tolterodine and oxybutynin in the treatment of specific , according to their urodynamic grade of severity , population s with overactive detrusor . METHODS In this open , r and omized , two-way crossover study 128 women with urodynamically confirmed , idiopathic detrusor overactivity were recruited . Patients were categorized in 4 grade s of severity groups , according to the characteristics of the first overactive detrusor contraction during filling cystometrogram : high volume-low pressure ( grade -group I ) , high volume-high pressure ( grade -group II ) , low volume-low pressure ( grade -group III ) and low volume-high pressure ( grade -group IV ) . The primary outcome measure was average volume of voided urine per micturition . RESULTS 107 patients successfully completed the study protocol and were included in the analyses : 40 in group IV , 36 in III , 25 in II and 6 in group I. In groups IV and III both oxybutynin and tolterodine significantly increased the average volume of voided urine per micturition but the differences between the drugs were not significant ( p > 0.05 ) . In group II neither of the drugs achieved significant changes in the outcome measure ( p > 0.05 ) . CONCLUSIONS Tolterodine and oxybutynin are clinical ly equipotent in treating detrusor overactivity in specific severity groups of patients , although urodynamic effects are somewhat different PURPOSE We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Irel and . MATERIAL S AND METHODS In a r and omized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder ( a urinary frequency of 8 or more voids per 24 hours with urgency and /or urge incontinence , that is 1 or more urge incontinence episodes per 24 hours ) received 10 weeks of treatment with 2 mg . tolterodine twice daily/or an initial dose of 2.5 mg . oxybutynin twice daily , increasing to 5 mg . twice daily after 2 weeks of treatment . The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessment s. RESULTS Patients treated with tolterodine had significantly fewer adverse events ( 69 % versus 81 % , p = 0.01 ) , notably dry mouth ( 37 % versus 61 % , p < 0.0001 ) , as well as a lower incidence of dose reduction ( 6 % versus 25 % , p < 0.0001 ) than those in the oxybutynin group . Each agent had comparable efficacy for improving urinary symptoms . Tolterodine and oxybutynin caused a significant decrease ( p = 0.0001 ) in the mean number of voids per 24 hours ( -1.7 or -15 % and -1.7 or -15 % , respectively ) , urge incontinence episodes per 24 hours ( -1.3 or -54 % and -1.8 or -62 % , respectively ) and mean voided volume per void ( 33 ml . or 22 % and 34 ml . or 23 % ) after 10 weeks of treatment . CONCLUSIONS Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability . The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition OBJECTIVES Propiverine and tolterodine were compared with respect to efficacy , tolerability and impact on the quality of life in the treatment of patients with idiopathic detrusor overactivity . METHODS In a r and omised , double-blind , multicentre clinical trial , patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2 mg tolterodine twice daily over a period of 28 days . The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy . The difference of both values was used as the primary endpoint . Secondary endpoints were voided volume per micturition , evaluation of efficacy ( by the investigator ) , tolerability , post void residual urine , and quality of life . RESULTS The mean maximum cystometric capacity increased significantly ( p < 0.01 ) in both groups . The volume at first urge and the frequency/volume chart parameters also showed relevant improvements during treatment . 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events . The most common adverse event , dry mouth , occurred in 20 patients in the propiverine group and in 19 patients in the tolterodine group . The scores for the quality of life improved comparably in both groups . CONCLUSION The study demonstrates comparable efficacy , tolerability , and improvement in the quality of life of 15 mg propiverine twice-daily and 2 mg tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor overactivity PURPOSE We evaluated the efficacy , tolerability and safety of the new antimuscarinic agent fesoterodine relative to placebo for overactive bladder syndrome . MATERIAL S AND METHODS This was a r and omized , double-blind , placebo controlled , multicenter trial performed in the United States . Overall 836 subjects with urinary frequency , urinary urgency or urgency urinary incontinence were r and omized to placebo ( 274 ) , 4 mg fesoterodine ( 283 ) or 8 mg fesoterodine ( 279 ) once daily for 12 weeks . The primary efficacy end point was the change in the number of micturitions per 24 hours . Co- primary end points were the change in the number of urgency urinary incontinence episodes per 24 hours and the treatment response . Secondary efficacy end points were other bladder diary variables , such as the change in mean voided volume per micturition , number of continent days and number of urgency episodes per 24 hours . Tolerability and safety were assessed by evaluating adverse events , electrocardiograms , post-void residual urine volume , laboratory parameters and treatment withdrawals . RESULTS Treatment with 4 or 8 mg fesoterodine result ed in statistically significant and clinical ly relevant improvements from baseline to end of treatment for the primary and co- primary end points compared with placebo ( p < 0.05 ) . Results for most secondary end points , including mean voided volume per micturition , number of continent days and number of urgency episodes per 24 hours , were also significantly improved vs placebo . The adverse events reported more frequently with fesoterodine than with placebo were dry mouth , constipation and urinary tract infection . CONCLUSIONS The 2 doses of fesoterodine were well tolerated and they statistically significantly improved overactive bladder symptoms Introduction : This study aims to compare the efficacy of propiverine hydrochloride immediate release ( IR ) , propiverine hydrochloride extended release ( ER ) and placebo for the treatment of overactive bladder syndrome . The primary outcome measure is incontinence episode frequency , with secondary outcome measures including mean volume per void and quality of life as assessed on King ’s Health Question naire . Material and Methods : The double-blind , double-dummy , r and omized study compared IR 15 mg twice daily , ER 30 mg once daily and placebo in 3 parallel groups . After a run-in period of 7 days , the patients were treated for 32 days . Nine hundred and eighty-eight patients were r and omized , and 910 patients completed the protocol without major violations . Results : The number of incontinence episodes/24 h decreased by 2.26 in the IR group ( p < 0.001 vs. placebo ) , by 2.46 in the ER group ( p < 0.0001 vs. placebo ) and by 1.75 in the placebo group . The most frequent adverse event was dry mouth with 22.8 % of the patients in the IR group , 21.7 % in the ER group and 6.4 % in the placebo group . The overall tolerability was rated ‘ very good ’ or ‘ good ’ by more than 80 % of the investigators and patients in all 3 groups . Conclusions : Propiverine ER 30 mg once daily and propiverine IR 15 mg twice daily significantly reduce the number of incontinence episodes/24h within a treatment period of 32 days . Both formulations are safe and well tolerated . The extended release formulation of propiverine is a suitable new option for the treatment of the overactive bladder Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder To assess the tolerability and efficacy of propiverine and oxybutynin in patients with urgency and urge incontinence in a r and omized , double‐blind placebo‐controlled clinical trial Abstract This study evaluated the efficacy and tolerability of new extended-release ( ER ) tolterodine for the treatment of overactive bladder in women . In this sub population analysis of a double-blind multicenter trial , 1235 female patients were r and omized to oral therapy with tolterodine ER 4 mg once daily ( n=417 ) , tolterodine IR 2 mg twice daily ( n=408 ) or placebo ( n=410 ) for 12 weeks . Both formulations reduced the mean number of urge incontinence episodes per week ( both P=0.001 vs placebo ) ; tolterodine ER was more effective than tolterodine IR ( P=0.036 ) . Both formulations significantly improved all other micturition chart variables compared to placebo . Dry mouth was the most common adverse event . There were no safety concerns . Toltrodine ER 4 mg once daily is effective and well tolerated in the treatment of women with overactive bladder , and reduces urge incontinence episodes more than the existing IR twice-daily formulation OBJECTIVE To investigate the efficacy and safety of tolterodine , a new antimuscarinic agent , and define the optimum dosage in patients with symptoms of detrusor instability ( urgency , increased frequency of micturition and /or urge incontinence ) . PATIENTS AND METHODS A double-blind , placebo-controlled , multicentre study was carried out ; after a 1-week run-in period to establish baseline values , 81 patients were r and omized to receive placebo or tolterodine 0.5 , 1 , 2 or 4 mg twice daily for 2 weeks . Micturition ( diary ) variables , urodynamics and subjective urinary symptoms were assessed after 2 weeks ' treatment . RESULTS A per- protocol analysis of efficacy in 64 patients showed dose-related improvements in recorded micturition and urodynamic variables , e.g. at a dosage of 2 mg twice daily , the frequency of micturition , episodes of incontinence and pad use were reduced by 20 % , 46 % and 29 % , respectively , while the volume at first contraction increased by 89 mL. The 4 mg dosage was associated with a large increase in residual urinary volume and an increased incidence of dry mouth . The incidence of adverse events ( mainly mild or moderate antimuscarinic effects ) was comparable with placebo at tolterodine dosages of < or = 2 mg . No serious adverse events were observed and tolterodine had no clinical ly significant impact on electrocardiographic or laboratory findings . CONCLUSION The results indicate that tolterodine offers an effective treatment for the symptoms of detrusor instability . The optimum dosage appears to be 1 - 2 mg twice daily OBJECTIVE The aim of this study was to evaluate the efficacy and safety of a new PO controlled-release ( CR ) QD oxybutynin tablet relative to PO immediate-release ( IR ) TID oxybutynin in patients with urge urinary incontinence ( UI ) . METHODS In this multicenter , double-blind trial , patients with UI ( > or = 7 episode/wk ) and frequency ( > or = 8 micturitions/d ) were r and omized to CR or IR oxybutynin for 6 weeks . Patients initiated treatment at 15 mg/d and the dose was adjusted ( in 5-mg/d increments ) over 2 weeks according to tolerability . Efficacy ( UI episodes , voids , absorbent pads used , urgency , and volume voided per micturition ) was assessed during the final 2 weeks of treatment . Tolerability was assessed by evaluating adverse events and treatment withdrawals . RESULTS Of the 125 patients r and omized , 94 ( 75 % ) were evaluable for efficacy ; tolerability was assessed in all patients . In the CR group , 48 patients ( 91 % ) were women and 5 ( 9 % ) were men ; the mean ( SD ) age was 58.0 ( 12.4 ) years ( range , 26 - 78 years ) . In the IR group , 37 patients ( 90 % ) were women and 4 ( 10 % ) were men ; the mean ( SD ) age was 60.6 ( 14.8 ) years ( range , 26 - 83 years ) . Both CR and IR oxybutynin significantly reduced the mean number of total UI episodes per week ( both P < 0.001 vs baseline ) . Both treatments produced equivalent reductions in mean voiding frequency and urinary urgency ( all P < 0.001 vs. baseline ) . Significantly more patients rated CR oxybutynin tolerable on the initial dose of 15 mg/d ( P = 0.020 ) and completed the study at a dose of > or = 15 mg/d ( P = 0.018 ) . Dry mouth was the most common adverse event , reported by 68 % and 72 % of patients in the CR and IR oxybutynin groups , respectively . CONCLUSIONS Among the patients with urge UI included in this study , CR oxybutynin was as effective as IR oxybutynin for improving primary symptoms , with the additional benefit of QD administration Oxybutynin has long been used for the treatment of patients with detrusor overactivity and urinary urge incontinence . The short half-life of oxybutynin administered as a conventional tablet formulation or syrup requires 2 - 3 times daily dosage to be effective . A new controlled release ( CR ) tablet for once-daily administration has been developed . The efficacy and tolerability of this new controlled release tablet was compared to that of a 5-mg conventional oxybutynin tablet administered twice daily . Seventeen female incontinent patients were studied in a double-dummy crossover trial . Efficacy and tolerability were assessed by using a voiding diary , pad-weighing test , visual-analogue scale ( VAS ) , and question naire . Adverse events were recorded spontaneously on a question naire by the patients themselves throughout the study . Serum concentrations of oxybutynin and its active metabolite N-desethyloxybutynin were studied after both a single dose and multiple dosage . There was no difference in efficacy between the two formulations . Depending on the parameters tested , the change from baseline values in a positive direction ranged from 15 to 53 % . The incidence of adverse events was similar with both formulations . Oxybutynin or its metabolite showed no cumulation during the multiple dosage with a 10-mg CR tablet . The controlled release tablet formulation is as effective and as well-tolerated as the conventional one , but has the advantage of only once-a-day dosage , enhancing treatment compliance PURPOSE We compared the short-term efficacy , safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence . MATERIAL S AND METHODS Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study . Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent r and omization to transdermal or oral treatment . Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily . Dose titration was based on anticholinergic symptoms . Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary , a visual analog scale for efficacy and anticholinergic symptoms reported on a question naire . Safety monitoring included adverse events and skin tolerability of the transdermal system . RESULTS A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment . Mean age in the transdermal and oral groups was 64 and 63 years , and 87 % and 97 % were female , respectively . Daily incontinent episodes decreased in the transdermal and oral groups ( 7.3 to 2.4 [ 66 % ] and 7.4 to 2.6 [ 72 % ] , respectively , p = 0.39 ) . The visual analog scale reduction in urinary leakage improved from washout in both groups ( p < 0.0001 ) with no difference between them ( p = 0.9 ) . Dry mouth occurred in significantly fewer patients in the transdermal ( 38 % ) compared with those in the oral group ( 94 % , p < 0.001 ) . Of the patients in the transdermal group 67 % noticed a reduction in dry mouth severity compared with previous oral treatment , and 90 % had none or mild skin erythema . CONCLUSIONS Transdermal delivery of oxybutynin result ed in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence Summary Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder , a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence , usually in combination with urinary frequency and nocturia . This study consisted of two trials ; in one , patients with overactive bladder were r and omized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine ( TER ) , and in the other to 5 mg or 10 mg of extended-release oxybutynin ( OER ) . The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other , or for geographical location . A total of 1289 patients were enrolled , 669 in the tolterodine trial ( TER 2 mg , n = 333 ; TER 4 mg , n = 336 ) and 620 in the oxybutynin trial ( OER 5 mg , n = 313 ; OER 10 mg , n = 307 ) . Fewer patients prematurely withdrew from the trial in the TER 4 mg group ( 12 % ) than either the OER 5 mg ( 19 % ; p = 0.01 ) or OER 10 mg groups ( 21 % ; p = 0.002 ) . More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability ( 13 % vs 6 % ; p = 0.001 ) . After 8 weeks , 70 % of patients in the TER 4 mg group perceived an improved bladder condition , compared with 60 % in the TER 2 mg group , 59 % in the OER 5 mg group and 60 % in the OER 10 mg group ( all p < 0.01 vs TER 4 mg ) . Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline ( TER 4 mg 77 % vs OER 10 mg 65 % ; p < 0.01 ) . Dry mouth was dose-dependent with both agents , although differences between doses only reached statistical significance in the oxybutynin trial ( OER 5 mg vs OER 10 mg ; p = 0.05 ) . Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg . In conclusion , the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg PURPOSE We compared the efficacy and safety of once daily controlled and immediate release oxybutynin for incontinence . MATERIAL S AND METHODS This multicenter , r and omized , double-blind , active control , parallel study was design ed to evaluate urge urinary incontinence episodes using a 7-day diary . RESULTS A total of 97 women and 8 men 34 to 76 years old with urge incontinence or mixed incontinence with a clinical ly significant urge component were enrolled in the study . The number of weekly urge incontinence episodes decreased from 27.4 to 4.8 after controlled and from 23.4 to 3.1 after immediate release oxybutynin ( p = 0.56 ) , and total incontinence episodes decreased from 29.3 to 6 and from 26.3 to 3.8 , respectively ( p = 0.6 ) . Weekly urge incontinence episodes from baseline to end of study also decreased to 84 % after controlled and 88 % after immediate release oxybutynin ( p = 0.7 ) . Continence was achieved in 41 % of the controlled and 40 % of the immediate release group ( p = 0.9 ) . Dry mouth of any severity was reported by 68 and 87 % of the controlled and immediate release groups , respectively ( p = 0.04 ) , and moderate or severe dry mouth occurred in 25 and 46 % , respectively ( p = 0.03 ) . CONCLUSIONS Participants taking a single daily does of controlled release oxybutynin had similar reductions in urge incontinence and total incontinence episodes compared to those taking oxybutynin 1 to 4 times daily . A lower incidence of dry mouth was reported for controlled release oxybutynin |
2,653 | 27,823,975 | CONCLUSIONS Compared with WLI-TUR , NBI-TUR can reduce the recurrence risk of NMIBC . | CONTEXT Compared with white light imaging ( WLI ) cystoscopy , narrow b and imaging ( NBI ) cystoscopy could increase the visualization and detection of bladder cancer ( BC ) at the time of transurethral resection ( TUR ) .
NBI cystoscopy could increase the detection of BC , but it remains unclear whether narrow b and imaging-assisted transurethral resection ( NBI-TUR ) could reduce the recurrence risk of non-muscle invasive bladder cancer ( NMIBC ) .
Several r and omized clinical trials ( RCTs ) have recently tested the efficacy of NBI-TUR for NMIBC .
OBJECTIVE To perform a systematic review and meta- analysis of RCTs and evaluate the efficacy of NBI-TUR for NMIBC compared with white light imaging-assisted transurethral resection ( WLI-TUR ) . | PURPOSE As shown in various studies 5-aminolevulinic acid ( ALA ) induces fluorescence of malignant and dysplastic bladder tissue and increases tumor detection rates by about 20 % . However , data on the long-term benefits are sparse . Thus , the 5-year outcome data of a prospect i ve r and omized trial comparing patients who initially underwent bladder tumor resection ( TUR ) under st and ard white light or with ALA induced fluorescence were evaluated . MATERIAL S AND METHODS A total of 115 patients with suspected superficial bladder cancer were r and omized to undergo st and ard or ALA assisted TUR . After the second look TUR at 6 weeks patients were followed for a median of 39 ( st and ard ) and 42 ( ALA ) months . RESULTS Median time to first recurrence was 5 months in the st and ard and 12 months in the ALA group . Recurrence-free survival was 25 % in the st and ard and 41 % in the ALA group . The recurrence rate at 2 , 12 , 36 and 60 months after initial TUR was 41 % , 61 % , 73 % and 75 % , and 16 % , 43 % , 59 % and 59 % in the white light and ALA groups , respectively . The total number of recurrences was 82 in the st and ard and 61 in the ALA group . Tumor progression occurred in 9 patients in the st and ard and 4 in the ALA group . Cost analysis suggests a considerable economical advantage of ALA fluorescence assisted TUR compared to the st and ard procedure . CONCLUSIONS The initial advantage of improved tumor detection and decreased recurrence rates by ALA fluorescence assisted TUR is maintained for years , and effectively reduces morbidity and costs in patients with superficial bladder tumors Abstract Objectives : A prospect i ve study was performed aim ing to evaluate the surgical efficacy , perioperative safety profile , diagnostic accuracy and medium term results of a multi-modal approach consisting in narrow b and imaging ( NBI ) cystoscopy and bipolar plasma vaporization ( BPV ) when compared to the st and ard protocol represented by white light cystoscopy ( WLC ) and transurethral resection of bladder tumors ( TURBT ) . Material s & Methods : A total of 260 patients with apparently at least one bladder tumor over 3 cm were included in the trial . In the first group , 130 patients underwent conventional and NBI cystoscopy followed by BPV , while in a similar number of cases of the second arm , classical WLC and TURBT were applied . In all non-muscle invasive bladder tumors ’ ( NMIBT ) pathologically confirmed cases , st and ard monopolar Re-TUR was performed at 4 - 6 weeks after the initial intervention , followed by one year ’ BCG immunotherapy . The follow-up protocol included abdominal ultrasound , urinary cytology and WLC , performed every 3 months for a period of 2 years . Results : The obturator nerve stimulation , bladder wall perforation , mean hemoglobin level drop , postoperative bleeding , catheterization period and hospital stay were significantly reduced for the plasma vaporization technique by comparison to conventional resection . Concerning tumoral detection , the present data confirmed the NBI superiority when compared to st and ard WLC regardless of tumor stage ( 95.3 % vs. 65.1 % for CIS , 93.3 % vs. 82.2 % for pTa , 97.4 % vs. 94 % for pT1 , 95 % vs. 84.2 % overall ) . During st and ard Re-TUR the overall ( 6.3 % versus 17.4 % ) and primary site ( 3.6 % versus 12.8 % ) residual tumors ’ rates were significantly lower for the NBI-BPV group . The 1 ( 7.2 % versus 18.3 % ) and 2 ( 11.5 % versus 25.8 % ) years ’ recurrence rates were substantially lower for the combined approach . Conclusions : NBI cystoscopy significantly improved diagnostic accuracy , while bipolar technology showed a higher surgical efficiency , lower morbidity and faster postoperative recovery . The combined technique offered a reduced rate of residual tumors at Re-TUR , both globally as well as for orthotopic tumors . Substantially lower recurrence rates were found at 1 and 2 years among the NBI-BPV cases Purpose To investigate whether narrow b and imaging (NBI)-assisted transurethral resection ( TUR ) ( NBI-TUR ) has an impact on non-muscle invasive bladder cancer ( NMIBC ) residual tumour rate compared to white light (WL)-assisted TUR ( WL-TUR ) . Methods Patients with NMIBC treated with either NBI- or WL-TUR were compared in a frequency-matched index-control setting . During NBI-TUR , all suspicious lesions identified by either WL or NBI were resected . Index patients ( NBI-TUR , n = 40 ) were prospect ively recruited and control patients ( WL-TUR , n = 120 ) were retrospectively collected , whilst being blinded for their first follow-up (fFU)-status . Non-radical TUR cases , patients without evidence of urothelial carcinoma in the pathology specimen and those with isolated carcinoma in situ or muscle invasive disease were excluded . Matching was based on the risk of tumour recurrence defined by ( a ) the EORTC risk score for recurrence and ( b ) the administration or not of one single chemotherapeutic intravesical instillation immediately after TUR . All patients underwent routine follow-up with WL cystoscopy supplemented with cytology at 3 months or re-TUR in selected cases . The residual tumour rates at fFU ( RR-fFU ) of patients with NMIBC su bmi tted to either NBI- or WL-TUR were compared . Results Baseline patient and tumour characteristics were comparable between groups . The RR-fFU for WL- and NBI-TUR was 30.5 % ( 36 out of 118 patients ) and 15.0 % ( 6 out of 40 patients ) , respectively ( OR : 2.7 , one-sided 95 % CI : 1.2–6.1 ; P = 0.03 ) . Conclusion NBI-TUR decreases residual tumour rate significantly when compared to a matched cohort of WL-TUR OBJECTIVE To compare the differential effects of narrow b and imaging (NBI)-assisted holmium laser with transurethral resection on the 1-year recurrence rate of non-muscle invasive bladder cancer ( NMIBC ) , and to evaluate the clinical values of NBI-assisted holmium laser resection for NMIBC ( NBI-HoLRBt ) . METHODS During the period of February 2013 to February 2014 , 178 cases of NMIBC were r and omly divided into NBI-HoLRBt group and white light imaging ( WLI ) assisted transurethral resection of bladder tumor ( WLI-TURBt ) group . In NBI-HoLRBt , all suspicious lesion identified by either WLI or NBI were resected with WLI and in NBI mode for lesion only visible with NBI . At the end of the procedure , a NBI cystoscopic examination was performed to assess the margins of the resection areas and to identify eventual residual lesions . In WLI-TURBt group , only WLI and TURBt were applied . All patients underwent routine follow-up with WLI and NBI cystoscopy supplemented with cytology every 3 month . The recurrence risk of patients with NMIBC subjected to either NBI-HoLRBt or WLI-TURBt was compared at 3 and 12 month . RESULTS The 3-month and 1-year recurrence rate was 18.48 % ( 17/92 ) and 38.04 % ( 35/92 ) respectively in the WLI-TURBt group , it was 5.81 % ( 5/86 ) and 18.60 % ( 16/86 ) in the NBI-HoLRBt group ( both P<0.05 ) . In addition , the in situ recurrence rate was less in the NBI-HoLRBt than WLI-TURBt group ( 2.33 % vs 14.13 % , P<0.05 ) . CONCLUSION NBI-assisted holmium laser resection of bladder tumor can reduce the 3-month and 1-year recurrence risk of NMIBC and should be considered a valuable clinical therapeutic method for NMIBC Introduction : The objective of this study was to investigate the value of narrow-b and imaging ( NBI ) cystoscopy in the detection of patients with positive voided urine cytology ( VUC ) who have no evidence of disease after st and ard initial investigations . Patients and Methods : Between February 2009 and December 2010 , 12 patients with positive or suspicious VUC but no regular endoscopic evidence of cancer were investigated with NBI flexible cystoscopy . All the specimens were biopsied both under NBI and white light imaging ( WLI ) . R and om biopsies of bladder and prostatic urethra were performed in cases without suspect lesions . Results : Fourteen NBI cystoscopies were carried out in 12 patients . Non-muscle-invasive bladder cancer was diagnosed in 5 of 12 ( 42 % ) patients on the first NBI . One patient had carcinoma in situ diagnosed on repeat NBI 3 months later . The sensitivity and specificity in diagnosing unconfirmed positive VUC was 78 and 91 % for NBI vs. 50 and 80 % for WLI . Conclusions : NBI cystoscopy significantly improves detection of unconfirmed positive VUC over WLI . It should be carried out early in the investigation of such patients before r and om biopsies and ureteroscopy PURPOSE The role of a routine second transurethral resection in evaluating and managing bladder tumors is defined . MATERIAL S AND METHODS From January to October 1998 , 150 patients with new or recurrent bladder tumors underwent repeat transurethral resection within 2 to 6 weeks after the initial resection , and the results , including the presence of residual tumor and tumor stage , were compared . RESULTS Of the 150 cases 36 ( 24 % ) had no and 114 ( 76 % ) had residual tumor on repeat transurethral resection . Of 96 cases with superficial ( Ta , Tis , T1 ) bladder tumors 72 ( 75 % ) had residual noninvasive tumor and 28 ( 29 % ) were up staged to invasive tumor . Among 54 patients with a muscle invasive tumor 12 ( 22 % ) had no residual tumor on repeat transurethral resection . Results of the second resection changed tumor treatment in 50 patients ( 33 % ) . CONCLUSIONS Many patients with bladder tumors have tumor present after an initial trans-urethral resection . Routine repeat resection is advised to control noninvasive tumors and to detect residual tumor invasion Recent advances in imaging technology may offer the ability to augment bladder cancer diagnosis , staging , and treatment . Fluorescence cystoscopy has been shown in numerous clinical studies to improve the detection of papillary and flat bladder lesions over conventional cystoscopy . Photosensitizing agents like aminolevulinic acid ( ALA ) and its derivative hexaminolevulinate ( HAL ) have undergone the most extensive investigation . Prospect i ve clinical trials have demonstrated improved diagnostic ability , enhanced tumor resection , and reduced tumor recurrence . Optical coherence tomography is an emerging technology that shows promise in revealing subsurface information about bladder lesions in real-time , potentially leading to more accurate staging . Narrow-b and imaging may augment st and ard endoscopic tools by providing increased contrast between normal and abnormal tissue . Virtual cystoscopy may allow non-invasive tumor diagnosis , treatment planning , and surveillance . We aim to provide an overview of the strengths and weaknesses of these imaging modalities and examine their potential impact on the diagnosis and management of bladder cancer PURPOSE We compared the outcomes of repeat transurethral resection plus intravesical mitomycin C with initial transurethral resection of bladder plus intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma of the bladder in terms of recurrence , progression and overall survival . MATERIAL S AND METHODS Of 148 newly diagnosed patients with T1 bladder cancer 142 were prospect ively r and omized in 2 groups between January 2001 and January 2005 . A total of 74 patients underwent second TURB and received adjuvant MMC intravesically ( group 1 ) and 68 patients received adjuvant MMC following the initial TURB ( group 2 ) . All repeat TURB operations were performed 2 to 6 weeks following initial TURB . Patients with incomplete resection , Cis or muscle invasive disease were excluded from study . The first dose of mitomycin C ( 40 mg per week for a total of 8 weeks ) was instilled intravesically in all patients during the first 24 hours after the last surgery . RESULTS Mean followup was 31.5 months ( range 6 to 48 ) with no difference between the 2 groups . The rate of recurrence-free survival was 86.35 % ( SE 0.4 % ) , 77.67 % and 68.72 % in group 1 , and 47.08 % , 42.31 % and 37.01 % in group 2 for the first , second and third year , respectively ( overall 74.32 % vs 36.76 % , log rank 0.0001 ) . Recurrence was observed in 19 of the 74 ( 25.68 % ) patients in group 1 and in 43 of the 68 ( 63.24 % ) patients in group 2 . Ten of the 19 ( 52.63 % ) patients in group 1 and 35 of the 43 ( 81.39 % ) patients in group 2 had recurrence within 12 months . Recurrence was observed in 17.6 % , 25 % and 60 % of patients with G1 , G2 and G3 tumors , respectively , in group 1 . The same rates for group 2 were 25 % , 64 % and 90 % . The RFS rate was significantly worse in the high grade group ( G2 and G3 ) ( p < 0.001 ) . Progression was observed at 4.05 % for group 1 compared to 11.76 % for group 2 ( log rank 0.0974 ) . OS was 91.89 % and 89.71 % in group 1 and 2 , respectively ( log rank 0.732 ) . CONCLUSIONS The high recurrence rate in patients who did not undergo ReTUR is due to a high residual tumor rate following initial TURB . The benefit of ReTUR is especially true for high grade tumors . Since intravesical MMC was present in both groups , this study has shown that intravesical chemotherapy does not compensate for inadequate resection . Progression does not seem to be affected by ReTUR although there was a trend favoring the ReTUR group . We recommend ReTUR for patients with primary high grade T1 disease to achieve better recurrence-free survival UNLABELLED Narrow-b and imaging ( NBI ) cystoscopy detects more bladder tumors than st and ard white-light imaging ( WLI ) cystoscopy , but it is unclear whether NBI improves transurethral resection ( TUR ) of bladder tumors . This study compares 2-yr recurrence-free survival ( RFS ) of patients with non-muscle-invasive bladder tumors following restaging TUR using NBI or WLI cystoscopy . Patients were r and omized 1:1 to undergo NBI-assisted TUR ( NBI-TUR ) or WLI-assisted TUR ( WLI-TUR ) . The main outcome was number of patients free of tumor recurrence after 2-yr follow-up and 2-yr RFS times . Of 254 patients , 127 underwent NBI-TUR and 127 had WLI-TUR . Within 2 yr , 22 % of the patients in the NBI-TUR group recurred compared with 33 % after WLI-TUR ( p=0.05 ) . The mean RFS time was 22 mo ( 95 % confidence interval [ CI ] , 20 - 23 ) for the NBI-TUR group versus 19 mo ( 95 % CI , 18 - 21 ) for the WLI-TUR group ( p=0.02 ) . Limitations are that this was a single-surgeon study and that a 20 % difference in the number of patients free of recurrence was not achieved , suggesting the study was underpowered . In addition , observer bias may have contributed to results because NBI-TUR was performed after both WLI and NBI cystoscopy was used to inspect the bladder . Although the results suggest reduced recurrence rates and improved RFS times after restaging NBI-TUR compared with WLI-TUR , a larger study is needed . PATIENT SUMMARY Narrow-b and imaging enhances visibility of bladder tumors over conventional white-light cystoscopy . This report compares transurethral resection of bladder tumors using narrow-b and cystoscopy with white-light cystoscopy . The results show that narrow-b and cystoscopy improves surgical removal of bladder tumors , which reduces the frequency of early and later tumor recurrences PURPOSE We compared hexaminolevulinate ( Hexvix ) fluorescence cystoscopy with white light cystoscopy for detecting carcinoma in situ . MATERIAL S AND METHODS In this multicenter study 298 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate for 1 hour . Cystoscopy was then performed , first using st and ard white light and then hexaminolevulinate fluorescence cystoscopy . Lesions or suspicious areas identified under the 2 illumination conditions were mapped and biopsied for histological examination . In addition , 1 directed biopsy was obtained from an area appearing to be normal . RESULTS Of 196 evaluable patients 29.6 % ( 58 of 196 ) had carcinoma in situ , including 18 with carcinoma in situ alone , and 35 with carcinoma in situ and concomitant papillary disease , which was only detected on r and om biopsy in 5 . Of the 18 patients with no concomitant papillary disease carcinoma in situ was detected only by hexaminolevulinate fluorescence in 4 and only by white light in 4 . In the group with concomitant papillary disease carcinoma in situ was found only by hexaminolevulinate fluorescence in 5 patients and only by white light in 3 . The proportion of patients in whom 1 or more carcinoma in situ lesions were found only by hexaminolevulinate cystoscopy was greater than the hypothesized 5 % ( p=0.0022 ) . Overall more carcinoma in situ lesions were found by hexaminolevulinate than by white light cystoscopy in 22 of 58 patients ( 41.5 % ) , while the converse occurred in 8 of 58 ( 15.1 % ) . Biopsy results confirmed cystoscopy findings . Of a total of 113 carcinoma in situ lesions in 58 patients 104 ( 92 % ) were detected by hexaminolevulinate cystoscopy and 77 ( 68 % ) were detected by white light cystoscopy , while 5 were detected only on directed visually normal mucosal biopsy . Hexaminolevulinate instillation was well tolerated with no local or systemic side effects . CONCLUSIONS In patients with bladder cancer hexaminolevulinate fluorescence cystoscopy with blue light can diagnose carcinoma in situ that may be missed with white light cystoscopy . Hexaminolevulinate fluorescence cystoscopy can be used in conjunction with white light cystoscopy to aid in the diagnosis of this form of bladder cancer Objective We investigated whether narrow-b and imaging ( NBI ) was superior to white light imaging ( WLI ) for detecting primary non-muscle invasive bladder cancer ( NMIBC ) in a r and omized imaging sequence modality , as the increased detection rate by NBI maybe result from the “ second look ” inspection of the bladder . Methods Between February 2009 and May 2010 , NBI and WLI flexible cystoscopy were prospect ively performed on 78 patients with primary suspected NMIBC . According to r and omization protocol , the bladder was mapped using WLI then NBI or vice versa within the same observation time . Suspicious lesions together with controlled normal-appearing mucosa were biopsied and examined by a pathologist blinded to the imaging sequence . The tumors detected on patient and tumor level , sensitivity , specificity , and accuracy were compared in both imaging . Results Sixty-nine of 78 ( 88.5 % ) patients were diagnosed with bladder cancer including 211 tumors totally . Of these , 36 ( 17.1 % ) tumors in 13 patients were detected by NBI only , while 4 ( 1.9 % ) tumors in 3 patients found by WLI only . NBI identified significantly more additional tumors than WLI ( P < 0.01 ) . The sensitivity of WLI versus NBI for detecting primary bladder tumors was 77.7 versus 92.9 % ( P < 0.0001 ) , the specificity 82.7 versus 73.5 % ( P > 0.05 ) , and the accuracy 79.3 versus 86.7 % ( P < 0.05 ) . The sensitivity of WLI versus NBI for detecting carcinoma in situ ( CIS ) was 68.3 versus 87.8 % ( P < 0.05 ) , the specificity 82.9 versus 77.1 % ( P > 0.05 ) , and the accuracy 75 versus 82.9 % ( P > 0.05 ) . Conclusions The “ second look ” did not compromise the superiority of NBI over st and ard WLI flexible cystoscopy for detecting primary NMIBC including CIS lesions OBJECTIVE Photodynamic diagnosis ( PDD ) for the detection of bladder cancer has become a diagnostic tool in several hospitals . Several studies have reported different rates of false positive biopsies using 5-aminolevulinic acid induced fluorescence . In this study we evaluated the effect of previous intravesical therapy on the false positive biopsy rate . METHODS Two hours prior to endoscopy 1.5 g ALA dissolved in 50ml 1.4 % NaHCO(3 ) solution was instilled intravesically . For fluorescence excitation a blue light source ( D-light , Karl Storz ) was used . Under white and fluorescence light guidance , tumor locations were recorded , cold cup biopsies were taken and tumors were resected . Patients were divided into 3 groups , last intravesical therapy ( IVT ) less than 6 months prior to PDD , last IVT longer than 6 months before PDD and no previous IVT . RESULTS In total 917 biopsies were taken in 249 procedures of fluorescent and non-fluorescent areas . White light endoscopy revealed 270 and PDD 378 of in total 390 tumors , result ing in a sensitivity of 97 % and specificity of 49 % for PDD . Pathologic evaluation considered 270 fluorescent biopsies as false positive . The rate of false positive biopsies was 25.7 % in the group No IVT , 30.6 % in the group PDD-IVT > 6 months , whereas in the group " within 6 months after intravesical therapy " the rate was 39.6 % ( p<0.025 ) . When premalignant lesions such as dysplasia II are considered tumor the difference between the groups is even more significant ( p<0.001 ) . CONCLUSIONS The procedure has a high sensitivity for superficial bladder cancer and decreases the number of overlooked lesions . Recent intravesical therapy results in significantly more false positive fluorescent biopsies . Since patient outcome might predominantly be determined by the early detection and subsequent treatment of (pre)malignant tissue we suggest that PDD is justified even shortly after intravesical therapy PURPOSE We evaluated the use of narrow-b and imaging ( NBI ) cystoscopy for the detection of bladder cancer and analyzed its diagnostic efficacy in cases of carcinoma in situ ( CIS ) and in cases with known urine cytology results . PATIENTS AND METHODS A prospect i ve controlled study of NBI was conducted in 104 consecutive patients with definite or suspected bladder cancer . Transurethral targeted biopsies were performed after white light imaging ( WLI ) and NBI cystoscopy , and the histologic outcomes were compared . RESULTS A total of 313 biopsies were taken , including 161 from sites identified as potentially abnormal by NBI and /or WLI cystoscopy , and 152 from apparently normal sites . The percentage of malignancies in the sites identified only by NBI was 55.7 % ( 39/70 places ) . In 26.9 % of patients ( 28/104 ) , bladder tumors were detected only by NBI . The sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and likelihood ratio of a negative test ( NLR ) for the detection of bladder tumors using NBI in all patients were 92.7 % , 70.9 % , 63.4 % , 94.7 % , and 0.10 , respectively . The sensitivity , specificity , PPV , NPV , and NLR for the detection of CIS using NBI were 89.7 % , 74.5 % , 78.8 % , 87.2 % , and 0.14 , respectively . The sensitivity , specificity , PPV , NPV , and NLR for the detection of bladder tumors using NBI in patients with positive vs negative urine cytology were 85.4 % vs 98.4 % , 75.7 % vs 66.3 % , 61.2 % vs 64.5 % , 92.0 % vs 98.5 % , and 0.19 vs 0.02 , respectively . CONCLUSIONS NBI is a simple and effective method for identifying bladder tumors including CIS without the need for dyes because of its high sensitivity , high NPV , and low NLR PURPOSE We compared hexaminolevulinate fluorescence cystoscopy with white light cystoscopy for detecting Ta and T1 papillary lesions in patients with bladder cancer . MATERIAL S AND METHODS A total of 311 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM HAL for 1 hour . The bladder was inspected using white light cystoscopy , followed by blue light ( fluorescence ) cystoscopy . Papillary lesions were mapped and resected for histological examination . RESULTS Noninvasive pTa tumors were found in 108 of 196 evaluable patients ( 55.1 % ) . In 31 patients ( 29 % ) at least 1 more tumor was detected by HAL than by white light cystoscopy ( p<0.05 ) . Six of these patients had no lesions detected by white light , 12 had 1 lesion detected by white light and more than 1 by HAL , and 13 had multiple Ta lesions detected by the 2 methods . Conversely at least 1 more tumor was detected by white light cystoscopy than by HAL cystoscopy in 10 patients ( 9 % , 95 % CI 5 - 16 ) . Tumors invading the lamina propria ( T1 ) were found in 20 patients ( 10.2 % ) . At least 1 additional T1 tumor was detected by HAL but not by white light cystoscopy in 3 of these patients ( 15 % ) , while at least 1 more T1 tumor was detected by white light cystoscopy than by HAL cystoscopy in 1 patient ( 5 % , 95 % CI 0 - 25 ) . Detection rates for Ta tumors were 95 % for HAL cystoscopy and 83 % for white light cystoscopy ( p=0.0001 ) . Detection rates were 95 % and 86 % , respectively , for T1 tumors ( p=0.3 ) . HAL instillation was well tolerated with few local or systemic side effects . CONCLUSIONS HAL fluorescence cystoscopy detected at least 1 more Ta and T1 papillary tumor than white light cystoscopy in approximately a third of the patients with such tumors . Whether this would translate to improved patient outcomes has yet to be determined BACKGROUND Narrow b and imaging ( NBI ) is an optical enhancement technology that filters white light into two b and widths of illumination centered on 415 nm ( blue ) and 540 nm ( green ) . NBI cystoscopy can increase bladder cancer ( BCa ) visualization and detection at the time of transurethral resection ( TUR ) . NBI may therefore reduce subsequent relapse following TUR . OBJECTIVE Assess the impact of NBI modality on 1-yr non-muscle-invasive BCa ( NMIBC ) recurrence risk . DESIGN , SETTING , AND PARTICIPANTS Consecutive patients with overt or suspected BCa were included in a prospect i ve study powered to test a 10 % difference in 1-yr recurrence risk in favor of cases su bmi tted to NBI TUR . Excluding patients with muscle-invasive BCa , negative pathologic examination , or without follow-up , the study population was composed of 148 subjects r and omized from August 2009 to September 2010 to NBI TUR ( 76 cases ) or white light ( WL ) TUR ( 72 cases ) . INTERVENTION TUR was performed in NBI or st and ard WL modality . MEASUREMENTS The 1-yr recurrence risks in NBI or WL TUR groups were compared using odds ratio ( OR ) point and interval estimates derived from logistic regression modeling . RESULTS AND LIMITATIONS The 1-yr recurrence-risk was 25 of 76 patients ( 32.9 % ) in the NBI and 37 of 72 patients ( 51.4 % ) in the WL group ( OR=0.62 ; p=0.0141 ) . Simple and multiple logistic regression analyses provided similar OR points and interval estimates . CONCLUSIONS TUR performed in the NBI modality reduces the recurrence risk of NMIBC by at least 10 % at 1 yr OBJECTIVES To determine whether narrow b and imaging ( NBI ) improves detection of non-muscle-invasive bladder cancer over white-light imaging ( WLI ) cystoscopy . METHODS We conducted a prospect i ve , within-patient comparison on 103 consecutive procedures on 95 patients scheduled for ( re- ) transurethral resection of a bladder tumor ( 84 ) or bladder biopsies ( 19 ) in the Academic Medical Center , Amsterdam ( September 2007-July 2009 ) and in the General Faculty Hospital , Prague ( January 2009-July 2009 ) . WLI and NBI cystoscopy were subsequently performed by different surgeons who independently indicated all tumors and suspect areas on a bladder diagram . The lesions identified were resected/biopsied and sent for histopathological examination . Number of patients with additional tumors detected by WLI and NBI were calculated ; mean number of urothelial carcinomas ( UCs ) per patient , detection rates , and false-positive rates of both techniques were compared . RESULTS A total of 78 patients had a confirmed UC ; there were 226 tumors in total . In 28 ( 35.9 % ) of these patients , a total of 39 additional tumors ( 17.3 % ) ( 26pTa , 6pT1 , 1pT2 , 6pTis ) were detected by NBI , whereas 4 additional tumors ( 1.8 % ) ( 1pTa , 1pT1 , 2pTis ) within 3 patients ( 2.9 % ) were detected by WLI . The mean ( SD , range ) number of UCs per patient identified by NBI was 2.1 ( 2.6 , 0 - 15 ) , vs 1.7 ( 2.3 , 0 - 15 ) by WLI ( P < .001 ) . The detection rate of NBI was 94.7 % vs 79.2 % for WLI ( P < .001 ) . The false-positive rate of NBI and WLI was 31.6 % and 24.5 % , respectively ( P < .001 ) . CONCLUSIONS NBI cystoscopy improves the detection of primary and recurrent nonmuscle invasive bladder cancer over WLI . However , further validation of the technique with comparative studies is required |
2,654 | 23,908,515 | 15 van der Veen MJ , Dinant HJ , van BoomaFrankfort C et al. Can methotrexate be used as a steroid-sparing agent in the treatment of polymyalgia rheumatica and giant cell arteritis ? | 9 Pease CT , Haugeberg G , Morgan AW et al. Diagnosing late onset rheumatoid arthritis , polymyalgia rheumatica , and temporal arteritis in patients presenting with polymyalgic symptoms .
10 Falsetti P , Acciai C , Volpe A , Lenzi L. Ultrasonography in early assessment of elderly patients with polymyalgic symptoms : a role in predicting diagnostic outcome ?
11 Hernández-Rodríguez J , Cid MC , LópezSoto A et al. Treatment of polymyalgia rheumatica : a systematic review .
16 Caporali R , Cimmino MA , Ferraccioli G et al. Prednisone plus methotrexate for polymyalgia rheumatica : a r and omized , double-blind , placebo-controlled trial .
17 De Silva M , Hazleman BL .
Azathioprine in giant cell arteritis/polymyalgia rheumatica : a double-blind study .
18 Cimmino MA , Salvarani C , Macchioni P et al. Long-term follow-up of polymyalgia rheumatica patients treated with methotrexate and steroids . | OBJECTIVE The use of colchicine to prevent acute gout flares during initiation of allopurinol therapy is widely practice d despite lack of proven benefit . We investigated if colchicine administration during initiation of allopurinol for chronic gouty arthritis reduces the frequency and /or severity of acute gout flares . METHODS Patients starting allopurinol for crystal-proven chronic gouty arthritis were r and omized to receive colchicine 0.6 mg po bid or placebo in a r and omized , prospect i ve , double blind , placebo controlled trial . Subjects were followed for evidence of acute gout flares and remained on study drug for 3 months beyond attaining a serum urate concentration < 6.5 mg/dl . Treatment arms were analyzed regarding frequency of flares , likelihood of any flare or multiple flares , severity of flares on the visual analog scale ( VAS ) , and length of flares in days . RESULTS Forty-three subjects were studied . Subjects treated with colchicine experienced fewer total flares ( 0.52 vs 2.91 , p = 0.008 ) , fewer flares from 0 to 3 months ( 0.57 vs 1.91 , p = 0.022 ) , fewer flares 3 - 6 months ( 0 vs 1.05 , p = 0.033 ) , less severe flares as reported on VAS ( 3.64 vs 5.08 , p = 0.018 ) , and fewer recurrent gout flares ( p = 0.001 ) . Colchicine was well tolerated . CONCLUSION Colchicine prophylaxis during initiation of allopurinol for chronic gouty arthritis reduces the frequency and severity of acute flares , and reduces the likelihood of recurrent flares . Treating patients with colchicine during initiation of allopurinol therapy for 6 months is supported by our data OBJECTIVE To determine if lowering of serum uric acid ( SUA ) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout . METHODS A prospect i ve study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl . We recalled all 57 patients who were available during 1999 . Patients were divided into 2 groups : Group A , with SUA still > 6 mg/dl , and Group B , with SUA < or = 6 mg/dl . A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals . RESULTS There were no differences between the groups in age , sex , duration of gout , or serum creatinine . Group A ( n = 38 ) had a mean of 6 attacks of gout for the recent year , those with tophi having the most frequent attacks . Among the 16 patients in this group who agreed to knee aspiration , monosodium urate ( MSU ) crystals were found in 14 , although they were asymptomatic at the time . Nineteen patients ( Group B ) were able to maintain serum urate levels < or = 6 mg/dl for > 12 months . Nearly half of them had no attack of gout for 2 or more years , with a mean of 1 attack in the last year for the whole group . Three patients in whom tophi were found did not have major flares of gout within the past year . Knee joint aspiration was done on 16 asymptomatic patients . Seven ( 44 % ) still had MSU crystals present in their knees . Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years , although the frequency of attacks was less in those who continued colchicine . CONCLUSION A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to < or = 6 mg/dl for several years . The mechanisms for persistence in some patients , and whether such crystals have clinical implication s , are not known . Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks CONTEXT Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition . Pegloticase , monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase , was developed to fulfill this need . OBJECTIVE To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout . DESIGN , SETTING , AND PATIENTS Two replicate , r and omized , double-blind , placebo-controlled trials ( C0405 and C0406 ) were conducted between June 2006 and October 2007 at 56 rheumatology practice s in the United States , Canada , and Mexico in patients with severe gout , allopurinol intolerance or refractoriness , and serum uric acid concentration of 8.0 mg/dL or greater . A total of 225 patients participated : 109 in trial C0405 and 116 in trial C0406 . INTERVENTION Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion ( biweekly treatment group ) , pegloticase alternating with placebo at successive infusions ( monthly treatment group ) , or placebo ( placebo group ) . MAIN OUTCOME MEASURE Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6 . RESULTS In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group ( 47 % ; 95 % CI , 31%-62 % ) , 8 of 41 patients in the monthly group ( 20 % ; 95 % CI , 9%-35 % ) , and in 0 patients treated with placebo ( 0/20 ; 95 % CI , 0%-17 % ; P < .001 and < .04 for comparisons between biweekly and monthly groups vs placebo , respectively ) . Among patients treated with pegloticase in trial C0406 , 16 of 42 in the biweekly group ( 38 % ; 95 % CI , 24%-54 % ) and 21 of 43 in the monthly group ( 49 % ; 95 % CI , 33%-65 % ) achieved the primary end point ; no placebo-treated patients reached the primary end point ( 0/23 ; 95 % CI , 0%-15 % ; P = .001 and < .001 , respectively ) . When data in the 2 trials were pooled , the primary end point was achieved in 36 of 85 patients in the biweekly group ( 42 % ; 95 % CI , 32%-54 % ) , 29 of 84 patients in the monthly group ( 35 % ; 95 % CI , 24%-46 % ) , and 0 of 43 patients in the placebo group ( 0 % ; 95 % CI , 0%-8 % ; P < .001 for each comparison ) . Seven deaths ( 4 in patients receiving pegloticase and 3 in the placebo group ) occurred between r and omization and closure of the study data base ( February 15 , 2008 ) . CONCLUSION Among patients with chronic gout , elevated serum uric acid level , and allopurinol intolerance or refractoriness , the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months result ed in lower uric acid levels compared with placebo . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00325195 BACKGROUND Steroids are the st and ard treatment for polymyalgia rheumatica . The efficacy of the c and i date drug methotrexate has not yet been demonstrated in controlled studies . OBJECTIVE To compare the efficacy and safety of prednisone plus methotrexate and prednisone alone in patients with polymyalgia rheumatica . DESIGN Multicenter r and omized , double-blind , placebo-controlled trial . SETTING 5 Italian rheumatology clinics . PATIENTS 72 patients with newly diagnosed polymyalgia rheumatica . MEASUREMENTS The proportion of patients no longer taking prednisone , the number of flare-ups , and the cumulative prednisone dose after 76 weeks . INTERVENTION Prednisone dosage ( 25 mg/d ) was tapered to 0 mg/d within 24 weeks and was adjusted if flare-ups occurred . Oral methotrexate ( 10 mg ) or placebo , with folinic acid supplementation ( 7.5 mg ) , was given weekly for 48 weeks . RESULTS Twenty-eight of 32 patients in the methotrexate group and 16 of 30 patients in the placebo group were no longer taking prednisone at 76 weeks ( P = 0.003 ) . The risk difference was 34 percentage points ( 95 % CI , 11 to 53 percentage points ) . Similar results were obtained after adjustment for C-reactive protein level and duration of symptoms in a multivariate model . Fifteen of 32 patients in the methotrexate group and 22 of 30 patients in the placebo group had at least 1 flare-up by the end of follow-up ( P = 0.04 ) . The median prednisone dose was 2.1 g in the methotrexate group and 2.97 g in the placebo group ( P = 0.03 ) . The rate and severity of adverse events were similar . LIMITATIONS Follow-up was short , and a high dose of folinic acid and a relatively high starting dosage of prednisone were used . Ten of 72 patients ( 14 % ) discontinued treatment or were lost to follow-up . CONCLUSIONS Prednisone plus methotrexate is associated with shorter prednisone treatment and steroid sparing . It may be useful in patients at high risk for steroid-related toxicity OBJECTIVE To evaluate the effect of local application of ice on duration and severity of acute gouty arthritis . METHODS Nineteen patients with acute gout were enrolled and r and omized into 2 groups . Group A ( n = 10 ) received topical ice therapy , oral prednisone 30 mg PO tapered to 0 over 6 days and colchicine 0.6 mg/day . Group B was the control group ( n = 9 ) , given the same regimen but without the ice therapy . The patients were followed for one week . RESULTS The mean reduction in pain for those patients treated with ice therapy was 7.75 cm ( on 10 cm visual analog scale ) with st and ard deviation + /- 2.58 compared with 4.42 cm ( + /- SD 2.96 ) for the control group . Using a Wilcoxon rank-sum test there was a significant difference ( p = 0.021 ) in pain reduction between the ice therapy and control groups . Joint circumference and synovial fluid volume also tended to be more effectively reduced after one week of therapy in the ice group compared with controls , but these did not achieve statistical significance . CONCLUSION The group treated with ice had a significantly greater reduction in pain compared with the control group . Although the clinical improvement was impressive , due to the small sample size we could not show statistically significant improvement in all the variables that tended to suggest that effect was more than simply analgesic . Cold applications may be a useful adjunct to treatment of acute gouty arthritis OBJECTIVE A series of patients with polymyalgia rheumatica ( PMR ) who received the steroid-sparing combination therapy , prednisone and methotrexate ( MTX ) , underwent a long-term follow-up study at five years to investigate possible reductions of steroid-related side effects . Additional end-points were the number of patients still in need of steroid treatment , the cumulative steroid dose , and the number of flare-ups of PMR . PATIENTS AND METHODS Fifty-seven PMR patients who were enrolled in a double-blind placebo-controlled r and omised trial on the efficacy of MTX added to st and ard steroid treatment were review ed after 5 years . Information was collected on the patients ' previous health conditions or causes of death through a st and ardized question naire by direct visit , chart review , or interviews with relatives . RESULTS After 6 years from initiation of therapy , MTX-treated patients had lower ESR ( 17.1+/-9.7 mm/h vs. 26.8+/-22.9 mm/h , p=0.08 ) and CRP ( 2.7+/-2.3 mg/L vs. 10.2+/-16.4 mg/L , p=0.04 ) . 31 % MTX-treated patients were still on steroids in comparison with 39.3 % controls . The mean cumulative dosage of prednisone in MTX-treated patients was 2.6+/-3.8 g in comparison with 3.2+/-4.1 g for controls ( p=0.6 ) . PMR flare-ups were seen in 30.8 % of MTX-treated patients and in 44.4 % of controls ( p=0.39 ) . During the follow-up , 58 and 55 side effects were observed in MTX-treated patients and in controls , respectively . CONCLUSIONS MTX-treated patients showed slightly less residual inflammation than controls , with the same incidence of steroid-related side effects . PMR is not a benign condition , as often reported , since one third of patients need steroid treatment for more than 6 years OBJECTIVE Steroids are the only treatment of polymyalgia rheumatica ( PMR ) . We report the effects of methotrexate ( MTX ) plus prednisone versus prednisone alone in PMR . METHODS Twenty-four patients with recent onset PMR were studied in a r and omized prospect i ve study lasting one year . Patients were given MTX ( MTX arm ) 10 mg intramuscularly plus prednisone every week , or prednisone alone ( Pred arm ) . After 6 months an attempt was made to stop prednisone , and to use the lowest possible dose over the next 6 months . RESULTS At the 12th month , all patients were in clinical remission , acute phase reactants were in the normal range in both arms of the study , 6 patients were no longer taking steroids in the MTX arm versus 0/12 in the Pred arm , and the amount of prednisone in the 2 groups was statistically different ( 1.84 versus 3.2 g ; p < 0.0001 ) . In addition , bone mineral density was significantly decreased in the Pred arm , but not in the MTX arm . CONCLUSION The MTX regimen allowed the use of much less prednisone over one year to obtain full control of PMR with no loss of efficacy . It also allowed sparing of bone in elderly patients at increased risk of osteoporotic fractures The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate ( i.m . MP ) with oral prednisolone ( OP ) in the treatment of polymyalgia rheumatica ( PMR ) , a common steroid-treated illness where prolonged therapy can lead to steroid side-effects . The cumulative dose with i.m . MP injections given every 3 - 4 weeks is considerably smaller than that with conventional OP , and may therefore be associated with fewer long-term side-effects . A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks . The study was multicentre hospital out-patient based and included 60 patients with untreated PMR . In the double-blind phase , either 120 mg 3-weekly i.m . MP or gradually tapering daily OP ( initial dose 15 mg ) were administered . In the open phase , subjects continued their active treatment with gradual tapering of the steroid dosage . The remission rate at 12 , 48 and 96 weeks , and other measures of disease activity , i.e. sedimentation rate , pain and morning stiffness , and percentage of adverse reactions and serious complications such as fractures , were the main outcome measures . Sixty patients entered ( 30 OP:30 i.m . MP ) and 49 ( 25 OP:24 i.m . MP ) completed the study . There were similar remission rates after the double-blind phase ( 60.6 % OP and 66.6 % i.m . MP , respectively ) and similar disease control in the succeeding open phase . With steroid tapering , the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms . At 96 weeks , the cumulative mean steroid dose in subjects treated with i.m . MP was equivalent to 56 % that of subjects treated with OP . There were eight fractures with OP compared to one on i.m . MP . Mean weight gain was significantly greater with OP than i.m . MP ( 3.42 vs 0.82 kg , P < 0.005 ) . Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m . MP . Only patients on OP reported moon face , hypertension , cataracts , back pain and depression , but the numbers were small . It is possible to achieve equivalent long-term disease control in PMR with i.m . MP compared to OP . I.m . MP was associated with far fewer fractures and lesser weight gain , presumably related to lower cumulative dose . These findings may have implication s in the steroid treatment of PMR , and other rheumatic and non-rheumatic diseases We have performed the first controlled study of colchicine in acute gout , to determine its efficacy and toxicity , and to define the natural history of acute gout . Two-thirds of colchicine-treated patients improved after 48 hours , but only one-third of the patients receiving placebo demonstrated similar improvement . The colchicine-treated patients responded earlier ; significant differences from placebo were shown after 18 - 30 hours . All patients given colchicine developed diarrhea after a median time of 24 hours ( mean dose of colchicine 6.7 mg ) . This side effect occurred before relief of pain in most patients OBJECTIVE : To investigate whether methotrexate ( MTX ) has a steroid sparing effect in the treatment of polymyalgia rheumatica ( PMR ) and giant cell arteritis ( GCA ) . METHODS : We carried out a r and omised double blind , placebo controlled study in 40 patients with PMR , six of whom also had clinical symptoms of GCA . A temporal artery biopsy specimen was available from 37 patients ; GCA was found in six of the specimens . Among the six patients with clinical signs of GCA , three had a positive biopsy specimen . All patients were started on prednisone 20 mg/day , irrespective of clinical signs and biopsy result , supplemented with a weekly , blinded capsule containing either MTX 7.5 mg or placebo . The prednisone dose was decreased as soon as clinical symptoms disappeared and erythrocyte sedimentation rate , C reactive protein level , or both , had normalised . RESULTS : Twenty one patients were followed for two years , or at least one year after discontinuing medication . No differences were found between the MTX group and the placebo group concerning time to achieve remission , duration of remission , number of relapses , or cumulative prednisone doses . After 21 weeks the mean daily prednisone dose was reduced by 50 % . Forty percent of all patients were able to discontinue prednisone within two years . Median duration of steroid treatment was 47.5 weeks ( range 3 - 104 ) . No serious complications from GCA were encountered . CONCLUSIONS : With a ( rapid ) steroid tapering regimen , it was possible to reduce the mean daily prednisone dose by 50 % in 21 weeks and to cease prednisone in 40 % of the patients within two years . With this regimen , no steroid sparing effect of MTX in a dosage of 7.5 mg/week was found Objective : To study the usefulness of ultrasonography ( US ) in predicting the diagnostic outcome in patients with polymyalgic symptoms . Methods : Sixty-one elderly patients with polymyalgic syndrome were recruited in a secondary care setting and followed up in a prospect i ve way . Clinical , laboratory , and US data obtained at onset were re-evaluated after 1 year when diagnostic outcome was defined . Results : A diagnostic shift was observed in 32 polymyalgic patients ( 52 % ) . Calcium pyrophosphate deposition disease ( CPDD ) was diagnosed in nine patients , elderly-onset rheumatoid arthritis ( EORA ) in 18 , and elderly-onset spondyloarthritis ( EOSpA ) in five . In polymyalgia rheumatica ( PMR ) patients US demonstrated synovitis in 90 % of cases , in both proximal ( 90 % ) and peripheral joints ( 41 % ) . The best predictive US model for the definitive diagnosis of PMR comprised : the presence of subacromial-subdeltoid bursitis [ odds ratio ( OR ) 5.603 , p = 0.003 ] , low frequency of wrist ( OR 0.074 , p < 0.001 ) , metacarpophalangeal ( OR 0.052 , p < 0.001 ) , and metatarsophalangeal effusion/synovitis ( OR 0.107 , p < 0.027 ) , low frequency of knee menisci chondrocalcinosis ( OR 0.091 , p = 0.013 ) , tendinous calcaneal calcifications ( OR 0.078 , p = 0.006 ) , and Achilles enthesitis ( OR 0.107 , p = 0.027 ) , and low power Doppler US ( PDUS ) scores at wrist ( OR 0.052 , p < 0.001 ) . Conclusions : US and PDUS can be useful in distinguishing , at onset of disease , pure PMR from other diseases mimicking this condition The ability of azathioprine to reduce the maintenance prednisolone requirement of 31 patients with polymyalgia rheumatica ( PMR ) or giant cell arteritis ( GCA ) , or both , was tested in a double-blind placebo controlled study over one year . Clinical and laboratory assessment s were made at four-weekly intervals over a period of 52 weeks . A statistically significant difference ( p less than 0.05 ) in mean prednisolone dose was noted between the two groups at the end of 52 weeks , there being a fall in steroid requirement in the azathioprine treated group OBJECTIVE The optimal serum urate levels necessary for elimination of tissue deposits of monosodium urate in patients with chronic gout is controversial . This observational , prospect i ve study evaluates the relationship between serum urate levels during therapy and the velocity of reduction of tophi in patients with chronic tophaceous gout . METHOD Sixty-three patients with crystal-confirmed tophaceous gout were treated with allopurinol , benzbromarone , or combined therapy to achieve serum uric acid levels less than the threshold for saturation of urate in tissues . The tophi targeted for evaluation during followup were the largest in diameter found during physical examination . RESULTS Patients taking benzbromarone alone or combined allopurinol and benzbromarone therapy achieved faster velocity of reduction of tophi than patients taking allopurinol alone . The velocity of tophi reduction was linearly related to the mean serum urate level during therapy . The lower the serum urate levels , the faster the velocity of tophi reduction . CONCLUSION Serum urate levels should be lowered enough to promote dissolution of urate deposits in patients with tophaceous gout . Allopurinol and benzbromarone are equally effective when optimal serum urate levels are achieved during therapy . Combined therapy may be useful in patients who do not show enough reduction in serum urate levels with single-drug therapy OBJECTIVE Despite widespread use of colchicine , the evidence basis for oral colchicine therapy and dosing in acute gout remains limited . The aim of this trial was to compare low-dose colchicine ( abbreviated at 1 hour ) and high-dose colchicine ( prolonged over 6 hours ) with placebo in gout flare , using regimens producing comparable maximum plasma concentrations in healthy volunteers . METHODS This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study compared self-administered low-dose colchicine ( 1.8 mg total over 1 hour ) and high-dose colchicine ( 4.8 mg total over 6 hours ) with placebo . The primary end point was > or = 50 % pain reduction at 24 hours without rescue medication . RESULTS There were 184 patients in the intent-to-treat analysis . Responders included 28 of 74 patients ( 37.8 % ) in the low-dose group , 17 of 52 patients ( 32.7 % ) in the high-dose group , and 9 of 58 patients ( 15.5 % ) in the placebo group ( P = 0.005 and P = 0.034 , respectively , versus placebo ) . Rescue medication was taken within the first 24 hours by 23 patients ( 31.1 % ) in the low-dose group ( P = 0.027 versus placebo ) , 18 patients ( 34.6 % ) in the high-dose group ( P = 0.103 versus placebo ) , and 29 patients ( 50.0 % ) in the placebo group . The low-dose group had an adverse event ( AE ) profile similar to that of the placebo group , with an odds ratio ( OR ) of 1.5 ( 95 % confidence interval [ 95 % CI ] 0.7 - 3.2 ) . High-dose colchicine was associated with significantly more diarrhea , vomiting , and other AEs compared with low-dose colchicine or placebo . With high-dose colchicine , 40 patients ( 76.9 % ) had diarrhea ( OR 21.3 [ 95 % CI 7.9 - 56.9 ] ) , 10 ( 19.2 % ) had severe diarrhea , and 9 ( 17.3 % ) had vomiting . With low-dose colchicine , 23.0 % of the patients had diarrhea ( OR 1.9 [ 95 % CI 0.8 - 4.8 ] ) , none had severe diarrhea , and none had vomiting . CONCLUSION Low-dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high-dose colchicine , with a safety profile indistinguishable from that of placebo |
2,655 | 29,371,271 | For most elderly patients with breast cancer , the non-significant negative change in the QoL was transient .
A significant increase in the QoL during the course of temozolomide in elderly patients with glioblastoma but a decreasing trend in QoL after radiotherapy was shown .
This review also shows a uniform trend of stable or improved QoL during adjuvant therapy and at follow-up evaluations across the studies with prostate , colon or cervical cancer population .
This review suggests that adjuvant chemotherapy and radiotherapy may not have detrimental effects on QoL in most elderly patients with solid tumours | OBJECTIVES The measurement of quality of life ( QoL ) in elderly cancer population is increasingly being recognised as an important element of clinical decision-making and the evaluation of treatment outcome .
This systematic review aim ed to summarise the evidence of QoL during and after adjuvant therapy in elderly patients with cancer . | The Qualitator is a daily diary card to measure Quality of Life , developed for use in chemotherapy trials for patients with advanced breast cancer . In a trial at King 's College Hospital , 29 patients completed the Qualitator and their scores were compared with scores in the Linear Analogue Self- Assessment and Nottingham Health Profile taken four-weekly . In a separate study at Guy 's Hospital , 31 patients completed the diary . The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use BACKGROUND Given the more comorbidities with a decline in physiologic reserve , it can be challenging to make appropriate treatment decisions in the elderly . PATIENTS AND METHODS Here , we prospect ively evaluated and compared the health-related quality of life ( HRQOL ) of patients aged ≥ 65 with aged < 65 who were treated with a postoperative chemotherapy for completely resected stage Ib , II or IIIa non-small-cell lung cancer ( NSCLC ) . Either four cycles of paclitaxel (Taxol)-carboplatin ( PC ) or vinorelbine-cisplatin ( NP ) was used . The HRQOL was assessed with EORTC QLQ-C30 and EORTC QLQ-LC13 . RESULTS Between October 2008 and October 2011 , a total of 139 patients ( aged < 65 , n = 73 ; ≥ 65 , n = 66 ) were enrolled , and 127 ( 91.4 % ) completed the question naire . Overall , the quality of life ( QOL ) in elderly patients did not significantly deteriorate with adjuvant chemotherapy and the time trend of QOL in elderly patients was similar to that of younger patients . Although the elderly suffered from increased treatment-related adverse events involving sore mouth , peripheral neuropathy and alopecia compared with the baseline , the same time trends were also observed in younger group . The mean dose intensities ( MDIs ) for PC and NP regimen were not significantly different between the two age groups . CONCLUSIONS Postoperative chemotherapy did not substantially reduce HRQOL in elderly NSCLC patients , and HRQOL during and after adjuvant chemotherapy did not significantly differ by age Background Quality of life ( QoL ) is now established as an important outcome for evaluating the impact of disease , and for assessing the efficacy of treatments . However , individuals change with time and the basis on which they make a QoL judgement may also change , a phenomenon increasingly referred to as response shift . Here , the individual may change his or her internal st and ards , values , and /or conceptualization on the target construct as a result of external factors such as a treatment or a change in health status . This has important implication s for assessing the effects of treatments as a change in QoL may reflect a response shift , a treatment effect , or a complex combination of both . In this study , we used an individualised quality of life ( IQoL ) measure , the SEIQoL , together with a then-test to determine whether response shift would influence the measurement of treatment efficacy in edentulous patients . Methods Data are reported here for the first phase of a r and omised controlled clinical trial design ed to assess the impact , on IQoL , of implant supported dentures compared with high quality conventional dentures . IQoL was measured using the SEIQoL-DW in 117 patients ( mean age 64.8 ; 32 % male ) at baseline ( T1 ) and 3 months ( T2 ) after receiving high quality conventional dentures . The work was carried out in dental teaching hospitals in Dublin and Belfast . Results Unadjusted SEIQoL index scores revealed no significant impact of treatment at three months ( baseline : 75.0 ; 3 months : 73.2 , p = .33 , n.s . ) . However , the then-test at 3 months revealed that patients retrospectively rated their baseline IQoL as significantly lower ( P < .001 ) than they had rated it at the time ( then-test baseline : 69.2 ) . Comparison of the 3 month scores with this readjusted baseline indicated a significant treatment effect ( then-test baseline : 69.2 ; 3 months : 73.2 , p = 0.016 ) . 81 % of patients nominated at least one different IQoL domain at 3 months . Conclusion The positive impact of denture treatment for edentulous patients on IQoL was seen only when response shifts were taken into consideration . The nature of the response shifts was highly complex but the data indicated a degree of re-conceptualisation and reprioritisation . Assessment of the impact of treatments using patient-generated reports must take account of the adaptive nature of patients Introduction There are few studies on the effect on quality of life ( QL ) of cancer-related illness and treatment in elderly patients . The aim of this work was to evaluate prospect ively QL in a sample of elderly patients with stages I – III breast cancer who started radiotherapy treatment and compare their QL with that of a sample of younger patients . Material s and methods Forty-eight patients , ≥ 65 years of age completed the European Organization for Research and Treatment of Cancer ( EORTC ) QL question naires QLQ-C30 and QLQ-BR23 , and the Interview for Deterioration in Daily Living Activities in Dementia ( IDDD ) daily activities scale three times throughout treatment and follow-up periods . Clinical and demographic data were also recorded . Fifty patients ages 40–64 years with the same disease stage and treatment modality had previously completed the QL question naires . QL scores , changes in them among the three assessment s , differences between groups based on clinical factors , and differences between the two sample s were calculated . Results QL scoring was good and stable ( > 70/100 points ) in most areas , in line with clinical data . Light and moderate limitations occurred in global QL and some emotional , sexual , and treatment-related areas . Moderate decreases ( 10–20 ) appeared in some toxicity-related areas , which recovered during the follow-up period . Breast-conservation and sentinel-node patients presented higher scores in emotional areas . There were few QL differences among age-based sample s. Conclusions QL and clinical data indicate radiotherapy was well tolerated . Age should not be the only factor evaluated when deciding upon treatment for breast cancer patients Objectives The optimal treatment for elderly patients ( age > 70 years ) with glioblastoma ( GBM ) remains controversial . We conducted a prospect i ve trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy ( RT ) followed by adjuvant temozolomide . Patients and methods Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status ( KPS ) ≥ 60 were treated with hypofractionated RT ( 6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks ) followed by up to 12 cycles of adjuvant temozolomide ( 150–200 mg/m2 for 5 days during each 28 day cycle ) . The HRQOL was assessed with the EORTC Quality of Life Question naire C30 . The primary endpoint was overall survival ( OS ) . Secondary endpoints included progression free survival ( PFS ) , toxicity and quality of life . Results The median OS was 9.3 months and the median PFS was 6.3 months . The 6 and 12 month survival rates were 86 % and 35 % , respectively . The 6 and 12 month PFS rates were 55 % and 12 % , respectively . In multivariate analysis KPS was the only significant independent predictive factor of survival ( P = 0.008 ) . Neurological deterioration occurred during or after RT in 16 % of patients and was resolved in most cases with the use of steroids . Grade 3–4 hematologic toxicity occurred in 28 % of patients during the adjuvant chemotherapy treatment with temozolomide . The treatment had no negative effect on HRQOL , however , fatigue ( P = 0.02 ) and constipation ( P = 0.01 ) scales worsened over time . Conclusions Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM . It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors BACKGROUND Evidence on adjuvant chemotherapy in older women with breast cancer is poor . We tested whether weekly docetaxel is more effective than st and ard chemotherapy . PATIENTS AND METHODS We carried out a multicenter , r and omized phase III study . Women aged 65 - 79 , operated for breast cancer , with average to high risk of recurrence , were allocated 1 : 1 to CMF ( cyclophosphamide 600 mg/m² , methotrexate 40 mg/m² , fluorouracil 600 mg/m² , days 1 , 8) or docetaxel ( 35 mg/m(2 ) days 1 , 8 , 15 ) every 4 weeks , for four or six cycles according to hormone receptor status . Primary end point was disease-free survival ( DFS ) . A geriatric assessment was carried out . Quality of life ( QoL ) was assessed with EORTC C-30 and BR-23 question naires . RESULTS From July 2003 to April 2011 , 302 patients were r and omized and 299 ( 152 allocated CMF and 147 docetaxel ) were eligible . After 70-month median follow-up , 109 DFS events were observed . Unadjusted hazard ratio ( HR ) of DFS for docetaxel versus CMF was 1.21 [ 95 % confidence interval ( CI ) 0.83 - 1.76 , P = 0.32 ] ; DFS estimate at 5 years was 0.69 with CMF and 0.65 with docetaxel . HR of death was 1.34 ( 95 % CI 0.80 - 2.22 , P = 0.26 ) . There was no interaction between treatment arms and geriatric scales measuring patients ' ability or comorbidities . Hematological toxicity , mucositis and nausea were worse with CMF ; allergy , fatigue , hair loss , onychopathy , dysgeusia , diarrhea , abdominal pain , neuropathy , cardiac and skin toxicity were worse with docetaxel . One death was attributed to CMF and two to docetaxel . Increasing age , impairment in instrumental daily living activities , number of comorbidities and docetaxel treatment were independently associated with severe nonhematological toxicity . QoL was worse with docetaxel for nausea-vomiting , appetite loss , diarrhea , body image , future perspective , treatment side-effects and hair loss items . CONCLUSIONS Weekly docetaxel is not more effective than st and ard CMF as adjuvant treatment of older women with breast cancer and worsens QoL and toxicity . CLINICAL TRIALSGOV NCT00331097 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 This study was conducted to analyze the feasibility of adjuvant capecitabine therapy using a tailored-dose escalation strategy in elderly patients with colon cancer ( CC ) . METHODS CC patients ( ≥ 70 years of age ) who received adjuvant capecitabine were enrolled . The starting dosage of capecitabine was 2000 mg/m(2)/day ( days 1 - 14 , every 3 weeks ) . On the second cycle , the dosage was escalated to 2500 mg/m(2)/day if the patient tolerated the first cycle . Dose intensity ( DI ) , toxicity , and the change in quality of life ( QoL ) were evaluated . RESULTS Of 82 patients enrolled , 67 completed eight cycles . Dose escalation to 2500 mg/m(2)/day was possible in 56 patients , and this dosage was maintained in 24 patients until the completion of chemotherapy ( eight cycles ) . Forty-one patients completed therapy with a DI ≥ 1333 mg/m(2)/day [ relative dose intensity ( RDI ) ≥ 80 % ] . Toxic effects were tolerable and the QoL was not compromised during treatment . Creatinine clearance < 50 ml/min and Charlson-Age comorbidity index ≥ 8 were related to a reduced capecitabine dosage ( RDI < 80 % ) . CONCLUSIONS A tailored-dose escalation strategy was feasible in elderly CC patients receiving adjuvant capecitabine chemotherapy . Decreased renal function and an increased number of comorbidities were independently predictive of reduced administration of the capecitabine dose Mastectomy and breast-conserving treatment have proven equally effective in terms of survival in early breast cancer , but studies continue to provide evidence that patients undergoing breast-conserving procedures have a better quality of life ( QOL ) . Age is not considered to be a contraindication for breast-conserving treatment , but retrospective studies have indicated that elderly patients are less likely to be treated conservatively . In the present study , survival , QOL and treatment preference have been investigated in a multicentre , r and omised clinical trial of elderly patients with early breast cancer undergoing mastectomy or tumour excision plus tamoxifen . Eligible patients were aged 70 years or more and had histologically- or cytologically-confirmed operable breast cancer . A QOL question naire consisting of 36 items was constructed covering 9 scales assessing different QOL domains . Patients completed their assessment between 2 and 12 months after r and omisation . 136 patients ( 65 in the mastectomy arm and 71 in the local excision arm ) from six centres filled out a QOL form during the first year of follow-up . No significant difference in the duration of survival between the two treatment arms was observed when including patients included in the QOL sub- study ( P=0.33 ) . Patients undergoing tumour excision and tamoxifen did not differ from those undergoing mastectomy in terms of fatigue , emotional functioning , fear of recurrence , social support , physical functioning and leisure time activities . However , conservatively treated patients reported fewer arm problems ( P=0.04 ) and a shift , although borderline significant , in the direction of a benefit in body image ( P=0.06 ) . As QOL seems to be better after conservative treatment , such treatment is to be preferred in both elderly and younger patients Non-r and omised studies of the effects of interventions are critical to many areas of healthcare evaluation , but their results may be biased . It is therefore important to underst and and appraise their strengths and weaknesses . We developed ROBINS-I ( “ Risk Of Bias In Non-r and omised Studies - of Interventions ” ) , a new tool for evaluating risk of bias in estimates of the comparative effectiveness ( harm or benefit ) of interventions from studies that did not use r and omisation to allocate units ( individuals or clusters of individuals ) to comparison groups . The tool will be particularly useful to those undertaking systematic review s that include non-r and omised studies OBJECTIVES To examine the toxicity experienced by a cohort of older women receiving adjuvant chemotherapy for breast cancer and the longitudinal effect on their functional status and quality of life ( QOL ) . DESIGN A geriatric assessment measuring functional status , comorbidity , mood , nutritional status , and QOL was performed before chemotherapy , at the end of chemotherapy , and 6 months later . SETTING This prospect i ve longitudinal study was conducted at Memorial Sloan-Kettering Cancer Center , New York , New York . PARTICIPANTS Fifty patients aged 65 and older with Stage I to III breast cancer receiving any adjuvant chemotherapy ; 49 were evaluable . MEASUREMENTS The chemotherapy regimen and the toxicity to chemotherapy were recorded . A geriatric assessment was performed before the start of chemotherapy , on completion of chemotherapy , and 6 months after completion of chemotherapy . QOL testing was performed at the same times . RESULTS Patients ( mean age 68 , range 65 - 84 ) received an anthracycline-based chemotherapy regimen ( n=15 ) or cyclophosphamide 600 mg/m2 intravenously ( i.v . ) , methotrexate 40 mg/m2 i.v . , 5-fluorouracil 600 mg/m2 i.v . every 3 weeks for eight cycles ( n=34 ) . Grade 3 or 4 toxicity occurred in 53 % ( n=26 ) , hematological toxicity in 27 % ( n=13 ) , and nonhematological toxicity in 31 % ( n=15 ) . Despite toxicity , there was no significant longitudinal change in functional status or QOL . CONCLUSION Despite toxicity from adjuvant chemotherapy , this cohort of relatively young older patients maintained their functional status and QOL from before chemotherapy to 6 months postchemotherapy . Subtle changes in higher-order functioning would require assessment using different geriatric assessment tools PURPOSE A phase III trial ( Cancer and Leukemia Group B CALGB-49907 ) was conducted to test whether older patients with early-stage breast cancer would have equivalent relapse-free and overall survival with capecitabine compared with st and ard chemotherapy . The quality of life ( QoL ) sub study tested whether capecitabine treatment would be associated with a better QoL than st and ard chemotherapy . PATIENTS AND METHODS QoL was assessed in 350 patients r and omly assigned to either st and ard chemotherapy ( cyclophosphamide , methotrexate , and fluorouracil [ CMF ] or doxorubicin and cyclophosphamide [ AC ] ; n = 182 ) or capecitabine ( n = 168 ) . Patients were interviewed by telephone before treatment ( baseline ) , midtreatment , within 1 month post-treatment , and at 12 , 18 , and 24 months postbaseline by using question naires from the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 ( EORTC QLQ-C30 ) , a breast systemic adverse effects scale ( EORTC BR23 ) , and the Hospital Anxiety and Depression Scale ( HADS ) . RESULTS Compared with patients who were treated with st and ard chemotherapy , patients who were treated with capecitabine had significantly better QoL , role function , and social function , fewer systemic adverse effects , less psychological distress , and less fatigue during and at the completion of treatment ( P ≤ .005 ) . Capecitabine treatment was associated with less nausea , vomiting , and constipation and with better appetite than st and ard treatment ( P ≤ .004 ) , but worse h and -foot syndrome and diarrhea ( P < .005 ) . These differences all resolved by 12 months . CONCLUSION St and ard chemotherapy was superior to capecitabine in improving relapse-free and overall survival for older women with early-stage breast cancer . Although capecitabine was associated with better QoL during treatment , QoL was similar for both groups at 1 year . The brief period of poorer QoL with st and ard treatment is a modest price to pay for a chance at improved survival BACKGROUND There is no community st and ard for the treatment of glioblastoma in patients 70 years of age or older . We conducted a r and omized trial that compared radiotherapy and supportive care with supportive care alone in such patients . METHODS Patients 70 years of age or older with a newly diagnosed anaplastic astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher were r and omly assigned to receive supportive care only or supportive care plus radiotherapy ( focal radiation in daily fractions of 1.8 Gy given 5 days per week , for a total dose of 50 Gy ) . The primary end point was overall survival ; secondary end points were progression-free survival , tolerance of radiotherapy , health-related quality of life , and cognition . RESULTS We r and omly assigned 85 patients from 10 centers to receive either radiotherapy and supportive care or supportive care alone . The trial was discontinued at the first interim analysis , which showed that with a preset boundary of efficacy , radiotherapy and supportive care were superior to supportive care alone . A final analysis was carried out for the 81 patients with glioblastoma ( median age , 73 years ; range , 70 to 85 ) . At a median follow-up of 21 weeks , the median survival for the 39 patients who received radiotherapy plus supportive care was 29.1 weeks , as compared with 16.9 weeks for the 42 patients who received supportive care alone . The hazard ratio for death in the radiotherapy group was 0.47 ( 95 % confidence interval , 0.29 to 0.76 ; P=0.002 ) . There were no severe adverse events related to radiotherapy . The results of quality -of-life and cognitive evaluations over time did not differ significantly between the treatment groups . CONCLUSIONS Radiotherapy results in a modest improvement in survival , without reducing the quality of life or cognition , in elderly patients with glioblastoma . ( Clinical Trials.gov number , NCT00430911 [ Clinical Trials.gov ] . ) OBJECTIVES : To evaluate the relationship of age with symptoms and interference with daily function and QOL during RT . DESIGN : A prospect i ve observational study . SETTING : A university-based radiation oncology department . PARTICIPANTS : 903 cancer patients who received radiation therapy ( RT ) . The mean age was 61 yrs ( 18 - 92 ) and 41 % were ≥ 65 yrs . MEASUREMENTS : A symptom inventory was administered pre- and post-RT . Patients rated 10 symptoms and their interference with daily function and QOL on a Likert scale from 0 ( not present ) to 10 ( as bad as possible ) . A total symptom score was calculated by adding the ratings of individual symptoms . T-tests , Pearson correlation coefficients , and mixed modeling were used to investigate relationships between symptoms and their interference with daily function and QOL . RESULTS : For older and younger patients , the total symptom score worsened during RT ( p 's < .001 ) . There were no differences in the change in total symptom burden and interference with QOL between older and younger patients during RT . After RT , although younger patients reported significantly worse pain ( p = .03 ) , nausea ( p < .01 ) , and sleep disturbance ( p < .01 ) , symptom interference with walking was more severe in older patients ( p = .01 ) . Mixed modeling showed that older age ( p=<.001 ) , time of survey ( after RT , p<.001 ) , and age*time interaction ( p<.001 ) increased the likelihood of reporting that symptoms interfered with walking . CONCLUSION : The prevalence of symptoms was similar for older and younger patients during RT . Older patients are more likely to report that symptoms interfere with walking after RT A question naire has been developed for use as an outcome measure in clinical trials of adjuvant chemotherapy in women with stage II breast cancer . The selection of items for this Breast Cancer Chemotherapy Question naire ( BCQ ) was based on the problems and experiences felt to be most important by women undergoing adjuvant chemotherapy . The BCQ consists of 30 questions that focus on loss of attractiveness , fatigue , physical symptoms , inconvenience , emotional distress , and feelings of hope and support from others . The BCQ , other instruments that evaluate quality -of-life ( Spitzer , Karnofsky , and R and ) , and patient and physician global assessment s were administered serially to 418 patients taking part in a r and omized trial comparing a 12-week regimen and a 36-week regimen of adjuvant chemotherapy . The validity of the BCQ is supported by its correlation with the R and Emotional ( r = .58 ) , R and Physical ( r = .60 ) , and Spitzer ( r = .62 ) question naires . The BCQ correlated more strongly with global ratings of both physical and emotional function by the patients and their physicians than the other instruments . A comparison of the quality -of-life outcomes of patients in the two treatment groups in the period beyond 3 months after initiation of treatment , when one group had completed the treatment course and the other was still on treatment , revealed that the BCQ and Karnofsky were the only instruments able to demonstrate differences between the groups ( P less than .0001 ) . Hence , the BCQ is a valid and responsive method of assessing treatment-related morbidity in patients receiving adjuvant chemotherapy for stage II breast cancer Abstract Despite increasing evidence of benefit from adjuvant chemotherapy , older women with breast cancer are commonly given less aggressive treatment than younger patients . Conflicting prior data regarding age-related toxicity prompted this prospect i ve study . Forty-four women ( aged 35–79 years ) with early-stage breast cancer were treated with four cycles of adjuvant therapy with doxorubicin 60 mg/m2 i.v . and cyclophosphamide 600 mg/m2 i.v . every 21 days . They were monitored for my-elosuppression , cardiotoxicity , and decrease in quality of life . Pharmacokinetics were analyzed using cycle 1 plasma sample s. Bone marrow granulocyte and macrophage colony-forming units ( CFU-GM ) were assayed in vitro for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle 1 . There was moderate evidence of age-related decrease in nadir absolute neutrophil count ( ANC ) when age was viewed as a continuous variable . On average there was a 10/μl drop in cycle 1 nadir ANC for every year increase in age ( p = 0.02 ) . However , when age was viewed as a categorical variable ( age < 65 vs. ≥65 years ) , a similar proportion of women in each group reached an ANC < 100 ( 18 % vs. 19 % ) . Neither neutropenic complications , alteration in cardiac function , nor change in quality of life scores were significantly age related ( p > 0.12 ) . Pharmacokinetic analyses did not demonstrate age-related differences in the clearance of either doxorubicin or cyclophosphamide ( p ≥ 0.8 ) . Pharmacodynamic analysis of individual patient bone marrow progenitor cell sensitivity did not reveal any correlation with age ( p > 0.48 ) . In women undergoing adjuvant therapy for breast cancer , no clinical ly significant age-related trends in toxicity were observed . These data suggest that older age alone should not exclude patients from receiving adjuvant therapy with doxorubicin and cyclophosphamide PURPOSE Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited . We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII . PATIENTS AND METHODS Postmenopausal women with operable , node-positive breast cancer were r and omized to receive either tamoxifen alone for 5 years ( 306 patients ) or tamoxifen plus three consecutive cycles of classical cyclophosphamide ( 100 mg/m(2 ) orally days 1 to 14 ) , methotrexate ( 40 mg/m(2 ) intravenous days 1 and 8) , and fluorouracil ( 600 mg/m(2 ) intravenous days 1 and 8) every 28 days ( CMF ; 302 patients ) . The median follow-up was 8.0 years . RESULTS Among the 299 patients who received at least one dose of CMF , women 65 years of age or older ( n = 76 ) had higher grade s of toxicity compared with women less than 65 years old ( n = 223 ) ( P = .004 ) . More women in the older age group compared with the younger women experienced grade 3 toxicity of any type ( 17 % v 7 % , respectively ) , grade 3 hematologic toxicity ( 9 % v 5 % , respectively ) , and grade 3 mucosal toxicity ( 4 % v 1 % , respectively ) . Older patients also received less than their expected CMF dose compared with younger postmenopausal women ( P = .0008 ) . The subjective burdens of treatment , however , were similar for younger and older patients based on quality -of-life measures ( performance status , coping , physical well-being , mood , and appetite ) . For older patients , the 5-year disease-free survival ( DFS ) rates were 63 % for CMF plus tamoxifen and 61 % for tamoxifen alone ( hazards ratio [ HR ] , 1.00 ; 95 % confidence interval [ CI ] , 0.65 to 1.52 ; P = .99 ) . For younger patients , the corresponding 5-year DFS rates were 61 % and 53 % ( HR , 0.70 ; 95 % CI , 0.53 to 0.91 ; P = .008 ) , but the test for heterogeneity of CMF effect according to age group was not statistically significant . The reduced effectiveness of CMF among older women could not be attributed to dose reductions according to dose received . CONCLUSION CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years . The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients PURPOSE As glioblastoma progresses , patients experience a decline in health-related quality of life ( HRQoL ) . Delaying this decline is an important treatment goal . In newly diagnosed glioblastoma , progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide ( RT/TMZ ) versus placebo plus RT/TMZ ( phase III AVAglio study ; hazard ratio , 0.64 ; 95 % CI , 0.55 to 0.74 ; P < .001 ) . To ensure that addition of bevacizumab to st and ard-of-care therapy was not associated with HRQoL detriment , HRQoL assessment was a secondary objective . PATIENTS AND METHODS Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Question naires C30 and BN20 at each tumor assessment ( Appendix Table A1 , online only ) . Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated ( stable : < 10-point change ; clinical ly relevant deterioration/improvement : ≥ 10-point change ) . Deterioration-free survival was the time to deterioration/progression/death ; time to deterioration was the time to deterioration/death . RESULTS Most evaluable patients who had not progressed ( > 74 % ) completed all HRQoL assessment s for at least 1 year of treatment , and almost all completed at least one HRQoL assessment at baseline ( 98.3 % and 97.6 % , bevacizumab and placebo arms , respectively ) . Mean changes from baseline did not reach a clinical ly relevant difference between arms for most items . HRQoL declined at progression in both arms . The addition of bevacizumab to RT/TMZ result ed in statistically longer ( P < .001 ) deterioration-free survival across all items . Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm ( v bevacizumab ) for any HRQoL item . CONCLUSION The addition of bevacizumab to st and ard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period OBJECTIVE The EORTC Quality of Life Group has developed a question naire for evaluating Quality of Life in international clinical trials : EORTC QLQ-C30 , which is widely used in many countries . The purpose of this study was to assess the psychometric properties of the third version of this question naire , EORTC QLQ-C30 ( version 3.0 ) , when applied to Spanish prostate cancer patients . METHODS A sample of 137 prostate cancer patients prospect ively filled in the question naire three times : on the first and last day of the treatment , and in the followup period . Psychometric evaluation of the structure , reliability and validity was made . RESULTS Multitrait scaling analysis showed that most item-scale correlation coefficients met the st and ards of convergent and discriminant validity . Few exceptions appeared mainly in CF Most scales had low to moderate inter-correlations . Cronbach 's coefficients of the scales were above 0.7 , except for the CF and NV values . Group comparison analyses showed better QL in patients with higher Performance Status . Changes in functioning and symptom areas appeared throughout the different measurements , which were in line with the treatment process . CONCLUSIONS The EORTC QLQC30 ( version 3.0 ) appeared as a reliable and valid instrument when applied to a sample of Spanish prostrate cancer patients . The results are in line with previous studies OBJECTIVE Adjuvant pelvic radiotherapy ( XRT ) after radical surgery for uterine cancer may cause various ( mainly gastrointestinal ) side effects capable of affecting a patient 's lifestyle . This prospect i ve study used a diary card to evaluate toxicity and daily quality of life changes in uterine cancer patients given postoperative pelvic radiotherapy . METHODS The self-completed diary card listed 12 items concerning lifestyle changes and side effects . The patients were stratified by age ( < /=65 vs > 65 years ) . RESULTS Twenty-five patients were evaluable , and a total of 848 days were assessed ( 82.6 % of the 1027 days of XRT ) . The mean number of daily stools progressively increased during treatment ( P < 0.01 ) . No statistically significant differences were observed in terms of nausea or pain . There was a significant decrease in appetite ( P < 0.01 ) . Vaginal symptom scores did not significantly change during treatment , and no significant differences were found in terms of anxiety , daily activities , or compliance to therapy . The subjective perception of overall well-being and the quality of life score progressively and significantly decreased over time ( P < 0.01 ) . The younger patients had significantly more bowel movements , less appetite , more pain and vaginal burning , less vaginal bleeding , more anxiety , a greater reduction in daily activities and therapeutic compliance , a poorer subjective perception of overall well-being , and a lower quality of life score . CONCLUSIONS The use of a diary card may be an adequate means of detecting the extent of treatment-related changes in the lifestyle of uterine cancer patients receiving postoperative radiotherapy PURPOSE To describe the quality of life ( QOL ) in elderly patients with glioblastoma ( GBM ) treated with an abbreviated course of radiation therapy ( RT ; 40 Gy in 15 fractions ) plus concomitant and adjuvant temozolomide ( TMZ ) . METHODS AND MATERIAL S Health-related QOL ( HRQOL ) was assessed by European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire Core-30 ( QLQ-C30 , version 3 ) and EORTC Quality of Life Question naire Brain Cancer Module ( QLQ-BN20 ) . Changes from baseline in the score of 9 preselected domains ( global QLQ , social functioning , cognitive functioning , emotional functioning , physical functioning , motor dysfunction , communication deficit , fatigue , insomnia ) were determined 4 weeks after RT and thereafter every 8 weeks during the treatment until disease progression . The proportion of patients with improved HRQOL scores , defined as a change of 10 points or more , and duration of changes were recorded . RESULTS Sixty-five patients completed the question naires at baseline . The treatment was consistently associated with improvement or stability in most of the preselected HRQOL domains . Global health improved over time ; mean score differed by 9.6 points between baseline and 6-month follow-up ( P=.03 ) . For social functioning and cognitive functioning , mean scores improved over time , with a maximum difference of 10.4 points and 9.5 points between baseline and 6-month follow-up ( P=.01 and P=.02 ) , respectively . By contrast , fatigue worsened over time , with a difference in mean score of 5.6 points between baseline and 4-month follow-up ( P=.02 ) . CONCLUSIONS A short course of RT in combination with TMZ in elderly patients with GBM was associated with survival benefit without a negative effect on HRQOL until the time of disease progression |
2,656 | 16,682,568 | The addition of clinical pharmacist services in the care of in patients generally result ed in improved care , with no evidence of harm .
Interacting with the health care team on patient rounds , interviewing patients , reconciling medications , and providing patient discharge counseling and follow-up all result ed in improved outcomes . | BACKGROUND The role of clinical pharmacists in the care of hospitalized patients has evolved over time , with increased emphasis on collaborative care and patient interaction .
The purpose of this review was to evaluate the published literature on the effects of interventions by clinical pharmacists on processes and outcomes of care in hospitalized adults . | BACKGROUND Previous studies found that medication errors result from lack of sufficient information during the prescribing step . Therefore , it is proposed that having a pharmacist available when patients are evaluated during the rounding process may reduce the likelihood of preventable adverse drug events ( ADEs ) . The objectives of this study were to evaluate the impact of having a pharmacist participate with a physician rounding team on preventable ADEs in general medicine units and to document pharmacist interventions made during the rounding process . METHODS A single-blind , st and ard care-controlled study design was used to compare patients receiving care from a rounding team including a pharmacist with patients receiving st and ard care ( no pharmacist on rounding team ) . Patients admitted to and discharged from the same general medicine unit were included in the study . The main outcome measure of this study was preventable ADEs . Patient records were r and omly selected and evaluated by a blinded process involving independent senior pharmacist specialists and a senior staff physician . Interventions made by the pharmacists in the treatment group were documented . RESULTS The rate of preventable ADEs was reduced by 78 % , from 26.5 per 1000 hospital days to 5.7 per 1000 hospital days . There were 150 documented interventions recommended during the rounding process , 147 of which were accepted by the team . The most common interventions were ( 1 ) dosing-related changes and ( 2 ) recommendations to add a drug to therapy . CONCLUSION Pharmacist participation with the medical rounding team on a general medicine unit contributes to a significant reduction in preventable ADEs OBJECTIVES to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients . DESIGN r and omized controlled trial . SUBJECTS AND SETTING S we r and omized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care . INTERVENTIONS the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient . A copy was given to the patient and to all relevant professionals and carers . This was followed by a domiciliary assessment by a community pharmacist . In the control group , patients were discharged from hospital following st and ard procedures that included a discharge letter to the general practitioner listing current medications . OUTCOMES the primary outcome was re-admission to hospital within 6 months . Secondary outcomes included the number of deaths , attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period , together with patients ' general well-being , satisfaction with the service and knowledge of and adherence to prescribed medication . RESULTS we recruited 362 patients , of whom 181 were r and omized to each group . We collected hospital and general practice data on at least 91 and 72 % of patients respectively at each follow-up point and interviewed between 43 and 90 % of the study subjects . There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months . There were no significant differences in any of the secondary outcomes . CONCLUSIONS we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes BACKGROUND Hospitalization and subsequent discharge home often involve discontinuity of care , multiple changes in medication regimens , and inadequate patient education , which can lead to adverse drug events ( ADEs ) and avoidable health care utilization . Our objectives were to identify drug-related problems during and after hospitalization and to determine the effect of patient counseling and follow-up by pharmacists on preventable ADEs . METHODS We conducted a r and omized trial of 178 patients being discharged home from the general medicine service at a large teaching hospital . Patients in the intervention group received pharmacist counseling at discharge and a follow-up telephone call 3 to 5 days later . Interventions focused on clarifying medication regimens ; review ing indications , directions , and potential side effects of medications ; screening for barriers to adherence and early side effects ; and providing patient counseling and /or physician feedback when appropriate . The primary outcome was rate of preventable ADEs . RESULTS Pharmacists observed the following drug-related problems in the intervention group : unexplained discrepancies between patients ' preadmission medication regimens and discharge medication orders in 49 % of patients , unexplained discrepancies between discharge medication lists and postdischarge regimens in 29 % of patients , and medication nonadherence in 23 % . Comparing trial outcomes 30 days after discharge , preventable ADEs were detected in 11 % of patients in the control group and 1 % of patients in the intervention group ( P = .01 ) . No differences were found between groups in total ADEs or total health care utilization . CONCLUSIONS Pharmacist medication review , patient counseling , and telephone follow-up were associated with a lower rate of preventable ADEs 30 days after hospital discharge . Medication discrepancies before and after discharge were common targets of intervention The impact of discharge counseling was measured in a veteran patient population in a large tertiary-care government medical center . Upon discharge , seventy patients were r and omly assigned to one of two groups : one group received verbal medication counseling from a pharmacist , the other group did not . Medication knowledge and compliance were assessed by interviewing each patient approximately 6 weeks after discharge . Sixty patients ( 31 counseled , 29 uncounseled ) completed the study . Forty-five patients were from our rehabilitation division ( housing psychiatric , intermediate , and long-term care patients ) , and 15 patients were from our acute-care division . Overall , counseled patients were no more knowledgeable or compliant than uncounseled patients . However , among those patients discharged from our acute-care division , counseled patients were more knowledgeable and compliant than uncounseled patients . In all patients , medication knowledge and compliance decreased as their number of medications increased . Our discharge counseling program had little impact when examining all study patients . But in acute-care patients , discharge counseling did increase both medication knowledge and compliance . Our study also showed that , in both counseled and uncounseled patients , medication knowledge and compliance decreased as the number of discharge medications increased , and additional pharmacist counseling would likely prove beneficial to those patients discharged on multiple medications BACKGROUND Although numerous reports have described interventions design ed to influence antibiotic utilization , to our knowledge none have been evaluated in a r and omized study . METHODS Adult in patients receiving 1 or more of 10 design ated parenteral antibiotics for 3 or more days during a 3-month period were r and omized to an intervention ( n = 141 ) and a control ( n = 111 ) group using an unblocked , computer-generated r and om number table . Obstetric patients and those seen in infectious disease consultation were excluded . The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist . Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospect i ve chart review s and analysis of the hospital 's administrative data base . RESULTS Sixty-two ( 49 % ) of the intervention group patients received a total of 74 suggestions . Sixty-three ( 84 % ) of these suggestions were implemented ; the majority involved changes in antibiotic choice , dosing regimen , or route of administration . Per patient antibiotic charges were nearly $ 400 less in the intervention group vs controls ( P = .05 ) . Almost all the savings were related to lower intravenous antibiotic charges . Clinical and microbiological response , antibiotic-associated toxic effects , in-hospital mortality , and readmission rates were similar for both groups . Multiple linear regression analysis identified r and omization to the intervention group and female sex as the sole predictors of lower antibiotic charges . There was a trend toward a shorter length of stay for the intervention group ( 20 vs 24.7 days , P = .11 ) . CONCLUSIONS This is the first r and omized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety . We demonstrate that 50 % of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense CONTEXT Pharmacist review of medication orders in the intensive care unit ( ICU ) has been shown to prevent errors , and pharmacist consultation has reduced drug costs . However , whether pharmacist participation in the ICU at the time of drug prescribing reduces adverse events has not been studied . OBJECTIVE To measure the effect of pharmacist participation on medical rounds in the ICU on the rate of preventable adverse drug events ( ADEs ) caused by ordering errors . DESIGN Before-after comparison between phase 1 ( baseline ) and phase 2 ( after intervention implemented ) and phase 2 comparison with a control unit that did not receive the intervention . SETTING A medical ICU ( study unit ) and a coronary care unit ( control unit ) in a large urban teaching hospital . PATIENTS Seventy-five patients r and omly selected from each of 3 groups : all admissions to the study unit from February 1 , 1993 , through July 31 , 1993 ( baseline ) and all admissions to the study unit ( postintervention ) and control unit from October 1 , 1994 , through July 7 , 1995 . In addition , 50 patients were selected at r and om from the control unit during the baseline period . INTERVENTION A senior pharmacist made rounds with the ICU team and remained in the ICU for consultation in the morning , and was available on call throughout the day . MAIN OUTCOME MEASURES Preventable ADEs due to ordering ( prescribing ) errors and the number , type , and acceptance of interventions made by the pharmacist . Preventable ADEs were identified by review of medical records of the r and omly selected patients during both preintervention and postintervention phases . Pharmacists recorded all recommendations , which were then analyzed by type and acceptance . RESULTS The rate of preventable ordering ADEs decreased by 66 % from 10.4 per 1000 patient-days ( 95 % confidence interval [ CI ] , 7 - 14 ) before the intervention to 3.5 ( 95 % CI , 1 - 5 ; P<.001 ) after the intervention . In the control unit , the rate was essentially unchanged during the same time periods : 10.9 ( 95 % CI , 6 - 16 ) and 12.4 ( 95 % CI , 8 - 17 ) per 1000 patient-days . The pharmacist made 366 recommendations related to drug ordering , of which 362 ( 99 % ) were accepted by physicians . CONCLUSIONS The presence of a pharmacist on rounds as a full member of the patient care team in a medical ICU was associated with a substantially lower rate of ADEs caused by prescribing errors . Nearly all the changes were readily accepted by physicians Objective : To evaluate the impact of a hospital based community liaison pharmacy service on a range of outcomes in patients aged more than 55 years and taking more than 3 prescribed drugs , who had been admitted to the medical unit of a district general hospital in Northern Irel and . Methods : Having recruited 243 patients , a total of 162 patients completed the full protocol ( 81 r and omly assigned to intervention and 81 to control ; mean age of control patients 75 years ; mean age of intervention patients 73 years ) . The interventions by the community liaison pharmacist included : preparation of an accurate medication record following a full review of current medication use ; medication counselling ; provision of a medicines record sheet informing the patient how to take their drugs ; provision of a pharmaceutical discharge letter detailing changes made to drug therapy ( this was faxed to the patient 's GP and community pharmacist on the day of discharge ) ; provision of a Medicines Helpline . Results : The key findings were as follows : problems were identified in 80 % of the intervention patients ' prescription charts , 49 % of which related to drug omissions from the patients ' domiciliary prescriptions . The GP practice record was the most accurate ( mean error rate 12.6 % ) while the GP referral letter was the least accurate ( mean error rate 47.3 % ) source of medication information . Drugs patients brought to hospital were also an inaccurate source ( mean error rate 44.0 % ) . The intervention group patients , when compared with control patients , had a significant reduction ( P=0.005 ) in drug mismatch between drugs prescribed at discharge and taken at home , and had a greater knowledge of their drug regimen 10–14 days after discharge ( P |Ld 0.001 ) . The vast majority of patients ( 96 % ) felt that the provision of a medicine helpline was a useful service . Conclusions : The study indicated clear benefits from the involvement of a hospital based community liaison pharmacist in achieving seamless pharmaceutical care between the primary and secondary healthcare setting In a prospect i ve , r and omized study , 75 adults receiving aminogly-cosides were followed by a clinical pharmacokinetic service and 70 followed as controls . The two groups were similar in age , gender , height , and APACHE II score . A cost-to-charge ratio was used to derive direct costs of hospitalization and calculate cost-benefit . Excluded from this comparison were patients with incomplete acceptance of pharmacokinetic service recommendations and patients followed by other clinical pharmacists . Pharmacokinetic service patients had shorter hospitalizations ( 322.67 ± 270.28 h ; controls 442.89 ± 536.81 , p = 0.087 ) and febrile periods ( 50.05 ± 79.38 h ; controls 92.23 ± 122.50 , p < 0.05 ) . More pharmacokinetic service patients had adequate peak levels . Pharmacokinetic service direct costs were lower ( 7,102.56 ± 9,898.19 ; controls 13,758.64 ± 22,874.31 , p < 0.05 ) . Calculated direct cost of the service was 85.00/patient . Annual savings for 500 patients is 2,220,540.00 Results of the 2001 ASHP national survey of pharmacy practice in hospital setting s that pertain to prescribing and transcribing are presented . A stratified r and om sample of pharmacy directors at 1091 general and children 's medical-surgical hospitals in the United States was surveyed by mail . SMG Marketing Group , Inc. , supplied data on hospital characteristics ; the survey sample was drawn from SMG 's hospital data base . The response rate was 49.0 % . During 2001 , nearly all hospitals are estimated to have pharmacy and therapeutics ( P&T ) committees that meet an average of seven times per year . It is estimated that more than 90 % of P&T committees are responsible for formulary development and management , drug policy development , adverse-drug-reaction review , and medication-use evaluation . More than 90 % of hospitals use clinical and therapeutic , cost , and pharmacoeconomic information in the formulary management process , while nearly two thirds consider quality -of-life issues . Nearly 70 % use clinical practice guidelines in the formulary management process , and 78 % have a medication-use evaluation program design ed to improve prescribing . Pharmacists in more than 75 % of hospitals provide consultations on drug information , dosage adjustments for patients with renal impairment , antimicrobials , and pharmacokinetics . Further , a majority of hospitals ensure accurate transcription of medication orders by clarifying illegible orders before transcription or entry into medication administration records ( MARs ) , using st and ardized prescriber order forms , requiring prescribers to countersign all oral orders , and reconciling MARs and pharmacy patient profiles at least daily . In 2001 , large hospitals are most likely to use prescriber order-entry systems to improve patient safety and are least likely to require the reentry of medication orders into the pharmacy computer system . The 2001 ASHP survey results suggest that pharmacists in hospital setting s have positioned themselves well to improve the prescribing and transcribing components of the medication-use process To evaluate a program to discontinue intravenous antibiotics at two teaching hospitals , 102 in patients meeting eligibility criteria were r and omly assigned to two groups . In one group , patients ' physicians were contacted by pharmacists with recommendations to discontinue intravenous antibiotic therapy ; in the other , patients were simply observed . Measured outcomes were antibiotic costs , length of stay , need to restart intravenous antibiotics , in-hospital mortality , and 30-day readmissions . The intervention significantly reduced mean antibiotic costs per patient ( $ 19.82 vs $ 35.84 , p = 0.03 ) , but related labor costs exceeded this benefit . Readmissions were significantly more frequent in the intervention group than in the control group ( 29 % vs 9.8 % p = 0.02 ) , but they were not infection related . No impact was demonstrated on the other measured outcomes . Institutions considering such programs or with one in place should conduct similar evaluations OBJECTIVE : To document differences in the outcome of vancomycin therapy in patients managed through a therapeutic drug monitoring ( TDM ) service and patients managed empirically , without the participation of a TDM service . DESIGN : Prospect i ve , cohort study . SETTING : An 1100-bed , tertiary-care , teaching hospital . PATIENTS : Those who received vancomycin for more than four days , were at least 18 years old , had an estimated creatinine clearance of more than 0.33 mL/s ( 20 mL/min ) , were not neutropenic at the start of vancomycin therapy , and were not treated in a critical care unit were enrolled in the study . A total of 116 patients ( 61 TDM ; 55 non-TDM ) were monitored prospect ively from June 1990 through March 1991 . INTERVENTIONS : Patients in the TDM group had vancomycin drug therapy monitored daily by a pharmacist and vancomycin dosages adjusted following a pharmacokinetic analysis of vancomycin serum concentrations . For patients in the non-TDM group , the pharmacist only completed a data collection form . The patients and physicians were unaware of the monitoring . MAIN OUTCOME MEASURES : Duration of therapy , total vancomycin dosage , infection site , concomitant antibiotics , body temperature , and white blood cell counts were compared between the two groups . Length of stay data were also compared . Nephrotoxicity was evaluated by comparing serum creatinine concentration and estimated creatinine clearance . RESULTS : TDM of vancomycin appeared to reduce the incidence of vancomycin-related renal insufficiency ( TDM 7 percent ; non-TDM 24 percent ) . Patients managed through the TDM service received an average of 5 g less of vancomycin than did the patients in the non-TDM group . The duration of vancomycin therapy was an average of 2 days less for patients in the TDM group . Mean length of stay was 38.0 days for the TDM group and 44.5 days for the non-TDM group . Other measures of efficacy , infection site , and concomitant antibiotics were the same for both groups . CONCLUSIONS : TDM of vancomycin was associated with fewer cases of vancomycin-related renal insufficiency . Vancomycin efficacy was not compromised by TDM . Provision of TDM for vancomycin therapy aided in patient management The impact of clinical pharmacists ' consultations on geriatric drug prescribing was studied in a prospect i ve r and omized controlled trial of patients 65 years of age and over discharged on 3 or more medications for chronic conditions from a 450-bed community hospital . The pharmacists provided consultation to experimental patients and their physicians at hospital discharge and at periodic intervals for 3 months postdischarge . Using a st and ardized tool , a physician-pharmacist panel , blinded to study group assignment of patients , evaluated the appropriateness of prescribing for a r and om sample of 236 patients . Eighty-eight percent had at least one or more clinical ly significant drug problems , and 22 % had at least one potentially serious and life-threatening problem . Drug-therapy problems were divided into six categories : 1 ) inappropriate choice of therapy ; 2 ) dosage ; 3 ) schedule ; 4 ) drug-drug interactions ; 5 ) therapeutic duplication ; and 6 ) allergy . Experimental patients were less likely to have one or more prescribing problems in any of the categories ( P = 0.05 ) or in the appropriateness ( P = 0.02 ) or dosage ( P = 0.05 ) categories . A summary score , measuring the appropriateness of the patient 's total drug regimen , indicated that experimental patients ' regimens were more appropriate than those of controls ( P = 0.01 ) . Results of this trial reveal that clinical pharmacists can improve the appropriateness of geriatric drug prescribing in outpatient setting The current study was performed to document the cost savings and need for a therapeutic drug monitoring program for phenytoin . The methodology employed a prospect i ve , r and omized , crossover design that utilized two control and two therapeutic drug monitoring phases . The therapeutic drug monitoring program significantly decreased the average number of assays performed per patient from 2.14 to 0.61 . Withdrawal of the program result ed in a significant increase in the average number of assays performed per patient ( from 0.61 to 2.41 ) , the average number of assays drawn incorrectly ( from 0.39 to 1.89 ) , and in the average number of assays used inappropriately ( from 0.50 to 2.07 ) . Withdrawal of the program was also associated with a significant increase in the average number of readmissions ( from 0 to 0.19 ) within 3 months of discharge . Reinstitution of the program was associated with a significant decrease in the average number of readmissions ( from 0.19 to 0.03 ) within 3 months of discharge . The cost savings from decreasing the number of assays performed was estimated to be $ 100.00 for the first year We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections . Patients were r and omized to a control ( dosing based on physician choice ; n = 75 ) or experimental group ( dosing based on the bayesian program ; n = 72 ) . Both groups used serum aminoglycoside concentration data when making dosing decisions . Improved response rates were seen in the experimental ( 60 % ; 42/68 ) compared with the control group ( 48 % ; 36/68 ) . A higher , but not statistically significant , incidence of toxicity was found in the control ( 7/75 ; 9.7 % ) versus the experimental group ( 4/72 ; 5.1 % ) . Mean length of total hospital stay was significantly longer for patients in the control group ( 20.3 days ) compared with the experimental group ( 16.0 days ) ( p = 0.028 ) . The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy . On the basis of a reduced length of stay , a potential cost savings of $ 1311 per patient can be achieved Our aim was to identify financial and outcome benefits of therapeutic intervention by a multidisciplinary antimicrobial treatment team composed of pharmacists , a clinical microbiologist , and an infectious disease specialist . Of 252 consecutive in patients receiving suboptimal intravenous antibiotics identified by the clinical pharmacist , 127 were prospect ively r and omized to intervention and 125 to a control group . The groups were similar with regard to severity of illness , infection type , and time from admission to r and omization . Physicians received timely , detailed review s of relevant microbiologic and clinical data with recommendations of possible optimal antibiotic choices , dosages , and rationale s. Median length of stay after r and omization for control and intervention groups was 9.0 days and 5.7 days , respectively ( 3.3-day difference , p=0.0001 ) . Fifteen ( 12.0 % ) and eight patients ( 6.3 % ) , respectively , died , although the time-specific mortality risk was not significantly different when length of postr and omization follow-up and time to death were taken into account . Physician acceptance of suggestions was 89 % . Median patient charges for radiology , laboratory , pharmacy , and room were reduced by $ 4404/intervention , and median hospital costs were reduced by $ 2642/intervention . A multidisciplinary antimicrobial therapy team can be a useful information source for physicians , improve outcomes in hospitalized patients receiving intravenous antimicrobials , and result in substantial cost savings AIMS To investigate how seamless pharmaceutical care could be delivered . METHODS Elderly patients discharged from hospital , to their own home , were r and omized into control and study groups . Control and study group patients received the normal discharge information . The study group were also counselled about their medicines and informed about their pharmaceutical care plan . Copies of the plan were given to the study patients . All patients received a domiciliary visit between 7 and 10 days after discharge . Their current medication was compared with that on discharge and contact was made with the General Practitioner as appropriate . RESULTS Twenty-eight study and 25 control patients with a mean ( s.d . ) age of 77.5 ( 7.3 ) and 77.6 ( 6.1 ) years completed the study . A pharmaceutical domiciliary visit was necessary for 21 ( 75 % ) and 24 ( 96 % ) of the study and control patients respectively . Compliance was better ( P < 0.01 ) in the study group . Unintentional changes to the medication of 31 ( 14 study and 17 control ) patients were found during the visit and after contact with the prescriber all but one prescription was restored to that on discharge . CONCLUSIONS At present it is difficult to ensure seamless pharmaceutical care . A pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic care and thus avoid unnecessary healthcare events and costs after a patient is discharged home We conducted a prospect i ve cohort study to evaluate clinical and economic end points achieved by a pharmacist-managed anticoagulation service compared with usual care ( 50 patients /group ) . The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold . The primary economic end point was the direct variable cost of hospitalization from admission to discharge . No significant differences between groups were noted for the primary therapeutic end point . Total hospital costs were significantly lower for patients receiving pharmacist-managed care than for those receiving usual care ( $ 1594 and $ 2014 , respectively , 1997 dollars , p=0.04 ) . Earlier start of warfarin ( p=0.05 ) and shorter hospital stay ( 5 and 7 days , p=0.05 ) were associated with the pharmacist-managed group OBJECTIVE : To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy . DESIGN : Comparison of a historical control cohort with a prospect i ve cohort matched for treatment indication . SETTING : A 400-bed university teaching hospital . PATIENTS : Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time , with anticoagulation therapy managed by physicians , were compared with 60 patients matched for warfarin indication hospitalized in 1995 , but with anticoagulation therapy managed with pharmacy consultation . RESULTS : Pharmacist management of initial warfarin therapy result ed in a significant reduction in the length of hospitalization compared with physician dosing , from 9.5 ± 5.6 days to 6.8 ± 4.4 days ( p = 0.009 ) . The number of patients and patient-days with international normalized ratio ( INR ) values > 3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days , respectively ( p < 0.001 ) . Similarly , the number of patients and patient-days with INR > 6.0 were reduced from 20 patients and 50 days to two patients and six days , respectively ( p < 0.001 ) . There were six documented bleeding complications in 1992 compared with one in 1995 ( p = 0.11 ) . The mean INR at discharge was significantly lower in the pharmacy surveillance group , 2.6 ± 0.58 , compared with the physician cohort , 3.3 ± 2.1 ( p = 0.07 ) . Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five ( at 1 mo ) and 10 ( at 3 mo ) to two and five readmissions , respectively , by pharmacist intervention ( p = 0.43 ) . The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower ( 6 vs. 13 ; p = 0.02 ) in the pharmacy surveillance group . CONCLUSIONS : Among patients starting warfarin for the first time , daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy . These findings translate into improved quality of care and potentially significant cost savings UNLABELLED Geriatric assessment units have improved pharmacotherapy for their patients by decreasing the number of medications prescribed . The Senior Care Study , a r and omized controlled trial , compared a multidisciplinary-team approach to patient care to the st and ard medical practice of the institution . As a part of the trial , the effectiveness of an interdisciplinary team intervention in improving the use of medications was studied . Study goals were to decrease medications used , decrease unnecessary medications , and improve medication choices in our acutely ill inpatient population . A pharmacist interviewed all experimental patients and patient records , and presented medication concerns and recommendations at a team conference . MEDICATIONs were counted on admission and on the third day , sixth week , and third month after r and omization . MEDICATIONs were paired with patient problems . MEDICATION problem pairs were judged as inappropriate choices if there were potential side effects that would affect patient function , and if better alternatives were available . The 215 control and 221 experimental patients in the study were similar in age , sex , place of origin , and number of medications on admission . Experimental patients took fewer medications than controls on the third day ( 5.3 versus 5.9 , P less than .05 ) . Experimental patients received fewer multiple unpaired medications ( 11 % versus 19 % , P less than .025 ) and fewer inappropriate medication choices ( 20 % versus 37 % , P less than .005 ) . The results suggest that the team intervention was effective in improving pharmacotherapy in the acute-care setting The effects of pharmacokinetics consultation by a pharmacist on the quality of drug therapy were studied in a 500-bed teaching hospital . Data were collected retrospectively for three time periods : three months before , four months during , and three months after a period of intervention by a pharmacist with special responsibilities for pharmacokinetic monitoring of patients on a medical team . For the four-month intervention period , data were also collected for a parallel group of patients managed by another medical team that included pharmacy residents and students . Patients were included in the study if they had received either an aminoglycoside or a theophylline preparation . The preintervention , postintervention , and parallel groups were r and om sample s of patients on the study ward , and the intervention group included all patients admitted to the pharmacist intervener 's medical team who had received a drug covered by the study . Of serum drug concentration determinations ( SDCDs ) in the pharmacist intervention phase , 54 % were appropriate , compared with 16 % before intervention , 21 % in the postintervention phase , and 46 % in the patients of the other medical team . In the pharmacist intervention group , greater numbers of SDCDs were obtained appropriately and used appropriately in making therapeutic decisions , as evidence d by more subsequent measurements in the therapeutic range . Pharmacist intervention did not affect the number of adverse drug reactions or medical specialty consultations or the average length of stay . De central ized pharmacokinetics services can have a positive effect on the quality of serum drug concentration determinations , dosage adjustments , and drug therapy The financial impact of pharmacist participation on a medical team in a tertiary-care teaching hospital was studied prospect ively . Two medical teams , one with and one without a pharmacist , operated simultaneously for 11 months . Physicians and a pharmacist on the teams rotated monthly during the first five months of the study . Subsequently , the hospital administrator , who was unaware that the controlled study was under way , permanently assigned an attending physician to the team that did ot have a pharmacist . After patients ' discharge , pharmacy costs , pharmacy charges , hospital charges , and length of stay ( LOS ) were compared for the two teams . Data analysis was separated into four phases : phase 1 , during which attending physicians rotated monthly ; phase 2 , with a permanent attending physician ; phase 3 , which encompassed the entire 11 months ; and phase 4 , which encompassed the 11-month period but omitted patients whose LOS exceeded 30 days . Data were analyzed for a total of 619 patients on the two teams . In phase 1 , the team with a pharmacist had significantly lower per-patient pharmacy costs , pharmacy charges , hospital charges , and LOS . In phase 2 , no significant differences were found between the teams . In phase 3 , the only significant difference was that the team with a pharmacist had lower pharmacy costs and pharmacy charges . In phase 4 , the team that included a pharmacist had significantly lower pharmacy costs ( $ 105 difference ) , pharmacy charges ( $ 368 difference ) , hospital charges ( $ 2065 difference ) , and LOS ( 1.3-day difference ) . Participation of pharmacists on the medical team can significantly reduce pharmacy costs and charges , hospital charges , and LOS Length of stay ( LOS ) , total cost per admission ( TCA ) , and pharmacy cost per admission ( DCA ) were determined for two drug-use control systems in a 1058-bed university hospital ; a central ized unit dose drug distribution system served as a control . The two study systems were ( 1 ) pharmacist monitoring of drug therapy in the patient-care area and ( 2 ) central ized pharmacist monitoring of computerized patient profiles . LOS data were collected retrospectively for 659 patients admitted during a seven-month control interval . LOS , TCA , and DCA data were collected prospect ively for 496 patients admitted during a five-month experimental interval . Each study system was assigned to one of three teams making rounds among intact patient groups . LOS differences were compared between intervals and by month . After corrections were made for differences in patient mix , the drug-use control system in which pharmacists were assigned to the patient-care area yielded a 1.5-day-shorter average LOS , $ 1293 lower average TCA ( p less than 0.05 ) , and $ 155 lower average DCA than under the unit dose system . The drug-use control system in which pharmacists were assigned to monitor patients ' drug therapy from a central location was associated with a 0.13-day-shorter average LOS , $ 235 lower average TCA , and $ 55.13 lower average DCA than under the unit dose system . No systematic differences between teams , other than drug-use control system , appeared to explain the differences in LOS , TCA , and DCA . A drug-use control system based in a patient-care area , overseen by clinical ly experienced pharmacists , may result in shorter LOSs and lower total costs than central ized systems for general-medical in patients of teaching hospitals A r and omized , controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy . Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were r and omly assigned to one of three groups : usual physician-directed dosing ( Group 1 ) , pharmacist-assisted dosing ( Group 2 ) , or pharmacist-directed dosing ( Group 3 ) . Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program , whereas Group 1 served as the control group . Individualized dosing result ed in higher mean postinfusion ( peak ) serum aminoglycoside levels , higher ratios of mean peak level to minimum inhibitory concentration ( peak/MIC ratios ) , and a trend toward lower trough serum levels . Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups . However , the incidence of nephrotoxicity ( > or = 100 % increase in serum creatinine ) was not different among the three groups ( 16 , 27 , and 16 % in Groups 1 , 2 , and 3 , respectively ) . Similarly , severity of toxicity was not affected by the dosing intervention . Risk factors for toxicity included duration of therapy , shock , treatment with furosemide , older age , and liver disease . After controlling for these factors , the dosing intervention still had no effect on nephrotoxicity . It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy BACKGROUND Hospital pharmacists make many recommendations that improve patients ' quality of care and /or reduce drug costs . While the impact of quality -of-care interventions is difficult to quantify , those limited to cost savings could be assessed in a prospect i ve , r and omized fashion . OBJECTIVE To assess the impact of pharmacist-initiated interventions on cost savings . METHODS Six pharmacists at a large university hospital recorded patient-specific recommendations for 30 days . All quality -of-care interventions were completed by the pharmacists , but those strictly aim ed at reducing costs were stratified by drug class and r and omized to an intervention or control group . Pharmacists contacted physicians with cost-saving recommendations in the intervention group , while control group patients were simply observed . MAIN OUTCOME MEASURE Drug costs after r and omization . RESULTS Most ( n=967 [ 79 % ] ) of the 1226 interventions recorded were aim ed at improving quality of care . The remaining 259 ( 21 % ) provided equivalent quality of care , but at less expense . These cost-saving interventions typically involved streamlining therapy to less expensive agents ( 39 % ) , discontinuing an unnecessary medication ( 25 % ) , or modifying the route of administration ( 24 % ) . The group r and omized to receive a pharmacist 's intervention had drug costs that were 41 % lower than those in the control group ( mean , $ 73.75 vs $ 43.40 ; P<.001 ) . Interventions involving anti-infective agents had the greatest cost savings ( mean , $ 104.08 vs $ 58.45 ; P<.001 ) . For our institution , this extrapolates to an annual savings of approximately $ 394,000 ( 95 % confidence interval , $ 46,000-$742,000 ) . As expected , these interventions had no impact on length of hospital stay , in-hospital mortality , 30-day readmissions , or the need to readminister the targeted medication or restart intravenous therapy . CONCLUSIONS While interventions solely aim ed at reducing costs represent a small portion of a pharmacist 's activities , they can result in significant savings for an institution AIMS The use of medication and information discharge summaries ( MIDS ) has become a st and ard procedure in many hospitals . We have evaluated if these summaries , together with in-patient pharmaceutical counselling backed up with a simple medicine reminder card , may help with the delivery of seamless pharmaceutical care . METHODS Elderly patients prescribed more than four items discharged to their own home received the st and ard discharge policy including a recently introduced MIDS and medicine reminder card . Each patient 's GP was sent a copy on discharge . Pre-discharge a pharmacist counselled study patients about their medicines and compliance . A research pharmacist visited patients in their home approximately 2 - 3 weeks and at 3 months post-discharge to determine their drug knowledge , compliance , home medicine stocks and any healthcare related events . RESULTS Forty-three study and 40 control patients completed both visits . Their mean ( s.d . ) ages were 80.2 ( 5,7 ) and 81.1 ( 5,8 ) years and they were prescribed 7.1 ( 1.8 ) and 7.1 ( 2.3 ) items , respectively . At visit 1 knowledge ( P < 0.01 ) and compliance ( P < 0.001 ) was better in the study group . At visit 2 compliance had improved in the study group ( P < 0.001 ) . Unplanned visits to the GP and readmission to hospital amongst the study group were 19 and 5 , respectively , which were both significantly less ( P < 0.05 ) than 27 and 13 in the control group . At visit 2 for the study group the 24 unplanned GP visits and three re-admissions were significantly ( P < 0.05 ) less than the respective 32 and 15 in the control group . At visit 1 , two study group patients had altered their own medication compared with 10 control patients . At visit 2 these reduced to 0 and 4 , respectively . CONCLUSIONS In-patient pharmaceutical counselling , linked to a medication and information discharge summary and a medicine reminder card , contributed to better drug knowledge and compliance together with reduced unplanned visits to the doctor and re-admissions . A pharmaceutical domiciliary visit consoli date d the improved healthcare outcomes This study assessed the impact of clinical pharmacists ' consultations on drug regimens , compliance , and health service use of geriatric hospitalized patients ( N = 706 ) discharged on 3 or more medications . Pharmacists consulted with experimental patients at discharge and 3 months thereafter , and with physicians as needed . Controls received usual care . At 6 - 8 weeks after enrollment , experimental patients were more knowledgeable about regimens than controls . At 12 - 14 weeks , they were on fewer medications and less complex regimens , and had better compliance scores . There was no effect on service use or charges , perhaps due to inadequate sample size and lack of targeted drug groups analysis . The authors conclude that clinical pharmacists ' consultations can improve geriatric patients ' drug regimens and compliance . Findings further suggest the need for replication among large cohorts of patients at high risk , due to the use of medications most likely to have a potential for serious outcomes and to be vulnerable to physician prescribing error |
2,657 | 16,437,470 | MAIN RESULTS The three placebo-controlled , r and omized trials did not find evidence supporting a causal association between combination oral contraceptives or a combination skin patch and weight gain .
Most comparisons of different combination contraceptives showed no substantial difference in weight .
In addition , discontinuation of combination contraceptives because of weight gain did not differ between groups where this was studied .
Available evidence was insufficient to determine the effect of combination contraceptives on weight , but no large effect was evident | BACKGROUND Weight gain is often considered a side effect of combination hormonal contraceptives , and many women and clinicians believe that an association exists .
Concern about weight gain can limit the use of this highly effective method of contraception by deterring the initiation of its use and causing early discontinuation among users .
However , a causal relationship between combination contraceptives and weight gain has not been established .
OBJECTIVES The aim of the review was to evaluate the potential association between combination contraceptive use and changes in weight . | In a parallel , multicenter study in Norway and Finl and involving a total of 196 healthy women ( mean age 22.4 years , range 18–30 ) , the effects on serum lipids and lipoproteins of two multiphasic oral contraceptives containing ethinyl estradiol ( EE ) but different progestins were examined . One formulation contained EE 35 μg and norethisterone ( NET ) 0.5 mg on days 1–7 and days 17–21 and elevated NET 1.0 mg during the midphase ( days 8–16 ) . The other formulation contained EE 30 μg on days 1–6 and days 12–21 and 40 μg on days 7–11 and phased levonorgestrel ( LGN ) : 50 μg ( days 1–6 ) , 75 μg ( days 7–11 ) and 125 μg ( days 12–21 ) . Both formulations induced significant elevation of total cholesterol ( 6.7 and 4.1 % ) , Apo B ( 8.1 and 7.0 % ) as well as HDL ( 6.4 and 3.7 % ) for the EE/NET and EE/LGN formulation respectively . Mean serum levels of triglycerides were significantly elevated ( 58 and 47 % ) . However , all mean serum lipid and lipoprotein values remained within the normal range , and no change in the calculated cholesterol ratio ( HDL/total cholesterol ) nor lipoprotein ratio ( HDL/(HDL+LDL ) ) was observed . No significant difference between the formulations could be detected with respect to the effect on serum lipids and lipoproteins measured . The change in total cholesterol was smaller than reported in many studies of monophasic preparations . Taken together , these data suggest that only small alterations in lipid metabolism are elicited by these oral contraceptives PURPOSE This open-label , r and omized study evaluated the effect of two different oral contraceptives on body weight and composition during one cycle of treatment . METHOD Eighty women ( mean age , 24.6 years ) were r and omized into three groups and given one of the following contraceptive methods : ethinylestradiol 15 mug/gestodene 60 mug ( EE/GST , n=25 ) , ethinylestradiol 30 mug/drospirenone 3 mg ( EE/DRS , n=29 ) or male condom ( control group , n=26 ) . Bioelectric impedance analysis ( BIA ) was carried out on the first , 10th and 21st days during the use of oral contraceptives or in the menstrual cycle ( control group ) , and total body water ( TBW ) , fat mass ( FM ) and fat-free mass ( FFM ) were measured . RESULTS No significant variations in TBW , FM or FFM were observed in the three groups during the cycle . Intergroup analysis showed no differences in TBW or FM ; however , users of EE/GST showed a statistically significant increase in FFM compared to the control group . CONCLUSION The different doses of ethinylestradiol associated with gestodene or drospirenone showed no statistically significant effects on TBW or FM during one cycle of observation In an open , r and omized study in an outpatient clinic of a large teaching hospital , thirty-one female volunteers with regular cycles and established ovulation by ultrasonography were given one of two triphasic oral contraceptives containing ethinylestradiol combined with levonorgestrel or desogestrel during six cycles of treatment . The main outcome measures were transvaginal ultrasonography and serum E2 and P measurements in pill cycles 1 , 3 and 6 . No ovarian activity was found in 10 subjects . Among the remaining 21 women who showed ovarian activity , most follicle-like structures developed in the pill-free week and decreased in size or disappeared in the first pill week . One women taking triphasic desogestrel had evidence of a luteinized unruptured follicle and one women taking triphasic levonorgestrel had a possible ovulation . The latter women also showed symptoms of lower abdominal pain . A statistically significant difference in ovarian activity between the two oral contraceptives could not be established . The two triphasic oral contraceptives suppressed ovarian activity to the same degree . A trend was seen towards increasing ovarian activity with duration of use in both treatment groups 398 new users of oral contraceptives at the Research Clinic of the Southwest Foundation Texas were asked if they experienced nausea vomiting headache or breast discomfort nervousness or depression and had weight and blood pressure recorded in the pretreatment cycle and at monthly visits . Each received placebo Oracon ( sequential ) Ovulen-21 ( combination ) Norinyl-1 or .5 mg chlormadinone acetate in a double-blind protocol incorporating a pretreatment placebo cycle crossover to an active pill for 4 cycles and 2 more crossovers for Cyles 5 and 6 . The only symptoms significantly higher than in the pretreatment ( placebo ) cycle were nausea and vomiting with Oracon ( p greater than .05 ) and headache with Ovulen ( p greater than .05 ) . Pointing out that the highest incidence of complaints occurred in the placebo cycle the authors conclude that controls are necessary in contraceptive trials but the first cycle is not valid for comparison A phase III clinical study was carried out among 5680 fertile Chinese women to evaluate efficacy and side effects of three monthly injectable contraceptives : Mesigyna , Cyclofem and Chinese Injectable No. 1 . When used in a once-a-month treatment schedule ( part 1 of study ) , the effectiveness of Chinese Injectable No. 1 was unacceptably low ; 36 pregnancies occurred during the first 1743 women-months of use , 16 before the second injection . The study was restarted with a revised injection schedule for Injectable No. 1 : two injections separated by 9 + /- 1 days during the first month and subsequent injections given 10 - 12 days after the onset of bleeding , or if no bleeding occurred , 28 days after previous injection . In part 2 of the study , 988 , 990 and 992 subjects were provided Mesigyna , Cyclofem and Injectable No. 1 , respectively . Life-table pregnancy rates at one year were 0.41 % , 0 % and 0.77 % ( p < 0.05 ) , respectively ; the overall discontinuation rates at one year were 13.9 % , 19.1 % and 20.4 % ( p < 0.001 ) . Discontinuation rates for bleeding problems were significantly different between the groups : discontinuation rates for amenorrhea were 0.58 % , 3.71 % and 0.68 % ( p < 0.001 ) for Mesigyna , Cyclofem and Injectable No. 1 ; for other bleeding problems , the rates were 4.88 % , 8.38 % and 12.64 % ( p < 0.001 ) . There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons . Mean weight changes after one year of use were small : 0.73 , 0.86 and 0.17 kg for the three groups , respectively . Both Mesigyna and Cyclofem were very effective for contraception , but Mesigyna appeared to be tolerated slightly better with regard to cycle control ; the modified dose regimen for Injectable No. 1 also gave a low pregnancy rate but was associated with higher rates of discontinuation OBJECTIVE : To compare bleeding profiles and satisfaction among women using a norelgestromin/ethinyl estradiol ( E2 ) transdermal contraceptive patch in an extended regimen to those among women using a traditional 28-day patch regimen . METHODS : Healthy , regularly menstruating women ( N = 239 ) were r and omly assigned ( 2:1 ratio ) to receive the norelgestromin/ethinyl E2 transdermal patch in an extended regimen ( weekly application for 12 consecutive weeks , 1 patch-free week , and 3 more consecutive weekly applications , n = 158 ) or a cyclic regimen ( 4 consecutive cycles of 3 weekly applications and 1 patch-free week , n = 81 ) . Subjects recorded bleeding data daily and completed satisfaction question naires . Subjects and investigators provided overall assessment s of the regimens . RESULTS : Extended use of the norelgestromin/ethinyl E2 transdermal patch result ed in fewer median bleeding days ( 6 compared with 14 , P < .001 ) , bleeding episodes ( 1 compared with 3 , P < .001 ) , and bleeding or spotting episodes ( 2 compared with 3 , P < .001 ) compared with cyclic use during days 1–84 ; median numbers of bleeding or spotting days were similar between regimens ( 14 compared with 16 , P = .407 ) during this time . Extended use delayed median time to first bleeding to 54 days compared with 25 days with cyclic ( P < .001 ) . Subjects were highly satisfied with both regimens . Although not statistically significant , slightly more adverse events were reported with the extended than with the 28-day regimen . CONCLUSION : Compared with cyclic use , extended use of the norelgestromin/ethinyl E2 transdermal patch delayed menses and result ed in fewer bleeding days . This regimen may represent a useful alternative for women who prefer fewer episodes of withdrawal bleeding . LEVEL OF EVIDENCE : PURPOSE To determine the effect of oral contraceptives ( OC ) on bone mass and stress fracture incidence in young female distance runners . METHODS One hundred fifty competitive female runners ages 18 - 26 yr were r and omly assigned to OC ( 30 microg of ethinyl estradiol and 0.3 mg of norgestrel ) or control ( no intervention ) for 2 yr . Bone mineral density ( BMD ) and content ( BMC ) were measured yearly by dual x-ray absorptiometry . Stress fractures were confirmed by x-ray , magnetic resonance imaging , or bone scan . RESULTS R and omization to OC was unrelated to changes in BMD or BMC in oligo/amenorrheic ( N=50 ) or eumenorrheic runners ( N=100 ) . However , treatment-received analyses ( which considered actual OC use ) showed that oligo/amenorrheic runners who used OC gained about 1 % per year in spine BMD ( P<0.005 ) and whole-body BMC ( P<0.005 ) , amounts similar to those for runners who regained periods spontaneously and significantly greater than those for runners who remained oligo/amenorrheic ( P<0.05 ) . Dietary calcium intake and weight gain independently predicted bone mass gains in oligo/amenorrheic runners . R and omization to OC was not significantly related to stress fracture incidence , but the direction of the effect was protective in both menstrual groups ( hazard ratio [ 95 % CI ] : 0.57 [ 0.18 , 1.83 ] ) , and the effect became stronger in treatment-received analyses . The trial 's statistical power was reduced by higher-than-anticipated noncompliance . CONCLUSION OC may reduce the risk for stress fractures in female runners , but our data are inconclusive . Oligo/amenorrheic athletes with low bone mass should be advised to increase dietary calcium and take steps to resume normal menses , including weight gain ; they may benefit from OC , but the evidence is inconclusive This open-label r and omized study compared the effects of two combined oral contraceptives ( OCs ) containing 3 mg drospirenone (DRSP)/30 microg ethinyl estradiol ( EE ) with 150 microg levonorgestrel (LNG)/30 microg EE on the prevalence and changes from baseline of premenstrual symptoms after six cycles . The symptoms were measured using the Women 's Health Assessment Question naire . Subjects receiving DRSP/EE had fewer prevalence of premenstrual symptoms than those receiving LNG/EE after six cycles . A significantly lower score of negative affect category in the premenstrual phase was demonstrated in those receiving DRSP/EE more than LNG/EE . The DRSP/EE group showed a greater improvement of mean scores from baseline in the premenstrual phase compared with those who received LNG/EE on negative affect as seen in the items on anxiety , irritability , feeling sad or blue and weight gain in the category of water retention . In conclusion , OCs containing DRSP have beneficial effects in reducing the prevalence of premenstrual symptoms especially the symptoms of negative affect and weight gain , particularly when compared to LNG/EE . Hence , it should be recommended for women who are susceptible to these adverse symptoms The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospect i ve , open , group-comparative , r and omized , multicenter trial of women asking for contraception . In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thail and , 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were r and omly allocated to one of the two study groups . An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles . Criteria of cycle control , side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1 , 3 and 6 . Furthermore , the efficacy was evaluated after the last cycle . No pregnancies occurred with either of the contraceptives . The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle . Acne improved in both groups . Blood pressure and body weight remained unchanged . The two oral contraceptives were found to be effective and acceptable in Thai women . Compared to Caucasian women , the incidences of irregular bleeding and side effects were apparently lower in these Asian women . Furthermore , the effects of both oral contraceptives were comparable Blinding embodies a rich history spanning over two centuries . Most research ers worldwide underst and blinding terminology , but confusion lurks beyond a general comprehension . Terms such as single blind , double blind , and triple blind mean different things to different people . Moreover , many medical research ers confuse blinding with allocation concealment . Such confusion indicates misunderst and ings of both . The term blinding refers to keeping trial participants , investigators ( usually health-care providers ) , or assessors ( those collecting outcome data ) unaware of the assigned intervention , so that they will not be influenced by that knowledge . Blinding usually reduces differential assessment of outcomes ( information bias ) , but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment ( sometimes called co-intervention ) . Many investigators and readers naïvely consider a r and omised trial as high quality simply because it is double blind , as if double-blinding is the sine qua non of a r and omised controlled trial . Although double blinding ( blinding investigators , participants , and outcome assessors ) indicates a strong design , trials that are not double blinded should not automatically be deemed inferior . Rather than solely relying on terminology like double blinding , research ers should explicitly state who was blinded , and how . We recommend placing greater credence in results when investigators at least blind outcome assessment s , except with objective outcomes , such as death , which leave little room for bias . If investigators properly report their blinding efforts , readers can judge them . Unfortunately , many articles do not contain proper reporting . If an article cl aims blinding without any accompanying clarification , readers should remain sceptical about its effect on bias reduction The aim of this study was to compare contraceptive reliability , cycle control , and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol ( EE2 ) and 75 micrograms gestodene ( GSD ) , with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol . A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive . For the 20 micrograms EE2 preparation , 47.4 % of all women reported spotting at least once over a period of 12 treatment cycles , whereas this figure was 35.5 % for the 30 micrograms EE2 pill ( p < 0.05 ) . However , the incidence was within a range that corresponds to that of other OCs . The cumulative breakthrough bleeding rates ( at least once during the one year of treatment ) of 14.5 % ( 20 micrograms EE2 ) and 11.8 % ( 30 micrograms EE2 ) of women were not significantly different . In relation to all cycles , the intermenstrual bleeding rates were remarkably lower , indicating that the majority of the volunteers experienced such events only in few cycles under treatment : the spotting rate was 11.5 % ( 20 micrograms EE2 ) and 7.2 % ( 30 micrograms EE2 ) of all cycles , and the breakthrough bleeding rate was 2.6 % and 1.6 % of all cycles , respectively . Three pregnancies were recorded during the study ( one in the 20 micrograms EE2 + 75 micrograms GSD group , two in the 30 micrograms EE2 + 75 micrograms GSD group ) . All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect . The influence of both treatments on the blood pressure and body weight proved to be extremely slight . Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent . The discontinuation rate due to adverse events , including intermenstrual bleeding , was low ( 9.8 % for 20 micrograms EE2 + 75 micrograms GSD , and 7.2 % for 30 micrograms EE2 + 75 micrograms GSD ) and was in the lower range known for other oral contraceptives . Both preparations were well accepted by the volunteers . The data obtained demonstrate clinical ly acceptable cycle control , good tolerance , and a high st and ard of contraceptive reliability for both drugs . Prescription of the 20 micrograms EE2 preparation could be the first-line therapy in order to provide the lowest amount of EE2 possible . In case of persistent cycle control problems , a switch to the 30 micrograms EE2 drug should be considered OBJECTIVE To examine weight changes in a large cohort of obese and nonobese adolescent girls initiating depot medroxyprogesterone acetate ( DMPA ) , an oral contraceptive ( OC ) , or no hormonal contraceptive method ( control ) . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve study of 450 adolescent girls , aged 12 to 18 years , who attended 4 urban health clinics and selected DMPA , OC , or control . Data collection occurred at baseline and at 6 , 12 , and 18 months ; consisted of structured interview and measurement of height and weight ; and occurred from April 19 , 2000 , through September 26 , 2003 . MAIN OUTCOME MEASURE Weight was examined as mean change over 18 months and actual weight at each study visit . On the basis of preliminary analyses , we stratified the sample according to baseline obesity status ( nonobese , body mass index [ calculated as weight in kilograms divided by the square of height in meters ] < 30 ; obese , body mass index > or = 30 ) . RESULTS Adolescent girls who were obese at initiation of DMPA gained significantly more weight than did obese girls starting OC or control ( P<.001 for both ) . At 18 months , mean weight gain was 9.4 , 0.2 , and 3.1 kg for obese girls receiving DMPA , receiving OC , and control , respectively . Weight gain in obese girls receiving DMPA was also greater than weight gain in all nonobese categories ( 4.0 kg , DMPA ; 2.8 kg , OC ; 3.5 kg , control ; P<.001 ) . A significant interaction ( P = .006 ) between length of time receiving DMPA and weight gain was evident for obese subjects . CONCLUSIONS Over 18 months , DMPA use was associated with increasing rates of weight gain in obese subjects . The potential contribution to severe obesity in this population is concerning A r and omized multicenter study was performed in order to investigate the acceptance of a low-dose OC ( 30 micrograms of ethinyloestradiol and 150 micrograms of desogestrel ) , using a 9 weeks on and 1 week off schedule ( prolonged regimen , n = 198 ) , compared to a traditional 3 weeks on , 1 week off schedule ( st and ard regimen , n = 96 ) . Haemoglobin and blood pressure remained the same in both groups during the study . No significant differences were found in body weight changes between the two groups . There was significantly more breakthrough bleeding and spotting in the group with prolonged regimen than in the group with st and ard regimen , but both breakthrough bleeding and spotting decreased during the trial . Irregular bleeding was significantly less in women who were already using OC , compared to " new starters . " No serious side effects occurred . Significantly more women stopped the trial because of bleeding problems in the group with prolonged regimen , while there were significantly more women who stopped the trial because of headache in the group with st and ard regimen . After completing 12 months , or after premature withdrawal from the study , each women completed a question naire . Sixty-three per cent of the women preferred the studied alternative and twenty-six per cent preferred the traditional OC The efficacy , cycle-control and tolerance of Microgynon-30 , a widely prescribed levonorgestrel containing oral contraceptive , and Femodene , a new oral-contraceptive containing gestodene , were compared in a r and omised , double-blind study involving 456 healthy women over a 6 month period . 229 women were allocated to receive Femodene and 227 received Microgynon-30 . No differences between the groups in terms of obstetric and gynaecological history , previous contraceptive history , smoking habits , blood-pressure or body weight at admission were observed . No pregnancies were reported in either group , despite tablet-taking errors recorded in 6.3 % of the Femodene group and 7.6 % of the Microgynon-30 group . Both oral contraceptives were compared in terms of cycle length , intensity of the withdrawal bleed and side effects . Cycle-control was similar in the two groups . However , significantly fewer subjects reported breakthrough bleeding ( with or without spotting ) in the Femodene group ( 18 % of patients ) compared with the Microgynon-30 group ( 26 % of patients ) . The incidence of absent withdrawal bleeds was 1 % or less in both groups and no significant effects on body weight or blood pressure were observed OBJECTIVE To compare the cycle control and tolerability of two oral contraceptives containing 20 micrograms ethinylestradiol and either 150 micrograms desogestrel or 75 micrograms gestodene . METHODS A r and omized , multicenter study was conducted in which 1016 healthy adult women received the desogestrel ( n = 509 ) or the gestodene ( n = 507 ) preparation for six treatment cycles . RESULTS No significant differences in bleeding patterns were detected between the two treatments . The incidence and duration of irregular bleeding decreased markedly , and to a similar extent , during each treatment . The occurrence of irregular bleeding per cycle decreased from 24.6 to 9.4 % in the desogestrel group and from 19.7 to 8.6 % in the gestodene group . Its duration fell from 1.1 to 0.2 days and from 0.9 to 0.3 days , respectively . There was a consistently low incidence of amenorrhea ( 1.0 - 2.8 % ) . There were no significant differences between treatments for the incidence , intensity or emergence of dysmenorrhea . During both treatments , the incidence of premenstrual syndrome and complaints such as breast tenderness , nausea and headache dropped markedly . CONCLUSION Ultra low-dose oral contraceptives containing desogestrel or gestodene offer equivalent , good cycle control and improvements in dysmenorrhea and premenstrual syndrome and have similar , excellent tolerability profiles Although weight gain is among the most common complaints of women using oral contraceptives ( OC ) and a frequent reason for discontinuation , studies demonstrate little basis for this perception . We explored this issue by analyzing the daily weights of 128 women during four cycles of triphasic OC use . The mean weight at the end of the fourth cycle of use was the same as baseline weight ( average weight change , 0.0 pounds ) . The largest proportion of women , 52 % , remained within 2 pounds ( 0.9 kg ) of their starting weight , and 72 % of women had either no weight change or a loss . Over each menstrual cycle , regular but minor weight shifts were observed , with the mean weight rising by one-half pound ( 0.2 kg ) during the first weeks of each cycle and falling by the same amount during the last few days . These results emphasize the lack of association of OC use with weight gain but OC may be blamed at least in part , based on cyclic fluctuations . Counseling should emphasize weight gain as a misperception and stress the fact that a highly effective and safe form of contraception should not be ruled out or discontinued because of concern about weight OBJECTIVE To compare menstrual patterns and side effects between transdermal contraceptive patch and oral contraceptive use in Thai women over 35 years old . DESIGN Open labeled r and omized control trial . SETTING Family Planning Clinic , King Chulalongkorn Memorial Hospital , Bangkok , Thail and . MATERIAL AND METHOD Ninety-six women above the age of 35 years old were r and omized to receive either transdermal contraceptive patch ( n = 48 ) or oral contraceptive ( n = 48 ) . The patch regimen was three consecutive 7-day patches ( 21 days ) followed by 1 patch-free week per cycle ; the oral contraceptive contained with ethinyl estradiol ( EE ) 30 microg and levonorgestrel 150 microg . RESULTS There were no statistically significant differences between the two groups in terms of cycle length . The mean duration in the transdermal contraceptive group was longer than the COC group with statistically significant difference . More patients in the COC group experienced spotting than the transdermal contraceptive group . Neither amenorrhea nor pregnancies occurred in both groups . CONCLUSION Transdermal contraceptive patch provides reliable contraceptive efficacy . It also provides good cycle control equal to COC in Thai women aged above 35 years old . However , a higher incidence of minor adverse effects such as breast tenderness and nausea were demonstrated when compared to oral contraceptive containing with ethinyl estradiol ( EE ) 30 microg and levonorgestrel 150 microg OBJECTIVE The objective of this study was to compare cycle control , tolerability and sexual well-being with the use of three hormonal contraceptives . METHODS In this prospect i ve r and omized study , the effects of two combined oral contraceptives [ 20 microg of ethinylestradiol (EE)/100 microg of levonorgestrel and 15 microg of EE/60 microg of gestodene ] were compared with those of the vaginal ring ( 15 microg of EE/120 microg of etonogestrel ) . One-year data from 280 women were obtained . We investigated the pattern of menstrual cycle and the incidence of weight gain , nausea , headache , breast tenderness , irritability , depression and vaginal dryness . Moreover , desire and sexual satisfaction were evaluated . Finally , the cumulative rate of discontinuation in the three groups was estimated . CONCLUSION The analysis of adverse events revealed two crucial points for acceptability , compliance and continuation : poor cycle control and disturbance of sexual intercourse due to vaginal dryness and loss of desire The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism Thirty-five young women completed the Profile of Mood States and tests of automatization and perceptual restructuring ability before and after commencing one of three forms of oral contraception ( OC ) or one form of intrauterine contraception ( the loop ) . For each subject on each experimental variable the difference between the first and second tests was computed . These data were then analysed by covariance and discriminant function analyses . Two sets of functions were derived . The first distinguished the loop users from the OC users . The latter exhibited significantly greater increases in anger and significantly greater reductions in vigor than the former . The second set of discriminant functions distinguished users of Neogynon from the women in the other three groups . Neogynon users ' performances on the Color Words Test ( a measure of automatization ability ) worsened and their anger , vigor and tension scores had decreased to a greater extent than was the case for members of the other groups . It is suggested that the changes in affect demonstrated by the first discriminant function were related to personal and attitudinal variables associated with the Loop users . The second discriminant function was interpreted as an indication that the varying progestagen content of OC may have differential effects upon both affect and automatization ability Objective The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg ( EE/GSD ) with ethinylestradiol 0.03 mg/drospirenone 3 mg ( EE/DRSP ) administered according to conventional 21/7 regimen on body mass index ( BMI ) , blood pressure ( BP ) , lipid metabolism and hemostatic parameters . Method In this study , 160 healthy women were r and omized to EE/GSD mg or EE/DRSP for 12 months . Mean differences in BMI , high density lipoprotein-cholesterol ( HDL-C ) and low density lipoprotein-cholesterol ( LDL-C ) , total cholesterol ( TC ) levels and BP compared to baseline were assessed . Results One hundred and forty-five ( 89 % ) of the women completed all 12 treatment cycles . The subjects r and omly assigned into two treatment groups . Group EE/GSD ( n = 71 ) and group EE/DRSP ( n = 72 ) . In group B , BMI values were significantly lower than baseline at the sixth cycle . DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group . The difference between the two preparations was not statistically significant at the end of the study . TC levels remained similar in both groups throughout the study period . In both groups LDL-C levels decreased , triglyceride and HDL-C levels significantly increased from baseline levels . These changes result in increasing HDL-C/LDL-C ratio , demonstrating anti-atherogenic effect . Menstrual cycle patterns and the incidence of adverse events were similar between groups . The duration of withdrawal bleeding decreased during the study for both groups and was similar . Conclusion The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events . Compared with the EE/GSD preparation , the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean . The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP OBJECTIVE To compare a traditional 28‐day cycle to an extended 49‐day cycle of the 30 μg ethinyl estradiol (E2)/300 μg norgestrel monophasic birth control pill regimen . METHODS Ninety subjects r and omized to either 28‐day cycles with 21 active pills or 49‐day cycles with 42 active pills for a prospect i ve open label trial over four 84‐day reference periods or trimesters . Bleeding , pill taking , and symptom diaries were completed . The sample size with 80 % power to detect a 40 % reduction in bleeding days required 24 subjects in each arm . RESULTS Of the 90 women , 24 subjects ( 54.5 % ) on the 28‐day cycle and 29 ( 63 % ) on the 49‐day cycle completed the entire study ( P = .41 ) . There were no statistically significant differences between the two groups in demographics or continuation rates . There was a significant reduction in bleeding days in the experimental arm beginning in the first trimester ( 28‐day = 10.9 , 49‐day = 6.4 mean days of bleeding , P < .001 ) and continuing to the fourth trimester ( 28‐day = 11.3 , 49‐day = 5.8 mean days , P = .005 ) . The number of spotting days was similar between both schedules in the first trimester ( 28‐day = 4.8 , 49‐day = 3.7 mean days , P = .24 ) and continued into the fourth trimester ( 28‐day = 3.4 , 49‐day = 2.9 mean days , P = .30 ) . Annual expenditure for hygiene products was significantly less for extended use subjects ( 28‐day = $ 41.45 , 49‐day = $ 17.54 spent , P < .001 ) . CONCLUSION Extension of the 28‐day oral contraceptive ( OC ) cycle to a 49‐day cycle result ed in fewer bleeding days and no increase in mean spotting days or bleeding episodes The contraceptive efficacy , cycle control , and safety of a new low-dose , triphasic desogestrel/ethinyl estradiol oral contraceptive ( CTR 77 , Cyclessa(TM ) ) was compared to that of a marketed , triphasic norethindrone/ethinyl estradiol oral contraceptive ( Ortho-Novum(R ) 7/7/7 ) . Two identical multicenter , open-label , r and omized , parallel group , comparative Phase III 6-cycle trials were design ed to each enroll 4200 healthy women . The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here . Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy . Despite a lower ethinyl estradiol dose ( 25 microg/day vs. 35 microg/day ) , the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed ( p = 0.001 ) , lack of early withdrawal bleed ( p = 0.01 ) , and breakthrough bleeding/spotting ( p = 0.001 ) . For each of the months of the study , the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group ( breakthrough bleeding , p = 0.006 ; breakthrough spotting , p = 0.001 ) . The incidence of other adverse events was similar among treatment groups , an observation that supports the safety of both formulations . There was significantly less weight gain ( p = 0.0002 ) and less increase in the body mass index ( BMI ) ( p = 0.0002 ) in the Cyclessa group . The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7 . Cyclessa provides significantly improved cycle control with no weight gain OBJECTIVE To assess the contraceptive efficacy , cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene . METHODS In a r and omized , open-label , six-cycle , group-comparative , multicenter study performed in Brazil , pregnancies , cycle-control parameters , incidence of side-effects and the presence and severity of acne vulgaris were assessed , and blood pressure and body weight were measured at pretreatment and after one , three and six cycles of oral contraceptive use . RESULTS Of the 595 women enrolled , 274 ( 86.7 % ) in the desogestrel/ethinylestradiol group and 227 ( 81.4 % ) in the gestodene/ethinylestradiol group completed the six cycles , providing data for 1753 and 1487 treatment cycles , respectively . Two pregnancies occurred , one of which ( in the desogestrel/ethinylestradiol group ) was attributed to user failure , whilst the other ( in the gestodene/ethinylestradiol group ) was thought to result from method failure . Cycle control was observed to be excellent ; the incidences of irregular bleeding and minor side-effects were low in both groups and decreased after an initial increase in the first cycle . Pre-existing acne improved in both groups , whereas blood pressure and body weight remained essentially unchanged . CONCLUSIONS Both desogestrel/ethinylestradiol and gestodene/ethinylestradiol provide effective oral contraception with comparable cycle control and acceptability Drospirenone is a new synthetic progestogen with both progestational , antimineralocorticoid and anti and rogenic properties . In combination with ethinylestradiol , it is being developed as an oral contraceptive which will contain 30 μg ethinylestradiol and 3 mg drospirenone ( Yasmin ® , Schering AG , Germany ) . The effects of drospirenone alone , and in combination with ethinylestradiol , upon the renin – angiotensin – aldosterone system ( RAAS ) have been evaluated in healthy female volunteers . RAAS activity was assessed by measurement of plasma renin substrate ( PRS ) concentration ( otherwise known as angiotensinogen ) , plasma renin activity ( PRA ) , and plasma aldosterone ( P-Aldo ) concentration . An antimineralocorticoid effect was observed when volunteers received drospirenone alone at doses in the range 0.5–3.0 mg/day for one cycle . The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA . When ethinylestradiol ( 30 μg ) was combined with either 2 mg or 3 mg drospirenone and given to volunteers for three cycles , an increase in PRS was observed with both preparations , which was indicative of estrogenic stimulation , and increases in PRA and P-Aldo were shown which were indicative of an antimineralocorticoid effect of drospirenone . Increases in PRA and P-Aldo were significantly higher with the preparation containing 3 mg drospirenone in cycle 1 but not in cycle 3 . The effect of the preparation containing 30 μg ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that of a commercially available preparation also containing 30 μg ethinylestradiol but combined with 150 μg desogestrel ( Marvelon ® ) . Over a period of 13 cycles , increases in PRS were seen with both treatments , the effect being slightly more pronounced with 30 μg ethinylestradiol/150 μg desogestrel . A markedly greater increase in PRA was seen following treatment with 30 μg ethinylestradiol/3 mg drospirenone , and , in cycle 3 , this difference was statistically significant . In contrast , P-Aldo was increased markedly with 30 μg ethinylestradiol/3 mg drospirenone in all measured cycles , whereas , in the 30 μg ethinylestradiol/150 μg desogestrel group , changes were minimal . The increases in PRA and P-Aldo are interpreted as endogenous counter-regulation against the antimineralocorticoid activity of drospirenone . PRS increases under all combinations are an expression of estrogenic stimulation . Measurement of body weight and blood pressure in the studies with combined ethinyl-estradiol and drospirenone revealed that drospirenone was associated with either stable body weight or with a slight loss in body weight , while blood pressure remained largely unchanged . Overall , the results indicate that 30 μg ethinylestradiol/3 mg drospirenone has a distinct antimineralocorticoid effect Objective To investigate ovulation inhibition with drospirenone , a novel progestogen that has a profile similar to natural progesterone , when given alone or in combination with ethinylestradiol . Method Hormonal parameters ( LH , FSH , 17ß-estradiol and progesterone ) and peripheral parameters ( cervical score , spinnbarkeit and crystallization ) , as well as follicle size assessed by ultrasonography , were measured in two groups of healthy women . Forty-eight women aged 19–35 years were r and omly assigned to receive 0.5 mg , 1.0 mg , 2.0 mg or 3.0 mg of drospirenone over a single treatment cycle , and 52 women aged 20–35 years were r and omized to receive either 2 mg drospirenone/30 μg ethinylestradiol or 3 mg drospirenone/30 μg ethinylestradiol over three treatment cycles . Baseline measurements were taken during a control pretreatment cycle . Results Adequate ovarian suppression with drospirenone alone was evident at dose levels of 2 and 3 mg , and at 3 mg all subjects had anovulatory cycles . Although both combined preparations ( 2 mg and 3 mg drospirenone/30 μg ethinylestradiol ) inhibited the hypothalamic – pituitary – ovarian axis , follicular maturation leading to escape ovulation was observed in three subjects in the 2 mg drospirenone/30 μg ethinylestradiol group . Only one of these ovulations was considered to be definitely the result of treatment failure . All cycles in the 3 mg drospirenone/30 μg ethinylestradiol group were anovulatory . No statistically significant difference was found between treatment groups . Conclusion The combination of 3 mg drospirenone/30 μg ethinylestradiol ( Yasmin ® , Schering AG ) reliably inhibits ovulation , with a low frequency of follicular maturation , and provides a reasonable safety margin PURPOSE This r and omized multicenter , open-label , trial compared efficacy , acceptability , tolerability and compliance of NuvaRing with a combined oral contraceptive ( COC ) , containing 30 microg of ethinyl estradiol ( EE ) and 3 mg of drospirenone . METHOD In this 13-cycle study , 983 women were r and omized and treated ( intent-to-treat population ) with NuvaRing or COC . RESULTS One in-treatment pregnancy occurred with NuvaRing ( Pearl Index=0.25 ) ( 95 % confidence interval [ CI ] : 0.006 , 1.363 ) and four with the COC ( Pearl Index=0.99 ) ( 95 % CI : 0.269 , 2.530 ) . For both groups , compliance ( 89.2 % NuvaRing , 85.5 % COC ) and satisfaction ( 84 % NuvaRing ; 87 % COC ) were high ; the vast majority of women found NuvaRing easy to insert ( 96 % ) and remove ( 97 % ) . Tolerability was similar ; the most frequent adverse events with NuvaRing were related to ring use , whereas estrogen-related events were more common with the COC . CONCLUSION NuvaRing has comparable efficacy and tolerability to a COC containing 30 microg of EE and 3 mg drospirenone . User acceptability of both methods was high This study was design ed to determine the effects of two low-dose oral contraceptives , most frequently given in our area , monophasic desogestrel/ethinylestradiol ( DG/EE ) and triphasic levonorgestrel/ethinylestradiol ( LNG/EE ) , on lipoprotein parameters , especially LDL particle size and HDL subclass distribution ( determined by lipid-stained 2%-20 % polyacrylamide gradient gel electrophoresis ) in 37 healthy normolipidemic women aged 19 to 27 years . Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use . Results reflected the estrogen-progestin balance . As compared with baseline values , with both formulations , plasma total cholesterol , phospholipids , and HDL3 cholesterol increased , and LDL-predominant peak size decreased , with a translation of LDL pattern A towards pattern I. With DG/EE , plasma triglycerides , apolipoproteins AI and B increased . With LNG/EE , LDL cholesterol increased , and HDL2 cholesterol decreased . All these modifications were moderate , within threshold limits . Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE , since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol Body weight , fasting blood glucose ( GP ) ( BFG ) , serum immunoreactive insulin ( IRI ) , serum growth hormone ( GH ) and serum glycosylated proteins were longitudinally followed in 2 groups of women during two years ' oral contraception . One group ( n = 10 ) received a combination of 0.030 mg ethinylestradiol and 0.150 mg levonorgestrel and the other ( n = 10 ) a combination of 0.030 mg ethinylestradiol and 0.150 mg of desogestrel . There was a significant increase in BFG during the study and the values were still rising , when examined 2 months after discontinuation of the pill . Two subjects , reaching the level of 5.5 mmol/l showed normal pretreatment values , when investigated one year later . After 6 months ' use of either preparation , GH significantly increased , remained on that level throughout the study and returned to the pretreatment level after discontinuation of the pill . Body weight , IRI and GPP did not change significantly during the study BACKGROUND Women often stop hormonal contraception because of perceived weight change . We conducted a r and omized trial comparing the contraceptive vaginal ring to a low-dose oral contraceptive ( OC ) . We examined the difference between women 's reported and measured baseline weights and looked at factors affecting perceived weight change . METHODS We r and omized 201 participants to either the vaginal ring or an OC for three cycles . We weighed participants upon enrollment ( n=194 ) and at exit ( n=167 ) , using the same instrument for all measurements . Participants also provided self-reported height and their reactions to perceived weight changes . RESULTS Baseline weight and body mass index were similar for both groups ( mean weight=145.9 lb ) . Measured weight was , on average , 4.4 lb more than reported weight ; this difference was greater in overweight and obese participants . Participants gained an average of 2.8 lb over 3 months ; this gain did not differ between groups or by baseline weight . Subjects who reported a " bad change " in weight at exit ( n=34 ) gained an average of 4.4 lb , whereas those who reported " no change " ( n=112 ) gained 2.2 lb and those who reported a " good change " ( n=14 ) gained 3.3 lb . CONCLUSION Participants underreported their weight , and this difference was greater for heavier women . There was little weight change for the women in our study . Participants ' opinions about weight change were not correlated with measured weight changes OBJECTIVE To compare bleeding profiles of a traditional 28-day oral contraceptive pill cycle with continuous administration . METHODS After a 28-day run-in cycle , women were r and omized to either 28-day cycles ( 21 active pills and a pill-free week ) or continuous use of the same 20-μg ethinyl estradiol/100-μg levonorgestrel formulation for 12 study cycles ( 336 days ) . The number of bleeding and spotting days were measured by daily diary . A subset underwent cycle 1 ( n = 16 ) , and nine ( n = 14 ) pelvic ultrasound and endometrial histology sampling . Blood pressure , weight , hemoglobin , and adverse events were measured at revisit . The sample size with 80 % power to detect a 67 % reduction in bleeding days required 27 subjects in each arm . RESULTS Of the 79 subjects r and omized , 28 ( 70 % ) of the 28-day cycle and 32 ( 82 % ) of the continuous-use subjects completed the entire study ( P = .6 ) . With continuous use , 49 % , 68 % , and 88 % of women reported no bleeding during cycles 2 , 6 , and 12 , respectively . Amenorrhea or infrequent bleeding was present in 68 % of continuous users during cycles 1–3 and increased to 88 % during cycles 10–12 . Spotting during cycle days 1–21 increased initially with continuous use but reduced over time , and by 9 months was less than the spotting reported by cyclic users . Adverse events , blood pressure , weight , and hemoglobin findings were similar between groups . CONCLUSION Extension of the 28-day oral contraceptive cycle to continuous use with a low-estrogen dose combination oral birth control pill result ed in significantly fewer bleeding days Abstract Objective : To compare the cycle control , efficacy , and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20μg and drospirenone 3 mg with an established formulation containing ethinylestradiol 20μg and desogestrel 150μg . Methods : This was a r and omized , open-label , parallel-group , multicenter study of healthy women ( aged 18–35 years ) over seven treatment cycles . Both combined oral contraceptives were administered once daily for 21 consecutive days followed by a 7-day hormone-free interval . Results : A total of 445 women were r and omized to treatment ; of these , 441 ( ethinylestradiol 20μg/drospirenone 3 mg , n = 220 ; ethinylestradiol 20μg/desogestrel 150μg , n = 221 ) went on to receive study medication . There was a trend towards reduced intracyclic bleeding with continued treatment in both treatment groups , consistent with clinical experience . Intracyclic bleeding was highest during the first treatment cycle in both treatment groups , but was generally much lower in subsequent cycles . More than 90 % of women in each of the groups experienced withdrawal bleeding during the study . The duration of withdrawal bleeding remained fairly constant throughout the study . The maximum intensity was mainly bleeding , rather than spotting . Overall , cycle control , efficacy , and safety profiles were comparable between both groups . Adverse events were generally of mild-to-moderate intensity and were those typical of hormonal contraceptive use . Conclusion : In conclusion , both ethinylestradiol 20μg/drospirenone 3 mg and ethinylestradiol 20μg/desogestrel 150μg are effective and well tolerated contraceptives that provide good cycle control Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives ( OCs ) containing 20 microg ethinyl estradiol ( EE ) have not been demonstrated in placebo-controlled trials . Two placebo-controlled , r and omized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females ( n = 704 ; > or=14 years old ) with regular menstrual cycles and moderate facial acne . Patients were r and omized to receive 20 microg EE/100 microg levonorgestrel ( LNG ) or placebo for six cycles . Body weight was measured at baseline and during Cycles 1 , 3 , and 6 . The occurrence of adverse events was recorded at each visit . Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [ 0.72 kg + /- 2.64 ( SD ; n = 349 ) ] and placebo [ 0.56 kg + /- 2.64 ( SD ; n = 355 ; p > 0.05 ) ] for the last measured weight of each patient . Rates of headache , nausea , weight gain , and breast pain , side effects commonly attributed to OCs , were also similar between groups ( p > 0.05 ) . No serious , unexpected , drug-related adverse events occurred during the study . The low-dose OC containing 20 microg EE/100 microg LNG is safe , well tolerated , and does not cause weight gain Objective : This study compared 84-day bleeding patterns after immediate initiation of a triphasic oral contraceptive with a 25-&mgr;g daily dose of ethinyl estradiol ( E2 ) compared with the contraceptive vaginal ring , which has a 15-&mgr;g daily dose of ethinyl E2 . Methods : This was an open-label controlled trial . We r and omly assigned 201 women to immediate start of a contraceptive pill or immediate start of the ring in a 1:1 allocation ratio . Our primary outcome was difference in mean bleeding – spotting days per woman according to treatment assignment . Secondary outcomes were differences in World Health Organization — defined menstrual indices , differences in perceived bleeding changes , and differences in bleeding according to cycle day at the start of method . Results : The mean bleeding – spotting days in the 84-day reference period for all subjects was 19.2 days ( 17.0 days for ring users and 21.4 days for pill users , mean difference 4.4 days ) . Using the World Health Organization menstrual indices , the ring users experienced fewer days or episodes of bleeding – spotting and shorter intervals . Among ring users , no baseline characteristics were associated with bleeding outcomes . Older nulliparous pill users , however , reported more bleeding – spotting days . Significantly more ring users reported a decrease in duration of bleeding compared with pill users ( P < .01 ) . We found no significant differences in bleeding patterns based on analysis of cycle day at study enrollment . Conclusion : Our study shows advantageous bleeding patterns for subjects using the contraceptive vaginal ring . It also confirms our previous findings that immediate start of hormonal contraception is an acceptable alternative to waiting for menses . Level of Evidence : OBJECTIVE To determine in a prospect i ve study if the use of two low-dose estrogen oral contraceptives is associated with changes in weight or body composition . DESIGN 80 out patients referring to the family planning service , aged 18 - 43 years were r and omly assigned to a treatment with the EE/desogestrel or EE/gestodene association , 20 patients with IUD , aged 26 - 40 years , were selected as a control group . Anthropometric data and body composition were taken at enrollment and after 6 and 12 months . MAIN OUTCOME MEASURES Anthropometric measurements included body mass index ( BMI ) , body composition estimated by mean of Bioelectrical Impendance Analysis ( BIA ) . RESULTS In the three groups weight , BMI , and total body water ( TBW ) , and body cellular mass ( BCM ) remained unchanged during the study period . CONCLUSIONS The use of EE/desogestrel and EE/gestodene is not associated with significant variations of body weight and body composition during one year treatment The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days . The study was design ed as a double-blind , r and omized , multicenter trial in 60 women . A pre-treatment cycle , three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH , FSH , 17 beta-estradiol and progesterone measurements every other day . No ovulation and no luteinized , unruptured follicle were observed . Suppression of ovarian activity was more pronounced by the 23-day regimen . 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less ( p < 0.05 ) in the 23-day regimen . The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study . The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations Metabolic parameters were studied in 30 patients over 12 treatment cycles in a double-blind r and omized comparative trial of the new progestogen gestoden in a triphasic formulation against a fixed dose combination pill containing desogrestrel , in B and ung , Indonesia . The results of this laboratory experience affirm findings in similar previous metabolic studies that : ( 1 ) the changes induced by modern low-dose pills are clinical ly and statistically insignificant ; ( 2 ) throughout the treatment cycles , the values of the various laboratory tests remain well within the normal range ; and ( 3 ) the favorable balance between coagulation and fibrinolysis is maintained . Results of lipoprotein , coagulation , fibrinolytic and liver function tests in 27 patients are presented . Gestoden 's pharmacologic profile , and the worldwide clinical experience with the triphasic gestoden formulation in 4285 women are discussed . ResuméA B and ung en Indonésie , on a procédé à une étude des paramètres métaboliques chez trente patientes pendant 12 cycles de traitement dans le cadre d'un essai r and omisé en double-aveugle . Cette étude comparait un nouveau protestogène , le gestoden , de formule triphasique , à une pillule comportant un mélange fixe contenant du désogestrel . Les résultats de cette expérience en laboratoire confirment les constatations faites précédemment lors d'études métaboliques similaires , à savoir que : ( 1 ) les changements apportés par les pillules modernes minidoses ne sont pas significatifs des points de vue clinique et statistique : ( 2 ) pendant les cycles de traitement , les valeurs des divers tests en laboratoire restent bien dans les limites normales ; et ( 3 ) l'équilibre entre coagulation et fibrinolyse est maintenu de façon favorable . Cette étude présente les résultats des tests , chez 27 patientes , de lipoprotéine , de coagulation , de fibrinolyse et de la fonction hépatique . Elle examine également le profil pharmacologique du gestoden ainsi que l'expérience clinique sur le plan mondial de la formule triphasique du gestoden sur 4285 femmes . ResumenEn B and ung , Indonesia , se realizó un estudio de los parámetros metabólicos de treinta pacientes durante 12 ciclos de tratamiento , en un ensayo al azar doble ciego . Este estudio comparaba un nuevo progestógeno , gestoden , de fórmula trifásica , con una píddora combinada de dosis fija que contenía desogestrel . Los result ados de esta experiencia de laboratorio confirman las constataciones hechas anteriormente en estudios metabólicos similares , a saber , que : 1 ) los cambios aportados por las píldoras modernas de dosis baja no son significativos desde el punto de vista clínico y estadístico ; 2 ) durante los ciclos de tratamiento , los valores de las diversas pruebas de laboratorio permanecen esencialmente dentro de los límites normales ; 3 ) el equilibro entre la coagulación y la fibrinólisis se mantiene de modo favorable . Este estudio presenta los result ados de las pruebas , entre 27 pacientes , de lipoprotreína , coagulación , fibrinólisis y función hepática . Examina asimismo el perfil farmacológico del gestoden así como la experiencia clínica mundial de la fórmula trifásica del gestoden en 4.285 mujeres 150 women participated in a double-blind clinical trial comparing 2 dosages of an oral contraceptive agent : 250 mcg d-norgestrel + 50 mcg ethinyl estradiol and 150 mcg d-norgestrel + 30 mcg ethinyl estradiol . The 150/30 combination result ed in shorter cycles , longer menses ( p.001 ) , shorter latent period ( p.001 ) , and a higher instance of breakthrough bleeding and spotting ( p.05 and p.001 ) . The 250/50 dose caused a significantly higher incidence of breast discomfort ( p.001 ) , leg cramps ( .02 ) , and nausea ( .001 ) . More 250/50 dose women dropped out for more than 1 reason than in the lower dose group This study compares the contraceptive reliability , cycle control , and tolerability of two oral contraceptive preparations containing 20 micrograms of ethinyl estradiol combined with either 75 micrograms of gestodene ( EE/GSD ) or 150 micrograms of desogestrel ( EE/DSG ) . Women received the trial preparations daily for 21 days , followed by a 7-day pill-free interval . Contraceptive efficacy , cycle control , and tolerability were evaluated over a period of 12 cycles . Efficacy data of 14,700 treatment cycles ( EE/GSD : 7299 ; EE/DSG : 7401 ) were obtained from 1476 women ( EE/GSD , n = 740 ; EE/DSG , n = 736 ) . Both preparations provided effective contraception and good cycle control with a similarly low incidence of both spotting and breakthrough bleeding . The spotting rates in both treatment groups decreased from 35.1 % ( EE/GSD ) and 37.5 % ( EE/DSG ) in the first treatment cycle to approximately 10 % in the fourth treatment cycle . The spotting incidence as percent of the total number of cycles was 12.7 % for EE/GSD and 14.3 % for EE/DSG . The breakthrough bleeding incidence was 5.2 % of all cycles for EE/GSD and 6.0 % of all cycles for EE/DSG . For 84.7 % of the cycles in the gestodene group and for 82.5 % of the cycles in the desogestrel group , neither spotting nor breakthrough bleeding were recorded . Overall , the spotting and breakthrough bleeding incidence tended to be lower with EE/GSD than with EE/DSG . However , the difference was not statistically significant . Amenorrhea was recorded in 2.7 % of the cycles with EE/GSD and in 2.9 % with EE/DSG . Both preparations were well tolerated and showed a similar pattern of adverse events . More than 83 % of the women in both groups either did not gain weight or lost more than 2 kg . Both preparations had a beneficial effect on dysmenorrhea . Both regimens provided reliable contraception and good cycle control . The incidence of adverse events was relatively low and both preparations were well tolerated Body weight , systolic and diastolic blood pressure and plasma renin activity ( PRA ) were longitudinally followed in two groups of women during 2 years ' oral contraception . One group ( n = 10 ) received a combination of 0.150 mg levonorgestrel plus 0.030 mg ethinyloestradiol and the other ( n = 10 ) a combination of 0.150 mg desogestrel plus 0.030 mg ethinyloestradiol . Three subjects discontinued the study due to relocation . No statistically significant changes occurred in any of the measured parameters This open-label , r and omized , Phase III study compared the efficacy and tolerability of and compliance with NuvaRing , a combined contraceptive vaginal ring releasing 15 microg of ethinylestradiol ( EE ) and 120 microg of etonogestrel daily , with those of and with a combined oral contraceptive ( COC ) containing 150 microg of levonorgestrel ( LNG ) and 30 microg of EE . Subjects received NuvaRing or a COC for 13 cycles ( 3 weeks of ring/pill treatment followed by a 1-week ring-/pill-free period ) . A total of 1030 subjects ( NuvaRing , n=512 ; COC , n=518 ) was r and omized and started treatment ( intent-to-treat [ ITT ] population ) . The percentage of women in the ITT population who completed the trial was 70.9 % for the NuvaRing group and 71.2 % for the COC group . Five in-treatment pregnancies occurred in each group , giving Pearl indices of 1.23 for NuvaRing and 1.19 for the COC . Compliance with both treatments was excellent and both were well tolerated . In conclusion , NuvaRing has comparable efficacy and tolerability with a COC containing 150 microg of LNG and 30 microg of EE and does not require daily dosing Blood pressure was prospect ively studied in 57 women during pregnancy labor the late postpartum period and after 6 cycles of oral contraceptive ( OC ) use . The women were r and omly given either a combination type ( COC ) or sequential type ( SOC ) OC . There were no significant differences between the groups in age parity weight weight gain while using OCs or development of hypertension during pregnancy . 8 women using the COD ( 33 % ) developed hypertension ( diastolic blood pressure 90 + mm Hg ) as opposed to 1 ( 3 % ) using the SOC ( p less than .05 ) . When the absolute blood pressures for the 2 groups were compared the mean diastolic pressure for the COC group of 77.3 mm Hg is significantly higher than that of the SOC group of 72.0 . Of the 9 women who developed hypertension during OC use 7 also had hypertension during pregnancy . The different progestins in the OCs may have different direct effects on the cardiovascular system Desogestrel ( DSG ) is a less- and rogenic progestogen than levonorgestrel ( LNG ) . This difference in and rogenicity may be responsible for observed differences in metabolic effects between oral contraceptive ( OC ) formulations containing almost equivalent estrogen doses but with either DSG or LNG as a progestogen . To test the hypothesis , a prospect i ve 9-month r and omized comparison of plasma lipids , glucose , insulin , hemostasis , and sex hormone binding globulin ( SHBG ) was conducted in 66 healthy women using phasic formulations of OCs containing either DSG ( DSG-OC ) or LNG ( LNG-OC ) . The study results showed that SHBG increased 3-fold with DSG-OC and 2-fold with LNG-OC . DSG-OC increased HDL-C , HDL(2)-C and HDL(3)-C ; LDL-C decreased transiently . LNG-OC decreased HDL(2)-C and increased HDL(3)-C ; HDL-C was unchanged and LDL-C decreased transiently . Both formulations increased VLDL-C and triglycerides , more with DSG-OC , but apolipoprotein B levels increased equally . Apo A-I and A-II increased more with DSG-OC than with LNG-OC . Neither formulation altered Lp(a ) or fasting glucose and insulin levels . Postpr and ially , both formulations decreased glucose and increased insulin responses , but to an equivalent degree . Both OCs slightly enhanced procoagulant and profibrinolytic parameters to the same extent except for internally compensating decreases in Factor V and protein S with DSG-OC . In summary , at almost equivalent estrogen doses , a phasic OC containing DSG compared with LNG has a less and rogenic effect on lipoproteins and SHBG , similar effects on hemostatic parameters with lower protein S and factor V activity and equivalent effects on carbohydrate metabolism . The lipoprotein , SHBG , and protein S and factor V differences are likely due to the lesser and rogenicity of DSG allowing for a greater expression of the dose of estrogen This multicenter study compared the contraceptive efficacy , cycle control , and safety of a new triphasic norgestimate ( 180/215/250 microg)/ethinyl estradiol 25 microg regimen ( Ortho Tri-Cyclen Lo ) ( n = 1,723 ) with that of norethindrone acetate 1 mg/ethinyl estradiol 20 microg ( Loestrin Fe 1/20 ) ( n = 1,171 ) . Healthy women were treated for up to 13 cycles . Demographics were similar between regimens . Contraceptive efficacy was comparable for Ortho Tri-Cyclen Lo and Loestrin Fe 1/20 . The overall and method failure probabilities of pregnancy through 13 cycles were 1.9 % and 1.5 % , respectively , with Ortho Tri-Cyclen Lo and 2.6 % and 2.4 % , respectively , with Loestrin Fe 1/20 . Breakthrough bleeding and spotting was reported by a significantly lower percentage of participants in the Ortho Tri-Cyclen Lo group compared with the Loestrin Fe 1/20 group . At representative Cycles 1 , 3 , 6 , 9 , and 13 , breakthrough bleeding and spotting rates were 16.3 , 11.5 , 10.3 , 7.9 , and 7.7 % , respectively , in the Ortho Tri-Cyclen Lo group and 34.9 , 22.9 , 22.2 , 15.9 , and 13.1 % , respectively , in the Loestrin Fe 1/20 group . Compliance and safety data were similar for the two regimens PURPOSE To examine the effect of oral contraceptives ( OC ) on body weight , fat mass , percent body fat , and lean mass in young female distance runners . METHODS The study population consisted of 150 female competitive distance runners aged 18 - 26 yr who had participated in a 2-yr r and omized trial of the effect of the OC Lo/Ovral ( 30 microg of ethinyl estradiol and 0.3 mg of norgestrel ) on bone health . Weight and body composition were measured approximately yearly by balance beam scales and dual-energy x-ray absorptiometry , respectively . RESULTS Women r and omized to the OC group tended to gain slightly less weight ( adjusted mean difference ( AMD ) = -0.54 + /- 0.31 kg.yr , P = 0.09 ) and less fat ( AMD = -0.35 + /- 0.25 kg.yr , P = 0.16 ) than those r and omized to the control group . OC assignment was associated with a significant gain in lean mass relative to controls among eumenorrheic women ( those who had 10 or more menstrual cycles in the year before baseline ; AMD = 0.77 + /- 0.17 kg.yr , P < 0.0001 ) but not among women with fewer than 10 menstrual cycles in that year ( AMD = 0.02 + /- 0.35 kg.yr , P = 0.96 ) . Treatment-received analyses yielded similar results . CONCLUSION This r and omized trial confirms previous findings that OC use does not cause weight or fat mass gain , at least among young female runners . Our finding that this OC is associated with lean mass gain in eumenorrheic runners , but not in those with irregular menses , warrants examination in other studies OBJECTIVE To compare the effect of 2 oral contraceptives ( OCs ) on body weight . STUDY DESIGN A r and omized , parallel-group , multicenter study of 1,723 women taking an OC with norgestimate ( NGM ) 180/215/250 microg/ethinyl estradiol ( EE ) 25 microg vs. 1,171 women taking on OC with norethindrone acetate 1 mg/EE 20 microg for 6 - 13 cycles was performed . Body weight changes between baseline and cycle 6 and baseline and cycle 13 were analyzed . Analysis included not only changes in mean body weight but also the distribution of changes that were within 5 % of baseline weight , 5 - 10 % of baseline weight and > 10 % of baseline weight . Only the 10 % change was felt to be clinical ly significant . RESULTS The distribution of body weight changes did not statistically differ between the 2 OC groups for any parameter measured . The mean weight change after 6 months for the NGM/EE and norethindrone acetate/EE groups was + 0.71 kg and + 0.57 kg , respectively . At 13 cycles for the NGM/EE and norethindrone acetate/ EE groups , the mean body weight change was + 0.93 kg and + 0.62 kg , respectively . Only 0.3 % of subjects in both OC groups experienced a 10 % change in weight . CONCLUSION Use of OCs does not substantially affect body weight for most women OBJECTIVE : To estimate whether young women taking the first pill on the day of prescription had higher continuation rates and lower pregnancy rates than women who waited until menses to start the oral contraceptive pill ( OCP ) . METHODS : We recruited 1,716 women aged younger than 25 years seeking to initiate the oral contraceptive at three publicly funded family planning clinics , and r and omly assigned them to conventional initiation of the pill ( conventional start ) or immediate , directly observed ingestion of the first pill ( quick start ) during the clinic visit . Women underwent follow-up interviews at 3 and 6 months . RESULTS : Sixty percent of participants discontinued the pill , and 8 % became pregnant during follow-up . Women who took the first pill in the clinic were more likely to continue to the second OCP pack ( odds ratio 1.5 , 95 % confidence interval 1.0–2.1 . ) ; however , the Quick Start approach did not improve OCP continuation rates at 3 and 6 months . Those assigned to Quick Start were slightly less likely to become pregnant within 6 months from the time they started the pill ( hazard ratio 0.90 , 95 % confidence interval 0.64—1.25 ) . Eighty-one percent of women rated the Quick Start approach as acceptable or preferable to waiting . Rates of serious adverse events were low and similar in the two groups . CONCLUSION : Protocol s that require a woman to wait until the next menses to start hormonal contraceptives are an obstacle to contraceptive initiation . Directly observed , immediate initiation of the pill improves short-term continuation . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00068848 LEVEL OF EVIDENCE : OBJECTIVES Poor cycle control and tolerability can be reasons for irregular pill intake . This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control . METHODS In this open , group-comparative , r and omized multicenter trial in Germany and the Netherl and s , women received either 20 microg ethinylestradiol plus 150 microg desogestrel ( 20EE/DSG ; n = 500 ) or 20 microg ethinylestradiol plus 100 microg levonorgestrel ( 20EE/LNG ; n = 498 ) for six treatment cycles . Cycle control , dysmenorrhea and premenstrual syndrome ( PMS ) were assessed using diary cards . Tolerability was assessed using the self-administered question naires Psychological General Well-Being Index ( PGWBI ) and the Profile of Mood States ( POMS ) . Acne was assessed by objective ( acne counts ) and subjective ( no , moderate , mild , severe ) acne scoring of the facial area at baseline and treatment cycles 1 , 3 and 6 . RESULTS A total of 404 ( 78.1 % ) and 384 ( 75.3 % ) women in the 20EE/DSG and 20EE/LNG groups , respectively , completed the trial . The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG ( 0.18 vs. 0.13 ; p < 0.05 ) . The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG ( 0.63 vs. 0.48 ; p < 0.05 ) . Early withdrawal bleeding was more frequent with 20EE/LNG ( 0.15 vs. 0.08 ; p < 0.005 ) , whereas continued withdrawal bleeding was more frequent with 20EE/DSG ( 0.32 vs. 0.45 ; p < 0.001 ) ; absence of withdrawal bleeding was comparable ( 0.06 vs. 0.04 , respectively ) . Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding ( p < 0.05 ) . Dysmenorrhea and PMS decreased comparably in both groups . There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points . Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles ( p < 0.05 ) . The subjective acne scores supported this finding . CONCLUSIONS 20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding . There were no apparent differences between the two groups regarding tolerability and quality of life . There was less acne with 20EE/DSG Objectives To evaluate the effects of an oral contraceptive containing 3 mg drospirenone ( DRSP ) and 30 μg ethinyl oestradiol ( EE ) on somatic and psychological symptoms related to water retention , and on body weight . Methods This prospect i ve study was performed in 26 centres in Canada over six treatment cycles . The first primary efficacy variable was the individual change in the water retention score of the Moos Menstrual Distress Question naire ( MDQ ) from baseline to the final examination in women with significant somatic symptoms related to water retention ( n = 43 ) . The second primary target variable was the change in body weight ( n = 305 ) . Results Forty-three women met the criteria for the first primary target variable . In the premenstrual phase , the score decreased from 6.49 ( SEM 0.45 ) at baseline to 3.19 ( SEM 0.54 ) at the final examination ( p = 0.0001 ) . The data for the menstrual phase were 4.70 ( SEM 0.30 ) at baseline and 2.35 ( SEM 0.32 ) at the final examination ( p < 0.0001 ) . Baseline data from 299 women were assessed for the second primary target variable . Body weight did not change significantly , having increased only by 0.14 kg ( SEM 0.13 ) at the final visit ( p = 0.3082 ) . Conclusion An oral contraceptive containing 3 mg DRSP and 30 μg EE significantly reduced the clinical symptoms of water retention . Body weight did not change BACKGROUND The objective of this study was to compare cycle control , cycle-related characteristics and bodyweight effects of NuvaRing with those of a combined oral contraceptive ( COC ) containing 30 microg of ethinyl estradiol and 3 mg of drospirenone . METHODS A r and omized , multicentre , open-label trial in which 983 women were treated ( intent-to-treat population ) with NuvaRing or the COC for 13 cycles . RESULTS Breakthrough bleeding or spotting during cycles 2 - 13 was in general less frequent with NuvaRing than that with the COC ( 4.7 - 10.4 % ) and showed a statistically significant odds ratio of 0.61 ( 95 % confidence interval : 0.46 , 0.80 ) with longitudinal analysis . Intended bleeding was significantly better for all cycles with NuvaRing ( 55.2 - 68.5 % ) than that with the COC ( 35.6 - 56.6 % ) ( P < 0.01 ) . Changes from baseline in mean bodyweight and body composition parameters were relatively small for both groups with no notable between-group differences . CONCLUSION NuvaRing was associated with better cycle control than the COC , and there was no clinical ly relevant difference between the two groups in bodyweight This prospect i ve , r and omized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles . Women were allocated to two groups , one group ( n = 207 ) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily , and the other group ( n = 209 ) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel , daily . Follicular development was monitored by transvaginal ultrasonography of the ovaries , during days 18 - 21 in the pretreatment cycle and in treatment cycles 1 , 3 , 6 , 9 and 12 . Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene . For all cycles , follicles of 10 - 30 mm were found in 18 % of women in the desogestrel group , compared with 9.7 % in the gestodene group , whilst follicles with a diameter of > 30 mm were present in 5 % of the desogestrel group compared with 1.9 % of the gestodene group . The difference between the treatment groups with respect to follicle diameters of 10 - 30 mm and > 30 mm was statistically significant ( p < 0.05 and p < 0.001 , respectively ) . No ruptured follicles were observed in either group throughout the study , suggesting that there was no escape ovulation , however , there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills . It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity , and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size OBJECTIVE The study was undertaken to determine the side effects , including depression , of oral contraceptives ( OCs ) in adolescent girls . METHODS We conducted a r and omized trial of OCs for dysmenorrhea , which assessed side effects and depression . Seventy-six adolescents received an OC ( 20 microg of ethinyl estradiol/100 mg of levonorgestrel ) or a placebo in a double-blind fashion for 3 months . We ascertained OC side effects using open-ended and closed question formats . Participants self-administered the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depressive symptoms . RESULTS Fifty-seven participants ( 77 % ) reported at least one side effect ( median=2 , range=0 - 8 , interquartile range=1.0 - 3.25 ) . The number and the type of side effects reported in the OC group and in the placebo group were similar . Mean exit CES-D scores were comparable between groups [ OC group , 14.0 ( SD=9.2 ) ; placebo group , 14.4 ( SD=8.1 ) ; p=.86 ] . CONCLUSION Adolescents treated with an OC or a placebo experienced similar numbers and types of OC side effects , as well as depressive symptoms Two combined contraceptive vaginal rings ( CVR ) each releasing approximately 1 mg norethindrone acetate ( NET-Ac ) and either 20 micrograms or 15 micrograms ethinyl estradiol over 24 h were tested at three clinic sites in Los Angeles , San Francisco , and Sydney . A total of 61 women were enrolled to use the ring on a schedule of 3 weeks in/1 week out for four treatment cycles . Serum estradiol , progesterone , norethindrone ( NET ) , and ethinyl estradiol ( EE ) levels were assayed twice weekly in all four treatment cycles . Both CVR performed well , with no pregnancies occurring and only one cycle of luteal activity suggestive of ovulation ( serum progesterone > 32 nmol/L ) occurring with each ring ( 0.9 % of cycles with the 1/15 ring and 1.2 % of cycles with the 1/20 ring ) . Although there was significantly more luteal activity in women using the 1/15 CVR ( 5.9 % compared with 1.2 % of cycles ) , only three cycles with a marked degree of luteal activity ( progesterone > 10 nmol/L ) occurred among compliant women . Serum levels of NET and EE were consistently elevated during use of both rings . There was no significant difference between serum levels with the two rings because of wide interindividual variations , although both NET and EE levels tended to be higher with the 1/20 ring . However , there was a significant difference in EE levels between the women in Los Angeles and Sydney using the same dose rings . Total cholesterol , HDL , and LDL cholesterol values were not significantly changed during treatment . Triglycerides increased but remained within the normal range . Overall cycle control was good with both formulations , but there was slightly more cycle disturbance with the lower dose ring . There was no change in mean body weight during the study , and individual weight changes appeared to be idiosyncratic . Side effects were infrequent and similar to those reported with other steroidal contraceptive methods . Three women complained of vaginal discharge , one with accompanying itch and one with a vaginal C and ida infection in cycle 1 . Overall , both of these EE/NET-Ac rings performed well , with only minor and mainly nonsignificant differences in effect on serum EE , NET , E2 , and progesterone levels and lipids , and on vaginal bleeding patterns The effect of two triphasic oral contraceptives ( Triquilar [ TRQ ] and Trisiston [ TRS ] ) containing ethinyl estradiol ( EE ) and levonorgestrel ( LNG ) on various hormonal parameters was investigated in 26 women during a cross-over study . TRS consisted of 0.03 mg EE + 0.05 mg LNG ( six tablets ) , 0.04 mg EE + 0.075 mg LNG ( six tablets ) , and 0.03 mg EE + 0.15 mg LNG ( nine tablets ) , whereas TRQ was different in the second phase ( five tablets ) and third phase ( 10 tablets ) . Blood sample s were taken on days 6 , 11 , 21 , and 28 of the control and washout cycles and the third treatment cycle . Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins , free testosterone , and dehydroepi and osterone sulfate in a time-dependent manner , whereas estradiol and testosterone were already suppressed on day 6 , indicating a direct suppressive effect on ovarian steroid synthesis . Prolactin , which rose sporadically in some women , was not significantly changed . In contrast , the levels of sex hormone binding globulin , corticosteroid binding globulin , and cortisol were significantly elevated by 100 % . During the hormone-free interval of 7 days , all parameters returned at least partly to baseline . There was no significant difference between the effects of both formulations . The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene ( EE/GSD ) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate ( EE/NGM ) . Blood sample s were collected from 46 women on days 2 , 11 , and 21 of the preceding control cycle and of the third , sixth and twelfth treatment cycle . There was no significant difference in the influence on any hormonal parameter between both formulations . Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepi and rosterone sulphate ( DHEA-S ) by 20 - 30 % ( p < 0.01 ) and a reduction of 5 alpha- and rostane-3 alpha , 17 beta-diol glucuronide by 50 - 60 % ( p < 0.01 ) during each treatment cycle , while and rostenedione levels were reduced by 25 % ( p < 0.01 ) . There was also a significant decrease in the levels of total testosterone by 30 - 35 % ( p < 0.01 ) and free testosterone by 60 % ( p < 0.01 ) , while sex hormone-binding globulin ( SHBG ) was increased by 200 - 240 % on days 11 and 21 ( p < 0.01 ) . During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100 % as compared to the pretreatment values . The serum levels of corticosteroid-binding globulin ( CBG ) which is known to be influenced only by the estrogenic component of combination pills , increased significantly by 170 % ( p < 0.01 ) during each treatment cycle . During the pill-free interval of 7 days , the CBG levels decreased but were still elevated by 90 - 100 % as compared to the control cycle . Similarly , the serum levels of cortisol were significantly elevated by 110 - 140 % ( p < 0.01 ) during treatment with both preparations . The results demonstrate a profound suppression of and rogen levels and peripheral and rogen metabolism OBJECTIVE : To investigate whether contraceptive vaginal ring use results in similar estimated genital symptoms , signs , examination , and laboratory findings compared with oral contraceptive use . METHODS : Women were r and omly assigned to either contraceptive vaginal ring or a 20 μg ethinyl estradiol oral contraceptive pill use for 3 consecutive 28-day cycles , directly followed by 3 cycles of the study drug not initially assigned . Subjects scored genital symptoms on a daily diary using a 0–4 scale and underwent a baseline , cycle 2 , cycle 4 , and exit pelvic examination including vaginal discharge evaluation , vaginal Gram stain and white cell count , and culture for yeast and Lactobacillus , including colony count and hydrogen peroxide production . RESULTS : Of the 40 subjects assigned to each arm , 33 ( 82.5 % ) subjects in the ring-first arm and 31 ( 77.5 % ) subjects in the pill-first arm completed all study visits ( P = .58 ) . Most subjects reported few genital symptoms with either method , but 63 % of subjects reported vaginal wetness during ring use compared with 43 % during pill use . During ring use larger numbers of Lactobacillus colonies present were positive for hydrogen peroxide production ( fold difference 2.67 , 95 % confidence interval 1.49 , 4.78 , P < .001 ) . All other laboratory data , including yeast colony counts , Nugent Gram stain score , vaginal white blood cell count , vaginal pH , and discharge weight , were not significantly different by method . CONCLUSION : Some women may notice an increase in vaginal wetness during contraceptive ring use yet the method is well tolerated and appears to improve the vaginal flora . LEVEL OF EVIDENCE : Objective : To compare the bleeding patterns and tolerability of 3 different extended ring regimens with those of the st and ard 28-day cycle with 21 days of contraceptive vaginal ring use followed by 7 ring-free days . Methods : Following a run-in 28-day ring cycle , women were r and omized to 1 of 4 regimens : monthly ( 28-day cycle ) , every other month ( 49-day cycle ) , every third month ( 91-day cycle ) , or continuous ( 364-day cycle ) . Treatment duration was 1 year . Daily bleeding diary , interval visit question naire , and examination data were collected . Results : A total of 561 women were enrolled , 429 were subsequently r and omized , and 289 ( 67.4 % ) women completed the entire year . All schedules were well tolerated and acceptable to women , but study completion rates were higher for the shorter cycles . Bleeding days were reduced with postponement of the withdrawal bleeding ( ring-free ) week , but spotting days increased . For example , women using the continuous or 364-day ring cycle reported a median of zero bleeding days but 10–12 days of spotting during the first 3 months of extended use . Unscheduled bleeding during ring use was the lowest with the traditional 28-day cycle . Adverse events , blood pressure , body weight , and laboratory findings were comparable over the 4 treatment groups . Conclusion : The combination vaginal contraceptive ring can be used for extended cycles to alter the bleeding schedule . Women willing to tolerate some spotting might choose the longer extensions to have fewer menstrual periods . Level of Evidence : A comparative study of two low-dose oral contraceptives , gestodene ( GES ) 75 mcg/ethinyl oestradiol ( EE ) 30 mcg and desogestrel ( DES ) 150 mcg/EE 20 mcg , was conducted in women over 30 years of age . This r and omised , open-label study was organised in Denmark , Italy , New Zeal and and United Kingdom . A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles . The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline . However , the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment . The mean age ( + /- SD ) was 35 + /- 4 years in the GES/EE group and 35 + /- 5 years in the DES/EE group . The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group , data for 2796 cycles . There were no pregnancies on medication with either preparation . The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6 . Irregular bleeding between withdrawal bleeds occurred in 10 % of GES/EE and 18.5 % of DES/EE cycles . Absence of all bleeding was reported in 29 ( 1 % ) and 63 ( 2 % ) cycles , respectively . The incidence of missed pills was low in both groups ( 11 % of cycles ) . No significant differences were observed in cycle length or withdrawal bleeding episode length . Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE . However , for both preparations , the mean intensity was close to light bleeding . No clinical ly significant differences were noted in weight , blood pressure , Papanicolaou smears or laboratory data . Sixty-eight ( 13.5 % ) subjects in the GES/EE group and 64 ( 12.8 % ) in the DES/EE group discontinued before the end of the study . Among them , 37 ( 7 % ) and 40 ( 8 % ) in the respective groups withdrew because of adverse reactions . There was no difference between groups in terms of primary reasons for withdrawal . The most frequently reported complaints that led to discontinuation in both groups were headache , nausea and metrorrhagia . Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group . These results show excellent cycle control , efficacy and very low rate of side effects with both GES/EE and DES/EE . These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results |
2,658 | 14,578,316 | The turbidimetric D-dimer test is sensitive but nonspecific for the detection of PE in the emergency department setting .
D-Dimer tests using latex turbidimetric methods appear to have test characteristics comparable to those for ELISA methods | BACKGROUND Clinicians in outpatient clinics and emergency departments desire an accurate quantitative D-dimer assay .
The study objective was to evaluate the diagnostic performance characteristics of the latex turbidimetric D-dimer test in the diagnosis of pulmonary embolism ( PE ) in the emergency department population . | Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising studies for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding . Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) The SimpliRed D-dimer assay is a whole blood agglutination test for the exclusion of pulmonary embolism ( PE ) and has been advocated as a reliable rapid bedside alternative to more time-consuming quantitative assays . However , widely differing negative predictive values ( 77 - 100 % ) are reported . This study assessed the intra- and interobserver variability as a possible cause for this wide accuracy range and evaluated the accuracy of the SimpliRed test in 81 consecutive patients with clinical ly suspected PE . Absolute D-dimer concentration was measured using the Tinaquant ( Roche Diagnostics GmbH , Mannheim , Germany ) assay . Every assay was immediately scored by one observer and then photographed . Photos were r and omised and read twice by two other independent observers . The intraobserver reproducibility was good : kappa=0.81 and 0.73 . However , we found poor interobserver reproducibility with kappa=0.47 . This seems due to the fact that the SimpliRed test proved difficult to interpret in the 0.3 - 1.3 microg/mL plasma concentration D-dimer range , which contained 32/81 ( 40 % ) patients , 8 of whom had PE . Using pulmonary angiograms and ventilation perfusion lung scans with a concurrent spiral computed tomography scan as a gold st and ard ( 25 patients had PE ) , SimpliRed 's accuracy to exclude PE was moderate , with negative predictive values of 0.78 and 0.84 . In particular , the two observers scored the SimpliRed test as normal in 12 of 25 and 5 of 25 patients with proven PE . We conclude that SimpliRed is strongly observer-dependent . This explains the varying sensitivities for the detection of venous thromboembolism as reported in previous studies We investigated 128 patients with suspected deep vein thrombosis and 26 patients with suspected pulmonary embolism . Plasma cross-linked fibrin degradation products were measured instantly by a new rapid and fully quantitative immunoturbidimetric assay ( Boehringer Mannheim ) which recognizes the D-dimer epitope by antibody-coated latex particles . Diagnosis of deep vein thrombosis was established by either ascending venography ( n = 105 ) or colour duplex ultrasound ( n = 8) , whereas for the exclusion of deep vein thrombosis only venography was accepted . The sensitivity/specificity for the diagnosis of deep vein thrombosis was 98%/44 % . Patients with suspected pulmonary embolism were examined by pulmonary angiography ( n = 19 ) or perfusion lung scanning alone ( n = 6 ) , if sufficient . One pulmonary embolism was diagnosed at post-mortem examination . For pulmonary embolism , sensitivity/specificity was 100%/50 % . These findings indicate that the new immunoturbidimetric technique is as reliable as former ELISA methods and allows to rule out thromboembolic disorders . D-dimers showed a correlation to the extent of the deep vein thrombosis , proximal thrombosis producing higher D-dimer levels . Patients presenting immediately after the onset of symptoms were found to have higher D-dimers than patients examined after a few days . A quantitative D-dimer measurement thus seems to provide precious additional information of the duration and the extent of thromboembolic disease The performance of a new automated ELISA for a rapid , individual and quantitative measurement of plasma D-dimer ( VIDAS D-dimer ) has been evaluated . First , a study of 100 patients was performed in order to choose the best couple of antibodies in comparison with an already clinical ly vali date d ELISA . Then the results were certified in a prospect i ve study including 195 consecutive patients suspected of pulmonary embolism ( PE ) . For a cut-off level of 500 ng/ml VIDAS D-dimer showed a sensitivity of 100 % ( 95 % confidence interval 92 - 100 ) , a specificity of 37.6 % , a negative predictive value of 100 % ( 95 % CI 93.3 - 100 ) and a positive predictive value of 33.1 % . During a 6 months ' follow-up no patient ( 95 % CI 0 - 6.4 ) with D-dimer < 500 ng/ml presented a new suspicion of venous thromboembolic disease . These results suggest that this rapid and single-dose ELISA provides a very useful tool for the clinician to exclude on a day-to-day basis the diagnosis of PE The practical utility and diagnostic accuracy of two new rapid , automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 r and omly selected patients with suspected VTE . The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles . The VIDAS D-dimer automated Elisa was used as the reference method . Diagnosis was confirmed in 51 patients ( 29 PE , 19 DVT , 3 DVT+PE ) . The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines ( r = 0.82 , MDA vs VIDAS ; r = 0.75 , STA vs VIDAS ) and areas under the curve of ROC plots ( VIDAS 0.83 ; STA 0.83 ; MDA 0.81 ) . At a discriminant value of 500 ng/mL , all three D-dimer assays showed high sensitivity ( 96 - 98 % ) , high NPV ( 93 - 97 % ) and moderate specificity ( 39 - 42 % ) . Reproducibility of results around the cut-off is an important aspect of the diagnostic utility of D-dimer assays . CV 's of duplicate determinations in this critical zone showed average values of 5.4 % and 17.0 % for MDA and STA , respectively . These data demonstrate that such rapid and automated latex-based methods for the quantitative measurement of D-dimer hold promise as reliable and cost-efficient approaches for the exclusion of VTE . Prospect i ve patient management studies will be required to confirm this BACKGROUND The reported operating characteristics of the plasma fibrin D-dimer level for the diagnosis of acute pulmonary embolism vary widely . OBJECTIVE To determine the sensitivity , specificity , predictive value , and clinical utility of the D-dimer for the diagnosis of pulmonary embolism , and to describe the effect of D-dimer assay method ( enzyme-linked immunosorbent assay [ ELISA ] , latex agglutination , membrane ELISA ) and discriminate level , patient location at onset , comorbid disease , duration and intensity of concurrent heparin administration , and duration of symptoms on these operating characteristics . DESIGN Prospect i ve laboratory investigation . SETTING Community and tertiary care teaching hospital . PATIENTS Consecutive patients with suspected acute pulmonary embolism referred for pulmonary angiography from April 1993 through March 1996 . MEASUREMENTS Baseline characteristics , the duration and intensity of heparin anticoagulation , the time interval between symptom onset and plasma D-dimer testing , pulmonary angiography , and the D-dimer level on the day of pulmonary angiography . RESULTS Of 105 consenting patients , 33 ( 31 % ) had a positive pulmonary angiogram . The D-dimer sensitivity/ negative predictive value for the ELISA , latex agglutination ( American Bioproducts Co/Diagnostica Stago and Biopool International ) , and membrane ELISA were 100%/100 % , 94%/94 % , 100%/100 % , and 97%/96 % , respectively , at a discriminate level of 250 microg/L or less . The clinical utility , defined as the prevalence of a negative test , ranged from 17 % to 33 % . D-dimer sensitivity was unaffected by patient location at onset , comorbid disease , or heparin therapy but was inversely related to the duration of symptoms . CONCLUSIONS The sensitivity of the plasma fibrin D-dimer for the diagnosis of pulmonary embolism depends on the assay method , the assay-specific discriminate level , and the duration of symptoms . At the appropriate discriminate level , the plasma D-dimer is a sensitive but nonspecific test for the diagnosis of pulmonary embolism |
2,659 | 30,592,392 | On the basis of the research it can be concluded that the consumption of at least 5 servings of F&V per day may prevent the progression of periodontal diseases , especially periodontitis , and even tooth loss .
Moreover , incorporation of specific F&V into the diet or , alternatively , their lyophilized forms , and nutritional education activities seem to support the st and ard of care therapy of gingivitis and periodontitis . | Periodontal diseases affect up to 90 % of the population worldwide .
Deficiencies in vitamins , minerals and polyphenolic compounds , whose main sources are fruit and vegetables ( F&V ) , may predispose to these diseases .
The PICO ( Patient , Intervention of interest , Comparison or Control Intervention , and Outcome ) question was : What is the effect of F&V intake on the outcomes of periodontal diseases , observed in either experimental or observational studies of human population s suffering from periodontitis or gingivitis , compared to controls without intervention or healthy people . | Material & Methods We have analyzed the loss of enamel and dentine after exposure to different non-alcoholic drinks with a simple new method using bovine teeth . 100 enamel and 100 dentine specimens from freshly extracted bovine incisors were r and omly attributed to 10 groups ( n=10 for enamel and dentine each ) . Prior to the start of the experiment all specimens were weighed using a precision balance . The mean initial masses ( SD ) were 35.8 mg ( 7.2 ) for enamel and 24.7 mg ( 7.0 ) for dentine . No statistically significant differences were found between groups for initial masses ( p>0.05 , ANOVA with Bonferroni post hoc test ) . Thereafter , all specimens of one group were simultaneously placed in 200 ml of the following fluids : Coca-Cola , Coca-Cola light , Sprite , apple juice , Red Bull , orange juice , Bonaqua Fruits ( Mango-Acai ) , tap water , chlorinated swimming pool water , and lemon juice . Fluids were continuously ventilated at 37 ° C for 7 days . Thereafter the specimens were weighed again and the mean mass loss was calculated . Results The values were ( enamel/dentine ) : Coca-Cola 7.5 mg/6.6 mg ; Coca-Cola light 5.2 mg/3.5 mg , Sprite 26.1 mg/17.7 mg , apple juice 27.1 mg/15.2 mg , Red Bull 16.6 mg/17.0 mg , orange juice 24.3 mg/20.2 mg , Bonaqua Fruits ( Mango-Acai ) 17.8 mg/16.2 mg , tap water -0.2 mg/-0.3 mg , swimming pool water -0.3 mg/-0.2 mg , and lemon juice 32.0 mg/28.3 mg . From all drinks , Cola and Cola light showed the least erosivity ( p<0.001 , ANOVA with Bonferroni post hoc test ) whereas lemon juice showed statistically significant higher erosivity than all other drinks except Sprite and apple juice ( p<0.01 , ANOVA with Bonferroni post hoc test ) . Conclusions In conclusion , erosivity of common non-alcoholic drinks varies widely . For example , Sprite , apple juice , and orange juice are about five times more erosive than Coca-Cola light . The findings from the present study should be taken into account in choosing a diet that provides satisfactory nutrition while minimizing tooth erosion Bioactive molecules in berries may be helpful in reducing the risk of oral diseases . The aim of this study was to determine the effect of bilberry consumption on the outcome of a routine dental clinical parameter of inflammation , bleeding on probing ( BOP ) , as well as the impact on selected biomarkers of inflammation , such as cytokines , in gingival crevicular fluid ( GCF ) in individuals with gingivitis . Study individuals who did not receive st and ard of care treatment were allocated to either a placebo group or to groups that consumed either 250 or 500 g bilberries daily over seven days . The placebo group consumed an inactive product ( starch ) . A study group , receiving st and ard of care ( debridement only ) was also included to provide a reference to st and ard of care treatment outcome . Cytokine levels were assayed using the Luminex MagPix system . The mean reduction in BOP before and after consumption of test product over 1 week was 41 % and 59 % in the groups that consumed either 250 or 500 g of bilberries/day respectively , and was 31 % in the placebo group , and 58 % in the st and ard of care reference group . The analysis only showed a significant reduction in cytokine levels in the group that consumed 500 g of bilberries/day . A statistically significant reduction was observed for IL-1β ( p = 0.025 ) , IL-6 ( p = 0.012 ) and VEGF ( p = 0.017 ) in GCF sample s in the group that consumed 500 g of bilberries daily . It appears that berry intake has an ameliorating effect on some markers of gingival inflammation reducing gingivitis to a similar extent compared to st and ard of care Objective : Many previous studies have reported that fruit and vegetable consumption is associated with a reduced risk of various disease , but whether or not their consumption is associated with the oral health-related quality of life ( OHRQoL ) is unclear . The objective of this study was to examine the association between the frequency of fruit and vegetable consumption and the OHRQoL in elderly subjects by sex . Methods : We analyzed cross-sectional data from a population -based Kyoto-Kameoka Study in 2012 of 3112 men and 3439 women ( age ≥ 65 years ) . The frequencies of fruit and vegetable consumption were assessed using a vali date d food frequency question naire . We evaluated the OHRQoL using the General Oral Health Assessment Index ( GOHAI ) , a self-reported measure design ed to assess the oral health problems in old adults . Results : After adjusting for age , body mass index , alcohol , smoking , education , socioeconomic status , history of disease , medication use , mobility disability , and total energy intake , a higher frequency of combined fruit and vegetable consumption showed a significant positive association with the GOHAI score in both men and women ( p-trend < 0.001 in both sexes ) . These associations remained significant after adjustment for poor mastication and denture use ( p-trend all < 0.05 in both sexes ) . We observed a significant positive association even when the frequencies of fruit or vegetable consumption were analyzed separately ( all p-trend < 0.05 in both sexes ) . Conclusions : A higher frequency of fruit and /or vegetable consumption independently showed a strong positive association with the OHRQoL in both men and women . Further prospect i ve studies are needed to confirm these findings Aim A double-blind r and omized controlled trial to determine whether dietary supplementation with fruit/vegetable/berry juice powder concentrates , simultaneously with non-surgical periodontal therapy , improved 2-month treatment outcomes . Methods Volunteers with chronic periodontitis were r and omly assigned to one of three groups : fruit/vegetable ( FV ) , fruit/vegetable/berry ( FVB ) or placebo . Supplements were taken daily during non-surgical debridement and maintenance and outcomes assessed at 2 , 5 and 8 months after completion . Primary outcomes were mean probing pocket depth ( PPD ) , clinical attachment gain , % sites bleeding on probing ( % BOP ) at 2 months . Adherence and plasma β-carotene were determined . Results Sixty-one nutritionally replete ( by serum biochemistry ) volunteers enrolled and 60 ( n = 20 per arm ) completed the 2-month review . Clinical outcomes improved in all groups at 2 months , with additional improvement in PPD versus placebo for FV ( p < 0.03 ) . Gingival crevicular fluid volumes diminished more in supplement groups than placebo ( FVB ; p < 0.05 ) at 2 months , but not at later times . The % BOP ( 5 months ) and cumulative plaque scores ( 8 months ) were lowered more in the FV group ( p < 0.05 ) . Conclusions Adjunctive juice powder concentrates appear to improve initial pocket depth reductions in nutritionally replete patients , where plasma micronutrient bioavailability is attainable . Definitive multicentre studies in untreated and treated patients are required to ascertain the clinical significance of such changes OBJECTIVE We hypothesise that a difference in nutrition influences dental caries and periodontal disease . There are few previous studies especially longitudinal ones which have evaluated this hypothesis . This study investigated the relationship between nutritional intake , including milk and milk products ( MMP ) , and dental disease , controlling for several confounding factors . MATERIAL AND METHODS A group of 600 subjects aged 70 , r and omly selected for this study , included approximately the same number of male and female subjects . The number of teeth on which root caries had occurred or where there was a periodontal event over a 6-year period was measured . To determine quantitative food intake at baseline , a semi-quantitative food frequency question naire was used during face-to-face interviews by dieticians . The stepwise method of multiple linear regression analysis was used to identify independent predictors of the number of root caries or periodontal disease events during the 6 years . Intake of the six food groups includes ( i ) fish , shellfish , meat , beans and eggs ; ( ii ) MMP ; ( iii ) dark green and yellow vegetables ( DYV ) ; ( iv ) other vegetables and fruits ; ( v ) cereals , nuts and seeds , sugar and sweeteners , confectioneries ( CNSC ) and ( vi ) fats and oils . The alcohol , gender and anthropometric evaluation including measurements of weight and height for the calculation of body mass index , educational level , the number of family members and the number of remaining teeth were used as independent variables . RESULTS According to stepwise multiple regression analysis , two variables ( quantity of MMP , and gender ) were negatively associated with the number of root caries events during the 6 years . The st and ardised coefficients were -0.14 ( p = 0.035 ) and -0.17 ( p = 0.007 ) respectively . In addition , DYV were negatively , and three other variables ( CNSC ; alcohol ; and the number of remaining teeth at baseline ) were positively associated with the number of periodontal disease events during the 6 years . The st and ardised coefficients were -0.16 ( p = 0.001 ) , 0.11 ( p = 0.042 ) , 0.10 ( p = 0.041 ) and 0.58 ( p < 0.001 ) respectively . CONCLUSION Our results suggest that the intake of MMP in this elderly population correlated with root caries events . In addition , intake of vegetables negatively correlated , and intake of ' CNSC ' positively correlated with periodontal disease events 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 Previous studies demonstrate a relationship between a lack of vitamin C and increased risk of periodontal disease . In the present study we examine the vitamin C plasma levels and inflammatory measures in periodontitis patients before and after the consumption of grapefruit . Subjects and methods Fifty-eight patients with chronic periodontitis were assigned to the test group ( non-smokers n=21 , smokers n=17 ) and a diseased control group ( non-smokers n=11 , smokers n=9 ) . Furthermore , 22 healthy subjects were recruited to compare vitamin C plasma levels between periodontally diseased and healthy subjects . Clinical evaluations , including plaque index ( PI ) , sulcus bleeding index ( SBI ) , probing pocket depths ( PPD ) and plasma vitamin C levels , were performed at baseline , and after two weeks of grapefruit consumption . Results At baseline , we observed significantly reduced plasma vitamin C levels in the test group and diseased controls in comparison with the healthy controls . On principle , smokers showed lower levels of vitamin C ( mean 0.39 ± 0.17 mg dl−1 ) than non-smokers ( mean 0.56±0.29 mg dl−1 ) . After grapefruit consumption , the mean plasma vitamin C levels rose significantly in the test group compared to the diseased controls ( non-smokers : 0.87±0.39 mg dl−1 , smokers : 0.74±0.30 mg dl−1 ) . Furthermore the SBI was reduced in the test group ( non-smokers : from 1.68±0.6 to 1.05±0.6 , p<0.001 ) , whereas PI and PPD were unaffected . Conclusion The present results show that periodontitis patients are characterised by plasma vitamin C levels below the normal range , especially in smokers . The intake of grapefruit leads to an increase in plasma vitamin C levels and improves sulcus bleeding scores . Longer term studies are necessary to determine whether other periodontal outcomes improve with such supplementation especially in smokers OBJECTIVES To determine whether foods that are good to excellent sources of fiber reduce periodontal disease progression in men . DESIGN Prospect i ve , observational study . SETTING Greater Boston , Massachusetts , metropolitan area . PARTICIPANTS Six hundred twenty-five community-dwelling men participating in the Department of Veterans Affairs Dental Longitudinal Study . MEASUREMENTS Dental and physical examinations were conducted every 3 to 5 years . Diet was assessed using food frequency question naires ( FFQs ) . Mean follow-up was 15 years ( range : 2 - 24 years ) . Periodontal disease progression on each tooth was defined as alveolar bone loss ( ABL ) advancement of 40 % or more , probing pocket depth ( PPD ) of 2 mm or more , or tooth loss . Good and excellent fiber sources provided 2.5 g or more of fiber per serving . Multivariate proportional hazards regression estimated hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) of periodontal disease progression and tooth loss in relation to fiber sources , stratified according to age younger than 65 versus 65 and older , and controlled for smoking , body mass index , calculus , baseline periodontal disease level , caries , education , exercise , carotene , thiamin and caffeine intake , and tooth brushing . RESULTS In men aged 65 and older , each serving of good to excellent sources of total fiber was associated with lower risk of ABL progression ( HR = 0.76 , 95 % CI = 0.60 - 0.95 ) and tooth loss ( HR = 0.72 , 95 % CI = 0.53 - 0.97 ) . Of the different food groups , only fruits that were good to excellent sources of fiber were associated with lower risk of progression of ABL ( HR = 0.86 per serving , 95 % CI = 0.78 - 0.95 ) , PPD ( HR = 0.95 , 95 % CI = 0.91 - 0.99 ) , and tooth loss ( HR = 0.88 , 95 % CI = 0.78 - 0.99 ) . No significant associations were seen in men younger than 65 . CONCLUSION Benefits of higher intake of high-fiber foods , especially fruits , on slowing periodontal disease progression are most evident in men aged 65 and older BACKGROUND AND OBJECTIVE Physical inactivity and an unhealthy diet have been implicated as risk factors for several chronic diseases that are known to be associated with periodontitis , such as cardiovascular diseases , obesity and diabetes . Studies investigating the relationship between periodontitis and physical activity and diet are limited . Therefore , this study was conducted to determine the relationship between physical activity , healthy eating habits and periodontal health status . MATERIAL AND METHODS A systematic r and om sample of 340 persons , 18 - 70 years of age , was selected from persons accompanying their relative patients who attended the outpatient clinics in the medical center of Jordan University of Science and Technology in north of Jordan . Data collected included socio-demographic and clinical characteristics , anthropometric measurements , physical activity level and dietary assessment . RESULTS Individuals who were highly physically active had a significantly lower average plaque index , average gingival index , average clinical attachment loss ( CAL ) and percentage of sites with CAL ≥ 3 mm compared to individuals with a low level of physical activity and individuals with a moderate level of physical activity . Those who had a poor diet had a significantly higher average number of missing teeth and an average CAL compared with those who had a good diet . In the multivariate analysis , a low level of physical activity and a poor diet ( diets with a healthy eating index score of < 50 points ) were significantly associated with increased odds of periodontitis . CONCLUSIONS A low physical activity level and a poor diet were significantly associated with increased odds of periodontal disease . Further studies are needed to underst and this relationship in greater detail BACKGROUND Dietary modification may be important in the prevention and control of chronic adult periodontitis . The role of promoting an adequate consumption of fruits , vegetables and whole grains in chronic periodontitis has not been thoroughly investigated . The main aim of this dietary intervention study was to assess the influence of a customised dietary intervention ( aim ing to increase the consumption of fruits , vegetables and whole grains ) on antioxidant status in adults with chronic periodontitis . METHODS Fifty-one participants , aged 30 - 65 years , were recruited from a U.K. Dental Hospital and r and omly allocated to an intervention or control group . Both groups received normal clinical treatment but customised dietary advice was delivered to the intervention group by a community nutrition assistant . Dietary intakes , anthropometric parameters and biochemical indices with respect to blood and saliva and periodontal indices were evaluated at baseline , as well as at 3 and 6 months post-dietary intervention . RESULTS At 3 and 6 months post-intervention , the intervention group showed a significant ( P < 0.05 ) increase in plasma total antioxidant capacity measured by Trolox equivalent antioxidant capacity assay compared to the control group . At 3 and 6 months after dietary intervention , the intervention group had significantly higher intakes of fruits and vegetables compared to the control group . The intake of whole grain was significantly higher in the intervention group than in the control group , 6 months post-intervention . No significant differences were observed with respect to periodontal indices between groups . CONCLUSIONS It is suggested that dietary advice may help to improve dietary habits and , consequently , the antioxidant status of patients with chronic periodontitis . However , the impact of such intervention on periodontal indices needs further investigation Periodontal disease is highly prevalent worldwide , and consumption of certain foods , such as fruits , seem to improve the effectiveness of periodontal therapy ( PT ) due to their antiadhesive , immunomodulatory , and antioxidative properties . We hypothesized that the cranberry functional beverage ( CFB ) consumed for eight weeks improves gingival inflammation indices via inhibition of dental plaque , and alterations in antioxidant status , and systemic inflammation in patients with gingivitis . In this two-arm r and omized controlled study , fifty participants were divided into an experimental group ( CFB ) , administered daily with 750 ml CFB , or a control group administered the same amount of water . All patients underwent nonsurgical PT prior to the intervention . Gingival ( GI ) and bleeding on probing ( BoP ) indices of inflammation , plaque ( PI ) and approximal plaque ( API ) indices of dental plaque deposition , saliva and serum total antioxidant status ( TAS ) , serum malonylodialdehyde level ( MDA ) , and interleukin 1-beta level ( IL-1beta ) were measured pre- and postintervention . A risk of caries development was determined by Streptococcus mutans ( SM ) and Lactobacillus spp . ( LAB ) counts in supragingival dental plaque . Changes in GI and PI but not BoP and API were significantly more pronounced in the CFB group compared to the control group . Serum or saliva TAS , IL-1beta , and MDA did not differ between groups . The number of SM reduced in CFB , but not in the control group . We demonstrated that the consumption of CFB improves gingival and plaque indices without posing a risk of caries development . Thus CFB can be recommended as a safe adjunct for nonsurgical PT in patients with gingivitis |
2,660 | 21,412,868 | Lung function ( measured as forced expired volume in one second ) was higher and exacerbations of lung infection ( by different measures ) were less in the antibiotic-treated group .
Resistance to antibiotics increased more in the antibiotic-treated group than in placebo group when results were reported .
No auditory or renal impairment was found ; analysis showed tinnitus , voice alteration , hemoptysis and cough were more frequent with tobramycin than placebo .
AUTHORS ' CONCLUSIONS Inhaled antibiotic treatment probably improves lung function and reduces exacerbation rate , but a pooled estimate of the level of benefit is not possible .
The best evidence is for inhaled tobramycin . | BACKGROUND Inhaled antibiotics are commonly used to treat persistent airway infection that contributes to lung damage in people with cystic fibrosis ( CF ) .
OBJECTIVES To examine the evidence that inhaled antibiotic treatment in people with CF reduces frequency of exacerbations of infection , and improves lung function , quality of life and survival .
To examine adverse effects of inhaled antibiotic treatment . | RATIONALE Inhaled tobramycin has been shown to transiently clear Pseudomonas from lower airways in early cystic fibrosis ( CF ) , but does not markedly reduce lung inflammation , a key factor in disease progression . OBJECTIVE Test the hypothesis that systemic antibiotics are more effective than inhaled antibiotics for reducing lower airways inflammation . METHODS Clinical ly stable CF children with recent Pseudomonas were r and omized to receive 4 weeks of inhaled tobramycin or 2 weeks of systemic antibiotics ( intravenous ceftazidime and tobramycin ) . Bronchoalveolar lavage fluid was obtained just before and 4 - 6 weeks after treatment . The primary outcome was change in % neutrophils in lavage fluid . RESULTS Fifteen subjects ( inhaled = 6 , systemic = 9 ) completed the protocol . Three Systemic Group subjects could not have central venous access established and were treated with oral ciprofloxacin ( plus inhaled tobramycin ) for 2 weeks as an alternative " systemic " regimen , per protocol . Groups were well matched in age , markers of disease severity , and initial % neutrophils . The Systemic Group showed a modest median change in percent neutrophils ( -7 % ) which was not statistically significant compared to inhaled ( + 5.4 % , P = 0.07 ) . However , the Systemic Group had significantly greater reductions in total cells ( -50 % vs. -3 % , P < 0.01 ) and neutrophils ( -74 % vs. -10 % , P = 0.02 ) per ml lavage fluid . Both groups had reduced bacterial quantity after treatment , but there was no significant difference between groups . CONCLUSIONS In clinical ly stable children with CF , systemic antibiotics result in greater short-term reduction in lower airways inflammation than inhaled antibiotics Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract , completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo . The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo BACKGROUND Pulmonary administration of colistin is one of the antimicrobial treatments used in Cystic Fibrosis ( CF ) patients chronically infected with Pseudomonas aeruginosa . Dry powder inhalation of colistin may be an attractive alternative to nebulization of colistin . However , nebulized colistin can cause bronchoconstriction in CF patients . Therefore , in the progress of developing a dry powder formula , the choice of the inhaler and its contents should be guided by optimal efficacy and the least possible side effects . To investigate the side effects , a study was initiated to compare the tolerability of colistin sulphate to colistin sulphomethate per nebulization in CF- patients . METHODS Nine CF- patients chronically infected with P. aeruginosa participated in a double blind , r and omized cross over study . On two visits to the outpatient clinic , patients were su bmi tted to either nebulized colistin sulphate or colistin sulphomethate solution . Lung function tests were performed immediately before and 15 and 30 min after nebulization . RESULTS Nebulization of colistin sulphate caused a significant larger mean decrease in lung function compared to nebulized colistin sulphomethate . A significant decrease in mean changes ( SD ) in FEV1 at 30 min and FVC at 15 and 30 min after nebulization compared to baseline of -7.3 % ( 8.6 % ) , -5.7 % ( 7.3 % ) and -8.4 % ( 7.5 % ) respectively was seen after colistin sulphate nebulization compared to colistin sulphomethate ( P < 0.05 ) . Seven patients were not able to complete the nebulization of colistin sulphate because of throat irritation and severe cough . CONCLUSION Based on these results it was concluded that inhalation with nebulized colistin sulphate is not suitable for treatment of CF patients chronically infected with P. aeruginosa . Colistin sulphomethate is the drug of choice for pulmonary administration of colistin A r and omized cross-over study was undertaken to compare nebulized ( 1 ) ceftazidime with ( 2 ) a combination of gentamicin and carbenicillin , and ( 3 ) saline , each given for 4 months , in patients with cystic fibrosis infected with Pseudomonas aeruginosa . Mean peak expiratory flow on ceftazidime , 299 litres/min , and on gentamicin and carbenicillin , 297 litres/min , were greater than on saline , 278 litres/min ( P less than 0.02 and P less than 0.05 respectively ) . Similarly mean forced expiratory volume in 1 second on ceftazidime , 1.70 litres , and on gentamicin and carbenicillin , 1.70 litres , were greater than on saline , 1.48 litres ( P less than 0.02 and P less than 0.01 respectively ) . Mean forced vital capacity on gentamicin and carbenicillin , 2.93 litres , was also greater than on saline ( P less than 0.05 ) . We were unable to demonstrate any difference in efficacy between the antibiotic regimens . The patients were admitted to hospital less frequently during the study year compared with the previous year ( P less than 0.05 ) . Sixty-nine per cent of patients had a clinical ly significant ( 20 % ) increase in forced expiratory volume in 1 second on an antibiotic regimen compared with that on entry to study , but a minority of patients appear not to respond to this form of treatment BACKGROUND Aztreonam lysine for inhalation ( AZLI ) is being developed for treatment of CF patients with Pseudomonas aeruginosa airway infection . METHODS This double-blind , r and omized , placebo-controlled Phase 2 study evaluated the safety , tolerability and efficacy of 75 and 225 mg AZLI administered BID for 14 days using the eFlow Electronic Nebulizer ( Pari Innovative Manufacturers , Inc. , Midlothian , VA ) . Patients were 13 years and older with FEV1>or=40 % predicted , chronic P. aeruginosa infection , and had used no anti-pseudomonal antibiotics for 56 days . RESULTS Of 131 patients screened , 105 received AZLI or placebo . Mean age was 26 years and mean FEV1 percent predicted was 77 % at baseline . There was a statistically significant reduction , compared to placebo , in P. aeruginosa CFU density in each AZLI group at Days 7 and 14 ( P<0.001 ) . The planned primary analysis , percent change in FEV1 at Day 14 , demonstrated no statistically significant difference . Post hoc analysis demonstrated significant increase in FEV1 at Day 7 for the subset of patients with baseline FEV1<75 % predicted in the 225 mg AZLI group . Bronchodilator use was associated with greater improvement in FEV1 , as well as greater reduction in P. aeruginosa bacterial density and higher plasma aztreonam concentrations in the 225 mg AZLI group . Adverse events were similar between placebo and AZLI although there was a trend toward increased respiratory symptoms in the 225 mg AZLI group . CONCLUSION These data support the further development of AZLI and provide information for the design of subsequent studies Aminoglycoside-resistance mechanisms were characterized in Pseudomonas aeruginosa isolates from cystic fibrosis ( CF ) patients during a recent clinical trial of inhaled tobramycin . Impermeability , in which bacteria have reduced susceptibility to all aminoglycosides , was the predominant mode of resistance in isolates obtained both before and after 6 months of cyclic treatment with tobramycin or placebo administered by aerosol . Enzymatic resistance mechanisms were found in fewer than 10 % of resistant isolates . P. aeruginosa from individual patients could be grouped on the basis of genetic relatedness . When enzymatic resistance was involved , all isolates in a group had elevated tobramycin MICs . When impermeability occurred , MICs of a genotypic group varied from susceptible to resistant . These findings suggest that impermeability resistance occurs in only a fraction of the P. aeruginosa population in lungs of persons with CF and that this form of resistance arises by a process involving multiple small changes in MIC STUDY OBJECTIVE To determine the effect of long-term suppression of Pseudomonas aeruginosa on lung function and other clinical end points in adolescent patients with cystic fibrosis ( CF ) . DESIGN Two identical , r and omized , placebo-controlled trials followed by three open-label follow-on trials . SETTING Sixty-nine CF study centers in the United States . INTERVENTIONS Active drug consisting of a 300-mg tobramycin solution for inhalation ( TSI ) . PATIENTS One hundred twenty-eight adolescent CF patients ( aged 13 to 17 years ) with P aeruginosa and mild-to-moderate lung disease ( FEV(1 ) percent predicted > or = 25 % and < or = 75 % ) . MEASUREMENTS Pulmonary function , P aeruginosa colony forming unit density , incidence of hospitalization and IV antibiotic use , weight gain , and aminoglycoside toxicity were monitored . RESULTS At the end of the first three 28-day cycles of TSI treatment , patients originally r and omized to TSI and placebo treatments exhibited improvements in FEV(1 ) percent predicted of 13.5 % and 9.4 % , respectively . FEV(1 ) percent predicted was maintained above the value at initiation of TSI treatment in both groups . At the end of the last " on-drug " period ( 92 weeks ) , patients originally r and omized to TSI and placebo treatments showed improvements of 14.3 % and 1.8 % , respectively . Improvement in pulmonary function was significantly correlated with reduction in P aeruginosa colony forming unit density ( p = 0.0001 ) . The average number of hospitalizations and IV antibiotic courses did not increase over time . TSI treatment was associated with increased weight gain and body mass index . P aeruginosa susceptibility to tobramycin decreased slightly over time , but this was not correlated with clinical response . CONCLUSIONS TSI treatment improved pulmonary function and weight gain in adolescent patients with CF over a 2-year period of long-term , intermittent use The major cause of morbidity and mortality in patients with cystic fibrosis ( CF ) is respiratory disease ( Penketh et al. , Thorax 1987 ; 42 : 526 - 532 ) . Recent studies in the USA have shown that intermittent administration of inhaled tobramycin is beneficial to patients with CF who are chronically infected with Pseudomonas aeruginosa ( Ramsey et al. , N Engl J Med 1999 ; 340 : 23 - 30 ; Ramsey et al. , Proceedings of the 12th Annual North American Cystic Fibrosis Conference , 1998 , Montreal , Canada ; Ramsey et al. , Abstract from 23rd European Cystic Fibrosis Conference , 1999 , the Hague , Netherl and s ) . In Europe , the use of nebulised colistin in patients chronically infected with P. aeruginosa is widespread . A recently published study compared the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients . One hundred and fifteen patients were r and omised to receive either TNS or colistin in a multi-centre open-labelled study that assessed change from baseline in FEV(1 ) and sputum P. aeruginosa density . TNS produced a mean 6.7 % improvement in lung function ( P=0.006 ) , whilst there was no significant improvement in the colistin-treated patients . The TNS-treated patients had a significantly greater improvement in lung function than those treated with colistin ( P=0.008 ) . The safety profile of both treatments was good . We conclude that patients treated with TNS for 1 month experience improved lung function compared with patients treated with colistin Chronic infection with Pseudomonas aeruginosa is associated with progressive deterioration in lung function in cystic fibrosis ( CF ) patients . The purpose of this trial was to assess the efficacy and safety of tobramycin nebuliser solution ( TNS ) and nebulised colistin in CF patients chronically infected with P. aeruginosa . One-hundred and fifteen patients , aged ≥6 yrs , were r and omised to receive either TNS or colistin , twice daily for 4 weeks . The primary end point was an evaluation of the relative change in lung function from baseline , as measured by forced expiratory volume in one second % predicted . Secondary end points included changes in sputum P. aeruginosa density , tobramycin/colistin minimum inhibitory concentrations and safety assessment s. TNS produced a mean 6.7 % improvement in lung function ( p=0.006 ) , whilst there was no significant improvement in the colistin-treated patients ( mean change 0.37 % ) . Both nebulised antibiotic regimens produced a significant decrease in the sputum P. aeruginosa density , and there was no development of highly resistant strains over the course of the study . The safety profile for both nebulised antibiotics was good . Tobramycin nebuliser solution significantly improved lung function of patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa , but colistin did not , in this study of 1-month 's duration . Both treatments reduced the bacterial load OBJECTIVES This r and omized , double-blind , cross-over study evaluated the risk of bronchoconstriction with two preparations of inhaled tobramycin in children with cystic fibrosis ( CF ) infected with Pseudomonas aeruginosa with and without airway hyperreactivity . DESIGN Of 19 children with CF ( age range , 7 to 16 years ) with mild-to-moderate pulmonary disease , 10 children were at high risk ( HR ) for bronchospasm ( family history of asthma and previous response to bronchodilators ) and 9 children were at low risk ( LR ) for bronchospasm ( no family history of asthma or previous response to bronchodilators ) . Two solutions of tobramycin were administered : ( 1 ) 80 mg in a 2-mL vial diluted with 2 mL of saline solution containing the preservatives phenol and bisulfites ( IV preparation ) ; and ( 2 ) 300 mg in a preservative-free preparation in a 5-mL solution . Following a bronchodilator-free period of 12 h , the patients inhaled either one or the other preparation in r and om order on two different occasions , 2 weeks apart . RESULTS Prechallenge and postchallenge results for the LR group showed a percentage of fall in FEV(1 ) ( DeltaFEV(1 ) ) of 12 + /- 9 % ( mean + /- SD ) for the IV preparation , compared to 4 + /- 5 % for the preservative-free preparation ( p = 0.046 ) . An DeltaFEV(1 ) of > 10 % was seen in six of nine patients for the IV preparation and in one of nine patients for preservative-free preparation . For the HR group , the DeltaFEV(1 ) was 17 + /- 13 % for the IV-preparation group , compared to 16 + /- 12 % for the preservative-free group ( p = 0.4 ) . In this group , equal numbers of patients ( 8 of 10 patients ) had an DeltaFEV(1 ) > 10 % after inhaling each preparation . The largest DeltaFEV(1 ) was 44 % ( HR group with the preservative-free preparation that forced the early termination of inhalation ) . CONCLUSIONS Both preparations caused significant bronchoconstriction in the HR group , and the preservative-containing IV preparation caused more bronchospasm in LR group than the preservative-free solution . Heightened airway reactivity in children with CF places them at risk of bronchospasm from inhalation therapy In chronic Pseudomonas aeruginosa pulmonary infection of patients with cystic fibrosis ( CF ) , antibiotic therapy generally fails to eradicate the bacterial pathogen . The mucoid bacterial phenotype , high sputum production by the host , and low airway levels of antibiotics seem to be responsible for the observed decrease in antibiotic efficacy . We hypothesized that early antibiotic treatment by inhalation in CF patients may be able to prevent or at least delay airway infection . In a prospect i ve placebo-controlled , double-blind , r and omized multicenter study , 22 CF patients received either 80 mg b.i.d . of aerosolized tobramycin or placebo for a period of 12 months shortly after the onset of P. aeruginosa pulmonary colonization . Two patients in the tobramycin and six patients in the placebo group stopped inhalation before the 12 month treatment period . Using life table analysis , the time to conversion from a P. aeruginosa-positive to a P. aeruginosa-negative respiratory culture was significantly shorter in the tobramycin-treated group than in the placebo group ( P < 0.05 , log rank test ) . Lung function parameters and markers of inflammation did not change in either group during treatment . The results of this study suggest that early tobramycin inhalation may prevent and /or delay P. aeruginosa pulmonary infection in CF patients BACKGROUND Inhalation of hypertonic nebulised colistin causes chest tightness and is a reason for discontinuing the treatment . This study examines the relationship of chest tightness and change in lung function in response to the inhalation of a range of tonicities of nebulised colistin and their influence on patients ' preference . METHODS Twenty seven adult patients with cystic fibrosis and a mean forced expiratory volume in one second ( FEV1 ) of 54 % predicted ( range 24 - 98 ) were studied . They inhaled a nebulised solution of hypertonic , isotonic , and hypotonic colistin over three consecutive days in r and om order in a double blind fashion . Measurements of chest tightness , using a visual analogue scale ( VAS ) , and FEV1 were recorded before and 0 , 15 , 30 , 60 , and 90 minutes following inhalation . The solution preferred by each patient was determined at the end of the three days . RESULTS All tonicities caused a significant fall in FEV1 % predicted and an increase in chest tightness , with no differences between the solutions . However , the mean ( SE ) time to the maximum fall in FEV1 % predicted was significantly different between the solutions ( hypertonic 7.8 ( 2.1 ) min , isotonic 19.2 ( 5.5 ) min , and hypotonic 34.2 ( 5.9 ) min ) with a mean difference ( 95 % CI ) between hypotonic and hypertonic solutions of 28.04 ( 14.6 to 41.5 ) min , between isotonic and hypertonic solutions of 12.0 ( -0.1 to 24.1 ) min , and between hypotonic and isotonic solutions of 15.6 ( 1.8 to 29.4 ) min . Positive correlations existed for the maximum fall in FEV1 % predicted between the hypertonic and isotonic solutions ( r = 0.62 , p < 0.001 ) and between the hypotonic and isotonic solutions ( r = 0.64 , p < 0.001 ) . There was no correlation between the objective and subjective measurements for any solution . The patients ' preference varied . CONCLUSIONS All tonicities of colistin caused equal symptoms of chest tightness and reduction in pulmonary function . It is recommended that the patient is challenged with nebulised colistin before prescription of the drug and that the challenge is preceded by an inhaled bronchodilator . Most of the patients preferred the isotonic or hypotonic solutions . The isotonic solution reflects a fall in FEV1 representative of all the solutions . The fall in FEV1 to the hypotonic solution occurred over a longer period and may be better tolerated by some patients Abstract Background and aim Progressive respiratory failure due to Pseudomonas aeruginosa colonization is the most significant morbidity in patients with cystic fibrosis ( CF ) . This trial was design ed to investigate the efficacy and safety of a highly concentrated ( 300mg/4mL ) tobramycin solution for inhalation ( TSI ) [ Bramitob ® ] in patients with CF and P. aeruginosa infection . Methods Fifty-nine patients were r and omized to receive a 4-week treatment with tobramycin or placebo administered twice daily via the Pari LC Plus ® nebulizer and Pari TurboBoy ™ compressor , followed by a 4-week run-out phase . Pulmonary function ( forced expiratory volume in 1 second [ FEV1 ] , forced vital capacity [ FVC ] , and forced expiratory flow at the midportion of vital capacity [ FEF25–75 % ] ) , P. aeruginosa susceptibility , microbiologic results , and in vitro minimum inhibitory concentration for 90 % of strains ( MIC90 ) were the efficacy outcome measures , while safety was monitored by the recording of adverse events , audiometry ( bone conduction at 250–8000Hz frequency ) , laboratory tests , physical examination and general health condition . The concentration of tobramycin attained in sputum was measured in a cohort of 21 patients . Results FEV1 significantly increased from baseline in the tobramycin group compared with no change in the placebo group : the absolute difference between groups ( intent-to-treat population ) of predicted normal was 13.2 % at week 2 ( p = 0.002 ) and 13.3 % at week 4 ( p = 0.003 ) . Significant differences in favor of the tobramycin group were also observed for FVC and FEF25–75 % . The microbiologic results at the end of the treatment period ( P. aeruginosa-negative culture , persistence , superinfection ) showed a significantly better outcome in the tobramycin group compared with placebo ( p = 0.033 ) . The effects of tobramycin on pulmonary function and microbiology were not maintained at the end of the run-out phase . Mean sputum concentrations of tobramycin after the first dose ( 695.6 ± 817.0 µg/mL ) were similar to those measured after the last dose ( 716.9 ± 799 µg/mL ) and were superior to the detected specific MIC90.The proportion of patients with drug-related adverse events was lower in the tobramycin group and no signs of renal or auditory toxicity were observed . Conclusions The 4-week administration of a highly concentrated TSI significantly improved pulmonary function and microbiologic outcome compared with placebo and was well tolerated . The results of this study should be confirmed in further long-term trials in larger population BACKGROUND AND METHODS We conducted two multicenter , double-blind , placebo-controlled trials of intermittent administration of inhaled tobramycin in patients with cystic fibrosis and Pseudomonas aeruginosa infection . A total of 520 patients ( mean age , 21 years ) were r and omly assigned to receive either 300 mg of inhaled tobramycin or placebo twice daily for four weeks , followed by four weeks with no study drug . Patients received treatment or placebo in three on-off cycles for a total of 24 weeks . The end points included pulmonary function , the density of P. aeruginosa in sputum , and hospitalization . RESULTS The patients treated with inhaled tobramycin had an average increase in forced expiratory volume in one second ( FEV1 ) of 10 percent at week 20 as compared with week 0 , whereas the patients receiving placebo had a 2 percent decline in FEV1 ( P<0.001 ) . In the tobramycin group , the density of P. aeruginosa decreased by an average of 0.8 log10 colony-forming units ( CFU ) per gram of expectorated sputum from week 0 to week 20 , as compared with an increase of 0.3 log10 CFU per gram in the placebo group ( P<0.001 ) . The patients in the tobramycin group were 26 percent ( 95 percent confidence interval , 2 to 43 percent ) less likely to be hospitalized than those in the placebo group . Inhaled tobramycin was not associated with detectable ototoxic or nephrotoxic effects or with accumulation of the drug in serum . The proportion of patients with P. aeruginosa isolates for which the minimal inhibitory concentration of tobramycin was 8 microg per milliliter or higher increased from 25 percent at week 0 to 32 percent at week 24 in the tobramycin group , as compared with a decrease from 20 percent at week 0 to 17 percent at week 24 in the placebo group . CONCLUSIONS In a 24-week study of patients with cystic fibrosis , intermittent administration of inhaled tobramycin was well tolerated and improved pulmonary function , decreased the density of P. aeruginosa in sputum , and decreased the risk of hospitalization Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospect i ve double-blind placebo-controlled study of colistin inhalation . Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline . Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group ( 18 versus 11 ) . Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score , maintenance of pulmonary function and inflammatory parameters . We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy BACKGROUND Dry powder inhalation ( DPI ) may be an alternative to nebulisation of drugs in the treatment of chest infections in cystic fibrosis ( CF ) patients . In a pilot study the feasibility of a colistin dry powder inhaler ( prototype Twincer ) by a single dose in CF- patients was assessed and compared to nebulised colistin . METHODS Ten CF- patients , chronically infected with P. aeruginosa , participated in a r and omised cross over study . On two visits to the outpatient clinic , patients inhaled colistin sulphomethate as 25 mg dry powder ( Twincer ) or as 158 mg nebulised solution ( Ventstream nebuliser , PortaNeb compressor ) . Pulmonary function tests were performed before , 5 and 30 min after inhalation . Serum sample s were drawn prior to each dose and at 15 , 45 min , 1.5 ; 2.5 ; 3.5 and 5.5 h after inhalation . RESULTS The DPI was well tolerated by the patients : no significant reduction in FEV1 was observed . Relative bioavailability of DPI to nebulisation was approx . 140 % based on actual dose and approx . 270 % based on drug dose label cl aim . CONCLUSIONS The colistin DPI ( Twincer inhaler ) is well tolerated and appreciated by CF- patients . Optimisation with respect to particle size and internal resistance of the inhaler is necessary to attain equivalent pulmonary deposition to liquid nebulisation OBJECTIVE The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin , supplemented by amikacin inhalation therapy . METHODS Twenty-one patients were r and omly assigned to oral ciprofloxacin alone ( Group I ) and 23 received ciprofloxacin plus inhaled amikacin ( Group II ) . RESULTS Negative sputum cultures were achieved in 34 patients ( 77 % ) at the end of intensive therapy ( 19 Group I and 15 Group II ) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I ( 26 % ) and in 8 of the 15 responders in Group II ( 53 % ) . Resistance to ciprofloxacin was found in 7 of 31 ( 23 % ) sputum isolates at the end of ciprofloxacin therapy . During maintenance therapy , continued improvement in clinical symptoms was observed in 14 patients in both treatment groups ; 6 in each group had further improvements whereas only 4 patients were clinical failures . There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance . Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age . There were no severe or serious adverse events , no signs of quinolone-related arthropathy and no growth impairment . CONCLUSION Ciprofloxacin was efficacious , safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients . These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted The effect of prophylactic antibiotics on bacterial colonization of the respiratory tract and on general progression of cystic fibrosis was studied in a two-year prospect i ve study of 47 mildly to moderately affected patients . One group of patients received inhaled cephaloridine and the other received no inhaled antibiotic ; both groups received cloxacillin orally . Carriage of Haemophilus influenzae was greater in the group not receiving inhaled antibiotic ( 55 % vs 20 % ) . Rates of carriage of Staphylococcus aureus ( 23 % ) . Pseudomonas aeruginosa ( greater than 90 % ) . Pseudomonas cepacia ( 45 % ) , and other organisms were similar in both groups . There were no significant differences between the two groups in incidence of respiratory tract infections or hospital admissions , clinical scores , radiologic scores , or rate of change of pulmonary function . Although continuous antistaphylococcal antibiotic prophylaxis may be successful in suppressing colonization with S. aureus , it may also contribute to the high rates of carriage of Ps . aeruginosa and Ps . cepacia observed in patients with cystic fibrosis Burkholderia cepacia is an aggressive pathogen that colonizes cystic fibrosis ( CF ) patients , causing greatly increased morbidity and mortality . It is resistant to most antibiotics , but sensitive in vitro to a novel agent , taurolidine . This has not previously been used against B. cepacia , nor given in nebulized form . We assessed the effect of nebulized taurolidine on United Kingdom epidemic ( ET12 ) B. cepacia infection in 20 adult CF patients attending our regional adult cystic fibrosis outpatient clinic using a prospect i ve , r and omized , double-blinded placebo-controlled crossover trial . Nebulized taurolidine ( 4 mL 2 % solution ) or saline ( 4 mL 0.9 % solution ) was given twice daily . Each arm lasted 4 weeks , with a 2-week intervening washout period . Sputum B. cepacia colony counts ( primary outcome measure ) , spirometry , and symptoms ( secondary outcome measures ) were assessed . Eighteen patients completed the study . There was no change in B. cepacia colony counts or spirometry , nor symptom scores . We conclude that , although taurolidine is well tolerated in nebulized form , in this study it had no in vivo anti-B. cepacia activity OBJECTIVE Two identical 24-week , double-blind , placebo-controlled trials of tobramycin solution for inhalation ( TOBI [ PathoGenesis Corporation , Seattle , Washington ] ) in cystic fibrosis patients with chronic Pseudomonas aeruginosa infection were conducted in the United States . The aim of the present study was to extrapolate the US trial data to a Canadian setting , using Canadian costs to estimate the savings in direct medical costs that might result from use of a similar 24-week TOBI regimen versus usual care in 2 Canadian provinces . BACKGROUND Cystic fibrosis is a genetic disease in which persistent respiratory infection , usually due to P. aeruginosa infection , is the major cause of morbidity and mortality . METHODS The US trials demonstrated that TOBI produced significant improvements in pulmonary function test results , reduced sputum levels of P. aeruginosa , and result ed in a 26 % reduction in the probability of hospitalization ( 95 % CI , 2%-43 % vs placebo in the clinical trials ) . Individual patient data from the US trials were used to calculate the mean number of days in hospital as well as the mean number of days of home intravenous or oral antibiotic therapy . To adjust for Canadian pricing , pertinent economic data were obtained from Statistics Canada and the Ontario and Quebec health ministries . Demographic and baseline data were obtained from health surveys conducted by the Canadian Cystic Fibrosis Foundation . RESULTS Economic analysis showed that the use of TOBI for 24 weeks would result in estimated mean per-patient savings in direct medical costs ( in Canadian dollars ) of $ 4055 in Ontario and $ 4916 in Quebec , which would substantially offset the Canadian acquisition price of $ 8602 for the same 24-week period . CONCLUSIONS Assuming that the percentage of reduction in hospital days observed in the US trials would also occur in the Canadian clinical setting , use of TOBI would reduce the use of health care services , particularly hospital days , and lead to substantial savings in direct medical costs that would offset its acquisition price . Whether this reduction actually occurs after TOBI enters the Canadian market is a subject for future investigation Abstract Background and objectives To compare in vitro characteristics and pharmacokinetics of Bramitob ® , a preservative-free tobramycin solution for nebulization , and Tobi ® in patients with cystic fibrosis ( CF ) and Pseudomonas aeruginosa infection . Methods In vitro characteristics of Bramitob ® and Tobi ® were evaluated using Pari TurboBoy ™ /LC Plus ® and the Systam 290 LS ™ nebulizers . In the r and omized , double-blind , two-way crossover pharmacokinetic study , 11 patients with CF received a single nebulized dose ( 300 mg ) of Bramitob ® or Tobi ® , separated by a 7-day washout period . Plasma and sputum tobramycin concentrations were measured immediately before and over 24 hours after administration . Results Bramitob ® and Tobi ® performed alike during nebulization . The fine particle fraction was 33–37 % and the mass median aerodynamic diameter was < 5 µm . Nine patients completed the pharmacokinetic study . Tobramycin plasma profiles after administration of Bramitob ® or Tobi ® were similar , with a peak at 90 and 72 minutes after inhalation of Bramitob ® and Tobi ® , respectively . The elimination half-life was ∼5 hours for both products . The relative bioavailability of Bramitob ® to Tobi ® was 1.01 , indicating comparable systemic exposure . Peak sputum concentration of tobramycin was 816 ± 681 µg/g for Tobi ® and 1289 ± 851 µg/g for Bramitob ® and was > 400 µg/g ( threshold sufficient for an antibacterial effect against P. aeruginosa ) in 5 out of 9 patients receiving Tobi ® and 8 out of 9 patients receiving Bramitob ® . All adverse events were considered mild and judged not related to the study drugs . Conclusions In vitro performance of Bramitob ® was similar when nebulized with Pari TurboBoy ™ /LC Plus ® and Systam 290 LS ™ nebulizers and comparable to that of Tobi ® . The systemic bioavailability of tobramycin was similar after administration of either Bramitob ® or Tobi ® ; however , in sputum sample s the tobramycin peak concentration was slightly greater after administration of Bramitob ® than after Tobi ® BACKGROUND Direct aerosol delivery of aminoglycosides such as tobramycin to the lower airways of patients with cystic fibrosis may control infection with Pseudomonas aeruginosa and improve pulmonary function , with low systemic toxicity . We conducted a r and omized crossover study to evaluate the safety and efficacy of aerosolized tobramycin in patients with cystic fibrosis and P. aeruginosa infections . METHODS Seventy-one patients with stable pulmonary status were recruited from seven U.S. centers for the treatment of cystic fibrosis and r and omly assigned to one of two crossover regimens . Group 1 received 600 mg of aerosolized tobramycin for 28 days , followed by half-strength physiologic saline ( placebo ) for two 28-day period . Group 2 received placebo for 28 days , followed by tobramycin for two 28-day periods . Pulmonary function , the density of P. aeruginosa in sputum , ototoxicity , nephrotoxicity , and the emergence of tobramycin-resistant P. aeruginosa were monitored . RESULTS In the first 28-day period , treatment with tobramycin was associated with an increase in the percentage of the value predicted for forced expiratory volume in one second ( 9.7 percentage points higher than the value for placebo ; P < 0.001 ) , forced vital capacity ( 6.2 percentage points higher than the value for placebo ; P = 0.014 ) , and forced expiratory flow at the midportion of the vital capacity ( 13.0 percentage points higher than the value for placebo ; P < 0.001 ) . A decrease in the density of P. aeruginosa in sputum by a factor of 100 ( P < 0.001 ) was found during all periods of tobramycin administration . Neither ototoxicity nor nephrotoxicity was detected . The frequency of the emergence of tobramycin-resistant bacteria was similar during both tobramycin and placebo administration . CONCLUSIONS The short-term aerosol administration of a high dose of tobramycin in patients with clinical ly stable cystic fibrosis is an efficacious and safe treatment for endobronchial infection with P. aeruginosa STUDY OBJECTIVE Inhaled colistin is used for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis ( CF ) patients despite reports of chest tightness and bronchospasm . The main objective of the study was to assess whether bronchospasm occurred in pediatric CF patients with or without clinical evidence of airway hyperreactivity . DESIGN AND METHODS A prospect i ve placebo-controlled clinical trial with crossover design was devised using challenge tests with 75 mg colistin in 4 mL saline solution and a placebo solution of the same osmolarity using a breath-enhanced nebulizer for administration . Subjects were recruited as follows : high risk ( HR ) for bronchospasm due to a personal history of recurrent wheezing , a family history of asthma and /or atopy , or bronchial lability , as demonstrated in pulmonary function tests ; or low risk ( LR ) without these characteristics . RESULTS The mean FEV(1 ) ( expressed as the mean [ + /- SD ] fall from baseline ) of the HR group ( n = 12 ) fell 12 + /- 9 % after placebo was administered , and fell 17 + /- 10 % after colistin was administered . For the LR group ( n = 8) , the mean FEV(1 ) fell 9 + /- 4 % following placebo administration and 13 + /- 8 % following colistin administration . There was a greater number of subjects in the HR group compared to the LR group , which had a mean fall in FEV(1 ) of > /= 15 % ( p < 0.01 ) after inhaling colistin . The differences between placebo and colistin therapy in the LR group were not significant . CONCLUSION The results demonstrated that colistin can cause bronchospasm , particularly in those patients with coexisting CF and asthma Nebulized antibiotics are being used increasingly in children with cystic fibrosis . We assessed the effect of nebulized antibiotic solutions of varying tonicity on lung function in 12 children aged 5 - 15 yrs with cystic fibrosis . Baseline forced expiratory volume in one second and ( FEV1 ) was measured , followed by a single nebulization of normal saline ( 272 mosmol.kg-1 ) , tobramycin ( 248 mosmol.kg-1 ) , or ticarcillin ( 3,080 mosmol.kg-1 ) . All children received each of these , administered r and omly , one per day . FEV1 was remeasured 5 , 15 and 30 min after completion of the nebulization . Ticarcillin ( mean fall 10.7 % ( SD 8.9 ) ) caused a larger fall in FEV1 than normal saline ( 4.8 % ( 4.3 ) , p less than 0.05 ) . The fall in FEV1 for ticarcillin was greater than for tobramycin ( 1.2 % ( 2.0 ) , p less than 0.05 ) . Normal saline did not result in a significantly larger fall in FEV1 than tobramycin ( p greater than 0.05 ) . Bronchoconstriction to ticarcillin persisted at 30 min . We conclude that nebulized antibiotics can affect lung function in children with cystic fibrosis if the solutions are hypertonic Our objective was to study the effect of tobramycin solution for inhalation ( TSI ; TOBI , Chiron Corp. ) on lung function decline rate in 400 young persons with cystic fibrosis ( CF ) and mild lung disease . Effects on hospitalization , antibiotic use , school days missed , and nutritional status also were determined . This was an open-label , r and omized ( stratified by sex and age group , i.e. , 6 - 10 and 11 - 15 years ) , parallel-group , multicenter study . Routine subject management ( control group ) was compared to routine management plus 28 days of twice-daily TSI inhalation , followed by 28 days off the drug ( TSI group ) for 56 weeks . Primary efficacy endpoints included rate of lung function decline ( as measured by forced expiratory volume in 1 sec ; FEV(1 ) ) , hospitalization , and concomitant antibiotic use . Safety was assessed by analysis of treatment-emergent adverse events . Only 184 of 400 planned subjects were recruited and r and omized ( 93 to the TSI group , and 91 to the control group ) . Enrollment was ended after 2 years because of difficult recruitment . An interim safety review showed a 2.42-fold risk of respiratory hospitalization for control group subjects ( P = 0.020 ) , and the study was terminated . Sixty-three subjects ( 34.2 % ) completed the entire study ( 30 in the TSI group , or 32.3 % ; and 33 in the control group , or 36.3 % ) . Significantly fewer TSI subjects were hospitalized for worsening of respiratory symptoms ( 11.0 % vs. 25.6 % ; P = 0.011 ) , and fewer TSI subjects were hospitalized overall ( 16.5 % vs. 27.8 % ; P = 0.065 ) . Fewer TSI subjects received antibiotics other than the study drug ( 78.0 % vs. 95.6 % ) , and significantly fewer received oral antibiotics ( 76.9 % vs. 91.1 % ; P = 0.009 ) . No other safety or adverse event differences were observed . In conclusion , significant reductions in respiratory hospitalizations , concomitant antibiotic use , and a trend towards improvement in percent predicted forced expiratory flow ( FEF(25 - 75 ) ) provide evidence of a clinical benefit of TSI use in young persons with CF and mild lung disease . An effect on lung function decline rate could not be evaluated as planned , due to inadequate enrollment and early study termination We conducted a double-blind , placebo-controlled , multicenter , r and omized trial to test the hypothesis that 300 mg of tobramycin solution for inhalation administered twice daily for 28 days would be safe and result in a profound decrease in Pseudomonas aeruginosa ( Pa ) density from the lower airway of young children with cystic fibrosis . Ninety-eight subjects were to be r and omized ; however , the trial was stopped early because of evidence of a significant microbiological treatment effect . Twenty-one children under age 6 years were r and omized ( 8 active ; 13 placebo ) and underwent bronchoalveolar lavage at baseline and on Day 28 . There was a significant difference between treatment groups in the reduction in Pa density ; no Pa was detected on Day 28 in 8 of 8 active group patients compared with 1 of 13 placebo group patients . We observed no differences between treatment groups for clinical indices , markers of inflammation , or incidence of adverse events . No abnormalities in serum creatinine or audiometry and no episodes of significant bronchospasm were observed in association with active treatment . We conclude that 28 days of tobramycin solution for inhalation of 300 mg twice daily is safe and effective for significant reduction of lower airway Pa density in young children with cystic fibrosis The development of drug resistance is a major theoretical concern with the long-term delivery of aerosolized antibiotics via inhalation . A r and omized , placebo-controlled , double-blind study , which compared inhaled tobramycin plus st and ard cystic fibrosis ( CF ) care to placebo plus st and ard CF care , examined the following microbiological parameters : percentage of patients with at least one Pseudomonas aeruginosa ( PA ) strain with a minimal inhibitory concentration ( MIC ) > 16 microg/mL ( ie , the breakpoint for tobramycin resistance delivered by the parenteral route ) ; changes in the levels of the lowest concentration required to inhibit the growth of 50 % of strains tested ( MIC(50 ) ) and 90 % of strains tested ( MIC(90 ) ) ; the percentage of patients with an increase , decrease , or change in the MIC of the most resistant and most prevalent PA strains ; and the percentage of patients in whom the PA strain with the highest MIC also was the most prevalent . During the first 6 months , which included three on-drug and off-drug cycles of 4 weeks ' duration each , the percentage of tobramycin-treated patients with at least one PA isolate and with an MIC > 16 microg/mL was 13 % at baseline , 26 % at 20 weeks , and 23 % at 24 weeks vs 10 % , 17 % , and 8 % , respectively , for placebo-treated patients . No significant change was observed in MIC(50 ) at 20 and 24 weeks . The increase in MIC(90 ) was not statistically significant . At 24 weeks , there was no increase in the percentage of patients in either group in whom the PA strain with the highest MIC became most the prevalent strain . After the third on-drug cycle , 33 % of the tobramycin group showed an increase in the MIC of the strain with the highest MIC . This decreased to 26 % after 1 month off drug therapy . A preliminary analysis of the 12-month and 18-month data showed a decrease in the proportion of resistant PA isolates after each off-drug cycle . This return to susceptibility following an off-drug cycle was not observed at 24 months . The mechanism of resistance in this setting is believed to be increased impermeability to drug . At all time points , pulmonary function improved even in patients with MICs of > or = 128 microg/mL. At 6 months , no increase was seen in the rates of superinfection with tobramycin-resistant , Gram-negative pathogens . Increases in Stenotrophomonas maltophilia were detected in patients after 18 and 24 months of tobramycin therapy and were similar to those rates in patients receiving placebo . These rates may be independent of inhalation therapy Twenty-seven patients with cystic fibrosis and endobronchial colonization with Pseudomonas aeruginosa were r and omly assigned to inhale either 2 mL saline ( 12 patients ) or 80 mg tobramycin solution ( 15 patients ) 3 times daily . One control patient died ; all others completed the study ( mean duration 32 months ) . No significant differences were found between the two groups at enrollment . The treatment group showed no change , while the control group had a significant decline in both pulmonary function and clinical status over the study period . Individually , 11 of 12 patients in the control group showed deterioration , while 9 of 15 in the treatment group with susceptible P. aeruginosa at enrollment acquired resistant organisms . There was no evidence of significant nephro- or ototoxicity . Although inhaled tobramycin appeared to arrest the decline in pulmonary status , further work is required to identify patients most likely to respond STUDY OBJECTIVE To determine whether adequate concentrations of a new formulation of tobramycin could be delivered to the lower respiratory tract of patients with cystic fibrosis ( CF ) using a jet nebulizer delivery system . DESIGN A multicenter , open-label , r and omized , crossover study . SETTING Ten tertiary care , university-affiliated , teaching hospitals in the United States . PATIENTS AND CONTROL SUBJECTS Sixty-eight patients recruited from 10 CF Foundation centers and who were at least 8 years of age , had a diagnosis of CF , and expectorated daily sputum . No control subjects enrolled . INTERVENTIONS Each patient received one administration of aerosolized tobramycin from each of the three nebulizer systems in r and om order . Each administration was separated by a minimum of 48 h. The two jet nebulizer systems tested were the Sidestream ( Medic-Aid ; Sussex , UK ) , and the Pari LC ( Pari Respiratory Equipment ; Richmond , Va ) , with a DeVilbiss Pulmoaide compressor ( DeVilbiss Health Care ; Somerset , Pa ) , both administering 300 mg tobramycin in 5 mL of 1/4 normal saline solution ( NS ) . Patients were also administered 600 mg tobramycin in 30 mL of 1/2 NS with the UltraNeb 99/100 ( DeVilbiss ) . MEASUREMENTS Sputum and serum tobramycin concentration and pulmonary function were monitored . An adequate peak sputum tobramycin concentration was defined as > 128 microg/g sputum at any of three time points ( 10 , 60 , or 120 min ) after completion of treatments . RESULTS The peak tobramycin concentrations in expectorated sputum were 687+/-663 microg/g ( mean+/-SD ) with the Pari LC and 489+/-402 microg/g with the Sidestream . Adequate peak sputum tobramycin concentration was achieved in 93 % of the patients with the Sidestream , and in 87 % of the patients with the Pari LC . Peak sputum concentrations were found to be substantially higher when patients received tobramycin administered with the UltraNeb 99/100 , 1,498+/-1,331 microg/g with 30 % of patients having levels exceeding 2,000 microg/g . Serum tobramycin concentrations were < or = 4 microg/mL for all patients following administration with each nebulizer . CONCLUSIONS Adequately high sputum tobramycin concentrations were documented in sputum in > 85 % of patients following the administration of 300 mg/5 mL formulation of tobramycin aerosolized by the two jet nebulizer delivery systems , Sidestream and Pari LC . The single tobramycin administration delivered by these two systems is well-tolerated Aerosolized antibiotics are associated with a high treatment burden that can result in non-adherence to chronic therapy . We evaluated the pharmacokinetics ( PK ) and safety of tobramycin inhalation powder ( TIP ) , a novel dry-powder formulation design ed to deliver a high payload of tobramycin topically to the lungs for management of chronic Pseudomonas aeruginosa infections . This was a multi-center , open-label , sequential-cohort , single-dose , dose-escalation study using the st and ard 300 mg dose of tobramycin solution for inhalation ( TSI ) as an active control . Subjects were r and omized to TIP or TSI in a 3:1 ratio in each of five cohorts . Measurements included serum and sputum tobramycin concentrations , administration time , serum chemistries , acute change in lung function , and adverse events ( AEs ) . Out of 90 r and omized subjects , 86 had data for safety analysis ; and 84 had data for PK analysis . Serum tobramycin PK profiles were similar for TIP and TSI . Four capsules of 28 mg TIP ( total tobramycin dose 112 mg ) produced comparable systemic exposure to 300 mg TSI , in less than one-third the administration time . The most common AEs associated with TIP were cough ( 20 % ) and dysgeusia ( 17 % ) . TIP allows for faster and more efficient pulmonary delivery of tobramycin than TSI and has a safety profile that supports continued clinical investigation . The increased rate of local respiratory tract irritation noted with TIP is not unexpected with a high-payload powder formulation . The development of dry powder inhaled antibiotics may represent an important advance in the treatment of chronic lung infections BACKGROUND Inhaled tobramycin has been shown to improve lung function in cystic fibrosis ( CF ) patients chronically infected with Pseudomonas aeruginosa . However , to date no comparative data are available for different dose regimens used in clinical practice . OBJECTIVES To compare the clinical efficacy of the two most commonly used treatment regimens of inhaled tobramycin in patients with CF . METHODS In an open crossover study of CF patients , subjects were r and omly allocated to receive either 80 mg tobramycin twice-daily continuous treatment or 300 mg tobramycin twice daily in cycles of 28 days on and 28 days off treatment . After three months , patients were switched to the alternative treatment regimen . RESULTS A total of 32 patients with a mean ( + /- SD ) age of 18.5+/-8.6 years were included in the study . Compared with the treatment period using colistin , forced expiratory volume in 1 s decreased by -2.1+/-13.8 % in the 80 mg tobramycin group and increased by + 2.3+/-13.0 % in the 300 mg group . Similar changes were observed in forced vital capacity ( -2.5+/-12.9 % in the 80 mg tobramycin group versus + 2.5+/-9.6 % in the 300 mg tobramycin group ) . Variability in responses was large but the differences were not statistically significant . Personal preference indicated that the majority of patients preferred the high-dose cycle compared with the lower dose continuous inhalation , but this was not linked to objective data on efficacy . CONCLUSIONS The present trial fails to provide convincing evidence for superiority in efficacy of either of the two treatment regimens of inhaled tobramycin in CF patients To assess whether chronic pulmonary colonisation with Pseudomonas aeruginosa in cystic fibrosis is preventable , 26 patients who had never received anti-pseudomonas chemotherapy were r and omly allocated to groups receiving either no anti-pseudomonas chemotherapy or oral ciprofloxacin and aerosol inhalations of colistin twice daily for 3 weeks , whenever Ps aeruginosa was isolated from routine sputum cultures . During the 27 months of the trial , infection with Ps aeruginosa became chronic in significantly fewer treated than untreated subjects ( 2 [ 14 % ] vs 7 [ 58 % ] ; p less than 0.05 ) and there were significantly fewer Ps aeruginosa isolates in routine sputum cultures in the treated group ( 49/214 [ 23 % ] vs 64/158 [ 41 % ] ; p = 0.0006 ) . Thus , chronic colonisation with Ps aeruginosa can be prevented in cystic fibrosis by early institution of anti-pseudomonas chemotherapy Pseudomonas aeruginosa endobronchial infection causes significant morbidity and mortality among cystic fibrosis patients . Microbiology results from two multicenter , double-blind , placebo-controlled trials of inhaled tobramycin in cystic fibrosis were monitored for longitudinal changes in sputum microbial flora , antibiotic susceptibility , and selection of P. aeruginosa isolates with decreased tobramycin susceptibility . Clinical response was examined to determine whether current susceptibility st and ards are applicable to aerosolized administration . Treatment with inhaled tobramycin did not increase isolation of Burkholderia cepacia , Stenotrophomonas maltophilia , or Alcaligenes xylosoxidans ; however , isolation of C and ida albicans and Aspergillus species did increase . Although P. aeruginosa tobramycin susceptibility decreased in the tobramycin group compared with that in the placebo group , there was no evidence of selection for the most resistant isolates to become most prevalent . The definition of resistance for parenteral administration does not apply to inhaled tobramycin : too few patients had P. aeruginosa with a tobramycin MIC > /=16 microgram/mL to define a new break point on the basis of clinical response OBJECTIVES Despite the central importance of pulmonary exacerbations ( PExs ) as an outcome measure in cystic fibrosis clinical trials , no st and ardized definition of PEx exists . We conducted a prospect i ve , multicenter study to establish a st and ardized PEx definition and score for use in clinical trials , based on clinical status rather than on treatment decisions . STUDY DESIGN Subjects were 246 patients enrolled in the placebo arm of a r and omized , controlled trial of tobramycin for inhalation . Physician-investigators completed PEx question naires on all subjects at scheduled intervals during the 6-month study , indicating new or worsening symptoms , physical examination findings , and impression of PEx status ( presence or absence and severity ) . Logistic regression was used to assess the relative importance of each of the characteristics in predicting a PEx . RESULTS We developed 2 PEx scores that use easily ascertained symptoms and chest examination findings ; one also includes change in forced expiratory volume in 1 second over the preceding month . Both scores were sensitive and specific for predicting the presence of a PEx ( sensitivity , 86 % ; specificity , 86 % ) . The scores were vali date d in subjects in the intervention arm of the trial . CONCLUSION We hope that the proposed PEx score might serve as a st and ardized outcome measure for future clinical trials in cystic fibrosis , allowing meaningful comparisons of study results To determine the potential toxicity of prolonged aerosol tobramycin administration , 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks . Prior to , four times during administration and approximately 6 weeks after discontinuation of treatment , we assessed pulmonary function , weight , height , body temperature , eighth cranial nerve function , serum creatinine , blood urea nitrogen , urinary creatinine clearance , plasma iothalamate clearance , urinary beta-2 microglobulin concentration , and Pseudomonas aeruginosa density in sputum . There was no detectable laboratory evidence of nephrotoxicity . Neither a decrease in auditory acuity ( range 250 - 20,000 Hz ) nor vestibular dysfunction was detected . Pulmonary function tests significantly improved during the first month in all subjects ( P less than 0.05 ) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol . Sputum P. aeruginosa density initially decreased from a mean of 10(7 ) cfu/gm to a mean of 10(4 ) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout . Coincident with the reduced bacterial density , a reduction in cough frequency and sputum production , as well as a weight gain was observed . Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration . However , 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin . We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity . Transient emergence of tobramycin resistant P. aeruginosa may occur RATIONALE The effectiveness and safety of aztreonam lysine for inhalation ( AZLI ) in patients with cystic fibrosis ( CF ) on maintenance treatment for Pseudomonas aeruginosa ( PA ) airway infection was evaluated in this r and omized , double-blind , placebo-controlled study . OBJECTIVES To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF . METHODS After r and omization and a 28-day course of tobramycin inhalation solution ( TIS ) , patients ( n = 211 ; > or = 6 yr ; > or =3 TIS courses within previous year ; FEV(1 ) > or = 25 % and < or = 75 % predicted values ) were treated with 75 mg AZLI or placebo , twice or three times daily for 28 days , then monitored for 56 days . The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics . Secondary endpoints included changes in respiratory symptoms ( CF Question naire-Revised [ CFQ-R ] Respiratory Scale ) , pulmonary function ( FEV(1 ) ) , and sputum PA density . Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored . MEASUREMENTS AND MAIN RESULTS AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days , compared with placebo ( AZLI , 92 d ; placebo , 71 d ; P = 0.007 ) . AZLI improved mean CFQ-R respiratory scores ( 5.01 points , P = 0.02 ) , FEV(1 ) ( 6.3 % , P = 0.001 ) , and sputum PA density ( -0.66 log(10 ) cfu/g , P = 0.006 ) compared with placebo ; no AZLI dose-response was observed . Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease . Susceptibility of PA to aztreonam at baseline and end of therapy were similar . CONCLUSIONS AZLI was effective in patients with CF using frequent TIS therapy . AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics , improved respiratory symptoms and pulmonary function , and was well tolerated . Clinical trial registered with www . clinical trials.gov ( NCT 00104520 ) Abstract Background and aim Chronic infection with Pseudomonas aeruginosa in patients with cystic fibrosis ( CF ) causes progressive deterioration in lung function . The purpose of this trial was to assess the efficacy and tolerability of a tobramycin highly concentrated solution for inhalation ( TSI ) [ 300mg/4mL ; Bramitob ® ] when added to other antipseudomonal therapies in CF patients with chronic P. aeruginosa infection . Methods In a multinational , double-blind , multicenter study , CF patients with chronic P. aeruginosa infection were r and omized to receive nebulized tobramycin or placebo over a 24-week study period in which 4-week treatment periods ( ‘ on ’ cycles ) were followed by 4-week periods without treatment ( ‘ off ’ cycles ) . Forced expiratory volume in 1 second ( FEV1 ) percentage of predicted normal was used as the primary efficacy outcome parameter . Forced vital capacity ( FVC ) , forced expiratory flow at 25–75 % of FVC ( FEF25–75 % ) , P. aeruginosa susceptibility , minimum concentration required to inhibit 90 % of strains ( MIC90 ) , rates of P. aeruginosa-negative culture , P. aeruginosa persistence and superinfection , need for hospitalization and parenteral antipseudomonal antibiotics , loss of school/working days due to the disease , and nutritional status ( bodyweight and body mass index ) were considered as secondary efficacy outcome parameters . Adverse events reporting , audiometry , and renal function were monitored to evaluate the tolerability and safety of TSI . Results A total of 247 patients were r and omized in the study . At endpoint time assessment ( week 20 ) , FEV1 was significantly increased in the tobramycin group and the adjusted mean difference between groups ( intention-to-treat population ) was statistically significant ( p < 0.001 ) . At the same time , clinical ly relevant improvements in FVC and FEF25–75 % were detected in the TSI group ( p = 0.022 and p = 0.001 , respectively ) . The microbiologic outcomes at the end of the last ‘ on ’ cycle period were significantly better in the TSI group than the placebo group ( p = 0.024 ) , although there was a concomitant trend toward an increase in the MIC of isolated P. aeruginosa strains . The percentage of patients hospitalized as well as the need for parenteral antipseudomonal antibiotics was significantly lower in the TSI group ( p = 0.002 and p = 0.009 , respectively ) . Patients treated with TSI had fewer lost school/working days due to the disease ( p < 0.001 ) . A favorable effect of tobramycin in terms of an increase in bodyweight and body mass index was also noted , when compared with placebo , at all timepoints ( p < 0.01 and p < 0.001 , respectively ) . No significant changes in serum creatinine and auditory function were detected . The proportion of patients with drug-related adverse events was 15 % in both treatment groups . Conclusions Long-term , intermittent administration of this aerosolized tobramycin formulation ( 300mg/4mL ) in CF patients with P. aeruginosa chronic infection significantly improved pulmonary function and microbiologic outcome , decreased hospitalizations , increased nutritional status , and was well tolerated In a previously published placebo-controlled trial , tobramycin solution for inhalation ( TSI ) was shown to improve lung function and other outcomes in patients with cystic fibrosis ( CF ) . The objectives of the current study were to examine the effects of TSI on global ratings of health-related quality of life ( HRQOL ) by patients ( or their parents ) and physicians blind to group assignment , and to determine whether any perceived benefits persisted over time . The global ratings of HRQOL in 520 patients with CF and chronic Pseudomonas aeruginosa infection were analyzed retrospectively . Patients were r and omly assigned to receive 24 weeks of placebo or treatment with TSI 300 mg b.i.d . , both administered in cycles of 28 days on drug ( or placebo ) followed by 28 days off , for a total of three cycles . After each on-drug cycle , patients or parents , and physicians , were asked to rate whether the patient 's condition was better , unchanged , or worse . There was strong agreement between the paired patient/parent and physician global HRQOL ratings across the three cycles . Regression analyses demonstrated that patients in the TSI group were significantly more likely to report improvements in HRQOL than were patients in the placebo group . This effect was found to be both immediate ( end of on-drug cycle 1 ) and delayed ( end of subsequent on-drug cycles 2 and 3 ) ( P < 0.05 ) . In addition , change in forced expired volume in 1 sec ( FEV(1 ) ) % predicted values was a significant predictor of improvement in HRQOL ratings by patients and parents . After controlling for change in FEV(1 ) % predicted , physician ratings showed significant improvement only at the end of cycle 1 . Finally , controlling for initial lung disease severity , longitudinal growth models revealed that patients on TSI and their physicians reported higher HRQOL ratings than did placebo patients and their physicians across the three cycles ; however , the magnitude of this effect decreased over time . Results of this study provided consistent evidence that TSI was associated with improved global ratings of HRQOL completed by both patients or parents , and physicians . Although these results are promising , they are limited by the use of a single-item rating of health . Future studies of the effects of TSI should utilize a well-vali date d , disease-specific measure of HRQOL Tobramycin nebuliser solution ( TNS ) has been investigated in several clinical trials , including a large , placebo-controlled study that demonstrated efficacy over a 24-week period . The open-label extension phase of this trial enabled observations to be conducted for an additional period of almost 18 months . Patients from both treatment arms ( n=396 ) entered the open-label phase and received up to nine 28-day on , 28-day off cycles of TNS 300 mg by aerosol twice daily ( b.i.d . ) . Mean lung function in patients who had received placebo during the double-blind phase improved during the first three cycles of the open-label treatment . However , lung function in these patients did not recover to the levels seen in those patients who had received TNS throughout the double-blind and open-label phases . In both groups of patients , improvement was maintained during the study . Greater improvements were seen in adolescents compared with older patients . Adverse events were generally uncommon , with a notably lower incidence of fever , anorexia , abdominal pain and vomiting than was observed in the double-blind phase among patients who received placebo , and a generally low incidence of tinnitus . We conclude that long-term TNS administration is safe and effective Eighty-seven patients with cystic fibrosis were admitted to hospital with an acute exacerbation of pulmonary symptoms associated with isolation of Pseudomonas aeruginosa from sputum . The patients were r and omly allocated to receive intravenously administered ceftazidime ( 250 mg/kg/day ) and amikacin ( 33 mg/kg/day ) alone or with inhaled amikacin ( 100 mg twice a day ) . Other aspects of the 2-week treatment were constant . The two therapy groups were comparable in all aspects . At the completion of therapy , the addition of aerosolized amikacin produced temporary eradication of P. aeruginosa in 70 % of the patients , compared with 41 % in the intravenous therapy only group ( P less than 0.02 ) . Suppression of P. aeruginosa in sputum cultures was correlated with the amikacin sputum concentrations . However , both regimens result ed in similar improvements in clinical , radiologic , laboratory , and pulmonary function measurements , and within 4 to 6 weeks most patients were recolonized with P. aeruginosa . There was no serious toxicity or adverse effect . In patients with cystic fibrosis , the addition of aerosol aminoglycoside to systemic antipseudomonal combination therapy is not clinical ly beneficial |
2,661 | 24,173,771 | In young children with acute diarrhoea who are not predominantly breast-fed , change to a lactose-free diet may result in earlier resolution of acute diarrhoea and reduce treatment failure .
There are no trials from low-income countries , where mortality for diarrhoea is high , and malnutrition is more common | BACKGROUND Young children with acute diarrhoea , typically due to infectious gastroenteritis , may temporarily stop producing lactase , the intestinal enzyme that digests lactose .
This means they may not digest lactose , the main sugar in milk , and this may worsen or prolong the diarrhoeal illness .
However , there is uncertainty whether avoiding lactose-containing milk or milk products helps young children recover from acute diarrhoea more quickly .
OBJECTIVES To assess if avoiding or reducing intake of lactose-containing milk or milk products shortens the duration and severity of illness in young children with acute diarrhoea .
We also sought other indicators of morbidity and overall mortality . | Two hundred well hydrated babies of 6 weeks to 12 months of age who had been fed on formula feeds and who were admitted with acute gastroenteritis were r and omly allocated to receive either a st and ard return to full milk feeds , or immediate full strength feeds with one of three milk formulas , HN25 , SMA Gold Cap , or Formula S. There were significant differences in weight change among the four treatment groups at two and five days , with initial weight loss recorded only for the group of babies who were receiving the grade d return to full feeding . There was no difference in the duration of diarrhoea after admission , nor in the time to discharge . Eighteen babies were classified as failures of treatment . None had long term complications . Well hydrated infants with acute gastroenteritis may resume full milk feeding immediately Early feeding is generally recommended for children with acute diarrhea . The concentration at which the milk should be given to children weaned at an early age remains a matter of debate . The aim of the study was therefore to evaluate the role of milk dilution in the first 24 hours on the outcome of diarrhea . Sixty-nine well nourished and weaned children , aged 1 to 9 months and with moderate watery acute diarrhea were included after oral rehydration therapy ( ORT ) in a r and omised controlled study to receive either half-strength ( diluted group ) or full strength ( undiluted group ) milk . Both groups displayed the same clinical characteristics except for the weight . The outcome of the diarrhea until cessation was the same in the 2 groups . No failure requiring a specific treatment was observed . The duration of diarrhea and the total stool output were not statistically different in the 2 groups , i.e. 39 + /- 7 hrs in diluted vs 47 + /- 8 in undiluted , and 883 + /- 205 g in diluted vs 924 + /- 161 g in undiluted . These results are strengthened by the lack of significant differences in the weight gain , the number and volume of vomiting , the volume of ORT and milk intake . However , the energy intake was significantly higher in the group receiving full strength milk . These results suggest that there is no immediate clinical advantage to dilute the milk in the first 24 hours of feeding well nourished children with moderate acute watery diarrhea , if early feeding is associated with the ORT recommended by the WHO Sixty two babies under the age of 6 months who were admitted with gastroenteritis completed a study of gradual refeeding compared with abrupt refeeding after a period of rehydration . There was no difference in the incidence of recurrence of diarrhoea due to lactose intolerance , effect on weight , or duration of hospital stay . Twenty six babies ( 42 % ) had recurrence of diarrhoea after refeeding , all of whom settled with the introduction of a lactose free soya based formula . Well nourished babies under 6 months of age with mild to moderately severe gastroenteritis can be fed immediately with full strength milk feeds after rehydration . The introduction of a lactose free soya based preparation may provide an alternative to repeated attempts at regrading with cows ' milk feeds in those patients with lactose intolerance There is concern that feeding full-strength animal milk to infants aged less than 6 months with diarrhoea may have adverse consequences . We assessed the effects on clinical course of two feeding regimens in 159 Guatemalan and Brazilian infants aged 2 weeks to 6 months who had had acute diarrhoea for 120 h or less , showed signs of mild to moderate dehydration , and had no complications . After correction of dehydration , infants were assigned r and omly to receive continued full-strength milk feeding or initial feeding with diluted milk with regrading to full-strength milk over 48 h. There were no significant differences between feeding groups in rate of treatment failures ( -1 % , 95 % Cl -14 to 12 % ) or mean ( SD ) total stool output ( full-strength milk 335 [ 268 ] g/kg , diluted milk 338 [ 354 ] g/kg ) and duration of diarrhoea ( 92 [ 50 ] vs 92 [ 44 ] h ) . A significant association was found between presence of reducing substances in stools and treatment failure ( OR 4.3 , 95 % CI 1.1 to 16.8 ) , but reducing substances in stools were common both in treatment successes ( 61 % ) and in failures ( 87 % ) . Our study supports the conclusion that , for infants under 6 months of age with diarrhoea whose only food is animal milk or formula , the milk or formula normally given should be provided in full strength as soon as dehydration has been corrected To assess the best possible method of reintroducing milk in children suffering from acute gastroenteritis , 150 children ( 76 males and 74 females ) admitted with acute gastroenteritis were allocated to one of three regimens : a. clear fluids initially , followed by increasing strengths of milk , in quarter strength steps ; b. clear fluids initially and then reintroducing full strength milk ; c. regimen of continuing full strength milk . There was no difference between the three groups in the outcome or in the length of stay in the hospital , but those who were continued on full strength milk gained more weight . The weight gain did not attain statistical significance ; it is our impression on clinical grounds that this weight gain may be important in the malnourished infant who is more prone to enteritis We determined the efficacy of a soy‐based formula compared with a cow 's milk formula in infant re‐feeding after acute diarrhea in a r and omized controlled double‐blind clinical trial . Infants 2–12 months of age with diarrhea of less than one week 's duration and mild or moderate dehydration admitted to a pediatric hospital or in the practice of a participating primary care pediatrician were investigated . Seventy‐six patients were enrolled and 73 completed the study ; 39 infants received a soy‐based formula ( Isomil ) and 34 received a cow 's milk formula ( SMA ) . Hospitalized patients were rehydrated with an oral glucose‐electrolyte solution or an iv dextrose‐sodium solution . Out patients received oral glucose‐electrolyte solution . In all patients , the study formula was commenced ad libitum during the first 24 h as determined by the attending pediatrician . The primary outcome measure was duration of diarrhea , defined as time to first normal stool , when subsequent stools were normal for a 24‐h period . In addition , a predetermined secondary outcome was proportion of treatment failures , defined as the need to reinstitute clear fluids because of emesis , refusal to accept study formula , need for iv fluids due to negative fluid balance or diarrhea persisting beyond 7 days after enrollment . Total duration of diarrhea was significantly longer ( p= 0.03 ) in those receiving cow 's milk ( mean±SD 6.6 ± 4.2 days ) than in those receiving soy‐based formula ( 4.5 ± 3.6 days ) . Volume of formula intake and weight gain at 14 days were not different in the two groups . There were 18 treatment failures in the cow 's milk formula recipients and 13 failures in the soy formula recipients ( p= 0.08 ) . Soy‐based formula significantly shortened the duaration of acute diarrhea in well nourished infants compared with cow 's milk formula To compare the efficacy of a low-lactose hydrolyzed milk formula , a lactose-free corn syrup-based milk formula , and a st and ard lactose-containing formula during refeeding after rehydration in infants with gastroenteritis , 135 patients older than 2 years were studied by r and omized trial . Clearly demonstrated disadvantages in terms of early weight loss and longer duration of diarrhea were observed with the lactose-based formula compared with early weight gains on both the low-lactose formulae , and thus the lactose-containing formula was discontinued after 91 patients . The early weight loss with the lactose-containing formula was statistically significantly related to the degree of relative ( rehydrated ) underweight . The two low-lactose formulae were further compared in the remaining 44 patients . Early weight gain ( 48 h ) was significantly greater with the lactose-hydrolyzed formula compared with the corn syrup-based formula , but no statistically significant differences were observed in duration of diarrhea , energy intake , treatment failures , or late weight gain . We conclude that the routine use of a low-lactose formula during refeeding after rehydration in infants with gastroenteritis may have some advantages in underweight infants and toddlers in whom it is important to prevent further weight loss BACKGROUND St and ard treatment of infants who are dehydrated as a result of acute gastroenteritis is to administer oral rehydration therapy ( ORT ) . Traditionally , food has been withdrawn for 24 - 48 h , but there is no conclusive evidence that this is of any real benefit to the patient . Immediate modified feeding , in which an infant on ORT is not starved but administered a limited diet , may have benefits in the treatment of gastroenteritis , especially in children who are nutritionally compromised before they develop the illness . AIM A pilot study was carried out to investigate the effects of giving infants suffering from acute gastroenteritis a limited modified diet in conjunction with ORT . METHOD Infants recruited into the study by their general practitioner or by a research doctor in the hospital casualty unit of Bristol Children 's Hospital were r and omly allocated to receive ORT with or without immediate modified feeding . The duration of diarrhoea , weight change , and incidence of vomiting and lactose intolerance were measured in both treatment groups , and the results were compared . RESULTS Of the infants studied , 27 received ORT and immediate modified feeding , and 32 ORT alone . The duration of diarrhoea , and incidence of vomiting or lactose intolerance were no greater in the group receiving immediate modified feeding . Patients who received ORT and immediate modified feeding appeared to gain more weight than the infants who were starved for 24 - 48 h , but this difference was not statistically significant . CONCLUSION Immediate modified feeding is safe and effective , and may have nutritional advantages over traditional ORT with starvation . A similar but multicentre study using unmodified diet , i.e. child 's normal diet , is being carried out by a working group of The European Society of Paediatrics , Gastroenterology and Nutrition ( ESPGAN ) A blind controlled trial was performed to test the hypothesis that early introduction of full-strength cow 's milk ( FCM ) during an attack of acute infantile gastroenteritis does not prolong the course of the illness . A total of 74 children matched for age was admitted to the trial , which compared the effect of FCM with that of graduated milk ( the strength of which was gradually increased ) . Thirteen children ( 17.5 % ) were withdrawn because of lactose malabsorption ; of those remaining , 29 were given FCM and 32 graduated milk . The mean duration of diarrhoea was 2,62 days for those on FCM and 2,64 days for those given graduated milk ( P = 0,71 , not significant ) . Early introduction of FCM therefore does not prolong the course of acute infantile gastroenteritis . Because of the prevalence of malnutrition in South Africa the practice of giving clear fluids or diluted milk during an attack of gastro-enteritis is unnecessary and dangerous OBJECTIVE To evaluate the effect of feeding infants a soy-based formula with lactose compared with a soy-based formula with sucrose during an acute diarrheal episode . PARTICIPANTS AND METHODS Two hundred boys , aged 3 to 18 months , who were admitted to the hospital with acute diarrhea and signs of dehydration were r and omly assigned to receive a soy-based formula with lactose or sucrose after initial rehydration . Intake and output ( stool , urine , and vomit ) were measured and recorded every 3 hours until diarrhea resolved . RESULTS The stool output during the first 24 hours of maintenance therapy , the total stool output during maintenance therapy , and the stool output during the entire illness ( measured in grams per kilograms ) were significantly lower among patients who received the soy-based formula with sucrose ( P<.05 , P<.001 , and P<.001 , respectively ) than among patients who received the soy-based formula with lactose . The duration of diarrhea was significantly shorter among patients who received the soy-based formula with sucrose ( P<.001 ) . The relative risk of being withdrawn from the study increased to 1.95 ( 95 % confidence interval , 0.65 - 9.2 ) and the relative risk of recurrence of dehydration after feeding was initiated increased significantly to 3.49 ( 95 % confidence interval , 1.1 - 9.6 ; P<.01 ) in the group receiving the soy-based formula with lactose . CONCLUSION During diarrheal episodes , feeding infants a soy-based formula with sucrose has a better outcome ( lower stool output , shorter duration of diarrhea , and lower failure rates ) than feeding infants a soy-based formula with lactose Thirty-eight moderately to severely malnourished children with severe acute or subacute diarrhea were treated according to two different feeding schemes , divided at r and om half of the children received semi-elemental diet ( SED ) with an osmolarity of 302 milliosmol per liter , a low lactose content and a relatively high content of lactalbumine hydrolysate ( 1 g/100 ml ) . The other half of the patients received available proprietory formulas or diluted cow 's milk with added carbohydrates . The results obtained showed that the children who were fed the SED had a better average weight gain during the first three weeks of hospitalization compared to the control group . The children receiving the SED also required a smaller number or rehydrations Children with mild acute gastroenteritis have not been observed for specific evidence of lactose intolerance yet are frequently fed a nonlactose formula . To determine whether such intervention is justified , 85 infants with mild acute gastroenteritis were followed prospect ively . Infants were blindly and r and omly assigned to 20 calorie/oz formula containing one of four carbohydrates : lactose , sucrose , polycose , or combined sucrose-polycose . Daily diaries were kept by parents , and patients were reexamined on days 2 , 7 , and 14 of the study . Evidence for rotavirus was detected in 23 infants , and five had bacterial pathogens . Symptoms resolved in most patients within 7 days , but five infants were subsequently hospitalized . Stool frequency , weight gain , and need for hospitalization did not differ significantly among the groups . Recovery from mild acute gastroenteritis occurred within 2 weeks irrespective of carbohydrate ingested OBJECTIVE To determine whether the routine use of a lactose free formula ( AL-110 , Nestle Labs . ) in hospitalized children aged one to 24 months reduces the duration of acute diarrhea ( AD ) . METHODS After being stratified according to age and nutritional state , 28 and 24 patients were r and omly allocated to receive AL-110 or lactose formula , respectively . The main outcome was the duration of diarrhoea after refeeding , both in hours and days . Secondary outcomes were evaluated by blind observers . Results were compared using t test , the Mann-Whitney test and Chi square . RESULTS No differences were found between the diets without and with lactose regarding duration of diarrhoea in hours ( mean , 41.9 h vs 54.4 h ; p = 0.247 ) or days ( median , 0 d vs 0 d ; p = 0.717 ) , the percentage of failures ( 3.6 % vs 8.3 ; p = 0.2 ) , and the mean weight increment ( 0.78 kg vs. 0.82 kg ; p = 0.788 ) . The study power to find a 50 % ( 27h ) reduction of AD duration was 71 % . CONCLUSION Although the power of this trial was slightly below that previously fixed ( 80 % ) , the results suggest that routine use of lactose free formula does not reduce the duration of AD in hospitalized children A r and omized clinical trial was completed to study the severity , duration , and nutritional outcome of acute diarrhea in 85 Peruvian children between 5 and 24 months of age who received a soy-protein-isolate , lactose-free formula ( group SF ) or one of two mixtures of home-available foods , all in amounts up to 110 kcal/kg of body weight/day . The mixed diets contained either wheat flour , pea flour , carrot flour , sucrose , and vegetable oil ( group WP ) or potato flour , dried whole milk , carrot flour , sucrose , and oil ( group PM ) . The characteristics of the children in each group were generally similar initially . There were no differences in treatment failure rate by diet group . Fecal outputs were similar in all groups during the first day of treatment , averaging 60 to 65 g/kg/day . However , stool outputs were greater for the PM group than for other groups on days 3 and 4 , and were less for the SF group than the other groups on days 5 and 6 . The estimated median duration s of diarrhea in the WP group ( 52 h ) and PM group ( 53 h ) were significantly less than in the SF group ( 154 h , p = 0.005 ) . Energy intakes , energy absorption , and nitrogen retention ( % of intake ) were generally similar in all dietary groups , although there were minor differences in the absorption of specific macronutrients . Children in all groups gained weight during hospitalization , and there were no significant differences by diet group in the change in anthropometric status during treatment . We conclude that these locally available , low-cost staple food mixtures offer a safe and nutritionally adequate alternative to a commercially produced lactose-free formula for the dietary management of young children with acute diarrhea in this setting Two prospect i ve studies compare the dietary treatment of acute diarrhoea ( gastroenteritis in infancy with either partially adapted formula or with special formula ( HN 25 ) with a low lactose content ( 1.8 % ) , or virtually free of lactose ( 0.05 % ) , including only infants with acute diarrhoea , a loss in weight not exceeding 8 % , and without parenteral fluid intake . There is no difference in the duration of hospitalization . However , the time until normalization of the stools was significantly shorter when lactose-reduced formula or formula virtually free of lactose was fed ( 4.4 resp . 3.1 vs. 5.1 days ) . There were 9 relapses in the control group fed partially adapted formula , and none in the trial group fed special formula . The present results show that in mild and moderate diarrhoea a dietary treatment with lactose-reduced formula should be preferred to a treatment with infant formula OBJECTIVE To compare three low-lactose milk formulas differing in osmolality and degree of protein hydrolysis in the treatment of diarrhoea and malnutrition in subjects with high rates of lactose intolerance , osmotic diarrhoea and a tropical/environmental enteropathy . METHODS A r and omized double-blind trial of 180 Aboriginal children under 3 years of age admitted with acute diarrhoea and /or malnutrition was carried out . The intervention milk formulas were : ( i ) De-Lact , a low-osmolality lactose-free formula ; ( ii ) O-Lac , a lactose-free formula ; and ( iii ) Alfaré , a partially hydrolysed formula . Outcome measures were diarrhoeal severity , weight gain , formula palatability and changes in intestinal permeability ( L/R ratios ) . RESULTS The duration of diarrhoea in days ( mean ; 95 % confidence interval ) was significantly longer on Alfaré ( 8.5 ; 7.0 - 10.0 ) compared to De-Lact ( 6.1 ; 5.0 - 7.2 ) and O-Lac ( 6.9 ; 5.6 - 8.1 ; P = 0.04 ) . There were no differences in mean intake between formulas , but palatability of Alfaré was significantly worse ( P < 0.01 ) than the other formulas . Over the trial 5 days , improvement in L/R ratios was significantly greater ( P = 0.05 ) for De-Lact ( 18.6 ; 10.6 - 26.6 ) than for Alfaré ( 8.5 ; 2.1 - 14.9 ) . Weight gain was not significantly different between the three formulas , except in a malnourished subgroup who had better weight gain on De-Lact ( P = 0.05 ) . CONCLUSIONS In these Aboriginal children with diarrhoea and growth failure , a low osmolality milk was associated with better outcomes and a partially hydrolysed formula with less improvement in mucosal recovery , suggesting that cow 's milk protein intolerance is not contributing to greater diarrhoeal severity or enteropathy in Aboriginal children A r and omized double blind clinical trial was conducted to assess the efficacy of a special infant formula containing Lactobacillus rhamnosus LMG P-22799 ( probiotic : 5 x 10(8 ) CFU/100mL ) , inulin ( prebiotic : 0.15 g/100mL ) , dietary fiber ( soy polysaccharides : 0.2 g/100mL ) and increased amounts of zinc+iron ( + 0.4 and + 0.6 mg/100mL , respectively ) as active ingredients for the early dietary management of 58 Indonesian well-nourished male infants aged 3 - 12 months suffering from acute diarrhea with moderate dehydration . After adequate oral rehydration , the patients were r and omly assigned to receive either a low lactose infant formula supplemented with added precooked rice ( 1.5 g/100mL ) with the above active ingredients ( study group ) or a low lactose infant formula with added precooked rice without the above active ingredient supplement ( control group ) . No antibiotic , anti-secretory drug or antiemetic was given at all . Both study and control groups showed similar outcomes for weight gain and stool weight . The duration of diarrhea was significantly shorter in the study group than in the control group ( 1.63 versus 2.45 days ; p<0.05 ; for the study and control group respectively ) . No treatment failure or other side effects were observed during the course of the study . The present study supports the evidence for the efficacy of a special anti-diarrhea infant formula containing probiotic , prebiotic , fiber and iron+zinc after oral rehydration by shortening the duration of infantile diarrhea in developing countries . However , from the results of our study we can not discern the individual contribution of the active ingredients and also not whether they may act independent from each other or in a synergistic way Acute infantile diarrhea is often managed by introducing lactose-free diets empirically from the time of diagnosis , in addition to conventional rehydration therapy . In order to assess the efficacy of this , a therapeutic trial was undertaken in which hospitalized gastroenteritis patients previously on milk-formula feeds were r and omly fed , from the time of admission , either their original feed or a lactose-free soya preparation ; patients previously on human milk with or without a supplement continued to receive this during their diarrheal illness . The results show that in nonrotaviral gastroenteritis , there is no difference in the duration of the illness irrespective of the type of feed given . In rotaviral gastroenteritis , continued breast-feeding significantly reduces the duration of acute diarrhea , while lactose-free soya feeds do not lead to a significant reduction in the duration of the illness when compared to cow 's milk-formula feeds . Hence , it is concluded that ( a ) breast-feeding should be continued during an episode of infantile diarrhea , and that ( b ) empirical use of soya preparations from the time of hospital admission is not justified ; however , the latter should be considered in infants whose purging rate goes up or diarrheal disease severity worsens 3 to 4 days after the onset of diarrhea or hospital stay and who are passing significant amounts of reducing sugars in their stool Lactose intolerance interferes with the recovery phase in patients with severe diarrhoea . A controlled comparison of a lactose-free soy isolate formula ( Isomil ® ) and a st and ard cow 's milk-based formula in 112 infants with severe diarrhoea showed a significant advantage for the lactose-free formula . All the infants were dehydrated on admission and required initial intravenous therapy . The response rate in the two groups was , respectively , 93 % and 75 % The effects of two different formulas in the treatment of acute diarrhea were tested in a prospect i ve study with 40 infants . The formulas differ in content of lactose , fructose , starch , sodium and potassium . Both groups reached normal food intake at the same time and could be discharged from clinical observation . The patients were divided into two groups with equal degrees of diarrhea . During nutrition with lactose-reduced formula , body-weight was rising and the water-binding capacity of chymus seemed to be better . From significant higher percentages of prae-beta-liproproteins in electrophoresis better endogenous metabolic efficiency could be derived . Phospholipids were also significantly increased when lactose-reduced formula was given . The comparative formula led , due to the higher content of potassium to significantly higher serum levels . The results of this investigation indicate , that reduction of lactose in the formula for infants with diarrhea has some advantages . Whether more effectiveness of formulas in diarrhea could be expected from addition of medium chain triglycerides ( Gracey et al. 1970 , Schreier und Porath 1971 ) requires further investigations Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital ( 49 admissions ) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder . Infants fed the lactose hydrolysed milk gained 70 % more weight than those receiving normal milk . Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage st and ard weight for age , the presence of diarrhoea on admission to the trial , and stool sugar concentrations . The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world OBJECTIVE To study the efficiency of lactose-free formula feeding as an adjunctive therapy in infants with acute diarrhea . METHODS A rigorous double-blind , r and omized , controlled equivalence trial was performed . One hundred and twenty infants with acute diarrhea were r and omly divided into two groups : lactose-free formula and conventional formula feeding . The two groups were given conventional medical treatment and oral rehydration therapy . The therapeutic effects were observed 1 week after treatment . RESULTS The cure rate and the total effective rate were 58.3 % and 96.7 % respectively in the lactose-free formula group , and they were 8.3 % and 85.0 % respectively in the conventional formula group . There were significant differences in the therapeutic effect between the two groups ( p<0.05 ) . The duration of diarrhea remission ( 3.17+/-1.04 days ) in the lactose-free formula group was significantly shorter than that in the conventional formula group ( 5.25+/-1.58 days ) ( p<0.05 ) . After treatment the incidence of fecal flora disturbance was lower in the lactose-free formula group than that in the conventional formula group ( p<0.05 ) . No aderverse events were observed in the two groups . CONCLUSIONS Lactose-free formula feeding together with conventional therapy can significantly shorten the disease course and improve the treatment outcome in infants with acute diarrhea The purpose of this study was to determine which infant formula among five would be the most efficacious for the refeeding of infants during an acute episode of diarrhea . Fifty male infants less than 12 months of age with severe diarrhea and at least 5 % dehydration were admitted to a metabolic unit and studied in a prospect i ve , single-blind protocol . Ten infants r and omly received one of five types of formula : two-thirds diluted cow milk , cow milk formula ( Nanon , Nestle , Inc. , São Paulo , Brazil ) , Portagen , Pregestimil , or Prosobee ( Mead Johnson & Co. Division , Evansville , Ind. ) . They continued to receive the same formula for 72 hours unless dehydration occurred . There were no associated infections , and they received no prior antibiotic treatment . Oral hydration together with intravenous fluid therapy was given to all patients during the initial treatment . During the first 72 hours of refeeding , patients fed Portagen excreted the least amount of stool and required reduced quantities of intravenous fluids or oral hydration . In contrast , patients fed diluted cow milk or any other formula had more severe diarrhea . Nine of the 10 patients fed Portagen completed the 72-hour treatment , whereas only 2 of 10 fed diluted cow milk tolerated it . Similarly , the cumulative proportions for high purging rate , dehydration , carbohydrate intolerance , and vomiting were more favorable for Portagen and least acceptable for diluted cow milk . No differences were found among the remaining three formulas tested . These data show that diluted cow milk is poorly tolerated by infants with severe diarrhea , whereas Portagen is more effective Prolonged diarrhea following an acute episode of dehydrating gastroenteritis in infants is often treated by the empirical removal of both cow 's milk protein and lactose from the feed , as they both have been implicated in the prolongation of diarrhea . In order to assess the efficacy of this policy and to determine whether there are any advantages in using a lactose-free semi-elemental feed in this situation , infants with prolonged dehydrating gastroenteritis from a developing community in South Africa were studied . Male black children between the ages of 6 weeks and 2 years with prolonged dehydrating gastroenteritis ( requiring intravenous fluids for longer than 72 h to maintain hydration ) were r and omly assigned to receive one of four feeds if the stool weight was greater than 30 g/kg body weight/24 h on the fourth day of admission . The four formula feeds were a partially modified cow 's milk formula ; a lactose-free , casein-containing formula ; a lactose-free , soy-protein-containing formula ; and a lactose-free , whey-hydrolysate-containing formula . Stool weights were measured for the following 3 days . Seventy-two children were enrolled into the study . Stool weights were similar in the four groups at the start of the trial , and fell significantly over the trial period in those groups receiving the lactose-free feeds . Mean stool weight in the cow 's milk formula group did not change . Thus , it appears that the continued feeding of a cow 's milk-based lactose-containing formulae to infants with prolonged dehydrating gastroenteritis adversely affects their recovery . ( ABSTRACT TRUNCATED AT 250 WORDS Children admitted with acute gastroenteritis were managed with clear fluids and then given either the st and ard graduated feeding regimen or an abrupt re introduction of normal feeds . The rapid refeeding group lost less weight , went home sooner , and had no increase in complication rate . Rapid refeeding is a reasonable option in the management of acute gastroenteritis An estimated 38 % of children under five years of age suffer from moderate and 5 % from severe malnutrition in 83 developing countries , representing three billion people ( 1 ) . As a child grows beyond six months of age , the amount of mother ’s milk becomes increasingly inadequate and growth faltering occurs because the usual weaning foods in the subcontinent are made of staples with low energy density and are often given in infrequent meals . Thick , energy dense porridge is regarded as unsuitable . Amylolytic enzymes , developed during germination of cereals , hydrolyse starch and liquify a sticky semi-solid porridge by reducing viscosity , thus making it more suitable for children during their critical weaning period of 6 - 24 months . This strategy of improving nutrient density of weaning foods has been widely promoted but limited quantitative information is available on its benefits ( 2 - 6 ) . Furthermore , maintaining intake of adequate calories during diarrhoea1 illness has a beneficial effect on the nutritional outcome of acute diarrhoea in infants and children ( 7 ) . Food intake during acute diarrhoea decreases substantially , except for breast milk ( 8) , and no data are available on the usefulness of energy dense porridge liquified by amlylase in infants with diarrhoeal illness . In this study we have examined the usefulness of germinated wheat flour as a source of amylase to liquify thick , sticky rice porridge , rice being the staple for a large population in developing countries . Wheat grains were germinated by soaking them overnight and keeping them moist with a black cloth for 48 h ; germinated grains were oven dried at 50 ° C overnight and ground into a flour using a kitchen blender ; when stored in sealed polythelene bags at room temperature the liquifying effect of this flour was good for a t least six weeks . To make 100 g of porridge , 18 g of rice , 6 g of lentil and 3 g of soya oil were cooked with 0.5 g of common salt and a small amount of mild spices and water , and mashed in a blender . To 100 g of porridge , 2 g of germinated wheat flour was added which liquified the porridge in a few minutes . Viscosity was measured by a Brookfield viscometer model RVT using spindle RV-2 for liquified porridge and T-spindle size D for thick sticky porridge at 2.5 rpm . In a preliminary adult taste test the liquified porridge was found to be tasty and sweet . In a r and omized trial , infants 5 - 12 months of age of either sex with acute watery diarrhoea of three days or less and mild moderate dehydration , attending the treatment centre of ICDDR , B , were allocated to receive a single meal of an energy dense , liquified porridge or a thick , sticky porridge after they were rehydrated completely with oral rehydration salt solution ( usually 6 - 8 h after admission ) and at a time when a meal was usually offered to the infants . One type of porridge was offered ad libitum over a period of 30 min . A food balance with 0.1 g sensitivity was used to measure the amount consumed by substracting th ? final weight from the initial weight of the food offered . Mothers fed their infants with a spoon and a cup after they had been instructed and shown how to feed the child . Mothers were also asked about the porridge using a semistructured question naire . Viscosity ( Table 1 ) of the porridge ( eight Sixty children less than 2 years of age suffering from mild acute gastroenteritis with less than 5 % dehydration were r and omly assigned to two different isocaloric feeding regimens , viz . , a locally prepared milk-free formulation ( group A ) of rice , lentil , sugar , and coconut oil and a spray dried commercial cow 's milk formula ( group B ) . There were two treatment failures in group A and one in group B. The postintervention duration of diarrhea ( days ) in group A ( 11.0 + /- 10.0 ) was higher than in group B ( 7.6 + /- 10.8 ) , but these differences were not significant ( p greater than 0.05 ) . The energy intake ( kcal/kg/24 h ) on postintervention day 4 was 78.7 + /- 31.7 in group A and 101.3 + /- 41.1 in group B ( p greater than 0.05 ) . The corresponding values for day 7 were 74.2 + /- 29.1 and 110.0 + /- 41.1 , respectively ( p less than 0.05 ) . The mean weight gain ( g/kg/24 h ) between admission and the day of recovery in group A ( 2.0 + /- 4.2 ) was significantly lower ( p less than 0.05 ) than in group B ( 5.8 + /- 7.8 ) . Similar trends in weight gain were observed at days 4 and 7 . These findings suggest that a cow 's milk-based formula is well tolerated by majority of the infants with mild acute gastroenteritis after initial rehydration with ORS . The infants who were fed the milk-free cereal-based diet showed significantly less energy intake and gained weight less rapidly than those who were fed the cow 's milk-based formula Forty weaned male infants were studied during their first year of life , all hospitalized with acute diarrhea in the Gastroenterology and Metabolism Unit of the Hospital " Umberto I " , São Paulo , SP , Brazil . We evaluated and quantified water fecal losses , employing the metabolic bed technique , relating the feeding formula employed with the different causal enteropathogenic agents . 67.5 % of the studied infants were under six months and 40 % under three months of age . Two groups were r and omly assembled to receive , lactose or lactose free feeding formulae . Twenty one patients received a lactose-containing formula ( Ninho 10 % ) and the other 19 children were fed caseine ( Portagen ) formulae . According to coproculture results and identification of enteropathogenic agents , we divided the studied infants relating feeding formula with the presence or absence of the enteropathogenic Escherichia coli ( EPEC ) : I-13 with positive coproculture for EPEC and diets which included lactose--(L/EPEC+ ) ; II -- eight with negative coproculture for EPEC and diets which included lactose--(L/EPEC- ) ; III -- seven with positive coproculture for EPEC and lactose free diets--(G/EPEC+ ) ; IV--12 with negative coproculture for EPEC and lactose free diets . ( G/EPEC- ) . The most frequently isolated agent at coproculture was EPEC , in 20 of the cases ( 50 % ) , followed by Campylobacter ( 7.5 % ) . It was also possible to observe that the frequencies of EIEC , Salmonella and Rotavirus were all equal ( 2.5 % ) . Mixed infections occurred only between EPEC and EIEC , registering a frequency of 5 % . The EIEC sample s , associated to EPEC 0111 were serotyped as 0 28 ac : H- and 0 152:H- . The use of metabolic bed made the evaluation of fecal volumes possible by a simple and quick technique , thus allowing a closer clinical monitoring , as well as a more reliable evaluation of the patients hospitalized with acute diarrhea . Average acceptance volumes of the formulae -- either with or without lactose -- were always below the amount recommended by FAO/WHO ( 100 kcal/day ) which shows the impact of acute diarrhea on the decrease of food intake . The average volumes of watery fecal losses found among any of the studied subgroups may be considered quite relevant when compared to st and ard values . Especially within the L/EPEC+ group fecal losses , both on the first day ( 83.56 ml/kg/day ) and , mainly , on the second ( 119.44 ml/kg/day ) reached exceedingly high levels indicating a disastrous association between the presence of EPEC in the small intestine and lactose offer in the diet . Thus , the results show that there exists a positive and significant association between poor lactose absorption and the presence of EPEC in the feces . WHO 's recommendation proposing the use of diluted cow milk , in universal and indiscriminate administration , in the two first days of the disease , may represent a risk factor , not only for malnutrition , but also for the survival rates of children with severe diarrhea , especially those under six months of age and hospitalized with EPEC enteroinfection Twenty-two infants hospitalized for severe , nonbacterial diarrhea were given at r and om either soy-protein , isolate formula or skim milk formula , following a variable period of intravenous rehydration . There was no difference in admission weight , age , duration of diarrhea , number of stools on the day prior to admission , or degree of dehydration between the two groups . The infants receiving skim milk had many more treatment failures . There was no great difference in serum electrolyte concentrations in the two feeding groups . The data suggest that during the recovery phase of gastroenteritis in young infants , a lactose-free , soy-based formula has definite advantages 46 children ( 26 boys and 20 girls ) admitted with mild acute gastroenteritis were r and omly allocated to a regimen of continuing on full-strength milk , or to one of taking clear fluids until the diarrhoea settled before full-strength milk was reintroduced either immediately , or gradually in quarter-strength steps . There was no difference in length of hospital stay between the three groups Dietary restriction in cases of mild infantile diarrhea is often advocated but has not been shown to be effective . We enrolled 176 healthy infants less than 1 year of age in a r and omized controlled trial to determine the effects of diet on the course of mild diarrhea . When diarrhea occurred ( 56 episodes ) , infants were r and omly assigned to a treatment diet ( 24 hours of electrolyte solution then dilute soy formula , dilute cow 's milk formula , or undiluted soy formula ) or their usual formula . Parents recorded daily weights , stool losses , and oral intake . The difference in effects of unrestricted and treatment diets was small and not clinical ly significant . Patients on an unrestricted diet averaged 0.7 fewer days of diarrhea ( 95 % confidence interval [ CI ] , -1.43 to 0.02 ) , 5.0 fewer total stools ( 95 % CI , -10.26 to 0.33 ) , and 1 % less weight loss ( 95 % CI , 2 % to -1 % ) compared with those receiving a treatment diet . Treatment failures were similar in both groups . An unrestricted diet does not appear to affect the course or symptoms of mild diarrhea Sixty infants were r and omly assigned to one of three groups on admission to hospital with a diagnosis of gastroenteritis . After rehydration , Group A received a low‐lactose , low‐fat feed ( HN25 ) in full strength ; Group B were re grade d on to a conventional formula ( SMA ) ; Group C received a hydrolysed soya and collagen feed ( Prejomin ) in full strength . All feeds were continued for 5 days . The median duration of loose stools from starting the feed was 24 hours in Group A , compared to 119 hours and 95 hours in Groups B and C , respectively . Group A showed a mean percentage increase in weight of 2.34 % , Group B showed a mean loss of 1.45 % , and Group C a mean increase of 0.15 % . These differences were statistically significant . Recovery from gastroenteritis is hastened by the use of a low‐lactose , low‐fat feed in the initial post‐rehydration phase of the disease All accident and emergency ( A&E ) attendances over a one year period were prospect ively studied in order to determine common medical presenting problems . Data were collected on children ( 0–15 years ) attending a paediatric A&E department in Nottingham between February 1997 and February 1998 . A total of 38 982 children were seen . The diagnoses of 26 756 ( 69 % ) were classified as trauma or surgical , and 10 369 ( 27 % ) as medical ; 1857 ( 4 % ) could not be classified . The commonest presenting problems reported for “ medical ” children were breathing difficulty ( 31 % ) , febrile illness ( 20 % ) , diarrhoea with or without vomiting ( 16 % ) , abdominal pain ( 6 % ) , seizure ( 5 % ) , and rash ( 5 % ) . The most senior doctor seeing these patients in A&E was a senior house officer ( intern or junior resident ) in 78 % of cases , paediatric registrar ( senior resident ) in 19 % , consultant ( attending physician ) in 1.4 % , and “ other ” in 2.6 % . Guidelines developed for A&E should target the commonest presenting problem categories , six of which account for 83 % of all medical attendances , and be directed towards senior house officers BACKGROUND Refeeding of artificially fed infants with lactose-containing formula after oral rehydration therapy in the treatment of acute diarrhea was concluded to be indifferent to non-lactose formula by a meta- analysis . In Thai as well as Asian infants and children with low lactase level from genetically determinant and with rotavirus infection , lactose malabsorption is most likely to occur and cause delayed recovery . The aim of this study was to compare the effect of a lactose-free and a lactose-containing formula in dietary management of acute childhood diarrhea . PATIENTS AND METHOD A r and omized , double-blind clinical trial of 80 male children , formula-fed , aged 3 to 24 months , admitted with acute watery diarrhea and mild or moderate dehydration , was carried out . All children received oral rehydration therapy for the first 4 hours . After appropriate rehydration , they were fed either a lactose-free formula ( Dumex Lactose-Free Formula ; treatment group , n = 40 ) or a lactose-containing formula ( Dumex Infant Formula ; control group , n = 40 ) in adjunction with oral rehydration solution . In addition , the infants were fed rice gruel as tolerated . Comparisons of duration of diarrhea , weight gain , vomiting , biochemical changes , stool frequency and weight and unscheduled intravenous fluid were made . RESULTS Three children ( 2 treatment , and 1 control ) dropped out from the study . The total number of unscheduled intravenous infusions were 6 of 80 children ( 7.5 % ) , including 2 ( 5.0 % ) in the treatment group and 4 ( 10.0 % ) in the control group . Three children in the control group did not resolve from diarrhea within 7 days of treatment . Rotavirus was identified in approximately 50 % of the children in each group . Using survival analysis , the median duration of diarrhea was significantly shortened by 20.5 hours in the treatment group compared to the control group ( 77.0 hours in the treatment group vs 97.5 hours in the control group ; P = 0.002 ) . Significantly decrease in stool frequency and increase in percent weight gain were seen in the treatment group at 24 hours . Moderate acidosis cleared up to near normal at 24 hours in the treatment group but acidosis persisted in the control group . In the rotavirus diarrhea subgroup , moderate acidosis turned to be mild in treatment group , but acidosis was unchanged with increased plasma chloride level in the control at 24 hours thus suggesting that the children in the control group might have lactose malabsorption and osmotic diarrhea . Duration of rotavirus diarrhea was shortened 23.6 hours in treatment group compared to the control ( P = 0.0034 ) . CONCLUSIONS In this study , lactose-free formula was shown to be effective in the dietary management of acute childhood diarrhea . Duration of diarrhea was shortened , weight gain was better , and stool frequency was less when compared to lactose-containing formula . Moderate acidosis cleared up spontaneously at 24 hours . Unscheduled IV could be decreased by 50 % . Children receiving lactose-free formula tolerated it well . Data of subgroup analysis of rotavirus diarrhea revealed lactose-free formula scored higher than the control group for all parameters studied A r and omized , prospect i ve study was performed on 73 male children between 3 and 14 months of age with mild to moderate dehydration caused by acute diarrhea , and who were rehydrated with WHO-ORS , and then at 4 h after admission were fed either cow 's milk or an experimental diet based on chicken , plantain , and coconut oil . There were no statistically significant differences in the admission characteristics . The group of children fed cow 's milk had a higher total volume of diarrheic evacuations ( p < 0.05 ) . The average duration of diarrhea was 20 h shorter in the group of infants on the milk-free formula . A significant correlation was observed between the volume of diarrhea and the WHO-ORS consumed during the first 48 h , but not to the volume of diet intake Sixty-eight bottle-fed babies under 9 months of age with mild acute gastroenteritis were observed to evaluate current feeding regimens following acute gastroenteritis in infancy . All babies were fed for 24 h with a glucose-electrolyte mixture ( GEM ) and then r and omly assigned to either a gradual re introduction to their normal milk , i.e. , slow re grade ; immediate return to full-strength formula ; or a rapid re grade to a hypoallergenic whey hydrolysate formula . All groups were well matched for age , sex , ethnic origin , nutritional state , and degree of hydration . There was no significance difference in stool frequency or reducing substances , vomiting , and duration of hospital stay between the three groups . Many infants ( 6/24 ) refused to take the whey hydrolysate formula , presumably because of unpalatability . Weight gain was more rapid when full-strength milk was given . Clinical relapse developed in 12 ( 17 % ) of patients . An enteric pathogen was detected in eight of this group and cow 's milk protein intolerance in three ( one from each feeding group ) . No infant had clinical ly significant lactose intolerance , in marked contrast to previous experience at Queen Elizabeth Hospital . In this group of previously healthy , well-nourished babies with mild acute gastroenteritis , there was no advantage in regrading slowly to milk or a hypoallergenic formula . An immediate return to normal formula 24 h after GEM feeding was well tolerated and simpler for parents A comparison is made between two groups of children aged 1 - 24 months and admitted to a teaching University Hospital due to acute diarrhea and severe dehydration . One group ( n = 119 ) received a diluted cow 's milk formula and the other ( n = 109 ) a full-strength formula . Duration of diarrhea was similar : In the group that received full-strength milk weight gain was greater during diarrhea ( 5.03 vs. 1.80 g/kg/day , P < 0.01 ) and during the hospital stay ( 5.39 vs. 2.33 g/kg/day , P < 0.001 ) . Weight for height z-scores and weight for height as percentage of median improved during the hospital stay only in the group that received the full-strength formula . Full-strength cow 's milk seems to be an adequate routine regimen even for children with acute diarrhea that must be treated for severe dehydration . In developing countries diarrhea and dehydration are a disease of small children . As rates of exclusive breast feeding are low , mainly in the urban setting , cow 's milk is the main and sometimes the only food available . Lactose-free formulae are priced out of reach of the poor people and in Latin America there is no accepted tradition for use of fermented milk products . Our study is an indication that use of undiluted cow 's milk may be effective for the routine treatment of acute diarrhea in children that must be treated as in patients due to severe dehydration In a prospect i ve r and omized study we investigated in 28 mainly bottle-fed infants younger than 60 days whether in acute gastroenteritis a hypoallergenic formula could prevent the development of cow 's milk protein intolerance . Group 1 ( 14 infants ) was fed with a formula adapted to human milk , Group 2 ( 14 infants ) got a semi-elementary formula ( Alfaré ) . After 3 months group II was exposed to cow 's milk protein with a st and ardized challenge and the incidence of CMPI in both groups was calculated . All cases with the acute form of CMPI occurred in group II ( 5/12 ) whereas in group I only one infant suffered from the protracted mild form of the disease . Inspite of the relatively small number of prob and s we conclude from our results that in infants who are not totally breast-fed in the post-enteritic period feeding with a formula adapted to human milk is preferable to hypoallergenic semi-elementary preparations . An allergen free period of 3 months seems to induce symptoms of cow 's milk intolerance , probably as a booster-effect to early sensibilisation Soy protein formulas are often poorly tolerated by infants with chronic nonspecific or postinfectious diarrhea syndrome . We found that these adverse responses may be prevented by using lactose , instead of sucrose or dextrimaltose , in soy formula . We studied 40 infants diagnosed as soy intolerant . They were given soy formula with differing carbohydrate contents in a r and omized , blinded prospect i ve study . Stool output , stool sodium content , and symptoms were significantly improved in infants receiving a soy-lactose formula ; no difference was seen in formulas with sucrose or maltose . Improvement occurred in three to five days in most infants . Furthermore , the characteristic frequency distribution of the favorable response to lactose suggested a specific mechanism for the inhibition of water and electrolyte losses through the bowel . The results indicate that , in the absence of lactose intolerance , a soy-lactose formula could be useful in treating chronic diarrhea and secondary protein intolerance Les result ats suggerent que l'absorption de lactose est meilleure apres ingestion de yaourt que de lait et suggerent que la diarrhee peut etre reduite par le remplacement du lait par le A r and omized , double-masked clinical trial was completed to compare the effects of four dietary regimens for the nutritional management of 116 Peruvian children between 3 and 24 months of age with acute diarrhea . Diets consisted of a modified whole milk formula ( group M ) , a lactose-hydrolyzed milk formula ( HM ) , wheat noodles and whole milk ( N-M ) , or wheat noodles and lactose-hydrolyzed whole milk ( N-HM ) , all offered in amounts up to 55 kcal/kg body weight/day for the first 2 days of treatment and up to 110 kcal/kg/day for 4 days thereafter . The clinical characteristics of the patients in each group were similar initially . Treatment failure rates in the two milk groups combined ( M = 14.3 % , HM = 20.0 % ) were greater than in the two noodle-milk groups combined ( N-M = 3.4 % , N-HM = 3.4 % ) , p = 0.03 . The average stool outputs by children in both M groups ( range 40 - 66 g/kg body weight per day on all study days ) were consistently greater than those by children in both N-M groups ( range 29 - 50 g/kg/day ) . The differences by dietary group were statistically significant on days 3 and 4 ( p less than 0.04 , analysis of variance ) . The estimated median duration s of illness [ and 95 % confidence limits ( CL ) ] in each milk group ( M = 138 h , CL : 88 - 214 ; HM = 113 h , CL : 75 - 170 ) were significantly greater than in each noodle-milk group ( N-M = 52 h , CL : 35 - 76 ; N-HM = 67 h , CL : 45 - 100 ) , p less than 0.001 - 0.071 . In this group of patients , noodle-milk mixtures produced fewer treatment failures , lower fecal outputs , and shorter duration s of diarrhea than did milk alone , regardless of the lactose contents of the respective milks or mixed diets . Small differences in intestinal absorption and changes in body weight by dietary group that were identified were of minor clinical importance during the short duration of study . Thus , the noodle-milk diets employed during this study were safer than the milk diets for the dietary management of children with acute diarrhea |
2,662 | 31,905,882 | The results of this work will provide recommendations on the use of digital interventions for the promotion of psychological well-being at work . | OBJECTIVE Psychological well-being has been associated with desirable individual and organisational outcomes .
This systematic review aims to assess the effectiveness of digital interventions for the improvement of psychological well-being and /or the prevention/management of poor mental well-being in the workplace . | Background : Mindfulness trainings are increasingly offered in workplace environments in order to improve health and productivity . Whilst promising , there is limited research on the effectiveness of mindfulness interventions in workplace setting s. Objective : To examine the feasibility and effectiveness of a Workplace Mindfulness Training ( WMT ) in terms of burnout , psychological well-being , organizational and team climate , and performance . Methods : This is a preliminary field study in four companies . Self-report question naires were administered up to a month before , at start of , and right at the end of the WMT , result ing in a pre-intervention and an intervention period . There was no separate control group . A total of 425 participants completed the surveys on the different time points . Linear mixed model analyses were used to analyze the data . Results : When comparing the intervention period with the pre-intervention period , significantly greater improvements were found in measures of burnout ( mean difference = 0.3 , p < 0.001 ) , perceived stress ( mean difference = -0.2 , p < 0.001 ) , mindfulness [ mean difference = 1.0 for the Freiburg Mindfulness Inventory ( FMI ) and 0.8 for the Mindfulness Attention Awareness Scale ( MAAS ) , both p < 0.001 ] , and well-being ( mean difference = 0.4 , p < 0.001 ) . Additionally , greater increases in team climate , organizational climate and personal performance were reported during the intervention compared to the pre-intervention period with largest improvements in team cooperation ( mean difference = 0.3 , p < 0.001 ) , productivity ( mean difference = 0.5 , p < 0.001 ) , and stress ( mean difference = -0.4 , p < 0.001 ) . Effect sizes were large for mindfulness ( d > 0.8 ) , moderate for well-being , burnout and perceived stress ( d = 0.5–0.8 ) , and ranged from low to moderate for organizational and team climate and personal performance ( d = 0.2–0.8 ) . Conclusion : These preliminary data suggest that compared to the pre-intervention period , the intervention period was associated with greater reductions in burnout and perceived stress , improvements in mindfulness , well-being , and increases in team and organizational climate and personal performance . Due to design limitations , no conclusions can be drawn on the extent to which the WMT or non-specific factors such as time have contributed to the findings . Further studies , preferably using r and omized controlled design s with longer follow up periods are needed to evaluate whether the associations found can be attributed to the WMT and whether these sustain after the training Background Internet- and mobile based stress-management interventions ( iSMI ) may be an effective means to address the negative consequences of occupational stress . However , available results from r and omised controlled trials are conflicting . Moreover , it is yet not clear whether guided or unguided self-help iSMI provide better value for money . Internet-based mental health interventions without guidance are often much less effective than interventions including at least some guidance from a professional . However , direct comparisons in r and omised controlled trials are scarce and , to the best of our knowledge , the comparative (cost)-effectiveness of guided vs. unguided iSMI has not yet been studied . Hence , this study investigates the acceptability and ( cost- ) effectiveness of minimal guided and unguided iSMI in employees with heightened levels of perceived stress . Methods A three-armed r and omised controlled trial ( RCT ) will be conducted to compare a minimal guided and unguided iSMI with a waiting list control condition ( WLC ) . Both active conditions are based on the same iSMI , i.e. GET.ON Stress , and differ only with regard to the guidance format . Employees with heightened levels of perceived stress ( PSS ≥ 22 ) will be r and omised to one of three conditions . Primary outcome will be comparative changes in perceived stress ( PSS ) . Secondary outcomes include changes in self-reported depression , work-engagement , presenteeism and absenteeism . Moreover , a cost-effectiveness analysis will be conducted from a societal perspective , including both direct medical costs and costs related to productivity losses . In addition , a cost-benefit analysis will be conducted from the employer ’s perspective . Incremental net-benefit regression analyses will address the question if there are any baseline factors ( i.e. subgroups of employees ) associated with particularly favorable cost-effectiveness when the experimental intervention is offered . Assessment s take place at baseline , 7 weeks post-treatment and 6 months after r and omisation . Discussion Online-based ( guided ) self-help interventions could be an acceptable , effective and economically sustainable approach to offer evidence -based intervention alternatives to reduce the negative consequences associated with work-related stress . This study evaluates the ( cost- ) effectiveness of two versions of an iSMI , minimal guided and unguided iSMI . Thus , the present study will further enhance the evidence -base for iSMI and provide valuable information about the optimal balance between outcome and economic costs . Trial registration German Clinical Trial Registration ( DRKS ) : DRKS00005687 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background R and omised controlled trials ( RCTs ) of social interventions are often criticised as failing to open the ‘ black box ’ whereby they only address questions about ‘ what works ’ without explaining the underlying processes of implementation and mechanisms of action , and how these vary by context ual characteristics of person and place . Realist RCTs are proposed as an approach to evaluation science that addresses these gaps while preserving the strengths of RCTs in providing evidence with strong internal validity in estimating effects . Methods In the context of growing interest in design ing and conducting realist trials , there is an urgent need to offer a worked example to provide guidance on how such an approach might be practically taken forward . The aim of this paper is to outline a three-staged theoretical and method ological process of undertaking a realist RCT using the example of the evaluation of a whole-school restorative intervention aim ing to reduce aggression and bullying in English secondary schools . Discussion First , informed by the findings of our initial pilot trial and sociological theory , we elaborate our theory of change and specific a priori hypotheses about how intervention mechanisms interact with context to produce outcomes . Second , we describe how we will use emerging findings from the integral process evaluation within the RCT to refine , and add to , these a priori hypotheses before the collection of quantitative , follow-up data . Third , we will test our hypotheses using a combination of process and outcome data via quantitative analyses of effect mediation ( examining mechanisms ) and moderation ( examining context ual contingencies ) . The results are then used to refine and further develop the theory of change . Conclusion The aim of the realist RCT approach is thus not merely to assess whether the intervention is effective or not , but to develop empirically informed mid-range theory through a three-stage process . There are important implication s for those involved with reporting and review ing RCTs , including the use of new , iterative protocol s . Trial registration Current Controlled Trials IS RCT N10751359 ( Registered 11 March 2014 Background Mental health complaints are quite common in health care employees and can have adverse effects on work functioning . The aim of this study was to evaluate an e-mental health ( EMH ) approach to workers ' health surveillance ( WHS ) for nurses and allied health professionals . Using the waiting-list group of a previous r and omized controlled trial with high dropout and low compliance to the intervention , we studied the pre- and posteffects of the EMH approach in a larger group of participants . Methods We applied a pretest – posttest study design . The WHS consisted of online screening on impaired work functioning and mental health followed by online automatically generated personalized feedback , online tailored advice , and access to self-help EMH interventions . The effects on work functioning , stress , and work-related fatigue after 3 months were analyzed using paired t tests and effect sizes . Results One hundred and twenty-eight nurses and allied health professionals participated at pretest as well as posttest . Significant improvements were found on work functioning ( p = 0.01 ) and work-related fatigue ( p < 0.01 ) . Work functioning had relevantly improved in 30 % of participants . A small meaningful effect on stress was found ( Cohen d = .23 ) in the participants who had logged onto an EMH intervention ( 20 % , n = 26 ) . Conclusion The EMH approach to WHS improves the work functioning and mental health of nurses and allied health professionals . However , because we found small effects and participation in the offered EMH interventions was low , there is ample room for improvement BACKGROUND Nursing is a notoriously high-stress occupation - emotionally taxing and physically draining , with a high incidence of burnout . In addition to the damaging effects of stress on nurses ' health and well being , stress is also a major contributor to attrition and widespread shortages in the nursing profession . Although there exist promising in-person interventions for addressing the problem of stress among nurses , the experience of our group across multiple projects in hospitals has indicated that the schedules and workloads of nurses can pose problems for implementing in-person interventions , and that web-based interventions might be ideally suited to addressing the high levels of stress among nurses . PURPOSE The purpose of this study was to evaluate the effectiveness of the web-based BREATHE : Stress Management for Nurses program . METHODS The r and omized controlled trial was conducted with 104 nurses in five hospitals in Virginia and one hospital in New York . The primary outcome measure was perceived nursing-related stress . Secondary measures included symptoms of distress , coping , work limitations , job satisfaction , use of substances to relieve stress , alcohol consumption , and underst and ing depression and anxiety . RESULTS Program group participants experienced significantly greater reductions than the control group on the full Nursing Stress Scale , and six of the seven subscales . No other significant results were found . Moderator analysis found that nurses with greater experience benefitted more . CONCLUSION Using a web-based program holds tremendous promise for providing nurses with the tools they need to address nursing related stress |
2,663 | 32,038,320 | Conclusions : We observed that transitional interventions with bridging components were no more effective in reducing readmission than treatment as usual ; however , these results are based on limited evidence .
Nevertheless , transitional interventions with bridging components are preferred by service users and could be an alternative to strategies regularly employed | Background : The transition from psychiatric hospital to community is often hindered by challenges that influence community adjustment and continuity of care .
Transitional interventions with bridging components are provided prior to discharge and continue beyond inpatient care .
They provide continuity of care and may be effective in preventing readmission .
We aim ed to assess the effectiveness of transitional interventions with predischarge and postdischarge components in reducing readmissions and improving health-related or social outcomes of patients discharged from psychiatric hospitals . | Objectives To improve engagement with care and prevent psychiatric readmission , a transitional case management intervention has been established to link with primary and secondary care . The intervention begins during hospitalization and ends 1 month after discharge . The goal of this study was to assess the effectiveness of this short intervention in terms of the level of engagement with outpatient care and the rate of readmissions during 1 year after discharge . Methods Individuals hospitalized with common mental disorders were r and omly assigned to be discharged to routine follow-up by private psychiatrists or general practitioners with ( n = 51 ) or without ( n = 51 ) the addition of a transitional case management intervention . Main outcome measures were number of contacts with outpatient care and rate of readmission during 12 months after discharge . Results Transitional case management patients reported more contacts with care service in the period between 1 and 3 months after discharge ( p = 0.004 ) . Later after discharge ( 3–12 months ) , no significant differences of number of contacts remained . The transitional case management intervention had no statistically significant beneficial impact on the rate of readmission ( hazard ratio = 0.585 , p = 0.114 ) . Conclusion The focus on follow-up after discharge during hospitalization leads to an increased short-term rate of engagement with ambulatory care despite no differences between the two groups after 3 months of follow-up . This short transitional intervention did , however , not significantly reduce the rate of readmissions during the first year following discharge . Trial registration number : Clinical Trials.gov Identifier NCT02258737 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 There is a need for interventions that effectively reduce compulsory admission to psychiatry . We conducted a r and omised controlled trial to investigate whether an innovative intervention programme prevents compulsory re-admission in people with serious mental illness . METHODS The programme addresses primarily patients ' self-management skills . It consists of individualised psychoeducation focusing on behaviours prior to and during illness-related crises , crisis cards and , after discharge from the psychiatric hospital , a 24-month preventive monitoring . A total of 238 in patients with compulsory admission(s ) in the past were r and omised to the intervention group or to treatment as usual ( TAU ) . RESULTS Fewer participants who completed the 24-month programme were compulsorily readmitted to psychiatry ( 28 % ) , compared with those receiving TAU ( 43 % ) . Likewise , the number of compulsory readmissions per patient was significantly lower ( 0.6 v. 1.0 ) and involuntary episodes were shorter ( 15 v. 31 days ) , compared with TAU . A negative binomial regression model showed a significant intervention effect ( RR 0.6 ; 95 % confidence interval 0.3 - 0.9 ) ; further factors linked to the risk of compulsory readmission were the number of compulsory admissions in the patient 's history ( RR 2.8 ) , the diagnosis of a personality disorder ( RR 2.8 ) , or a psychotic disorder ( RR 1.9 ) . Dropouts ( 37 % intervention group ; 22 % TAU ) were characterised by a high number of compulsory admissions prior to the trial , younger age and foreign nationality . CONCLUSIONS This study suggests that this intervention is a feasible and valuable option to prevent compulsory re-hospitalisation in a high-risk group of people with severe mental health problems , social disabilities , and a history of hospitalisations Discharge from psychiatric inpatient care is frequently described as chaotic , stressful , and emotionally charged . Following discharge , service users are vulnerable to becoming overwhelmed by the challenges involved in readapting to their home environments , which could result in serious problems and lead to readmission . The short transitional intervention in psychiatry ( STeP ) is a bridging intervention that includes pre- and post-discharge sections . It aims to prepare patients for specific situations in the period immediately following discharge from a psychiatric hospital . We conducted a quasi-experimental pilot study to determine the feasibility of the intervention , and gain insight into the effects of the STeP. Two inpatient wards at a Swiss psychiatric hospital participated in the study , and represented the intervention and control arms . Patient recruitment and baseline assessment were performed 2 weeks prior to discharge . Follow-up data were collected 1 week subsequent to discharge . Question naires measured coping , admission and health-care usage , self-efficacy , working alliance , experience of transition , and the number of difficulties experienced following discharge . Fourteen and 15 patients completed the follow-up assessment in the control and intervention groups , respectively . The STeP did not affect primary or secondary outcomes ; however , it was shown to be feasible , and patients ' feedback highlighted the importance of post-discharge contact sessions . Further research is required to improve underst and ing of the discharge experience , identify relevant patient outcomes , and assess the effectiveness of the intervention in an adequately-powered r and omized , controlled trial Background : Only 42 % of initial appointments following psychiatric hospitalization are kept nationally . Missed appointments increase the likelihood of rehospitalization and increase costs of outpatient care . Objective : This study explored the feasibility , outcomes , and cost of a transition intervention on attendance at the first postdischarge appointment . Design : A pilot study using a one-group prospect i ve design interviewed 15 patients hospitalized with psychosis to address potential barriers to attendance at the first postdischarge appointment . Patients also identified an agenda for this appointment and received a reminder letter . Results : Twelve ( 92 % ) of 13 patients attended the postdischarge appointment compared with the previous rate of 44 % . Two additional patients were unable to attend because they had been rehospitalized before the scheduled time of the first appointment . Discussion : Contact with a clinician who can bridge the gap between discharge and the first postdischarge appointment is feasible and may be helpful in increasing attendance rates This pilot r and omized control trial was motivated by the discovery that many individuals with mental health problems are re-hospitalized within a year , with many being unable to fully adjust to community living . A solution was proposed in the form of an intervention called transitional discharge . The transitional discharge model included : ( 1 ) peer support , which is assistance from former patients who provide friendship , underst and ing and encouragement ; and ( 2 ) overlap of inpatient and community staff in which the inpatient staff continue to work with the discharged patient until a working relationship is established with a community care provider . The overall aim of this study was to test the discharge model design ed to assist patients discharged from acute admission wards to adjust to community living . This aim was tested through a number of related hypotheses , which suggest that , 5 months following discharge from an acute admission ward of a psychiatric hospital , individuals participating in a transitional discharge model : ( 1 ) report fewer symptoms ; ( 2 ) report better levels of functioning ; ( 3 ) have better quality of life ; ( 4 ) are less likely to have been re-admitted to hospital . The study used a r and omized experimental design with two conditions : experimental and usual treatment . In general , both the control and the experimental group demonstrated significant improvements in symptom severity and functional ability after 5 months . Usual treatment subjects in the control group were more than twice as likely to be re-admitted to hospital . This study needs to be replicated in Scotl and with a larger sample and with a modified variation of the intervention called the Transitional Care Intervention OBJECTIVES This study tested the accuracy of models for predicting rehospitalization in a managed behavioral health organization and tested the effectiveness of different care management strategies for enhancing outpatient treatment follow-up . METHODS In a controlled study , patients with an inpatient mental health or substance use admission received one of three types of care management , distinguished by the level of care managers ' involvement in discharge planning and postdischarge outreach : usual ( N=31 ) , enhanced ( N=94 ) , and intensive ( N=74 ) . The groups were compared with each other and with a cohort admitted in the year before the study that received usual care management ( N=192 ) to determine whether differences existed in time to outpatient follow-up , amount of postdischarge care , and rehospitalization at 30 , 60 , and 180 days . RESULTS No differences between groups were found . The majority of patients ( 69 percent ) received outpatient care within 30 days of discharge . Prediction models using logistic regression suggested that the number of clinical and sociodemographic risk factors identified by care managers was related to the rate of rehospitalization at 60 and 180 days . Patients authorized to receive intermediate care ( partial hospitalization or residential care ) and those who failed to attend intermediate care if it was authorized were more likely than other patients to be rehospitalized at 30 , 60 , and 180 days . CONCLUSIONS Outpatient follow-up after psychiatric hospitalization did not improve with increasingly intensive discharge planning and outreach . Improvement in prediction of risk of rehospitalization may increase opportunities to provide intensive interventions for difficult-to-engage patients The objective of this study was to determine the cost and effectiveness of a transitional discharge model ( TDM ) of care with clients who have a chronic mental illness . The model was tested in a r and omized clinical trial using a cluster design . This model consisted of : ( 1 ) Peer support for 1 year and ( 2 ) Ongoing support from hospital staff until a therapeutic relationship was established with the community care provider . Participants ( n = 390 ) were interviewed at discharge , 1 month post-discharge , 6 months post-discharge and 1 year post-discharge . Data collected included demographics , quality of life , health care utilization , levels of functioning and the degree of intervention received . The intervention group post-discharge costs and quality of life were not significantly improved compared with the control group . Although not predicted a priori , intervention subjects were discharged an average of 116 days earlier per person . Based on the hospital per diem rate this would be equivalent to 12 M dollars CDN hospital costs . Both under-implementation among implementation wards and contamination in control wards were found . This study demonstrates some of the multiple challenges in health system research OBJECTIVES This study assessed the effectiveness of a brief three-month critical time intervention ( B-CTI ) model in improving continuity of psychiatric outpatient care for individuals with serious mental illness who are discharged from inpatient psychiatric treatment facilities . METHODS A total of 135 consenting veterans who were diagnosed as having serious mental illness and were discharged from an acute inpatient unit were r and omly assigned to receive either B-CTI or usual care . The three-month B-CTI intervention begins before discharge . A B-CTI clinician meets with the patient , assesses needs , and maintains a high level of patient contact after discharge . Participants completed interviews at baseline and three months later . Chart review s provided data on service utilization in the six months postdischarge . RESULTS Compared with the control group , the B-CTI group had significantly fewer days between their hospital discharge and their first outpatient service . B-CTI participants were more likely to have had an outpatient visit and to have had more total mental health and substance abuse visits within 30 and 180 days of discharge . They had greater continuity of care as evidence d by a greater number of two-month blocks with two or more outpatient visits over 180 days . Participants in the B-CTI group reported receiving more help in making and keeping medical and mental health appointments , making family contact and community connections , and receiving information on prescribed medications . CONCLUSIONS This study provides evidence that a B-CTI targeted at the point of inpatient discharge can be helpful in promoting postdischarge continuity of care for persons with serious mental illness . The limited association of improved continuity of care with patient outcomes in this brief intervention dem and s further study AIMS AND OBJECTIVES To investigate the effectiveness of discharge planning on the knowledge , clinical symptoms and frequency of hospitalisation of persons with schizophrenia . BACKGROUND Discharge planning is associated with decreases in the duration of hospitalisation , readmission to hospitals and decreases in medical costs . Yet , there is little known about the effectiveness of discharge planning among persons with schizophrenia in Iran . DESIGN Longitudinal clinical trial . METHODS In this longitudinal clinical trial , 46 persons with schizophrenia admitted to psychiatric hospitals were selected and classified into either intervention or control groups . For the intervention group , the discharge planning was design ed using the nursing process model . The intervention was implemented across six sessions in the hospital and six sessions in patient 's home ( up to three months after discharge ) . Friedman test , independent t-tests , chi-squared test , Mann-Whitney U-test and Mc-Nemar 's test were used to analyse demographic characteristics , knowledge scores , clinical symptoms and the frequency of hospitalisation . RESULTS The intervention group demonstrated improved clinical symptoms between the time of discharge and three months after discharge and had higher knowledge levels compared with the control group . In addition , the frequency of patients ' hospitalisation preintervention and three months postintervention was statistically significantly lower in the intervention group , while no such differences were found among the control group during this same time period . CONCLUSION This study suggests that there are a number of advantages to discharge planning including an increase in the knowledge of patients , a decline in clinical symptoms and a reduction in the frequency of admission to hospitals . RELEVANCE TO CLINICAL PRACTICE Due to high frequency of relapse , rehospitalisation and high remedial costs of persons with schizophrenia , it is important to consider discharge planning as a therapeutic approach for patients Background Several previous observational studies have reported the risk factors associated with readmission in people with mental illness . While patient-reported experiences and outcomes have become increasingly important in healthcare , only a few studies have examined these parameters in terms of their direct association with readmission in an acute psychiatric setting . This project will investigate multiple factors associated with readmission and community living in acute psychiatric patients in Japan . This study will primarily investigate whether patient-reported experiences at discharge , particularly quality of life ( QoL ) , are associated with future readmission and whether readmission after the index hospitalization is associated with changes in patient-reported outcomes during the study period . Here , we describe the rationale and methods of this study . Methods This multicenter prospect i ve cohort study is being conducted in 21 participating Japanese hospitals , with a target sample of approximately 600 participants admitted to the acute psychiatric ward . The study has four planned assessment points : time of index admission ( T1 ) , time of discharge ( from the index admission ) ( T2 ) , 6 months after discharge from the index admission ( T3 ) , and 12 months after discharge from the index admission ( T4 ) . Participants will complete self-reported measures including a QoL scale , a subjective disability scale , and an empowerment- and self-agency-related scale at each assessment point ; additionally , service satisfaction , subjective view of need for services , and subjective relationships with family members will be assessed at T2 and T3 . We will assess the participants ’ hospitalization during the study period and evaluate several potential individual- and service-level factors associated with readmission and patient-reported experiences and outcomes . Multivariate analyses will be conducted to identify potential associations between readmission and patient-reported experiences and outcomes . Discussion The present study may produce evidence on how patient-reported experiences at discharge influence readmission and on the influence of readmission on the course of patient-reported outcomes from admission to community living after discharge . The study may contribute to improving care for both patients ’ subjective views of their own health conditions and their community lives in an acute psychiatric setting .Trial registration University Hospital Medical Information Network— Clinical Trials Registry ( UMIN-CTR ) UMIN000034220 . Registered on September 20 , 2018 OBJECTIVE : People with multiple and persistent mental and physical health problems have high rates of transition failures when transferring from a hospital level of care to home . The transitional care model ( TCM ) is evidence -based and demonstrated to improve posthospital outcomes for elderly with physical health conditions , but it has not been studied in the population with serious mental illness . METHOD : Using a r and omized controlled design , 40 in patients from two general hospital psychiatric units were recruited and r and omly assigned to an intervention group ( n = 20 ) that received the TCM intervention that was delivered by a psychiatric nurse practitioner for 90 days posthospitalization , or a control group ( n = 20 ) that received usual care . Outcomes were as follows : service utilization , health-related quality of life , and continuity of care . RESULTS : The intervention group showed higher medical and psychiatric rehospitalization than the control group ( p = .054 ) . Emergency room use was lower for intervention group but not statistically significant . Continuity of care with primary care appointments were significantly higher for the intervention group ( p = .023 ) . The intervention group ’s general health improved but was not statistically significant compared with controls . CONCLUSIONS : A transitional care intervention is recommended ; however , the model needs to be modified from a single nurse to a multidisciplinary team with expertise from a psychiatric nurse practitioner , a social worker , and a peer support specialist . A team approach can best manage the complex physical/mental health conditions and complicated social needs of the population with serious mental illness |
2,664 | 27,146,257 | There are no data available on the role of HDC-ASCT for PTCL from r and omized controlled trials .
The achievement of first CR ( CR1 ) before ASCT appears to be a strong predictor of improved survival .
However , this observation reflects selection bias : patients who achieve CR1 have inherently more chemo-sensitive disease and are more likely to proceed to HDCASCT . | Peripheral T-cell lymphomas ( PTCL ) are typically associated with poor prognosis .
Anthracycline-containing regimens , such as CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisolone ) , are commonly used as first-line treatment for PTCL despite a lack of high-level evidence , rational design or biological basis .
In the retrospective International T-cell Project ( ITcP ) , in which 85 % of patients received CHOP-based chemotherapy , the 5-year failure-free survival ( FFS ) was 20 % , 18 % and 36 % for PTCL-not otherwise specified ( PTCL-NOS ) , angioimmunoblastic T-cell lymphoma ( AITL ) and anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma ( ALCL ) respectively ( Vose et al , 2008 ) .
In a recent phase III study , the 2-year event-free-survival ( EFS ) was 41 % for CHOP-treated PTCL ( Simon et al , 2010 ) .
Attempts to improve outcomes in CHOP-treated PTCL have included the addition of another agent , such as etoposide ( CHOEP ) , alemtuzumab , romidepsin and brentuximab although , to- date , no survival advantage has been unequivocally demonstrated .
Given the disappointing outcome data with CHOP for PTCL , high-dose chemotherapy followed by autologous stem cell transplant ( HDC-ASCT ) has been widely employed as consolidation therapy for patients with PTCL in first response , notwithst and ing an absence of r and omized studies to support this treatment approach . | AIM To analyze toxicity , response and outcome of a phase II trial with intensive chemotherapy plus autologous stem-cell transplantation ( ASCT ) for young patients with peripheral T-cell lymphoma ( PTCL ) . PATIENTS AND METHODS Forty-one patients [ 30 males and 11 females , median age 47 years ] consecutively diagnosed with PTCL received three courses of high-dose cyclophosphamide 2000 mg/m(2)/day , adriamycin 90 mg/m(2)/day , vincristine and prednisone alternating with three courses of etoposide , cisplatin , cytarabine and prednisone . Responders were su bmi tted to ASCT . RESULTS Sixty-eight percent of patients received the planned treatment . After chemotherapy , 20 patients reached complete response ( CR ) , 4 partial response and 17 failed . ASCT was carried out in 17 of 24 c and i date s due to lack of mobilization ( three cases ) , toxicity ( two ) , early relapse and patient decision ( one each ) . CR rate after treatment was 51 % . With a median follow-up of 3.2 years , 5 of 21 CR patients relapsed and 2 died in CR due to secondary neoplasms . Four-year progression-free survival was 30 % . Twenty-two patients have died , with a 4-year overall survival of 39 % . International Prognostic Index was the main variable predicting survival . No differences were seen among the 24 c and i date s according to whether or not they underwent ASCT . CONCLUSION This intensive regimen result ed in moderate CR rate , with manageable toxicity in PTCL . The contribution of ASCT in preventing relapse is debatable . Novel strategies to increase CR warrant investigation Peripheral T‐Cell lymphomas ( PTCL ) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B‐cell lymphomas . Despite unsatisfactory results with the cyclophosphamide , doxorubicin , vincristine , prednisone ( CHOP ) regimen , it remains the reference front‐line therapy in these diseases , but has not been challenged in phase III trials . The Groupe Ouest Est d’Etude des Leucémies et Autres Maladies du Sang ( GOELAMS ) devised an alternative therapeutic schedule including etoposide , ifosfamide , cisplatin alternating with doxorubicin , bleomycin , vinblastine , dacarbazine ( VIP‐reinforced‐ABVD ; VIP‐rABVD ) and compared it to CHOP/21 as front‐line treatment in non‐cutaneous PTCL . All newly diagnosed patients were eligible . The primary objective was to improve the 2‐year event‐free survival ( EFS ) rate . Secondary objectives were to compare the response rate , overall survival , and toxicities as well as identify prognostic factors . Eighty‐eight patients were identified between 1996 and 2002 . Both arms were well balanced for patients ’ characteristics in terms of histological and clinical presentation . No significant difference was observed between the two arms in terms of 2‐year EFS . Anaplastic large cell lymphoma type and Ann Arbor stage I – II were identified as two independent favourable prognostic factors influencing survival . VIP‐rABVD was not superior to CHOP/21 in terms of EFS as first‐line treatment of PTCL , confirming that CHOP/21 remains the reference regimen in these lymphomas We report the results of two prospect i ve phase II studies investigating the role of high-dose sequential chemotherapy , followed by autologous stem cell transplantation ( ASCT ) in 62 patients with advanced stage peripheral T-cell lymphomas ( PTCLs ) at diagnosis . Conditioning regimen consisted of mitoxantrone ( 60 mg/m2 ) and melphalan ( 180 mg/m2 ) or carmustine , etoposide , Ara-C and melphalan followed by peripheral blood stem cell autografting . In an intent-to-treat analysis , 46 out of 62 patients ( 74 % ) completed the whole programme , whereas 16 patients did not undergo ASCT , mainly because of disease progression . At a median follow-up of 76 months , the estimated 12-year overall ( OS ) , disease-free and event-free survival ( EFS ) were 34 , 55 and 30 % , respectively . OS and EFS were significantly better in patients with anaplastic lymphoma-kinase (ALK)-positive anaplastic large-cell lymphoma ( ALCL ) , as compared with the remaining PTCL . Multivariate analysis showed that patients attaining complete remission ( CR ) before ASCT had a statistically significant benefit in terms of OS and EFS ( P<0.0001 ) . Overall treatment-related mortality rate was 4.8 % . In conclusion , our findings indicate ( 1 ) up-front high-dose therapy and ASCT are feasible , but could induce a high rate of long-term CR only in patients with ALK-positive ALCL and ( 2 ) the achievement of CR before autografting is a strong predictor of better survival OBJECTIVE Retrospective data shows that peripheral T-cell lymphoma ( PTCL ) patients sensitive to conventional chemotherapy for aggressive lymphomas may respond better if this treatment is consoli date d with frontline autologous stem cell transplantation ( ASCT ) . Here , we present data from a prospect i ve phase II trial of high-dose chemotherapy and ASCT as a frontline consolidation therapy for aggressive nodal PTCL . METHODS This study involved 26 gallium-scan-positive patients with high-risk nodal PTCL [ excluding anaplastic lymphoma kinase ( ALK ) positive ] . Patients received three courses of MegaCHOP before they were evaluated , and those that were gallium-scan-negative at this stage then received another course of MegaCHOP and ASCT . Patients who remained gallium-scan-positive received two courses of an IFE regimen ( ifosfamide 10 g/m(2 ) , etoposide 150 mg/m(2)/12 h on days 1 - 3 ) and if they at least achieved PR , they then received the transplant . RESULTS Complete response ( CR ) was achieved by 12 patients ( 46 % ) after three courses of MegaCHOP and 12 patients received IFE as a salvage therapy . After the ASCT ( n = 19 ) , 89 % of patients achieved CR . In contrast , six patients ( 23 % ) did not receive the transplant because of the progression of the disease ( n = 5 ) or lethal toxicity ( n = 1 ) . One patient in first-line CR refused ASCT . After a median follow-up of 35 months , the overall survival ( OS ) and progression-free survival ( PFS ) at 3 yr was 73 % and 53 % , respectively . Moreover , the OS , PFS and disease-free survival ( DFS ) were 84 % , 56 % and 63 % , respectively 2 yr after transplant in patients who received ASCT consolidation ( n = 19 ) . CONCLUSIONS Early salvage therapy for patients with high-risk aggressive nodal PTCL that do not achieve CR after three courses of chemotherapy and ASCT frontline consolidation for chemosensitive patients may improve treatment outcome To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High- Grade Non-Hodgkin Lymphoma Study Group ( DSHNHL ) . Two hundred eighty-nine patients belonged to 1 of the 4 major T-cell lymphoma subtypes : anaplastic large cell lymphoma ( ALCL ) , anaplastic large cell lymphoma kinase (ALK)-positive ( n = 78 ) ; ALCL , ALK-negative ( n = 113 ) ; peripheral T-cell lymphoma , unspecified ( PTCLU ; n = 70 ) ; and angioimmunoblastic T-cell lymphoma ( AITL ; n = 28 ) . Treatment consisted of 6 - 8 courses of CHOP ( cyclophosphamide , doxorubicin , vincristine , prednisone/prednisolone ) or etoposide plus ( CHOEP ) . Three-year event-free survival ( EFS ) and overall survival were 75.8 % and 89.8 % ( ALK-positive ALCL ) , 50.0 % and 67.5 % ( AITL ) , 45.7 % and 62.1 % ( ALK-negative ALCL ) , and 41.1 % and 53.9 % ( PTCLU ) , respectively . The International Prognostic Index ( IPI ) was effective in defining risk groups with significantly different outcomes . For patients , ≤ 60 years with lactate dehydrogenase ≤ upper normal value ( UNV ) , etoposide improved improved 3-year EFS : 75.4 % versus 51.0 % , P = .003 . In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the st and ard therapy . Patients with ALK-negative ALCL , PTCLU , or AITL presenting with IPI > 1 have a poor prognosis and should be considered c and i date s for novel treatment strategies PURPOSE Systemic peripheral T-cell lymphomas ( PTCLs ) respond poorly to conventional therapy . To evaluate the efficacy of a dose-dense approach consoli date d by up-front high-dose chemotherapy ( HDT ) and autologous stem-cell transplantation ( ASCT ) in PTCL , the Nordic Lymphoma Group ( NLG ) conducted a large prospect i ve phase II study in untreated systemic PTCL . This is the final report , with a 5-year median follow-up , of the NLG-T-01 study . PATIENTS AND METHODS Treatment-naive patients with PTCL age 18 to 67 years ( median , 57 years ) were included . Anaplastic lymphoma kinase ( ALK ) -positive anaplastic large-cell lymphoma ( ALCL ) was excluded . An induction regimen of six cycles of biweekly CHOEP ( cyclophosphamide , doxorubicin , vincristine , etoposide , and prednisone ) was administered ( in patients age > 60 years , etoposide was omitted ) . If in complete or partial remission , patients proceeded to consolidation with HDT/ASCT . RESULTS Of 166 enrolled patients , 160 had histopathologically confirmed PTCL . The majority presented with advanced-stage disease , B symptoms , and elevated serum lactate dehydrogenase . A total of 115 underwent HDT/ASCT , with 90 in complete remission at 3 months post-transplantation . Early failures occurred in 26 % . Treatment-related mortality was 4 % . At 60.5 months of median follow-up , 83 patients were alive . Consoli date d 5-year overall and progression-free survival ( PFS ) were 51 % ( 95 % CI , 43 % to 59 % ) and 44 % ( 95 % CI , 36 % to 52 % ) , respectively . Best results were obtained in ALK-negative ALCL . CONCLUSION Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44 % of treatment-naive patients with PTCL . This represents an encouraging outcome , particularly considering the high median age and adverse risk profile of the study population . Therefore , dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantation-eligible patients with PTCL |
2,665 | 29,516,474 | Our systematic review demonstrates a probable temporal association between different measures of psychological stress and onset , recurrence , and severity of psoriasis . | Psoriasis is estimated to affect around 2 - 3 % of the general population .
More than one-third of Australians report having a significant level of distress in their daily lives .
Psychological stress has long been shown to play an important role in the natural history of psoriasis , but the details of this relationship remain to be clearly defined .
We performed a systematic review of the literature with the aim of determining whether there is a temporal association between psychological stress as the predictor and onset and /or exacerbation of psoriasis as the outcome measure .
Our secondary aim was to establish whether there is a relationship between the degree of psychological stress and clinical severity of psoriasis . | Objective This study tests the hypothesis that stress reduction methods based on mindfulness meditation can positively influence the rate at which psoriasis clears in patients undergoing phototherapy or photochemotherapy treatment . Methods Thirty-seven patients with psoriasis about to undergo ultraviolet phototherapy ( UVB ) or photochemotherapy ( PUVA ) were r and omly assigned to one of two conditions : a mindfulness meditation-based stress reduction intervention guided by audiotaped instructions during light treatments , or a control condition consisting of the light treatments alone with no taped instructions . Psoriasis status was assessed in three ways : direct inspection by unblinded clinic nurses ; direct inspection by physicians blinded to the patient 's study condition ( tape or no-tape ) ; and blinded physician evaluation of photographs of psoriasis lesions . Four sequential indicators of skin status were monitored during the study : a First Response Point , a Turning Point , a Halfway Point , and a Clearing Point . Results Cox-proportional hazards regression analysis showed that subjects in the tape groups reached the Halfway Point ( p = .013 ) and the Clearing Point ( p = .033 ) significantly more rapidly than those in the no-tape condition , for both UVB and PUVA treatments . Conclusions A brief mindfulness meditation-based stress reduction intervention delivered by audiotape during ultraviolet light therapy can increase the rate of resolution of psoriatic lesions in patients with psoriasis Psoriasis is a chronic inflammatory skin disease with important socioeconomic consequences . Data on psoriasis prevalence in Greece is scarce and circumstantially reported . The aim of this study was the recording of psoriatic patients ' demographic data , clinical characteristics of the disease , and exacerbating factors . Seven hundred and eighty four patients were enrolled in 6 centres ( 4 in Athens and 2 in Thessaloniki ) in a multicenter epidemiologic prospect i ve study . The mean age of patients was 43.2 ( st and ard deviation , SD 17.44 ) years ( median 42 years ) , while the men : women ratio was 1.8:1 . Additionally , 35 % of patients reported a positive family history of psoriasis . The mean age of patients at the first episode of psoriasis was 31.3 ( SD 16.39 ) years ( median 28 years ) . Psoriasis vulgaris was the most common form of psoriasis in the population participating in this study . Flares of psoriasis occurred 2.6 times per year on average . The patients considered stress as the main cause for psoriasis exacerbation . Most frequent target points of psoriasis included elbows , legs , scalp and knees . The most common symptoms reported were scaling , and itching . On average , patients visited dermatologists 2.4 times per year for issues related to psoriasis . This study provides epidemiological information regarding psoriasis in Greece . Results of this survey could assist in delineation of patient profiles , and improve communication between doctors and patients OBJECTIVES To study the clinical spectrum of psoriasis and the incidence in the general population and to identify risk factors associated with the occurrence of psoriasis . DESIGN Prospect i ve cohort study with nested case-control analysis . SETTING The data source was the United Kingdom General Practice Research Data base containing computerized clinical information entered by general practitioners ( GPs ) . PATIENTS The study population comprised patients receiving a first-ever diagnosis of psoriasis between January 1 , 1996 , and December 31 , 1997 , and free of cancer . INTERVENTIONS Diagnosis of psoriasis was vali date d in a r and om sample of 14 % of all ascertained cases requesting confirmation by the GPs . Nested case-control analysis included 3994 cases of psoriasis and a r and om sample of 10 000 controls frequency matched to cases by age , sex , and calendar year . MAIN OUTCOME MEASURES Incidence rate of psoriasis and estimates of the odds ratio ( OR ) and 95 % confidence interval ( CI ) for psoriasis as associated with selected risk factors . RESULTS The incidence rate of psoriasis was 14 per 10 000 person-years . Patients with antecedents of skin disorders and skin infection within the last year carried the highest risk of developing psoriasis ( OR , 3.6 [ 95 % CI , 3.2 - 4.1 ] , and OR , 2.1 [ 95 % CI , 1.8 - 2.4 ] , respectively ) . Also , smoking was found to be an independent risk factors for psoriasis ( OR , 1.4 [ 95 % CI , 1.3 - 1.6 ] ) . We did not find an association between risk of psoriasis and antecedents of stress , diabetes , hypertension , hyperlipidemia , cardiovascular disease , or rheumatoid arthritis . CONCLUSIONS The incidence rate in our study was higher than those published in other studies , probably owing to our case definition that considered cases recorded by the GPs independently of a specialist confirmation . Our results confirm the association between psoriasis , skin disorders , and smoking Ro 10 - 9359 is a retinoic acid derivative , selected for study because of a better tolerance than retinoic acid , shown in animal experiments . Doses of 25 mg b.i.d . , 25 mg t.i.d . and 50 mg b.i.d . were administered orally to 27 patients suffering from severe chronic generalized psoriasis . The clinical efficacy was evaluated by means of a new index , psoriasis area and severity index ( PASI ) based on severity and area of psoriatic lesions . At doses of 25 mg t.i.d . or 50 mg b.i.d . Ro 10 - -9359 proved to be an extremely potent antipsoriatic drug . A more than 90 % reduction of psoriatic lesions could be seen in 10 patients out of 20 after 4 - 8 weeks of treatment . This good effect lasted about 5 weeks after treatment . Side effects were frequent , but mostly mild and completely reversible after termination of treatment To analyze the effect of possible risk factors , including breastfeeding , on the development of childhood-onset psoriasis , a multicenter case-control study with prospect i ve collection of data was performed . Using a st and ard question naire , personal and specific variables including family history of psoriasis , maternal and environmental tobacco smoke exposure , body mass index ( BMI ) , exclusive and partial breastfeeding for at least 3 and 12 months , cow 's milk intake before 1 year , birth delivery method , and stressful life events were collected during 2009 from 537 patients with psoriasis and 511 controls younger than 18 . Overall , patients more frequently reported exposure to environmental tobacco smoke at home and stressful life events in the year preceding the diagnosis than controls . The odds ratios ( OR ) for smoking and stressful life events were 2.90 ( 95 % confidence interval [CI]=2.27 - 3.78 ) and 2.94 ( 95 % CI=2.28 - 3.79 ) , respectively . In addition , children with psoriasis were more likely to have a higher BMI ( > 26 ) than controls ( OR=2.52 ; 95 % CI=1.42 - 4.49 ) . High BMI , environmental tobacco smoke exposure at home , and stressful life events may influence the development of pediatric psoriasis BACKGROUND Psoriasis is generally thought to be worsened by stress . This presumption has been supported primarily by retrospective studies using question naires . No controlled prospect i ve study on this issue has been performed . METHODS Nine women with moderate plaque psoriasis were enrolled in the study . They all believed that their psoriasis was worsened by stress . They filled in a daily diary with estimations of actual stress levels and grade s of psoriasis . The study of each patient started when her skin disease was in a stable phase and was concluded when her psoriasis was worsened by at least 25 % from the starting level . Psoriasis area severity index scores were recorded at the start , as soon as possible after exacerbation and 2 weeks later . Stress-related blood sample s were taken at the same visits . The study was analysed as a nine-case study . RESULTS No clear pattern was found between stress levels and worsening of psoriasis in our nine patients . One patient had elevated stress levels 13 days before exacerbation of psoriasis , but for at least seven patients , there were no identifiable time relationships between stress and psoriasis appearance . For two patients , there were clear elevations of stress levels after psoriasis outbreak . CONCLUSION This limited study does not support the assumption that stress is a worsening factor in psoriasis Summary Background Patients with psoriasis may experience significant psychological and social disabilities . Stress or distress are proposed aggravators of the disease process in psoriasis . Preliminary studies to date have suggested that adjunctive psychological therapies may be effective in the clinical management of psoriasis |
2,666 | 28,593,456 | The number of high quality trials evaluating the effect of protocol ized hemodynamic management directed towards a meaningful treatment goal in critically ill patients in comparison to st and ard of care treatment is too low to prove or exclude a reduction in mortality | The effect of hemodynamic optimization in critically ill patients has been challenged in recent years .
The aim of the meta- analysis was to evaluate if a protocol ized intervention based on the result of hemodynamic monitoring reduces mortality in critically ill patients . | Background : The authors hypothesized that goal -directed hemodynamic therapy , based on the combination of functional and volumetric hemodynamic parameters , improves outcome in patients with cardiac surgery . Therefore , a therapy guided by stroke volume variation , individually optimized global end-diastolic volume index , cardiac index , and mean arterial pressure was compared with an algorithm based on mean arterial pressure and central venous pressure . Methods : This prospect i ve , controlled , parallel-arm , open-label trial r and omized 100 coronary artery bypass grafting and /or aortic valve replacement patients to a study group ( SG ; n = 50 ) or a control group ( CG ; n = 50 ) . In the SG , hemodynamic therapy was guided by stroke volume variation , optimized global end-diastolic volume index , mean arterial pressure , and cardiac index . Optimized global end-diastolic volume index was defined before and after weaning from cardiopulmonary bypass and at intensive care unit ( ICU ) admission . Mean arterial pressure and central venous pressure served as hemodynamic goals in the CG . Therapy was started immediately after induction of anesthesia and continued until ICU discharge criteria , serving as primary outcome parameter , were fulfilled . Results : Intraoperative need for norepinephrine was decreased in the SG with a mean ( ±SD ) of 9.0 ± 7.6 versus 14.9 ± 11.1 µg/kg ( P = 0.002 ) . Postoperative complications ( SG , 40 vs. CG , 63 ; P = 0.004 ) , time to reach ICU discharge criteria ( SG , 15 ± 6 h ; CG , 24 ± 29 h ; P < 0.001 ) , and length of ICU stay ( SG , 42 ± 19 h ; CG , 62 ± 58 h ; P = 0.018 ) were reduced in the SG . Conclusion : Early goal -directed hemodynamic therapy based on cardiac index , stroke volume variation , and optimized global end-diastolic volume index reduces complications and length of ICU stay after cardiac surgery OBJECTIVE To compare the efficacy of fluid resuscitation as guided by lactate clearance rate ( LCR ) and central venous oxygen saturation ( ScvO2 ) in patients with sepsis . METHODS A prospect i ve r and omized control study was conducted . Fifty patients diagnosed with severe sepsis or septic shock from January 2011 to February 2012 in department of critical care medicine of Fourth Hospital of Hebei Medical University were enrolled in the study . The patients were r and omly divided into two groups according to the sequence ( each n=25 ) : ScvO2 group and LCR group . After ICU admission , the patients were treated symptomatically timely , and fluid resuscitation was started as early as possible according to Surviving Sepsis Campaign guidance for management of severe sepsis and septic shock 2008 . Central venous pressure (CVP)≥8 mm Hg ( 1 mm Hg=0.133 kPa ) , mean arterial pressure (MAP)≥65 mm Hg and ScvO2≥0.70 served as goal values to accomplish the fluid resuscitation therapy in ScvO2 group , while CVP≥8 mm Hg , MAP≥65 mm Hg , LCR≥10 % served as goal value to accomplish the fluid resuscitation therapy in LCR group . The general condition and clinical characteristics on arrival in ICU , changes in CVP , MAP , ScvO2 , lactate level and /or LCR before ( 0 hour ) and 3 , 6 , 72 hours after the start of fluid resuscitation and the other related conditions during the therapy were recorded . RESULTS There was no significant difference in general data or clinical characteristics before the start of therapy , occurrence of organ dysfunction , or treatment measures during different time periods after start of fluid resuscitation . Compared with the condition immediately before fluid resuscitation , at 3 hours after start of fluid resuscitation , CVP were improved in LCR and ScvO2 groups ( 8.58±1.17 mm Hg vs. 6.33±1.21 mm Hg , 9.08±2.43 mm Hg vs. 5.33±0.98 mm Hg , both P<0.05 ) ; at 6 hours after start of fluid resuscitation , heart rate ( HR ) and respiratory rate ( RR ) were lowered in LCR and ScvO2 groups ( HR : 96±18 bpm vs. 127±13 bpm , 98±13 bpm vs. 116±19 bpm , RR : 23±3 times/min vs. 33±9 times/min , 24±5 times/min vs. 35±6 times/min , all P<0.05 ) , oxygenation index ( PaO2/FiO2 ) was increased in LCR and ScvO2 groups ( 179±41 mm Hg vs. 86±21 mm Hg , 202±33 mm Hg vs. 95±17 mm Hg , both P<0.05 ) , and there was no significant difference in MAP in both groups . There was no significant difference in all indexes between two groups . In LCR group , 3 hours after start of fluid resuscitation , lactate level was significantly decreased ( 2.81±0.18 mmol/L vs. 3.43±1.31 mmol/L , P<0.05 ) . Compared with the value 3 hours after start of fluid resuscitation , LCR was significantly improved at 6 hours and 72 hours after start of fluid resuscitation in LCR group [ (42.69±8.75)% , (48.87±9.69)% vs. (20.32±4.58)% , both P<0.05 ] . Compared with that immediately before fluid resuscitation , ScvO2 was significant improved in ScvO2 group at 3 hours after start of fluid resuscitation ( 0.65±0.04 vs. 0.53±0.06 , P<0.05 ) . There was no significant difference in success rate of fluid resuscitation comparing that of 6 hours and that of 72 hours [ 6 hours : 72 % ( 18/25 ) vs. 64 % ( 16/25 ) , χ(2)=0.368 , P=0.762 ; 72 hours : 88 % ( 22/25 ) vs. 88 % ( 22/25 ) , χ(2)=0.000 , P=1.000 ] , length of ICU stay ( 8±3 days vs. 10±4 days , t=0.533 , P=0.874 ) , length of hospital stay ( 29±11 days vs. 35±16 days , t=0.692 , P=0.531 ) , improvement rate [ 84 % ( 21/25 ) vs. 76%(19/25 ) , χ(2)=0.500 , P=0.480 ] or 28-day mortality [ 20 % ( 5/25 ) vs. 28 % ( 7/25 ) , χ(2)=0.439 , P=0.742 ] between LCR and ScvO2 groups . CONCLUSIONS Both LCR and ScvO2 can be taken as the index in confirming the endpoint of fluid resuscitation for patients with severe sepsis and septic shock . Fluid resuscitation therapy under the guidance of LCR is accurate and reliable in patients with severe sepsis and septic shock BACKGROUND In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock , mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal -directed therapy ( EGDT ) , in which intravenous fluids , vasopressors , inotropes , and blood transfusions were adjusted to reach central hemodynamic targets , than among those receiving usual care . We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary . METHODS In 31 emergency departments in the United States , we r and omly assigned patients with septic shock to one of three groups for 6 hours of resuscitation : protocol -based EGDT ; protocol -based st and ard therapy that did not require the placement of a central venous catheter , administration of inotropes , or blood transfusions ; or usual care . The primary end point was 60-day in-hospital mortality . We tested sequentially whether protocol -based care ( EGDT and st and ard-therapy groups combined ) was superior to usual care and whether protocol -based EGDT was superior to protocol -based st and ard therapy . Secondary outcomes included longer-term mortality and the need for organ support . RESULTS We enrolled 1341 patients , of whom 439 were r and omly assigned to protocol -based EGDT , 446 to protocol -based st and ard therapy , and 456 to usual care . Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids , vasopressors , inotropes , and blood transfusions . By 60 days , there were 92 deaths in the protocol -based EGDT group ( 21.0 % ) , 81 in the protocol -based st and ard-therapy group ( 18.2 % ) , and 86 in the usual-care group ( 18.9 % ) ( relative risk with protocol -based therapy vs. usual care , 1.04 ; 95 % confidence interval [ CI ] , 0.82 to 1.31 ; P=0.83 ; relative risk with protocol -based EGDT vs. protocol -based st and ard therapy , 1.15 ; 95 % CI , 0.88 to 1.51 ; P=0.31 ) . There were no significant differences in 90-day mortality , 1-year mortality , or the need for organ support . CONCLUSIONS In a multicenter trial conducted in the tertiary care setting , protocol -based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes . ( Funded by the National Institute of General Medical Sciences ; ProCESS Clinical Trials.gov number , NCT00510835 . ) OBJECTIVE To evaluate the effects of increased oxygen delivery on mortality and morbidity . DESIGN R and omized , controlled trial . SETTING Medical-surgical ICU of a tertiary care hospital . PATIENTS Sixty-three patients classified according to predetermined criteria as having severe sepsis or septic shock . INTERVENTIONS The patients were r and omly assigned to one of two groups : the control group ( n = 32 ) received conventional therapy with a normal targeted value of oxygen delivery , and the treatment group ( n = 31 ) received therapy with a targeted oxygen delivery index ( DO2I ) value of > 600 mL/min/m2 . The therapeutic approach to maintain BP , arterial saturation , hemoglobin concentration , and pulmonary artery occlusion pressure was similar in both groups . MEASUREMENTS AND MAIN RESULTS The hemodynamic , oxygen transport , and gastric intramucosal pH measurements were recorded at the time of admission to the study and every 6 h for the next 96 h. The outcome measures were the rate of patient mortality and the number of organ dysfunctions occurring during the ICU stay . The study groups were similar with respect to demographics and admission hemodynamic variables , but the percentage of patients with positive blood cultures was significantly higher in the control group than in the treatment group , respectively : 34 vs 13 % ( p = 0.04 ) . The average cardiac index was significantly higher in the treatment group than in the control group , respectively : 3.96 vs 3.05 L/min/m2 ( p = 0.01 ) . This factor did not significantly affect the DO2I . Nine of the 31 treatment group patients reached an average DO2I value of > 600 mL/min/m2 . The rate of mortality in the control group patients up to the time of ICU discharge ( 66 % ) was similar to that seen in the treatment group ( 74 % ) , respectively : 21 of 32 vs 23 of 31 ( p = 0.46 ) . The number of dysfunctional organs per patient was also similar in the control and treatment groups , respectively : 2.1+/-1.1 vs 2.6+/-1.2 ( p = 0.12 ) . CONCLUSION Treatment aim ed at maximizing oxygen delivery in patients with severe sepsis or septic shock does not reduce mortality or morbidity Introduction Several single-center studies and meta-analyses have shown that perioperative goal -directed therapy may significantly improve outcomes in general surgical patients . We hypothesized that using a treatment algorithm based on pulse pressure variation , cardiac index trending by radial artery pulse contour analysis , and mean arterial pressure in a study group ( SG ) , would result in reduced complications , reduced length of hospital stay and quicker return of bowel movement postoperatively in abdominal surgical patients , when compared to a control group ( CG ) . Methods 160 patients undergoing elective major abdominal surgery were r and omized to the SG ( 79 patients ) or to the CG ( 81 patients ) . In the SG hemodynamic therapy was guided by pulse pressure variation , cardiac index trending and mean arterial pressure . In the CG hemodynamic therapy was performed at the discretion of the treating anesthesiologist . Outcome data were recorded up to 28 days postoperatively . Results The total number of complications was significantly lower in the SG ( 72 vs. 52 complications , p = 0.038 ) . In particular , infection complications were significantly reduced ( SG : 13 vs. CG : 26 complications , p = 0.023 ) . There were no significant differences between the two groups for return of bowel movement ( SG : 3 vs. CG : 2 days postoperatively , p = 0.316 ) , duration of post anesthesia care unit stay ( SG : 180 vs. CG : 180 minutes , p = 0.516 ) or length of hospital stay ( SG : 11 vs. CG : 10 days , p = 0.929 ) . Conclusions This multi-center study demonstrates that hemodynamic goal -directed therapy using pulse pressure variation , cardiac index trending and mean arterial pressure as the key parameters leads to a decrease in postoperative complications in patients undergoing major abdominal surgery . Trial registration Clinical Trial.gov , NCT01401283 Background Fluid challenges ( FCs ) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units . There are clear benefits and harms from fluid therapy . Limited data on the indication , type , amount and rate of an FC in critically ill patients exist in the literature . The primary aim was to evaluate how physicians conduct FCs in terms of type , volume , and rate of given fluid ; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC . Methods This was an observational study conducted in ICUs around the world . Each participating unit entered a maximum of 20 patients with one FC . Results 2213 patients were enrolled and analyzed in the study . The median [ interquartile range ] amount of fluid given during an FC was 500 ml ( 500–1000 ) . The median time was 24 min ( 40–60 min ) , and the median rate of FC was 1000 [ 500–1333 ] ml/h . The main indication for FC was hypotension in 1211 ( 59 % , CI 57–61 % ) . In 43 % ( CI 41–45 % ) of the cases no hemodynamic variable was used . Static markers of preload were used in 785 of 2213 cases ( 36 % , CI 34–37 % ) . Dynamic indices of preload responsiveness were used in 483 of 2213 cases ( 22 % , CI 20–24 % ) . No safety variable for the FC was used in 72 % ( CI 70–74 % ) of the cases . There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive , with an uncertain or with a negatively judged response . Conclusions The current practice and evaluation of FC in critically ill patients are highly variable . Prediction of fluid responsiveness is not used routinely , safety limits are rarely used , and information from previous failed FCs is not always taken into account Introduction Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and /or low dose inotropic therapy . The mechanisms underlying this benefit remain uncertain . The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery . Methods R and omised , controlled , single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery . For eight hours after surgery , intra-venous fluid therapy was guided by measurements of central venous pressure ( CVP group ) , or stroke volume ( SV group ) . In a third group stroke volume guided fluid therapy was combined with dopexamine ( 0.5 mcg/kg/min ) ( SV & DPX group ) . Results 135 patients were recruited ( n = 45 per group ) . In the SV & DPX group , increased global oxygen delivery was associated with improved sublingual ( P < 0.05 ) and cutaneous microvascular flow ( P < 0.005 ) ( sublingual microscopy and laser Doppler flowmetry ) . Microvascular flow remained constant in the SV group but deteriorated in the CVP group ( P < 0.05 ) . Cutaneous tissue oxygen partial pressure ( PtO2 ) ( Clark electrode ) improved only in the SV & DPX group ( P < 0.001 ) . There were no differences in serum inflammatory markers . There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group ( CVP group ten patients ( 22 % ) ; pooled SV and SV & DPX groups seven patients ( 8 % ) ; P = 0.03 ) ( post hoc analysis ) . Conclusions Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery , microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery . These observations may explain improved clinical outcomes associated with this treatment in previous trials . Trial registration numberIS RCT N BACKGROUND Early goal -directed therapy ( EGDT ) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock . However , its effectiveness is uncertain . METHODS In this trial conducted at 51 centers ( mostly in Australia or New Zeal and ) , we r and omly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care . The primary outcome was all-cause mortality within 90 days after r and omization . RESULTS Of the 1600 enrolled patients , 796 were assigned to the EGDT group and 804 to the usual-care group . Primary outcome data were available for more than 99 % of the patients . Patients in the EGDT group received a larger mean ( ±SD ) volume of intravenous fluids in the first 6 hours after r and omization than did those in the usual-care group ( 1964±1415 ml vs. 1713±1401 ml ) and were more likely to receive vasopressor infusions ( 66.6 % vs. 57.8 % ) , red-cell transfusions ( 13.6 % vs. 7.0 % ) , and dobutamine ( 15.4 % vs. 2.6 % ) ( P<0.001 for all comparisons ) . At 90 days after r and omization , 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group , for rates of death of 18.6 % and 18.8 % , respectively ( absolute risk difference with EGDT vs. usual care , -0.3 percentage points ; 95 % confidence interval , -4.1 to 3.6 ; P=0.90 ) . There was no significant difference in survival time , in-hospital mortality , duration of organ support , or length of hospital stay . CONCLUSIONS In critically ill patients presenting to the emergency department with early septic shock , EGDT did not reduce all-cause mortality at 90 days . ( Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation ; ARISE Clinical Trials.gov number , NCT00975793 . ) CONTEXT Goal -directed resuscitation for severe sepsis and septic shock has been reported to reduce mortality when applied in the emergency department . OBJECTIVE To test the hypothesis of noninferiority between lactate clearance and central venous oxygen saturation ( ScvO2 ) as goals of early sepsis resuscitation . DESIGN , SETTING , AND PATIENTS Multicenter r and omized , noninferiority trial involving patients with severe sepsis and evidence of hypoperfusion or septic shock who were admitted to the emergency department from January 2007 to January 2009 at 1 of 3 participating US urban hospitals . INTERVENTIONS We r and omly assigned patients to 1 of 2 resuscitation protocol s. The ScvO2 group was resuscitated to normalize central venous pressure , mean arterial pressure , and ScvO2 of at least 70 % ; and the lactate clearance group was resuscitated to normalize central venous pressure , mean arterial pressure , and lactate clearance of at least 10 % . The study protocol was continued until all goals were achieved or for up to 6 hours . Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment . MAIN OUTCOME MEASURE The primary outcome was absolute in-hospital mortality rate ; the noninferiority threshold was set at Delta equal to -10 % . RESULTS Of the 300 patients enrolled , 150 were assigned to each group and patients were well matched by demographic , comorbidities , and physiological features . There were no differences in treatments administered during the initial 72 hours of hospitalization . Thirty-four patients ( 23 % ) in the ScvO2 group died while in the hospital ( 95 % confidence interval [ CI ] , 17%-30 % ) compared with 25 ( 17 % ; 95 % CI , 11%-24 % ) in the lactate clearance group . This observed difference between mortality rates did not reach the predefined -10 % threshold ( intent-to-treat analysis : 95 % CI for the 6 % difference , -3 % to 15 % ) . There were no differences in treatment-related adverse events between the groups . CONCLUSION Among patients with septic shock who were treated to normalize central venous and mean arterial pressure , additional management to normalize lactate clearance compared with management to normalize ScvO2 did not result in significantly different in-hospital mortality . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00372502 BACKGROUND Early , goal -directed therapy ( EGDT ) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock . However , adoption has been limited , and uncertainty about its effectiveness remains . METHODS We conducted a pragmatic r and omized trial with an integrated cost-effectiveness analysis in 56 hospitals in Engl and . Patients were r and omly assigned to receive either EGDT ( a 6-hour resuscitation protocol ) or usual care . The primary clinical outcome was all-cause mortality at 90 days . RESULTS We enrolled 1260 patients , with 630 assigned to EGDT and 630 to usual care . By 90 days , 184 of 623 patients ( 29.5 % ) in the EGDT group and 181 of 620 patients ( 29.2 % ) in the usual-care group had died ( relative risk in the EGDT group , 1.01 ; 95 % confidence interval [ CI ] , 0.85 to 1.20 ; P=0.90 ) , for an absolute risk reduction in the EGDT group of -0.3 percentage points ( 95 % CI , -5.4 to 4.7 ) . Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids , vasoactive drugs , and red-cell transfusions and reflected by significantly worse organ-failure scores , more days receiving advanced cardiovascular support , and longer stays in the intensive care unit . There were no significant differences in any other secondary outcomes , including health-related quality of life , or in rates of serious adverse events . On average , EGDT increased costs , and the probability that it was cost-effective was below 20 % . CONCLUSIONS In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation , hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome . ( Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme ; ProMISe Current Controlled Trials number , IS RCT N36307479 . ) OBJECTIVE To investigate the relationship of mortality to early resuscitation using two levels of oxygen delivery ( DO2 ) in critically ill surgical patients > or = 50 yrs of age who were stratified into groups : age < or = 75 yrs ( age 50 to 75 yrs group ) ; and age > 75 yrs ( age > 75 yrs group ) . DESIGN A prospect i ve , r and omized trial , continued from a previous project . SETTING Surgical intensive care unit , university affiliated . PATIENTS Consecutive patients , > 50 yrs of age , unable to generate a DO2 of > or = 600 mL/min/m2 with fluid resuscitation alone , with a diagnosis of systemic inflammatory response syndrome , sepsis , severe sepsis , septic shock , and /or acute respiratory distress syndrome . INTERVENTIONS During the first 24 hrs of resuscitation , patients were r and omized to receive fluids , blood transfusions , and vasoactive agents in order to achieve DO2 treatment goals of > or = 600 mL/ min/m2 in the protocol group and 450 to 550 mL/min/m2 in the control group . MEASUREMENTS AND MAIN RESULTS One hundred five patients completed the study . In patients aged 50 to 75 yrs , the mortality rate was 21 % ( 9/43 ) in the protocol group and 52 % ( 12/23 ) in the control group ( p=.01 , 95 % confidence interval of -58 % to -4 % ) . In patients > 75 yrs of age , the mortality rate was 57 % ( 12/21 ) in the protocol group and 61 % ( 11/18 ) in the control group . Oxygen extraction ratios ( O2ER ) and oxygen consumption values were significantly ( p=.02 ) lower in the age > 75 yrs group compared with the age 50 to 75 yrs group . CONCLUSIONS Patients 50 to 75 yrs of age receiving a DO2 of > or = 600 mL/min/m2 demonstrated a statistically significant ( p=.01 ) improved survival rate over patients in the control group . Patients > 75 yrs of age demonstrated no benefit from attempts to increase DO2 to > 600 mL/min/m2 , and they may have been overtreated as reflected by the lower O2ER values in this age group . Treating to an O2ER that reflects a balance between oxygen consumption and DO2 may be an alternative goal that allows individual titration Background Low mixed or central venous saturation ( S(c)vO2 ) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients . Early goal directed therapy ( EGDT ) , aim ing at an ScvO2 ≥ 70 % , has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines . Methods In this prospect i ve observational multi-center study , we determined central venous pressure ( CVP ) , hematocrit , pH , lactate and ScvO2 or SvO2 in a heterogeneous group of critically ill patients early after admission to the intensive care units ( ICUs ) in three Dutch hospitals . Results Data of 340 acutely admitted critically ill patients were collected . The mean SvO2 value was > 65 % and the mean ScvO2 value was > 70 % . With mean CVP of 10.3 ± 5.5 mmHg , lactate plasma levels of 3.6 ± 3.6 and acute physiology , age and chronic health evaluation ( APACHE II ) scores of 21.5 ± 8.3 , the in-hospital mortality of the total heterogeneous population was 32.0 % . A subgroup of septic patients ( n = 125 ) showed a CVP of 9.8 ± 5.4 mmHg , mean ScvO2 values of 74.0 ± 10.2 % , where only 1 % in this subgroup revealed a ScvO2 value < 50 % , and lactate plasma levels of 2.7 ± 2.2 mmol/l with APACHE II scores 20.9 ± 7.3 . Hospital mortality of this subgroup was 26 % . Conclusion The incidence of low ScvO2 values for acutely admitted critically ill patients is low in Dutch ICUs . This is especially true for patients with sepsis/septic shock Introduction Esophageal Doppler was confirmed as a useful non-invasive tool for management of fluid replacement in elective surgery . The aim of this study was to assess the effect of early optimization of intravascular volume using esophageal Doppler on blood lactate levels and organ dysfunction development in comparison with st and ard hemodynamic management in multiple-trauma patients . Methods This was a r and omized controlled trial . Multiple-trauma patients with blood loss of more than 2,000 ml admitted to the intensive care unit ( ICU ) were r and omly assigned to the protocol group with esophageal Doppler monitoring and to the control group . Fluid resuscitation in the Doppler group was guided for the first 12 hours of ICU stay according to the protocol based on data obtained by esophageal Doppler , whereas control patients were managed conventionally . Blood lactate levels and organ dysfunction during ICU stay were evaluated . Results Eighty patients were r and omly assigned to Doppler and 82 patients to control treatment . The Doppler group received more intravenous colloid during the first 12 hours of ICU stay ( 1,667 ± 426 ml versus 682 ± 322 ml ; p < 0.0001 ) , and blood lactate levels in the Doppler group were lower after 12 and 24 hours of treatment than in the control group ( 2.92 ± 0.54 mmol/l versus 3.23 ± 0.54 mmol/l [ p = 0.0003 ] and 1.99 ± 0.44 mmol/l versus 2.37 ± 0.58 mmol/l [ p < 0.0001 ] , respectively ) . No difference in organ dysfunction between the groups was found . Fewer patients in the Doppler group developed infectious complications ( 15 [ 18.8 % ] versus 28 [ 34.1 % ] ; relative risk = 0.5491 ; 95 % confidence interval = 0.3180 to 0.9482 ; p = 0.032 ) . ICU stay in the Doppler group was reduced from a median of 8.5 days ( interquartile range [ IQR ] 6 to16 ) to 7 days ( IQR 6 to 11 ) ( p = 0.031 ) , and hospital stay was decreased from a median of 17.5 days ( IQR 11 to 29 ) to 14 days ( IQR 8.25 to 21 ) ( p = 0.045 ) . No significant difference in ICU and hospital mortalities between the groups was found . Conclusion Optimization of intravascular volume using esophageal Doppler in multiple-trauma patients is associated with a decrease of blood lactate levels , a lower incidence of infectious complications , and a reduced duration of ICU and hospital stays Introduction The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures . In the evolution of these recommendations , indirect measures of the balance between systemic oxygen delivery and dem and s using central venous or superior vena cava oxygen saturation ( ScvO2 ≥ 70 % ) in a goal -directed approach have been added . However , while these additional goal -directed endpoints are based on evidence -based adult studies , the extrapolation to the paediatric patient remains unvali date d. Objective The purpose of this study was to compare treatment according to ACCM/PALS guidelines , performed with and without ScvO2 goal -directed therapy , on the morbidity and mortality rate of children with severe sepsis and septic shock . Design , participants and interventions Children and adolescents with severe sepsis or fluid-refractory septic shock were r and omly assigned to ACCM/PALS with or without ScvO2 goal -directed resuscitation . Measurements Twenty-eight-day mortality was the primary endpoint . Results Of the 102 enrolled patients , 51 received ACCM/PALS with ScvO2 goal -directed therapy and 51 received ACCM/PALS without ScvO2 goal -directed therapy . ScvO2 goal -directed therapy result ed in less mortality ( 28-day mortality 11.8 % vs. 39.2 % , p = 0.002 ) , and fewer new organ dysfunctions ( p = 0.03 ) . ScvO2 goal -directed therapy result ed in more crystalloid ( 28 ( 20–40 ) vs. 5 ( 0–20 ) ml/kg , p < 0.0001 ) , blood transfusion ( 45.1 % vs. 15.7 % , p = 0.002 ) and inotropic ( 29.4 % vs. 7.8 % , p = 0.01 ) support in the first 6 h. Conclusions This study supports the current ACCM/PALS guidelines . Goal -directed therapy using the endpoint of a ScvO2 ≥ 70 % has a significant and additive impact on the outcome of children and adolescents with septic shock AIM Determine current resuscitation practice s and outcomes in patients presenting to the emergency department ( ED ) with sepsis and hypoperfusion or septic shock in Australia and New Zeal and ( ANZ ) . METHODS Three-month prospect i ve , multi-centre , observational study of all adult patients with sepsis and hypoperfusion or septic shock in the ED of 32 ANZ tertiary-referral , metropolitan and rural hospitals . RESULTS 324 patients were enrolled ( mean [ SD ] age 63.4 [ 19.2 ] years , APACHE II score 19.0 [ 8.2 ] , 52.5 % male ) . Pneumonia ( n=138/324 , 42.6 % ) and urinary tract infection ( n=98/324 , 30.2 % ) were the commonest sources of sepsis . Between ED presentation and 6hours post-enrolment ( T6hrs ) , 44.4 % ( n=144/324 ) of patients received an intra-arterial catheter , 37 % ( n=120/324 ) a central venous catheter and 0 % ( n=0/324 ) a continuous central venous oxygen saturation ( ScvO(2 ) ) catheter . Between enrolment and T6hrs , 32.1 % ( n=104/324 ) received a vasopressor infusion , 7.4 % ( n=24/324 ) a red blood cell transfusion , 2.5 % ( n=8/324 ) a dobutamine infusion and 18.5 % ( n=60/324 ) invasive mechanical ventilation . Twenty patients ( 6.2 % ) were transferred from ED directly to the operating theatre , 36.4 % ( n=118/324 ) were admitted directly to ICU , 1.2 % ( n=4/324 ) died in the ED and 56.2 % ( n=182/324 ) were transferred to the hospital floor . Overall ICU admission rate was 52.4 % ( n=170/324 ) . ICU and overall in-hospital mortality were 18.8 % ( n=32/170 ) and 23.1 % ( n=75/324 ) respectively . In-hospital mortality was not different between patients admitted to ICU ( 24.7 % , n=42/170 ) and the hospital floor ( 21.4 % , n=33/154 ) . CONCLUSIONS Management of ANZ patients presenting to ED with sepsis does not routinely include protocol ised , ScvO(2)-directed resuscitation . In-hospital mortality compares favourably with reported mortality in international sepsis trials and nationwide surveys of resuscitation practice Abstract Objective To assess whether a nurse led , flow monitored protocol for optimising circulatory status in patients after cardiac surgery reduces complications and shortens stay in intensive care and hospital . Design R and omised controlled trial . Setting Intensive care unit and cardiothoracic unit of a university teaching hospital . Participants 174 patients who underwent cardiac surgery between April 2000 and January 2003 . Interventions Patients were allocated to conventional haemodynamic management or to an algorithm guided by oesophageal Doppler flowmetry to maintain a stroke index above 35 ml/m2 . Results 26 control patients had postoperative complications ( two deaths ) compared with 17 ( four deaths ) protocol patients ( P = 0.08 ) . Duration of hospital stay in the protocol group was significantly reduced from a median of nine ( interquartile range 7 - 12 ) days to seven ( 7 - 10 ) days ( P = 0.02 ) . The mean duration of hospital stay was reduced from 13.9 to 11.4 days , a saving in hospital bed days of 18 % ( 95 % confidence interval −12 % to 47 % ) . Usage of intensive care beds was reduced by 23 % ( −8 % to 59 % ) . Conclusion A nurse delivered protocol for optimising circulatory status in the early postoperative period after cardiac surgery may significantly shorten hospital stay Introduction Goal -directed therapy ( GDT ) has been shown to improve outcome when commenced before surgery . This requires pre-operative admission to the intensive care unit ( ICU ) . In cardiac surgery , GDT has proved effective when commenced after surgery . The aim of this study was to evaluate the effect of post-operative GDT on the incidence of complications and duration of hospital stay in patients undergoing general surgery . Methods This was a r and omised controlled trial with concealed allocation . High-risk general surgical patients were allocated to post-operative GDT to attain an oxygen delivery index of 600 ml min-1 m-2 or to conventional management . Cardiac output was measured by lithium indicator dilution and pulse power analysis . Patients were followed up for 60 days . Results Sixty-two patients were r and omised to GDT and 60 patients to control treatment . The GDT group received more intravenous colloid ( 1,907 SD ± 878 ml versus 1,204 SD ± 898 ml ; p < 0.0001 ) and dopexamine ( 55 patients ( 89 % ) versus 1 patient ( 2 % ) ; p < 0.0001 ) . Fewer GDT patients developed complications ( 27 patients ( 44 % ) versus 41 patients ( 68 % ) ; p = 0.003 , relative risk 0.63 ; 95 % confidence intervals 0.46 to 0.87 ) . The number of complications per patient was also reduced ( 0.7 SD ± 0.9 per patient versus 1.5 SD ± 1.5 per patient ; p = 0.002 ) . The median duration of hospital stay in the GDT group was significantly reduced ( 11 days ( IQR 7 to 15 ) versus 14 days ( IQR 11 to 27 ) ; p = 0.001 ) . There was no significant difference in mortality ( seven patients ( 11.3 % ) versus nine patients ( 15 % ) ; p = 0.59 ) . Conclusion Post-operative GDT is associated with reductions in post-operative complications and duration of hospital stay . The beneficial effects of GDT may be achieved while avoiding the difficulties of pre-operative ICU admission BACKGROUND Occult hypovolaemia is a key factor in the aetiology of postoperative morbidity and may not be detected by routine heart rate and arterial pressure measurements . Intraoperative gut hypoperfusion during major surgery is associated with increased morbidity and postoperative hospital stay . We assessed whether using intraoperative oesophageal Doppler guided fluid management to minimize hypovolaemia would reduce postoperative hospital stay and the time before return of gut function after colorectal surgery . METHODS This single centre , blinded , prospect i ve controlled trial r and omized 128 consecutive consenting patients undergoing colorectal resection to oesophageal Doppler guided or central venous pressure (CVP)-based ( conventional ) intraoperative fluid management . The intervention group patients followed a dynamic oesophageal Doppler guided fluid protocol whereas control patients were managed using routine cardiovascular monitoring aim ing for a CVP between 12 and 15 mm Hg . RESULTS The median postoperative stay in the Doppler guided fluid group was 10 vs 11.5 days in the control group P<0.05 . The median time to resuming full diet in the Doppler guided fluid group was 6 vs 7 for controls P<0.001 . Doppler patients achieved significantly higher cardiac output , stroke volume , and oxygen delivery . Twenty-nine ( 45.3 % ) control patients suffered gastrointestinal morbidity compared with nine ( 14.1 % ) in the Doppler guided fluid group P<0.001 , overall morbidity was also significantly higher in the control group P=0.05 . CONCLUSIONS Intraoperative oesophageal Doppler guided fluid management was associated with a 1.5-day median reduction in postoperative hospital stay . Patients recovered gut function significantly faster and suffered significantly less gastrointestinal and overall morbidity BACKGROUND Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients . We studied whether increasing the cardiac index to a supranormal level ( cardiac-index group ) or increasing mixed venous oxygen saturation to a normal level ( oxygen-saturation group ) would decrease morbidity and mortality among critically ill patients , as compared with a control group in which the target was a normal cardiac index . METHODS A total of 10,726 patients in 56 intensive care units were screened , among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were r and omly assigned to the three groups ( 252 to the control group , 253 to the cardiac-index group , and 257 to the oxygen-saturation group ) . RESULTS The hemodynamic targets were reached by 94.3 percent of the control group , 44.9 percent of the cardiac-index group , and 66.7 percent of the oxygen-saturation group ( P < 0.001 ) . Mortality was 48.4 , 48.6 , and 52.1 percent , respectively ( P = 0.638 ) , up to the time of discharge from the intensive care unit and 62.3 , 61.7 , and 63.8 percent ( P = 0.875 ) at six months . Among patients who survived , the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups . No differences in mortality among the three groups were found for any diagnostic category . A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates : 44.8 , 40.4 , and 39.0 percent , respectively ( P = 0.478 ) . CONCLUSIONS Hemodynamic therapy aim ed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients Purpose Response to fluid challenge is often defined as an increase in cardiac index ( CI ) of more than 10–15 % . However , in clinical practice CI values are often not available . We evaluated whether changes in mean arterial pressure ( MAP ) correlate with changes in CI after fluid challenge in patients with septic shock . Methods This was an observational study in which we review ed prospect ively collected data from 51 septic shock patients in whom complete hemodynamic measurements had been obtained before and after a fluid challenge with 1,000 ml crystalloid ( Hartman ’s solution ) or 500 ml colloid ( hydroxyethyl starch 6 % ) . CI was measured using thermodilution . Patients were divided into two groups ( responders and non-responders ) according to their change in CI ( responders : % CI > 10 % ) after the fluid challenge . Statistical analysis was performed using a two-way analysis of variance test followed by a Student ’s t test with adjustment for multiple comparisons . Pearson ’s correlation and receiver operating characteristic curve analysis were also used . Results Mean patient age was 67 ± 17 years and mean Sequential Organ Failure Assessment ( SOFA ) upon admittance to the intensive care unit was 10 ± 3 . In the 25 responders , MAP increased from 69 ± 9 to 77 ± 9 mmHg , pulse pressure ( PP ) increased from 59 ± 15 to 67 ± 16 , and CI increased from 2.8 ± 0.8 to 3.4 ± 0.9 L/min/m2 ( all p < 0.001 ) . There were no significant correlations between the changes in MAP , PP , and CI . Conclusions Changes in MAP do not reliably track changes in CI after fluid challenge in patients with septic shock and , consequently , should be interpreted carefully when evaluating the response to fluid challenge in such patients BACKGROUND The balance between the benefits and the risks of pulmonary-artery catheters ( PACs ) has not been established . METHODS We evaluated the relationship of benefits and risks of PACs in 1000 patients with established acute lung injury in a r and omized trial comparing hemodynamic management guided by a PAC with hemodynamic management guided by a central venous catheter ( CVC ) using an explicit management protocol . Mortality during the first 60 days before discharge home was the primary outcome . RESULTS The groups had similar baseline characteristics . The rates of death during the first 60 days before discharge home were similar in the PAC and CVC groups ( 27.4 percent and 26.3 percent , respectively ; P=0.69 ; absolute difference , 1.1 percent ; 95 percent confidence interval , -4.4 to 6.6 percent ) , as were the mean ( + /-SE ) numbers of both ventilator-free days ( 13.2+/-0.5 and 13.5+/-0.5 ; P=0.58 ) and days not spent in the intensive care unit ( 12.0+/-0.4 and 12.5+/-0.5 ; P=0.40 ) to day 28 . PAC-guided therapy did not improve these measures for patients in shock at the time of enrollment . There were no significant differences between groups in lung or kidney function , rates of hypotension , ventilator setting s , or use of dialysis or vasopressors . Approximately 90 percent of protocol instructions were followed in both groups , with a 1 percent rate of crossover from CVC- to PAC-guided therapy . Fluid balance was similar in the two groups , as was the proportion of instructions given for fluid and diuretics . Dobutamine use was uncommon . The PAC group had approximately twice as many catheter-related complications ( predominantly arrhythmias ) . CONCLUSIONS PAC-guided therapy did not improve survival or organ function but was associated with more complications than CVC-guided therapy . These results , when considered with those of previous studies , suggest that the PAC should not be routinely used for the management of acute lung injury . ( Clinical Trials.gov number , NCT00281268 . ) Objective The aim of this study was to compare the accuracy of the CeVOX monitor measuring continuous central venous saturation ( ScvO2 ) with laboratory blood gas oximetry under clinical circumstances . Design Prospect i ve , multicentre , observational study . Setting Five adult general intensive care units . Patients and participants Fifty-three critically ill patients . Interventions The fibre-optic probe was inserted into an ordinary central venous catheter 's distal lumen . Blood sample s were taken from this line via a Y-adapter every 8 h and ScvO2 was measured with a laboratory co-oximeter . Patients were observed for a maximum of 5 days . Results were compared using linear regression and the Bl and and Altman plots . Measurements and results The 526 matched pairs of ScvO2 showed a significant correlation between the two methods ( r = 0.79 , p < 0.001 ) . Bl and –Altman plots showed an overall mean bias of –0.3 % and moderate agreement ( lower and upper levels of agreement : –13.2 % and 12.5 % ) . Correlation for the first time point , and for differences between the first two time points for each method revealed good correlation : ( n = 53 ) : r = 0.79 , p < 0.001 ; ( n = 50 ) : r = 0.58 , p < 0.001 , respectively . Conclusion These results in a heterogeneous group of critically ill patients show that continuous ScvO2 monitoring by the CeVOX technology yielded results comparable with those obtained by laboratory co-oximetry and therefore can be relied on in everyday clinical practice Purpose To compare treatment based on either PiCCO-derived physiological values or central venous pressure ( CVP ) monitoring , we performed a prospect i ve r and omized controlled trial with group sequential analysis . Methods Consecutive critically ill patients with septic shock and /or ARDS were included . The planned total sample size was 715 . The primary outcome was 28-day mortality after r and omization . Participants underwent stratified r and omization according to the classification of ARDS and /or septic shock . Caregivers were not blinded to the intervention , but participants and outcome assessors were blinded to group assignment . Results The study was stopped early because of futility after enrollment of 350 patients including 168 in the PiCCO group and 182 in the control group . There was no loss to follow-up and data from all enrolled participants were analyzed . The result showed that treatment based on PiCCO-derived physiological values was not able to reduce the 28-day mortality risk ( odds ratio 1.00 , 95 % CI 0.66–1.52 ; p = 0.993 ) . There was no difference between the two groups in secondary outcomes such as 14-day mortality ( 40.5 vs. 41.2 % ; p = 0.889 ) , ICU length of stay ( median 9 vs. 7.5 days ; p = 0.598 ) , days free of vasopressors ( median 14.5 vs. 19 days ; p = 0.676 ) , and days free of mechanical ventilation ( median 3 vs. 6 days ; p = 0.168 ) . No severe adverse event was reported in both groups . Conclusion On the basis of our study , PICCO-based fluid management does not improve outcome when compared to CVP-based fluid management BACKGROUND Ever since Charles Baxter 's recommendations the st and ard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury . A growing number of studies on invasive monitoring in burn shock , however , have raised a debate regarding the adequacy of this regime . The purpose of this prospect i ve , r and omised study was to compare goal -directed therapy guided by invasive monitoring with st and ard care ( Baxter formula ) in patients with burn shock . PATIENTS AND METHODS Fifty consecutive patients with burns involving more than 20 % body surface area were r and omly assigned to one of two treatment groups . The control group was resuscitated according to the Baxter formula ( 4 ml/kg BW/% BSA burn ) , the thermodilution ( TDD ) group was treated according to a volumetric preload endpoint ( intrathoracic blood volume ) obtained by invasive haemodynamic monitoring . RESULTS The baseline characteristics of the two treatment groups were similar . Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group ( P = 0.0001 ) . The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters . Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups . Mortality and morbidity were independent on r and omisation . CONCLUSION Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn . Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration . Increased crystalloid infusion does not improve preload or cardiac output parameters . This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock Objective : Regional variables of organ dysfunction are thought to be better monitoring variables than global pressure-related hemodynamic variables . Whether a difference exists between regional and global volume-related variables in critically ill patients after resuscitation is unknown . Design : Prospect i ve diagnostic test evaluation . Setting : University-affiliated mixed intensive care unit . Patients : Twenty-eight critically ill patients . Interventions : Using st and ardized resuscitation , hemodynamic optimization was targeted at mean arterial pressure , heart rate , occlusion pressure , cardiac output , systemic vascular resistance , and urine output . Primary outcome variable was in-hospital mortality . Measurements and Main Results : During resuscitation , global volume-related hemodynamic variables were measured simultaneously and compared with regional variables . At admission no variable was superior as a predictor of outcome . During resuscitation , significant changes were seen in mean arterial pressure , central venous pressure , oxygen delivery , systemic vascular resistance , total blood volume , right heart and ventricle end-diastolic volume , right ventricle ejection fraction , right and left stroke work index , intramucosal carbon dioxide pressure , gastric mucosal pH , mucosal-end tidal Pco2 gap , indocyanine green blood clearance , indocyanine green plasma clearance , and plasma disappearance rate . Multivariate analysis identified lactate , gastric mucosal pH , mucosal-end tidal Pco2 gap , mucosal-arterial Pco2 gap , indocyanine green plasma clearance , and plasma disappearance rate of dye as nondependent predictors of outcome . Patients who subsequently died had a significantly lower gastric mucosal pH , higher intramucosal carbon dioxide pressure and mucosal-end tidal Pco2 gap , and lower indocyanine green blood clearance , indocyanine green plasma clearance , plasma disappearance rate , and right ventricular end-diastolic volume index , of which gastric mucosal pH , mucosal-end tidal Pco2 gap , and indocyanine green blood clearance were the most important predictors of outcome . Conclusions : Initial resuscitation of critically ill patients with shock does not require monitoring of regional variables . After stabilization , however , regional variables are the best predictors of outcome OBJECTIVE To observe the clinical effects of 10 % , 30 % lactate clearance rate and early goal -directed therapy ( EGDT ) as 6-hour resuscitation goals directing treatment in septic shock patients with severe pneumonia . METHODS In this r and omized , perspective study , septic shock patients with severe pneumonia were divided into control group and experimental group , which included 10 % lactate clearance rate group and 30 % lactate clearance rate group , adopting r and om number method . The control group was treated with 6-hour EGDT strategy , and the experimental groups were treated with 10 % lactate clearance rate protocol and 30 % lactate clearance rate protocol respectively , beside the EGDT . RESULTS There were 19 patients in control group , and 43 patients in experimental group , which included 22 patients in 10 % lactate clearance rate group and 21 patients in 30 % lactate clearance rate group . Patients were well matched by basic features . After 48 hours , the acute physiology and chronic health evaluation II ( APACHE II ) score of both 10 % lactate clearance rate group ( 13.76 ± 6.00 , P < 0.05 ) and 30 % lactate clearance rate group ( 13.60 ± 6.18 , P < 0.05 ) were lower than that of control group ( 18.15 ± 6.62 ) . There were no differences in time of mechanical ventilation ( hours ) between control group and experimental group ( 10 % group 136.90 ± 100.02 , 30 % group 97.00 ± 75.20 , control group 152.32 ± 96.51 , P > 0.05 ) . The length in intensive care unit ( ICU , days ) of 10 % and 30 % lactate clearance rate groups were significantly shorter than control group ( 10 % group 7.94 ± 6.00 , 30 % group 7.51 ± 3.99 , control group 11.31 ± 5.97 , both P < 0.05 ) . The three groups had no differences in 7-day mortality rate ( 10 % group 18.18 % , 30 % group 14.29 % , control group 21.05 % , all P > 0.05 ) , but the 28-day mortality of 10 % and 30 % lactate clearance rate groups were significantly lower than control group ( 10 % group 36.36 % , 30 % group 28.57 % , control group 63.16 % ) , especially in 30 % lactate clearance rate group ( P < 0.05 ) . CONCLUSION For the septic shock patients with severe pneumonia , prompt archiving EGDT strategy and 6-hour lactate clearance more than 30 % were associated with an optimal outcome STUDY OBJECTIVE The noninvasive cardiac output monitor and passive leg-raising maneuver has been shown to be reasonably accurate in predicting fluid responsiveness in critically ill patients . We examine whether using a noninvasive protocol would result in more rapid lactate clearance after 3 hours in patients with severe sepsis and septic shock in the emergency department . METHODS In this open-label r and omized controlled trial , 122 adult patients with sepsis and serum lactate concentration of greater than or equal to 3.0 mmol/L were r and omized to receive usual care or intravenous fluid bolus administration guided by measurements of change of stroke volume index , using the noninvasive cardiac output monitor after passive leg-raising maneuver . The primary outcome was lactate clearance of more than 20 % at 3 hours . Secondary outcomes included mortality , length of hospital and ICU stay , and total hospital cost . Analysis was intention to treat . RESULTS Similar proportions of patients in the r and omized intervention group ( 70.5 % ; N=61 ) versus control group ( 73.8 % ; N=61 ) achieved the primary outcome , with a relative risk of 0.96 ( 95 % confidence interval [ CI ] 0.77 to 1.19 ) . Secondary outcomes were similar in both groups ( P>.05 for all comparisons ) . Hospital mortality occurred in 6 patients ( 9.8 % ) each in the intervention and control groups on or before 28 days ( relative risk=1.00 ; 95 % CI 0.34 to 2.93 ) . Among a subgroup of patients with underlying fluid overload states , those in the intervention group tended to receive clinical ly significantly more intravenous fluids at 3 hours ( difference=975 mL ; 95 % CI -450 to 1,725 mL ) and attained better lactate clearance ( difference=19.7 % ; 95 % CI -34.6 % to 60.2 % ) compared with the control group , with shorter hospital lengths of stay ( difference=-4.5 days ; 95 % CI -9.5 to 2.5 days ) . CONCLUSION Protocol -based fluid resuscitation of patients with severe sepsis and septic shock with the noninvasive cardiac output monitor and passive leg-raising maneuver did not result in better outcomes compared with usual care . Future studies to demonstrate the use of the noninvasive protocol -based care in patients with preexisting fluid overload states may be warranted OBJECTIVE To investigate the efficacy and effect on outcome of goal -directed therapy in patients with septic shock compared with conventional therapy . METHODS Sixteen patients with septic shock were r and omly assigned to receive goal -directed therapy , with central venous pressure ( CVP ) 8 - 12 mm Hg ( 1 mm Hg=0.133 kPa ) , mean arterial pressure ( MAP ) > or=65 mm Hg , venous oxygen saturation ( SvO(2))>0.70 ( superior vena cava saturation ) , and urine output > or=0.5 ml/min as therapeutic goals . Another 17 patients received conventional therapy as controls . The arterial oxygen saturation ( SaO(2 ) ) , SvO(2 ) , MAP , CVP , heart stroke volume cardiac index ( CI ) , serum lactate , volume of fluid , amount of vasopressors , the numbers of organ injured and patients who needed continuity blood purification ( CBP ) and /or ventilation were recorded serially for 6 - 48 hours , and they were compared between the two groups . The mortality of the patients in two groups on 7 days and 14 days were also recorded . RESULTS There were no significant differences between the groups with respect to base-line characteristics . During the interval from 24 to 48 hours , the patients assigned to goal -directed therapy had a significantly higher in SaO(2 ) , SvO(2 ) , MAP , CVP , CI ( P<0.05 or P<0.01 ) , a lower lactate concentration ( P<0.01 ) , significantly more fluid during 6 - 24 hours and less vasopressors ( both P<0.01 ) . Seven and 14 days in-hospital mortality were lower in goal -directed therapy group as compared with the control group(P<0.05 ) . CONCLUSION The efficacy of goal -directed therapy in patients with septic shock is significantly better than conventional therapy in ameliorating outcome of shock and can be easily used in intensive care unit ( ICU ) BACKGROUND : Esophageal Doppler monitoring ( EDM ) is utilized in numerous clinical setting s. This study examines the relationship between pulmonary artery catheter ( PAC ) and EDM-derived hemodynamic parameters , concentrating on gender- and age-related EDM measurement biases . MATERIAL S AND METHODS : Prospect i ve study of EDM use in ventilated surgical ICU patients . Parameters examined included demographics , diagnosis , resuscitation endpoints , cardiac output ( CO ) and stroke volume from both devices , number of personnel and time needed to place equipment , time to data acquisition , duration of use , complications of placement . RESULTS : Fifteen patients ( 11 men , 4 women , mean age 47 years ) were included . Most common diagnoses included trauma ( 7/15 ) and sepsis ( 4/15 ) . Insertion time and time to data acquisition were shorter for EDM than for PAC ( P<0.001 ) . The EDM required an average of 1.1 persons to place ( 2.4 for PAC , P=0.002 ) . Mean EDM utilization time was 12.4 h. There was a fair CO correlation between EDM and PAC ( r = 0.647 , P<0.001 ) . Overall , the EDM underestimated CO relative to PAC ( bias -1.42 ± 2.08 , 95 % CI : -5.58 - 2.74 ) , with more underestimation in women ( mean bias difference of -1.16 , P<0.001 ) . No significant age-related measurement bias differences between PAC and EDM were noted . Significant reductions in lactate and norepinephrine requirement were noted following EDM monitoring periods . CONCLUSIONS : This study found that the EDM significantly underestimated cardiac output in women when compared to PAC . Clinicians should be aware of this measurement bias when making therapeutic decision based on EDM data . Significant reductions in lactate and norepinephrine requirement during EDM monitoring periods support the clinical usefulness of EDM technology OBJECTIVE To investigate the effect of early goal -directed therapy ( EGDT ) on treatment of critical patients with severe sepsis/septic shock . METHODS A multi-center , prospect i ve , r and omized , controlled study was deployed . Totally 314 critical patients , from eight comprehensive hospitals in Zhejiang Province admitted during January , 2005 to January , 2008 , suffering from severe sepsis/septic shock were r and omized into conventional treatment group ( n=151 ) and EGDT group ( n=163 ) , the patients of the former underwent fluid resuscitation guided by central venous pressure ( CVP ) , systolic blood pressure ( SBP ) or mean artery pressure ( MAP ) and urinary output ( UO ) , and the latter guided by CVP , SBP or MAP and UO plus central venous oxygen saturation ( ScvO2 ) . The patients were treated with fluid , blood transfusions and cardiac stimulants in a period of 6 hours after enrollment to reach the goal . The difference of 28-day survival rate and intensive care unit ( ICU ) mortality ( primary end points ) , the length of ICU stay , the duration of mechanical ventilation , duration of antibiotics treatment , incidence of newly occurred infection , and severity scores ( secondary end points ) were compared between two groups . RESULTS Finally , a total of 303 patients were eligible to enter this study , with 157 patients in EGDT group and 146 patients in conventional treatment group . In comparison with conventional treatment group , the 28-day survival rate of EGDT group was increased by 17.7 % ( 75.2 % vs. 57.5 % , P=0.001 ) and the ICU mortality of EGDT group was decreased by 15.7 % ( 35.0 % vs. 50.7 % , P=0.035 ) , the acute physiology and chronic health evaluation II ( APACHEII ) score ( 14.4+/-8.5 vs. 18.0+/-7.1 , P=0.043 ) , multiple organ dysfunction syndrome ( MODS ) score ( 5.8+/-3.1 vs. 8.9+/-3.7 , P=0.014 ) and sepsis-related organ failure assessment ( SOFA ) score ( 5.6+/-2.9 vs. 10.4+/-3.7 , P=0.001 ) were significantly decreased in EGDT group . Meanwhile , a significant shortening of duration of using antibiotics was also found [ ( 13.4+/-10.0 ) days vs. ( 19.7+/-13.5 ) days , P=0.004 ] , with a lowering of incidence of occurrence of new infection ( 37.6 % vs. 53.4 % , P=0.014 ) . There were no differences in other parameters for secondary end points . CONCLUSION EGDT improves 28-day survival rate and clinical scores , and it shows beneficial effects on outcome of critical patients with severe sepsis/septic shock OBJECTIVE To explore the effect of early goal -directed therapy ( EGDT ) according to pulse indicated continuous cardiac output ( PiCCO ) on septic shock patients . METHODS Eighty-two septic shock patients in Subei People 's Hospital of Jiangsu Province from January 2009 to December 2012 were enrolled and r and omly divided into two groups using a r and om number table , st and ard surviving sepsis bundle group ( n=40 ) and modified surviving sepsis bundles group ( n=42 ) . The patients received the st and ard EGDT bundles in st and ard surviving sepsis bundle group . PiCCO catheter was placed in modified surviving sepsis bundles group . Fluid resuscitation was guided by intrathoracic blood volume index ( ITBVI ) with the aim of 850 - 1 000 mL/m(2 ) . Dobutamine was used to improve the heart function according to left ventricular contractile index ( dPmax ) and stroke volume index ( SVI ) . The mean arterial blood pressure ( MAP ) was maintained 65 mmHg ( 1 mmHg=0.133 kPa ) or above with norepinephrine . Extra-vascular lung water was monitored for the titration of liquid and diuretics . The acute physiology and chronic health evaluation II ( APACHEII ) score , sequential organ failure assessment ( SOFA ) score , the number of patients needed vasopressor , serum procalcitonin ( PCT ) , lactic acid and lactate extraction ratio , the amount of fluid resuscitation , duration of mechanical ventilation , duration of intensive care unit ( ICU ) stay , hospital mortality were recorded in both groups . RESULTS After treatment , the APACHEII score , SOFA score and the number of patients needed vasopressor were gradually reduced in both groups , and those in modified surviving sepsis bundle group were significantly lower than those of st and ard sepsis bundle group at 72 hours ( APACHEII score : 13.1±6.5 vs. 20.9±7.5 , SOFA score : 8.8±4.3 vs. 14.6±4.9 , the number of patients needed vasopressor : 8 vs. 17 , all P<0.05 ) . Arterial blood lactate clearance rate was gradually increased after treatment in both groups . Lactate clearance rate in modified surviving sepsis bundle group was significantly higher than that of st and ard surviving sepsis bundle group [ 6 hours : (18.2±8.3)% vs. (10.8±7.5)% , t=-6.036 , P=0.001 ; 12 hours : (22.6±7.3)% vs. (12.4±8.1)% , t=-4.536 , P=0.001 ; 24 hours : (27.8±5.6)% vs. (16.4±9.5)% , t=-5.882 , P=0.000 ] . The amount of fluid resuscitation within 6 hours in modified surviving sepsis bundle group increased significantly compared with st and ard surviving sepsis bundle group ( 3 608±715 mL vs. 2 809±795 mL , t=-3.865 , P=0.033 ) . The amount of fluid resuscitation within 24 , 48 and 72 hours in modified surviving sepsis bundle group was significantly less than that of st and ard modified surviving sepsis bundle group with the nadir at 72 hours ( 918±351 mL vs. 1 805±420 mL , t=5.907 , P=0.037 ) . Duration of mechanical ventilation ( 98.4±20.3 hours vs. 143.3±29.6 hours , t=9.766 , P=0.001 ) and ICU stay ( 7.1±3.1 days vs. 9.5±2.5 days , t=2.993 , P=0.004 ) were significantly reduced in modified surviving sepsis bundle group compared with st and ard surviving sepsis bundle group . The hospital mortality in modified surviving sepsis bundle group was slightly lower than that in st and ard surviving sepsis bundle group [ 16.7 % ( 7/42 ) vs. 17.5%(7/40 ) , χ (2)=0.010 , P=0.920 ] . CONCLUSIONS Modified surviving sepsis bundle treatment according PiCCO can reduce the severity of disease in patients with septic shock , can make more accurately guide fluid resuscitation , and can reduce lung water and duration of mechanical ventilation and ICU stay . It has great clinical significance Purpose To describe the current practice s of volume expansion in French intensive care units ( ICU ) . Methods In 19 ICUs , we prospect ively observed the prescription and monitoring practice s of volume expansion in consecutive adult patients with shock [ sustained hypotension and /or need of vasopressor therapy , associated with at least tachycardia and /or sign ( s ) of hypoperfusion ] . Patients were included at the time of prescription of the first fluid bolus ( FB ) . Thereafter , all the FBs administered during the 96 h following shock onset were surveyed . An FB was defined as an intravenous bolus of at least 100 ml of a blood volume exp and er intended to rapidly improve the patient ’s circulatory condition . Results We included 777 patients [ age : 63 ± 15 years ; female gender : 274 ( 35 % ) ; simplified acute physiology score II : 55.9 ± 20.6 ; ICU length of stay : 6 days ( interquartile range ( IQR ) 3–13 ) ; ICU mortality : 32.8 % ] and surveyed 2,694 FBs . At enrolment mean arterial pressure was 63 mmHg ( IQR 55–71 ) . The most frequent triggers of FB were hypotension , low urine output , tachycardia , skin mottling and hyperlactataemia . Amount of fluid given at each FB was highly variable between centres . Crystalloids were used in 91 % ( 2,394/2,635 ) and synthetic colloids in 3.3 % ( 87/2,635 ) of FBs . Overall , clinicians used any kind of haemodynamic assessment ( central venous pressure measurement , predictive indices of fluid responsiveness , echocardiography , cardiac output monitoring or a combination of these ) in 23.6 % ( 635/2,694 ) of all FBs surveyed , with an important between-centre heterogeneity . Conclusions High between-centre variability characterised all the aspects of FB prescription and monitoring , but overall haemodynamic exploration to help guide and monitor FB was infrequent OBJECTIVE To compare two thermodilution methods for the determination of cardiac output (CO)-thermodilution in the pulmonary artery ( COpa ) and thermodilution in the femoral artery (COa)-with each other and with CO determined by continuous pulse contour analysis ( COpc ) in terms of reproducibility , bias , and correlation among the different methods . Good agreement between the methods would indicate the potential of pulse contour analysis to monitor CO continuously and at reduced invasiveness . DESIGN Prospect i ve criterion st and ard study . SETTING Cardiac surgical intensive care unit in a university hospital . PATIENTS Twenty-four postoperative cardiac surgery patients . INTERVENTIONS Without interfering with st and ard hospital cardiac recovery procedures , changes in CO as a result of the postsurgical course , administration of vasoactive substances , and /or fluid administration were recorded . CO was first recorded after a 1-hr stabilization period in the intensive care unit and hourly thereafter for 6 hrs , and by subsequent determinations at 9 , 12 , and 24 hrs . MEASUREMENTS AND MAIN RESULTS There were 216 simultaneous determinations of COpa , COa , and COpc . COpc was initially calibrated using COa , and no further recalibration of COpc was performed . COpa ranged from 3.0 to 11.8 L/min , and systemic vascular resistance ranged from 252 to 2434 dyne x sec/cm5 . The mean difference ( bias ) + /-2 SD of differences ( limits of agreement ) was -0.29+/-1.31 L/min for COpa vs. COa , 0.07+/-1.4 L/min for COpc vs. COpa , and -0.22+/-1.58 L/min for COpc vs. COa . In all but four patients COpc correlated with COa after the initial calibration . Correlation and precision of COpc vs. COa was stable for 24 hrs . CONCLUSIONS Femoral artery pulse contour CO correlates well with both COpa and COa even during substantial variations in vascular tone and hemodynamics . Additionally , CO determined by arterial thermodilution correlates well with COpa . Thus , COa can be used to calibrate COpc Objective To evaluate the clinical utility of a new device for continuous noninvasive cardiac output monitoring ( NICOM ) based on chest bio-reactance compared with cardiac output measured semi-continuously by thermodilution using a pulmonary artery catheter ( PAC-CCO ) . Design Prospect i ve , single-center study . Setting Intensive care unit . Patients Consecutive adult patients immediately after cardiac surgery . Interventions Cardiac output measurements obtained from NICOM and thermodilution were simultaneously recorded minute by minute and compared in 110 patients . We evaluated the accuracy , precision , responsiveness , and reliability of NICOM for detecting cardiac output changes . Tolerance for each of these parameters was specified prospect ively . Measurements and results A total of 65,888 pairs of cardiac output measurements were collected . Mean reference values for cardiac output ranged from 2.79 to 9.27 l/min . During periods of stable PAC-CCO ( slope < ± 10 % , 2SD/mean < 20 % ) , the correlation between NICOM and thermodilution was R = 0.82 ; bias was + 0.16 ± 0.52 l/min ( + 4.0 ± 11.3 % ) , and relative error was 9.1 % ± 7.8 % . In 85 % of patients the relative error was < 20 % . During periods of increasing output , slopes were similar with the two methods in 96 % of patients and intra-class correlation was positive in 96 % . Corresponding values during periods of decreasing output were 90 % and 84 % , respectively . Precision was always better with NICOM than with thermodilution . During hemodynamic challenges , changes were 3.1 ± 3.8 min faster with NICOM ( p < 0.01 ) and amplitude of changes did not differ significantly . Finally , sensitivity of the NICOM for detecting significant directional changes was 93 % and specificity was 93 % . Conclusion Cardiac output measured by NICOM had most often acceptable accuracy , precision , and responsiveness in a wide range of circulatory situations IMPORTANCE Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic therapy algorithm . OBJECTIVE To evaluate the clinical effectiveness of a perioperative , cardiac output-guided hemodynamic therapy algorithm . DESIGN , SETTING , AND PARTICIPANTS OPTIMISE was a pragmatic , multicenter , r and omized , observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom . An up date d systematic review and meta- analysis were also conducted including r and omized trials published from 1966 to February 2014 . INTERVENTIONS Patients were r and omly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope ( dopexamine ) infusion during and 6 hours following surgery ( n=368 ) or to usual care ( n=366 ) . MAIN OUTCOMES AND MEASURES The primary outcome was a composite of predefined 30-day moderate or major complications and mortality . Secondary outcomes were morbidity on day 7 ; infection , critical care-free days , and all-cause mortality at 30 days ; all-cause mortality at 180 days ; and length of hospital stay . RESULTS Baseline patient characteristics , clinical care , and volumes of intravenous fluid were similar between groups . Care was nonadherent to the allocated treatment for less than 10 % of patients in each group . The primary outcome occurred in 36.6 % of intervention and 43.4 % of usual care participants ( relative risk [ RR ] , 0.84 [ 95 % CI , 0.71 - 1.01 ] ; absolute risk reduction , 6.8 % [ 95 % CI , -0.3 % to 13.9 % ] ; P = .07 ) . There was no significant difference between groups for any secondary outcomes . Five intervention patients ( 1.4 % ) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group . Findings of the meta- analysis of 38 trials , including data from this study , suggest that the intervention is associated with fewer complications ( intervention , 488/1548 [ 31.5 % ] vs control , 614/1476 [ 41.6 % ] ; RR , 0.77 [ 95 % CI , 0.71 - 0.83 ] ) and a nonsignificant reduction in hospital , 28-day , or 30-day mortality ( intervention , 159/3215 deaths [ 4.9 % ] vs control , 206/3160 deaths [ 6.5 % ] ; RR , 0.82 [ 95 % CI , 0.67 - 1.01 ] ) and mortality at longest follow-up ( intervention , 267/3215 deaths [ 8.3 % ] vs control , 327/3160 deaths [ 10.3 % ] ; RR , 0.86 [ 95 % CI , 0.74 - 1.00 ] ) . CONCLUSIONS AND RELEVANCE In a r and omized trial of high-risk patients undergoing major gastrointestinal surgery , use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality . However , inclusion of these data in an up date d meta- analysis indicates that the intervention was associated with a reduction in complication rates . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N04386758 |
2,667 | 29,228,403 | Recent studies have shown proprioceptive deficits , in both the injured and contralateral knees , with the clinical relevance of findings limited by testing methodology and the small differences found . | Abstract Mechanoreceptors , within the anterior cruciate ligament ( ACL ) , are believed to have importance in proprioception , contributing to dynamic knee stability .
The potential for reinnervation of the ACL graft is one of the proposed advantages of remnant‐preserving reconstruction .
The aim of this review is to summarize advances in the basic science underpinning this function , alongside recent clinical studies , to define the current role for remnant‐preservation .
Contemporary work , using immunohistological staining , has shown mechanoreceptors primarily within proximity to the bony attachments of the ACL ( peripherally in the subsynovial layer ) .
The number of these receptors has been shown to decrease rapidly , following rupture , with adhesion to the posterior cruciate ligament slowing this decline . | PURPOSE The purpose of this study was to analyze differences in the clinical results between a remnant-preserving augmentation and a double-bundle reconstruction . METHODS Between March 2008 and February 2009 , we prospect ively analyzed 100 cases of anterior cruciate ligament reconstruction with a minimum follow-up period of 2 years . There were 55 cases of remnant-preserving augmentation and 45 cases of double-bundle reconstruction . We clinical ly compared the preoperative and postoperative range of motion , visual analog scale score , Lysholm score , Tegner score , International Knee Documentation Committee knee evaluation form score , anterior drawer test , Lachman test , pivot-shift test , KT-1000 arthrometer ( MEDmetric , San Diego , CA ) test , and anterior translation on Telos stress radiographs ( Telos , Weiterstadt , Germany ) . RESULTS There were no significant differences in the postoperative range of motion , visual analog scale score , Lysholm score , Tegner score , and International Knee Documentation Committee knee evaluation form score between the 2 groups ( P > .05 ) . The anterior drawer test was significantly better in the remnant-preserving augmentation group than the double-bundle reconstruction group ( P = .038 ) . However , there were no significant differences in the Lachman test , pivot-shift test , anterior translation on Telos stress radiographs , and KT-1000 arthrometer test between the 2 groups ( P > .05 ) . CONCLUSIONS Clinical outcomes of a remnant-preserving augmentation and a double-bundle reconstruction showed similar results in terms of anterior and rotary stability and clinical scores . LEVEL OF EVIDENCE Level IV , therapeutic case series There is a dearth of reliable and valid instrumentation that measures disability following injury and /or surgery of the knee joint that is responsive to clinical ly significant changes over time . The purpose of this investigation was to determine whether performance-based or patient-reported measures of function are more effective in estimating disability in individuals with an anterior-cruciate-ligament (ACL)-deficient knee . Subjective rating of knee function was used as the criterion measure for disability , and selected performance-based and patient-reported measures were used as estimation variables . Twenty-nine individuals with an ACL-deficient knee participated in this investigation . Step-wise regression analysis revealed that the Cincinnati Knee Scale , Lysholm Knee Scale , and hop index were the most effective estimates of disability . The results demonstrate that patient-reported measures are more related to the patient 's level of disability in individuals with an ACL-deficient knee . More research is necessary to substantiate these findings Background : There is controversy regarding the efficacy of remnant tissue preservation on graft healing in anterior cruciate ligament ( ACL ) reconstruction . Hypothesis : The preserved remnant tissue will ( 1 ) adhere to the graft surface and undergo a remodeling process , ( 2 ) accelerate graft revascularization , ( 3 ) increase the number of graft mechanoreceptors by 4 weeks , and ( 4 ) improve anteroposterior knee laxity and structural properties of the graft by 12 weeks . Study Design : Controlled laboratory study . Methods : Forty-two sheep were r and omly divided into 2 groups of 21 animals . In group I , the ACL was completely removed . In group II , the ACL was transected at the midsubstance but not debrided . ACL reconstruction was performed using a semitendinosus tendon autograft in both groups . Histological changes of the grafted tendon and the remnant tissue were evaluated at 4 and 12 weeks after surgery . Biomechanically , anterior translation and knee joint stiffness under an anterior drawer force and the structural properties of the femur-graft-tibia complex were evaluated . Results : The preserved remnant tissue was histologically distinct from the graft at 4 weeks , while the tissue partially adhered to the graft surface at 12 weeks . The ACL remnant tissue significantly accelerated revascularization in the grafted tendon at 4 weeks and significantly increased the number of mechanoreceptors at 4 and 12 weeks . In addition , remnant preservation significantly improved anterior translation ( 9.3 ± 2.1 mm and 5.4 ± 1.7 mm at 60 ° of knee flexion in groups I and II , respectively ) and knee joint stiffness at 12 weeks . However , there were no significant differences in the structural properties between the 2 groups at 4 and 12 weeks after surgery . Conclusion : Preservation of the ACL remnant tissue in ACL reconstruction enhanced cell proliferation , revascularization , and regeneration of proprioceptive organs in the reconstructed ACL and reduced anterior translation . However , remnant preservation did not improve the structural properties of the graft . Clinical Relevance : These results imply that preservation of the ACL remnant tissue may improve graft healing after ACL reconstruction PURPOSE Our purpose was ( 1 ) to compare the structural integrity and healing capacity of the acutely repaired anterior cruciate ligament ( ACL ) remnants and ( 2 ) to determine whether the short-term postoperative biomechanical results of the acute remnant-repairing anterior cruciate ligament reconstruction ( ACLR ) were superior to the conventional ACLR . METHODS An acute complete ACL femoral detachment model was created in 50 rabbits . The rabbits were immediately r and omly allocated into the remnant-repairing ACLR group ( group 1 , n = 25 ) and the conventional ACLR group ( group 2 , n = 25 ) . Each animal in both groups was subjected to unilateral ACLR with semitendinosus tendon autografts . During ACLR , the ACL remnants were acutely repaired with the femoral-tensioning technique in group 1 , whereas the ACL remnants were debrided in group 2 . The outcomes of the remnant were macroscopically evaluated in group 1 . The remnant 's structural integrity and remnant-to-graft healing capacity were divided into 3 categories ( grade A , good ; grade B , fair ; or grade C , poor ) according to 2 distinct criteria . Biomechanical tests including the anterior tibial translation test at 30 ° and 90 ° of knee flexion and tensile tests were compared between groups . All the macroscopic evaluations and biomechanical tests were performed postoperatively at week 12 . RESULTS The macroscopic evaluations of the ACL remnants in group 1 ( n = 25 ) showed that the remnants ' structural integrity was grade A ( well-maintained continuity with an adequate amount of tissue and tension on probing ) in 10 specimens ( 40 % ) , grade B ( fairly maintained continuity with thin and slack fibers detected ) in 5 ( 20 % ) , and grade C ( resorption with no remnant left in situ ) in 10 ( 40 % ) . The remnant-to-graft healing capacities among the specimens with surviving remnants ( grade s A and B for structural integrity , n = 15 ) were all classified as grade C ( an obvious remnant-to-graft interval through the entire length of the graft ) . For the biomechanical tests , there were no significant differences between the groups ( 25 in each group ) with respect to the anterior tibial translation test at 30 ° ( P = .15 ) and 90 ° ( P = .91 ) of knee flexion and stiffness ( P = .66 ) , ultimate failure load ( P = .11 ) , and elongation at failure ( P = .92 ) . CONCLUSIONS In our rabbit model of ACL femoral detachment , the acutely repaired ACL remnants showed a high resorption rate , low healing capacity , and poor biomechanical properties . The acute remnant-repairing ACLR had no evident superiority over the conventional ACLR in rabbits . CLINICAL RELEVANCE The findings did not support the contention that the remnant-repairing ACLR , even performed in the acute setting , could produce better postoperative knee joint stability outcomes than the conventional ACLR BACKGROUND Anterior cruciate ligament ( ACL ) reconstruction with remnant preservation technique had been thought to be a more favorable milieu for graft reinnervation , revascularization , and ligamentization . However , the influence of preserving tibial residual fibers on mRNA expression during the graft remodeling process has never been investigated . MATERIAL S AND METHODS Healthy mature New Zeal and white rabbits were r and omly assigned to one of four groups : remnant dissected , remnant preserved , sham operated , and normal control . Ligament tissue was dissected at 2 , 6 , and 12 wk after surgery , and real-time PCR was performed using primers for VEGF , TGF-β1 , COLlAl , COL3A1 , GAP-43 , and NT-3 . RESULTS In the remnant preservation group , mRNA levels for matrix components COL l Al , COL3A1 , growth factor TGF-β1 , and nerve-related genesGAP-43 all increased 6 wk after surgery , compared with the remnant dissection group ( P < 0.05 ) . An increased level of VEGF mRNA was also detected in the remnant preservation group 12 wk after operation ( P < 0.05 ) . An increased level of NT-3 mRNA was also observed in the remnant preservation group 2 and 12 wk after operation ( P < 0.05 ) . CONCLUSIONS Our results suggest that there is a time dependent alteration of angiogenesis-promoting , repair-related , and nerve-related gene expression after ACL reconstruction during the process of graft remodeling . Furthermore , they demonstrate that remnant preservation in ACL reconstruction determines the different molecular profiles of these target genes , especially during the early stages of graft remodeling , which perhaps explains the potential role in promoting revascularization , reinnervation , and ligamentization We prospect ively studied knee proprioception following ACL reconstruction in 40 patients ( 34 men and six women ; mean age 31 years ) . The patients were allocated into two equal groups ; group A underwent reconstruction using hamstrings autograft , and group B underwent reconstruction using bone-patellar tendon-bone autograft . Proprioception was assessed in flexion and extension by the joint position sense ( JPS ) at 15 ° , 45 ° and 75 ° , and time threshold to detection of passive motion ( TTDPM ) at 15 ° and 45 ° , preoperatively and at 3 , 6 and 12 months postoperatively . The contralateral healthy knee was used as internal control . No statistical difference was found between the ACL-operated and the contralateral knees in JPS 15 ° , 45 ° and 75 ° at 6 and 12 months , in both study groups . No statistical difference was found between the ACL-operated and the contralateral knees in TTDPM 15 ° at 6 and 12 months , nor regarding TTDPM 45 ° at 3 , 6 and 12 months , in group A. No statistical difference was found in JPS and TTDPM between the two grafts , at any time period . Knee proprioception returned to normal with ACL reconstruction at 6 months postoperatively , without any statistically significant difference between the autografts used STUDY DESIGN Nonr and omized prospect i ve study . OBJECTIVE To evaluate proprioception in 2 groups of patients with anterior cruciate ligament ( ACL ) deficiency who had different severity of symptoms . BACKGROUND Defective proprioception has previously been found in patients with ACL-deficient knees . It has been suggested that sensory receptors of the ACL and other knee joint ligaments contribute to proprioception and knee joint function and stability . METHODS AND MEASURES A total of 17 patients with ACL deficiency ( mean [ SD ] age , 28.8 + /- 5.6 years ; range , 22 - 39 years ) with few , if any , symptoms were compared with 20 patients with ACL deficiency ( mean [ SD ] age , 26.6 + /- 6.1 years ; range , 18 - 39 years ) having instability and episodes of giving way . The groups were compared with each other and with an age-matched reference group of 19 nonimpaired subjects . Their mean ( SD ) age was 25.6 + /- 3.7 years ( range , 20 - 37 years ) . Three tests of proprioception were used : threshold to detection of passive motion from 2 starting positions ( 20 degrees and 40 degrees of knee flexion ) toward flexion and extension , active reproduction of a 30 degrees passive angle change , and visual reproduction of a 30 degrees passive angle change . The Wilcoxon rank sum test was used for between-group comparisons . RESULTS Symptomatic patients had higher threshold to detection of passive motion in their injured side in the flexion trial from 20 degrees ( median of 1.5 degrees vs median of 0.5 degree ) and in the extension trial from 40 degrees ( median of 1.0 degree vs median of 0.5 degree ) than the asymptomatic patients . No differences were found in the other threshold tests , active or visual reproduction tests . CONCLUSIONS Patients with severe symptoms related to ACL deficiency were found to have inferior proprioceptive ability in some measurements compared with patients with a good knee function . The findings indicate that proprioceptive deficits might influence the outcome of an ACL injury treated nonoperatively Objective The aim of this work was to compare the prevalence of cyclops lesions after anterior cruciate ligament reconstruction ( ACLR ) using the single-bundle and remnant bundle preservation techniques . Material s and methods One hundred consecutive patients , who had undergone postoperative MRI of the knee followed by arthroscopic ACLR with the remnant bundle preservation technique ( R ) between February 2007 and August 2010 , were enrolled in this study . Thirty-six consecutive patients who underwent ACLR using the single-bundle technique ( S ) were also included in this study as a control group . The MR findings were scored based on the presence of pre-ACL graft lesion as 0 , 1 , 2 , or 3 on the sagittal images . The sixty-one specimens by second-look surgery ( 20 in S , 41 in R ) were pathologically examined . Results The numbers of patients with scores of 0 , 1 , 2 , and 3 were 1 , 18 , 14 , and 3 in group S and 4 , 60 , 29 , and 7 , in group R , respectively . Of the 61 patients who underwent second-look surgery ( 20 in S , 41 in R ) , eight had a cyclops lesion ( three in group S and five in group R ) . The prevalence of cyclops lesion was not significantly different in group R and group S ( p = 0.761 ) . Conclusions The prevalence of a cyclops lesion was similar in both groups Background : Loss of proprioceptive function occurs after anterior cruciate ligament ( ACL ) rupture . Clinical , motor , and proprioceptive function is known to improve after ACL reconstruction but does not return to normal . While histological studies of human ACL allografts have been unable to demonstrate mechanoreceptor reinnervation , animal data suggest that reinnervation may occur when an autograft is used . Purpose : To compare the presence or absence of mechanoreceptors between allograft versus autograft after ACL reconstruction in humans . Study Design : Cohort study ; Level of evidence , 3 . Methods : Ten patients with previous ACL reconstruction presenting for either revision ACL surgery or knee arthroscopy for other reasons were enrolled in a prospect i ve , comparative study . Five patients had a previous autograft ACL and 5 patients had an allograft . Biopsies , either from intact or ruptured grafts , were taken from identical locations as close to the femoral and tibial insertions as possible . Specimens were stained with hematoxylin-eosin ( H-E ) and monoclonal antibodies against neurofilament protein ( NFP ) , known to be present in mechanoreceptor tissue . Immunohistochemical examination was carried out , and the number of NFP+ neural tissue analogs was counted and compared with that of native ACL tissue . Results : The mean time between original graft and biopsy was 6.9 years ( range , 0.5 - 15 years ) . Histological examination showed significantly less NFP+ neural analogs in allograft and autograft patients than control tissue ( mean number of NFP+ analogs per high-power field , 0.7 ± 0.9 [ allograft ] and 0.5 ± 0.8 [ autograft ] vs 4.7 ± 0.9 [ controls ] ; P < .0001 ) . There was no significant difference in NFP analogs between autograft and allograft tissue . Conclusion : We found a reduced concentration of NFP+ neural analogs in ACL grafts compared with native ACL tissue . This deficit exists irrespective of whether allograft or autograft is used . These findings may explain the continued proprioceptive deficits seen clinical ly after ACL reconstruction We assessed proprioception using threshold levels for the perception of knee movement at slow angular velocities ( 0.1 degrees/s to 0.85 degrees/s ) in 20 patients with unilateral tears of the anterior cruciate ligament ( ACL ) and 15 age-related control subjects . Failure to detect movement was also analysed . The threshold levels of detection did not differ between the damaged and undamaged knees in the patients or between the patients and the control group . Failure to appreciate movement , however , was significantly greater in knees with ACL loss compared with the undamaged knees of patients and the control group . Our findings show a proprioceptive deficit in the absence of the ACL . Measurements of threshold levels of detection of passive movement alone are not suitable for the evaluation of proprioceptive loss in ACL deficiency ; assessment of failure to appreciate movement is essential We studied the effect that chronic anterior cruciate ligament disruption , functional bracing , and a neoprene sleeve have on knee proprioception by measuring the threshold to detection of passive knee motion in all three conditions . The threshold to detection of passive knee motion was worse in knees with chronic anterior cruciate ligament insufficiency when compared with uninjured knees . This difference was small , on average an additional 0.28 ° of flexion-extension rotation was required for the anterior cruciate ligament-deficient knee before the subject detected motion , and of question able significance from a clinical and functional perspective . Wearing a functional brace or neoprene sleeve on the anterior cruciate ligament-deficient knee did not significantly change the threshold to detection of passive motion in comparison with the same knee without a brace , although improvements were observed . There was no relationship between the most common clinical means of characterizing altered bio-mechanics of the anterior cruciate ligament-deficient knee ( that is , the magnitude of anterior-posterior knee laxity and the grade of pivot shift ) and the threshold to detection of passive knee motion Abstract . This study investigated the presence of neural mechanoreceptors in the remnants of the ruptured ACL as a possible source of reinnervation of the ACL autologous graft . The remainder of the torn ACL was selected for further histological investigation from 17 patients during ACL reconstruction 3 months to 3.5 years after injury . Perioperatively two types of ACL remnant were identified . Fifteen patients had portions of ACL adapted at the PCL . In all of these patients we found mechanoreceptors ( I and II ) . In five patients we found mushroomlike remnants which included either none or small numbers of mechanoreceptors . Free neural ends were found in both patient groups . There was a significant difference between the groups in regard to the mean number of mechanoreceptors I and II per slice . In conclusion , in patients with an ACL remnant adapted to the PCL , mechanoreceptors exist even 3 years after injury . If we accept that restoration of proprioception is the result of reinnervation of the ACL , leaving the ACL remnants as a source , if this is surgically possible without risk of Cyclop 's lesion , may be of potential benefit to the patient PURPOSE The purpose of this study was to determine , first , if there is measurable deficit in proprioception in an anterior cruciate ligament (ACL)-deficient knee , either compared to the contralateral knee or external controls ; second , if this deficit , if present , improves after ACL reconstruction ; and third , if improvement occurs , what the time course of improvement is . TYPE OF STUDY Prospect i ve cohort study . METHODS Patients undergoing ACL reconstruction at the University of Chicago , demonstrating a full and painless range of motion and no other knee ligament injury or history of previous knee surgery , were eligible . Twenty-six patients , with an average age of 25 years ( range , 16 to 48 ) were enrolled . Average time from injury to reconstruction was 8 weeks . The patients ' contralateral knee served as an internal control , and 26 age-matched and gender-matched healthy volunteers were enrolled as an external control group . ACL reconstructions were performed using a single-incision technique with either bone-patellar tendon-bone or quadrupled hamstring autograft . They were allowed immediate weightbearing as tolerated and participated in a st and ardized rehabilitation program , with the goal of returning to sport at approximately 6 months . Proprioception testing was carried out using an electrogoniometer , in a seated position . Joint position sense ( JPS ) and threshold to detection of passive motion ( TDPM ) were measured preoperatively and at 3 and 6 weeks and 3 and 6 months postoperatively . RESULTS Mean KT-2000 values 6 months postoperatively were 1.38 mm ( + /-2 ) . Modified Lysholm score improved significantly ( P < .01 ) . Calculated r values were 0.65 for JPS and 0.96 for TDPM . No significant differences in postoperative proprioception were found between hamstring and patellar tendon grafts or among patients with meniscus injury , meniscus repair , or chondral injury . Preoperatively , the mean TDPM in both the injured and contralateral knees was significantly higher ( worse ) than in the external control knees ( P = .008 ; P = .016 ) . Evaluation of changes in proprioception from preoperative to 6 months postoperative showed significant improvement in both injured and contralateral knees ( P = .04 ; P = .01 ) . At 6-month follow-up , there was no significant difference from controls . CONCLUSIONS TDPM was a more reliable method than JPS for testing proprioception before and after ACL reconstruction in this study . Bilateral deficits in knee joint proprioception ( TDPM ) were documented after unilateral ACL injury . Reconstruction of a mechanical restraint ( ACL graft ) was believed to have a significantly positive impact on early and progressive improvement in proprioception Background : Efforts still need to be made to improve the technique for surgical anterior cruciate ligament reconstruction ( ACLR ) . Several reports have cl aim ed that ACLR with the remnant preservation technique can obtain satisfactory clinical results . Purpose : To compare the short-term clinical outcome of remnant-preserving ACLR with st and ard ACLR . Study Design : R and omized controlled trial ; Level of evidence , 2 . Methods : A prospect i ve , r and omized controlled study was performed in 90 consecutive patients who underwent ACLR with the remnant preservation technique ( study group , n = 45 ) or the st and ard technique ( control group , n = 45 ) with the use of a 4-str and allograft . The Lysholm score , International Knee Documentation Committee ( IKDC ) grade , stability assessment s ( Lachman test , pivot-shift test , and KT-1000 arthrometer side-to-side differences ) , synovial coverage of the graft , and proprioception measurements were evaluated preoperatively and at the last follow-up . Results : All consecutive patients who were screened for eligibility between August 2008 and April 2010 were enrolled and followed clinical ly . There were 39 patients in the study group and 41 in the control group who were followed for at least 2 years ( mean follow-up , 25.7 months ) . At the last follow-up , the median Lysholm score was 99 in the study group and 95 in the control group ( P = .07 ) . The IKDC grade was A or B in 38 patients in the study group and 40 patients in the control group ( P = .548 ) . Lachman test results were negative in 38 patients in the study group and 40 patients in the control group ( P = .862 ) , and the pivot-shift test result was negative in 37 patients in the study group and 36 patients in the control group ( P = .523 ) . The mean KT-1000 arthrometer side-to-side difference averaged 1.6 ± 1.7 mm in the study group and 1.8 ± 1.8 mm in the control group ( P = .694 ) . Second-look arthroscopy was performed to evaluate synovial coverage of the graft . Normal or nearly normal synovial coverage , grade d as A or B , was 71.4 % ( 20/28 ) in the study group and 70.4 % ( 19/27 ) in the control group ( P = .966 ) . The passive angle reproduction test result at 15 ° was 3.6 ° ± 1.8 ° in the study group and 3.9 ° ± 2.2 ° in the control group ( P = .739 ) . Conclusion : This short-term study showed that , in terms of stability , synovial coverage , and proprioception recovery , remnant preservation ACLR using an allograft had no evident advantages in clinical outcome over the st and ard technique Proprioception was quantified in a group of patients who had documented complete ACL tears . Threshold to detection of passive change in position of the knee was measured using a well-described test . Eleven pa tients with arthroscopically proven complete ACL tears and findings consistent with moderate to severe anter olateral rotatory instability were tested . Testing was done within the 30 ° to 40 ° range of knee flexion . Patients were blindfolded and the injured and uninjured knees were tested in r and om sequence so that the normal knee could serve as an internal control . Testing was also done in a blind manner , i.e. , the examiner did not know which knee had been injured . An age- matched control group underwent identical testing . Po tentially significant variables such as age , time from injury , and degree of rehabilitation as measured by thigh circumference and isokinetic testing of the knee were included in a multivariate analysis . Control subjects demonstrated virtually identical threshold values between their two knees , the mean variation being less than 2 % . The test group , however , showed a significantly higher mean threshold value for the injured versus the noninjured knee ( P < 0.01 ) , the mean variation being over 25 % . Multivariate analysis demonstrated that changes recorded in the propriocep tion of the injured knee were attributable to the loss of the ACL rather than to other variables . Patients who have complete ACL tears and moderate to severe rotatory instability may also experience a decline in proprioceptive function of their knee Animal studies have shown that implanted anterior cruciate ligament ( ACL ) grafts initially undergo a process of revascularisation prior to remodelling , ultimately increasing mechanical strength . We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans . We undertook a r and omised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-str and hamstring tendon grafts . R and omised by the use of sealed envelopes , 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method . Three patients were excluded from the study . All patients underwent MR scanning postoperatively at 2 , 6 and 12 months , together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee ( IKDC ) evaluation . All observations were made by investigators blinded to the surgical technique . Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament . Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months ( paired t-test , p = 0.002 ) . There was a significant reduction of mid-substance signal six months after the minimal debridement technique ( paired t-test , p = 0.00007 ) . No statistically significant differences were found in tunnel placement , incidence of Cyclops lesions , blood loss , IKDC scores , range of movement or Lachman test between the two groups Background Few prospect i ve long-term studies of more than 10 years have reported changes in knee function and radiologic outcomes after anterior cruciate ligament ( ACL ) reconstruction . Purpose To examine changes in knee function from 6 months to 10 to 15 years after ACL reconstruction and to compare knee function outcomes over time for subjects with isolated ACL injury with those with combined ACL and meniscal injury and /or chondral lesion . Furthermore , the aim was to compare the prevalence of radiographic and symptomatic radiographic knee osteoarthritis between subjects with isolated ACL injuries and those with combined ACL and meniscal and /or chondral lesions 10 to 15 years after ACL reconstruction . Study Design Cohort study ; Level of evidence , 2 . Methods Follow-up evaluations were performed on 221 subjects at 6 months , 1 year , 2 years , and 10 to 15 years after ACL reconstruction with bone-patellar tendon-bone autograft . Outcome measurements were KT-1000 arthrometer , Lachman and pivot shift tests , Cincinnati knee score , isokinetic muscle strength tests , hop tests , visual analog scale for pain , Tegner activity scale , and the Kellgren and Lawrence classification . Results One hundred eighty-one subjects ( 82 % ) were evaluated at the 10- to 15-year follow-up . A significant improvement over time was revealed for all prospect i ve outcomes of knee function . No significant differences in knee function over time were detected between the isolated and combined injury groups . Subjects with combined injury had significantly higher prevalence of radiographic knee osteoarthritis compared with those with isolated injury ( 80 % and 62 % , P = .008 ) , but no significant group differences were shown for symptomatic radiographic knee osteoarthritis ( 46 % and 32 % , P = .053 ) . Conclusion An overall improvement in knee function outcomes was detected from 6 months to 10 to 15 years after ACL reconstruction for both those with isolated and combined ACL injury , but significantly higher prevalence of radiographic knee osteoarthritis was found for those with combined injuries |
2,668 | 21,670,974 | A RIETE score of 0 point was moderately predictive of the absence of major bleeding .
None of the CPRs exhibited sufficient predictive accuracy or had sufficient validation to be recommended for routine use in practice .
None of the available CPRs exhibit sufficient predictive accuracy or have trials evaluating the impact of their use on patient outcomes . | This study aim ed to determine whether progress in developing bleeding risk estimation tools for patients on oral anticoagulant therapy has been made since 2006 when we last systematic ally review ed this topic , and to refresh previously published quantitative evaluations of the clinical prediction rules ( CPRs ) available for estimating bleeding risk in patients on oral anticoagulant therapy . | PURPOSE To determine the incidence of major bleeding in out patients treated with warfarin and to identify predictive factors known at the start of therapy . PATIENTS AND METHODS The records of 565 patients starting outpatient therapy with warfarin upon discharge from a university hospital were review ed . Follow-up information was obtained for 562 patients ( 99.5 % ) . Bleeding was classified as major or minor using explicit criteria . The cumulative incidence of bleeding was estimated by means of survival analysis . Independent risk factors for major bleeding were identified using Cox regression analysis in 375 r and omly chosen patients ; they were tested in the remaining 187 patients . RESULTS Major bleeding occurred in 65 patients ( 12 % ) and was fatal in 10 patients ( 2 % ) . The cumulative incidences of major bleeding at one , 12 , and 48 months were 3 % , 11 % , and 22 % , respectively . The monthly risk of major bleeding decreased over time , from 3 % during the first month of outpatient therapy to 0.3 % per month after the first year of therapy . Five independent risk factors for major bleeding -- age 65 years or greater , history of stroke , history of gastrointestinal bleeding , a serious comorbid condition ( recent myocardial infa rct ion , renal insufficiency , or severe anemia ) , atrial fibrillation -- predicted major bleeding in the testing group ; the cumulative incidence of major bleeding at 48 months was 2 % in 57 low-risk patients , 17 % in 110 middle-risk patients , and 63 % in 20 high-risk patients . CONCLUSION These findings provide a quantitative basis for evaluating the risk of major bleeding in individual patients at the start of outpatient therapy with warfarin . Whether the risk of bleeding can be reduced in high-risk patients without reducing the benefit of therapy remains to be determined BACKGROUND The Outpatient Bleeding Risk Index ( BRI ) prospect ively classified patients who were at high , intermediate , or low risk for warfarin-related major bleeding . However , there are only 2 published validation studies of the index and neither included veterans . OBJECTIVE To determine the accuracy of the BRI in patients attending a Veterans Affairs ( VA ) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation . DESIGN Retrospective cohort study . PATIENTS AND MEASUREMENTS Using the BRI , all patients managed by the Anticoagulation Clinic between January 1 , 2001 and December 31 , 2002 were classified as high , intermediate , or low risk for major bleeding . Bleeds were identified via quality -assurance reports . Poisson regression was used to determine whether there was an association between the index and the development of bleeding . RESULTS The rate of major bleeding was 10.6 % , 2.5 % , and 0.8 % per patient-year of warfarin in the high- , intermediate- , and low-risk groups , respectively . Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group ( incidence rate ratio ( IRR ) 14 ; 95 % confidence interval ( CI ) , 1.9 to 104.7 ) . The rate of major bleeding was significantly different between the high- and intermediate-risk categories ( P<.001 ) . Among those with atrial fibrillation , patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined ( IRR=6 ; 95 % CI , 2.4 to 15.3 ) . CONCLUSIONS The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic , including those with atrial fibrillation PURPOSE To evaluate the accuracy and clinical utility of the Outpatient Bleeding Risk Index for estimating the probability of major bleeding in out patients treated with warfarin . The index was previously derived in a retrospective cohort of 556 patients from a different hospital ( derivation cohort ) . SUBJECTS AND METHODS We enrolled 264 out patients starting warfarin ( validation cohort ) to vali date the index prospect ively . All patients were identified upon hospital discharge , and physician estimates of the probability of major bleeding were obtained before discharge in the validation cohort . RESULTS Major bleeding occurred in 87 of 820 out patients ( 6.5%/yr ) . The index included four independent risk factors for major bleeding : age 65 years or greater ; history of gastrointestinal bleeding ; history of stroke ; and one or more of four specific comorbid conditions . In the validation cohort , the index predicted major bleeding : the cumulative incidence at 48 months was 3 % in 80 low-risk patients , 12 % in 166 intermediate-risk patients , and 53 % in 18 high-risk patients ( c index , 0.78 ) . The index performed better than physicians , who estimated the probability of major bleeding no better than expected by chance . Of the 18 episodes of major bleeding that occurred in high-risk patients , 17 were potentially preventable . CONCLUSIONS The Outpatient Bleeding Risk Index prospect ively classified patients according to risk of major bleeding and performed better than physicians . Major bleeding may be preventable in many high-risk patients by avoidance of over-anticoagulation and nonsteroidal anti-inflammatory agents This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists ( VKAs ) is part of the American College of Chest Physicians Evidence -Based Clinical Practice Guidelines ( 8th Edition ) . It describes the antithrombotic effect of the VKAs , the monitoring of anticoagulation intensity , and the clinical applications of VKA therapy and provides specific management recommendations . Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks , burdens , and costs . Grade 2 recommendations suggest that the individual patient 's values may lead to different choices . ( For a full underst and ing of the grading , see the " Grade s of Recommendation " chapter by Guyatt et al , CHEST 2008 ; 133:123S-131S . ) Among the key recommendations in this article are the following : for dosing of VKAs , we recommend the initiation of oral anticoagulation therapy , with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals , with subsequent dosing based on the international normalized ratio ( INR ) response ( Grade 1B ) ; we suggest against pharmacogenetic-based dosing until r and omized data indicate that it is beneficial ( Grade 2C ) ; and in elderly and other patient subgroups who are debilitated or malnourished , we recommend a starting dose of < or = 5 mg ( Grade 1C ) . The article also includes several specific recommendations for the management of patients with nontherapeutic INRs , with INRs above the therapeutic range , and with bleeding whether the INR is therapeutic or elevated . For the use of vitamin K to reverse a mildly elevated INR , we recommend oral rather than subcutaneous administration ( Grade 1A ) . For patients with life-threatening bleeding or intracranial hemorrhage , we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR ( Grade 1C ) . For most patients who have a lupus inhibitor , we recommend a therapeutic target INR of 2.5 ( range , 2.0 to 3.0 ) [ Grade 1A ] . We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion , incorporating patient education , systematic INR testing , tracking , follow-up , and good patient communication of results and dose adjustments [ Grade 1B ] . In patients who are suitably selected and trained , patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management , with greater time in the therapeutic range and fewer adverse events . Patient self-monitoring or self-management , however , is a choice made by patients and physicians that depends on many factors . We suggest that such therapeutic management be implemented where suitable ( Grade 2B ) BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery , or subcutaneous enoxaparin 40 mg once daily ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate 150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery , with a similar safety profile A score that can accurately determine the risk of major bleeding during anticoagulant therapy may help to make decisions on anticoagulant use . RIETE is an ongoing registry of consecutive patients with acute venous thromboembolism ( VTE ) . We composed a score to predict the risk for major bleeding within three months of anticoagulant therapy . Of 19,274 patients enrolled , 13,057 ( 67 % ) were r and omly assigned to the derivation sample , 6,572 to the validation sample . In the derivation sample 314 ( 2.4 % ) patients bled ( fatal bleeding , 105 ) . On multivariate analysis , age > 75 years , recent bleeding , cancer , creatinine levels > 1.2 mg/dl , anemia , or pulmonary embolism at baseline were independently associated with an increased risk for major bleeding . A score was composed assigning 2 points to recent bleeding , 1.5 to abnormal creatinine levels or anemia , 1 point to the remaining variables . In the derivation sample 2,654 ( 20 % ) patients scored 0 points ( low risk ) ; 9,645 ( 74 % ) 1 - 4 points ( intermediate ) ; 758 ( 5.8 % ) > 4 points ( high risk ) . The incidences of major bleeding were : 0.3 % ( 95 % confidence interval [ CI ] : 0.1 - 0.6 ) , 2.6 % ( 95 % CI : 2.3 - 2.9 ) , and 7.3 % ( 95 % CI : 5.6 - 9.3 ) , respectively . The likelihood ratio test was : 0.14 ( 95 % CI : 0.07 - 0.27 ) for patients at low risk;2.96 ( 95 % CI : 2.18 - 4.02 ) for those at high risk . In the validation sample the incidence of major bleeding was : 0.1 % , 2.8 % , and 6.2 % , respectively . In conclusion , a risk score based on six variables documented at entry can identify VTE patients at low , intermediate , or high risk for major bleeding during the first three months of therapy Abstract Objective : To determine and compare physicians ' and patients ' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation . Design : Prospect i ve observational study . Setting : Tertiary and peripheral referral centres in Nova Scotia , Canada . Participants : 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation . Main outcome measures : Participants underwent a face to face interview with a probability trade-off tool . Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation . Results : The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians ( 1.8 ( SD 1.9 ) v 2.5 ( 1.6 ) , P=0.009 ) , whereas for aspirin there was no difference between patients and physicians ( 1.3 ( 1.3 ) v 1.6 ( 1.5 ) , P=0.29 ) . The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians ( warfarin 17.4 ( 7.1 ) v 10.3 ( 6.1 ) ; aspirin 14.7 ( 8.5 ) v 6.7 ( 6.2 ) ; P<0.001 for both comparisons ) . Conclusions : Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation . The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation . What is already known on this topic Several observational studies have shown an apparent underuse of antithrombotic drugs in patients with atrial fibrillation , despite evidence of efficacy What this study adds There is considerable variability between physicians and patients in their weighing up of the potential outcomes associated with atrial fibrillation and its treatment For anticoagulation treatment to be acceptable patients required less reduction in risk of stroke and were more tolerant of an increase in risk of bleeding than physicians Physicians varied considerably in how much risk of bleeding they thought was acceptable for a given reduction in risk of stroke associated with antithrombotic You are back where we put you in the previous article1 on diagnostic tests in this series on how to use the medical literature : in the library study ing an article that will guide you in interpreting ventilation-perfusion ( V/Q ) lung scans . Using the criteria in Table 1 , you have decided that the Prospect i ve Investigation of Pulmonary Diagnosis ( PIOPED ) study 2 will provide you with valid information . Just then , another BACKGROUND Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty ; oral regimens could enable shorter hospital stays . We aim ed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty . METHODS In a r and omised , double-blind , phase III study , 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily , beginning 6 - 8 h after surgery , or subcutaneous enoxaparin 30 mg every 12 h , starting 12 - 24 h after surgery . Patients had m and atory bilateral venography between days 11 and 15 . The primary efficacy outcome was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism , or death from any cause up to day 17 after surgery . Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per- protocol population ( absolute non-inferiority limit -4 % ) ; if non-inferiority was shown , we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population . The primary safety outcome was major bleeding . This trial is registered with Clinical Trials.gov , number NCT00362232 . FINDINGS The primary efficacy outcome occurred in 67 ( 6.9 % ) of 965 patients given rivaroxaban and in 97 ( 10.1 % ) of 959 given enoxaparin ( absolute risk reduction 3.19 % , 95 % CI 0.71 - 5.67 ; p=0.0118 ) . Ten ( 0.7 % ) of 1526 patients given rivaroxaban and four ( 0.3 % ) of 1508 given enoxaparin had major bleeding ( p=0.1096 ) . INTERPRETATION Oral rivaroxaban 10 mg once daily for 10 - 14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty . FUNDING Bayer Schering Pharma AG , Johnson & Johnson Pharmaceutical Research & Development BACKGROUND Long-term anticoagulation prevents recurrent thrombosis in patients with idiopathic deep venous thrombosis or pulmonary embolism , but with a risk of clinical ly important so-called major bleeding . Physician- and patient-based decisions on the optimal duration of therapy are sensitive to the bleeding risk . The Outpatient Bleeding Risk Index potentially provides a means of calculating the potential risk of bleeding using easily elicited clinical findings , but , to our knowledge , the authors of the index have provided the only published validation of it . We sought to determine the accuracy of the index in our population of patients . METHODS We prospect ively applied the Outpatient Bleeding Risk Index to consecutive patients in our clinic who had been objective ly diagnosed as having pulmonary embolism or deep venous thrombosis and who were about to undergo st and ard therapy . St and ard therapy consisted of a minimum of 5 days of low-molecular-weight heparin therapy overlapped with warfarin sodium therapy , and continuation of warfarin therapy for at least 3 months , with a target international normalized ratio of 2.5 . Patients were placed in 3 risk groups ( low , moderate , or high ) , as defined by the index . The survival curves of the groups , using major hemorrhages as the events , were then compared by the log-rank test . RESULTS Bleeding rates were lower than expected , but the index did discriminate between low- and moderate-risk groups ( P = .03 , log-rank test ) . The rate of major hemorrhage per 100 person-years was 0 % ( 95 % confidence interval , 0%-2.8 % ) in the low-risk group and 4.3 % ( 95 % confidence interval , 1.1%-11.1 % ) in the moderate-risk group . The rate in the high-risk group could not be defined because only 2 patients were at high risk . CONCLUSION The Outpatient Bleeding Risk Index discriminates between low- and moderate-risk patients , and could be used to guide decisions on the optimal duration of anticoagulant therapy BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement . Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety of these drugs after elective total knee replacement . METHODS In ADVANCE-2 , a multicentre , r and omised , double-blind phase 3 study , patients undergoing elective unilateral or bilateral total knee replacement were r and omly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily ( n=1528 ) or subcutaneous enoxaparin 40 mg once daily ( 1529 ) . The r and omisation schedule was generated by the Bristol-Myers Squibb r and omisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four . Investigators , patients , statisticians , adjudicators , and steering committee were masked to allocation . Apixaban was started 12 - 24 h after wound closure and enoxaparin 12 h before surgery ; both drugs were continued for 10 - 14 days , when bilateral ascending venography was scheduled . Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis , non-fatal pulmonary embolism , and all-cause death during treatment . The statistical plan required non-inferiority of apixaban before testing for superiority ; analysis was by intention to treat for non-inferiority testing . The study is registered at Clinical Trials.gov , number NCT00452530 . FINDINGS 1973 of 3057 patients allocated to treatment ( 1528 apixaban , 1529 enoxaparin ) were eligible for primary efficacy analysis . The primary outcome was reported in 147 ( 15 % ) of 976 apixaban patients and 243 ( 24 % ) of 997 enoxaparin patients ( relative risk 0.62 [ 95 % CI 0.51 - 0.74 ] ; p<0.0001 ; absolute risk reduction 9.3 % [ 5.8 - 12.7 ] ) . Major or clinical ly relevant non-major bleeding occurred in 53 ( 4 % ) of 1501 patients receiving apixaban and 72 ( 5 % ) of 1508 treated with enoxaparin ( p=0.09 ) . INTERPRETATION Apixaban 2.5 mg twice daily , starting on the morning after total knee replacement , offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin , without increased bleeding . FUNDING Bristol-Myers Squibb ; Pfizer OBJECTIVES The purpose of this study was to investigate predictors of bleeding in a cohort of anticoagulated patients and to evaluate the predictive value of several bleeding risk stratification schemas . BACKGROUND The risk of bleeding during antithrombotic therapy in patients with atrial fibrillation ( AF ) is not homogeneous , and several clinical risk factors have been incorporated into clinical bleeding risk stratification schemas . Current risk stratification schemas for bleeding during anticoagulation therapy have been based on complex scoring systems that are difficult to apply in clinical practice , and few have been derived and vali date d in AF cohorts . METHODS We investigated predictors of bleeding in a cohort of 7,329 patients with AF participating in the SPORTIF ( Stroke Prevention Using an ORal Thrombin Inhibitor in Atrial Fibrillation ) III and V clinical trials and evaluated the predictive value of several risk stratification schemas by multivariate analysis . Patients were anticoagulated orally with either adjusted-dose warfarin ( target international normalized ratio 2 to 3 ) or fixed-dose ximelagatran 36 mg twice daily . Major bleeding was central ly adjudicated , and concurrent aspirin therapy was allowed in patients with clinical atherosclerosis . RESULTS By multivariate analyses , significant predictors of bleeding were concurrent aspirin use ( hazard ratio [ HR ] : 2.10 ; 95 % confidence interval [ CI ] : 1.59 to 2.77 ; p < 0.001 ) ; renal impairment ( HR : 1.98 ; 95 % CI : 1.42 to 2.76 ; p < 0.001 ) ; age 75 years or older ( HR : 1.63 ; 95 % CI : 1.23 to 2.17 ; p = 0.0008 ) ; diabetes ( HR : 1.47 ; 95 % CI : 1.10 to 1.97 ; p = 0.009 ) , and heart failure or left ventricular dysfunction ( HR : 1.32 ; 95 % CI : 1.01 to 1.73 ; p = 0.041 ) . Of the tested schemas , the new HAS-BLED ( Hypertension , Abnormal Renal/Liver Function , Stroke , Bleeding History or Predisposition , Labile INR , Elderly , Drugs/Alcohol Concomitantly ) score performed best , with a stepwise increase in rates of major bleeding with increasing HAS-BLED score ( p(trend ) < 0.0001 ) . The c statistic for bleeding varied between 0.50 and 0.67 in the overall entire cohort and 0.68 among patients naive to warfarin at baseline ( n = 769 ) . CONCLUSIONS This analysis identifies diabetes and heart failure or left ventricular dysfunction as potential risk factors for bleeding in AF beyond those previously recognized . Of the contemporary bleeding risk stratification schemas , the new HAS-BLED scheme offers useful predictive capacity for bleeding over previously published schemas and may be simpler to apply |
2,669 | 28,151,437 | Hard water consumption seems to be protective against CVD . | This systematic review with meta- analysis , performed according to the Preferred Reporting Items for Systematic Review s and Meta- analysis ( PRISMA ) guidelines , aims at evaluating the potential correlation between magnesium and calcium concentration in drinking waters and the risk of cardiovascular diseases ( CVD ) , which impose a considerable burden in high-income countries . | To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure ( BP ) of 140 to 159 mm Hg and /or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension ( DASH ) study . Participants were fed a control diet for a 3-week period and were then r and omized to receive for 8 weeks either the control diet ; a diet rich in fruits and vegetables , but otherwise similar to control ; or a combination diet rich in fruits , vegetables , and low-fat dairy products , including whole grains , fish , poultry , and nuts , and reduced in fats , red meats , sweets , and sugar-containing beverages . Sodium intake and body weight were held constant throughout the study . The combination diet significantly reduced systolic BP ( -11.4 mm Hg , P < .001 ) and diastolic BP ( -5.5 mm Hg , P < .001 ) . The fruits- and -vegetables diet also significantly reduced systolic BP ( -7.2 mm Hg , P < .001 ) and diastolic BP ( -2.8 mm Hg , P = .013 ) . The combination diet produced significantly greater BP effects ( P < .05 ) than the fruits- and -vegetables diet . Blood pressure changes were evident within 2 weeks of starting the intervention feeding . After the 8-week intervention period , 70 % of participants eating the combination diet had a normal BP ( systolic BP < 140 and diastolic BP < 90 mm Hg ) compared with 45 % on the fruits- and -vegetables diet and 23 % on the control diet . In patients with hypertension , the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension 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 The role of water hardness as a risk factor for cardiovascular disease has been widely investigated and evaluated as regards regional differences in cardiovascular disease . This study was performed to evaluate the relation between calcium and magnesium in drinking water and diet and risk factors for cardiovascular disease in individuals living in hard and soft water areas with considerable differences in cardiovascular mortality . Methods A r and om sample of 207 individuals living in two municipalities characterised by differences in cardiovascular mortality and water hardness was invited for an examination including a question naire about health , social and living conditions and diet . Intake of magnesium and calcium was calculated from the diet question naire with special consideration to the use of local water . Household water sample s were delivered by each individual and were analysed for magnesium and calcium . Results In the total sample , there were positive correlations between the calcium content in household water and systolic blood pressure ( SBP ) and negative correlations with s-cholesterol and s-LDL-cholesterol . No correlation was seen with magnesium content in household water to any of the risk factors . Calcium content in diet showed no correlation to cardiovascular risk factors . Magnesium in diet was positively correlated to diastolic blood pressure ( DBP ) . In regression analyses controlled for age and sex 18.5 % of the variation in SBP was explained by the variation in BMI , HbA1c and calcium content in water . Some 27.9 % of the variation in s-cholesterol could be explained by the variation in s-triglycerides ( TG ) , and calcium content in water . Conclusions This study of individuals living in soft and hard water areas showed significant correlations between the content of calcium in water and major cardiovascular risk factors . This was not found for magnesium in water or calcium or magnesium in diet . Regression analyses indicated that calcium content in water could be a factor in the complexity of relationships and importance of cardiovascular risk factors . From these results it is not possible to conclude any definite causal relation and further research is needed We investigated the importance of magnesium and calcium in drinking water in relation to morbidity and mortality from acute myocardial infa rct ion . Cases were men and women 50 - 74 years of age living in 18 Swedish municipalities who had suffered an acute myocardial infa rct ion some time between October 1 , 1994 , and June 30 , 1996 . Controls were r and omly selected from the same study base . We interviewed the surviving cases ( N = 823 ) and controls ( N = 853 ) , focusing on risk factors for acute myocardial infa rct ion . We collected individual data on drinking water levels of magnesium and calcium . We classified subjects by quartile of water magnesium or calcium levels . The total number of cases was similar in the four quartiles . The risk of death was 7.6 % ( 95 % confidence interval = 2.1 - 13.1 ) lower in the quartile with high magnesium levels ( > or = 8.3 mg/liter ) . The odds ratio for death from acute myocardial infa rct ion in relation to water magnesium was 0.64 ( 95 % confidence interval = 0.42 - 0.97 ) for the highest quartile relative to the three lower ones . Multivariate analyses showed that other risk factors were not important confounders . For calcium , this study was inconclusive . The data suggest that magnesium in drinking water is associated with lower mortality from acute myocardial infa rct ion , but not with the total incidence Nutritional sodium , potassium and calcium are considered to be important regulators of blood pressure ( BP ) . The present study evaluates the effects of combined low-sodium ( LS ) , high-potassium ( HK ) , high-calcium ( HCa ) diet on BP in patients with mild essential hypertension . Thirty-six patients ( 26 M , 10 F ) , 24–67 years of age ( mean 46 ± 8) , participated in the study . Patients were divided into three groups and given a diet consisting of three 1-month segments , which they followed in different order . Group 1 ( n = 11 ) received LS diet followed by the addition of HCa and then HK . The order in Group 2 ( n = 12 ) was HK-LS-HCa ; and in Group 3 ( n = 13 ) it was HCa-HK-LS . The third month of the study all patients were eating a combined LS , HK and HCa diet . Urinary electrolytes were measured to confirm compliance with the diets . After 1 month of the LS diet urinary sodium excretion decreased significantly by 25 mmols/day ( 95 % CI , 1–48 mmols/day ) ; ( P < 0.05 ) . eighteen patients did not comply with the diet . systolic bp ( sbp ) only slightly decreased , from 142 mm hg ( 95 % ci , 137–146 mm hg ) to 138 mm hg ( 95 % ci , 133–142 mm hg ) ; ( P = 0.11 ) . The change in SBP was related to the change in urinary sodium excretion ( R = 0.46 ; P = 0.006 ) . After 1 month of the HK diet , urinary potassium excretion increased by only 5 mmols/day ( P = NS ) . BP was unaffected by HK and HCa diet . At the end of the study , urinary sodium excretion decreased from 183 mmols/day ( 95 % CI , 155–211 mmols/day ) to 148 mmols/day ( 95 % CI , 131–165 mmols/day ) ; ( P < 0.05 ) , urinary potassium excretion slightly increased from 75 mmols/day ( 95 % ci , 68–82 mmols/day ) to 85 mmols/day ( 95 % ci , 76–94 mmols/day ) ; ( P = 0.09 ) , and urinary calcium excretion remained unchanged . BP did not decrease . It is concluded that only the LS diet may be advantageous in patients with mild essential hypertension Background It has been previously suggested that hard drinking water in general , and in particular high calcium and magnesium intake from drinking water , protect against cardiovascular disease . Design Prospect i ve study of men from 24 British towns , with widely differing levels of hardness in drinking water . Methods A total of 7735 men aged 40–59 years were recruited during 1978–1980 . Estimates of town-level water hardness were available and tap water sample s , taken from 947 participants who also answered a question naire about water consumption , were used to calculate individual calcium and magnesium intakes . Men were followed for incident of major coronary heart disease ( CHD ) and stroke , and CHD mortality for 25 years . Results Water hardness varied from 0.27 to 5.28 mmol/l in the 24 towns . A weak inverse association was found between water hardness and incidence of cardiovascular disease ( CVD ) [ hazard ratio ( HR ) , 0.96 per two-fold increase , 95 % confidence interval ( CI ) , 0.91–1.01 , P = 0.08 after adjustment for age and seven established coronary risk factors ] . No association was observed with CHD incidence ( adjusted HR , 0.99 , 95 % CI , 0.94–1.04 , P = 0.62 ) or mortality ( adjusted HR , 0.96 , 95 % CI , 0.90–1.02 , P = 0.18 ) . Individual magnesium intake showed a positive , rather than an inverse , association with CHD incidence ( adjusted HR , 1.10 per two-fold increase , 95 % CI , 1.01–1.20 , P = 0.045 ) ; individual calcium intake was unrelated to CHD or CVD end points . Conclusions This study suggests that neither high water hardness , nor high calcium or magnesium intake appreciably protect against CHD or CVD . Initiatives to add calcium and magnesium to desalinated water can not be justified by these findings Cardiovascular disease ( CVD ) has been the first cause of mortality in the population of Puy de Dôme ( PDD ) ( France ) between 1988 and 1992 . The mortality rates are significantly higher than those observed in the whole population of France ( for the female population , 354.8 versus 327.3 per 100,000 persons/year and for the male population , 335.7 versus 287.9 per 100,000 persons/year ) . Moreover , an ecological study , which used the St and ardized Mortality Ratios ( SMR ) and performed at the canton level , has allowed a special variation of mortality from CVD in PDD to be described . A decreased gradient of mortality ( especially , " Ischemic Heart diseases " [ ICM-9 , codes 410 - 414 ] and " Cerebro-vascular Diseases " [ ICM-9 , codes 430 - 438 ] ) has been observed from the periphery ( rural area ) to the middle ( urban area ) of PDD . Moreover , a statistically significant negative relationship has been observed between the hardness of the drinking water supplies in PDD and the CVD mortality data ( i.e. , the lower the hardness of drinking water , the higher the SMR ) . Although , the low hardness of drinking water can contribute to the high CVD mortality observed among the PDD population , the role of other risk factors ( i.e. , biological , nutritional ) must also be taken into consideration in further prospect i ve studies PURPOSE This study compared the effects of a mineral water rich in calcium , magnesium , bicarbonate , and sulfate and a marketed mineral water with a composition similar to that of urban water on the lipid profile of dyslipidemic adults . METHODS In a r and omized controlled trial , 32 adults received one liter of " rich mineral water " daily for one month , and 37 adults drank the same amount of normal mineral water for the same period . Changes in lipid profiles were compared separately in each studied group at the end of one month . RESULTS RESULTS showed that mean cholesterol and low density lipoprotein LDL levels were significantly decreased in both studied groups after one month of drinking mineral water ( P<0.05 ) ; however , no significant differences in high density lipoprotein ( HDL ) and triglyceride ( TG ) levels were seen in either group one month after drinking . There were no statistically significant differences between the " rich mineral water " and the normal mineral water groups in any of the above-mentioned lipid levels ( P>0.05 ) . CONCLUSION A one-month intake of mineral water rich in calcium , magnesium bicarbonate , and sulfate decreased cholesterol and LDL levels but not TG or HDL levels in dyslipidemic adults |
2,670 | 21,718,569 | In this systematic review we present information relating to the effectiveness and safety of the following interventions : adjuvant systemic chemotherapy , preoperative radiotherapy , and routine intensive follow-up | INTRODUCTION Colorectal cancer is the third most common malignancy in the developed countries , and about a quarter of people present with intestinal obstruction or perforation .
Risk factors for colorectal cancer are mainly dietary and genetic .
Overall 5-year survival is about 50 % , with half of people having surgery experiencing recurrence of the disease .
METHODS AND OUTCOMES We conducted a systematic review and aim ed to answer the following clinical question : What are the effects of treatments for colorectal cancer ? | PURPOSE The r and omized , multicenter , phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin ( FULV ) versus FULV with oxaliplatin ( FLOX ) in stage II or III colon cancer . Definitive analysis revealed an increase in 4-year disease-free survival from 67.0 % to 73.2 % in favor of FLOX . This study compares neurotoxicity between the treatments . PATIENTS AND METHODS Neurotoxicity was recorded for all patients using st and ard adverse event reporting . Patients at select institutions completed a neurotoxicity question naire through 18 months of follow-up . RESULTS A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported sub study . Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study ( P < .0001 ) . During therapy , patients receiving oxaliplatin experienced significantly more h and /foot toxicity ( eg , " quite a bit " of cold-induced h and /foot pain 26 % FLOX v 2.6 % FULV ) and overall weakness ( eg , moderate weakness in 27.4 % FLOX v 16.2 % FULV ) . At 18 months , h and neuropathy had diminished , but patients who received oxaliplatin experienced continued foot discomfort ( eg , moderate foot numbness and tingling for 22.1 % FLOX v 4.6 % FULV ) . Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor . Sixty-eight percent in the FLOX group v 8 % in the FULV group had neurotoxicity at their first on-treatment assessment . Time to resolution was significantly longer for those receiving oxaliplatin , and continued beyond 2 years for more than 10 % in the oxaliplatin group . CONCLUSION Oxaliplatin causes significant neurotoxicity . It is experienced primarily in the h and s during therapy and in the feet during follow-up . In a minority of patients the neurotoxicity is long lasting The aims of our study were to assess the effect of follow-up on the quality of life of colorectal cancer patients and to assess the attitudes of patients towards follow-up as a function of patient characteristics . Patients who had been treated with curative intent were selected from four types of hospitals . Eighty-two patients were interviewed using a structured question naire , whereas 130 patients received the question naire by mail . To assess the effect of follow-up on the quality of life , the interviewed patients were r and omly allocated to three groups and interviewed at different times in relation to the follow-up visit . Analysis did not show an effect of the follow-up visit on quality of life . Patients reported a positive attitude towards follow-up : it reassured them , they judged the communication with the physician to be positive , and they experienced only slight nervous anticipation and few other disadvantages . Patients reported a strong preference for follow-up , and a large majority would prefer follow-up even if it would not lead to earlier detection of a recurrence . Apart from living situation , no patient characteristics were clearly associated with the attitude towards follow-up . Implication s for clinical practice are discussed BACKGROUND Adjuvant postoperative treatment with 5-fluorouracil ( 5-FU ) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrences and improves survival . The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in a long-term follow-up study in comparison with the effects of 5-FU plus levamisole in the prospect i ve multicenter trial adjCCA-01 . PATIENTS AND METHODS Patients with a curatively resected stage III ( International Union Against Cancer ) colon cancer were stratified according to tumor , node and grading category and r and omly assigned to receive one of the two adjuvant treatment schemes : 5-FU 400 mg/m2 body surface area intravenously in the first chemotherapy course , then 450 mg/m2 x 5 days , plus leucovorin 100 mg/m2 , 12 cycles ( arm A ) , or 5-FU plus levamisole ( Moertel scheme ; arm B ) . RESULTS Six hundred and eighty ( 96.9 % ) of 702 patients enrolled into this study were eligible . To date , 261 patients have died , 117 on arm A and 144 on arm B ( P = 0.007 ) . After a median follow-up time of 82 months , the 5-FU plus leucovorin combination significantly improved disease-free survival [ 79.8 months in arm A versus 69.3 months in arm B ( P = 0.012 ) ] and significantly increased median overall survival ( 88.9 months in arm A versus 78.6 months in arm B ; P = 0.003 ) . Adjuvant treatment with 5-FU plus levamisole as well as 5-FU plus leucovorin was generally well tolerated ; only a minority of patients experienced grade 3 and 4 toxicities . CONCLUSIONS After curative resection of a stage III colon cancer , adjuvant treatment with 5-FU plus leucovorin is generally well tolerated . This long-term follow-up study demonstrates that adjuvant treatment with 5-FU plus leucovorin given for 12 cycles is significantly more effective than 5-FU plus levamisole ( Moertel scheme ) in reducing tumor relapse and improving survival Background : Adjuvant chemotherapy for colon cancer has been established during the past decade . From 1990 until recently treatment with 5- fluorouracil ( 5-FU ) and levamisole ( LEV ) lasting 12 months was recommended as st and ard treatment . At the initiation of this study in 1993 improvement of adjuvant therapy was expected by the modulation of 5-FU with folinic acid ( FA ) . Therefore , we decided to perform a prospect i ve r and omized multicenter trial to compare st and ard 5-FU/LEV to 5-FU/FA for either 6 or 12 months . Patients and Methods : Patients with stage III colon cancer after curative en bloc resection were r and omized in 3 treatment groups : arm A ( 5-FU/LEV , weekly , 12 months ) , arm B ( 5-FU/FA , days 1–5 , every 4 weeks , 12 months ) and arm C ( like B , 6 months ) . Results : Between March 1993 and November 1997 , 180 patients were r and omized into the study , 155 were eligible for further evaluation . The interim analysis in November 2000 showed no significant difference for recurrence and disease-free survival in arm B and C , therefore the data from both 5-FU/FA treatment arms ( B+C ) were combined for comparison with 5-FU/LEV-treatment ( A ) . Most pronounced toxicity in all treatment arms was mild nausea , loss of appetite and leukopenia . A tendency for more diarrhea and stomatitis was observed in arm B+C. After a median follow-up of 36.2 months no significant difference was seen for diseasefree survival ( p = 0.9 ) and overall survival ( p = 1.0 ) . 3-year recurrence rates were 39.6 % in arm A and 39.1 % in arm B+C , 3-year survival rates amounted to 74.1 % in arm A and 74.9 % in arm B+C. Conclusion : Only a limited number of patients could be recruited in this study . The observed data support the results of other studies , which concluded that 6 months ( or 12 months ) treatment with 5-FU/FA is equivalent to 12 months treatment with 5-FU/LEV . Therefore the 6 months treatment with 5-FU/FA can be supported as st and ard for adjuvant therapy of stage III colon cancer BACKGROUND Current evidence suggests that high red meat intake is associated with increased colorectal cancer risk . High fish intake may be associated with a decreased risk , but the existing evidence is less convincing . METHODS We prospect ively followed 478 040 men and women from 10 European countries who were free of cancer at enrollment between 1992 and 1998 . Information on diet and lifestyle was collected at baseline . After a mean follow-up of 4.8 years , 1329 incident colorectal cancers were documented . We examined the relationship between intakes of red and processed meat , poultry , and fish and colorectal cancer risk using a proportional hazards model adjusted for age , sex , energy ( nonfat and fat sources ) , height , weight , work-related physical activity , smoking status , dietary fiber and folate , and alcohol consumption , stratified by center . A calibration sub study based on 36 994 subjects was used to correct hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for diet measurement errors . All statistical tests were two-sided . RESULTS Colorectal cancer risk was positively associated with intake of red and processed meat ( highest [ > 160 g/day ] versus lowest [ < 20 g/day ] intake , HR = 1.35 , 95 % CI = 0.96 to 1.88 ; Ptrend = .03 ) and inversely associated with intake of fish ( > 80 g/day versus < 10 g/day , HR = 0.69 , 95 % CI = 0.54 to 0.88 ; Ptrend<.001 ) , but was not related to poultry intake . Correcting for measurement error strengthened the associations between colorectal cancer and red and processed meat intake ( per 100-g increase HR = 1.25 , 95 % CI = 1.09 to 1.41 , Ptrend = .001 and HR = 1.55 , 95 % CI = 1.19 to 2.02 , Ptrend = .001 before and after calibration , respectively ) and for fish ( per 100 g increase HR = 0.70 , 95 % CI = 0.57 to 0.87 , Ptrend<.001 and HR = 0.46 , 95 % CI = 0.27 to 0.77 , Ptrend = .003 ; before and after correction , respectively ) . In this study population , the absolute risk of development of colorectal cancer within 10 years for a study subject aged 50 years was 1.71 % for the highest category of red and processed meat intake and 1.28 % for the lowest category of intake and was 1.86 % for subjects in the lowest category of fish intake and 1.28 % for subjects in the highest category of fish intake . CONCLUSIONS Our data confirm that colorectal cancer risk is positively associated with high consumption of red and processed meat and support an inverse association with fish intake PURPOSE To evaluate the effectiveness of 6-month therapy with leucovorin (LV)+5-fluorouracil ( 5-FU ) versus 12-month therapy with levamisole (LVS)+5-FU , as adjuvant chemotherapy in patients with completely resected Aster-Coller stage B(2 ) or C(1)/C(2 ) rectal cancer ( RC ) . PATIENTS AND METHODS One hundred and fifty patients with surgically resected RC were enrolled . Seventy patients with stage B(2 ) and 80 with stage C were r and omly assigned to adjuvant chemotherapy with 5-FU+LXx6 months or 5-FU+LVSx12 months . Patient characteristics were equally balanced between the examined groups . Adjuvant chemotherapy consisted of LV 20 mg/m(2 ) intravenously ( i.v . ) plus 5-FU 450 mg/m(2 ) i.v . bolus every week plus LVS tablets 50 mg t.i.dx3 days every 2 weeks for 1 year . RESULTS After a median follow up for survivors of 8.7 years ( range 1.8 - 10.5 ) , all of the patients were evaluable . There were no significant differences between the two treatment groups with respect to the recurrence rates ( p=0.821 ) . Moreover , there were no significant differences between the two tratment groups in disease-free survival ( DFS ) ( p=0.84 ) [ B(2)(p=0.805 ) and C ( p=0.978 ) ] and overall survival ( OS ) rates for patients of either stage B(2 ) or C ( p=0.78 ) . Toxicities were more frequent in the 5-FU+LVS versus 5-FU+LV group : myelosuppression ( grade 3 leucopenia , 12 versus 4 % , p<0.04 ) , diarrhea ( grade 0 , 60 versus 76 % , p<0.02 ) , and liver toxicity ( increase of transaminases > 3-fold , 12 patients versus 2 , p<0.03 . ) . No patient stopped chemotherapy because of toxicity , and there were no treatment-related deaths . CONCLUSION Adjuvant chemotherapy in RC with LV+5-FU for 6 months is equally effective and less toxic than LVS+5-FU for 12 months The purpose of this trial was to investigate the efficacy of adjuvant chemotherapy with 5-fluorouracil ( 5-FU ) and leucovorin ( LV ) in stage II colon cancer . Patients with stage II colon cancer were r and omised to either adjuvant chemotherapy with 5-FU/LV ( 100 mg m−2 LV+450 mg m−2 5-FU weekly , weeks 1–6 , in 8 weeks cycles × 7 ) or surveillance only . Five hundred patients were evaluable for analyses . After a median follow-up of 95.6 months , 55 of 252 patients ( 21.8 % ) have died in the 5-FU/LV arm and 58 of 248 patients ( 23.4 % ) in the surveillance arm . There was no statistically significant difference in overall survival ( OS ) between the two treatment arms ( hazard ratios , HR 0.88 , 95 % CI 0.61–1.27 , P=0.49 ) . The relative risk for tumour relapse was higher for patients on the surveillance arm than for those on the 5-FU/LV arm ; however , this difference was not statistically significant ( HR 0.69 , 95 % CI 0.45–1.06 , P=0.09 ) . Consequently , disease-free survival ( DFS ) was not significantly different between the two trial arms . In conclusion , results of this trial demonstrate a trend to a lower risk for relapse in patients treated with adjuvant 5-FU/LV for stage II colon cancer . However , in this study with limited power to detect small differences between the study arms , adjuvant chemotherapy failed to significantly improve DFS and OS Background Adjuvant postoperative treatment with 5-fluorouracil ( 5-FU ) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrence and improves survival . The impact of continuous 5-FU with and without leucovorin on survival and tumor recurrence was analyzed in this study compared with the effects of bolus 5-FU/leucovorin . Patients and methods Patients with a curatively resected UICC stage III colon cancer were stratified according to T , N and G category and r and omly assigned to receive one of the three adjuvant treatment schemes : 5-FU 450 mg/m2 and leucovorin 100 mg/m2 × 5 days every 4 weeks ; six cycles , arm A ; 24-h infusion of high-dose 5-FU/leucovorin 2,600 mg/m2 and 500 mg/m2 , two cycles of six applications , arm B ; 24-h infusion of high-dose 5-FU 2,600 mg/m2 , two cycles of six applications , arm C. Results One hundred and forty-five patients enrolled into this study were eligible . To date , 28 patients have died ; 9 on arm A , 11 on arm B , and 8 on arm C ( P was nonsignificant ) . After a median follow-up time of 45 months , there was no statistical difference in survival and tumor recurrence between the three treatment arms . Adjuvant treatment in all arms was generally well tolerated ; only a minority of patients experienced grade 3 and 4 toxicities . Conclusion There is no statistical difference in efficacy and toxicity in patients receiving either high-dose 5-FU with or without leucovorin or the st and ard 5-FU bolus regime after a curative resection of a stage III colon cancer BACKGROUND The aim of the QUASAR trial was to determine the size and duration of any survival benefit from adjuvant chemotherapy for patients with colorectal cancer at low risk of recurrence , for whom the indication for such treatment is unclear . METHODS After apparently curative resections of colon or rectal cancer , 3239 patients ( 2963 [ 91 % ] with stage II [ node negative ] disease , 2291 [ 71 % ] with colon cancer , median age 63 [ IQR 56 - 68 ] years ) enrolled between May , 1994 , and December , 2003 , from 150 centres in 19 countries were r and omly assigned to receive chemotherapy with fluorouracil and folinic acid ( n=1622 ) or to observation ( with chemotherapy considered on recurrence ; n=1617 ) . Chemotherapy was delivered as six 5-day courses every 4 weeks or as 30 once-weekly courses of intravenous fluorouracil ( 370 mg/m2 ) with high-dose ( 175 mg ) L-folinic acid or low-dose ( 25 mg ) L-folinic acid . Until 1997 , levamisole ( 12 courses of 450 mg over 3 days repeated every 2 weeks ) or placebo was added . After 1997 , patients who were assigned to receive chemotherapy were given fluorouracil and low-dose folinic acid only . The primary outcome was all-cause mortality . Analyses were done by intention to treat . This trial is registered with the International Clinical Trial Registry , number IS RCT N82375386 . FINDINGS At the time of analysis , 61 ( 3.8 % ) patients in the chemotherapy group and 50 ( 3.1 % ) in the observation group had missing follow-up . After a median follow-up of 5.5 ( range 0 - 10.6 ) years , there were 311 deaths in the chemotherapy group and 370 in the observation group ; the relative risk of death from any cause with chemotherapy versus observation alone was 0.82 ( 95 % CI 0.70 - 0.95 ; p=0.008 ) . There were 293 recurrences in the chemotherapy group and 359 in the observation group ; the relative risk of recurrence with chemotherapy versus observation alone was 0.78 ( 0.67 - 0.91 ; p=0.001 ) . Treatment efficacy did not differ significantly by tumour site , stage , sex , age , or chemotherapy schedule . Eight ( 0.5 % ) patients in the chemotherapy group and four ( 0.25 % ) in the observation group died from non-colorectal cancer causes within 30 weeks of r and omisation ; only one of these deaths was deemed to be possibly chemotherapy related . INTERPRETATION Chemotherapy with fluorouracil and folinic acid could improve survival of patients with stage II colorectal cancer , although the absolute improvements are small : assuming 5-year mortality without chemotherapy is 20 % , the relative risk of death seen here translates into an absolute improvement in survival of 3.6 % ( 95 % CI 1.0 - 6.0 ) From 1980 to 1985 , 471 patients with resectable rectal and rectosigmoid cancer were r and omly allocated to receive either preoperative short-term high-dose irradiation ( 25.5 Gy in one week ) for all patients or prolonged postoperative radiotherapy ( 60 Gy in seven to eight weeks ) only for patients with a Dukes B or C lesion . After a minimum follow-up of five years , the local recurrence rate was statistically significantly lower after preoperative than after postoperative radiotherapy ( 13 percentvs.22 percent;P=0.02 ) . No difference in overall survival was noted ( P=0.5 ) . To evaluate possible late side effects on the bowel , urinary bladder , or skin after surgery and additional preoperative or postoperative radiotherapy , all patients included in the r and omized trial , together with 58 patients from a preceding pilot study with the same preoperative regimen , were studied in a prolonged follow-up program . The hospital files of all patients were re-examined . Of the patients who were carefully examined , 176 had a survival exceeding five years and 19 had a survival exceeding 10 years . Overall , 7 percent ( 33/ 464 ) either were operated upon or have had a radiologic diagnosis of small bowel obstruction : 14/255 ( 5 percent ) after preoperative irradiation , 14/127 ( 11 percent ) after postoperative irradiation , and 5/82 ( 6 percent ) after surgery alone . The cumulative risk of developing a bowel obstruction was significantly increased after postoperative radiotherapy . Among the 98 patients alive after preoperative irradiation , significant morbidity from the bowel was noted in 11 patients , from the urinary bladder in two , and from the skin in six . In the postoperatively treated group of 34 patients , the bowel , urinary bladder , and skin morbidity were significant in five , two , and five patients , respectively . Corresponding morbidity in 44 nonirradiated patients was seen in five , one , and two patients , respectively . It is concluded that preoperative , short-term , high-dose radiotherapy decreases the local recurrence rate relative to postoperative radiotherapy , with no indications of increased late morbidity after a follow-up of 5 to 10 years A total of 401 eligible patients with resected stages B and C colorectal carcinoma were r and omly assigned to no-further therapy or to adjuvant treatment with either levamisole alone , 150 mg/d for 3 days every 2 weeks for 1 year , or levamisole plus fluorouracil ( 5-FU ) , 450 mg/m2/d intravenously ( IV ) for 5 days and beginning at 28 days , 450 mg/m2 weekly for 1 year . Levamisole plus 5-FU , and to a lesser extent levamisole alone , reduced cancer recurrence in comparison with no adjuvant therapy . These differences , after correction for imbalances in prognostic variables , were only suggestive for levamisole alone ( P = .05 ) but quite significant for levamisole plus 5-FU ( P = .003 ) . Whereas both treatment regimens were associated with overall improvements in survival , these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU ( P = .03 ) . Therapy was clinical ly tolerable with either regimen and severe toxicity was uncommon . These promising results have led to a large national intergroup confirmatory trial currently in progress BACKGROUND Postoperative chemoradiotherapy is the recommended st and ard therapy for patients with locally advanced rectal cancer . In recent years , encouraging results with preoperative radiotherapy have been reported . We compared preoperative chemoradiotherapy with postoperative chemoradiotherapy for locally advanced rectal cancer . METHODS We r and omly assigned patients with clinical stage T3 or T4 or node-positive disease to receive either preoperative or postoperative chemoradiotherapy . The preoperative treatment consisted of 5040 cGy delivered in fractions of 180 cGy per day , five days per week , and fluorouracil , given in a 120-hour continuous intravenous infusion at a dose of 1000 mg per square meter of body-surface area per day during the first and fifth weeks of radiotherapy . Surgery was performed six weeks after the completion of chemoradiotherapy . One month after surgery , four five-day cycles of fluorouracil ( 500 mg per square meter per day ) were given . Chemoradiotherapy was identical in the postoperative-treatment group , except for the delivery of a boost of 540 cGy . The primary end point was overall survival . RESULTS Four hundred twenty-one patients were r and omly assigned to receive preoperative chemoradiotherapy and 402 patients to receive postoperative chemoradiotherapy . The overall five-year survival rates were 76 percent and 74 percent , respectively ( P=0.80 ) . The five-year cumulative incidence of local relapse was 6 percent for patients assigned to preoperative chemoradiotherapy and 13 percent in the postoperative-treatment group ( P=0.006 ) . Grade 3 or 4 acute toxic effects occurred in 27 percent of the patients in the preoperative-treatment group , as compared with 40 percent of the patients in the postoperative-treatment group ( P=0.001 ) ; the corresponding rates of long-term toxic effects were 14 percent and 24 percent , respectively ( P=0.01 ) . CONCLUSIONS Preoperative chemoradiotherapy , as compared with postoperative chemoradiotherapy , improved local control and was associated with reduced toxicity but did not improve overall survival BACKGROUND Few prospect i ve studies have been performed about the impact of preoperative radiotherapy ( PRT ) or total mesorectal excision ( TME ) on health-related quality of life ( HRQL ) and sexual functioning in patients with resectable rectal cancer . This report describes the HRQL and sexual functioning of 990 patients who underwent TME and were r and omly assigned to short-term PRT ( 5 x 5 Gy ) . PATIENTS AND METHODS The Rotterdam Symptom Check List supplemented with additional items was used with question naires before treatment and at 3 , 6 , 12 , 18 , and 24 months after surgery . Patients without a recurrence the first 2 years were analyzed ( n = 990 ) . RESULTS Few differences were found in HRQL between patients treated with or without PRT . Daily activities were significantly less for PRT patients 3 months postoperatively . Irradiated patients recovered slower from defecation problems than TME-only patients ( P = .006 ) . PRT had a negative effect on sexual functioning in males ( P = .004 ) and females ( P < .001 ) . Irradiated males had more ejaculation disorders ( P = .002 ) , and erectile functioning deteriorated over time ( P < .001 ) . PRT had similar effects in patients who underwent a low anterior resection ( LAR ) versus an abdominoperineal resection ( APR ) . Patients with an APR scored better on the physical ( P = .004 ) and psychologic dimension ( P = .007 ) than LAR patients , but worse on voiding ( P = .0007 ) . CONCLUSION Short-term PRT leads to more sexual dysfunction , slower recovery of bowel function , and impaired daily activity postoperatively . However , this does not seriously affect HRQL . The comparison between LAR and APR patients demonstrates that the existence of a permanent stoma is not the only determinant of HRQL To verify the effectiveness of oral 1-hexylcarbamoyl-5-fluorouracil ( HCFU ) in improving the surgical cure rate in advanced colorectal cancer , a multicenter r and omized comparative study was conducted . A total of 429 patients who had had curative resection for stage II and III colorectal cancer were r and omly assigned to a study group receiving a 14-day course of 5-FU continuous infusion ( 320 mg/m2/day ) followed by oral HCFU for a year ( 300 mg/day ) , or to the control group receiving a 14-day course of 5-FU continuous infusion alone . In terms of background factors , no significant differences were found between the 214 patients in the study group and the 215 in the control group . Adverse reactions during the treatment were more frequently seen in the study group . But with few exceptions , the toxicities were mild and the compliance was acceptable . The 5-year overall survival rate of the study group was similar to that of the control group . The 5-year disease-free survival rate of the study group was better than that of the control group in the patients with colon cancer ( hazard ratio=1.87 ; 95 % confidence interval 1.03 - 3.38 ; p=0.037 ) . However , this benefit was not seen in the patients with rectal cancer . A significant improvement in the disease-free survival rate was demonstrated through the addition of HCFU to 5-FU continuous infusion for the patients with colon cancer . The usefulness of oral fluoropyrimidine as an adjuvant for curative surgery for colon cancer was further warranted BACKGROUND To determine whether the addition of leucovorin to the combination 5-fluorouracil plus levamisole prolongs disease-free survival and overall survival in patients with radically resected colon cancer ( Dukes ' B(2 - 3 ) and C ) . PATIENTS AND METHODS Patients ( 1703 ) were accrued between March 1992 and February 1995 in a large-scale clinical trial within five Italian cooperative groups . After stratification for center , patients were r and omized as follows : arm A , 5-fluorouracil [ 450 mg/m(2 ) intravenous ( i.v . ) bolus on days 1 - 5 ] and levamisole ( 150 mg orally for 3 days , every 14 days for 6 months ) versus arm B , 6-S-leucovorin ( 100 mg/m(2 ) i.v . bolus on days 1 - 5 ) followed by 5-fluorouracil ( 370 mg/m(2 ) i.v . bolus on days 1 - 5 ) , plus levamisole ( as arm A ) , every 4 weeks for six cycles . RESULTS After a median follow-up of 6.4 years no significant difference was seen for either disease-free survival ( 58 % versus 60 % , not significant ) or 5-year overall survival ( 68 % versus 71 % , not significant ) , respectively . Gastrointestinal toxicity ( World Health Organization grade 3/4 ) was more frequent in arm B ( 8 % versus 18 % , not significant ) . CONCLUSIONS In this trial the schedules used showed no statistically significant differences in terms of disease-free survival or overall survival in the treatment of colorectal cancer BACKGROUND The st and ard adjuvant treatment of colon cancer is fluorouracil plus leucovorin ( FL ) . Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer . We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting . METHODS We r and omly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months . The primary end point was disease-free survival . RESULTS A total of 1123 patients were r and omly assigned to each group . After a median follow-up of 37.9 months , 237 patients in the group given FL plus oxaliplatin had had a cancer-related event , as compared with 293 patients in the FL group ( 21.1 percent vs. 26.1 percent ; hazard ratio for recurrence , 0.77 ; P=0.002 ) . The rate of disease-free survival at three years was 78.2 percent ( 95 percent confidence interval , 75.6 to 80.7 ) in the group given FL plus oxaliplatin and 72.9 percent ( 95 percent confidence interval , 70.2 to 75.7 ) in the FL group ( P=0.002 by the stratified log-rank test ) . In the group given FL plus oxaliplatin , the incidence of febrile neutropenia was 1.8 percent , the incidence of gastrointestinal adverse effects was low , and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment , decreasing to 1.1 percent at one year of follow-up . Six patients in each group died during treatment ( death rate , 0.5 percent ) . CONCLUSIONS Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer PURPOSE To assess the effect of the addition of leucovorin to the combination of 5-fluorouracil (5-FU)-levamisole on recurrence risk and overall survival in patients after a resection with curative intent of a Dukes ' C colon cancer . PATIENTS AND METHODS Five hundred patients with Dukes ' C colon cancer were r and omly assigned to adjuvant treatment for one year with 5-fluorouracil ( 450 mg/m2 i.v . weekly ) and levamisole ( 150 mg p.o . every two weeks ) , the C-group or with leucovorin ( 20 mg/m2 i.v . ) , 5-fluorouracil and levamisole , the L-group . The median follow-up for patients still alive is 36 months . Four patients were ineligible because of advanced disease at the time of r and omisation . RESULTS Sixty percent of the patients have completed all courses of chemotherapy . Of the remaining 40 % of the patients who did not complete one-year treatment with chemotherapy , 46 % discontinued because of toxic and /or emotional reasons . They were equally divided over both treatment arms . The addition of leucovorin increased toxicity ( especially mucositis and conjunctivitis ) without a significant increase in treatment withdrawal . Five-year disease-free interval ( C-group : 49 % , L-group : 46 % ; log-rank test , P = 0.86 ) and overall survival ( C-group : 55 % , L-group : 59 % , log-rank test : P = 0.96 ) were very similar in both treatment arms . CONCLUSIONS The addition of low dose leucovorin to the combination of 5-fluorouracil and levamisole in a 12-month adjuvant therapy for curatively resected Dukes ' C colon cancer patients does not improve disease-free interval nor overall survival . The addition of leucovorin to the combination of 5-FU levamisole increases toxicity . Therefore leucovorin 5-FU levamisole is not recommended in a 12 months adjuvant regime of Dukes ' C colon cancer Colorectal cancer is one of the major malignant diseases and , recently , its incidence appears to be increasing . Surgical resectability is an important prognostic determinant ; however , recurrent tumors are commonly noted , even after apparently curative surgery . Because such metastatic disease can not be cured , better adjuvant therapies are urgently called for A prospect i ve controlled r and omized trial testing adjuvant postoperative combination chemotherapy ( 5‐fluorouracil , lomustine ( CNU ) and vincristine ) versus no adjuvant therapy in patients operated on for Dukes ' C colorectal cancer is reported . In total 334 patients aged less than 70 years were recruited : 205 patients with colonic and 99 with rectal cancer , but there were three protocol violations and these cases are excluded from further consideration . Twenty‐seven patients had a limited resection of their cancer . After 5 years follow‐up there was no significant difference in the tumour‐free survival rate or in the survival rate between the treated and control groups . Twenty‐nine of the 147 patients who started chemotherapy discontinued this treatment because of side‐effects , mainly from the gastrointestinal tract . In 30 patients treatment was discontinued because of recurrent disease . The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice PURPOSE This phase III clinical trial evaluated the impact on disease-free survival ( DFS ) of adding oxaliplatin to bolus weekly fluorouracil ( FU ) combined with leucovorin as surgical adjuvant therapy for stage II and III colon cancer . PATIENTS AND METHODS Patients who had undergone a potentially curative resection were r and omly assigned to either FU 500 mg/m2 intravenous ( IV ) bolus weekly for 6 weeks plus leucovorin 500 mg/m2 IV weekly for 6 weeks during each 8-week cycle for three cycles ( FULV ) , or the same FULV regimen with oxaliplatin 85 mg/m2 IV administered on weeks 1 , 3 , and 5 of each 8-week cycle for three cycles ( FLOX ) . RESULTS A total of 2,407 patients ( 96.6 % ) of the 2,492 patients r and omly assigned were eligible . Median follow-up for patients still alive is 42.5 months . The hazard ratio ( FLOX v FULV ) is 0.80 ( 95 % CI , 0.69 to 0.93 ) , a 20 % risk reduction in favor of FLOX ( P < .004 ) . The 3- and 4-year disease-free survival ( DFS ) rates were 71.8 % and 67.0 % for FULV and 76.1 % and 73.2 % for FLOX , respectively . Grade 3 neurosensory toxicity was noted in 8.2 % of patients receiving FLOX and in 0.7 % of those receiving FULV ( P < .001 ) . Hospitalization for diarrhea associated with bowel wall thickening occurred in 5.5 % of the patients receiving FLOX and in 3.0 % of the patients receiving FULV ( P < .01 ) . A total of 1.2 % of patients died as a result of any cause within 60 days of receiving chemotherapy , with no significant difference between regimens . CONCLUSION The addition of oxaliplatin to weekly FULV significantly improved DFS in patients with stage II and III colon cancer . FLOX can be recommended as an effective option in clinical practice PURPOSE To compare the efficacy of leucovorin-modulated fluorouracil ( FU+LV ) with that of fluorouracil and levamisole ( FU+LEV ) or with the combination of FU+LV and levamisole ( FU+LV+LEV ) . PATIENTS AND METHODS Between July 1989 and December 1990 , 2,151 patients with Dukes ' B ( stage II ) and Dukes ' C ( stage III ) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl Project protocol C-04 . Patients were r and omly assigned to receive FU+LV ( weekly regimen ) , FU + LEV , or the combination of FU+LV+LEV . The average time on study was 86 months . RESULTS A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival ( DFS ) in favor of the FU+LV group ( 65 % v 60 % ; P = .04 ) ; there was a small prolongation in overall survival that was of borderline significance ( 74 % v 70 % ; P = .07 ) . There was no difference in the pairwise comparison between patients who received FU+LV or FU+LV+LEV for either DFS ( 65 % v 64 % ; P = .67 ) or overall survival ( 74 % v 73 % ; P = .99 ) . There was no interaction between Dukes ' stage and the effect of treatment . CONCLUSION In patients with Dukes ' B and C carcinoma of the colon , treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV . The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV . These findings support the use of adjuvant FU+LV as an acceptable therapeutic st and ard in patients with Dukes ' B and C carcinoma of the colon PURPOSE The goal of this study was to determine the efficacy of intensive-course fluorouracil ( 5FU ) plus low-dose leucovorin given for 6 months following potentially curative resection of colon cancer . PATIENTS AND METHODS Three hundred seventeen patients with high-risk stage II or stage III colon cancer were r and omly assigned 3 to 4 weeks following surgery to receive either ( 1 ) chemotherapy with six cycles of 5FU ( 425 mg/m2 ) plus leucovorin ( 20 mg/m2 ) by rapid intravenous injection daily for 5 consecutive days every 4 to 5 weeks , or ( 2 ) observation . RESULTS The median follow-up duration is 72 months for patients still alive . Patients who received postoperative 5FU plus leucovorin experienced significant improvement in time to relapse ( P < .01 ) and survival ( P = .02 ) compared with control patients treated with surgery alone . Stomatitis , diarrhea , and leukopenia were the predominant chemotherapy toxicities . There were no treatment-related deaths . CONCLUSION These results indicate that intensive-course 5FU plus low-dose leucovorin is effective in preventing tumor relapse and improving survival in patients with high-risk colon cancer . These benefits were seen with only six cycles of treatment , using low-dose leucovorin in combination with 5FU on a schedule convenient for outpatient administration PURPOSE Preoperative short-term radiotherapy improves local control in patients treated with total mesorectal excision ( TME ) . This study was performed to assess the presence and magnitude of long-term side effects of preoperative 5 x 5 Gy radiotherapy and TME . Also , hospital treatment was recorded for diseases possibly related to late side effects of rectal cancer treatment . PATIENTS AND METHODS Long-term morbidity was assessed in patients from the prospect i ve r and omized TME trial , which investigated the efficacy of 5 x 5 Gy before TME surgery for mobile rectal cancer . Dutch patients without recurrent disease were sent a question naire . RESULTS Results were obtained from 597 patients , with a median follow-up of 5.1 years . Stoma function , urinary function , and hospital treatment rates did not differ significantly between the treatment arms . However , irradiated patients , compared with nonirradiated patients , reported increased rates of fecal incontinence ( 62 % v 38 % , respectively ; P < .001 ) , pad wearing as a result of incontinence ( 56 % v 33 % , respectively ; P < .001 ) , anal blood loss ( 11 % v 3 % , respectively ; P = .004 ) , and mucus loss ( 27 % v 15 % , respectively ; P = .005 ) . Satisfaction with bowel function was significantly lower and the impact of bowel dysfunction on daily activities was greater in irradiated patients compared with patients who underwent TME alone . CONCLUSION Although preoperative short-term radiotherapy for rectal cancer results in increased local control , there is more long-term bowel dysfunction in irradiated patients than in patients who undergo TME alone . Rectal cancer patients should be informed on late morbidity of both radiotherapy and TME . Future strategies should be aim ed at selecting patients for radiotherapy who are at high risk for local failure PURPOSE This study was design ed to evaluate the efficacy of leucovorin-modulated fluorouracil ( 5-FU ) as adjuvant therapy for patients with Dukes ' stage B and C colon cancer . PATIENTS AND METHODS Data are presented from 1,081 patients with Dukes ' stage B and C carcinoma of the colon entered into National Surgical Adjuvant Breast and Bowel Project ( NSABP ) protocol C-03 between August 1987 and April 1989 . Patients were r and omly assigned to receive either lomustine ( MeCCNU ) , vincristine , and 5-FU ( MOF ) , or leucovorin-modulated 5-FU ( LV + 5-FU ) . The mean time on study was 47.6 months . RESULTS Comparison between the two groups indicates a disease-free survival advantage for patients treated with LV + 5-FU ( P = .0004 ) . The 3-year disease-free survival rate for patients in this group was 73 % ( 95 % confidence interval , 69 % to 77 % ) , compared with 64 % ( 95 % confidence interval , 60 % to 68 % ) for patients receiving MOF . The corresponding percentage of patients surviving was 84 % for those r and omized to receive LV + 5-FU and 77 % for the MOF-treated cohort ( P = .003 ) . At 3 years of follow-up , patients treated with postoperative LV + 5-FU had a 30 % reduction in the risk of developing a treatment failure and a 32 % reduction in mortality risk compared with similar patients treated with MOF . CONCLUSION Treatment with LV + 5-FU significantly prolongs disease-free survival and results in a significant benefit relative to overall survival . These findings , when considered together with results from a recent meta- analysis demonstrating a benefit from LV + 5-FU in advanced disease , provide evidence to support the concept of metabolic modulation of 5-FU BACKGROUND We performed a multicentre r and omised trial to compare the efficacy and toxicity of 12 weeks of protracted venous infusion ( PVI ) 5-fluorouracil ( 5-FU ) against the st and ard bolus monthly regimen of 5-FU/leucovorin ( LV ) given for 6 months as adjuvant treatment in colorectal cancer ( CRC ) . PATIENTS AND METHODS Patients with curatively resected stage II and III CRC were r and omly assigned to 5-FU/LV [ 5-FU 425 mg/m(2 ) intravenously ( i.v . ) and LV 20 mg/m(2 ) i.v . bolus days 1 - 5 every 28 days for 6 months ] or to PVI 5-FU ( 300 mg/m(2)/day for 12 weeks ) . RESULTS Between 1993 and 2003 , 801 eligible patients were r and omised to 5-FU/LV ( n=404 ) or PVI 5-FU ( n=397 ) . With a median follow-up of 5.3 years , 231 relapses and 220 deaths have been observed . Five-year relapse-free survival ( RFS ) was 66.7 % [ 95 % confidence interval ( CI ) 61.6 % to 71.3 % ] and 73.3 % ( 95 % CI 68.4 % to 77.6 % ) with bolus 5-FU/LV and PVI 5-FU , respectively [ hazard ratio ( HR ) 0.8 ; 95 % CI 0.62 - 1.04 ; P=0.10 ] . Five-year overall survival ( OS ) was 71.5 % ( 95 % CI 66.4 % to 75.9 % ) and 75.7 % ( 95 % CI 70.8 % to 79.9 % ) with bolus 5-FU/LV and PVI 5-FU , respectively ( HR 0.79 ; 95 % CI 0.61 - 1.03 ; P=0.083 ) . There was a significant survival advantage for patients starting adjuvant chemotherapy within 8 weeks ( P=0.044 ) . Significantly less diarrhoea , stomatitis , nausea and vomiting , alopecia , lethargy , and neutropenia ( all with P < 0.0001 ) were seen with PVI 5-FU . CONCLUSIONS There was no OS difference between the two arms , although PVI 5-FU was associated with a trend towards better RFS and OS compared with bolus 5-FU/LV , as well as significantly less toxicity . Based on our results , the probability of 12 weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low ( P < 0.005 ) , and therefore shorter duration of adjuvant treatment should be explored further BACKGROUND Levamisole combined with 5-fluorouracil ( 5-FU ) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer . Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines . A clinical trial was design ed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy . PATIENTS AND METHODS Eight hundred seventy-eight patients who had undergone complete surgical resection of high-risk stage II/III colon cancer were stratified by known prognostic factors and r and omized to receive 1 of 2 treatment regimens : st and ard-dose levamisole combined with 5-FU and leucovorin ; or high-dose levamisole combined with the same chemotherapy . Serum neopterin was monitored in a cohort of patients to evaluate immune function . RESULTS Severe vomiting and neurologic side effects required reduction in the dose of levamisole that could be safely administered on the high-dose levamisole regimen . There were no significant differences in disease-free survival , overall survival , or levels of serum neopterin between the treatment regimens . CONCLUSION It was not possible to improve the efficacy of surgical adjuvant chemotherapy for patients with high-risk colon cancer by giving levamisole at its maximum tolerated dose in combination with 5-FU and leucovorin . High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen PURPOSE The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur ( UFT ) plus leucovorin ( LV ) with the efficacy of weekly intravenous fluorouracil ( FU ) plus LV in prolonging disease-free survival ( DFS ) and overall survival ( OS ) after primary surgery for colon carcinoma . PATIENTS AND METHODS Between February 1997 and March 1999 , 1,608 patients with stage II and III carcinoma of the colon were r and omly assigned to receive either oral UFT+LV or intravenous FU+LV . RESULTS Of the total patients , 47 % had stage II colon cancer , and 53 % had stage III colon cancer . Median follow-up time was 62.3 months . The estimated hazard ratio ( HR ) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 ( 95 % CI , 0.825 to 1.246 ) . The estimated HR for DFS was 1.004 ( 95 % CI , 0.847 to 1.190 ) . Cox proportional hazards model analyses with regard to age ( < 60 v > or = 60 years ) , stage , or number of involved nodes ( none v one to three v > or = four nodes ) revealed no interaction with OS or DFS . Toxicity was similar in the two groups . In the UFT+LV arm , 38.2 % of patients experienced any grade 3 or 4 toxic event compared with 37.8 % of patients in the FU+LV arm . Primary quality -of-life end points did not differ between the two regimens , although convenience of care analysis favored UFT+LV . CONCLUSION UFT+LV achieved similar DFS and OS when compared with an intravenous , weekly , bolus FU+LV regimen . The two regimens were equitoxic and generally well tolerated BACKGROUND Intravenous bolus fluorouracil plus leucovorin is the st and ard adjuvant treatment for colon cancer . The oral fluoropyrimidine capecitabine is an established alternative to bolus fluorouracil plus leucovorin as first-line treatment for metastatic colorectal cancer . We evaluated capecitabine in the adjuvant setting . METHODS We r and omly assigned a total of 1987 patients with resected stage III colon cancer to receive either oral capecitabine ( 1004 patients ) or bolus fluorouracil plus leucovorin ( Mayo Clinic regimen ; 983 patients ) over a period of 24 weeks . The primary efficacy end point was at least equivalence in disease-free survival ; the primary safety end point was the incidence of grade 3 or 4 toxic effects due to fluoropyrimidines . RESULTS Disease-free survival in the capecitabine group was at least equivalent to that in the fluorouracil-plus-leucovorin group ( in the intention-to-treat analysis , P<0.001 for the comparison of the upper limit of the hazard ratio with the noninferiority margin of 1.20 ) . Capecitabine improved relapse-free survival ( hazard ratio , 0.86 ; 95 percent confidence interval , 0.74 to 0.99 ; P=0.04 ) and was associated with significantly fewer adverse events than fluorouracil plus leucovorin ( P<0.001 ) . CONCLUSIONS Oral capecitabine is an effective alternative to intravenous fluorouracil plus leucovorin in the adjuvant treatment of colon cancer Background : The benefit of adjuvant therapy in curatively resected lymph node-positive colon cancer was established using 5-fluorouracil ( 5-FU ) and levamisole ( LEV ) for 12 months . 5-FU cytotoxicity can be modulated by folinic acid ( FA ) or interferon-α ( INF-α ) . The aim of this study was to investigate the efficacy of modulating 5-FU+ LEV by either FA or IFN-α in the adjuvant treatment of high-risk colon cancer . Methods : Patients with curatively resected colon cancer ( stages UICC IIb and III ) were stratified according to T , N , and participating center and r and omized to receive a 12-month treatment using 5-FU + LEV alone or in combination with FA or IFN-α . Results : A total of 855 of 904 entered patients ( 94.6 % ) were eligible . The median follow-up of all eligible patients was 4.6 years . Addition of FA to 5-FU + LEV improved recurrence-free and overall survival in comparison with 5-FU + LEV alone ( P = 0.007 and P = 0.004 , respectively , 1-sided ) . The 5-year overall survival rates were 60.5 % ( 95 % confidence interval , 54.3–66.7 ) and 72.0 % ( 95 % confidence interval , 66.5–77.5 ) for 5-FU + LEV and 5-FU + LEV + FA , respectively . Addition of INF-α showed a tendency to improve recurrence-free survival , however , without altering overall survival . Toxicities ( WHO III + IV ) were generally tolerable except one toxic death in the control arm and were observed in 9.9 % of the patients receiving 5-FU + LEV alone and in 13.3 % and in 30.7 % of patients receiving additional FA and IFN-α , respectively . Conclusions : Addition of IFN-α was associated with increased toxicity without markedly influencing the outcome and should therefore not be recommended for adjuvant treatment . Addition of FA increased the 5-year recurrence-free and overall survival rate by 9.3 and 11.5 percentage points , respectively . 5-FU + LEV + FA for 12 months may be an effective adjuvant treatment option for locally advanced high-risk colon cancer A joint study was performed by the Tokai HCFU study group , which included 41 institutions to study the usefulness of the concomitant therapy with Mitomycin C ( MMC ) and Carmofur ( HCFU ) as a postoperative adjuvant chemotherapy in patients with colorectal cancer who had curative resection . Patients were divided into two groups , Group MMC and Group MMC+HCFU , using the " envelope " method . Among the 172 patients who had the envelope opened , 149 evaluable cases were analyzed for evaluation of the drug . The cumulative 10-year survival rates of Group MMC+HCFU had a statistically significant increase in survival rate compared with Group MMC . In particular , the rate was statistically significant in patients with colorectal cancer who had lymph node invasion . There were no severe side effects due to the adjuvant chemotherapy with MMC+HCFU . Thus the adjuvant chemotherapy with MMC+HCFU is suggested to be a useful and safe postoperative adjuvant chemotherapy PURPOSE A prospect i ve study was design ed to r and omize locally advanced rectal carcinoma patients between either preoperative radiotherapy ( + /- postoperative chemotherapy ) or postoperative adjuvant chemoradiation . Two end points were evaluated , local recurrence and survival , aim ing at defining prognostic parameters that can help in the choice of the optimum treatment modality . PATIENTS AND METHODS This is a prospect i ve r and omized clinical study including patients with locally advanced low rectal cancer treated at the National Cancer Institute ( NCI ) , Cairo University , during the period from December 1994 to January 1999 . Fifty patients with previously untreated rectal cancer were r and omized into two groups , Group I : Subjected to surgery followed by radiation therapy ( 50Gy/5 weeks , 2Gy/fraction , 5 days/week ) plus chemotherapy and Group II , subjected to preoperative radiotherapy ( 46Gy/4.5 weeks , 2Gy/ fraction , 5 days/week ) followed by surgery + /- postoperative chemotherapy . Chemotherapy in the concomitant setting was given in the form of Leucovorin in a dose of 300mg/m2 as a short i.v . infusion followed by 5-FU in a dose of 350mg/m2 as a 6 hour i.v . infusion , whereas adjuvant chemotherapy consisted of 5- FU as 600mg/m2 short i.v . infusion weekly for 48 weeks , in addition to levamisole tablets . RESULTS The long-term treatment end results obtained showed that group I patients had a slightly higher 10-year overall survival ( OS ) rate when compared to group II patients ( 63 % versus 60 % , p=0.698 ) . The corresponding figures for the 10-year disease-free survival ( DFS ) were 65 % and 66 % , respectively , p=0.816 . Although the 10- year local failure rate ( persistent/relapsed disease ) was higher for the preoperative group , it was not of statistical significance , ( 30 % Vs . 8 % , p=0.057 ) . On the other h and , the 10-year distant metastasis free survival was higher in the preoperative group ( 88 % Vs . 72 % ) , yet this difference did not reach statistical significance ( p=0.16 ) . The rate of acute radiation reactions was higher in the postoperative group , with no increase in the operative complications in the preoperative group . Moreover , none of the 50 patients had grade 3 or more late radiation/surgical squealae . There were no grade 3 or 4 chemotherapy related toxicities . CONCLUSIONS This work showed equal results for DFS and OS rates between preoperative and postoperative radiation therapy with the same acceptable acute and late radiation toxicity . High dose preoperative irradiation did not cause any significant increase in acute or late radiation induced reactions , delay in wound healing or increased postoperative morbidity when compared to postoperative adjuvant radiochemotherapy . Duke ' s stage and response to preoperative irradiation proved to be of significance regarding DFS , while compliance to systemic therapy was of significance regarding both OS and DFS PURPOSE Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil ( FU ) an attractive alternative to FU plus leucovorin ( FU/LV ) for the adjuvant treatment of colorectal cancer . Intergroup trial 0153 ( Southwest Oncology Group trial 9415 ) was developed to compare the efficacy of continuous-infusion FU ( CIFU ) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes ' B2 and C1 or C2 colon cancer . PATIENTS AND METHODS After surgery , patients were r and omly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2 ) and LV 20 mg/m(2 ) daily for 5 days every 28 to 35 days for six cycles . All patients received levamisole 50 mg tid for 3 days every other week . The primary end point was overall survival ( OS ) . RESULTS The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio . A total of 1,135 patients were registered . At least one grade 4 toxicity occurred in 39 % of patients receiving FU/LV and 5 % of patients receiving CIFU . However , almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV . The 5-year OS is 70 % ( 95 % CI , 66 % to 74 % ) for FU/LV and 69 % ( 95 % CI , 64 % to 73 % ) for CIFU . The corresponding 5-year disease-free survival ( DFS ) is 61 % ( 95 % CI , 56 % to 65 % ) and 63 % ( 95 % CI , 59 % to 68 % ) , respectively . For all patients , 5-year OS is 83 % , 74 % , and 55 % ; 5-year DFS is 78 % , 67 % , and 47 % for N0 , N1 , and N2 - 3 , respectively . CONCLUSION CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV Background : Postoperative adjuvant chemoradiation treatment after curative resection for rectal cancer was needed to reduce recurrence and improve a survival rate . Intravenous 5-fluorouracil ( 5-FU ) and leucovorin has been a mainstay of chemotherapy , but oral 5-FU derivatives have been shown a comparable antitumor activity . Intravenous 5-FU and oral doxifluridine were compared with respect to therapeutic efficacy , drug toxicity , and quality of life . Methods : A total of 166 patients were r and omized to receive intravenous 5-FU ( 450 mg/m2/day ) or oral doxifluridine ( 900 mg/m2/day ) in combination with leucovorin ( 20 mg/m2/day ) for depth of invasion , nodal status , metastasis ( TNM ) stage II and III patients between October 1997 and February 1999 . Consecutive daily intravenous infusion for 5 days per every month for a total of 12 cycles ( IV arm , n = 74 ) and oral doxifluridine daily for 3 weeks and 1 week rest for a total of 12 cycles ( oral arm , n = 92 ) . Drug toxicity and quality of life were observed . Quality of life was scored according to 22 daily activity items ( good , ≥ 71 ; fair , < 70 ; poor , < 52 ) . Results : There was no difference of sex between two groups ( IV arm : male/female = 45/29 , oral arm : male/female = 59/33 ) . The mean age was 52.3 vs. 59.5 , respectively . There was also no difference of TNM stage distribution and type of operation between groups ( P = .05 ) . Mean numbers of chemotherapy cycles were 6.5 ± 3.7 ( IV arm ) vs. 7.2 ± 4.3 ( oral arm ) , respectively . The rate of recurrence was 9/74 ( 12.1 % ) in the IV arm and 6/92 ( 6.5 % ) in the oral arm , respectively ( P = .937 ) . Local recurrence was 2/74 ( stage III ; 2.7 % ) in the IV arm and 1/92 ( stage II;1.1 % ) in the oral arm , respectively . Systemic recurrence was 7/74 ( stage III ; 9.4 % ) in the IV arm and 5/92 ( stage III ; 5.4 % ) in the oral arm , respectively . The most common site of systemic recurrence was the liver . Toxicity profile was as follows : leukopenia ( 30/74 vs. 17/92 ) and alopecia ( 21/74 vs. 13/92 ) were statistically more common in the IV arm . Diarrhea was more common in the oral arm . Poor quality of life score between two groups was observed at 1 month ( 23.9 % vs. 13 % ) and 2 months ( 15.8 % vs. 3.7 % ) after chemotherapy . Good quality of life score was observed at 1 month ( 19.5 % vs. 49 % ) and 2 months ( 47 % vs. 72 % ) , respectively ( P < .05 ) . Conclusions : Oral doxifluridine with leucovorin shows a comparable therapeutic efficacy to intravenous 5-FU regimen with high quality of life as postoperative adjuvant therapy . The oral regimen also can be safely given with appropriate toxicity and tolerability PURPOSE R and omized studies have shown that irinotecan ( CPT-11 ) extends survival in metastatic colorectal cancer patients when administered in second-line and when added to fluorouracil ( FU ) plus leucovorin ( LV ) in first-line therapy of metastatic colorectal cancer . When this study was initiated , FU plus LV was st and ard adjuvant treatment for stage III colon cancer . We evaluated the efficacy and safety of weekly bolus CPT-11 plus FU plus LV in the treatment of patients with completely resected stage III colon cancer . METHODS A total of 1,264 patients were r and omly assigned to receive either st and ard weekly bolus FU plus LV regimen or weekly bolus CPT-11 plus FU plus LV . The primary end points of the study were overall survival ( OS ) and disease-free survival ( DFS ) . RESULTS Treatment arms were well-balanced for patient characteristics and prognostic variables . There were no differences in either DFS or OS between the two treatment arms . Toxicity , including lethal toxicity , was significantly higher on the CPT-11 plus FU plus LV arm . CONCLUSION The addition of CPT-11 to weekly bolus FU plus LV did not result in improvement in DFS or OS in stage III disease , but did increase both lethal and nonlethal toxicity . This trial demonstrates that advances in the treatment of metastatic disease do not necessarily translate into advances in adjuvant treatment , and it reinforces the need for r and omized controlled adjuvant studies BACKGROUND A joint study was performed by the Tokai HCFU study group , which included seven institutions , to examine the value of oral administration of Carmofur ( HCFU ) , a 5-fluorouracil ( 5-FU ) derivative , for postoperative adjuvant chemotherapy in patients with colorectal cancer undergoing curative resection . METHODS The patients were divided into two groups , a control group receiving no HCFU and a group administered HCFU for 1 year , using a central ized registration system by telephone . Among 173 patients entered into this study , 159 evaluable cases were analyzed for evaluation of the drug . RESULTS The cumulative 5-year disease-free rate of patients who received HCFU was significantly increased compared with the control group . In particular , the rate was much higher in patients with colon cancer . No severe side effects arose from adjuvant chemotherapy with HCFU . CONCLUSION Adjuvant chemotherapy with oral HCFU appears to provide a useful and safe postoperative treatment PURPOSE This r and omized , 2 x 2 factorial study compared a semimonthly regimen ( fluorouracil [ FU ] and leucovorin [ LV ] semi-monthly is LV5FU2 ) with a monthly regimen of FU and LV ( mFU/LV ) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer . PATIENTS AND METHODS LV5FU2 was administered semimonthly for 2 days as racemate ( dl ) or levogyre ( l- ; 200 or 100 mg/m(2 ) ) as a 2-hour infusion , followed by 400 mg/m(2 ) FU bolus and a 600-mg/m(2 ) FU 22-hour continuous infusion . FU and LV were administered monthly ( mFU/LV ) for 5 days as dl- or l-LV 15-minute infusion , followed by a 400 mg/m(2 ) FU 15-minute infusion . The primary end point was disease-free survival ( DFS ) . RESULTS Between September 1996 and November 1999 , 905 patients with stage II ( 43 % ) and III ( 57 % ) colon cancer were enrolled . The median follow-up was 6 years . There was no statistically significant difference between mFU/LV and LV5FU2 in terms of DFS ( 150 v 148 events ; hazard ratio [HR],1.01 ; 95 % CI , 0.806 to 1.269 ; P = .94 ) and overall survival ( OS ; 104 v 103 events ; HR,1.02 ; 95 % CI , 0.77 to 1.34 ; P = .91 ) . No statistical difference was observed between 24 or 36 weeks of chemotherapy . Median survival from metastatic relapse was 24 months . The survival of patients with metastatic relapse ( n = 243 ) was significantly longer for patients with a longer time from r and om assignment to relapse ( < 1 , 1 to 2 , > or= 2 years ; log-rank test for trend P , .0497 ) . CONCLUSION DFS and OS were not statistically different between treatment groups and treatment duration s. These data confirm the value of LV5FU2 as control arm in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer and Pan-European Trials in Adjuvant Colon Cancer studies BACKGROUND The National Surgical Adjuvant Breast and Bowel Project C-01 trial reported in 1988 that , for patients with adenocarcinoma of the colon , compared with surgery alone , 1 ) postoperative chemotherapy with 1-(2-chloroethyl)-3-(4-trans-methylcyclohexyl)-1-nitrosourea ( i.e. , MeCCNU or semustine ) , vincristine , and 5-fluorouracil was associated with better 5-year disease-free and overall survival and 2 ) postoperative immunotherapy with bacillus Calmette-Guérin was associated with better 5-year overall , but not disease-free , survival . We now provide a 10-year up date of this trial . METHODS Between November 11 , 1977 , and February 28 , 1983 , 1166 patients with resected Dukes ' stage B and C adenocarcinoma of the colon were stratified by Dukes ' stage , sex , and age ( < 65 years or > or = 65 years ) and then r and omly assigned to receive no further treatment ( surgery alone ; 394 patients ) , adjuvant chemotherapy ( 379 patients ) , or adjuvant immunotherapy ( 393 patients ) . Those eligible for follow-up included 375 ( 95.2 % ) patients in the surgery-alone group , 349 ( 92.1 % ) patients in the adjuvant-chemotherapy group , and 372 ( 94.7 % ) patients in the adjuvant-immunotherapy group . All statistical tests were two-sided . RESULTS No difference was observed between patients in the chemotherapy group and those in the surgery-alone group in 10-year disease-free survival ( hazard ratio [ HR ] = 1.14 , 95 % confidence interval [ CI ] = 0.94 to 1.39;P = .17 ) or overall survival ( HR = 1.12 , 95 % CI = 0.91 to 1.38 ; P=.27 ) . Immunotherapy did not appear to prevent tumor relapse after 10 years ( for surgery alone versus immunotherapy , relative risk [ RR ] = 0.99 , 95 % CI = 0.78 to 1.25 ; P = .93 ) but had a beneficial effect on 10-year overall survival ( for surgery alone versus immunotherapy , RR = 1.27 , 95 % CI = 1.03 to 1.56 ; P = .02 ) that apparently results from a reduction in deaths associated with comorbidities in the immunotherapy group . CONCLUSION The disease-free and overall survival benefit associated with chemotherapy in this patient population is of limited duration , disappearing after 10 years Objective : To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision ( TME ) surgery . Summary Background Data : Local recurrence is a major problem in rectal cancer treatment . Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery . The TME trial investigated the value of this regimen in combination with total mesorectal excision . Long-term results are reported after a median follow-up of 6 years . Methods : One thous and eight hundred and sixty-one patients with resectable rectal cancer were r and omized between TME preceded by 5 × 5 Gy or TME alone . No chemotherapy was allowed . There was no age limit . Surgery , radiotherapy , and pathologic examination were st and ardized . Primary endpoint was local control . Results : Median follow-up of surviving patients was 6.1 year . Five-year local recurrence risk of patients undergoing a macroscopically complete local resection was 5.6 % in case of preoperative radiotherapy compared with 10.9 % in patients undergoing TME alone ( P < 0.001 ) . Overall survival at 5 years was 64.2 % and 63.5 % , respectively ( P = 0.902 ) . Subgroup analyses showed significant effect of radiotherapy in reducing local recurrence risk for patients with nodal involvement , for patients with lesions between 5 and 10 cm from the anal verge , and for patients with uninvolved circumferential resection margins . Conclusions : With increasing follow-up , there is a persisting overall effect of preoperative short-term radiotherapy on local control in patients with clinical ly resectable rectal cancer . However , there is no effect on overall survival . Since survival is mainly determined by distant metastases , efforts should be directed towards preventing systemic disease The aim of the study was to determine whether modulation of 5-fluorouracil ( FU ) by methotrexate ( MTX ) improves survival compared to FU+6-s-leucovorin ( LV ) following potentially curative resection of stage II and III colon cancer . Within 8 weeks from surgery , 1945 patients with stage III ( 44 % ) or high-risk stage II ( 55 % ) colon cancer were r and omly assigned to receive either 6 monthly cycles of FU 370 mg m−2 i.v . bolus preceded by LV 100 mg m−2 i.v . bolus on days 1–5 , or 6 monthly cycles of sequential MTX 200 mg m−2 i.v . days 1 and 15 and FU 600 mg m−2 i.v . on days 2 and 16 followed by LV rescue ( 15 mg given p.o . q 6 h × 6 doses ) . Levamisole 50 mg p.o . t.i.d . on days 1–3 , every 14 days for 6 months , was planned to be given in both arms . After a median follow-up of 4.2 years , 568 patients have relapsed and 403 have died . Survival was similar with MTX → FU and FU+LV ( 77 vs 77 % at 5 years ; P=0.90 ) , as were 5-year disease-free survivals ( 67 vs 63 % ; P=0.44 ) . Efficacy results were similar for both stage III and II patients . There were two toxic deaths , two in the MTX → FU arm ( 0.2 % ) and zero in the control arm . We conclude that biochemical modulation of FU with LV or with MTX produces similar results in the adjuvant setting of colon cancer |
2,671 | 28,239,840 | These agents appear to have a beneficial effect on melasma improvement .
In conclusion , oral medications have a role in melasma treatment and have been shown to be efficacious and tolerable with a minimal number and severity of adverse events . | Currently available treatment options for melasma include prevention of UV radiation , topical lightening agents , chemical peels , and light-based and laser therapies .
However , none have shown effective and sustained results , with incomplete clearance and frequent recurrences .
There has been increasing interest recently in oral medications and dietary supplements in improving melasma .
We sought to evaluate the efficacy and safety/tolerability of oral medications and dietary supplements for the treatment of melasma . | Melasma ( or chloasma ) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women . The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects . Pycnogenol is a st and ardized extract of the bark of the French maritime pine ( Pinus pinaster ) , a well-known , potent antioxidant . Studies in vitro show that Pycnogenol is several times more powerful than vitamin E and vitamin C. In addition , it recycles vitamin C , regenerates vitamin E and increases the endogenous antioxidant enzyme system . Pycnogenol protects against ultraviolet ( UV ) radiation . Therefore its efficacy in the treatment of melasma was investigated . Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol with meals three times daily , i.e. 75 mg Pycnogenol per day . These patients were evaluated clinical ly by parameters such as the melasma area index , pigmentary intensity index and by routine blood and urine tests . After a 30-day treatment , the average melasma area of the patients decreased by 25.86 + /- 20.39 mm(2 ) ( p < 0.001 ) and the average pigmentary intensity decreased by 0.47 + /- 0.51 unit ( p < 0.001 ) . The general effective rate was 80 % . No side effect was observed . The results of the blood and urine test parameters at baseline and at day 30 were within the normal range . Moreover , several other associated symptoms such as fatigue , constipation , pains in the body and anxiety were also improved . To conclude , Pycnogenol was shown to be therapeutically effective and safe in patients suffering from melasma The objective of the present study was to assess the toxicology of melatonin ( 10 mg ) , administered for 28 days to 40 volunteers r and omly assigned to groups receiving either melatonin ( N = 30 ) or placebo ( N = 10 ) in a double-blind fashion . The following measurements were performed : polysomnography ( PSG ) , laboratory examinations , including complete blood count , urinalysis , sodium , potassium and calcium levels , total protein levels , albumin , blood glucose , triglycerides , total cholesterol , high-density lipoprotein ( HDL ) , low-density lipoprotein ( LDL ) , and very low-density lipoprotein ( VLDL ) , urea , creatinine , uric acid , glutamic-oxalacetic transaminase ( GOT ) , glutamic-pyruvate transaminase ( GPT ) , bilirubin , alkaline phosphatase , gama-glutamic transaminase ( GGT ) , T3 , T4 , TSH , LH/FSH , cortisol , and melatonin serum concentrations . In addition , the Epworth Somnolence Scale ( ESS ) and a sleep diary ( SD ) were also applied to the volunteers 1 wk before each PSG . In addition , the volunteers were asked about possible side effects ( SE ) that appeared during the treatment . The study was carried out according to the following timetable : Visit 0 , filling out the term of consent and inclusion criteria ; Visit 1 , PSG , laboratory examinations , ESS , SD , melatonin serum concentrations ; Visit 2 , SD , melatonin serum concentrations , SE ; Visit 3 , melatonin serum concentrations , PSG , ESS , SE ; Visit 4 , laboratory examinations , SE , melatonin serum concentrations , SD ; and Visit 5 , PSG , ESS , SE . Analysis of the PSG showed a statistically significant reduction of stage 1 of sleep in the melatonin group . No other differences between the placebo and melatonin groups were obtained . In the present study we did not observe , according to the parameters analyzed , any toxicological effect that might compromise the use of melatonin at a dose of 10 mg for the period of time utilized in this study BACKGROUND Glutathione ( GSH ) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed . Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk . Oral administration has been less successful in elevating plasma GSH levels . OBJECTIVES The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration . Substances that are absorbed through the buccal route go directly into the systemic circulation , effectively bypassing the gastrointestinal tract . METHODS Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks . RESULTS Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks . There were no serious adverse events , and laboratory examination findings remained normal . CONCLUSIONS The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women BACKGROUND UV radiation induces damage to human skin . Protection of skin by an oral photoprotective agent would have substantial benefits . Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos ( PL ) . METHODS A total of 9 healthy participants of skin types II to III were exposed to varying doses of artificial UV radiation without and after oral administration of PL ( 7.5 mg/kg ) . At 24 hours after exposure the erythema reaction was assessed and paired biopsy specimens were obtained from PL-treated and untreated skin . RESULTS A significant decrease in erythema was found in PL-treated skin ( P < .01 ) . Histologically , PL-treated biopsy specimens showed less sunburn cells ( P < .05 ) , cyclobutane pyrimidine dimers ( P < .001 ) , proliferating epidermal cells ( P < .001 ) , and dermal mast cell infiltration ( P < .05 ) . A trend toward Langerhans cell preservation was seen . CONCLUSION Oral administration of PL is an effective systemic chemophotoprotective agent leading to significant protection of skin against UV radiation BACKGROUND Melasma is associated with epidermal hyperpigmentation , weak basement membrane , vascular proliferation and increased numbers of mast cell . Tranexamic acid ( TXA ) , a plasmin inhibitor , is reported to improve melasma when injected locally . However , the effects of oral and topical TXA on melasma have not been well studied and the underlying mechanism remains unclear . OBJECTIVES To eluci date the effects of oral and topical TXA on melasma . METHODS A clinical study was conducted with 25 women for 8 weeks from March to July 2010 . Volunteers were instructed to take two TXA tablets three times a day and apply a TXA topical agent twice a day for 8 weeks . Skin pigmentation and erythema was measured using a Mexameter ( ® ) during each visit and skin biopsies were collected from eight subjects before and 8 weeks after treatment . Fontana-Masson , anti-CD31 , antitryptase and antitype IV collagen staining was performed . RESULTS Twenty-two subjects completed the study and no serious adverse events occurred during the study period . The mean lesional melanin index ( MI ) scores decreased significantly . Interestingly , the MI scores for the perilesional skin increased . The erythema index scores of lesional and perilesional skin also showed a similar pattern . Histological analysis showed significant reduction of epidermal pigmentation , vessel numbers and mast cell counts . Type IV collagen staining was not observed in all specimens . CONCLUSION TXA decreased epidermal pigmentation associated with melasma and also reversed melasma-related dermal changes , such as vessel number and increased numbers of mast cells Abstract Objective : To determine whether orally administered glutathione , 500 mg per day for 4 weeks , affects the skin melanin index , when compared with placebo . Methods : This r and omized , double-blind , two-arm , placebo-controlled study was set in the King Chulalongkorn Memorial Hospital , Bangkok , Thail and , a teaching hospital affiliated with a medical school . Sixty otherwise healthy medical students were r and omized to receive either glutathione capsules , 500 mg/day in two divided doses , or placebo for 4 weeks . The main outcome was mean reduction of melanin indices measured at six different sites . Several secondary outcomes , including UV spots , were recorded by VISIA ™ . Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates . Results : Sixty participants enrolled and completed the study . At 4 weeks , the melanin indices decreased consistently at all six sites in subjects who received glutathione . The reductions were statistically significantly greater than those receiving placebo at two sites , namely the right side of the face and the sun-exposed left forearm ( p-values = 0.021 and 0.036 , respectively ) . This was similarly reflected in the changes in the number of UV spots , as measured by VISIA . Both glutathione and placebo were very well tolerated . Conclusion : Oral glutathione administration results in a lightening of skin color in a small number of subjects . However , long-term safety has not been established and warrants more extensive clinical trials BACKGROUND Melasma is a common , acquired , symmetric hypermelanosis characterized by irregular brown to gray-brown macules on the cheeks , forehead , nasal bridge , cutaneous part of the upper lip , m and ible , and the upper arms . Few trials have been conducted regarding the potential benefits of oral procyanidin in melasma . AIM To assess the safety and efficacy of oral procyanidin + vitamins A , C , E among Filipino patients with epidermal melasma . METHODS A r and omized , double-blind , placebo-controlled trial lasting 8 weeks , involving 60 adult female volunteers with bilateral epidermal melasma , Fitzpatrick skin types III-V , was conducted at the Section of Dermatology , Research Institute for Tropical Medicine , Department of Health , Manila , Philippines . Patients received either the test drug or placebo , twice daily with meals . Changes in pigmentation were measured using a mexameter , the melasma area and severity index ( MASI ) , and a global evaluation by the patient and investigator . Safety evaluations were performed at each follow-up visit . RESULTS Fifty-six patients completed the trial . Mexameter results demonstrated a significant decrease in the degree of pigmentation in the left malar ( 165.85 + /- 70.909 ) and right malar ( 161.33 + /- 61.824 ) regions ( P < 0.0001 ) . MASI scores showed a significant improvement in the left malar ( 2.4862 + /- 1.67816 ) and right malar ( 1.8889 + /- 1.67110 ) regions ( P = 0.001 ) . Procyanidin + vitamins A , C , E proved to be safe and well tolerated , with minimal adverse events . CONCLUSIONS In this 8-week trial period , oral procyanidin + vitamins A , C , E proved to be safe and effective among Filipino women with epidermal melasma Background : Melasma is a common acquired cause of facial hyperpigmentation with no definitive therapy . Tranexamic acid , a plasmin inhibitor , has demonstrated depigmenting properties and combining this oral drug with other modalities of treatment has shown promising results . Objectives : To compare the efficacy of a combination of oral tranexamic acid and fluocinolone-based triple combination cream with that of fluocinolone-based triple combination cream alone in melasma among Indian patients . Material s and Methods : 40 patients of melasma of either sex attending to dermatology OPD were enrolled in this study . Participants were r and omly divided into two groups with 20 patients in each group . Group A patients were asked to apply the cream only and Group B patients received oral tranexamic acid 250 mg twice daily and applied a triple combination cream containing fluocinolone acetonide 0.01 % , tretinoin 0.05 % , and hydroquinone 2 % once daily for 8 weeks . Response was evaluated using melasma area severity index ( MASI ) at baseline , 4 weeks , and 8 weeks . Results : 40 patients completed the study . The MASI scores at baseline , 4 weeks and 8 weeks in group A were 15.425 + 1.09 , 11.075 + 9.167 and 6.995 + 6.056 respectively and in group B 18.243 + 1.05 , 6.135 + 4.94 and 2.19 + 3.38 . Intergroup comparison showed a faster reduction in pigmentation in Group B as compared to Group A and the results were statistically significant at 4 weeks ( P value 0.014 ) and 8 weeks ( P value 0.000 ) . The efficacy was maintained throughout the 6-month follow-up period . Conclusion : Addition of oral tranexamic acid to fluocinolone-based triple combination cream results in a faster and sustained improvement in the treatment of melasma OBJECTIVE The objective of this study was to determine the safety of oral Polypodium leucotomos extract administered twice daily to healthy adults for 60 days and assess its ability to provide protection against exposure to ultraviolet radiation . DESIGN This was a r and omized , double-blind , placebo-controlled study . SETTING A single clinical research center . PARTICIPANTS Healthy adult men and women between 18 and 65 years of age with Fitzpatrick skin types I to IV . MEASUREMENTS Safety assessment s included a physical examination , vital signs , and clinical laboratory parameters including hematology , comprehensive metabolic panel , and prothrombin time-partial thromboplastin time were obtained at baseline and at the end of the study . Reports of adverse events were recorded . Efficacy assessment s were changes in minimal erythema dose testing , ultraviolet-induced erythema intensity response , and sunburn history during the prior 60 days . RESULTS After two months of treatment , there were no changes in any safety assessment s. The subjects in the placebo group showed a greater likelihood of experiencing > 1 episodes of sunburn ( 2 vs. 8 subjects ; p=0.04 ) At Day 28 , Polypodium leucotomos extract-treated subjects showed greater likelihood of an increased minimal erythema dose ( 8 vs. 1 subject ; p=0.01 ) and greater likelihood of decreased ultraviolet-induced erythema intensity ( 10 subjects vs. 3 subjects ; p<0.01 ) . CONCLUSION Polypodium leucotomos extract 240 mg taken twice daily for 60 days was a safe and effective means for reducing the damaging effects of ultraviolet radiation . Based on the excellent safety profile of Polypodium leucotomos , additional studies using higher doses may be warranted BACKGROUND Postinflammatory hyperpigmentation ( PIH ) is the most common skin complication in Asians after invasive cosmetic treatments . OBJECTIVE To determine whether oral tranexamic acid ( TA ) reduces the incidence of PIH after Q‐switched ruby laser ( QSRL ) treatment . METHODS AND MATERIAL S Thirty‐two Japanese women underwent QSRL treatment for senile lentigines on the face . They were r and omly divided into two groups that did ( n=15 ) and did not ( n=17 ) receive oral TA treatment ( 750 mg/d ) for the first 4 weeks after QSRL treatment . Nineteen participants had melasma‐like maculae at baseline . Clinical and colorimetric assessment s were performed at baseline and 2 and 4 weeks later . RESULTS Pigmentation was effectively treated using QSRL at 2 weeks , but PIH was frequently seen at 4 weeks . There was no significant difference in the incidence of PIH between participants who received oral TA and those who did not . The presence of melasma did not influence the effectiveness of the treatment . CONCLUSION Although oral TA has been reported to have depigmentation effects , it may not be effective for preventing PIH after QSRL . Considering the dosage and duration of treatment , an optimal protocol may be needed to induce the efficacy of this treatment to achieve the PIH‐preventing effect of oral TA . The authors have indicated no significant interest with commercial supporters |
2,672 | 19,280,532 | Despite the lack of evidence to support or refute any survival benefit for follow-up colonoscopy after curative-intent CRC resection , surveillance colonoscopy is recommended by most guidelines .
For surveillance after CRC resection , it considered colonoscopy appropriate 1 year after resection .
Colonoscopy is recommended as a first-choice procedure for surveillance after polypectomy by all published guidelines and by the EPAGE II criteria .
Despite the limitations of the published studies , colonoscopy is also recommended by most of the guidelines and by EPAGE II criteria for surveillance after curative-intent CRC resection | BACKGROUND AND STUDY AIMS To summarize the published literature on assessment of appropriateness of colonoscopy for surveillance after polypectomy and after curative-intent resection of colorectal cancer ( CRC ) , and report appropriateness criteria developed by an expert panel , the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy , EPAGE II .
RESULTS Most CRCs arise from adenomatous polyps .
The characteristics of removed polyps , especially the distinction between low-risk adenomas ( 1 or 2 , small [ < 1 cm ] , tubular , no high- grade dysplasia ) vs. high-risk adenomas ( large [ > or = 1 cm ] , multiple [ > 3 ] , high- grade dysplasia or villous features ) , have an impact on advanced adenoma recurrence . | Background The possible benefit for patients from follow‐up examinations after curative surgery for colorectal cancer is unproven . The purpose of this study was to determine whether survival is improved by frequent follow‐up examinations BACKGROUND We tested the hypothesis that dietary intervention can inhibit the development of recurrent colorectal adenomas , which are precursors of most large-bowel cancers . METHODS We r and omly assigned 2079 men and women who were 35 years of age or older and who had had one or more histologically confirmed colorectal adenomas removed within six months before r and omization to one of two groups : an intervention group given intensive counseling and assigned to follow a diet that was low in fat ( 20 percent of total calories ) and high in fiber ( 18 g of dietary fiber per 1000 kcal ) and fruits and vegetables ( 3.5 servings per 1000 kcal ) , and a control group given a st and ard brochure on healthy eating and assigned to follow their usual diet . Subjects entered the study after undergoing complete colonoscopy and removal of adenomatous polyps ; they remained in the study for approximately four years , undergoing colonoscopy one and four years after r and omization . RESULTS A total of 1905 of the r and omized subjects ( 91.6 percent ) completed the study . Of the 958 subjects in the intervention group and the 947 in the control group who completed the study , 39.7 percent and 39.5 percent , respectively , had at least one recurrent adenoma ; the unadjusted risk ratio was 1.00 ( 95 percent confidence interval , 0.90 to 1.12 ) . Among subjects with recurrent adenomas , the mean ( + /-SE ) number of such lesions was 1.85+/-0.08 in the intervention group and 1.84+/-0.07 in the control group . The rate of recurrence of large adenomas ( with a maximal diameter of at least 1 cm ) and advanced adenomas ( defined as lesions that had a maximal diameter of at least 1 cm or at least 25 percent villous elements or evidence of high- grade dysplasia , including carcinoma ) did not differ significantly between the two groups . CONCLUSIONS Adopting a diet that is low in fat and high in fiber , fruits , and vegetables does not influence the risk of recurrence of colorectal adenomas PURPOSE To up date the 2000 American Society of Clinical Oncology guideline on colorectal cancer surveillance . RECOMMENDATIONS Based on results from three independently reported meta-analyses of r and omized controlled trials that compared low-intensity and high-intensity programs of colorectal cancer surveillance , and on recent analyses of data from major clinical trials in colon and rectal cancer , the Panel recommends annual computed tomography ( CT ) of the chest and abdomen for 3 years after primary therapy for patients who are at higher risk of recurrence and who could be c and i date s for curative-intent surgery ; pelvic CT scan for rectal cancer surveillance , especially for patients with several poor prognostic factors , including those who have not been treated with radiation ; colonoscopy at 3 years after operative treatment , and , if results are normal , every 5 years thereafter ; flexible proctosigmoidoscopy [ corrected ] every 6 months for 5 years for rectal cancer patients who have not been treated with pelvic radiation ; history and physical examination every 3 to 6 months for the first 3 years , every 6 months during years 4 and 5 , and subsequently at the discretion of the physician ; and carcinoembryonic antigen every 3 months postoperatively for at least 3 years after diagnosis , if the patient is a c and i date for surgery or systemic therapy . Chest x-rays , CBCs , and liver function tests are not recommended , and molecular or cellular markers should not influence the surveillance strategy based on available evidence Objective . Guidelines for surveillance of patients with previous sporadic colorectal adenomas are based on retrospective long-term follow-up and prospect i ve short-term studies . The aim of the present studies was to compare relative risk ( RR ) of new neoplasia as well as complications , using different intervals between examinations in long-term surveillance . Material and methods . Between l98l and l991 , patients with pedunculated and small , flat and sessile adenomas were allocated at r and om to a 24 months ( group A ) or 48 months ( group B ) interval between surveillance colonoscopies ( n=671 ) . Patients with flat and sessile adenomas greater than 5 mm in diameter were r and omized to intervals of 6 months ( group C ) or 12 months ( group D ) between l981 and 1987 ( n=73 ) . Finally , 200 patients with similar adenomas as in groups C and D were r and omized to 12 months ( group E ) or 24 months ( group F ) from 1988 to 2000 . The study ended in 2002 . Results . Advanced adenomas were equally as frequent in group A and group B , but colorectal cancer ( CRC ) was found significantly more often in group B ( RR = 6.2 ( 1.0–117.4 ) ) . Severe complications occurred in 4 patients in group A and 2 patients in group B. Advanced new adenomas tended to be more frequent in group D than in C ( p=0.08 ) , but only one CRC was detected and this was in group C. There was no significant difference in the risk of CRC between the E and F groups , but the two cancers in group E were both early stage , in contrast to those in group F. Severe complications were seen in one patient in group E and also in group F. Conclusions . The results suggest that 2-year intervals should be used between colonoscopies in patients with previous pedunculated adenomas and small , flat and sessile adenomas , whereas larger , flat and sessile adenomas may need intervals of 1 year BACKGROUND & AIMS Colonoscopic polypectomy is considered effective for preventing colorectal cancer ( CRC ) , but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated . We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high- grade dysplasia . METHODS Patients were drawn from 3 adenoma chemoprevention trials . All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions . We identified patients subsequently diagnosed with invasive cancer or adenoma with high- grade dysplasia . The timing , location , and outcome of all cases of cancer and high- grade dysplasia identified are described and risks associated with their development explored . RESULTS CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years ( incidence , 1.74 cancers/1000 person-years ) . The cancers were located in all regions of the colon ; 10 were at or proximal to the hepatic flexure . Although most of the cancers ( 84 % ) were of early stage , 2 participants died of CRC . Seven patients were diagnosed with adenoma with high- grade dysplasia during follow-up . Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high- grade dysplasia . CONCLUSIONS CRC is diagnosed in a clinical ly important proportion of patients following complete colonoscopy and polypectomy . More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed OBJECTIVE To determine whether an intensified follow-up of patients with colorectal cancer can lead to improved reresectability and a better long-term survival . DESIGN A prospect i ve r and omized trial of 106 patients . SETTING Oulu University Hospital , a referral center in northern Finl and . PATIENTS A total of 106 consecutive patients who underwent radical resection for colorectal cancer , 54 of whom were r and omized into a conventional follow-up group and 52 into an intensified follow-up group . MAIN OUTCOME MEASURES After a 5-year follow-up , the time of detection of recurrence , the recurrence rates , the first method showing recurrence , the mode of recurrence , reresectability , and survival were compared between the groups . RESULTS The recurrences were identified earlier in the intensified follow-up group than in the conventional follow-up group ( mean + /- SD , 10 + /- 5 months vs 15 + /- 10 months ) . The overall recurrence rate was 41 % , with 39 % in the conventional group and 42 % in the intensified group . Carcinoembryonic antigen determination was the most common method showing recurrence in both groups . Endoscopy and ultrasound were beneficial in the intensified follow-up group , but computed tomography failed to improve the diagnostics . The mode of recurrence did not differ between the groups . Radical resections were performed on 19 % ( 8/43 ) of the patients , 14 % ( 3/21 ) in the conventional group and 22 % ( 5/22 ) in the intensified group . The cumulative 5-year survival was 54 % in the conventional group and 59 % in the intensified group . CONCLUSION Earlier detection of recurrent colorectal cancer by intensified follow-up does not lead to either significantly increased reresectability or improved 5-year survival Context Patients who have had colorectal cancer can develop second primary colorectal cancer . The American Cancer Society recommends that surveillance colonoscopy be performed 1 year after surgery , then every 3 to 5 years if results are negative . This surveillance strategy is unproven . Contribution This study documented an incidence rate of 274 cases of second primary colon cancer per 100 000 person-years after surgery with curative intent and 5-fluorouracil-based chemotherapy . The incidence of second cancer was higher than the incidence of first colorectal cancer in the general population , despite surveillance . Caution s This study suggests that surveillance may need to be more vigilant than currently recommended . However , more data are needed to decide how often to do surveillance colonoscopy . The Editors Colorectal cancer is a major public health problem , with more than 130 000 new cases thought to have occurred in the United States in 2001 . Patients who have had colon cancer are at risk for second primary colon cancer , but the extent of this risk is unclear . The incidence and rate of development of second primary tumors have implication s for appropriate surveillance of the colon after diagnosis of colorectal cancer . After first primary colon cancer is diagnosed , resection with curative intent is possible in approximately 75 % of patients because the disease is limited to the bowel or to regional lymph nodes . The st and ard of care for patients with stage II or stage III disease is surgical resection , followed by adjuvant therapy for stage III disease . After surgery and adjuvant chemotherapy , patients frequently undergo some form of surveillance . Computed tomography of the abdomen , chest radiography , and measurement of carcinoembryonic antigen have been used to detect distant metastatic disease , although no convincing data show that these tests are cost-effective or improve survival ( 1 ) . Colonoscopy or barium enema combined with flexible sigmoidoscopy has been used to survey for second primary colorectal cancer . Surveillance for second primary colorectal cancer serves two purpose s : removal of premalignant polyps and early detection of malignancy . Most colorectal cancer is the product of slow , orderly progression from normal cells to malignancy . Surveillance with endoscopy and polypectomy has been shown to prevent colon cancer ( 2 , 3 ) . The most convincing data for this intervention come from the National Polyp Study , which found that in patients with adenomatous polyps , colonoscopic surveillance significantly decreased the incidence of colorectal carcinoma ( 3 ) . The National Polyp Study also examined the question of how frequently to perform colonoscopic surveillance by comparing two surveillance strategies in patients who had recently had adenomas removed by colonoscopy ( 4 ) . The study showed that repeated colonoscopy 3 years after colonoscopy and polypectomy in patients with adenomatous polyps was equivalent to more frequent surveillance . The authors conceded , however , that more frequent follow-up colonoscopy may be needed in patients with a history of colorectal cancer because they may have different biological characteristics and natural history . Current guidelines for surveillance of patients with a history of colon cancer are at least partially based on data from the National Polyp Study . The American Gastroenterological Association and the American Cancer Society recommend complete examination of the colon within 1 year of resection ; if findings on this or on complete preoperative examination are normal , examination should be repeated in 3 years and then , if findings are again normal , every 5 years ( 5 ) . In addition to finding new second primary tumors , surveillance within 1 year of colon cancer surgery may detect previously undetected polyps or synchronous tumors . Recent recommendations from the American Society of Clinical Oncology call for perioperative colonoscopy followed by colonoscopy every 3 to 5 years ( 1 ) . However , deciding whether to extrapolate surveillance recommendations for patients with polyps to patients with a history of colon cancer requires a better underst and ing of the absolute and relative risk for second colorectal cancer in such patients . In the general population , the best estimates of the risk ratio for second primary colorectal cancer compared with first primary colorectal cancer have ranged from 1.5 to 3.0 ( 6 , 7 ) . The studies that have addressed this issue have had several deficiencies : incomplete follow-up , incomplete reporting of new cases , reporting of cumulative incidence rates ( which do not consider length of follow-up ) , unknown surveillance practice s in the study sample , arbitrary time cutoffs to distinguish new metachronous primary cancer from missed synchronous cancer , and heterogeneous patient sample s ( 6 - 11 ) . Thus , we do not know enough about the incidence of second primary colorectal cancer in patients with a history of colon cancer to devise optimal surveillance strategies . The purpose of our study was to estimate the incidence of second primary colon cancer in patients with a history of high-risk stage II or stage III colon cancer and to compare this incidence with that of first primary colon cancer in the general population and the National Polyp Study . Methods Patients Our study is a historical cohort analysis of patients who entered a trial of adjuvant therapy after surgery for colon cancer . This trial was design ated Intergroup 0089 by the U.S. National Cancer Institute ( 12 ) and was approved by the Institutional Review Board of the University of Pennsylvania , Philadelphia , Pennsylvania . Patients with high-risk stage II or stage III cancer were r and omly assigned to one of four 5-fluorouracil-based treatments . Patients were enrolled at 683 institutions , 73 % of which were community-based medical centers . Surveillance guidelines for patients in the study included m and atory surveillance of the entire colon with colonoscopy or barium enema and flexible sigmoidoscopy at diagnosis , within 6 months of surgery , at 12 months , at 18 months , and then annually . At the discretion of each patient 's physician , surveillance could be done less frequently ( every 18 to 24 months after the 6-month surveillance ) . Data Collection Patients were required to visit the treating oncologist at least every 3 months during the first year of the study and then every 6 months for 4 years . After 5 years , follow-up material s were collected annually until death . At each visit , data forms that included information on surveillance and documentation of second primary colorectal cancer were completed . Data on the diagnostic procedures used to diagnose the original colon cancer and on whether the entire colon was visualized at diagnosis were not always available , since these were not primary objectives of the protocol . Original data collection and statistical analysis were done by the Eastern Cooperative Oncology Group . Reference Groups We compared the observed incidence rate of second primary colorectal cancer in Intergroup 0089 with the rates of first primary colorectal cancer expected in two reference groups . The Surveillance , Epidemiology , and End Results ( SEER ) program of the National Cancer Institute monitors the incidence of colorectal cancer in 10 statewide registries ( 13 ) . These data are routinely used as a surrogate for the average risk for colorectal cancer throughout the United States . We used age- , sex- , and ethnicity-specific rates for calendar years 1989 to 1993 since this period corresponded to the time during which patients were enrolled in Intergroup 0089 . The National Polyp Study was a prospect i ve study of 1418 patients who were referred for colonoscopy , during which one or more adenomas of the colon or rectum were removed ( 3 , 4 ) . The patients subsequently underwent periodic colonoscopy ( r and omly assigned to either years 1 and 3 or year 3 only ) during an average follow-up of 5.9 years , and the incidence of colorectal cancer was ascertained . The incidence rate of colorectal cancer was compared with rates in three reference groups : two population s of patients with adenomatous polyps who did not have all polyps removed , and the SEER program . Five cases of invasive colorectal cancer were detected in a total of 8401 person-years of follow-up . The National Polyp Study found that colonoscopy with polypectomy decreased the incidence of colon cancer by approximately 90 % compared with the other population s of high-risk patients and by 76 % compared with the SEER population . Statistical Analysis In Intergroup 0089 , the number of person-years at risk was calculated for each patient from the time of study entry until death , diagnosis of second primary colon cancer , or the last known time at which the patient was alive . Median time to second cancer and survival plots were calculated by using the Kaplan-Meier method . Incidence rates were defined as the total number of events divided by the total person-years of follow-up ; 95 % CIs were calculated by assuming a Poisson distribution . Our study primarily analyzed the diagnosis of second primary colorectal cancer . We established criteria to distinguish second primary cancer from an anastomotic recurrence or metastases . A tumor was classified as a second primary tumor if it was pathologically described as arising from a preexisting polyp or was found at a site distant from the original primary tumor ( not at the site of the anastomosis ) , without evidence of penetration from the serosa of the bowel . Only tumors discovered after the original resection were considered second primary tumors , and only invasive cancer was included . In situ tumors were excluded because they were not included in either of our comparison groups and because , given the lack of potential for metastatic spread , they are of less clinical relevance . In our primary analysis , we did not specify a minimum time interval between treatment of the original primary tumor and detection of a second BACKGROUND AND METHODS Laboratory , clinical , and epidemiologic evidence suggests that calcium may help prevent colorectal adenomas . We conducted a r and omized , double-blind trial of the effect of supplementation with calcium carbonate on the recurrence of colorectal adenomas . We r and omly assigned 930 subjects ( mean age , 61 years ; 72 percent men ) with a recent history of colorectal adenomas to receive either calcium carbonate ( 3 g [ 1200 mg of elemental calcium ] daily ) or placebo , with follow-up colonoscopies one and four years after the qualifying examination . The primary end point was the proportion of subjects in whom at least one adenoma was detected after the first follow-up endoscopy but up to ( and including ) the second follow-up examination . Risk ratios for the recurrence of adenomas were adjusted for age , sex , lifetime number of adenomas before the study , clinical center , and length of the surveillance period . RESULTS The subjects in the calcium group had a lower risk of recurrent adenomas . Among the 913 subjects who underwent at least one study colonoscopy , the adjusted risk ratio for any recurrence of adenoma with calcium as compared with placebo was 0.85 ( 95 percent confidence interval , 0.74 to 0.98 ; P=0.03 ) . The main analysis was based on the 832 subjects ( 409 in the calcium group and 423 in the placebo group ) who completed both follow-up examinations . At least one adenoma was diagnosed between the first and second follow-up endoscopies in 127 subjects in the calcium group ( 31 percent ) and 159 subjects in the placebo group ( 38 percent ) ; the adjusted risk ratio was 0.81 ( 95 percent confidence interval , 0.67 to 0.99 ; P=0.04 ) . The adjusted ratio of the average number of adenomas in the calcium group to that in the placebo group was 0.76 ( 95 percent confidence interval , 0.60 to 0.96 ; P=0.02 ) . The effect of calcium was independent of initial dietary fat and calcium intake . CONCLUSIONS Calcium supplementation is associated with a significant - though moderate - reduction in the risk of recurrent colorectal adenomas BACKGROUND / AIMS The frequency of colorectal adenomas , the precursor lesions for most cases of colorectal carcinoma , has been generally measured as prevalence rates of adenomas at autopsy or colonoscopy . The aim of this study was to estimate the incidence rate of adenomas and compare it with the adenoma recurrence rate . METHODS Data on colonoscopies performed in three New York City practice s were collected prospect ively . The cumulative rate of adenoma diagnosis on repeat colonoscopy was calculated for patients with no abnormalities on index colonoscopy ( " incidence " rate ) and for patients with adenomas on the index colonoscopy ( " recurrence " rate ) . RESULTS The cumulative incidence rate of adenomas at 36 months was 16 % , and the cumulative recurrence rate at 36 months was 42 % ( P < 0.004 ) . The recurrence rate was higher in patients with multiple adenomas than in those with a single adenoma on index colonoscopy , although the increase was not statistically significant . CONCLUSIONS Although the recurrence rate has always been assumed to be elevated , this study is the first to compare the recurrence rate of adenomas with the incidence rate directly and to show that the recurrence rate is indeed elevated PURPOSE Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival , it remains unknown whether a more intensive strategy provides any significant advantage . This prospect i ve , multicenter , r and omized , controlled trial was aim ed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability . PATIENTS AND METHODS Patients with stage II or III colorectal cancer were allocated r and omly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring , or an intensive strategy in which abdominal computed tomography or ultrasonography , chest radiograph , and colonoscopy were added . RESULTS A total of 259 patients were included : 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy . Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence . After a median follow-up of 48 months , there was no difference in the probability of overall survival in the whole series ( hazard ratio [ HR ] = 0.87 ; 95 % CI , 0.49 to 1.54 ; P = .62 ) . However , the intensive strategy was associated with higher overall survival in patients with stage II tumors ( HR = 0.34 ; 95 % CI , 0.12 to 0.98 ; P = .045 ) and in those with rectal lesions ( HR = 0.09 ; 95 % CI , 0.01 to 0.81 ; P = .03 ) , mainly due to higher rate of resectability for recurrent tumors . Colonoscopy was responsible for the detection of the highest proportion ( 44 % ) of resectable tumor recurrence in the intensive arm . CONCLUSION A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors . Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up , at least BACKGROUND The identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer . In current practice , the intervals between colonoscopies after polypectomy are variable , often a year long , and not based on data from r and omized clinical trials . We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years . METHODS Patients were eligible if they had one or more adenomas , no previous polypectomy , and a complete colonoscopy and all their polyps had been removed . They were r and omly assigned to have follow-up colonoscopy at one and three years or at three years only . The two study end points were the detection of any adenoma , and the detection of adenomas with advanced pathological features ( defined as those > 1 cm in diameter and those with high- grade dysplasia or invasive cancer ) . RESULTS Of 2632 eligible patients , 1418 were r and omly assigned to the two follow-up groups , 699 to the two-examination group and 719 to the one-examination group . The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent , as compared with 32.0 percent in the group examined at three years ( P = 0.006 ) . The percentage of patients with adenomas with advanced pathological features was the same in both groups ( 3.3 percent ) . CONCLUSIONS Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years . An interval of at least three years is recommended before follow-up colonoscopy after both one and three years . An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps . Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening Outpatient follow up may be performed to detect early recurrence or metastasis in the hope to be cured by further surgery . 909 patients have been prospect ively followed after resection for cure of colorectal carcinoma . The mean duration of this follow up was 48 months . 1 . Only 322 ( 35.4 % ) patients agreed to be su bmi tted to an strict regiment of frequent check up . 2 . Only 92 recurrences were diagnosed at times of follow up , the 308 others were discovered between regular follow up examination . 3 . Only 32 recurrences out of 92 detected by the follow up schedule were totally without symptoms . 4 . In the follow up group 30 patients ( 32.6 % ) benefited from second surgery versus 7 for the others ( 7.8 % ) p less than 0.001 . 5 . The comparison about the five years actuarial survival rates between the follow up group and the others is statistically significant : p less than 0.01 PURPOSE The identification of groups with a high risk of colorectal adenoma recurrence remains a controversial issue for clinicians . This study was design ed to assess the predictive value of initial patient and adenoma characteristics of the three-year recurrence . METHODS The study population was composed of 552 patients with resected colorectal adenomas who completed the European Fiber-Calcium Intervention trial . At both baseline and three-year examinations , the characteristics of adenomas were recorded according to a st and ardized protocol . The main outcomes measured were the three-year overall recurrence , recurrence of multiple adenomas , recurrence of advanced adenomas ( size ≥ 1 cm or tubulovillous/villous architecture or moderate/severe dysplasia ) , and proximal and distal recurrence . RESULTS A three-year recurrence was observed in 122 patients ( 22.1 percent ) , and more than one-half of them had recurrent adenomas on the proximal colon . After adjustment for patient characteristics and treatment allocation , the number of adenomas and their proximal location at baseline were the main predictors of recurrence . In comparison with patients who had one or two adenomas on the distal colon , patients with three or more adenomas with at least one of them located on the proximal colon had a much higher risk of overall recurrence ( 5.3 ; 95 percent confidence interval , 2.7–10.3 ) , proximal recurrence ( 8.5 ; 95 percent confidence interval , 4.1–18 ) , and advanced adenoma recurrence ( 5.5 ; 95 percent confidence interval , 2.4–12.6 ) . CONCLUSIONS Follow-up colonoscopies in patients with adenomas should include careful examination of the proximal colon . The time interval between follow-up examinations could probably be extended beyond three years in patients who have only one or two distal adenomas BACKGROUND AND AIMS The link between adenoma characteristics at baseline colonoscopy and adenoma recurrence is poorly understood . We assessed whether the number , size , location , or histology of resected adenomas was related to the probability of recurrence of advanced lesions . METHODS Analyses were based on 1287 men and women in the wheat bran fiber ( WBF ) study , a r and omized , double-blind trial of WBF as a means of decreasing the probability of adenoma recurrence over a period of 3 years . Multiple logistic regression was used to calculate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . RESULTS Recurrence of advanced adenomas ( > 1 cm or tubulovillous/villous histology ) was higher among individuals with adenomas > 1 cm compared with those with adenomas < 0.5 cm ( OR , 2.69 ; 95 % CI , 1.34 - 5.42 ) and among those with proximal than those with distal adenomas ( OR , 1.65 ; 95 % CI , 1.02 - 2.67 ) . No association was observed for adenoma number or histology . A shift in location from the distal colon and rectum at baseline ( 54.6 % ) to more proximal recurrent adenomas ( 45.2 % ) , including advanced lesions ( 42.8 % ) , was observed . CONCLUSIONS Large or proximally located adenomas are important indicators of recurrence of advanced lesions . Because most recurrences were detected in the proximal colon , careful surveillance of this area is warranted BACKGROUND & AIMS Epidemiologic and experimental studies have suggested that aspirin intake reduces the risk for colorectal carcinogenesis . However , the available data are not sufficient to serve as the basis for firm recommendations . METHODS We r and omly assigned 272 patients with a history of colorectal adenomas ( at least one more than 5 mm in diameter , or more than 3 ) to daily lysine acetylsalicylate ( 160 or 300 mg/day ) or placebo for 4 years . The primary end points were adenoma recurrence after 1 and 4 years . These results are those of the year 1 colonoscopy . RESULTS Among the 238 patients who completed the year 1 colonoscopy , at least one adenoma was observed in 38 patients of the 126 ( 30 % ) in the aspirin group and in 46 of the 112 ( 41 % ) in the placebo group ; relative risk was 0.73 ( 95 % confidence interval [ CI ] : 0.52 - 1.04 ; P = 0.08 ) . At least one adenoma of more than 5 mm diameter was observed in 13 patients ( 10 % ) in the aspirin group and 26 ( 23 % ) in the placebo group ( P = 0.01 ) . The corresponding numbers for adenomas more than 10 mm in diameter were one ( 1 % ) and 7 ( 6 % ) ( P = 0.05 ) . Stepwise regression showed that independent factors associated with lower adenoma recurrence are aspirin treatment ( adenoma > 5 mm , P = 0.01 ) , absence of personal history of adenoma before the entry colonoscopy ( P = 0.01 ) , and initial adenomatous polyp burden less than 10 mm ( P = 0.001 ) . CONCLUSIONS Daily soluble aspirin is associated with a reduction in the risk for recurrent adenomas found at colonoscopy 1 year after starting treatment BACKGROUND & AIMS Outcomes of colon surveillance after colorectal cancer screening with colonoscopy are uncertain . We conducted a prospect i ve study to measure incidence of advanced neoplasia in patients within 5.5 years of screening colonoscopy . METHODS Three thous and one hundred twenty-one asymptomatic subjects , age 50 to 75 years , had screening colonoscopy between 1994 and 1997 in the Department of Veterans Affairs . One thous and one hundred seventy-one subjects with neoplasia and 501 neoplasia-free controls were assigned to colonoscopic surveillance over 5 years . Cohorts were defined by baseline findings . Relative risks for advanced neoplasia within 5.5 years were calculated . Advanced neoplasia was defined as tubular adenoma greater than > or = 10 mm , adenoma with villous histology , adenoma with high- grade dysplasia , or invasive cancer . RESULTS Eight hundred ninety-five ( 76.4 % ) patients with neoplasia and 298 subjects ( 59.5 % ) without neoplasia at baseline had colonoscopy within 5.5 years ; 2.4 % of patients with no neoplasia had interval advanced neoplasia . The relative risk in patients with baseline neoplasia was 1.92 ( 95 % CI : 0.83 - 4.42 ) with 1 or 2 tubular adenomas < 10 mm , 5.01 ( 95 % CI : 2.10 - 11.96 ) with 3 or more tubular adenomas < 10 mm , 6.40 ( 95 % CI : 2.74 - 14.94 ) with tubular adenoma > or = 10 mm , 6.05 ( 95 % CI : 2.48 - 14.71 ) for villous adenoma , and 6.87 ( 95 % CI : 2.61 - 18.07 ) for adenoma with high- grade dysplasia . CONCLUSIONS There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance . Patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia Case-control studies and short term prospect i ve studies have suggested that selected groups of patients with precursors of colorectal cancer may benefit from colonoscopic surveillance after initial removal of adenomas . The aim of the present study was to demonstrate such a possible benefit from long term ( 1–24 years ) colonoscopic surveillance in a population of patients with all types of adenomas regardless of size and way of removal . Two thous and and forty-one patients with a first time diagnosis of colorectal adenoma were included in prospect i ve surveillance between year 1978 and 2002 . All adenomas were considered . Incidence of CRC and mortality from CRC was calculated , using age , sex , and calendar specific number of person years of follow-up for comparison with the st and ard Danish population . CRC was found in 27 patients , the expected number being 41 ( RR 0.65 , 95 % CI 0.43–0.95 ) . Three of the 27 patients died from CRC , the expected number being 25 ( RR 0.12 , 95 % CI 0.03–0.36 ) . A total of 6 289 colonoscopies result ed in severe complications in 20 patients and two died from complications . Long-term colonoscopic surveillance may reduce incidence of CRC as well as mortality in patients with sporadic adenomas . The benefit is reduced to a minor degree by complications from Purpose Because of their potential for malignancy , flat colorectal neoplasias are a current topic of debate . This study was design ed to investigate the clinicopathologic features of flat neoplasia and to compare them with those of polypoid neoplasia , as well as to identify the determinants of malignant transformation of both flat and polypoid colorectal neoplasia . Methods A prospect i ve , cross-sectional study of 3,360 patients diagnosed with adenomas via total colonoscopy and polypectomy was performed at 11 tertiary medical centers between July 2003 and July 2004 . In this study , potential risk factors for malignant transformation were analyzed . If multiple adenomas were identified , then only the adenoma with the most advanced degree of histology was recorded for the patient . Results Of a total of 3,360 neoplasias identified , we found that the incidence of flat and polypoid neoplasias were 207 ( 6.2 percent ) and 3,153 ( 93.8 percent ) , respectively . Patients with flat neoplasias tended to be older ( 59.6 vs. 57.1 , P < 0.01 ) , with the neoplaisa located more frequently in the right colon than polypoid neoplasias ( 49.3 percent vs. 32 percent , P < 0.01 ) . The incidence of high- grade dysplasia or cancer in flat neoplasias was similar to that of polypoid neoplasias ( 5.4 percent vs. 4.6 percent , P = 0.36 ) . Multivariate analysis revealed that a size of ≥11 mm ( odds ratio , 6.8 ; 95 percent confidence interval , 4.8–9.7 ) and location in the left colon ( odds ratio , 1.6 ; 95 percent confidence interval , 1.1–2.4 ) were significant determinants for the malignancy potential of colonic neoplasias . Conclusions The clinicopathologic indices for the propensity of malignant transformation in colorectal neoplasias were a size ≥11 mm and location in the left colon rather than flat gross morphology AIMS This paper aims to evaluate the diagnostic efficacy and costs of follow-up tailored according to risk of recurrence compared with minimal surveillance . METHODS A total of 358 patients treated by surgery alone for colorectal cancer were prospect ively divided into two groups of 200 and 158 patients considered at high and low risk of recurrence respectively , according to prognostic factors . They were further r and omized into two subgroups : group 1 , 192 patients undergoing risk-adapted follow-up , intensive and low-intensity ; group 2 , 145 patients undergoing minimal surveillance . Twenty-one cases dropped out . Median follow-up was 61.5 months and 42 months for cases at high risk ( intensive follow-up ) and at low risk ( low-intensity follow-up ) respectively . RESULTS At the end of the study , 52.6 % of patients undergoing risk-adapted follow-up and 57.2 % undergoing minimal follow-up had developed recurrence . In patients at high risk , a significant difference in the incidence of curative re-operations was observed between the subgroups undergoing risk-adapted follow-up and subgroups undergoing minimal surveillance ( P<0.05 ) . The actuarial 5 year survival of patients at high and at low risk of recurrence undergoing risk-adapted follow-up is significantly better than that of cases undergoing minimal follow-up . The economic costs for 34 patients in the intensive follow-up group and for the 57 patients in the low-intensity follow-up group who were free from disease after primary surgery was very similar . CONCLUSIONS Risk-adapted follow-up has significantly improved the targeting of curative re-operations and overall survival of patients independently of risk of recurrence and has allowed a reduction in the costs of following up of disease-free patients Background : Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma and therefore need to be kept under surveillance . It is essential to avoid unnecessary examinations by tailoring the frequency of follow up examinations to individual risk . Methods : A total of 3134 patients undergoing endoscopic removal of colorectal adenomas were prospect ively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996 . A multivariate analysis of 1159 patients on long term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology — that is , adenomas > 10 mm or with high grade dysplasia or invasive carcinoma . Results : Univariate analysis revealed that sex , parental history of colorectal carcinoma , and characteristics of the initial findings —that is , size , multiplicity , and amount of villous structure — were significant predictors of metachronous adenomas of advanced pathology . On the basis of multivariate analysis , two risk groups were identified : ( 1 ) patients with no parental history of colorectal carcinoma with only small ( ≤10 mm ) tubular adenomas at the initial clearing examination have a very low risk , and we estimated that 10 % will develop advanced metachronous adenomas after 10 years ; ( 2 ) the high risk group contained all other patients , 10 % of whom will show metachronous adenomas of advanced pathology at follow up after only three years . Conclusions : The risk of developing metachronous adenomas with advanced pathology can be stratified for various patient and adenoma characteristics . Surveillance intervals can be scheduled for low risk ( 10 years ) and high risk ( three years ) patients . Risk related follow up thus helps to avoid unnecessary examinations Abstract . In a prospect i ve r and omised study , 597 patients subjected to curative surgery for colorectal cancer were allocated to either a group with frequent follow-up or a control group with follow-up every 5 years . The pattern of recurrence is review ed . An equal number of recurrences was detected in the two groups , but the recurrence was diagnosed 9 months earlier in patients followed frequently , and the diagnostic characteristics of various tests dependent upon how often they were used . It is unlikely that frequent follow-up after curative surgery for colorectal cancer has a large positive influence upon survival , but a small benefit from an intensive follow-up program can not be ruled out . The present results indicate that clinical examination , digital rectal examination , proctoscopy , colonoscopy and chest x-ray should be included in such a programme , whereas others ( blood haemoglobin , faecal occult blood test , double contrast braium enema , serum alanine aminotransferase , and serum bilirubin ) should be avoided , having a low sensitivity for detecting recurrent colorectal cancer . Résumé . Cinq-cent-soixante-dix-sept patients ayant subi un traitement chirurgical curatif d'un cancer colo-rectal ont été inclus dans une étude prospect i ve r and omisée et ont été soumis soit à un follow-up fréquent soit à un contrôle tous les 5 ans . Les modalités de récidive sont analysés . Un nombre égal de patients ont développé des récidives dans les 2 groupes et la récidive est diagnostiquée 9 mois plus tôt dans le groupe ayant subi un follow-up à intervalles rapprochés ; les caractéristiques diagnostiques des différents tests utilisés dépendent de la fréquence de leur usage . Il est improbable qu'un follow-up à intervalles rapprochés et après chirurgie curative d'un cancer colo-rectal ait une influence très positive sur la survie des opérés mais un petit nombre de patients pourraient bénéficier d'un programme de follow-up intensif . Les résultats présents indiquent que l'examen clinique , le toucher rectal , la proctoscopie , la colonoscopie et la radio du thorax devraient être inclus dans un tel programme alors que d'autres investigations ( l'hémoglobine sanguine , la recherche de sang fécal occulte , un lavement barytéà double contraste , le dosage sérique de l'alanine aminotransférase et de la bilirubine sérique ) pourraient être évités car ces examens ne montrent qu'une faible sensitivité dans la délection des récidives de cancers colo-rectaux BACKGROUND & AIMS Guidelines on the type and frequency of follow-up of patients after curative surgery for colorectal cancer are unclear . The aim of this study was to determine the survival benefit of a planned follow-up program . METHODS Three hundred twenty-five patients who underwent curative resection of colorectal cancer were prospect ively r and omized to either intensive or st and ard follow-up . After stratification according to Dukes ' stage and site in the colon or rectum , patients were r and omized to intensive follow-up of yearly colonoscopy , computerized tomography ( CT ) of the liver , and chest radiography and clinical review and simple screening vs. structured clinical review and simple screening tests only . RESULTS On completion of 5-year follow-up , there was no significant difference in survival between the two groups . Yearly colonoscopy failed to detect any asymptomatic local recurrences . Only one asymptomatic curable metachronous colon tumor was detected . Liver CT result ed in earlier detection of hepatic metastases but did not increase the number of curative hepatectomies . Only 1 patient had an asymptomatic CT-detected liver metastasis , and another had an asymptomatic chest radiography-detected lung metastasis . Both had curative resections . CONCLUSIONS Yearly colonoscopy , liver CT , and chest radiography will not improve survival from colorectal cancer when added to symptom and simple screening review The natural history of untreated colonic polyps is uncertain . A retrospective review of Mayo Clinic records from a 6-yr period just before the advent of colonoscopy identified 226 patients with colonic polyps greater than or equal to 10 mm in diameter in whom periodic radiographic examination of the colon was elected over excisional therapy . In all patients , follow-up of polyps spanned at least 12 mo ( mean , 68 mo ; range , 12 - 229 mo ) and included at least two barium enema examinations ( mean , 5.2 ; range , 2 - 17 ) . During the follow-up period , 83 polyps ( 37 % ) enlarged . Twenty-one invasive carcinomas were identified at the site of the index polyp at a mean follow-up of 108 mo ( range , 24 - 225 mo ) . Actuarial analysis revealed that the cumulative risk of diagnosis of cancer at the polyp site at 5 , 10 , and 20 yr was 2.5 % , 8 % , and 24 % , respectively . In addition , 11 invasive cancers were found at a site remote from the index polyp during the same follow-up period . These data further support the recommendation for excision of all colonic polyps greater than or equal to 10 mm in diameter . Periodic examination of the entire colon is recommended in this group of patients to identify neoplasms arising at a site remote from the index polyp . Although this study has limitations inherent to any retrospective analysis , comparable prospect i ve data are unlikely to be available in the future because of the current widespread availability of colonoscopy PURPOSE : The authors evaluate the effectiveness of routine colonoscopy and marker evaluation in diagnosis of intraluminal recurrent cancer . METHODS : Chart review was conducted on 481 patients who underwent curative resection for colorectal cancer between 1980 and 1990 . Clinical visits were scheduled and carcinoembryonic antigen evaluation was performed every three months , and colonoscopy was performed preoperatively , 12 to 15 months after surgical treatment , and then with intervals of 12 to 24 months or when symptoms appeared . RESULTS : About 10 percent of patients developed intraluminal recurrences . More than one-half of metachronous lesions arose within the first 24 months , and median time to diagnosis was 25 months . Patients with left-sited tumors in the advanced stage had a higher risk of developing recurrent intraluminal disease . Twenty-nine patients underwent a second surgical operation , of which 17 cases were radical . In this group , the five-year survival was 70.6 percent , although no nonradically treated or nonresected patients survived longer than 31 months . Twenty-two patients were asymptomatic at time of diagnosis of recurrence , and of these , 12 patients underwent radical operation ; on the other h and , of the 24 symptomatic patients , only 5 were treated radically . Carcinoembryonic antigen was the first sign of recurrence in eight cases . Colonoscopy must be performed within the first 12 to 15 months after operation , whereas an interval of 24 months between examinations seems sufficient to guarantee early detection of metachronous lesions . CONCLUSION : Serial tumor marker evaluation is of help in earlier diagnosis of local recurrences . Asymptomatic patients more frequently undergo another operation for cure and thus have a better survival rate PURPOSE : This study investigated the value of intense follow-up compared with no follow-up after curative surgery of cancer in the colon or rectum . METHODS : One hundred seven patients were r and omized to no follow-up ( control group ; n=54 ) or intense follow-up ( follow-up group ; n=53 ) after surgery and early postoperative colonoscopy . Patients in the follow-up group were followed at frequent intervals with clinical examination , rigid proctosigmoidoscopy , colonoscopy , computed tomography of the pelvis ( in patients operated with abdominoperineal resection ) , pulmonary x-ray , liver function tests , and determinations of carcinoembryonic antigen and fecal hemoglobin . Follow-up ranged from 5.5 to 8.8 years after primary surgery . RESULTS : Tumor recurred in 18 patients ( 33 percent ) in the control group and in 17 patients ( 32 percent ) in the follow-up group . Reresection with curative intent was performed in three patients in the control group and in five patients ( four of whom were asymptomatic ) in the follow-up group . In the follow-up group two asymptomatic patients with elevated carcinoembryonic antigen levels were disease-free three and five and one-half years after reresection and were the only patients apparently cured by reresection . No patient underwent surgery for metastatic disease in the liver or lungs . Symptomatic metachronous carcinoma was detected in one patient ( control group ) after three years . Five-year survival rate was 67 percent in the control group and 75 percent in the follow-up group ( P > 0.05 ) ; the corresponding cancer-specific survival rates were 71 percent and 78 percent , respectively . CONCLUSION : Intense follow-up after resection of colorectal cancer did not prolong survival in this study BACKGROUND After patients have undergone colonoscopic polypectomy , it is uncertain whether colonoscopic examination or a barium enema is the better method of surveillance . METHODS As part of the National Polyp Study , we offered colonoscopic examination and double-contrast barium enema for surveillance to patients with newly diagnosed adenomatous polyps . Although barium enema was performed first , the endoscopist did not know the results . RESULTS A total of 973 patients underwent one or more colonoscopic examinations for surveillance . In the case of 580 of these patients , we performed 862 paired colonoscopic examinations and barium-enema examinations that met the requirements of the protocol . The findings on barium enema were positive in 222 ( 26 percent ) of the paired examinations , including 139 of the 392 colonoscopic examinations in which one or more polyps were detected ( rate of detection , 35 percent ; 95 percent confidence interval , 31 to 40 percent ) . The proportion of examinations in which adenomatous polyps were detected by barium enema colonoscopy was significantly related to the size of the adenomas ( P=0.009 ) ; the rate was 32 percent for colonoscopic examinations in which the largest adenomas detected were 0.5 cm or less , 53 percent for those in which the largest adenomas detected were 0.6 to 1.0 cm , and 48 percent for those in which the largest adenomas detected exceeded 1.0 cm . Among the 139 paired examinations with positive results on barium enema and negative results on colonoscopic examination in the same location , 19 additional polyps , 12 of which were adenomas , were detected on colonoscopic reexamination . CONCLUSIONS In patients who have undergone colonoscopic polypectomy , colonoscopic examination is a more effective method of surveillance than double-contrast barium enema PURPOSE A traditional end point for colon adjuvant clinical trials is overall survival ( OS ) , with 5 years demonstrating adequate follow-up . A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice . METHODS Individual patient data were pooled from 18 r and omized phase III colon cancer adjuvant clinical trials . Trials included 43 arms , with a pooled sample size of 20,898 patients . The primary hypothesis was that disease-free survival ( DFS ) , with 3 years of follow-up , is an appropriate primary end point to replace OS with 5 years of follow-up . RESULTS The recurrence rates for years 1 through 5 were 12 % , 14 % , 8 % , 5 % , and 3 % , respectively . Median time from recurrence to death was 12 months . Eighty percent of recurrences were in the first 3 years ; 91 % of patients with recurrence by 3 years died before 5 years . Correlation between 3-year DFS and 5-year OS was 0.89 . Comparing control versus experimental arms within each trial , the correlation between hazard ratios for DFS and OS was 0.92 . Within-trial log-rank testing using both DFS and OS provided the same conclusion in 23 ( 92 % ) of 25 cases . Formal measures of surrogacy were satisfied . CONCLUSION In patients treated on phase III adjuvant colon clinical trials , DFS and OS are highly correlated , both within patients and across trials . These results suggest that DFS after 3 years of median follow-up is an appropriate end point for adjuvant colon cancer clinical trials of fluorouracil-based regimens , although marginally significant DFS improvements may not translate into significant OS benefits PURPOSE Surgery remains the primary treatment of colorectal cancer . Data are lacking to delineate the optimal surveillance strategy following resection . A large-scale multi-center European study is underway to address this issue ( Gruppo Italiano di Lavoro per la Diagnosi Anticipata-GILDA ) . METHODS Following primary surgery with curative intent , stratification , and r and omization at GILDA headquarters , colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen . Rectal cancer patients undergoing curative resection are similarly r and omized , with their follow-up regimens placing more emphasis on detection of local recurrence . Target recruitment for the study will be 1500 patients to achieve a statistical power of 80 % ( assuming an alpha of 0.05 and a hazard-rate reduction of > 24 % ) . RESULTS Since the trial opened in 1998 , 985 patients have been r and omized from 41 centers as of February 2004 . There were 496 patients r and omized to the less intensive regimens , and 489 r and omized to the more intensive regimens . The mean duration of follow-up is 14 months . 75 relapses ( 15 % ) and 32 deaths ( 7 % ) had been observed in the two more intensive follow-up arms , while 64 relapses ( 13 % ) and 24 deaths ( 5 % ) had been observed in the two less intensive arms as of February 2004 . CONCLUSIONS This trial should provide the first evidence based on an adequately powered r and omized trial to determine the optimal follow-up strategy for colorectal cancer patients . This trial is open to US centers , and recruitment continues The results of a prospect i ve r and omized study of 1056 patients with colorectal adenomas are presented . After initial polypectomy from 1978 to 1992 , patients were allocated at r and om to different follow-up intervals varying from 6 to 48 months , except 53 patients who were allocated to intervals of 6 months . The examinations were mainly done by colonoscopy . Ten patients developed colorectal carcinoma , a number similar to that expected ( 7.96 ) , when compared with a sex- and age-matched normal Danish population . The expected number of carcinomas was also calculated from adenoma to carcinoma conversion rates estimated in other studies and compared with that observed . If all carcinomas develop in large ( > or = 10 mm ) adenomas or adenomas with severe dysplasia , the expected number of carcinomas would have been 62 and 110 , respectively , indicating a significant reduction of carcinomas in the present study . One patient died of colorectal carcinoma , which is significantly lower than the number expected ( 7.58 ) . Two patients died of complications from therapeutic and diagnostic colonoscopy -- that is , 2 deaths in 3959 colonoscopies . In conclusion , the follow-up strategy has result ed in a mortality from colorectal carcinoma which is reduced when compared with the normal population , in spite of an apparently similar incidence of carcinoma . However , previous suggested adenoma-carcinoma conversion rates indicate that a major reduction of incidence actually has taken place BACKGROUND Flat and depressed colorectal tumours were originally thought to be unique to the Japanese population . Recently there have been reports of flat and depressed lesions in western countries but they have been thought to be uncommon . METHODS In this prospect i ve study , 1000 consecutive patients attending for routine colonoscopy were examined for flat or depressed lesions . The examinations were done by one European colonoscopist using methods developed in Japan . FINDINGS 321 adenomas were found : 202 ( 63 % ) were polypoid , 36 % ( 117 ) were flat and 2 ( 0.6 % ) appeared depressed . Most adenomas contained areas of mild or moderate dysplasia but 10 % ( 31 ) were severely dysplastic . Six Dukes ' A adenocarcinomas were identified together with 25 more advanced adenocarcinomas . The likelihood of Dukes ' A cancer or severe dysplasia increased from 4 % ( 3/70 ) in small flat lesions , to 6 % ( 9/154 ) in small polyps , 16 % ( 8/50 ) in larger polyps , 29 % ( 14/49 ) in large flat lesions , and 75 % ( 3/4 ) in depressed lesions . 54 % ( 20/37 ) lesions containing severe dysplasia or Dukes ' A carcinoma were flat or depressed . INTERPRETATION The polyp-carcinoma hypothesis prompts colonoscopists to search only for polypoid lesions when screening for cancer , and many early colorectal neoplasms may therefore be missed . Colonoscopists require training in the recognition of flat and depressed lesions to detect colorectal tumours in the early stages The Polyp Prevention Trial ( PPT ) was a multicenter r and omized clinical trial to evaluate the effects of a high-fiber ( 18 g/1,000 kcal ) , high-fruit and -vegetable ( 3.5 servings/1,000 kcal ) , and low-fat ( 20 % of total energy ) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years . Although intervention participants reported a significantly reduced intake of dietary fat , and increased fiber , fruit , and vegetable intakes , their risk of recurrent adenomas was not significantly different from that of the controls . Since the PPT intervention lasted only 4 years , it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge , particularly if diet affects early events in the neoplastic process . The PPT-Continued Follow-up Study ( PPT-CFS ) was a post-intervention observation of PPT participants for an additional 4 years from the completion of the trial . Of the 1,905 PPT participants , 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants . The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years ( intervention group ) and 3.87 years ( control group ) . The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar . Even though the intervention group participants increased their fat intake and decreased their intakes of fiber , fruits , and vegetables during the PPT-CFS , they did not go back to their prer and omization baseline diet ( P < 0.001 from paired t tests ) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS ( P < 0.001 from t tests ) . As the CFS participants are a subset of the people in the PPT study , the non participants might not be missing completely at r and om . Therefore , a multiple imputation method was used to adjust for potential selection bias . The relative risk ( 95 % confidence intervals ) of recurrent adenoma in the intervention group compared with the control group was 0.98 ( 0.88 - 1.09 ) . There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma ( 1.06 ; 0.81 - 1.39 ) or multiple adenomas ( 0.92 ; 0.77 - 1.10 ) . We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS : the intervention-control relative risk ( 95 % confidence intervals ) for any adenoma recurrence was 1.04 ( 0.98 - 1.09 ) . This study failed to show any effect of a low-fat , high-fiber , high-fruit and -vegetable eating pattern on adenoma recurrence even with 8 years of follow-up . ( Cancer Epidemiol Biomarkers Prev 2007;16(9):1745–52 AIM To investigate the role of colonoscopy in the follow-up of patients undergoing curative resection of colorectal cancer . MATERIAL AND METHODS A prospect i ve study was performed of 102 patients with colorectal cancer who underwent surgery with curative intention . Postoperative colonoscopic follow-up was a minimum of 5 years . RESULTS There were 62 males and 40 females . The mean duration of follow-up was 73.4 months . Synchronous polyps were found in 44.1 % ( 114 in 45 patients ) and metachronous polyps in 33.4 % ( 64 in 34 patients ) . Synchronous carcinoma was detected in 7.8 % ( 9 in 8 patients ) , metachronous carcinoma in 1.9 % ( 2 in 2 patients ) and suture recurrence in 4.9 % ( 5 in 5 patients ) . Metachronous polyps developed in 55.5 % of the patients with synchronous polyps and in only 15.8 % of those with no synchronous polyps ( p < 0.00005 ) ; the odds ratio was 6.67 . Colonoscopy diagnosed 92 synchronous polyps and 64 metachronous polyps ; of these , 34 were found to be significant(in 22 patients ) . Colonoscopy diagnosed 5 synchronous carcinomas ; in 3 of these ( polyps with non-invasive carcinoma ) polypectomy constituted definitive therapy and in the remaining 2 , curative resection was achieved . Colonoscopy diagnosed 2 stage C2 metachronous carcinomas at 63 and 94 months . Curative resection was achieved in both cases . Colonoscopic follow-up diagnosed 2 suture recurrences and resection was potentially curative . CONCLUSIONS Colonoscopy was found to play an essential role in 30 % of the patients . The technique allowed the early diagnosis of synchronous carcinomas and curative treatment of metachronous carcinomas and demonstrated that the presence of synchronous polyps increases the risk of developing metachronous polyps PURPOSE : The aim of this study was to identify the high-risk groups for metachronous colorectal carcinoma among patients who undergo colorectal cancer surgery . METHODS : Three hundred forty-one patients undergoing colorectal cancer surgery who had undergone surveillance colonoscopy at least twice during a period of more than three years were analyzed . A metachronous colorectal carcinoma was defined as a new colorectal carcinoma detected by surveillance colonoscopy after surgery . RESULTS : Surveillance colonoscopy was performed 4.6 times per patient during an average of 6.2 years . Twenty-two metachronous colorectal carcinomas in 19 patients were detected , and 14 ( 64 percent ) of 22 were detected within five years of surgery . The cumulative incidence of developing colorectal carcinomas during a five-year period was 5.3 percent . Seventeen ( 77 percent ) of 22 carcinomas were 10 mm or less in size . Ten ( 71 percent ) of the 14 carcinomas in early stages showed a flat appearance . Univariate analysis showed that extracolonic malignancy , coexistence of adenoma , and synchronous multiple colorectal carcinoma were significant predictive factors for detecting colorectal carcinomas in surveillance colonoscopy and that family history of colorectal carcinoma was a possible predictive factor . Multivariate analysis performed with Cox proportional hazards regression model showed that extracolonic malignancy and the coexistence of adenoma were significant predictive factors . CONCLUSION : We recommend that patients with the above predictive factors receive surveillance colonoscopy meticulously and regularly BACKGROUND Most cases of colorectal cancer ( CRC ) develop from adenomas . Polypectomy is believed to reduce the incidence of CRC , but this effect has never been explored in prospect i ve controlled studies . The aim of the present study was to evaluate the effect of polypectomy on colorectal cancer incidence in a population -based screening program . METHODS In 1983 , 400 men and women aged 50 - 59 years were r and omly drawn from the population registry of Telemark , Norway . They were offered a flexible sigmoidoscopy and , if polyps were found , a full colonoscopy with polypectomy and follow-up colonoscopies in 1985 and 1989 . A control group of 399 individuals was drawn from the same registry . In 1996 both groups ( age , 63 - 72 years ) were invited to have a colonoscopic examination . Hospital files and the files of The Norwegian Cancer Registry were search ed to register any cases of CRC in the period 1983 - 96 . RESULTS At screening endoscopy 324 ( 81 % ) individuals attended in 1983 and 451 ( 71 % ) in 1996 . From 1983 to 1996 , altogether 10 individuals in the control group and 2 in the screening group were registered to have developed CRC ( relative risk , 0.2 ; 95 % confidence interval ( CI ) , 0.03 - 0.95 ; P = 0.02 ) . A higher overall mortality was observed in the screening group , with 55 ( 14 % ) deaths , compared with 35 ( 9 % ) in the control group ( relative risk , 1.57 ; 95 % CI , 1.03 - 2.4 ; P = 0.03 ) . CONCLUSION Endoscopic screening examination with polypectomy and follow-up was shown to reduce the incidence of CRC in a Norwegian normal population . The possible effect of screening on overall mortality should be addressed in larger studies BACKGROUND & AIMS To assess the prevalence of flat and depressed ( F&D ) colorectal adenomas in the United States , we performed a prospect i ve study of 211 American patients . METHODS Dye-assisted colonoscopy was performed in the presence of both an American and a Japanese investigator . RESULTS F&D lesions were found in 22.7 % of patients , and these were more likely to be adenomatous than polypoid lesions ( 82 % vs. 67 % ; P = 0.03 ) and contained more invasive cancer ( 4.5 % vs. 0 % ; P = 0.04 ) , which also appeared to be at a disproportionately advanced stage . The average size of all F&D advanced lesions ( high- grade dysplasia and cancer ) was significantly smaller than comparable polypoid lesions ( 10.75 + /- 2.7 mm vs. 20 + /- 2.9 mm ; P < 0.05 ) . F&D adenomas showed significantly stronger fragile histidine triad ( FHIT ) expression and lower p53 reactivity than similarly sized polypoid adenomas , whereas proliferative and apoptotic indices were similar in both groups . CONCLUSIONS We conclude that there is a significant prevalence of colonic F&D colorectal adenomas in this country and that these lesions have significantly different biologic features than polypoid lesions . The clinical and epidemiologic implication s of these findings for American patients need to be addressed in further studies PURPOSE : This prospect i ve , r and omized , single-center study was design ed to evaluate the influence of follow-up on detection and resectability of local recurrences and on survival after radical surgery for colorectal cancer . METHODS : Between 1987 and 1990 , 207 consecutive patients who underwent curative resections for primary untreated large-bowel carcinoma were r and omly assigned to a conventional follow-up group ( Group A ; n=103 ) and to an intense follow-up group ( Group B ; n=104 ) . All the patients were followed up prospect ively , and the outcome was known for all of them at five years . Patients in Group A were seen at six-month intervals for one year , and once a year thereafter . Patients in Group B were checked every three months during the first two years , at six-month intervals for the next three years , and once a year thereafter . RESULTS : Of the 103 patients in Group A , local recurrence was detected in 20 ; 9 ( 13 percent ) of these patients had colon cancer , and 11 ( 29 percent ) had rectal cancer . Of the 104 patients in Group B , local recurrence was detected in 26 ; 12 ( 16 percent ) of these patients had colon cancer , and 14 ( 45 percent ) had rectal cancer . Twelve cases ( 60 percent ) of local recurrence in Group A and 24 cases ( 92 percent ) in Group B were detected at scheduled visits ( P<0.05 ) . Local recurrences were detected earlier in patients of Group B ( 10.3±2.7vs . 20.2±6.1 months;P<0.0003 ) . Curative re-resection was possible in 2 patients ( 10 percent ) in Group A , 1 with colon cancer and 1 with rectal cancer , and in 17 patients ( 65 percent ) in Group B , 6 with colon cancer and 11 with rectal cancer ( P<0.01 ) . Of the Group B patients who had curative re-resections of local recurrence , 8 ( 47 percent ) were disease-free and long-term survivors as of the last follow-up , and 2 ( 11.7 percent ) were alive , but with a new recurrence . The 2 patients in Group A who had curative re-resections died as a result of cancer . The five-year survival rate in Group A was 58.3 percent and in Group B was 73.1 percent . The difference is statistically significant ( P < 0.02 ) . CONCLUSIONS : Our data support use of an intense follow-up plan after primary resection of large-bowel cancer , at least in patients with rectal cancer BACKGROUND We wanted to assess the influence of various surveillance intervals on the risk of new neoplasia after removal of pedunculated and small sessile tubular and tubulovillous adenomas . METHODS After initial colonoscopic polypectomy patients were r and omized to surveillance with either 2 years ( group A ) or 4 years ( group B ) between colorectal examinations . RESULTS The cumulated risk of a patient having new adenomas was 35.0 % ( 28.7 - 41.4 % ) in group A and 35.5 % ( 28.4 - 42.7 % ) in group B after 48 months . The risk increased to 44.9 % ( 36.0 - 53.9 % ) and 60.1 % ( 48.5 - 71.7 % ) , respectively , after 96 months . The risk of significant neoplasia ( carcinoma or adenoma with villous structure , severe dysplasia , or diameter > 10 mm ) was 5.2 % ( 2.3 - 8.1 % ) and 8.6 % ( 3.8 - 13.3 % ) after 48 months and 8.6 % ( 4.2 - 13.0 % ) and 17.4 % ( 7.6 - 27.2 % ) after 96 months . More than one adenoma at first examination was associated with higher risk of new adenomas . Furthermore , we found a tendency for age above 60 years and male gender to be associated with higher risk of new adenomas . More than two adenomas at first examination was the only factor found to be associated with a higher risk of new significant neoplasia . One patient in group A and two patients in group B developed cancer , which is not significantly different from the number expected ( 3.43 ) in the average Danish population ( RR = 0.9 , 0.2 - 2.6 ) . CONCLUSION After colonoscopy with removal of all polyps , colorectal examination at 4 years result ed in a similar risk of new adenomas compared with examinations at 2 and 4 years . However , new significant neoplasia tended to be more frequent when first surveillance was at 4 years . Extending the surveillance to 8 years also tended to increase the risk more in the group being examined every 4 years , but reduction of the number of surveillance examinations by more than 50 % and a probable reduction of complications from surveillance examinations themselves may justify a recommendation for the longest interval |
2,673 | 25,639,576 | Overall , evidence to support the use of antipsychotics to either prevent or treat delirium is lacking , and these medications can have adverse effects .
The pain , agitation , and delirium guidelines of the American College of Critical Care Medicine provide the strongest level of recommendation for the use of nonpharmacological approaches to prevent delirium , but questions remain about which nonpharmacological interventions are beneficial | Development of delirium in critical care patients is associated with increased length of stay , hospital costs , and mortality .
Delirium occurs across all inpatient setting s , although critically ill patients who require mechanical ventilation are at the highest risk . | Introduction This study hypothesised that a reduction of sound during the night using earplugs could be beneficial in the prevention of intensive care delirium . Two research questions were formulated . First , does the use of earplugs during the night reduce the onset of delirium or confusion in the ICU ? Second , does the use of earplugs during the night improve the quality of sleep in the ICU ? Methods A r and omized clinical trial included adult intensive care patients in an intervention group of 69 patients sleeping with earplugs during the night and a control group of 67 patients sleeping without earplugs during the night . The research ers were blinded during data collection . Assignment was performed by an independent nurse research er using a computer program . Eligible patients had an expected length of stay in the ICU of more than 24 hours , were Dutch- or English-speaking and scored a minimum Glasgow Coma Scale of 10 . Delirium was assessed using the vali date d NEECHAM scale , sleep perception was reported by the patient in response to five questions . Results The use of earplugs during the night lowered the incidence of confusion in the studied intensive care patients . A vast improvement was shown by a Hazard Ratio of 0.47 ( 95 % confidence interval ( CI ) 0.27 to 0.82 ) . Also , patients sleeping with earplugs developed confusion later than the patients sleeping without earplugs . After the first night in the ICU , patients sleeping with earplugs reported a better sleep perception . Conclusions Earplugs may be a useful instrument in the prevention of confusion or delirium . The beneficial effects seem to be strongest within 48 hours after admission . The relation between sleep , sound and delirium , however , needs further research .Trial registration Current Controlled Trials IS RCT 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 BACKGROUND Delirium is frequently diagnosed in critically ill patients and is associated with poor clinical outcomes . Haloperidol is the most commonly used drug for delirium despite little evidence of its effectiveness . The aim of this study was to establish whether early treatment with haloperidol would decrease the time that survivors of critical illness spent in delirium or coma . METHODS We did this double-blind , placebo-controlled r and omised trial in a general adult intensive care unit ( ICU ) . Critically ill patients ( ≥18 years ) needing mechanical ventilation within 72 h of admission were enrolled . Patients were r and omised ( by an independent nurse , in 1:1 ratio , with permuted block size of four and six , using a central ised , secure web-based r and omisation service ) to receive haloperidol 2.5 mg or 0.9 % saline placebo intravenously every 8 h , irrespective of coma or delirium status . Study drug was discontinued on ICU discharge , once delirium-free and coma-free for 2 consecutive days , or after a maximum of 14 days of treatment , whichever came first . Delirium was assessed using the confusion assessment method for the ICU ( CAM-ICU ) . The primary outcome was delirium-free and coma-free days , defined as the number of days in the first 14 days after r and omisation during which the patient was alive without delirium and not in coma from any cause . Patients who died within the 14 day study period were recorded as having 0 days free of delirium and coma . ICU clinical and research staff and patients were masked to treatment throughout the study . Analyses were by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Registry , number IS RCT N83567338 . FINDINGS 142 patients were r and omised , 141 were included in the final analysis ( 71 haloperidol , 70 placebo ) . Patients in the haloperidol group spent about the same number of days alive , without delirium , and without coma as did patients in the placebo group ( median 5 days [ IQR 0 - 10 ] vs 6 days [ 0 - 11 ] days ; p=0.53 ) . The most common adverse events were oversedation ( 11 patients in the haloperidol group vs six in the placebo group ) and QTc prolongation ( seven patients in the haloperidol group vs six in the placebo group ) . No patient had a serious adverse event related to the study drug . INTERPRETATION These results do not support the hypothesis that haloperidol modifies duration of delirium in critically ill patients . Although haloperidol can be used safely in this population of patients , pending the results of trials in progress , the use of intravenous haloperidol should be reserved for short-term management of acute agitation . FUNDING National Institute for Health Research The purpose of this r and omized controlled study was to determine the effects of music listening on acute confusion that is common in older adults after hip or knee surgery . A control group demonstrated greater decreases in cognition on the first postoperative day compared to a music-listening group ( F = 8.448 , p = .009 ) . In the 3-day postoperative period , the cognitive status of the control group improved ; on the third postoperative day , there was no significant difference between the two groups ( F = 3.52 , p = .075 ) . The music-listening group had higher scores on the NEECHAM Acute Confusion Scale across the 3-day postoperative period ( F = 7.28 , p = .014 ) OBJECTIVES Delirium ( or acute confusional state ) affects 35 % to 65 % of patients after hip-fracture repair , and has been independently associated with poor functional recovery . We performed a r and omized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture . DESIGN Prospect i ve , r and omized , blinded . SETTING Inpatient academic tertiary medical center . PARTICIPANTS 126 consenting patients 65 and older ( mean age 79 + /- 8 years , 79 % women ) admitted emergently for surgical repair of hip fracture . MEASUREMENTS Detailed assessment through interviews with patients and design ated proxies and review of medical records was performed at enrollment to ascertain prefracture status . Subjects were then r and omized to proactive geriatrics consultation , which began preoperatively or within 24 hours of surgery , or " usual care . " A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol . To ascertain study outcomes , all subjects underwent daily , blinded interviews for the duration of their hospitalization , including the Mini-Mental State Examination ( MMSE ) , the Delirium Symptom Interview ( DSI ) , and the Memorial Delirium Assessment Scale ( MDAS ) . Delirium was diagnosed using the Confusion Assessment Method ( CAM ) algorithm . RESULTS The 62 patients r and omized to geriatrics consultation were not significantly different ( P>.1 ) from the 64 usual-care patients in terms of age , gender , prefracture dementia , comorbidity , type of hip fracture , or type of surgical repair . Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively . A mean of 10 recommendations were made throughout the duration of the hospitalization , with 77 % adherence by the orthopedics team . Delirium occurred in 20 /62 ( 32 % ) intervention patients , versus 32 / 64 ( 50 % ) usual-care patients ( P = .04 ) , representing a relative risk of 0.64 ( 95 % confidence interval ( CI ) = 0.37 - 0.98 ) for the consultation group . One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group . There was an even greater reduction in cases of severe delirium , occurring in 7/ 60 ( 12 % ) of intervention patients and 18 / 62 ( 29 % ) of usual-care patients , with a relative risk of 0.40 ( 95 % CI = 0.18 - 0.89 ) . Despite this reduction in delirium , length of stay did not significantly differ between intervention and usual-care groups ( median + /- interquartile range = 5 + /- 2 days in both groups ) , likely because protocol s and pathways predetermined length of stay . In subgroup analyses , geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living ( ADL ) functional impairment . CONCLUSIONS Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair . Geriatrics consultation reduced delirium by over one-third , and reduced severe delirium by over one-half . Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients Objectives To develop and vali date a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers . Design Observational multicentre study . Setting Five intensive care units in the Netherl and s ( two university hospitals and three university affiliated teaching hospitals ) . Participants 3056 intensive care patients aged 18 years or over . Main outcome measure Development of delirium ( defined as at least one positive delirium screening ) during patients ’ stay in intensive care . Results The model was developed using 1613 consecutive intensive care patients in one hospital and temporally vali date d using 549 patients from the same hospital . For external validation , data were collected from 894 patients in four other hospitals . The prediction ( PRE-DELIRIC ) model contains 10 risk factors — age , APACHE-II score , admission group , coma , infection , metabolic acidosis , use of sedatives and morphine , urea concentration , and urgent admission . The model had an area under the receiver operating characteristics curve of 0.87 ( 95 % confidence interval 0.85 to 0.89 ) and 0.86 after bootstrapping . Temporal validation and external validation result ed in areas under the curve of 0.89 ( 0.86 to 0.92 ) and 0.84 ( 0.82 to 0.87 ) . The pooled area under the receiver operating characteristics curve ( n=3056 ) was 0.85 ( 0.84 to 0.87 ) . The area under the curve for nurses ’ and physicians ’ predictions ( n=124 ) was significantly lower at 0.59 ( 0.49 to 0.70 ) for both . Conclusion The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value . Clinical prediction by nurses and physicians performed significantly worse . The model allows for early prediction of delirium and initiation of preventive measures . Trial registration Clinical trials NCT00604773 ( development study ) and NCT00961389 ( validation study ) BACKGROUND Since in hospitalized older patients delirium is associated with poor outcomes , we evaluated the effectiveness of a multicomponent strategy for the prevention of delirium . METHODS We studied 852 patients 70 years of age or older who had been admitted to the general-medicine service at a teaching hospital . Patients from one intervention unit and two usual-care units were enrolled by means of a prospect i ve matching strategy . The intervention consisted of st and ardized protocol s for the management of six risk factors for delirium : cognitive impairment , sleep deprivation , immobility , visual impairment , hearing impairment , and dehydration . Delirium , the primary outcome , was assessed daily until discharge . RESULTS Delirium developed in 9.9 percent of the intervention group as compared with 15.0 percent of the usual-care group , ( matched odds ratio , 0.60 ; 95 percent confidence interval , 0.39 to 0.92 ) . The total number of days with delirium ( 105 vs. 161 , P=0.02 ) and the total number of episodes ( 62 vs. 90 , P=0.03 ) were significantly lower in the intervention group . However , the severity of delirium and recurrence rates were not significantly different . The overall rate of adherence to the intervention was 87 percent , and the total number of targeted risk factors per patient was significantly reduced . Intervention was associated with significant improvement in the degree of cognitive impairment among patients with cognitive impairment at admission and a reduction in the rate of use of sleep medications among all patients . Among the other risk factors per patient there were trends toward improvement in immobility , visual impairment , and hearing impairment . CONCLUSIONS The risk-factor intervention strategy that we studied result ed in significant reductions in the number and duration of episodes of delirium in hospitalized older patients . The intervention had no significant effect on the severity of delirium or on recurrence rates ; this finding suggests that primary prevention of delirium is probably the most effective treatment strategy OBJECTIVES To investigate whether an education program and a reorganization of nursing and medical care improved the outcome for older delirious patients . DESIGN Prospect i ve intervention study . SETTING Department of General Internal Medicine , Sundsvall Hospital , Sweden . PARTICIPANTS Four hundred patients , aged 70 and older , consecutively admitted to an intervention or a control ward . INTERVENTION The intervention consisted of staff education focusing on the assessment , prevention , and treatment of delirium and on caregiver-patient interaction . Reorganization from a task-allocation care system to a patient-allocation system with individualized care . MEASUREMENTS The patients were assessed using the Organic Brain Syndrome Scale and the Mini-Mental State Examination on Days 1 , 3 , and 7 after admission . Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , criteria . RESULTS Delirium was equally common on the day of admission at the two wards , but fewer patients remained delirious on Day 7 on the intervention ward ( n=19/63 , 30.2 % vs 37/62 , 59.7 % , P=.001 ) . The mean length of hospital stay+/-st and ard deviation was significantly lower on the intervention ward then on the control ward ( 9.4+/-8.2 vs 13.4+/-12.3 days , P<.001 ) especially for the delirious patients ( 10.8+/-8.3 vs 20.5+/-17.2 days , P<.001 ) . Two delirious patients in the intervention ward and nine in the control ward died during hospitalization ( P=.03 ) . CONCLUSION This study shows that a multifactorial intervention program reduces the duration of delirium , length of hospital stay , and mortality in delirious patients OBJECTIVES To ( 1 ) reduce deep sedation and delirium to permit mobilization , ( 2 ) increase the frequency of rehabilitation consultations and treatments to improve patients ' functional mobility , and ( 3 ) evaluate effects on length of stay . DESIGN Seven-month prospect i ve before/after quality improvement project . SETTING Sixteen-bed medical intensive care unit ( MICU ) in academic hospital . PARTICIPANTS 57 patients mechanically ventilated 4 days or longer . INTERVENTION A multidisciplinary team focused on reducing heavy sedation and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines . MAIN OUTCOME MEASURES Sedation and delirium status , rehabilitation treatments , functional mobility . RESULTS Compared with before the quality improvement project , benzodiazepine use decreased markedly ( proportion of MICU days that patients received benzodiazepines [ 50 % vs 25 % , P=.002 ] ) , with lower median daily sedative doses ( 47 vs 15 mg midazolam equivalents [ P=.09 ] and 71 vs 24 mg morphine equivalents [ P=.01 ] ) . Patients had improved sedation and delirium status ( MICU days alert [ 30 % vs 67 % , P<.001 ] and not delirious [ 21 % vs 53 % , P=.003 ] ) . There were a greater median number of rehabilitation treatments per patient ( 1 vs 7 , P<.001 ) with a higher level of functional mobility ( treatments involving sitting or greater mobility , 56 % vs 78 % , P=.03 ) . Hospital administrative data demonstrated that across all MICU patients , there was a decrease in intensive care unit and hospital length of stay by 2.1 ( 95 % confidence interval : 0.4 - 3.8 ) and 3.1 ( 0.3 - 5.9 ) days , respectively , and a 20 % increase in MICU admissions compared with the same period in the prior year . CONCLUSIONS Using a quality improvement process , intensive care unit delirium , physical rehabilitation , and functional mobility were markedly improved and associated with decreased length of stay BACKGROUND A wide variability in the approach towards delirium prevention and treatment in the critically ill results from the dearth of prospect i ve r and omised studies . METHODS We launched a two-stage prospect i ve observational study to assess delirium epidemiology , risk factors and impact on patient outcome , by enrolling all patients admitted to our Intensive Care Unit ( ICU ) over a year . The first step - from January to June 2008 was the observational phase , whereas the second one from July to December 2008 was interventional . All the patients admitted to our ICU were recruited but those with pre-existing cognitive disorders , dementia , psychosis and disability after stroke were excluded from the data analysis . Delirium assessment was performed according with Confusion Assessment Method for the ICU twice per day after sedation interruption . During phase 2 , patients underwent both a re-orientation strategy and environmental , acoustic and visual stimulation . RESULTS We admitted a total of respectively 170 ( I-ph ) and 144 patients ( II-ph ) . The delirium occurrence was significantly lower in ( II-ph ) 22 % vs. 35 % in ( I-ph ) ( P=0.020 ) . A Cox 's Proportional Hazard model found the applied reorientation strategy as the strongest protective predictors of delirium : ( HR 0.504 , 95 % C.I. 0.313 - 0.890 , P=0.034 ) , whereas age ( HR 1.034 , 95 % CI : 1.013 - 1.056 , P=0.001 ) and sedation with midazolam plus opiate ( HR 2.145 , 95 % CI : 2.247 - 4.032 , P=0.018 ) were negative predictors . CONCLUSION A timely reorientation strategy seems to be correlated with significantly lower occurrence of delirium OBJECTIVES To develop and test the effect of a nurse-led interdisciplinary intervention program for delirium on the incidence and course ( severity and duration ) of delirium , cognitive functioning , functional rehabilitation , mortality , and length of stay in older hip-fracture patients . DESIGN Longitudinal prospect i ve before/after design ( sequential design ) . SETTING The emergency room and two traumatological units of an academic medical center located in an urban area in Belgium . PARTICIPANTS 60 patients in an intervention cohort ( 81.7 % females , median age = 82 , interquartile range ( IQR ) = 13 ) and another 60 patients in a usual care/nonintervention cohort ( 80 % females , median age = 80 , IQR = 12 ) . INTERVENTION ( 1 ) Education of nursing staff , ( 2 ) systematic cognitive screening , ( 3 ) consultative services by a delirium re source nurse , a geriatric nurse specialist , or a psychogeriatrician , and ( 4 ) use of a scheduled pain protocol . MEASUREMENTS All patients were monitored for signs of delirium , as measured by the Confusion Assessment Method ( CAM ) . Severity of delirium was assessed using a variant of the CAM . Cognitive and functional status were measured by the Mini-Mental State Examination ( MMSE ) ( including subscales of memory , linguistic ability , concentration , and psychomotor executive skills ) and the Katz Index of activities of daily living ( ADLs ) , respectively . RESULTS Although there was no significant effect on the incidence of delirium ( 23.3 % in the control vs 20.0 % in the intervention cohort ; P = .82 ) , duration of delirium was shorter ( P = .03 ) and severity of delirium was less ( P = .0049 ) in the intervention cohort . Further , clinical ly higher cognitive functioning was observed for the delirious patients in the intervention cohort compared with the nonintervention cohort . Additionally , a trend toward decreased length of stay postoperatively was noted for the delirious patients in the intervention cohort . Despite these positive intervention effects , no effect on ADL rehabilitation was found . Results for risk of mortality were inconclusive . CONCLUSIONS This study demonstrated the beneficial effects of an intervention program focusing on early recognition and treatment of delirium in older hip-fracture patients and confirms the reversibility of the syndrome in view of the delirium 's duration and severity Bright light therapy is a method of maintaining or restoring the natural circadian rhythm by assisting daytime awakening using bright lights . Postoperative delirium is one of the potential complications encountered by patients receiving postoperative care in the intensive care unit ( ICU ) , but there have been no studies on the use of light for the prevention of postoperative delirium . The objective of this study was to examine whether the circadian rhythms of patients after surgery for oesophageal cancer can be adjusted and whether the postoperative delirium crisis rate can be reduced by bright light therapy . The subjects were 11 patients operated on for oesophageal cancer in Osaka University Hospital . After informed consent was obtained , they were divided into a study group and a control group by a r and om sampling method . After removal of the endotracheal tube , the study group was exposed to light . The light intensity was about 5000lx immediately before the eyes , and the distance from the light source was about 100 cm . The control group was placed in a natural lighting environment after extubation . In both groups , the rhythms of physical activities and autonomic activities were monitored after surgery , and delirium was evaluated . A significant difference was observed in the delirium score between the study group and control group on the morning of day 3 of bright light therapy by the Mann-Whitney U-test ( P=0.014 ) . The study group could begin ambulation about 2 days earlier than the control group . Bright light therapy may reduce the rate of postoperative delirium and make early ambulation possible . However , our study involved a very small sample size . We want to increase the sample in the future after having review ed clinical application methods Objectives : To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery . Design : Prospect i ve , r and omized , double-blind , and placebo-controlled trial in two centers . Setting : Intensive care units of two large tertiary teaching hospitals . Patients : Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery . Intervention : Haloperidol ( 0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs ; n = 229 ) or placebo ( n = 228 ) was r and omly administered from intensive care unit admission . Measures : The primary end point was the incidence of delirium within the first 7 days after surgery . Secondary end points included time to onset of delirium , number of delirium-free days , length of intensive care unit stay , all-cause 28-day mortality , and adverse events . Delirium was assessed using the confusion assessment method for the intensive care unit . Results : The incidence of delirium during the first 7 days after surgery was 15.3 % ( 35/229 ) in the haloperidol group and 23.2 % ( 53/228 ) in the control group ( p = .031 ) . The mean time to onset of delirium and the mean number of delirium-free days were significantly longer ( 6.2 days [ 95 % confidence interval 5.9−6.4 ] vs. 5.7 days [ 95 % confidence interval 5.4−6.0 ] ; p = .021 ; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days ; p = .027 , respectively ) , whereas the median length of intensive care unit stay was significantly shorter ( 21.3 hrs [ 95 % confidence interval 20.3−22.2 ] vs. 23.0 hrs [ 95 % confidence interval 20.9–25.1 ] ; p = .024 ) in the haloperidol group than in the control group . There was no significant difference with regard to all-cause 28-day mortality between the two groups ( 0.9 % [ 2/229 ] vs. 2.6 % [ 6/228 ] ; p = .175 ) . No drug-related side effects were documented . Conclusions : For elderly patients admitted to intensive care unit after noncardiac surgery , short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium . The therapy was well-tolerated OBJECTIVES To analyze the effectiveness of a multicomponent intervention integrated into daily practice for the prevention of in-hospital delirium in elderly patients . DESIGN Controlled study comparing an intervention in a geriatric unit ( GI ) with usual care in two internal medicine services ( UC ) . SETTING University hospital in Madrid , Spain . PARTICIPANTS Five hundred forty-two consecutive patients ( 170 GI , 372 UC ) , aged 70 and older , with any of the risk criteria for delirium ( cognitive impairment , visual impairment , acute disease severity , dehydration ) . INTERVENTION Educational measures and specific actions in seven risk areas ( orientation , sensory impairment , sleep , mobilization , hydration , nutrition , drug use ) . Daily monitoring of adherence . MEASUREMENTS Baseline characteristics , risk factors for delirium , and quality care indicators were analyzed . The primary endpoint was incidence of delirium assessed daily . The secondary endpoint was functional decline , defined as loss of independence in any of the activities of daily living . The intervention effect was evaluated using logistic regression analysis . RESULTS Delirium affected 11.7 % of the GI group and 18.5 % of the UC group ( P=.04 ) . After adjustment for confounders , the intervention was associated with lower incidence of delirium ( odds ratio=0.4 , 95 % confidence interval=0.24 - 0.77 ; P=.005 ) . In the patients who experienced delirium , severity , length , and recurrence of episodes were similar in both groups . Adherence to the intervention protocol s was 75.7 % . The intervention reduced the rate of functional decline ( 45.5 % in GI vs 56.3 % in UC , P=.03 ) and improved other quality indicators ( e.g. , mobilization and physical restraints reduction ) . CONCLUSION A multicomponent , nonpharmacological intervention integrated into routine practice reduces delirium during hospitalization in older patients , improves quality of care , and can be implemented without additional re sources in a public healthcare system BACKGROUND Delirium is a common problem for frail , older patients in hospital and a marker of poor outcome and mortality . The aim of this study was to test a volunteer-mediated delirium prevention programme for efficacy , cost-effectiveness and sustainability on an Australian geriatric ward . METHODS Two controlled before- and -after studies were conducted . In study 1 , 37 patients ( > 70 years , admitted to the geriatric wards ) were enrolled during 5 months in 2003 for intensive individual study . Twenty-one patients received usual care and 16 patients received the volunteer-mediated intervention of daily orientation , therapeutic activities , feeding and hydration assistance , vision and hearing protocol s. In study 2 , we examined the effects of a general implementation for the whole department by measuring use of assistants in nursing , who were employed for individual nursing of delirious patients . RESULTS In study 1 , we found a lower incidence ( intervention vs control , 6.3 % vs 38 % ; P = 0.032 ) and lower severity of delirium ( 1.2 vs 5.1 ; P = 0.045 ) . There was a trend towards decreased duration of delirium ( 5.0 vs 12.5 ; P = 0.64 ) . In study 2 , use of assistants in nursing was reduced by 314 h per month suggesting a total annual saving of 129,186 Australian dollars for the hospital . CONCLUSION The programme prevents delirium and improves outcomes for elderly in patients . Cost-effectiveness supports the continuation of the programme and extension to other geriatric units |
2,674 | 25,180,899 | From the available evidence , we are unable to demonstrate or refute a favourable effect of CAS for cruciate ligament reconstructions of the knee compared with conventional reconstructions .
However , the currently available evidence does not indicate that CAS in knee ligament reconstruction improves outcome . | BACKGROUND Anterior cruciate ligament ( ACL ) reconstruction is one of the most frequently performed orthopaedic procedures .
The most common technical cause of reconstruction failure is graft malpositioning .
Computer-assisted surgery ( CAS ) aims to improve the accuracy of graft placement .
Although posterior cruciate ligament ( PCL ) injury and reconstruction are far less common , PCL reconstruction has comparable difficulties relating to graft placement .
This is an up date of a Cochrane review first published in 2011 .
OBJECTIVES To assess the effects of computer-assisted reconstruction surgery versus conventional operating techniques for ACL or PCL injuries in adults . | Introduction Correct placement of both tibial and femoral tunnels is one of the main factors for a favorable clinical outcome after anterior cruciate ligament ( ACL ) reconstruction . We used an original system of computer assisted surgery ( CAS ) . The system , based on fluoroscopic guidance combined with special graphical software of image analyzing , showed to the surgeon , before drilling , the recommended placement of tibial and femoral tunnel centers . We compared the first anatomical and clinical results of this procedure to the usual one single incision technique . Material s and methods We conducted a prospect i ve study on 73 patients ; 37 patients were operated on with CAS and 36 without CAS , by the same senior surgeon . The mean age was 27 years for both groups . Every patient was review ed at an average of 2.2 years ( range 1–4.5 ) by an independent observer , using IKDC scoring system , KT-1000 , and passive stress radiographs . Results Time between ACL rupture and reconstruction averaged 30 months for both groups . CAS needed 9.3 min extra surgery time . Clinical evaluation was grade d from A to C as per the IKDC scoring system : 67.6 % A , 29.7 % B , 2.7 % C with CAS ; and 60 % A , 37.1 % B , 2.9 % C without CAS . IKDC subjective knee evaluation score averaged 89.7 with CAS and 89.5 without CAS . Pre operative KT-1000 maxi manual differential laxity averaged 7 . At revision time , all the patients after CAS had a differential laxity less than 2 and 97.7 % without CAS . Stress X-rays differential laxity averaged 2.4 mm with CAS and 3 mm without CAS . The area of dispersion of the tunnels ’ center was smaller on the femoral side using the CAS method . There was no statistically significant difference between both groups using IKDC score , KT-1000 and passive stress radiographs . Conclusions The CAS method provided a more accurate and reproducible tunnels placement without clinical significant effect BACKGROUND Accurate and precise tunnel placement is critical to the success of anterior cruciate ligament ( ACL ) reconstruction . A new development , computer-assisted surgery , aids in placement of the ACL bone tunnels during surgery . Our hypothesis was that computer-assisted ACL reconstruction would allow more accurate and precise tunnel placement compared with conventional surgery . METHODS In a prospect i ve , double-blind , r and omized clinical study , 100 patients eligible for ACL reconstruction with a transtibial technique were stratified by surgeon and r and omized to either conventional or computer-assisted surgery . Measurement of femoral and tibial tunnel placement with use of three-dimensional computed tomography ( CT ) was used as the primary outcome to compare conventional ACL surgery with computer-assisted surgery . RESULTS The placement of the femoral tunnel did not differ between groups ( mean , 39.7 % of the proximal-distal distance on the intracondylar axis [ Blumensaat line ] in the conventional group compared with 39.0 % in the computer-assisted surgery group ; p = 0.70 ) . The anterior-posterior positioning of the tibial tunnel on the tibial plateau also did not differ significantly ( 38.9 % in the conventional group compared with 38.2 % in the computer-assisted surgery group ; p = 0.58 ) . There was no significant difference in the precision of either the femoral or the tibial tunnel placement between the two groups . CONCLUSIONS There was no significant difference in either the accuracy or the precision of tunnel placement between conventional and computer-assisted ACL reconstruction Existing published knee rating systems that assess sports participation , knee function , and subjective symptomatology following ligamentous surgical procedures were analyzed . Major errors in question naire design and data reduction have led to invalid conclusions . A question naire containing a minimum set of rating criteria was formulated to validly assess athletic participation before and after treatment or surgery . Select questions and a data reduction format were established to assess the intensity of sports participation , changes in sports participation , the variables that produced the changes , self-assessed functional limitations , and the ability to participate in different types of sports . A clinical trial of the question naire was performed on 59 patients . An interview conducted upon completion of the question naire enabled the authors to detect difficulties or inconsistencies in the responses to the questions . The design format described in this report forms the basis for a subjective evaluation of ligamentous surgery . A st and ard format for analysis of sports participation and knee function is proposed to aid investigators in comparing variations in clinical results PURPOSE The purpose of this prospect i ve r and omized study was to assess biomechanical , radiographic , and functional results after single-bundle anterior cruciate ligament ( ACL ) reconstruction by use of a navigation system . METHODS ACL reconstruction was performed by use of the OrthoPilot navigation system ( B. Braun-Aesculap , Tuttlingen , Germany ) in 40 patients ( group 1 ) ; and in another 40 patients , surgery was done by the st and ard manual targeting technique ( group 2 ) . The anterior laxity was measured with a KT-1000 arthrometer ( MEDmetric , San Diego , CA ) . Femoral and tibial tunnel position was evaluated radiologically according to the method described by Bernard and Hertel and by Harner et al. , respectively . The question naire-based Lysholm and International Knee Documentation Committee scales were included to compare the functional state in both groups . RESULTS The knees in group 1 were as stable as those in group 2 during the arthrometer testing , with a lower value of dispersion . The postoperative Lysholm and International Knee Documentation Committee scores had the same value in both groups . Statistical differences existed with regard to anterior-posterior femoral tunnel placement when the navigated and st and ard techniques were compared ; in the navigated group , more exact results were found . No significant complications were observed . CONCLUSIONS The only difference that we found between the navigated and st and ard groups was in radiographic tunnel position measurement . The computer-assisted navigation technique in our study result ed in more accurate tunnel placement in the femur ( but not the tibia ) than the traditional arthroscopic technique . However , the performed st and ard radiographic measurements are of limited precision in principle . Functional scales and stability tests gave similar results in both groups . LEVEL OF EVIDENCE Level I , therapeutic study PURPOSE The purpose of this study was to evaluate the benefits of computer navigation on tunnel placement during anterior cruciate ligament reconstruction . METHODS A prospect i ve , r and omized , controlled study comparing computer navigation with manual operation was performed between December 2003 and April 2004 . We assigned 20 patients to the computer navigation group and 20 patients to the manual navigation group . Surgery was performed by use of a patellar tendon autograft with press-fit fixation . A lateral radiograph of the knee at maximum extension was used to determine the exact position of the tibial tunnel at 4 days postoperatively . Outcomes were evaluated with International Knee Documentation Committee 2000 , Tegner , and Lysholm scoring . There was an additional magnetic resonance imaging ( MRI ) evaluation of tunnel placement and graft quality at the most recent follow-up , approximately 24 months after surgery . RESULTS The postoperative radiographs and 2-year postoperative MRI scans showed no differences between groups for tibial or femoral tunnel placement . In both groups the mean tibial tunnel placement was 46 % of the maximal diameter of the tibia . There were no significant differences between groups for objective and subjective outcomes scoring . Although some qualitative differences existed between groups with respect to MRI graft appearance at 2 years , this had no correlation with overall results . CONCLUSIONS No significant differences were found between computer-assisted and manually navigated anterior cruciate ligament reconstruction with regard to tunnel placement and clinical results at a mean of 2 years postoperatively . LEVEL OF EVIDENCE Level I , r and omized , single-blinded , controlled trial Background Poor outcome in anterior cruciate ligament reconstruction is often related to tunnel position . Hypothesis Improving accuracy of the tunnel position will lead to improved outcome . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Sixty patients were r and omized to either st and ard instrumentation or computer-assisted guides to position the tibial and femoral tunnels . The results were evaluated on clinical outcome based on International Knee Documentation Committee form ( laxity ) and radiologic assessment : radiologic Lachman ( Telos at 150 and 200 N ) and analysis of the tunnel positions . Results International Knee Documentation Committee laxity was level A in 22 knees in the conventional group ( mean , 1.5 mm at 200 N ) compared with 26 navigated knees ( mean laxity , 1.3 mm ; P= .49 ) . Laxity was less than 2 mm in 96.7 % of the navigated group and 83 % of the conventional group ( P= .292 ) . The variability of laxity in the navigated group was significantly less than in the conventional group , with the st and ard deviation of the navigated group being smaller than that in the conventional group ( P= .0003 at 150 N and .0005 at 200 N Telos ) . A significant difference ( P= .03 ) was found between the groups in the ATB value ( distance between the projection of the Blumensaat line on the tibial plateau and the anterior edge of the tibial tunnel ) , characterizing the sagittal position of the tibial tunnel ( negative ATB values imply graft impingement in extension ) . In the conventional group , mean ATB was –0.2 ( –5 to + 4 ) , whereas it was 0.4 ( 0 to 3 ) in the navigated patients . There were no negative ATB values in the navigated group . Conclusion This study confirms that the accuracy and consistency of tibial tunnel position can be improved by the use of computer-assisted navigation and that the clinical result in terms of laxity is more reliable Background Next to graft fixation , correct positioning of the tibial and femoral tunnel is a deciding factor for the clinical result of anterior cruciate ligament reconstruction surgery . Computer-assisted navigation has been proposed as a method to improve tunnel positioning . Purpose To examine the differences in tibial tunnel placement between cruciate ligament operations using manual and computer-assisted navigation . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Between December 2003 and April 2004 , 53 athletes underwent anterior cruciate ligament reconstruction surgery with arthroscopic press-fit technique . The first group ( group N ; 24 athletes ) were operated on with the aid of a navigation system ( OrthoPilot , Aesculap AG & Co. KG , Braun ) , and the second group ( group M ; 29 athletes ) were “ manually ” operated on . A lateral radiograph of the knee at maximum extension was used to determine the exact position of the tibial tunnel four days postoperatively . In the measurements , the anterior and posterior boundaries of the tibial tunnel , as well as the center of the tibial tunnel in relation to the maximum tibia anteroposterior diameter were evaluated ( indicated in percent ) . An analysis of the tibial tunnel position proportional to the slope of the intercondylar roof was done to determine intercondylar impingement ( method according to Howell ) . The centers of the tibial tunnels were compared with the “ optimal ” position noted in previous studies . The st and ard deviation was determined for both groups to determine the variance of placement . Results The anterior tibial tunnel border was 19.4 mm in group M ( 29.7 % ) and 21.2 mm in group N ( 32.2 % ) ( P=.18 ) . The center of the tibial tunnel was located at 24.6 mm in group M ( 35.6 % ) and at 26.6 mm in group N ( 40.3 % ) ( P=.19 ) . In group M , the posterior tibial tunnel position was located at 30.2 mm ( 46.2 % ) , and in group N at 32.2 mm ( 49.1 % ) ( P=.21 ) . When comparing the centers of the tibial tunnels with the optimal 44 % found in previous studies , the value for group M ( 37.6 % ) varied significantly , while group N ( 40.5 % ) did not . However , there was no significant difference in the range variance for either group ; the st and ard deviation was 6.9 % ( 4.3 mm ) for group M and 5.9 % ( 3.5 mm ) for group N. One athlete showed moderate impingement in group N , and two athletes in group M. Conclusion Assisted navigation offers good support for correct placement of the tibial tunnel , although experienced surgeons can achieve essentially the same positioning as surgeons using computer-assisted navigation . Whether it is advisable to implement this procedure in daily surgical routine should be decided based on clinical results 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 |
2,675 | 24,596,021 | Plain Language summary Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria What is uncomplicated malaria and how might artesunate-pyronaridine work Uncomplicated malaria is the milder form of malaria which usually causes fever , with or without headache , tiredness , muscle pains , abdominal pains , nausea , and vomiting .
If left untreated , uncomplicated malaria can rapidly develop into severe malaria with kidney failure , fitting , unconsciousness , and eventually death .
Plasmodium falciparum is the most common parasite causing malaria in sub-Saharan Africa and causes most of the severe malaria worldwide .
Serious adverse events were rare in people treated with either artesunate-pyronaridine or other ACTs .
However , short-lasting liver toxicity was more frequent in people treated with artesunate-pyronaridine than with the other antimalarials ( moderate quality evidence ) .
Authors ' conclusions Artesunate-pyronaridine performed well compared to the other two ACT with which it has been compared , but further studies in African and Asian children are required to help clarify whether this combination is an option for first-line treatment | Background The World Health Organization ( WHO ) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy ( ACT ) .
ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action .
Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia , and is currently being evaluated as a partner drug for artesunate .
Objectives To evaluate the efficacy and safety of artesunate-pyronaridine compared to alternative ACTs for treating people with uncomplicated P. falciparum malaria .
The World Health Organization currently recommends countries use one of five different artemisinin-based combination therapies ( ACTs ) to treat malaria .
These combinations contain an artemisinin component ( artemether , dihydroartemisinin , or artesunate ) , which works quickly to clear the parasite from the person 's blood , and a longer-acting drug which clears the remaining parasites from the blood and may prevent new Plasmodium infections for several weeks .
Artesunate plus pyronaridine is a new combination and in this review we evaluate its effectiveness and safety compared to the other ACTs . | Background New antimalarials are needed for P. vivax and P. falciparum malaria . This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria . Methods and Findings This phase III r and omized , double-blind , non-inferiority trial included five centers across Cambodia , Thail and , India , and Indonesia . In a double-dummy design , patients ( aged > 3–≤60 years ) with microscopically confirmed P. vivax mono-infection were r and omized ( 1∶1 ) to receive pyronaridine-artesunate ( target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg ) or chloroquine ( st and ard dose ) once daily for three days . Each treatment group included 228 r and omized patients . Outcomes for the primary endpoint , Day-14 cure rate in the per- protocol population , were 99.5 % , ( 217/218 ; 95%CI 97.5 , 100 ) with pyronaridine-artesunate and 100 % ( 209/209 ; 95%CI 98.3 , 100 ) with chloroquine . Pyronaridine was non-inferior to chloroquine : treatment difference −0.5 % ( 95%CI −2.6 , 1.4 ) , i.e. , the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10 % . Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21 , 28 , 35 and 42 . Parasite clearance time was shorter with pyronaridine-artesunate ( median 23.0 h ) versus chloroquine ( 32.0 h ; p<0.0001 ) , as was fever clearance time ( median 15.9 h and 23.8 h , respectively ; p = 0.0017 ) . Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5 % with pyronaridine-artesunate , 6.1 % with chloroquine ( p = 0.048 , log-rank test ) . Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8 % and 12.4 % , respectively ( p = 0.022 , log rank test ) . There were no deaths . Adverse events occurred in 92/228 ( 40.4 % ) patients with pyronaridine-artesunate and 72/228 ( 31.6 % ) with chloroquine . Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate . Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine . As pyronaridine-artesunate is also efficacious against P. falciparum malaria , this combination has potential utility as a global antimalarial drug . Trial registration Clinical trials.gov Background Pyronaridine-artesunate ( PA ) is indicated for the treatment of acute uncomplicated Plasmodium falciparum and Plasmodium vivax malaria . Methods Individual patient data on safety outcomes were integrated from six r and omized clinical trials conducted in Africa and Asia in patients with microscopically confirmed P. falciparum ( five studies ) or P. vivax ( one study ) malaria . Efficacy against P. falciparum was evaluated across three Phase III clinical trials . Results The safety population included 2,815 patients r and omized to PA , 1,254 to comparators : mefloquine + artesunate ( MQ + AS ) , artemether-lumefantrine ( AL ) , or chloroquine . All treatments were generally well tolerated . Adverse events occurred in 57.2 % ( 1,611/2,815 ) of patients with PA versus 51.5 % ( 646/1,254 ) for comparators , most commonly ( PA ; comparators ) : headache ( 10.6 % ; 9.9 % ) , cough ( 5.9 % ; 5.6 % ) and anaemia ( 4.5 % ; 2.9 % ) . Serious averse events were uncommon for all treatments ( 0–0.7 % ) . Transient increases in alanine aminotransferase and aspartate aminotransferase were observed with PA but did not lead to any clinical sequelae . For P. falciparum malaria , day-28 PCR-corrected adequate clinical and parasitological response with PA was 93.6 % ( [ 1,921/2,052 ] 95 % CI 92.6 , 94.7 ) in the intent-to-treat population and 98.5 % ( [ 1,852/1,880 ] 95 % CI 98.0 , 99.1 ) in the per- protocol population . Median parasite clearance time was 24.1 h with PA , 31.9 h with MQ + AS , and 24.0 h with AL . Median fever clearance time was 15.5 h with PA , 15.8 h with MQ + AS , and 14.0 h with AL . By day 42 , P. falciparum gametocytes had declined to near zero for all treatments . Conclusions Pyronaridine-artesunate was well tolerated with no safety concerns with the exception of mostly mild transient rises in transaminases . Efficacy was high and met the requirements for use as first-line therapy . Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes . Trial registration Clinical trials.gov : NCT00331136 ; NCT00403260 ; NCT00422084 ; NCT00440999 ; NCT00541385 ; BACKGROUND Pyronaridine-artesunate is an artemisinin-based combination therapy under evaluation for the treatment of Plasmodium falciparum and P. vivax malaria . METHODS We conducted a phase 3 , open-label , multicenter , noninferiority trial that included 1271 patients between 3 and 60 years of age from Asia ( 81.3 % ) or Africa ( 18.7 % ) with microscopically confirmed , uncomplicated P. falciparum malaria . Patients underwent r and omization for treatment with a fixed-dose combination of 180 mg of pyronaridine and 60 mg of artesunate or with 250 mg of mefloquine plus 100 mg of artesunate . Doses were calculated according to body weight and administered once daily for 3 days . RESULTS Pyronaridine-artesunate was noninferior to mefloquine plus artesunate for the primary outcome : adequate clinical and parasitologic response in the per- protocol population on day 28 , corrected for reinfection with the use of polymerase-chain-reaction ( PCR ) genotyping . For this outcome , efficacy in the group receiving pyronaridine-artesunate was 99.2 % ( 743 of 749 patients ; 95 % confidence interval [ CI ] , 98.3 to 99.7 ) and that in the group receiving mefloquine plus artesunate was 97.8 % ( 360 of 368 patients ; 95 % CI , 95.8 to 99.1 ) , with a treatment difference of 1.4 percentage points ( 95 % CI , 0.0 to 3.5 ; P=0.05 ) . In the intention-to-treat population , efficacy on day 42 in the group receiving pyronaridine-artesunate was 83.1 % ( 705 of 848 patients ; 95 % CI , 80.4 to 85.6 ) and that in the group receiving mefloquine plus artesunate was 83.9 % ( 355 of 423 patients ; 95 % CI , 80.1 to 87.3 ) . In Cambodia , where there were 211 study patients , the median parasite clearance time was prolonged for both treatments : 64 hours versus 16.0 to 38.9 hours in other countries ( P<0.001 , on the basis of Kaplan-Meier estimates ) . Kaplan-Meier estimates of the recrudescence rate in the intention-to-treat population in Cambodia until day 42 were higher with pyronaridine-artesunate than with mefloquine plus artesunate ( 10.2 % [ 95 % CI , 5.4 to 18.6 ] vs. 0 % ; P=0.04 as calculated with the log-rank test ) , but similar for the other countries combined ( 4.7 % [ 95 % CI , 3.3 to 6.7 ] and 2.8 % [ 95 % CI , 1.5 to 5.3 ] , respectively ; P=0.24 ) . Elevated levels of aminotransferases were observed in those receiving pyronaridine-artesunate . Two patients receiving mefloquine plus artesunate had seizures . CONCLUSIONS Fixed-dose pyronaridine-artesunate was efficacious in the treatment of uncomplicated P. falciparum malaria . In Cambodia , extended parasite clearance times were suggestive of in vivo resistance to artemisinin . ( Funded by Shin Poong Pharmaceutical Company and the Medicines for Malaria Venture ; Clinical Trials.gov number , NCT00403260 . ) Background Children are most vulnerable to malaria . A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria . Methods This phase III , multi-center , comparative , open-label , parallel-group , controlled clinical trial included patients aged ≤12 years , bodyweight ≥5 to < 25 kg , with a reported history of fever at inclusion or in the previous 24 h and microscopically-confirmed uncomplicated P. falciparum malaria . Patients were r and omized ( 2:1 ) to pyronaridine-artesunate granules ( 60/20 mg ) once daily or artemether-lumefantrine crushed tablets ( 20/120 mg ) twice daily , both dosed by bodyweight , orally ( liquid suspension ) for three days . Results Of 535 patients r and omized , 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine . Day-28 adequate clinical and parasitological response ( ACPR ) , corrected for re-infection using polymerase chain reaction ( PCR ) genotyping ( per- protocol population ) was 97.1 % ( 329/339 ; 95 % CI 94.6 , 98.6 ) for pyronaridine-artesunate ; 98.8 % ( 165/167 ; 95 % CI 95.7 , 99.9 ) for artemether-lumefantrine . The primary endpoint was achieved : pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly > 90 % ( P < .0001 ) . Pyronaridine-artesunate was non-inferior to artemether-lumefantrine : treatment difference -1.8 % ( 95 % CI -4.3 to 1.6 ) . The incidence of drug-related adverse events was 37.2 % ( 132/355 ) with pyronaridine-artesunate , 44.4 % ( 80/180 ) with artemether-lumefantrine . Clinical biochemistry results showed similar mean changes versus baseline in the two treatment groups . From day 3 until study completion , one patient in each treatment group had peak alanine aminotransferase ( ALT ) > 3 times the upper limit of normal ( ULN ) and peak total bilirubin > 2xULN ( i.e. within the Hy ’s law definition ) . Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine . The adverse event profile was similar for the two comparators . Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes . Trial registration Clinical Trials.gov : identifier Pyronaridine is a new antimalarial agent developed in China . In this r and omized , unblinded study , the safety , tolerance , and clinical efficacy of pyronaridine ( n = 44 ) were evaluated and compared with those of chloroquine ( n = 44 ) , the st and ard first-line antimalarial drug in most of Africa , in 88 Cameroonian children with acute uncomplicated falciparum malaria . The target sample size was determined to detect a 35 % difference in in vivo resistance between the two treatment groups , with 95 % power . Clinical and parasitological responses were monitored for 14 days on an outpatient basis . Seven children ( 3 treated with pyronaridine and 4 treated with chloroquine ) were lost to follow-up and were excluded from the analysis . All 41 patients treated with pyronaridine were cured . Treatment failure was observed in 16 ( 40 % ) of the 40 children treated with chloroquine . In vitro assays indicated that 23 of 40 clinical isolates obtained from patients treated with pyronaridine were resistant in vitro to chloroquine . Side effects associated with pyronaridine intake were minor and transient . Pyronaridine is safe and well tolerated by symptomatic Cameroonian children , and it is highly efficacious in Africa , where chloroquine resistance is well established A new oral dosage regimen and formulation of pyronaridine basing on the pharmacokinetic studies and a theoretical dosage regimen reported previously , was clinical ly evaluated for its therapeutic and undesirable effects on falciparum malaria patients in west Hainan Province , where chloroquine-resistant falciparum malaria was prevalent . 32 cases were treated with pyronaridine by the new dosage regimen of 0.5 g in d1 , and 0.3 g in d2 in plain tablets ( group A ) , while additional 32 patients received enteric-coated tablets of pyronaridine by the current dosage regimen as a control ( group B ) , which was 0.4 g x 2 on d1 , and 0.4 g on d2 . The average fever clearance time for A and B groups was 27.0 + /- 14.1 and 30.2 + /- 13.8h respectively ( P greater than 0.05 ) , and the clearance time for asexual parasites was 57.2 + /- 10.2 and 57.9 + /- 8.7h . Upon 28d following-up examination the cure rates were found to be 100 % in group A and 93.8 % in group B. The undesirable responses were recorded in 18.8 % of group A patients ( 6/32 ) , and 28.1 % of group B ( 9/32 ) respectively , and they were light and tolerable and short in time duration . It was shown that the new dosage regimen of pyronaridine could retain the same therapeutic effect as that currently used , although the total dose was reduced by one third . Hence , an important basis was provided for more rational use and further study of pyronaridine in malaria therapy BACKGROUND The spread of chloroquine resistance poses a serious problem in Africa , where falciparum malaria transmission is the highest in the world . Pyronaridine , an acridine derivative , has been used successfully to treat malaria in China for over 20 years . We compared the efficacy of pyronaridine and chloroquine in African adult patients with acute uncomplicated falciparum malaria in Yaoundé , Cameroon , where chloroquine resistance is well established . METHODS 96 patients were r and omly assigned treatment with chloroquine 25 mg/kg or pyronaridine 32 mg/kg , both orally and divided over 3 days . Patients were followed up for at least 14 days on an outpatient basis . Analysis was by on-active-treatment . FINDINGS After losses from follow-up ( 11 ) or because of self-medication with quinine ( four ) , 41 patients treated with chloroquine and 40 treated with pyronaridine were analysed . Parasite clearance during the 14-day follow-up with chloroquine and pyronaridine was 44 % and 100 % , respectively . All patients treated with pyronaridine were afebrile by day 3 , and parasitaemia cleared by day 4 . No serious drug-related side-effects were noted in pyronaridine-treated patients . INTERPRETATION Pyronaridine was rapidly effective and well-tolerated in African patients with acute , uncomplicated falciparum malaria and may represent an alternative drug against chloroquine-resistant malaria BACKGROUND There is a need for new artemisinin-based combination therapies that are convenient , effective , and safe . We compared the efficacy and safety of pyronaridine-artesunate with that of artemether-lumefantrine for treatment of uncomplicated P falciparum malaria . METHODS This phase 3 , parallel-group , double-blind , r and omised , non-inferiority trial was undertaken in seven sites in Africa and three sites in southeast Asia . In a double-dummy design , patients aged 3 - 60 years with uncomplicated P falciparum malaria were r and omly assigned in a 2:1 ratio to receive pyronaridine-artesunate once a day or artemether-lumefantrine twice a day , orally for 3 days , plus respective placebo . R and omisation was done by computer-generated r and omisation sequence in blocks of nine by study centre . Intervention tablets contained 180 mg pyronaridine and 60 mg artesunate ; control tablets contained 20 mg artemether and 120 mg lumefantrine . Both treatments were given according to bodyweight . The primary efficacy outcome was PCR-corrected adequate clinical and parasitological response ( ACPR ) rate at day 28 in the per- protocol population . Non-inferiority was shown if the lower limit of the two-sided 95 % CI for the difference between groups was greater than -5 % . This study is registered with Clinical Trials.gov , number NCT00422084 . FINDINGS 1272 patients were r and omly assigned to treatment ( pyronaridine-artesunate , n=849 ; artemether-lumefantrine , n=423 ) . The per- protocol population consisted of 784 patients in the pyronaridine-artesunate group and 386 patients in the artemether-lumefantrine group . PCR-corrected ACPR rate at day 28 was 99.5 % ( 780 patients ; 95 % CI 98.7 - 99.9 ) in the pyronaridine-artesunate group and 99.2 % ( 383 patients ; 95 % CI 97.7 - 99.8 ) in the artemether-lumefantrine group ( treatment difference 0.3 % , 95 % CI -0.7 to 1.8 ; p=0.578 ) . There were 509 ( 60.0 % ) adverse events in 849 patients assigned to pyronaridine-artesunate and 241 ( 57.0 % ) in 423 patients assigned to artemether-lumefantrine . The most frequent drug-related adverse event was eosinophilia ( pyronaridine-artesunate , 53 events [ 6.2 % ] ; artemether-lumefantrine 24 events [ 5.7 % ] ) . 21 ( 2.5 % ) patients in the pyronaridine-artesunate group and seven ( 1.7 % ) in the artemether-lumefantrine group discontinued study drugs or were withdrawn from the study . Mild and transient increases in alanine aminotransferase and aspartate aminotransferase concentrations were seen in the pyronaridine-artesunate group but not in the artemether-lumefantrine group . INTERPRETATION Efficacy of pyronaridine-artesunate was non-inferior to that of artemether-lumefantrine for treatment of uncomplicated falciparum malaria . Pyronaridine-artesunate should be considered for inclusion in malaria treatment programmes . FUNDING Shin Poong Pharmaceutical and the Medicines for Malaria Venture OBJECTIVE To provide a combined medication scheme for the treatment of multi-drug resistant falciparum malaria . METHODS Combined administration of dihydroartemisinin and pyronaridine was given to the 32 cases of falciparum malaria cases with multi-drug resistance . The indices for evaluation on day 14 , 21 , and 28 after treatment included the mean fever subsidence time , mean asexual form clearance time , mean recrudescence time of asexual form and recrudescence rate , proportion of gametocyte carriers , mean density of gametocytes and its mean clearance time , cure rate and rate of side-effects . A double blind clinical test was performed with st and ard schemes of dihydroartemisinin ( 20 cases ) and pyronaridine ( 25 cases ) as control . RESULTS The mean fever subsidence time of treated patients by dihydroartemisinin/pyronaridine combination , dihydroartemisinin and pyronaridine was 35.7 + /- 24.7 h , 52.6 + /- 38.9 h and 35.8 + /- 16.5 h respectively , showing a significant difference between the combination group and dihydroartemisinin groups ( P < 0.01 ) . The mean asexual form clearance time was 23.8 + /- 10.1 h , 22.9 + /- 6.5 h and 49.4 + /- 20.3 h respectively , showing significantly faster in the combination group than the pyronaridine group ( P < 0.01 ) . The recrudescence rate was 0 , 4.2 % and 0 respectively . The proportion of gametocyte carriers was 20.0 % , 16.7 % and 60.9 % respectively , with a significantly higher rate in the group of pyronaridine than the group of combination ( P < 0.01 ) . CONCLUSION The combination of dihydroartemsinin and pyronaridine is an ideal medication scheme for the treatment of falciparum malaria cases with multi-drug resistance Field trials were carried out to assess the therapeutic effects including the combined use of piperaquine ( PQ ) with nitroquine ( NQ ) and pyronaridine ( PYR ) with NQ against falciparum malaria in regions of Hainan Province with chloroquine-resistance in 3 successive autumns from 1985 to 1987 . In an evaluation of PQ 750 mg with NQ 25 mg therapy in 33 falciparum malaria patients , the average fever subsidence time and parasite clearance time were 39 hours and 49 hours respectively , but within 28 days after medication , the recrudescence rates were 0 - 47 % in different regions . In evaluations of PYR 600 mg with NQ 25 mg in 11 cases , PYR 800 mg with NQ 40 mg in 43 cases , PYR 800 mg with NQ 80 mg in 31 cases , the fever subsidence time were 31 - 35 hours , the parasite clearance time were 46 - 53 hours and the 28 days recrudescence rates were 13 - 18 % . In the control , the use of PYR 1,200 mg alone in 42 cases , the average fever subsidence time and parasite clearance time were 33 hours and 48 hours respectively , the 28 days recrudescence rate was 12 % . There was no statistically significant difference among them in their effects . The side-effects of all groups were mild One hundred one adult patients with acute uncomplicated falciparum malaria were treated with pyronaridine . All patients were admitted to the Bangkok Hospital for Tropical Diseases for 28 days to exclude reinfection . Sixty-nine patients ( Group I ) received pyronaridine 1,200 mg over a three-day period and 32 patients ( Group II ) received 1,800 mg pyronaridine over a five-day period . Cure rates for the two groups were 63 % ( 38 of 60 ) for Group I and 88 % ( 23 of 26 ) for Group II ( P<0.05 ) . No RII or RIII type response was seen . Mean fever and parasite clearance times were not significantly different in the two groups . The drug was well-tolerated . In vitro drug sensitivity tests of the paired parasite isolates obtained prior to treatment and after recrudescence indicated that the Plasmodium falciparum isolates of the successfully treated patients had a lower mean concentration for 50 % inhibition of growth ( IC50 ) and a much narrower range of the individual IC50 values ( 15.69 + or- 3.82 ng per ml ( mean + or- SD ) ) as compared with those from the recrudescence cases ( 22.98 + or- 12.05 ng per ml ) . Nevertheless , there was no evidence of an increase of the IC50 and IC95 values after recrudescence . The results of the study show that pyronaridine alone at a total dose of 1,800 mg given over five days is well-tolerated in patients suffering from acute uncomplicated malaria and has evident activity against multidrug-resistant falciparum malaria . However , it can not be recommended for use in Thail and as long as the recrudescence rate is as high as 12 % . Further studies of its combinations with other antimalarial drugs are needed |
2,676 | 30,176,938 | Even when DDC was compared with either ticagrelor or prasugrel or TAPT , still no significant difference was observed in terms of bleeding outcomes .
Conclusions In patients with CAD , adverse clinical outcomes were not significantly different when DDC was compared to the other antiplatelet regimens .
In addition , bleeding events were also similarly manifested when DDC was compared to DAPT , TAPT or ticagrelor/prasugrel | Background Recently , several newer antiplatelet treatment strategies have been used in patients with coronary artery disease ( CAD ) .
Apart from the dual antiplatelet therapy ( DAPT ) consisting of aspirin and clopidogrel , double dose clopidogrel ( DDC ) , triple antiplatelet therapy ( TAPT ) consisting of aspirin , clopidogrel and cilostazol and other newer antiplatelet agents have shown to be effective in different ways .
In this analysis , we aim ed to systematic ally compare the adverse clinical outcomes and the bleeding events which were observed when DDC was compared to the other antiplatelet regimens in patients with CAD . | Background —High on-treatment platelet reactivity ( HTPR ) is associated with adverse outcomes . We aim to compare the novel thienopyridine prasugrel versus double-dose clopidogrel in patients with HTPR and explore the interaction between CYP2C19 genotype and both drugs . Methods and Results —Consecutive stable patients undergoing percutaneous coronary intervention were screened with the Multiplate Analyzer P2Y12 assay , defining HTPR as area under the curve > 450 . Those with HTPR were r and omized to prasugrel ( 10 mg/day ) or high-dose clopidogrel ( 150 mg/day ) for 2 weeks and then crossed-over to , respectively , clopidogrel and prasugrel , repeating the P2Y12 assay at the end of each cycle . Clinical follow-up ( until 3 months ) and CYP2C19 genotyping was performed in all patients . The primary end point was platelet reactivity after 14 days of prasugrel versus high-dose clopidogrel . Thirty-two patients were r and omized to prasugrel and then high-dose clopidogrel or to high-dose clopidogrel followed by prasugrel . Prasugrel was associated with a significantly lower platelet reactivity than high-dose clopidogrel was ( 325.8 versus 478.5 area under the curve , P=0.028 ) . No patient treated with prasugrel exhibited HTPR , whereas 9 ( 28.1 % ) receiving high-dose clopidogrel still had prevalence of HTPR ( P=0.001 ) . Similar findings were obtained changing cutoffs or considering platelet reactivity as a continuous variable . Genotyping showed the same efficacy between high-dose clopidogrel and prasugrel in the 18 ( 56.3 % ) CYP2C19 * 2 noncarriers ( HTPR in 12.5 % versus 0 , P=0.274 ) , whereas it was significantly worse in the 14 ( 43.7 % ) carriers ( HTPR in 43.7 % versus 0 , P=0.003 ) . Conclusions —HTPR is successfully abolished by therapy with prasugrel irrespective of CYP2C19 genotype . Conversely , high-dose clopidogrel can address HTPR only in CYP2C19 * 2 noncarriers . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT01465828 Background We investigated the pharmacodynamic effect of cilostazol addition ( 100 mg twice , Triple ) or clopidogrel doubling ( 150 mg daily , Double ) on st and ard dual antiplatelet therapy in type 2 diabetes mellitus ( T2DM ) patients with clopidogrel resistance undergoing a percutaneous coronary intervention . Methods and results This was a prospect i ve , r and omized , cross-over platelet function study . Percent inhibition less than 20 % was used as the cutoff value of clopidogrel resistance . After percutaneous coronary intervention , a total of 50 T2DM patients with clopidogrel resistance were assigned to receive cilostazol 100 mg twice daily or clopidogrel 150 mg daily for 28 days ; afterwards , they received cross-over treatment for another 28 days . Eight patients were excluded because of side effects and follow-up loss . The platelet function test using VerifyNow was performed at three time points : at baseline ( T0 ) , 28 days after r and omization ( T1 ) , and 28 days after cross-over treatment (T2).A total of 42 T2DM patients completed the study protocol . The clopidogrel resistance improved significantly following cilostazol addition or clopidogrel doubling treatment compared with baseline ( 52.9±27.0 in Triple , 45.4±16.8 % in Double , P<0.001 in both ) . This effect continued after cross-over treatment ( 58.1±26.1 and 41.0±20.0 % , respectively , both P<0.05 ) . A head-to-head comparison between two groups showed a lower P2Y12 reaction unit ( PRU ) and higher percentage of platelet inhibition in the Triple than those in the Double group ( PRU , 138.7±88.2 vs. 198.8±19.5 , P=0.049 ; % platelet inhibition , 58.1±26.1 vs. 40.97±20.0 , P=0.048 ) . Conclusion Adjunctive treatment with cilostazol in T2DM patients on st and ard dual antiplatelet therapy might be a more effective strategy for overcoming clopidogrel resistance than clopidogrel doubling treatment Aims Patients with diabetes mellitus ( DM ) have increased platelet reactivity and reduced platelet response to clopidogrel compared with patients without DM . Prasugrel , a more potent antiplatelet agent , is associated with greater reductions in ischaemic events compared with clopidogrel , particularly in patients with DM . The aim of this study was to perform serial pharmacodynamic assessment s of prasugrel with high-dose clopidogrel in patients with DM . Methods and results Optimizing anti-Platelet Therapy In diabetes MellitUS (OPTIMUS)-3 was a prospect i ve , r and omized , double-blind , crossover study in patients with type 2 DM and coronary artery disease ( CAD ) . Patients ( n= 35 ) were r and omly assigned to either prasugrel 60 mg loading dose (LD)/10 mg maintenance dose ( MD ) or clopidogrel 600 mg LD/150 mg MD over two 1-week treatment periods separated by a 2-week washout period . Platelet function was assessed by VerifyNow ® P2Y12 assay , light transmission aggregometry , and vasodilator-stimulated phosphoprotein phosphorylation at 0 , 1 , 4 , and 24 h and 7 days . Greater platelet inhibition by VerifyNow ® P2Y12 was achieved by prasugrel compared with clopidogrel at 4 h post-LD ( least squares mean , 89.3 vs. 27.7 % , P < 0.0001 ; primary endpoint ) . The difference in platelet inhibition between prasugrel and clopidogrel was significant from 1 h through 7 days ( P < 0.0001 ) . Similar results were obtained using all other platelet function measures . Prasugrel result ed in fewer poor responders at all time points irrespective of definition used . Conclusion In patients with type 2 DM and CAD , st and ard-dose prasugrel is associated with greater platelet inhibition and better response profiles during both the loading and maintenance periods when compared with double-dose clopidogrel . Clinical trial identifier : www . clinical trials.gov — OBJECTIVES The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic ( PD ) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease ( CAD ) and high-on-treatment platelet reactivity ( HTPR ) while on st and ard-dose clopidogrel before percutaneous coronary intervention ( PCI ) . BACKGROUND Patients with HTPR are at increased risk of adverse cardiovascular events after PCI . High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms , including antithrombotic effects . METHODS The ACHIDO ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity ) study was a r and omized PD study of high-dose ( 80 mg ) atorvastatin in addition to double-dose ( 150 mg ) clopidogrel ( atorvastatin group , n = 38 ) versus double-dose clopidogrel alone ( control group , n = 38 ) in patients with HTPR . HTPR was defined as P2Y(12 ) reaction units ( PRU ) ≥235 by the VerifyNow P2Y12 assay . Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days . RESULTS Patients r and omized to atorvastatin had lower PRU values ( 188 ± 48 vs. 223 ± 53 PRU , p < 0.01 ; primary endpoint ) and HTPR rates ( 16 % vs. 42 % , p < 0.01 ) at 30 days than patients in the control group . Statin treatment ( odds ratio [ OR ] : 3.8 , p = 0.011 ) , baseline PRU < 298 ( OR : 10.7 , p = 0.0001 ) , noncarrier status of CYP2C19 * 2 loss-of-function allele ( OR : 2.9 , p = 0.043 ) , and age ( OR : 0.94 , p = 0.032 ) were variables significantly associated with optimal PD response ( PRU < 235 ) at 30 days . No correlations were found between PRU and lipid fractions . CONCLUSIONS High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI ( Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ ACHIDO ] ; NCT01335048 ) In acute coronary syndromes ( ACS ) , a dual antiplatelet regimen with an adenosine diphosphate ( ADP ) receptor antagonist plus aspirin has become the cornerstone of treatment . The third-generation thienopyridine prasugrel and the cyclopentyl-triazolo-pyrimidine ticagrelor provide a greater , more rapid and consistent platelet inhibition compared to their predecessor clopidogrel . Based on their advantages over clopidogrel in two l and mark studies , both drugs received a class I recommendation for their use in ACS patients with and without ST segment elevation . Due to differences in ACS population s and conditions investigated , the relative merits of ticagrelor versus prasugrel in the treatment of ACS patients with planned invasive strategy can not be reliably estimated from independent trials . To date , no direct head-to-head comparison of ticagrelor and prasugrel in terms of clinical outcome exists . The aim of this multicenter , r and omized , open-label trial is to assess whether ticagrelor is superior to prasugrel in ACS patients with planned invasive strategy Background — The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation ( IPA ) . Prasugrel is a new thienopyridine that is more potent than st and ard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease . The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown . Methods and Results — Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation – Thrombolysis in Myocardial Infa rct ion 44 ( PRINCIPLE-TIMI 44 ) was a r and omized , double-blind , 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention . The primary end point of the loading-dose phase ( prasugrel 60 mg versus clopidogrel 600 mg ) was IPA with 20 & mgr;mol/L ADP at 6 hours . Patients with percutaneous coronary intervention entered the maintenance-dose phase , a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug . In this study , 201 subjects were r and omized . IPA at 6 hours was significantly higher in subjects receiving prasugrel ( mean±SD , 74.8±13.0 % ) compared with clopidogrel ( 31.8±21.1 % ; P<0.0001 ) . During the maintenance-dose phase , IPA with 20 & mgr;mol/L ADP was higher in subjects receiving prasugrel ( 61.3±17.8 % ) compared with clopidogrel ( 46.1±21.3 % ; P<0.0001 ) . Results were consistent across all key secondary end points ; significant differences emerged by 30 minutes and persisted across all time points . Conclusions — Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention , loading with 60 mg prasugrel result ed in greater platelet inhibition than a 600-mg clopidogrel loading dose . Maintenance therapy with prasugrel 10 mg/d result ed in a greater antiplatelet effect than 150 mg/d clopidogrel Background —Optimal platelet inhibition is an important therapeutic adjunct in patients acute myocardial infa rct ion ( AMI ) undergoing coronary stenting . Whether adjunctive cilostazol to dual antiplatelet therapy ( triple antiplatelet therapy ) can inhibit enhanced platelet reactivity in patients with AMI yet has not been determined . The aim of this study was to assess the degree of platelet inhibition by triple antiplatelet therapy in patients with AMI . Methods and Results —Immediately after emergency room arrival , patients with AMI received clopidogrel ( 600-mg loading dose , followed by 75 mg daily ) and aspirin ( 300-mg loading dose and 200 mg daily throughout the study period ) . After patients underwent coronary stenting ( n=90 ) , they were r and omly assigned to 1 of 3 groups before discharge : st and ard group , clopidogrel of 75 mg daily ( n=30 ) ; high maintenance dose ( MD ) group , clopidogrel of 150 mg daily ( n=30 ) ; and triple group , adjunctive cilostazol of 100 mg twice daily to clopidogrel of 75 mg daily ( n=30 ) . Platelet reactivity was assessed at predischarge and 30-day follow-up by conventional aggregometry and the VerifyNow P2Y12 assay . Predischarge platelet reactivities were similar in the 3 groups . At 30-day follow-up , inhibition of maximal aggregation with 20 & mgr;M ADP stimuli was 6.0 % in the st and ard group , 19.1 % in the high-MD group , and 42.4 % in the triple group ( P<0.001 ) , whereas inhibition of late aggregation with 20&mgr;M ADP stimuli was 10.8 % , 38.1 % , and 66.4 % , respectively ( P<0.001 ) . Similar results were demonstrated when 5 & mgr;M ADP was used . Furthermore , percent changes of P2Y12 reaction unit were significantly different among regimens ( 10.6 % in the st and ard group , 30.7 % in the high-MD group , and 43.0 % in the triple group ; P<0.001 ) . With respect to high-postclopidogrel platelet reactivity ( prespecified as 20 & mgr;M ADP-induced maximal aggregation > 50 % of light transmission ) , fewer patients in the triple group ( 13.3 % ) met the criteria as compared with those in the st and ard ( 76.7 % ) and high-MD groups ( 56.7 % ) at 30-day follow-up ( P<0.001 ) . In the triple group , there were more potent and consistent platelet inhibitions by all parameters as compared with the high-MD group except for percent changes of P2Y12 reaction unit ( P=0.071 ) . Conclusions —Among patients with AMI undergoing coronary stenting , triple antiplatelet therapy results in a greater antiplatelet effect at 30 days as compared with a high-MD clopidogrel or st and ard dual antiplatelet therapy Purpose Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown . Material s and Methods We studied 73 patients with hyporesponsiveness to clopidogrel on st and ard dual antiplatelet therapy for more than 2 weeks . Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units ( PRU ) < 30 % on VerifyNow P2Y12 assay . Patients were r and omly assigned to increased dose of clopidogrel ( aspirin 100 mg+clopidogrel 150 mg daily : group A , n=38 ) or to receiving additional cilostazol ( aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily : group B , n=35 ) . Results Baseline percent inhibition of PRU and PRU was similar between 2 groups ( 13.0±10.2 % versus 11.8±9.7 % , p=0.61 , and 286.3±54.7 versus 295.7±53.7 , p=0.44 , respectively ) . At follow-up , percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A ( 38.5±17.9 % versus 28.3±16.6 % , p=0.02 , and 207.3±68.2 versus 241.3±76.7 , p=0.050 , respectively ) . Among those still showing hyporesponsiveness to clopidogrel at follow-up ( 21 patients in group A , 10 patients in group B ) , 12 patients completed further crossover study . Compared to the baseline , magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover ( from 2.7±8.7 % to 15.8±18.4 % , p=0.08 , and from -18.6±58.0 to -61.9±84.3 , p=0.08 ) . Conclusion Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy Background — Individualizing antiplatelet therapy after platelet function testing did not improve outcome after coronary stenting in the Assessment by a Double R and omization of a Conventional Antiplatelet Strategy Versus a Monitoring-Guided Strategy for Drug-Eluting Stent Implantation and of Treatment Interruption Versus Continuation One Year After Stenting ( A RCT IC ) study . Whether results are different during the phase of secondary prevention starting after hospital discharge , when periprocedural events have been excluded , is unknown . Methods and Results — In A RCT IC , 2440 patients were r and omized before coronary stenting to a strategy of platelet function monitoring ( VerifyNow P2Y12/aspirin point-of-care assay ) with drug adjustment in suboptimal responders to antiplatelet therapy or to a conventional strategy without monitoring and without drug or dose changes . We performed a l and mark analysis starting at the time of hospital discharge evaluating the primary end point of death , myocardial infa rct ion , stent thrombosis , stroke , or urgent revascularization through 1 year . After discharge , the primary end point occurred in 8.6 % of patients in the monitoring arm and 7.9 % in the conventional arm ( hazard ratio , 1.105 ; 95 % confidence interval , 0.835–1.461 ; P=0.48 ) . Stent thrombosis or urgent revascularization occurred in 4.4 % and 4.5 % in the monitoring and conventional arms , respectively ( P=0.99 ) . There was no difference for any of the other ischemic end points . Major bleeding event rates were 1.8 % in the monitoring arm and 2.8 % in the conventional arm ( P=0.11 ) , whereas major or minor bleeding event rates were 2.3 % and 3.4 % , respectively ( P=0.10 ) . Conclusions — Detection of platelet hyper-reactivity by platelet function testing in patients undergoing coronary stenting with further therapeutic adjustment does not reduce ischemic recurrences after intervention . On-treatment platelet hyperreactivity can not be considered as a risk factor requiring intervention for secondary prevention after percutaneous coronary revascularization . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00827411 Background — After treatment with clopidogrel , patients with type 2 diabetes mellitus ( T2DM ) have reduced platelet inhibition compared with patients who are not diabetic . Whether platelet inhibition can be enhanced by increasing clopidogrel maintenance dosage in T2DM patients is unknown . The aim of this pilot study was to assess the functional impact of a high maintenance dose in T2DM patients with suboptimal clopidogrel-induced antiplatelet effects . Methods and Results — T2DM patients on chronic dual antiplatelet therapy were screened to identify suboptimal clopidogrel responders . The latter were r and omized to 30-day treatment with a st and ard ( 75 mg ; n=20 ) or high ( 150 mg ; n=20 ) daily maintenance dose . Platelet function was assessed at 3 time points : baseline , 30 days after r and omization , and 30 days after resuming st and ard dosing . Platelet function parameters included adenosine diphosphate – induced ( 20 and 5 & mgr;mol/L ) maximal and late platelet aggregation , inhibition of platelet aggregation , platelet disaggregation , and P2Y12 reactivity index . A total of 64 T2DM patients were screened to identify 40 suboptimal responders . After r and omization , maximal adenosine diphosphate – induced ( 20 & mgr;mol/L ) platelet aggregation was significantly reduced in the 150-mg group compared with the 75-mg group ( P=0.002 ; primary end point ) . However , suboptimal clopidogrel response was still present in 60 % of patients on the 150-mg regimen . All other platelet function parameters showed enhanced clopidogrel-induced antiplatelet effects with 150 mg , which returned to baseline values after resumption of st and ard dosing . Conclusions — A 150-mg maintenance dose of clopidogrel is associated with enhanced antiplatelet effects compared with 75 mg in high-risk T2DM patients . However , enhanced ex vivo platelet reactivity continues to persist , the clinical implication s of which are unknown and need to be evaluated in large-scale clinical trials OBJECTIVES This study sought to test the noninferiority of triple antiplatelet therapy ( TAT ) versus double-dose clopidogrel dual antiplatelet therapy ( DDAT ) in patients undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND Antiplatelet regimen is an integral component of medical therapy after PCI . A 1-week duration of doubling the dose of clopidogrel was shown to improve outcome at 1 month compared with the conventional dose in patients with acute coronary syndrome undergoing PCI . Yet in Asia , the addition of cilostazol is used more commonly than DDAT in high-risk patients . METHODS We r and omly assigned 3,755 all-comers undergoing PCI to either TAT or DDAT , which was continued for 1 month , to test the noninferiority of TAT versus DDAT . The primary outcome was the cumulative incidence of net clinical outcome at 1 month post-PCI defined as the composite of cardiac death , nonfatal myocardial infa rct ion , stent thrombosis , stroke , and PLATO ( Platelet Inhibition and Patient Outcomes ) major bleeding . RESULTS TAT was noninferior to DDAT with respect to the primary outcome , which occurred in 1.2 % and 1.4 % of patients , respectively ( -0.22 % absolute difference , 0.34 % 1-sided 97.5 % confidence interval , p = 0.0007 for noninferiority ; hazard ratio : 0.85 ; 95 % confidence interval : 0.49 to 1.48 ; p = 0.558 for superiority ) . The individual risks of cardiac death , nonfatal myocardial infa rct ion , stent thrombosis , stroke , and PLATO major bleeding did not differ significantly between the 2 groups . There were no significant between-group differences in the treatment effect with regard to the rate of the primary outcome . CONCLUSIONS The adjunctive use of cilostazol was noninferior to doubling the dose of clopidogrel for 1 month in all-comers undergoing PCI with exclusively drug-eluting stents . ( Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-SAfety & EffectiveneSS of Drug-ElUting Stents & Anti-platelet REgimen [ HOST-ASSURE ] ; NCT01267734 ) CONTEXT High platelet reactivity while receiving clopidogrel has been linked to cardiovascular events after percutaneous coronary intervention ( PCI ) , but a treatment strategy for this issue is not well defined . OBJECTIVE To evaluate the effect of high-dose compared with st and ard-dose clopidogrel in patients with high on-treatment platelet reactivity after PCI . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , active-control trial ( Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety [ GRAVITAS ] ) of 2214 patients with high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents at 83 centers in North America between July 2008 and April 2010 . INTERVENTIONS High-dose clopidogrel ( 600-mg initial dose , 150 mg daily thereafter ) or st and ard-dose clopidogrel ( no additional loading dose , 75 mg daily ) for 6 months . MAIN OUTCOME MEASURES The primary end point was the 6-month incidence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stent thrombosis . The key safety end point was severe or moderate bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries ( GUSTO ) definition . A key pharmacodynamic end point was the rate of persistently high on-treatment reactivity at 30 days . RESULTS At 6 months , the primary end point had occurred in 25 of 1109 patients ( 2.3 % ) receiving high-dose clopidogrel compared with 25 of 1105 patients ( 2.3 % ) receiving st and ard-dose clopidogrel ( hazard ratio [ HR ] , 1.01 ; 95 % confidence interval [ CI ] , 0.58 - 1.76 ; P = .97 ) . Severe or moderate bleeding was not increased with the high-dose regimen ( 15 [ 1.4 % ] vs 25 [ 2.3 % ] , HR , 0.59 ; 95 % CI , 0.31 - 1.11 ; P = .10 ) . Compared with st and ard-dose clopidogrel , high-dose clopidogrel provided a 22 % ( 95 % CI , 18%-26 % ) absolute reduction in the rate of high on-treatment reactivity at 30 days ( 62 % ; 95 % CI , 59%-65 % vs 40 % ; 95 % CI , 37%-43 % ; P < .001 ) . CONCLUSIONS Among patients with high on-treatment reactivity after PCI with drug-eluting stents , the use of high-dose clopidogrel compared with st and ard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes , nonfatal myocardial infa rct ion , or stent thrombosis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00645918 BACKGROUND Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention ( PCI ) . We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI . METHODS The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries . 25,086 individuals with acute coronary syndromes and intended early PCI were r and omly assigned to double-dose ( 600 mg on day 1 , 150 mg on days 2 - 7 , then 75 mg daily ) versus st and ard-dose ( 300 mg on day 1 then 75 mg daily ) clopidogrel , and high-dose ( 300 - 325 mg daily ) versus low-dose ( 75 - 100 mg daily ) aspirin . R and omisation was done with a 24 h computerised central automated voice response system . The clopidogrel dose comparison was double-blind and the aspirin dose comparison was open label with blinded assessment of outcomes . This prespecified analysis is of the 17,263 individuals who underwent PCI . The primary outcome was cardiovascular death , myocardial infa rct ion , or stroke at 30 days . Analyses were by intention to treat , adjusted for propensity to undergo PCI . This trial is registered with Clinical Trials.gov , number NCT00335452 . FINDINGS 8560 patients were assigned to double-dose and 8703 to st and ard-dose clopidogrel ( 8558 and 8702 completed 30-day follow-up , respectively ) , and 8624 to high-dose and 8639 to low-dose aspirin ( 8622 and 8638 completed 30-day follow-up , respectively ) . Compared with the st and ard dose , double-dose clopidogrel reduced the rate of the primary outcome ( 330 events [ 3·9 % ] vs 392 events [ 4·5 % ] ; adjusted hazard ratio 0·86 , 95 % CI 0·74 - 0·99 , p=0·039 ) and definite stent thrombosis ( 58 [ 0·7 % ] vs 111 [ 1·3 % ] ; 0·54 [ 0·39 - 0·74 ] , p=0·0001 ) . High-dose and low-dose aspirin did not differ for the primary outcome ( 356 [ 4·1 % ] vs 366 [ 4·2 % ] ; 0·98 , 0·84 - 1·13 , p=0·76 ) . Major bleeding was more common with double-dose than with st and ard-dose clopidogrel ( 139 [ 1·6 % ] vs 99 [ 1·1 % ] ; 1·41 , 1·09 - 1·83 , p=0·009 ) and did not differ between high-dose and low-dose aspirin ( 128 [ 1·5 % ] vs 110 [ 1·3 % ] ; 1·18 , 0·92 - 1·53 , p=0·20 ) . INTERPRETATION In patients undergoing PCI for acute coronary syndromes , a 7-day double-dose clopidogrel regimen was associated with a reduction in cardiovascular events and stent thrombosis compared with the st and ard dose . Efficacy and safety did not differ between high-dose and low-dose aspirin . A double-dose clopidogrel regimen can be considered for all patients with acute coronary syndromes treated with an early invasive strategy and intended early PCI . FUNDING Sanofi-Aventis and Bristol-Myers Squibb Background : Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs . Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events . The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies ( either double-dose clopidogrel [ DOUBLE ] or adjunctive cilostazol [ TRIPLE ] ) and conventional strategy ( ST AND ARD ) in patients after percutaneous coronary intervention . Methods : In this single-center , r and omized , controlled trial , we used thromboelastography , a platelet function test , to select 1078 patients undergoing percutaneous coronary intervention at high thrombotic risk and compared the intensified antiplatelet therapies with st and ard antiplatelet therapy . The primary outcome was the incidence of major adverse cardiac and cerebrovascular events at 18 months after percutaneous coronary intervention , defined as a composite of all-cause death , myocardial infa rct ion , target vessel revascularization , or stroke . Bleeding Academic Research Consortium defined bleeding complications ( types 1 , 2 , 3 , or 5 ) were the safety end points . Results : The primary end point occurred in 52 patients ( 14.4 % ) in the ST AND ARD group , 38 patients ( 10.6 % ) in the DOUBLE group , and 30 patients ( 8.5 % ) in the TRIPLE group ( hazard ratio , 0.720 ; 95 % confidence interval , 0.474–1.094 , DOUBLE versus ST AND ARD ; hazard ratio , 0.550 ; 95 % confidence interval , 0.349–0.866 , TRIPLE versus ST AND ARD ) . No significant difference in the rates of major bleeding ( Bleeding Academic Research Consortium grade ≥3 ) was found in the DOUBLE group ( 3.34 % versus 1.93 % in ST AND ARD , P=0.133 ) and the TRIPLE group ( 2.53 % versus 1.93 % in ST AND ARD , P=0.240 ) . The rate of Bleeding Academic Research Consortium – defined minor bleeding increased in the DOUBLE group ( 27.4 % versus 20.3 % in ST AND ARD , P=0.031 ) , but not in the TRIPLE group ( 23.6 % versus 20.3 % in ST AND ARD , P=0.146 ) . Conclusions : In patients with low responsiveness to clopidogrel , as measured by thromboelastography , the intensified antiplatelet strategies with adjunctive use of cilostazol significantly improved the clinical outcomes without increasing the risk of major bleeding . Decreased trend of negative outcomes could be observed in patients with double dosage of clopidogrel , but the difference was not significant . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifier : NCT01779401 OBJECTIVES The purpose of this study was to determine the impact of adjunctive cilostazol in patients with high post-treatment platelet reactivity ( HPPR ) undergoing coronary stenting . BACKGROUND Although addition of cilostazol to dual antiplatelet therapy enhances adenosine diphosphate (ADP)-induced platelet inhibition , it is unknown whether adjunctive cilostazol can reduce HPPR . METHODS Sixty patients with HPPR after a 300-mg loading dose of clopidogrel were enrolled . HPPR was defined as maximal platelet aggregation ( Agg(max ) ) > 50 % with 5 micromol/l ADP . Patients were r and omly assigned to receive either adjunctive cilostazol ( triple group ; n = 30 ) or high maintenance dose ( MD ) clopidogrel ( high-MD group ; n = 30 ) . Platelet function was assessed at baseline and after 30 days with conventional aggregometry and the VerifyNow assay . RESULTS Baseline platelet function measurements were similar in both groups . After 30 days , significantly fewer patients in the triple versus high-MD group had HPPR ( 3.3 % vs. 26.7 % , p = 0.012 ) . Percent inhibitions of 5 micromol/l ADP-induced Agg(max ) and late platelet aggregation ( Agg(late ) ) were significantly greater in the triple versus high-MD group ( 51.1 + /- 22.5 % vs. 28.0 + /- 18.5 % , p < 0.001 , and 70.9 + /- 27.3 % vs. 45.3 + /- 23.4 % , p < 0.001 , respectively ) . Percent inhibitions of 20 micromol/l ADP-induced Agg(max ) and Agg(late ) were consistently greater in the triple versus high-MD group . Percent change of P2Y12 reaction units demonstrated a higher antiplatelet effect in the triple versus high-MD group ( 39.6 + /- 24.1 % vs. 23.1 + /- 29.9 % , p = 0.022 ) . CONCLUSIONS Adjunctive cilostazol reduces the rate of HPPR and intensifies platelet inhibition as compared with a high-MD clopidogrel of 150 mg/day Abstract High on-treatment platelet reactivity ( HTPR ) is associated with poor prognosis in patients undergoing percutaneous coronary intervention ( PCI ) . The antiplatelet effect and safety of prasugrel was compared to that of double-dose clopidogrel in patients with stable coronary artery disease or acute coronary syndrome ( ACS ) exhibiting HTPR on clopidogrel and treated with PCI , using multiple electrode aggregometry ( MEA ) to assess platelet reactivity . Of 923 patients screened , 237 ( 25.7 % ) exhibited HTPR . Of these , 106 were eligible for participation in a r and omized trial comparing two intensified antiplatelet regimen : 52 were assigned to double maintenance-dose clopidogrel and 54 to st and ard-dose prasugrel . At 1 month , tailoring antiplatelet therapy improved platelet inhibition to a level considered as therapeutic in 73.1 % of patients . Prasugrel entailed greater platelet inhibition ( p = 0.02 ) and a lower rate of persisting HTPR at follow-up compared to double-dose clopidogrel ( HTPR persisted in 20.4 % and 42 % respectively , p = 0.02 ) . Within the 30-day follow-up , no major bleeds were observed and the incidence of major adverse cardiovascular events ( MACE ) was similar in the two treatment arms . Prasugrel demonstrated superiority to double-dose clopidogrel in overcoming HTPR and reducing platelet activity . Intensifying antiplatelet therapy in both ACS and stable angina pectoris ( SAP ) patients exhibiting HTPR prior to PCI was well tolerated |
2,677 | 27,176,573 | All tested dosages were efficacious against placebo without clear-cut evidence of a dose-response gradient .
However , duration of effect ( time until return to baseline TWSTRS-total score ) and risk of dry mouth and dysphagia were greater in the subgroup of participants treated with higher BtB doses .
Subgroup analysis showed a higher improvement with BtB among BtA-non-responsive participants , although there were no differences in the effect size between the BtA-responsive and non-responsive subgroups .
A single BtB-treatment session is associated with a significant and clinical ly relevant reduction of cervical dystonia impairment including severity , disability and pain , and is well tolerated , when compared with placebo .
However , BtB-treated patients are at an increased risk of dry mouth and dysphagia .
There are no RCT data to allow us to draw definitive conclusions on the optimal treatment intervals and doses , usefulness of guidance techniques for injection , and impact on quality of life | BACKGROUND This is an up date of a Cochrane review first published in 2004 , and previously up date d in 2009 ( no change in conclusions ) .
Cervical dystonia is a frequent and disabling disorder characterised by painful involuntary head posturing .
Botulinum toxin type A ( BtA ) is usually considered the first line therapy for this condition , although botulinum toxin type B ( BtB ) is an alternative option .
OBJECTIVES To compare the efficacy , safety and tolerability of botulinum toxin type B ( BtB ) versus placebo in people with cervical dystonia . | ABSTRACT Objectives : Evaluate the safety and efficacy of a sequential dose escalation of rimabotulinumtoxinB ( BoNT-B ) in cervical dystonia ( CD ) subjects . Methods : This multicenter , open-label , within-subject , sequential dose-escalation study ( BoNT-B dosed at 10,000 , 12,500 , and 15,000 Units ) evaluated subjects over each phase of treatment at preinjection and at periodic intervals postinjection . Adverse events , vital signs , and laboratory results were recorded . Efficacy measures included the Toronto Western Spasmodic Torticollis Rating Scale ( TWSTRS ) and three visual analog scales ( VASs ) . Results : 119 out of 145 CD subjects received all three doses in sequence . Dry mouth and dysphagia were the most common adverse events , and both decreased in frequency by the final injection , despite the increasing doses of the escalation . TWSTRS-Total and subscale scores demonstrated significant improvements following all doses at the week 2 , 4 , 8 , and 12 assessment s , with the exception of disability and pain at week 12 with the lowest dose . All VAS scores demonstrated similar improvements following all doses . The mean number of weeks in each phase of the study was 12.1 weeks ( 10,000 Units ) , 12.9 weeks ( 12,500 Units ) , and 13.9 weeks ( 15,000 Units ) . Conclusion : BoNT-B was well tolerated and efficacious at 10,000 , 12,500 , and 15,000 Units in this within-subject , sequential dose-escalation study in CD subjects Cervical dystonia ( CD ) is characterized by abnormal , involuntary contractions of the cervical and /or shoulder muscles . Direct injection of Botulinum toxin type A ( BTX-A ) into the affected muscles has been used successfully to treat this condition . However , clinical resistance to BTX-A therapy develops in a limited number of patients . Moreover , an unknown proportion of treated patients have a suboptimal response to their present therapy . BTX-B is antigenically distinct from BTX-A and possesses a different mechanism of action . Three r and omized , double-blind , placebo-controlled clinical trials evaluated the safety and efficacy of BTX-B ( Elan 's BTX-B evaluated as NeuroBloc ) as a treatment for patients with CD . Patients received a single dose of BTX-B ranging from 2,500 to 10,000 U. The primary efficacy evaluation for each of these studies used the Toronto Western Spasmodic Torticollis Rating Scale ( TWSTRS ) total score . Additional efficacy measures included the TWSTRS severity , disability , and pain subscale scores , as well as the Patient Analog Pain Assessment and Patient 's and Physician 's Global Assessment s of Change . In all three studies , groups receiving BTX-B displayed statistically significant improvements in TWSTRS total score and other efficacy end points compared with those who received placebo treatment . The clinical benefits after BTX-B treatment lasted 12 to 16 weeks and were observed in both BTX-A-responsive and BTX-A-resistant patients . In general , treatment with BTX-B was well tolerated and most of the reported adverse events were of short duration , mild to moderate in severity , and anticipated . The results from the three controlled clinical trials demonstrate the safety and efficacy of BTX-B in the treatment of patients with CD , including those who are resistant to BTX-A treatment OBJECTIVE To determine the safety and efficacy of botulinum toxin type B ( BoNT/B ) in patients with cervical dystonia ( CD ) . BACKGROUND BoNT/B is a form of chemodenervation therapy for the treatment of patients with CD . METHODS The authors performed a 16-week , r and omized , multicenter , double-blind , placebo-controlled trial of BoNT/B in patients with CD who continue to respond to botulinum toxin type A. Placebo , or 5,000 U or 10,000 U of BoNT/B was administered in two to four muscles involved clinical ly in CD . The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at week 4 was the primary efficacy measure . Clinical assessment s and adverse events were recorded for treatment day 1 and at weeks 2 , 4 , 8 , 12 , and 16 . RESULTS A total of 109 patients were enrolled r and omly across all three treatment groups . The mean improvement in the TWSTRS-Total scores in each group at week 4 was 4.3 ( placebo ) , 9.3 ( 5,000 U ) , and 11.7 ( 10,000 U ) . For the prospect ively defined primary contrast ( 10,000 U versus placebo ) , highly significant differences were noted for the primary ( TWSTRS-Total , baseline to week 4 , p = 0.0004 ) and supportive secondary ( Patient Global Assessment , baseline to week 4 , p = 0.0001 ) outcome measures . Improvement in pain , disability , and severity of CD occurred for patients who were treated with BoNT/B when compared with placebo-treated patients . Overall , improvements associated with BoNT/B treatment were greatest for patients who received the 10,000-U dose . The duration of treatment effect for BoNT/B was 12 to 16 weeks for both doses . CONCLUSION Botulinum toxin type B ( NeuroBloc ) is safe and efficacious at 5,000 U and 10,000 U for the management of patients with cervical dystonia We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind , placebo-controlled safety and efficacy study of botulinum toxin type B ( BotB ) . Both A-responsive and A-resistant patients were enrolled . Patients received intramuscular injections of either BotB ( 2,500 U , 5,000 U , or 10,000 U ) or placebo . The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration . Secondary measures of efficacy were TWSTRS-Severity , -Disability , and -Pain subscale scores , and Analog Pain Assessment , Investigator Global Assessment , Patient Global Assessment , and Sickness Impact Profile scores . Duration of effect was estimated with an intent-to-treat analysis of responders . Safety measures included clinical parameters , laboratory tests , and adverse events . The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response . BotB is safe , well tolerated , and efficacious in the treatment of cervical dystonia at the doses tested In this multicenter study of 100 patients with cervical dystonia , we examined the immunogenicity of botulinum toxin type B ( BTX-B ) and correlated the clinical response with the presence of blocking antibodies ( Abs ) using a novel mouse protection assay . One-third of the patients who were negative for BTX-B Abs at baseline became positive for BTX-B Abs at last visit . Thus , the high antigenicity of BTX-B limits its long-term efficacy To evaluate the immunogenicity of botulinum toxin type A ( BoNTA ; BOTOX ) in cervical dystonia ( CD ) . Subjects diagnosed with CD for > or = 1 year and previously naïve to BoNTs were treated with BoNTA in a prospect i ve , open-label , multicenter study . Serum sample s were analyzed for BoNTA neutralizing antibodies using the Mouse Protection Assay ( MPA ) . Clinical resistance was assessed with a test injection of 20 U BoNTA placed unilaterally into the frontalis ( Frontalis Antibody Test ; FTAT ) or corrugator muscle ( Unilateral Brow Injection ; UBI ) . Efficacy was assessed and adverse events were recorded . Of 326 subjects enrolled , 251 ( 77 % ) completed the study . Subjects received a median of 9 BoNTA treatments ( mean dose per session ranged from 148.4 to 213.0 U over a mean of 2.5 years [ range : 3.2 months-4.2 years ] ) . Only 4 of 326 subjects ( 1.2 % ) tested positive for antibodies in the MPA ; three of these subjects stopped responding clinical ly to BoNTA ( of whom one also showed clinical resistance in the FTAT ) and one continued to respond . Consistent improvements in the signs/symptoms of CD were noted . The most frequent treatment-related adverse events were mild to moderate weakness , dysphagia , neck pain , and injection-site pain . The current formulation of BoNTA rarely causes neutralizing antibody formation in CD subjects treated < or = 4 years Neck pain is reported in 75 % is strongly associated with greater disability and decreased quality of life . Botulinum toxin type B ( BoNT-B ; Myobloc ) is a new botulinum toxin that has been proven safe and effective in reducing the pain , severity , and disability of patients with cervical dystonia . We analyzed a subset of efficacy data from two r and omized , double blind , placebo-controlled clinical trials . The first study consisted of three treatment groups in patients who were responders to the type A toxin , including placebo ( n=36 ) , 5000 units ( U ) ( n=36 ) , 10,000 U ( n=37 ) . The second study consisted of placebo ( n=38 ) and 10,000-U treatment groups ( n=39 ) in patients not responding to the type A toxin . For this analysis , the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-subscale scores for pain and three visual analog scales ( Patient Analog Pain , Patient Global , and Principal Investigator Global Assessment s ) were evaluated . A dose-response effect was observed in the reduction of pain based on the TWSTRS-subscale scores . In both studies , mean improvements from baseline to week 4 for all patients were significant compared with placebo ( P<0.005 ) . BoNT-B also significantly improved mean values for all VAS assessment s. Our analysis confirms that BoNT-B significantly reduces the pain associated with cervical dystonia and improves patients ' overall condition . This clinical benefit suggests that BoNT-B may be useful in other pain syndromes involving involuntary muscle spasms or contractions Botulinum toxin ( BT ) has been used with great success to treat various muscle hyperactivity disorders . Occasionally , antibodies against BT ( BT-AB ) can be formed . When they are directed against the neurotoxin component of the BT drug , they are called neutralising antibodies . They can reduce the therapeutic effect partially or completely . We have measured neutralising BT-AB by use of the mouse diaphragm assay ( MDA ) in 42 adult patients with spasticity in the order of their appearance in the clinic . The patients had been treated for at least 2 years with BT type A ( BT-A ) and received on an average 14.2 ± 6.1 BT-A injection series . BT-A was applied as Botox only , Dysport only or by sequential application of both preparations . The mean cumulative doses were 4,610 ± 1,936 units Botox and 14,033 ± 7,566 units Dysport , respectively . The mean treatment time was 4.5 ± 1.8 ( 2–8 ) years . All patients were initially responsive to BT-A therapy . MDA detected BT-AB in 12 % ( 5/42 ) of patients . However , in three patients the BT-AB titre was very low ( < 0.3 mIU/ml ) , in one it was intermediate ( 0.6 mIU/ml ) and in one patient it was high ( > 1.0 mIU/ml ) . All BT-AB negative patients and also two of the patients with low BT-AB titre remained clinical ly responsive to BT therapy throughout the study . In conclusion , prevalence of BT-AB formation with clinical relevance ( 6 % , 3/42 ) in adult patients with spasticity is not higher than that of BT-treated patients with cervical dystonia and much lower than that of BT-treated patients with infantile cerebral palsy Botulinum neurotoxin ( BoNT ) serotype A is commonly used in the treatment of focal dystonia . Nevertheless , some patients are or become resistant to this serotype . Consequently , other different serotypes have to be used . A comparison of the neuromuscular blockade induced by BoNT type A and C in the extensor digitorum brevis muscles of voluntary subjects was studied , by evaluating the amplitude variation over the time ( until 90 days ) of the compound muscular action potential elicited by supramaximal electrical stimulation of the peroneal nerve at the ankle . A very similar effect and temporal profile , was observed for each serotype . On this basis , two patients with idiopathic facial hemispasm and one with blepharospasm were treated with BoNT serotype C with very beneficial long lasting effects In a double-blind trial in 21 patients with spasmodic torticollis botulinum-A toxin produced both subjective and objective improvement , including significant pain relief in 14 of the 16 patients presenting with pain . Side-effects were more frequently reported during placebo administration and no significant systemic adverse reactions were noted |
2,678 | 26,335,794 | On average , effects sizes were large ( g = 1.02 ) suggesting that most sort-term interventions are effective , however CBT-based interventions that were tailored to IPV survivors achieved the largest effect sizes . | Intimate partner violence ( IPV ) impacts millions of adults and children every year and can result in homicide , legal proceedings , the involvement of child welfare , and the need for emergency shelter for survivors and their families .
Survivors of IPV may develop psychological and somatic symptoms to the trauma , including anxiety , depression , and other mental health related disorders in addition to facing numerous safety , financial , and social challenges .
To reestablish stability , effective short-term interventions are needed in order to address these issues survivors face .
This systematic review and meta- analysis summarizes the extant literature on short-term interventions for survivors of IPV . | This article describes a second treatment- outcome study of cognitive trauma therapy for battered women with posttraumatic stress disorder ( PTSD ; CTT-BW ) . CTT-BW includes trauma history exploration : PTSD education ; stress management ; exposure to abuse and abuser reminders ; self-monitoring of negative self-talk ; cognitive therapy for guilt ; and modules on self-advocacy , assertiveness , and how to identify perpetrators . One hundred twenty-five ethnically diverse women were r and omly assigned to immediate or delayed CTT-BW . PTSD remitted in 87 % of women who completed CTT-BW , with large reductions in depression and guilt and substantial increases in self-esteem . White and ethnic minority women benefited equally from CTT-BW . Similar treatment outcomes were obtained by male and female therapists and by therapists with different levels of education and training . Gains were maintained at 3- and 6-month follow-ups Using a nationally representative sample of American married or cohabiting women , this prospect i ve study examined women who reported or denied intimate partner violence ( IPV ) at wave 1 and compared them on a range of psychosocial outcomes at a 5-year follow-up . This study also examined the rate of divorce or separation during the 5-year interval among women who reported IPV at wave 1 and explored whether certain predictors were related to ending an abusive relationship with an intimate partner during the period . Women with IPV at wave 1 , compared to women without IPV , were significantly more likely to experience a greater degree of depressive symptoms and functional impairment and less self-esteem and life satisfaction at the 5-year follow-up . Also , nearly half of the women in an abusive relationship left the relationship within the period . Leaving the abusive relationship was associated with lower individual income and more social support at wave 1 CTT-BW includes trauma history exploration , PTSD psychoeducation , stress management , psychoeducation about dysfunctional self-talk and self-monitoring of self-talk , exposure to abuse reminders , Cognitive Therapy for Trauma-Related Guilt ( E. S. Kubany & F. P. Manke , 1995 ) , and modules on assertiveness , managing contacts with former partners , self-advocacy strategies , and avoiding revictimization . Thirty-seven ethnically diverse women were assigned to Immediate or Delayed CTT-BW . PTSD remitted in 30 of 32 women who completed CTT-BW . Gains were maintained at 3-month follow-up . CTT-BW was efficacious across ethnic background s. Issues related to disseminability of CTT-BW are discussed BACKGROUND Evidence for a benefit of interventions to help women who screen positive for intimate partner violence ( IPV ) in health-care setting s is limited . We assessed whether brief counselling from family doctors trained to respond to women identified through IPV screening would increase women 's quality of life , safety planning and behaviour , and mental health . METHODS In this cluster r and omised controlled trial , we enrolled family doctors from clinics in Victoria , Australia , and their female patients ( aged 16 - 50 years ) who screened positive for fear of a partner in past 12 months in a health and lifestyle survey . The study intervention consisted of the following : training of doctors , notification to doctors of women screening positive for fear of a partner , and invitation to women for one-to-six sessions of counselling for relationship and emotional issues . We used a computer-generated r and omisation sequence to allocate doctors to control ( st and ard care ) or intervention , stratified by location of each doctor 's practice ( urban vs rural ) , with r and om permuted block sizes of two and four within each stratum . Data were collected by postal survey at baseline and at 6 months and 12 months post-invitation ( 2008 - 11 ) . Research ers were masked to treatment allocation , but women and doctors enrolled into the trial were not . Primary outcomes were quality of life ( WHO Quality of Life-BREF ) , safety planning and behaviour , mental health ( SF-12 ) at 12 months . Secondary outcomes included depression and anxiety ( Hospital Anxiety and Depression Scale ; cut-off ≥8 ) ; women 's report of an inquiry from their doctor about the safety of them and their children ; and comfort to discuss fear with their doctor ( five-point Likert scale ) . Analyses were by intention to treat , accounting for missing data , and estimates reported were adjusted for doctor location and outcome scores at baseline . This trial is registered with the Australian New Zeal and Clinical Trial Registry , number ACTRN12608000032358 . FINDINGS We r and omly allocated 52 doctors ( and 272 women who were eligible for inclusion and returned their baseline survey ) to either intervention ( 25 doctors , 137 women ) or control ( 27 doctors , 135 women ) . 96 ( 70 % ) of 137 women in the intervention group ( seeing 23 doctors ) and 100 ( 74 % ) of 135 women in the control group ( seeing 26 doctors ) completed 12 month follow-up . We detected no difference in quality of life , safety planning and behaviour , or mental health SF-12 at 12 months . For secondary outcomes , we detected no between-group difference in anxiety at 12 months or comfort to discuss fear at 6 months , but depressiveness caseness at 12 months was improved in the intervention group compared with the control group ( odds ratio 0·3 , 0·1 - 0·7 ; p=0·005 ) , as was doctor enquiry at 6 months about women 's safety ( 5·1 , 1·9 - 14·0 ; p=0·002 ) and children 's safety ( 5·5 , 1·6 - 19·0 ; p=0·008 ) . We recorded no adverse events . INTERPRETATION Our findings can inform further research on brief counselling for women disclosing intimate partner violence in primary care setting s , but do not lend support to the use of postal screening in the identification of those patients . However , we suggest that family doctors should be trained to ask about the safety of women and children , and to provide supportive counselling for women experiencing abuse , because our findings suggest that , although we detected no improvement in quality of life , counselling can reduce depressive symptoms . FUNDING Australian National Health and Medical Research Council This study evaluates the long-term efficacy of a brief psychotherapeutic cognitive-behavioral program in group format for female victims of violence by their intimate partner . 53 battered women were r and omized into one of two intervention programs : one including among others exposure technique ( n = 28 ) and another one in which exposure procedures were substituted by communication skills training ( n = 25 ) . Additionally , both programs included : psycho-education , breath control , training to improve self-esteem , cognitive restructuring , problem-solving , planning pleasant activities , and relapse prevention . The treatment was carried out in 8 weekly sessions . Measures of posttraumatic symptoms , anxiety , depression , self-esteem and anger expression were analyzed at pre- and post-treatment , and at 1- , 3- , 6- and 12-months follow-ups . Results show a pronounced decrease of posttraumatic , depressive and anxiety symptoms , which maintained in the different measure moments , with scarce difference between the two programs . The results and their clinical implication s are discussed This study developed a group intervention model appropriate for battered women in Korea and tested its effectiveness . The sessions in the group intervention were formatted to stress the following topics : assess trauma , identify major problems , deal with feelings , underst and self , identify batterer 's characteristics , improve stress management strategies , develop action plans , and promote empowerment . The major finding was that the trait anxiety scores of the 16 battered women in the experimental group significantly decreased after the intervention . The change in levels of state anxiety , self-esteem , and depression in the experimental group were not significantly different from those of the 17 the subjects in the control group OBJECTIVE This study examined ( a ) the efficacy of a manualized , culturally informed , empowerment-focused psychoeducational group intervention ( Nia ) design ed in accord with the theory of triadic influence or treatment as usual ( TAU ) for reducing psychological symptomatology ( suicidal ideation , depressive symptoms , posttraumatic stress symptoms , general psychological distress ) , and ( b ) the effect of Nia versus TAU on the relation between exposure to intimate partner violence ( IPV ) and psychological symptomatology in these women . METHOD Two hundred eight low-socioeconomic-status African American women with a recent history of IPV and a suicide attempt were r and omized to Nia or TAU and assessed at baseline , postintervention , and 6- and 12-month follow-up . They were assessed on their levels of IPV ( Index of Spouse Abuse ) , suicidal ideation ( Beck Scale for Suicidal Ideation ) , depressive symptoms ( Beck Depression Inventory-II ) , posttraumatic stress symptoms , and general psychological distress ( Brief Symptom Inventory ) . RESULTS Hierarchical linear modeling found that women receiving the culturally informed Nia intervention showed more rapid reductions in depressive symptoms and general distress initially , and the between-group difference in depressive symptoms persisted at follow-up . Following intervention , compared with women r and omized to TAU , women in Nia exhibited less severe suicidal ideation when exposed to physical and nonphysical IPV . CONCLUSIONS Findings highlight the value of incorporating Nia as an adjunctive intervention for abused , suicidal , low-income women . They underscore the ways the intervention needs to be bolstered to address more directly more mediating and moderating constructs , as well as the need to target more effectively the key outcomes This study assessed the initial feasibility , acceptability , and efficacy of an intervention aim ed at reducing depression and posttraumatic stress disorder ( PTSD ) in a sample of low-income pregnant women with recent intimate partner violence ( IPV ) . Fifty-four women were r and omly assigned to the intervention or control group . The intervention consisted of four sessions during pregnancy and one “ booster ” session within 2 weeks of delivery . Based on principles of Interpersonal Psychotherapy , the intervention was design ed to help participants improve their interpersonal relationships , including their social support networks , and master their role transition to motherhood . Assessment s were administered at four time points ( intake , 5–6 weeks post-intake , 2 weeks postpartum , 3 months postpartum ) to assess for depression , PTSD , and IPV . The intervention did not significantly reduce the likelihood of a major depressive episode , PTSD , or IPV during pregnancy or up to 3-month postpartum . However , we found moderate effects for the intervention in reducing symptoms of PTSD and depression during pregnancy and a large effect for PTSD symptoms from pregnancy up to 3 months postpartum . This study suggests some initial support for our intervention . Larger r and omized trials are needed to further examine the intervention both during and after pregnancy This study tests the feasibility , safety , and short-term preliminary effects of a relapse prevention and relationship safety ( RPRS ) intervention in reducing drug use and the experience of intimate partner violence ( IPV ) among women on methadone . For this r and omized controlled trial , 34 women who met IPV and drug use criteria were r and omly assigned to either the RPRS condition ( n = 16 ) or a one-session informational control ( IC ) condition ( n = 18 ) . RPRS participants were more likely than IC participants to report a decrease in minor physical or sexual IPV ( OR = 7.1 , p = .05 ) , minor psychological IPV ( OR = 5.3 , p = .03 ) and severe psychological IPV ( OR = 6.07 , p = .03 ) at the 3month follow-up . Data suggest that RPRS participants were also more likely than IC participants to report a decrease in any drug use at 3 months ( OR = 3.3 , p = .08 ) . This study provides preliminary evidence that the RPRS intervention is effective in reducing IPV and drug use among women on methadone PROBLEM/CONDITION Sexual violence , stalking , and intimate partner violence are public health problems known to have a negative impact on millions of persons in the United States each year , not only by way of immediate harm but also through negative long-term health impacts . Before implementation of the National Intimate Partner and Sexual Violence Survey ( NISVS ) in 2010 , the most recent detailed national data on the public health burden from these forms of violence were obtained from the National Violence against Women Survey conducted during 1995 - 1996 . This report examines sexual violence , stalking , and intimate partner violence victimization using data from 2011 . The report describes the overall prevalence of sexual violence , stalking , and intimate partner violence victimization ; racial/ethnic variation in prevalence ; how types of perpetrators vary by violence type ; and the age at which victimization typically begins . For intimate partner violence , the report also examines a range of negative impacts experienced as a result of victimization , including the need for services . REPORTING PERIOD January-December , 2011 . DESCRIPTION OF SYSTEM NISVS is a national r and om-digit-dial telephone survey of the noninstitutionalized English- and Spanish-speaking U.S. population aged ≥18 years . NISVS gathers data on experiences of sexual violence , stalking , and intimate partner violence among adult women and men in the United States by using a dual-frame sampling strategy that includes both l and line and cellular telephones . The survey was conducted in 50 states and the District of Columbia ; in 2011 , the second year of NISVS data collection , 12,727 interviews were completed , and 1,428 interviews were partially completed . RESULTS In the United States , an estimated 19.3 % of women and 1.7 % of men have been raped during their lifetimes ; an estimated 1.6 % of women reported that they were raped in the 12 months preceding the survey . The case count for men reporting rape in the preceding 12 months was too small to produce a statistically reliable prevalence estimate . An estimated 43.9 % of women and 23.4 % of men experienced other forms of sexual violence during their lifetimes , including being made to penetrate , sexual coercion , unwanted sexual contact , and noncontact unwanted sexual experiences . The percentages of women and men who experienced these other forms of sexual violence victimization in the 12 months preceding the survey were an estimated 5.5 % and 5.1 % , respectively . An estimated 15.2 % of women and 5.7 % of men have been a victim of stalking during their lifetimes . An estimated 4.2 % of women and 2.1 % of men were stalked in the 12 months preceding the survey . With respect to sexual violence and stalking , female victims reported predominantly male perpetrators , whereas for male victims , the sex of the perpetrator varied by the specific form of violence examined . Male rape victims predominantly had male perpetrators , but other forms of sexual violence experienced by men were either perpetrated predominantly by women ( i.e. , being made to penetrate and sexual coercion ) or split more evenly among male and female perpetrators ( i.e. , unwanted sexual contact and noncontact unwanted sexual experiences ) . In addition , male stalking victims also reported a more even mix of males and females who had perpetrated stalking against them . The lifetime and 12-month prevalences of rape by an intimate partner for women were an estimated 8.8 % and 0.8 % , respectively ; an estimated 0.5 % of men experienced rape by an intimate partner during their lifetimes , although the case count for men reporting rape by an intimate partner in the preceding 12 months was too small to produce a statistically reliable prevalence estimate . An estimated 15.8 % of women and 9.5 % of men experienced other forms of sexual violence by an intimate partner during their lifetimes , whereas an estimated 2.1 % of both men and women experienced these forms of sexual violence by a partner in the 12 months before taking the survey . Severe physical violence by an intimate partner ( including acts such as being hit with something hard , being kicked or beaten , or being burned on purpose ) was experienced by an estimated 22.3 % of women and 14.0 % of men during their lifetimes and by an estimated 2.3 % of women and 2.1 % of men in the 12 months before taking the survey . Finally , the lifetime and 12-month prevalence of stalking by an intimate partner for women was an estimated 9.2 % and 2.4 % , respectively , while the lifetime and 12-month prevalence for men was an estimated 2.5 % and 0.8 % , respectively . Many victims of sexual violence , stalking , and intimate partner violence were first victimized at a young age . Among female victims of completed rape , an estimated 78.7 % were first raped before age 25 years ( 40.4 % before age 18 years ) . Among male victims who were made to penetrate a perpetrator , an estimated 71.0 % were victimized before age 25 years ( 21.3 % before age 18 years ) . In addition , an estimated 53.8 % of female stalking victims and 47.7 % of male stalking victims were first stalked before age 25 years ( 16.3 % of female victims and 20.5 % of male victims before age 18 years ) . Finally , among victims of contact sexual violence , physical violence , or stalking by an intimate partner , an estimated 71.1 % of women and 58.2 % of men first experienced these or other forms of intimate partner violence before age 25 years ( 23.2 % of female victims and 14.1 % of male victims before age 18 years ) . INTERPRETATION A substantial proportion of U.S. female and male adults have experienced some form of sexual violence , stalking , or intimate partner violence at least once during their lifetimes , and the sex of perpetrators varied by the specific form of violence examined . In addition , a substantial number of U.S. adults experienced sexual violence , stalking , or intimate partner violence during the 12 months preceding the 2011 survey . Consistent with previous studies , the overall pattern of results suggest that women , in particular , are heavily impacted over their lifetime . However , the results also indicate that many men experience sexual violence , stalking , and , in particular , physical violence by an intimate partner . Because of the broad range of short- and long-term consequences known to be associated with these forms of violence , the public health burden of sexual violence , stalking , and intimate partner violence is substantial . RESULTS suggest that these forms of violence frequently are experienced at an early age because a majority of victims experienced their first victimization before age 25 years , with a substantial proportion experiencing victimization in childhood or adolescence . PUBLIC HEALTH ACTION Because a substantial proportion of sexual violence , stalking , and intimate partner violence is experienced at a young age , primary prevention of these forms of violence must begin early . Prevention efforts should take into consideration that female sexual violence and stalking victimization is perpetrated predominately by men and that a substantial proportion of male sexual violence and stalking victimization ( including rape , unwanted sexual contact , noncontact unwanted sexual experiences , and stalking ) also is perpetrated by men . CDC seeks to prevent these forms of violence with strategies that address known risk factors for perpetration and by changing social norms and behaviors by using byst and er and other prevention strategies . In addition , primary prevention of intimate partner violence is focused on the promotion of healthy relationship behaviors and other protective factors , with the goal of helping adolescents develop these positive behaviors before their first relationships . The early promotion of healthy relationships while behaviors are still relatively modifiable makes it more likely that young persons can avoid violence in their relationships |
2,679 | 26,259,048 | This review found low- quality evidence that early treatment with an AED compared with placebo or st and ard care reduced the risk of early post-traumatic seizures .
There was no evidence to support a reduction in the risk of late seizures or mortality .
There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin , a traditional AED , with another AED | BACKGROUND Head injury is a common event and can cause a spectrum of motor and cognition disabilities .
A frequent complication is seizures .
Antiepileptic drugs ( AED ) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy .
Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown .
This review attempted to address the effectiveness of these treatment interventions .
This review up date s and exp and s on the earlier Cochrane review .
OBJECTIVES To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo , usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury . | Objectives : To examine the neuropsychological side effects of valproate ( VPA ) given to prevent post-traumatic seizures . Methods : In a r and omized , double-masked , parallel group clinical trial , we compared the seizure prevention and neuropsychological effects of 1 or 6 months of VPA to 1 week of phenytoin . We studied 279 adult subjects who were r and omized within 24 hours of injury and examined with a battery of neuropsychological measures at 1 , 6 , and 12 months after injury . We examined drug effects cross-sectionally at 1 , 6 , and 12 months and longitudinally by examining differential change from 1 to 6 months and from 6 to 12 months as a function of protocol -dictated changes in treatment . Results : No significant adverse or beneficial neuropsychological effects of VPA were detected . Conclusions : Valproate ( VPA ) appears to have a benign neuropsychological side effects profile , making it a cognitively safe antiepileptic drug to use for controlling established seizures or stabilizing mood . However , based on this study , VPA should not be used for prophylaxis of posttraumatic seizures because it does not prevent posttraumatic seizures , there was a trend toward more deaths in the VPA groups , and it did not have positive effects on cognition Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Abstract Intravenous phenytoin has come under increased scrutiny with the introduction of the prodrug , fosphenytoin . We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use . Open-label r and omization of phenytoin or fosphenytoin in 256 Emergency Department patients prescribed 279 parenteral doses of a phenytoin-equivalent . All phenytoin was administered intravenously , and fosphenytoin was given intravenously or intramuscularly ( physician preference ) . Adverse events and Emergency Department length-of-stay were recorded ; re-presentation to the Emergency Department within three months was review ed for evidence of the purple glove syndrome . Nonparametric statistics were used to analyze the data . Seventy-seven patients received phenytoin and 202 fosphenytoin ; 28 ( 10.0 % ) received intramuscular fosphenytoin . The mean phenytoin-equivalent dose was similar between the groups . Eighteen patients required reduction in infusion rates because of an adverse event ( phenytoin = 6.5 % , fosphenytoin = 6.4 % ; OR 0.9 , 95 % CI 0.42.6 ; p = 1.0 ) . Adverse events occurred with similar frequency ( phenytoin 9.1 % , fosphenytoin 15.8 % ; OR 0.7 , 95 % CI 0.31.4 ; p = 0.3 ) . The most common events were : pruritis , pain on infusion , and paresthesias . One patient developed hypotension ( fosphenytoin ) ; there were no other serious adverse events , including phlebitis . Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for fosphenytoin ( p = 0.6 ) . In routine Emergency Department use , our data do not support formulary conversion from phenytoin to fosphenytoin , based on the incidence of adverse events or Emergency Department length-of-stay In this article the efficacy of carbamazepine for seizure prophylaxis in severe head injuries is tested . In addition , conditions with high risk of seizures requiring prophylactic regimen , were defined . One hundred and thirty-nine patients above 15 years of age with severe head injuries were included in the study . They were r and omly divided into two groups -- carbamazepine versus placebo . Prophylaxis was started immediately after the accident and was continued for one and a half to two years . Carbamazepine dosage was adjusted individually to provide serum levels within therapeutic range . In case of a seizure all the necessary clinical management was initiated . Patients on carbamazepine showed a lower probability of post-traumatic seizures than those on placebo ( p less than 0.05 ) . This difference was statistically significant with regard to early seizures within the first week and with regard to the follow-up time in total , but not regarding late seizures per se . Brain lesions with a high risk of post-traumatic seizures were situated in the parietal and temporal areas and included acute subdural haematomas in all locations , temporal lobe contusions , parietal epidural haematomas accompanied by other lesions and the deep stages of coma . Brain stem contusions were accompanied by a rather low probability of seizures . The above mentioned types and locations of brain lesions with the exception of brain stem contusions justify antiepileptic prophylaxis . The regimen consists of oral carbamazepine 100 mg three times daily by gastric tube during the first two days increasing to about 200 mg three times daily on the third day corresponding to the serum level . If oral medication is not possible within the initial twelve hours , phenytoin in a dose of 750 mg Phenhydan-Infusion Konzentrate is given on the first day , followed by an intravenous dose of 250 - 500 mg on the second day or until oral carbamazepine administration is tolerated . Treatment should be continued for one year OBJECTIVE : To determine the incidence of intravenous site reactions to phenytoin and valproate in a large population of patients with neurotrauma . DESIGN : Retrospective chart review of two double-blind , r and omized clinical trials evaluating the use of antiepileptic drugs to prevent posttraumatic seizures in patients with neurotrauma : phenytoin versus placebo ( n = 390 ) , and valproate versus phenytoin with placebo ( n = 385 ) . Information collected from the charts included the number , type , and location of intravenous lines and intravenous site events . SETTING : Tertiary care trauma and university teaching hospital . MAIN RESULTS : Intravenous site reactions occurred in 18 % and 25 % of patients receiving valproate or phenytoin , respectively , with the majority of events ( 70 % ) occurring in the first intravenous site . Patients received the neurosurgery study drug ( NSSD ) by either central or peripheral lines ; all intravenous site reactions occurred in peripheral administration sites . When patients who received the drug by central line during the course of therapy were excluded , the estimated incidence of site reactions was 21 % and 30 % for valproate and phenytoin , respectively ( p = 0.056 ) . The time to the first event was shorter with phenytoin compared with valproate ( 2.0 ± 1.3 vs. 3.0 ± 1.9 d ; p = 0.009 ) . Fewer adverse events were noted with phenytoin in the phenytoin-without-valproate study than in the phenytoin-with-valproate study , with 4.3 % and 8.2 % of intravenous site events recorded in patients receiving placebo or phenytoin , respectively . There was no significant difference in the number of intravenous lines per patient used during NSSD drug infusion for phenytoin versus placebo or phenytoin versus valproate . CONCLUSIONS : Both intravenous phenytoin and valproate result ed in intravenous site reactions , with the loading doses responsible for the majority of the events A r and omised , controlled , double-blind clinical trial design ed to determine the effectiveness of phenytoin in preventing epilepsy in patients who had suffered a serious head injury is reported . One hundred and sixty-four patients were r and omly assigned to treatment with phenytoin or placebo capsules for one year . Patients who had a fit within one week of injury were excluded . Drug levels were monitored throughout with appropriate dosage adjustment ; however only 48 % of the phenytoin group had plasma levels greater than 40 mumol/l . There were seven deaths during the study . Only 11 patients ( six in the phenytoin group and five in the placebo group ) developed post-traumatic epilepsy within one year ; a further four patients developed seizures between 1 and 2 years after injury . This low incidence of post-traumatic epilepsy ( 7 % ( SE 2 % ) at one year and 10 ( SE 2 % ) at two years ) means that future clinical trials of prophylaxis will have to be much larger ( at least six fold ) Levetiracetam ( LEV ) has antiepileptogenic effects in animals and is a c and i date for prevention of epilepsy after traumatic brain injury . Pharmacokinetics of LEV in TBI patients was unknown . We report pharmacokinetics of TBI subjects≥6years with high PTE risk treated with LEV 55mg/kg/day orally , nasogastrically or intravenously for 30days starting ≤8h after injury in a phase II safety and pharmacokinetic study . Forty-one subjects ( 26 adults and 15 children ) were r and omized to PK studies on treatment days 3 and 30 . Thirty-six out of forty-one r and omized subjects underwent PK study on treatment day 3 , and 24/41 subjects underwent PK study on day 30 . On day 3 , mean T(max ) was 2.2h , C(max ) was 60.2μg/ml and AUC was 403.7μg/h/ml . T(max ) was longer in the elderly than in children and non-elderly adults ( 5.96h vs. 1.5h and 1.8h ; p=0.0001 ) . AUC was non-significantly lower in children compared with adults and the elderly ( 317.4μg/h/ml vs. 461.4μg/h/ml and 450.2μg/h/ml ; p=0.08 ) . C(max ) trended higher in i.v.- versus tablet- or n.g.-treated subjects ( 78.4μg/ml vs. 59μg/ml and 48.2μg/ml ; p=0.07 ) . AUC of n.g . and i.v . administrations was 79 % and 88 % of AUC of oral administration . There were no significant PK differences between days 3 and 30 . Treatment of TBI patients with high PTE risk with 55mg/kg/day LEV , a dose with antiepileptogenic effect in animals , results in plasma LEV levels comparable to those in animal studies PURPOSE Preventing posttraumatic epilepsy has been a difficult challenge . In this study we evaluated the association between glucocorticoid administration after traumatic brain injury ( TBI ) and posttraumatic seizures . METHODS We examined a seizure-prevention trial data base of 404 patients with severe TBI for exposure to glucocorticoids in the early ( < 1 week ) posttraumatic period . After controlling for seizure risk , we compared the odds of developing first and second late posttraumatic seizures between those that received glucocorticoids and those that did not . RESULTS Patients dosed with glucocorticoids within 1 day of their TBI were more likely to develop first late seizures than were those without [ p = 0.04 ; hazard ratio = 1.74 ; 95 % confidence interval ( CI ) , 1.01 - 2.98 ] ; whereas those receiving glucocorticoids > or = 2 days after their injury had no similar association ( p = 0.66 ; hazard ratio = 0.77 ; 95 % CI , 0.23 - 2.56 ; p = 0.10 among the three groups ) . Receiving glucocorticoids within 1 day , or > or = 2 days after TBI was not associated with second late seizure development . CONCLUSIONS Glucocorticoid treatment after TBI is not associated with decreased late posttraumatic seizures , and early treatment is associated with increased seizure activity RATIONALE No large studies till date are available from India on post-traumatic seizures ( PTS ) . METHODS This is a prospect i ve observational study of 520 patients with traumatic brain injury ( TBI ) ( July 2007 - 2008 ) . Patients admitted after 24h of injury , with Glasgow coma scale (GCS)<or=4 were excluded . RESULTS At a median follow-up of 386 days , 59 ( 11.4 % ) patients developed PTS . Incidence of immediate , early and late onset seizure were 6.5 % , 2.1 % and 2.7 % respectively . In children , incidence of PTS was 18.3 % . On univariate analysis , females , of age < 10 years , with associated medical problems and with delayed loss of consciousness and poor GCS ( < 9 ) , following fall from height , had significantly higher odds of PTS . On multivariate analysis , the risk of PTS was 3.7 times higher in patients who had fallen from height , 4.4 times higher in associated medical problems , and 3.7 times higher in severe head injury ( GCS<9 ) at presentation . PTS was associated with poor Glasgow outcome score and higher incidence of behavioral abnormality on follow up . 32 % patient with PTS developed recurrent delayed seizures . Seizure recurrence was significantly higher in late onset PTS . PTS affected overall outcome of the patients in severe head injury . CONCLUSION The risk of PTS was higher in patients who sustained fall from height , in GCS<9 , and associated medical problems . About 1/3rd of the patients with early PTS developed recurrent delayed seizures STUDY OBJECTIVE We determine the efficacy of prophylactic phenytoin in preventing early posttraumatic seizures in children with moderate to severe blunt head injury . METHODS Children younger than 16 years and experiencing moderate to severe blunt head injury were r and omized to receive phenytoin or placebo within 60 minutes of presentation at 3 pediatric trauma centers . The primary endpoint was posttraumatic seizures within 48 hours ; secondary endpoints were survival and neurologic outcome 30 days after injury . A Bayesian decision-theoretic clinical trial design was used to determine the probability of remaining posttraumatic seizure free for each treatment group . RESULTS One hundred two patients were enrolled , with a median age of 6.1 years . Sixty-eight percent were boys . The 2 treatment groups were well matched . During the 48-hour observation period , 3 ( 7 % ) of 46 patients given phenytoin and 3 ( 5 % ) of 56 patients given placebo experienced a posttraumatic seizure . There were no significant differences between the treatment groups in survival or neurologic outcome after 30 days . According to these results , the probability that phenytoin has the originally hypothesized effect of reducing the rate of early posttraumatic seizures by 12.5 % is 0.0053 . The probability that phenytoin has any prophylactic efficacy is 0.383 . The median effect size in this trial was -0.015 ( seizure rate increased by 1.5 % in the phenytoin group ) , 95 % probability interval -0.127 to 0.091 ( 12.7 % higher rate of posttraumatic seizures to a 9.1 % lower rate of posttraumatic seizures with phenytoin ) . CONCLUSION The rate of early posttraumatic seizures in children may be much lower than previously reported . Phenytoin did not substantially reduce that rate OBJECTIVE To determine the incidence and risk factors for seizure recurrence after the onset of late posttraumatic seizures ( ie , seizures occurring more than 7 days after injury ) . DESIGN Longitudinal cohort design . SETTING Level 1 trauma center . PATIENTS Sixty-three moderately to severely head-injured adults who developed late posttraumatic seizures during the course of their participation in a r and omized , placebo-controlled study of the effectiveness of prophylactic phenytoin ( Dilantin ) for prevention of posttraumatic seizures . MAIN OUTCOME MEASURES Time from the first unprovoked late seizure to time of seizure recurrence . RESULTS The cumulative incidence of recurrent late seizures was 86 % by approximately 2 years . However , the frequency of recurrent seizures varied considerably across subjects : 52 % experienced at least five late seizures , and 37 % had 10 or more late seizures within 2 years of the first late seizure . The relative risk of recurrence was highest in patients with a history of acute subdural hematoma and prolonged coma ( ie , longer than 7 days ) . CONCLUSIONS When late seizures develop after severe head injury , the probability of recurrence is high , which suggests that patients be treated aggressively with anticonvulsant medication after a first unprovoked late seizure Phenobarbital ( PB ) was tested for its efficacy in averting post-traumatic epilepsy ( PTE ) in patients with non-missile head injuries . The protocol envisaged the administration of PB throughout a period of two years in r and omly assigned doses ranging from 0.5 to 1.5 and from 1.6 to 2.5 mg/kg/day . The study included neurologic examination , EEG and plasma PB levels . Ninety patients , 83 of whom with serious head injury , followed the prescribed treatment for the entire period . Two adult patients manifested seizures 5 and 10 months after the trauma . They were being treated with doses over 1.5 mg/kg/day . Another patient had a seizure six months after the end of the prophylaxis . Low doses of PB and monitoring permitted a reduction of side effects . The low incidence of PTE indicates that PB has an efficient prophylactic effect . The results also show that a low dosage has a favourable effect . SommarioÈ stata indagata l'efficacia di differenti dosi di fenobarbital ( PB ) nella profilassi dell'epilessia post-traumatica . Il protocol lo prevedeva la somministrazione di PB in quantità comprese fra 0.5 e 1.5 e fra 1.6 e 2.5 mg/kg/die , assegnate in modo r and omizzato indipendentemente dall'entità del trauma , per un periodo di due anni . La valutazione neurologica , EEG e dei livelli plasmatici di PB erano assicurati a tutti i pazienti . 90 pazienti , 83 dei quali con trauma cranico grave , seguirono il trattamento prescritto per l'intero periodo . Due presentarono crisi rispettivamente dopo 5 e 10 mesi dal trauma . Entrambi erano trattati con dosi superiori a 1.5 mg/kg/die . Un altro paziente ebbe una crisi sei mesi dopo il termine del trattamento . Questi risultati indicano che il PB svolge un'efficace prevenzione dell'epilessia post-traumatica e che un effetto favorevole può aversi anche con dosi non elevate In order to determine potential negative neurobehavioral effects of phenytoin given to prevent the development of posttraumatic seizures , 244 subjects were r and omized to phenytoin or placebo . They received neurobehavioral assessment s at 1 and 12 months postinjury while receiving their assigned drug and at 24 months while receiving no drugs . In the severely injured , phenytoin significantly impaired performance at 1 month . No significant differences were found as a function of phenytoin in the moderately injured patients at 1 month or in either severity group at 1 year . Patients who stopped receiving phenytoin according to protocol between 1 and 2 years improved more than corresponding placebo cases on several measures . We conclude that phenytoin has negative cognitive effects . This , combined with lack of evidence for its effectiveness in preventing posttraumatic seizures beyond the first week , raises questions regarding its use for long-term prophylaxis . Our findings do not negate phenytoin 's proven efficacy in controlling established seizures nor do they indicate that its cognitive effects are worse than other anticonvulsant drugs Aim : To assess the incidence of late post-traumatic epilepsy ( PTE ) in patients with very severe traumatic brain injury ( TBI ) who either received or did not receive anti-epileptic prophylactic treatment . Methods : Two population s were studied : 55 patients retrospectively and 82 subjects prospect ively . Results : Ten patients ( 18 % ) in the first population showed late PTE . Although the incidence was lower in patients who did not receive prophylactic treatment , the difference between the treated and the non-treated group was not statistically significant . Sixty-nine patients in the second group ( 84 % ) had prophylactic treatment . Twenty-seven patients ( 39 % ) suffered from late PTE during the 2-year follow-up period and 17 of them ( 63 % ) showed EEG epileptic abnormalities . No patient who did not receive preventive therapy suffered from late PTE during the observation period . Conclusions : Due to the negative cognitive effects of anti-epileptic drugs , the preliminary results are of considerable interest for the rehabilitation of patients with very severe TBI There is still a considerable controversy about the usefulness of antiepileptic prophylaxis after traumatic brain injury . Overall incidence of posttraumatic fits and epilepsy 's is well known , but an individual decision on prophylaxis requires knowledge about the individual risk . We performed a prospect i ve observational study on 612 patients with traumatic brain injury of every degree of severity . Follow-up by phone call included 96.2 % of the study population after 6 month and 91.2 % after 36 month , respectively . The overall incidence for early fits ( within 7 days after trauma ) , late fits ( up to 36 month ) and epilepsy ( as defined by the International League Against Epilepsy ) was 4.2 % , 3.7 % and 2.5 % , respectively . These incidences increased according to the severity of the trauma , but the most powerful single predictor was intracranial hemorrhage . There was no significant difference related to the hemorrhage localisation . Development of epilepsy was much more common after late fits ( 48 % ) than after early fits ( 17 % ) . These features established a hierarchy of risks for the development of epilepsy : no intracranial hemorrhage/no fit : 1 % ( 4/437 ) , intracranial hemorrhage/no fit : 8 % ( 10/122 ) , intracranial hemorrhage/early fit : 16 % ( 3/19 ) , intracranial hemorrhage/late fit : 53 % ( 7/13 ) . If prophylactic antiepileptic treatment is desired , but should be restricted to patients at high risk . These are patients with intracranial hemorrhage -- are a well defined high risk group -- when their first fit is a late fit OBJECTIVES To evaluate whether valproate ( VPA ) result ed in laboratory or clinical evidence of a change in bleeding-related measures associated with VPA therapy in patients sustaining a traumatic brain injury . METHODS Fibrinogen , platelet count and clot elastic shear modulus using the Thrombelastograph ( TEG ) coagulation analyzer were measured at baseline , 4 , 14 , 30 , and 180 days post-injury . Clinical ly significant events , defined as the trigger for requiring a transfusion , were identified and evaluated as to possible treatment effects . RESULTS Compared to baseline , the platelet count in the VPA groups was decreased on day 4 , increased by 100 % on day 14 , and returned to baseline levels by day 30 . Fibrinogen was significantly increased by day 4 and returned to baseline by day 30 . The platelet count was correlated with an increase in the maximum amplitude or width of the TEG tracing ; a measure of strength of the clot , suggesting that valproate did not alter the clot strength contributed by platelets . None of the clinical events requiring transfusions appeared to be treatment related . CONCLUSIONS No serious hemostatic adverse events occurred in the trauma patients receiving VPA or phenytoin that could be attributed to treatment BACKGROUND Antiepileptic drugs are commonly used to prevent seizures that may follow head trauma . However , previous controlled studies of this practice have been inconclusive . METHODS To study further the effectiveness of phenytoin ( Dilantin ) in preventing post-traumatic seizures , we r and omly assigned 404 eligible patients with serious head trauma to treatment with phenytoin ( n = 208 ) or placebo ( n = 196 ) for one year in a double-blind fashion . An intravenous loading dose was given within 24 hours of injury . Serum levels of phenytoin were maintained in the high therapeutic range ( 3 to 6 mumol of free phenytoin per liter ) . Follow-up was continued for two years . The primary data analysis was performed according to the intention to treat . RESULTS Between drug loading and day 7 , 3.6 percent of the patients assigned to phenytoin had seizures , as compared with 14.2 percent of patients assigned to placebo ( P less than 0.001 ; risk ratio , 0.27 ; 95 percent confidence interval , 0.12 to 0.62 ) . Between day 8 and the end of year 1 , 21.5 percent of the phenytoin group and 15.7 percent of the placebo group had seizures ; at the end of year 2 , the rates were 27.5 percent and 21.1 percent , respectively ( P greater than 0.2 for each comparison ; risk ratio , 1.20 ; 95 percent confidence interval , 0.71 to 2.02 ) . This lack of a late effect could not be attributed to differential mortality , low phenytoin levels , or treatment of some early seizures in patients assigned to the placebo group . CONCLUSIONS Phenytoin exerts a beneficial effect by reducing seizures only during the first week after severe head injury OBJECT Seizures frequently accompany moderate to severe traumatic brain injury . Phenytoin and carbamazepine are effective in preventing early , but not late , posttraumatic seizures . In this study the authors compare the safety and effectiveness of valproate with those of short-term phenytoin for prevention of seizures following traumatic brain injury . METHODS The study was a r and omized , double-blind , single-center , parallel-group clinical trial . Treatment began within 24 hours of injury . One hundred thirty-two patients at high risk for seizures were assigned to receive a 1-week course of phenytoin , 120 were assigned to receive a 1-month course of valproate , and 127 were assigned to receive a 6-month course of valproate . The cases were followed for up to 2 years . The rates of early seizures were low and similar when using either valproate or phenytoin ( 1.5 % in the phenytoin treatment group and 4.5 % in the valproate arms of the study ; p = 0.14 , relative risk [ RR ] = 2.9 , 95 % confidence interval [ CI ] 0.7 - 13.3 ) . The rates of late seizures did not differ among treatment groups ( 15 % in patients receiving the 1-week course of phenytoin , 16 % in patients receiving the 1-month course of valproate , and 24 % in those receiving the 6-month course of valproate ; p = 0.19 , RR = 1.4 , 95 % CI 0.8 - 2.4 ) . The rates of mortality were not significantly different between treatment groups , but there was a trend toward a higher mortality rate in patients treated with valproate ( 7.2 % in patients receiving phenytoin and 13.4 % in those receiving valproate ; p = 0.07 , RR = 2.0 , 95 % CI 0.9 - 4.1 ) . The incidence of serious adverse events , including coagulation problems and liver abnormalities , was similar in phenytoin- and valproate-treated patients . CONCLUSIONS Valproate therapy shows no benefit over short-term phenytoin therapy for prevention of early seizures and neither treatment prevents late seizures . There was a trend toward a higher mortality rate among valproate-treated patients . The lack of additional benefit and the potentially higher mortality rate suggest that valproate should not be routinely used for the prevention of posttraumatic seizures BACKGROUND Traumatic brain injuries represent an important and costly health problem . Supplemental magnesium positively affects many of the processes involved in secondary injury after traumatic brain injury and consistently improves outcome in animal models . We aim ed to test whether treatment with magnesium favourably affects outcome in head-injured patients . METHODS In a double-blind trial , 499 patients aged 14 years or older admitted to a level 1 regional trauma centre between August , 1998 , and October , 2004 , with moderate or severe traumatic brain injury were r and omly assigned one of two doses of magnesium or placebo within 8 h of injury and continuing for 5 days . Magnesium doses were targeted to achieve serum magnesium ranges of 1.0 - 1.85 mmol/L or 1.25 - 2.5 mmol/L. The primary outcome was a composite of mortality , seizures , functional measures , and neuropsychological tests assessed up to 6 months after injury . Analyses were done according to the intention-to-treat principle . This trial is registered with , number . FINDINGS Magnesium showed no significant positive effect on the composite primary outcome measure at the higher dose ( mean=55 average percentile ranking on magnesium vs 52 on placebo , 95 % CI for difference -7 to 14 ; p=0.70 ) . Those r and omly assigned magnesium at the lower dose did significantly worse than those assigned placebo ( 48 vs 54 , 95 % CI -10.5 to -2 ; p=0.007 ) . Furthermore , there was higher mortality with the higher magnesium dose than with placebo . Other major medical complications were similar between groups , except for a slight excess of pulmonary oedema and respiratory failure in the lower magnesium target group . No subgroups were identified in which magnesium had a significantly positive effect . INTERPRETATION Continuous infusions of magnesium for 5 days given to patients within 8 h of moderate or severe traumatic brain injury were not neuroprotective and might even have a negative effect in the treatment of significant head injury Objective : To investigate the effectiveness of maintaining blood glucose levels below 6.1 mmol/L with insulin as prevention of secondary injury to the central and peripheral nervous systems of intensive care patients . Methods : The authors studied the effect of intensive insulin therapy on critical illness polyneuropathy ( CIPNP ) , assessed by weekly EMG screening , and its impact on mechanical ventilation dependency , as a prospect ively planned sub analysis of a large r and omized , controlled trial of 1,548 intensive care patients . In the 63 patients admitted with isolated brain injury , the authors studied the impact of insulin therapy on intracranial pressure , diabetes insipidus , seizures , and long-term rehabilitation at 6 and 12 months follow-up . Results : Intensive insulin therapy reduced ventilation dependency ( p = 0.0007 ; Mantel – Cox log rank test ) and the risk of CIPNP ( p < 0.0001 ) . The risk of CIPNP among the 405 long-stay ( ≥7 days in intensive care unit ) patients was lowered by 49 % ( p < 0.0001 ) . Of all metabolic and clinical effects of insulin therapy , and corrected for known risk factors , the level of glycemic control independently explained this benefit ( OR for CIPNP 1.26 [ 1.09 to 1.46 ] per mmol blood glucose , p = 0.002 ) . In turn , prevention of CIPNP explained the ability of intensive insulin therapy to reduce the risk of prolonged mechanical ventilation ( OR 3.75 [ 1.49 to 9.39 ] , p = 0.005 ) . In isolated brain injury patients , intensive insulin therapy reduced mean ( p = 0.003 ) and maximal ( p < 0.0001 ) intracranial pressure while identical cerebral perfusion pressures were obtained with eightfold less vasopressors ( p = 0.01 ) . Seizures ( p < 0.0001 ) and diabetes insipidus ( p = 0.06 ) occurred less frequently . At 12 months follow-up , more brain-injured survivors in the intensive insulin group were able to care for most of their own needs ( p = 0.05 ) . Conclusions : Preventing even moderate hyperglycemia with insulin during intensive care protected the central and peripheral nervous systems , with clinical consequences such as shortening of intensive care dependency and possibly better long-term rehabilitation Continuous electroencephalography ( cEEG ) is increasingly used to detect both clinical and sub clinical seizures in patients with traumatic brain injury ( TBI ) or subarachnoid hemorrhage ( SAH ) . We assess whether EEG findings predict outcomes in TBI/SAH patients enrolled in a levetiracetam ( LEV ) vs. fosphenytoin ( fos-PHT ) seizure prevention trial ( NCT00618436 ) . This prospect i ve , single-blinded , comparative trial r and omized 52 patients with TBI or SAH to receive prophylactic LEV or fos-PHT . Continuous video EEG monitoring was conducted for the initial 72 h of medication administration . The association between EEG findings ( degree of generalized and focal slowing , presence and frequency of epileptiform discharges and seizures ) and outcomes ( Glasgow Outcomes Scale-Extended ( GOS-E ) and Disability Rating Scale ( DRS ) ) at discharge , 3 and 6 months was assessed using a generalized linear model . Severity of generalized slowing tended to be associated with outcomes in both treatment groups ( discharge DRS , p=0.042 ; discharge GOS-E , p=0.026 ; 3 month DRS , p=0.051 ) . The presence of focal slowing , the presence and frequency of epileptiform discharges and the presence of seizures were not predictive of outcome in either treatment group ( all p>0.15 ) . While it has been shown that LEV is associated with better outcome than fos-PHT when used as seizure prophylaxis in brain injury , aside from severity of generalized slowing , electrographic findings of focal slowing , epileptiform discharges , and seizures were not themselves associated with outcomes in patients with TBI or SAH enrolled in a r and omized clinical trial OBJECTIVES To ascertain the natural history and to stratify risks for the development of late posttraumatic seizures in individuals with moderate to severe traumatic brain injury ( TBI ) . DESIGN Prospect i ve , observational study of individuals with TBI admitted to 4 trauma centers within 24 hours of injury . SETTING Four tertiary care trauma centers in urban areas . PARTICIPANTS A total of 647 individuals ( > /=16 y ) with any of the following abnormal computed tomography ( CT ) scan findings : extent of midline shift and /or cisternal compression or presence of any focal pathology ( eg , punctate , subarachnoid , or intraventricular hemorrhage ; cortical or subcortical contusion ; extra-axial lesions ) during the first 7 days postinjury or best Glasgow Coma Scale ( GCS ) score of < /=10 during the first 24 hours post-TBI . Subjects were enrolled from August 1993 through September 1997 and followed for up to 24 months , until death or their first late posttraumatic seizures . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Cumulative probability , relative risk , and survival analyses were used to stratify risks for development of late postttraumatic seizures on the basis of demographic factors , etiology of injury , initial GCS , early posttraumatic seizures , time post-TBI , types of intracerebral lesion by CT scan , and number and types of intracranial procedures . RESULTS Sixty-six individuals had a late posttraumatic seizures ; 337 had no late posttraumatic seizures during full 24-month follow-up ; 167 had no late posttraumatic seizures during time followed ( < 24 mo ) ; and 54 were placed on anticonvulsants without a late posttraumatic seizures , whereas 23 died before their first late posttraumatic seizures . The highest cumulative probability for late posttraumatic seizures included biparietal contusions ( 66 % ) , dural penetration with bone and metal fragments ( 62.5 % ) , multiple intracranial operations ( 36.5 % ) , multiple subcortical contusions ( 33.4 % ) , subdural hematoma with evacuation ( 27.8 % ) , midline shift greater than 5 mm ( 25.8 % ) , or multiple or bilateral cortical contusions ( 25 % ) . Initial GCS score was associated with the following cumulative probabilities for development of late posttraumatic seizures at 24 months : GCS score of 3 to 8 , 16.8 % ; GCS score of 9 to 12 , 24.3 % ; and GCS score of 13 to 15 , 8.0 % . CONCLUSIONS Stratification by CT scan findings and neurosurgical procedures performed were the most useful findings in defining individuals at highest risk for late posttraumatic seizures BACKGROUND Traumatic brain injury is a major cause of death and disability . We sought to assess the safety and efficacy of dexanabinol , a synthetic cannabinoid analogue devoid of psychotropic activity , in severe traumatic brain injury . METHODS 861 patients with severe traumatic brain injury admitted to 86 specialist centres from 15 countries were included in a multi-centre , placebo-controlled , phase III trial . Patients were r and omised to receive a single intravenous 150 mg dose of dexanabinol or placebo within 6 h of injury . The primary outcome was the extended Glasgow outcome scale assessed at 6 months , with the point of dichotomisation into unfavourable versus favourable outcome differentiated by baseline prognostic risk . Prespecified subgroup analyses were defined by injury severity , recruitment rate , and time to dosing . Secondary analysis included control of intracranial pressure and quality of life . Analysis were prespecified in the protocol and the statistical analysis plan . This study is registered with Clinical Trials.gov , number NCT00129857 . FINDINGS 846 patients were included in the efficacy analysis . The extended Glasgow outcome scale at 6 months did not differ between groups ; 215 ( 50 % ) patients in the dexanabinol group and 214 ( 51 % ) patients in the placebo group had an unfavourable outcome ( odds ratio for a favourable response 1.04 ; 95 % CI 0.79 - 1.36 ) . Improvements in the control of intracranial pressure or quality of life were not recorded and subgroup analysis showed no indication of differential treatment effects . Dexanabinol was not associated with hepatic , renal , or cardiac toxic effects . INTERPRETATION Dexanabinol is safe , but is not efficacious in the treatment of traumatic brain injury OBJECT The goals of this study were to determine if the use of phenytoin to prevent early posttraumatic seizures following head injury was associated with significant adverse side effects and also to determine if the reduction in early posttraumatic seizures after phenytoin administration was associated with a change in mortality rates in head-injured patients . METHODS The authors performed a secondary analysis of the data obtained in a prospect i ve double-blind placebo-controlled study of 404 patients who were r and omly assigned to receive phenytoin or placebo for the prevention of early and late posttraumatic seizures . The incidence of adverse drug effects during the first 2 weeks of treatment , however , was low and not significantly different between the treated and placebo groups . Hypersensitivity reactions occurred in 0.6 % of the patients in the phenytoin-treated group compared with 0 % in the placebo group ( p = 1.0 ) during week 1 , and in 2.5 % of phenytoin-treated compared with 0 % of placebo-treated patients ( p = 0.12 ) for the first 2 weeks of treatment . Mortality rates were also similar in both groups . Although the mortality rate was higher in patients who developed seizures , this increase was related to the greater severity of the injuries sustained by these patients at the time of the original trauma . CONCLUSIONS The results of this study indicate that the incidence of early posttraumatic seizure can be effectively reduced by prophylactic administration of phenytoin for 1 or 2 weeks without a significant increase in drug-related side effects . Reduction in posttraumatic seizure during the 1st week , however , was not associated with a reduction in the mortality rate This study examined the relationship of posttraumatic seizures and head injury severity to neuropsychological performance and psychosocial functioning in 210 adults who were prospect ively followed and assessed 1 year after moderate to severe traumatic head injury . Eighteen percent ( n = 38 ) of the patients experienced 1 or more late seizures ( i.e. , seizures occurring 8 or more days posttrauma ) by the time of the 1-year followup . As expected , the head injured patients who experienced late posttraumatic seizures were those with the most severe head injuries , and they were significantly more impaired on the neuropsychological and psychosocial measures compared to those who remained seizure free . However , after the effects of head injury severity were controlled , there were no significant differences in neuropsychological and psychosocial outcome at 1 year as a function of having seizures . These findings suggest that worse outcomes in patients who develop posttraumatic seizures up to 1 year posttrauma largely reflect the effects of the brain injuries that cause seizures , rather than the effect of seizures A double-blind trial of phenytoin therapy following craniotomy was performed to test the hypothesis that phenytoin is effective in reducing postoperative epilepsy . A significant reduction in the frequency of epilepsy was observed in the group receiving the active drug up to the 10th postoperative week . Half of the seizures occurred in the first 2 weeks and two-thirds within 1 month of cranial surgery . High rates of epilepsy were observed after surgery in patients with meningioma , metastasis , aneurysm , and head injury . Routine prophylaxis with phenytoin ( in a dosage of 5 to 6 mg/kg/day ) would seem to be indicated , particularly in high-risk patients and , where possible , this treatment should be started 1 week preoperatively . Seizure control is best when therapeutic levels of phenytoin are maintained Posttraumatic seizures develop in up to 20 % of children following severe traumatic brain injury ( TBI ) . Children ages 6–17 years with one or more risk factors for the development of posttraumatic epilepsy , including presence of intracranial hemorrhage , depressed skull fracture , penetrating injury , or occurrence of posttraumatic seizure were recruited into this phase II study . Treatment subjects received levetiracetam 55 mg/kg/day , b.i.d . , for 30 days , starting within 8 h postinjury . The recruitment goal was 20 treated patients . Twenty patients who presented within 8–24 h post‐TBI and otherwise met eligibility criteria were recruited for observation . Follow‐up was for 2 years . Forty‐five patients screened within 8 h of head injury met eligibility criteria and 20 were recruited into the treatment arm . The most common risk factor present for pediatric inclusion following TBI was an immediate seizure . Medication compliance was 95 % . No patients died ; 19 of 20 treatment patients were retained and one observation patient was lost to follow‐up . The most common severe adverse events in treatment subjects were headache , fatigue , drowsiness , and irritability . There was no higher incidence of infection , mood changes , or behavior problems among treatment subjects compared to observation subjects . Only 1 ( 2.5 % ) of 40 subjects developed posttraumatic epilepsy ( defined as seizures > 7 days after trauma ) . This study demonstrates the feasibility of a pediatric posttraumatic epilepsy prevention study in an at‐risk traumatic brain injury population . Levetiracetam was safe and well tolerated in this population . This study sets the stage for implementation of a prospect i ve study to prevent posttraumatic epilepsy in an at‐risk population BACKGROUND Brain Trauma Foundation guidelines recommend seizure prophylaxis for preventing early posttraumatic seizure ( PTS ) . Phenytoin ( PHE ) is commonly used . Despite a paucity of data in traumatic brain injury , levetiracetam ( LEV ) has been introduced as a potential replacement , which is more costly but does not require serum monitoring . The purpose of this study was to compare the efficacy of PHE with that of LEV for preventing early PTS . METHODS Consecutive blunt traumatic brain injury patients undergoing seizure prophylaxis were prospect ively enrolled at two Level 1 trauma centers during a 33-month period . Seizure prophylaxis was administered according to local protocol . Patients were monitored prospect ively throughout their hospital stay for clinical evidence of seizure activity . PHE was compared with LEV with clinical early PTS as the primary outcome measure , defined as a seizure diagnosed clinical ly , occurring within 7 days of admission . RESULTS A total of 1,191 patients were screened for enrollment , after excluding 378 ( 31.7 % ) who did not meet inclusion criteria ; 813 ( 68.3 % ) were analyzed ( 406 LEV and 407 PHE ) . There were no significant differences between LEV and PHE in age ( 51.7 [ 21.3 ] vs. 53.6 [ 22.5 ] , p = 0.205 ) , male ( 73.9 % vs. 68.8 % , p = 0.108 ) , Injury Severity Score ( ISS ) ( 20.0 [ 10.0 ] vs. 21.0 [ 10.6 ] , p = 0.175 ) , Marshall score of 3 or greater ( 18.5 % vs. 14.7 % , p = 0.153 ) , or craniectomy ( 8.4 % vs. 11.8 % , p = 0.106 ) . There was no difference in seizure rate ( 1.5 % vs.1.5 % , p = 0.997 ) , adverse drug reactions ( 7.9 % vs. 10.3 % , p = 0.227 ) , or mortality ( 5.4 % vs. 3.7 % , p = 0.236 ) . CONCLUSION In this prospect i ve evaluation of early PTS prophylaxis , LEV did not outperform PHE . Cost and need for serum monitoring should be considered in guiding the choice of prophylactic agent . LEVEL OF EVIDENCE Therapeutic study , level III In a double-blind trial of phenytoin for the prevention of postoperative epilepsy in craniotomy patients , epilepsy was observed in 7.9 % ( 8/101 ) of patients treated with phenytoin and in 16.7 % ( 17/102 ) of those receiving placebo . Therapeutic drug levels were associated with a significant reduction in the frequency of epilepsy . Three-quarters of the fits occurred within a month of cranial surgery . High rates of epilepsy have been observed after cranial surgery in patients with meningioma , aneurysm , and head injury with or without intracranial clots , and routine prophylaxis with phenytoin would seem to be indicated in such patients The effects of chronic phenytoin therapy on serum calcium , phosphorus , folate , and various hematological indices were assessed . One hundred and fifty-one patients , ages 18 months to 81 years , received phenytoin in a previously-conducted , double-blind , placebo-controlled study . Of the patients receiving phenytoin , initially 127 were evaluable while for control patients receiving placebo , 116 were evaluable . All patients had various laboratory parameters monitored at one day post-loading dose , one week , 1,3,6,9,12,15,18,21 , and 24 months . Laboratory values examined were serum calcium , phosphorus , folate , white blood cell count with differential , hemoglobin , hematocrit , and red blood cell and platelet counts . A statistical analysis using the t-test method was employed to evaluate data . Data are reported as mean values ± st and ard deviation . Patients suffering early hypersensitivity , manifested by a morbilliform skin rash , were removed from the drug by day 30 and were not included in the chronic therapy review . Results indicate that the various laboratory values examined were not significantly affected by phenytoin administration in the patient population . Therefore , chronic phenytoin therapy following the initial hypersensitivity period does not cause abnormal laboratory values as followed in this study OBJECTIVE To compare the effects of prophylactic anticonvulsant use of phenytoin and carbamazepine on the cognitive and emotional status of the patient after brain injury . DESIGN Double-blind , placebo-controlled study with assessment s before and after withdrawal from drug treatment . SETTING Patients had been initially treated by neurosurgeons at a university hospital and were followed up during the study on an outpatient basis . PATIENTS Forty of 64 patients receiving phenytoin and 42 of 127 patients receiving carbamazepine from 6 to 44 months for seizure prophylaxis after brain injury met study criteria and were assigned to continue or discontinue treatment . Groups were balanced for age , sex , race , weight , intelligence , type of injury , duration of therapy , and drug plasma concentration at screening . INTERVENTION A battery of neuropsychological tests was administered twice during a 4-week baseline period , at the end of a 4- to 5-week period of continued drug treatment or placebo , and after 4 weeks of not receiving medication . MAIN OUTCOME MEASURES Attention and concentration , psychomotor speed , memory , verbal fluency , and emotional state . RESULTS No significant differences were found in the performance of patients in medication and placebo groups for either drug at the end of the placebo phase . Patients in the combined groups showed significant improvement ( P < .01 ) on several measures of motor and speeded performance following cessation of drug treatment . Multivariate analyses showed additional differences between phenytoin and carbamazepine and also suggested a significant practice effect on some measures used . CONCLUSIONS Both phenytoin and carbamazepine seem to have negative effects on cognitive performance , particularly on tasks with significant motor and speed components . Practice effects were noted and may account for much of the improvement when patients stopped taking the drugs . Overall effects of the drugs were small and of limited clinical significance , but differences among subjects were noted that may affect selection of a particular drug for the individual patient OBJECTIVES To evaluate the safety and tolerability of treatment with levetiracetam and determine the trough levels of levetiracetam in patients with traumatic brain injury ( TBI ) who are at high risk for posttraumatic epilepsy ( PTE ) . DESIGN Open-label , nonr and omized phase 2 study with 2 arms comparing levetiracetam treatment vs observation . SETTING Two level 1 trauma centers . PATIENTS A total of 422 participants 6 years or older with TBI who have a 20 % risk for PTE were screened . Of these participants , 205 ( 48.6 % ) were eligible . A total of 126 participants were enrolled : 86 adults and 40 children . A total of 66 participants were in the treatment group ( 46 adults and 20 children ) , and a total of 60 participants were in the observation group ( 40 adults and 20 children ) . Participants presenting within 8 hours after TBI received treatment , and those presenting more than 8 to 24 hours after TBI did not . INTERVENTION Treatment with levetiracetam ( 55 mg/kg/d ) for 30 days starting within 8 hours after injury . MAIN OUTCOME MEASURES Number of adverse events , mood score , number of infections , trough level of levetiracetam , and PTE . RESULTS Of the 66 participants treated with levetiracetam , 2 ( 3 % ) stopped treatment owing to toxicity ( somnolence ) . The most common adverse events were fatigue , headache , and somnolence . Mood scores and number of infections did not differ between the treatment and observation groups . Mean trough levels of levetiracetam on days 2 to 30 ranged from 19.6 to 26.7 μg/mL. At 2 years , 13 of 86 adults ( 15.1 % ) and 1 of 40 children ( 2.5 % ) developed PTE . At 2 years , 5 of 46 treated adults ( 10.9 % ) and 8 of 40 untreated adults ( 20.0 % ) developed PTE ( relative risk , 0.47 ; P=.18 ) . CONCLUSION Treatment with 55 mg/kg/d of levetiracetam ( a dose with an antiepileptogenic effect on animals ) for patients with TBI at risk for PTE is safe and well tolerated , with plasma levels similar to those in animal studies . The findings support further evaluation of levetiracetam treatment for the prevention of PTE . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01463033 Abstract Introduction Levetiracetam ( LEV ) is used in the setting of acute brain injury for seizure treatment or prophylaxis but its safety and efficacy in this setting is unknown . Method We retrospectively analyzed the patterns of use and safety/efficacy of LEV in 379 patients treated in the neuroscience intensive care unit ( NSICU ) . We extracted from the charts clinical data including diagnosis , AED therapy before and during stay in the NSICU , complications of treatment , length of stay , and clinical outcomes ( improvement , Glasgow Coma Scale , and death ) . We analyzed the data using binary and ordered ( multi-category ) logistic regression . Results Overall , our findings are that phenytoin used prior to the NSICU admission was frequently replaced with LEV monotherapy ( P < 0.001 ) . Patients treated with LEV monotherapy when compared to other AEDs had lower complication rates and shorter NSICU stays . Older patients and patients with brain tumors or strokes were preferentially treated with LEV for prevention and /or management of seizures ( all P ≤ 0.014 ) . Discussion The results of this study suggest that LEV is a frequently used AED in the setting of acute brain injury and that it may be a desirable alternative to phenytoin . Prospect i ve studies evaluating the long-term safety , efficacy and outcomes of LEV in this setting are indicated The high incidence rate and the invalidating nature of post-traumatic epilepsy after severe brain injury have encouraged the authors to review the prophylactic treatment of this type of epilepsy . Thirty-four out of 86 r and omised patients with brain injuries admitted into a neurotraumatology intensive care unit were treated prophylactically , immediately after the injury , with an intravenous hydantoin injection in a dose sufficient to provide stable and effective blood levels . This was followed by dose-adjusted oral administration maintained for a minimum period of 3 months . After a 2 years ' follow-up , there was a significant difference between treated and untreated patients , since only 6 per cent of the patients treated suffered from post-traumatic epilepsy , as against 42 percent in the untreated group OBJECT Current st and ard of care for patients with severe traumatic brain injury ( TBI ) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures . Phenytoin alters drug metabolism , induces fever , and requires therapeutic-level monitoring . Alternatively , levetiracetam ( Keppra ) does not require serum monitoring or have significant pharmacokinetic interactions . In the current study , the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI . METHODS Data were prospect ively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy . Patients underwent 1-hour electroencephalographic ( EEG ) monitoring if they displayed persistent coma , decreased mental status , or clinical signs of seizures . The EEG results were grouped into normal and abnormal findings , with abnormal EEG findings further categorized as seizure activity or seizure tendency . RESULTS Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring . In 7 of these 15 cases the results were normal and in 8 abnormal ; 1 patient had seizure activity , whereas 7 had seizure tendency . Twelve of 41 patients in the phenytoin group received EEG monitoring , with all results being normal . Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity ( p = 0.556 ) . Patients receiving levetiracetam had a higher incidence of abnormal EEG findings ( p = 0.003 ) . CONCLUSIONS Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis This r and omized double-blind placebo-controlled study was undertaken in a series of 179 patients to determine whether phenytoin administered soon after head injury lessens the incidence of late posttraumatic epilepsy . When delayed hypersensitivity to phenytoin developed , the patient was switched to phenobarbital . The patients were followed for 18 months to detect the occurrence of seizures and to serially measure plasma phenytoin concentrations . There was no significant difference in the percentage of patients having late seizures in the treated and placebo groups ( p = 0.75 ) . The time between injury and seizures did not significantly differ between the two groups . The results provide no support for the continued use of phenytoin in the low therapeutic range for prophylaxis against late posttraumatic seizures . It can not be concluded that higher phenytoin plasma concentrations and higher compliance rates than obtained in this study would not have significantly decreased the occurrence of late posttraumatic epilepsy . The finding that no patient with a phenytoin plasma concentration of 12 microgram/ml or higher had a seizure raises the question of whether phenytoin in blood concentrations in higher therapeutic ranges might lessen the occurrence of posttraumatic epilepsy , and should be studied further . Posttraumatic epilepsy is a major public health problem deserving a large cooperative trial to determine if phenytoin at higher blood levels than obtained in this study , or other currently available or newly developed drugs , can prevent the occurrence of posttraumatic epilepsy PURPOSE Secondary brain ischaemia ( SBI ) usually develops after aneurysmal subarachnoid haemorrhage ( SAH ) and severe traumatic brain injury ( TBI ) . Current approaches to managing these conditions are based either on intracranial pressure-targeted therapy ( ICP-targeted ) with cerebral microdialysis ( CM ) monitoring according to the modified Lund concept or cerebral perfusion pressure-targeted therapy ( CPP-targeted ) . We present a prospect i ve , r and omised controlled study comparing relative effectiveness of the two management strategies . METHODS Sixty comatose operated patients with SBI following aneurysmal SAH and severe TBI were r and omised into ICP-targeted therapy with CM monitoring and CPP-targeted therapy groups . Mortality rates in both groups were calculated and tissue biochemical signs of cerebral ischaemia were analysed using CM . Measured CM data were related to outcome ( Glasgow Outcome Scale [ GOS ] score 1 , 2 and 3 for poor outcome or GOS score 4 and 5 for good outcome ) . RESULTS Patients treated with ICP-targeted therapy with CM monitoring had significantly lower mortality rate as compared with those treated with CPP-targeted therapy ( P=0.03 ) . Patients monitored with CM who had poor outcome had lower mean values of glucose and higher mean values of glycerol and lactate/pyruvate ratio as compared with those who had good outcome ( glucose : P=0.003 ; glycerol : P=0.02 ; lactate/pyruvate ratio : P=0.01 ) . There was no difference in the mortality outcome between aneurysmal SAH and severe TBI in the two groups ( P=0.28 for ICP-targeted therapy with CM monitoring , P=0.36 for CPP-targeted therapy ) . Also , there were no differences in the CM values between patients with aneurysmal SAH and severe TBI who underwent ICP-targeted therapy ( glucose : P=0.23 ; glycerol : P=0.41 ; lactate/pyruvate ratio : P=0.40 ) . CONCLUSION The modified Lund concept , directed at bedside real-time monitoring of brain biochemistry by CM showed better results compared to CPP-targeted therapy in the treatment of comatose patients sustaining SBI after aneurysmal SAH and severe TBI Background Anti-epileptic drugs are commonly used for seizure prophylaxis after neurological injury . We performed a study comparing intravenous ( IV ) levetiracetam ( LEV ) to IV phenytoin ( PHT ) for seizure prophylaxis after neurological injury . Methods In this prospect i ve , single-center , r and omized , single-blinded comparative trial of LEV versus PHT ( 2:1 ratio ) in patients with severe traumatic brain injury ( sTBI ) or subarachnoid hemorrhage ( NCT00618436 ) patients received IV load with either LEV or fosphenytoin followed by st and ard IV doses of LEV or PHT . Doses were adjusted to maintain therapeutic serum PHT concentrations or if patients had seizures . Continuous EEG ( cEEG ) monitoring was performed for the initial 72 h ; outcome data were collected . Results A total of 52 patients were r and omized ( LEV = 34 ; PHT = 18 ) ; 89 % with sTBI . When controlling for baseline severity , LEV patients experienced better long-term outcomes than those on PHT ; the Disability Rating Scale score was lower at 3 months ( P = 0.042 ) and the Glasgow Outcomes Scale score was higher at 6 months ( P = 0.039 ) . There were no differences between groups in seizure occurrence during cEEG ( LEV 5/34 vs. PHT 3/18 ; P = 1.0 ) or at 6 months ( LEV 1/20 vs. PHT 0/14 ; P = 1.0 ) , mortality ( LEV 14/34 vs. PHT 4/18 ; P = 0.227 ) . There were no differences in side effects between groups ( all P > 0.15 ) except for a lower frequency of worsened neurological status ( P = 0.024 ) , and gastrointestinal problems ( P = 0.043 ) in LEV-treated patients . Conclusions This study of LEV versus PHT for seizure prevention in the NSICU showed improved long-term outcomes of LEV-treated patients vis-à-vis PHT-treated patients . LEV appears to be an alternative to PHT for seizure prophylaxis in this setting |
2,680 | 26,166,124 | IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT .
Overall mortality did not differ significantly . | Abstract There has not been a clear answer about the efficacy of intraoperative radiotherapy ( IORT ) for women with early-stage breast cancer .
The aim of this meta- analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy ( EBRT ) for women with early-stage breast cancer . | BACKGROUND After breast-conserving surgery , 90 % of local recurrences occur within the index quadrant despite the presence of multicentric cancers elsewhere in the breast . Thus , restriction of radiation therapy to the tumour bed during surgery might be adequate for selected patients . We compared targeted intraoperative radiotherapy with the conventional policy of whole breast external beam radiotherapy . METHODS Having safely piloted the new technique of single-dose targeted intraoperative radiotherapy with Intrabeam , we launched the TARGIT-A trial on March 24 , 2000 . In this prospect i ve , r and omised , non-inferiority trial , women aged 45 years or older with invasive ductal breast carcinoma undergoing breast-conserving surgery were enrolled from 28 centres in nine countries . Patients were r and omly assigned in a 1:1 ratio to receive targeted intraoperative radiotherapy or whole breast external beam radiotherapy , with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy . Neither patients nor investigators or their teams were masked to treatment assignment . Postoperative discovery of predefined factors ( eg , lobular carcinoma ) could trigger addition of external beam radiotherapy to targeted intraoperative radiotherapy ( in an expected 15 % of patients ) . The primary outcome was local recurrence in the conserved breast . The predefined non-inferiority margin was an absolute difference of 2.5 % in the primary endpoint . All r and omised patients were included in the intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00983684 . FINDINGS 1113 patients were r and omly allocated to targeted intraoperative radiotherapy and 1119 were allocated to external beam radiotherapy . Of 996 patients who received the allocated treatment in the targeted intraoperative radiotherapy group , 854 ( 86 % ) received targeted intraoperative radiotherapy only and 142 ( 14 % ) received targeted intraoperative radiotherapy plus external beam radiotherapy . 1025 ( 92 % ) patients in the external beam radiotherapy group received the allocated treatment . At 4 years , there were six local recurrences in the intraoperative radiotherapy group and five in the external beam radiotherapy group . The Kaplan-Meier estimate of local recurrence in the conserved breast at 4 years was 1.20 % ( 95 % CI 0.53 - 2.71 ) in the targeted intraoperative radiotherapy and 0.95 % ( 0.39 - 2.31 ) in the external beam radiotherapy group ( difference between groups 0.25 % , -1.04 to 1.54 ; p=0.41 ) . The frequency of any complications and major toxicity was similar in the two groups ( for major toxicity , targeted intraoperative radiotherapy , 37 [ 3.3 % ] of 1113 vs external beam radiotherapy , 44 [ 3.9 % ] of 1119 ; p=0.44 ) . Radiotherapy toxicity ( Radiation Therapy Oncology Group grade 3 ) was lower in the targeted intraoperative radiotherapy group ( six patients [ 0.5 % ] ) than in the external beam radiotherapy group ( 23 patients [ 2.1 % ] ; p=0.002 ) . INTERPRETATION For selected patients with early breast cancer , a single dose of radiotherapy delivered at the time of surgery by use of targeted intraoperative radiotherapy should be considered as an alternative to external beam radiotherapy delivered over several weeks . FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre , UCLH Charities , National Institute for Health Research Health Technology Assessment programme , Ninewells Cancer Campaign , National Health and Medical Research Council , and German Federal Ministry of Education and Research ( BMBF ) Background Since the results from the r and omized TARGIT A trial were published , intraoperative radiotherapy ( IORT ) is used more often . IORT can be provided as accelerated partial breast irradiation ( APBI ) or as a boost . The definition of suitable patients for IORT as APBI differs between different national societies ( e.g. ESTRO and ASTRO ) and different inclusion criteria of trials and so does the eligibility of patients . This analysis identifies eligible patients for IORT according to available consensus statements and inclusion criteria of the ongoing TARGIT trials . Methods Between 01/03 – 12/09 , 1505 breast cancer cases were treated at the breast cancer center at the University Medical Center Mannheim . Complete data sets for age , stage ( T , N , and M ) , histology and hormone receptor status were available in 1108 cases . Parameters to identify eligible patients are as follows : ESTRO : > 50 years , invasive ductal carcinoma/other favorable histology ( IDC ) , T1 - 2 ( ≤3 cm ) , N0 , any hormone receptor status , M0 ; ASTRO : ≥60 years , IDC , T1 , N0 , positive estrogen hormone receptor status , M0 ; TARGIT E “ elderly ” , risk adapted radiotherapy with IORT followed by external beam radiotherapy in case of risk factors in final histopathology , phase II : ≥70 years , IDC , T1 , N0 , any hormone receptor status , M0 ; TARGIT C “ consolidation ” , risk adapted radiotherapy , phase IV : ≥50 years , IDC , T1 , N0 , positive hormone receptor status , M0 ; TARGIT BQR “ boost quality registry ” : every age , every histology , T1 - 2 ( max . 3.5 cm ) , any hormone receptor status , N0/+ , M0/+ . Results Out of the 1108 cases , 379 cases ( 34.2 % ) were suitable for IORT as APBI regarding the ESTRO and 175 ( 15.8 % ) regarding the ASTRO consensus statements . 82 ( 7.4 % ) patients were eligible for the TARGIT E trial , 258 ( 23.3 % ) for the TARGIT C trial and 671 ( 60.6 % ) for the TARGIT BQR registry . According to the consensus statements of ASTRO ( 45.1 % ) and ESTRO ( 41.4 % ) about half of the eligible patients were treated with IORT as APBI . From the eligible patients fulfilling the criteria for IORT boost ( 35 % ) about one third was eventually treated . Conclusions Patient selection for IORT should be restrictive . For IORT as APBI the TARGIT trials are even more restrictive including patients than the ESTRO and ASTRO consensus statements BACKGROUND A r and omised trial was conducted comparing wide lumpectomy and breast irradiation with modified radical mastectomy . As the follow-up was long ( mean duration 22 years ) , we analysed the variation in the effect of treatment over time . PATIENTS AND METHODS The trial included 179 patients with a breast cancer measuring < /=2 cm at macroscopic examination . Eighty-eight patients had breast-conserving surgery and radiotherapy , and 91 underwent mastectomy . All patients had axillary dissection . The analyses were based on Cox models with time-dependent treatment effects . RESULTS The effect of treatment on death or metastasis did not vary with time . The risk of local recurrence was lower during the first 5 years for the breast-conserving surgery group as compared with the mastectomy group , but higher after 5 years ( P = 10(-4 ) for a different treatment effect over time ) . Similar results were found in a data base including 1847 patients with small breast tumours at diagnosis . In this analysis , late breast recurrences were also more frequent in the breast-conserving surgery group and this treatment effect was greater among younger patients ( < /=40 years at the time of diagnosis ) . CONCLUSIONS Late breast recurrences were more frequently observed in younger patients treated with breast-conserving treatment compared with those su bmi tted to mastectomy . These results require confirmation in other r and omised studies so that younger patients with early breast cancer can receive adequate counselling and so that a more stringent long-term follow-up policy can be adopted when breast-conserving treatment is planned PURPOSE Mastectomy versus excisional biopsy ( lumpectomy ) plus radiation for the treatment of stage I and II breast cancer was compared in a prospect i ve r and omized study . PATIENTS AND METHODS From 1979 to 1987 , 247 women were r and omized and 237 were treated on this study . All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin . Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed . RESULTS The minimum time on the study was 18 months and the median time on the study was 68 months . No differences in overall survival or disease-free survival were observed . Actuarial estimates at 5 years showed that 85 % of mastectomy-treated patients were alive compared with 89 % of the lumpectomy/radiation patients ( P2 = .49 ; 95 % two-sided confidence interval [ CI ] about this difference , 0 % to 9 % favoring lumpectomy plus radiation ) . The probability of failure in the irradiated breast was 12 % by 5 years and 20 % by 8 years according to actuarial estimates . Of 15 local breast failures , 14 were treated with and 12 were controlled by mastectomy ; the ultimate local-regional control was similar in both arms of the trial . CONCLUSION These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients BACKGROUND The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy ( TARGIT ) versus fractionated external beam radiotherapy ( EBRT ) for breast cancer . We report 5-year results for local recurrence and the first analysis of overall survival . METHODS TARGIT-A was a r and omised , non-inferiority trial . Women aged 45 years and older with invasive ductal carcinoma were enrolled and r and omly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT , with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy : r and omisation occurred either before lumpectomy ( prepathology stratum , TARGIT concurrent with lumpectomy ) or after lumpectomy ( postpathology stratum , TARGIT given subsequently by reopening the wound ) . Patients in the TARGIT group received supplemental EBRT ( excluding a boost ) if unforeseen adverse features were detected on final pathology , thus radiotherapy was risk-adapted . The primary outcome was absolute difference in local recurrence in the conserved breast , with a prespecified non-inferiority margin of 2·5 % at 5 years ; prespecified analyses included outcomes as per timing of r and omisation in relation to lumpectomy . Secondary outcomes included complications and mortality . This study is registered with Clinical Trials.gov , number NCT00983684 . FINDINGS Patients were enrolled at 33 centres in 11 countries , between March 24 , 2000 , and June 25 , 2012 . 1721 patients were r and omised to TARGIT and 1730 to EBRT . Supplemental EBRT after TARGIT was necessary in 15·2 % [ 239 of 1571 ] of patients who received TARGIT ( 21·6 % prepathology , 3·6 % postpathology ) . 3451 patients had a median follow-up of 2 years and 5 months ( IQR 12 - 52 months ) , 2020 of 4 years , and 1222 of 5 years . The 5-year risk for local recurrence in the conserved breast was 3·3 % ( 95 % CI 2·1 - 5·1 ) for TARGIT versus 1·3 % ( 0·7 - 2·5 ) for EBRT ( p=0·042 ) . TARGIT concurrently with lumpectomy ( prepathology , n=2298 ) had much the same results as EBRT : 2·1 % ( 1·1 - 4·2 ) versus 1·1 % ( 0·5 - 2·5 ; p=0·31 ) . With delayed TARGIT ( postpathology , n=1153 ) the between-group difference was larger than 2·5 % ( TARGIT 5·4 % [ 3·0 - 9·7 ] vs EBRT 1·7 % [ 0·6 - 4·9 ] ; p=0·069 ) . Overall , breast cancer mortality was much the same between groups ( 2·6 % [ 1·5 - 4·3 ] for TARGIT vs 1·9 % [ 1·1 - 3·2 ] for EBRT ; p=0·56 ) but there were significantly fewer non-breast-cancer deaths with TARGIT ( 1·4 % [ 0·8 - 2·5 ] vs 3·5 % [ 2·3 - 5·2 ] ; p=0·0086 ) , attributable to fewer deaths from cardiovascular causes and other cancers . Overall mortality was 3·9 % ( 2·7 - 5·8 ) for TARGIT versus 5·3 % ( 3·9 - 7·3 ) for EBRT ( p=0·099 ) . Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT ( four of 1720 vs 13 of 1731 , p=0·029 ) . INTERPRETATION TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol , as an alternative to postoperative EBRT . FUNDING University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre , UCLH Charities , National Institute for Health Research Health Technology Assessment programme , Ninewells Cancer Campaign , National Health and Medical Research Council , and German Federal Ministry of Education and Research BACKGROUND Intraoperative radiotherapy with electrons allows the substitution of conventional postoperative whole breast irradiation with one session of radiotherapy with the same equivalent dose during surgery . However , its ability to control for recurrence of local disease required confirmation in a r and omised controlled trial . METHODS This study was done at the European Institute of Oncology ( Milan , Italy ) . Women aged 48 - 75 years with early breast cancer , a maximum tumour diameter of up to 2·5 cm , and suitable for breast-conserving surgery were r and omly assigned in a 1:1 ratio ( using a r and om permuted block design , stratified for clinical tumour size [ < 1·0 cm vs 1·0 - 1·4 cm vs ≥1·5 cm ] ) to receive either whole-breast external radiotherapy or intraoperative radiotherapy with electrons . Study coordinators , clinicians , and patients were aware of the assignment . Patients in the intraoperative radiotherapy group received one dose of 21 Gy to the tumour bed during surgery . Those in the external radiotherapy group received 50 Gy in 25 fractions of 2 Gy , followed by a boost of 10 Gy in five fractions . This was an equivalence trial ; the prespecified equivalence margin was local recurrence of 7·5 % in the intraoperative radiotherapy group . The primary endpoint was occurrence of ipsilateral breast tumour recurrences ( IBTR ) ; overall survival was a secondary outcome . The main analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01849133 . FINDINGS 1305 patients were r and omised ( 654 to external radiotherapy and 651 to intraoperative radiotherapy ) between Nov 20 , 2000 , and Dec 27 , 2007 . After a medium follow-up of 5·8 years ( IQR 4·1 - 7·7 ) , 35 patients in the intraoperative radiotherapy group and four patients in the external radiotherapy group had had an IBTR ( p<0·0001 ) . The 5-year event rate for IBRT was 4·4 % ( 95 % CI 2·7 - 6·1 ) in the intraoperative radiotherapy group and 0·4 % ( 0·0 - 1·0 ) in the external radiotherapy group ( hazard ratio 9·3 [ 95 % CI 3·3 - 26·3 ] ) . During the same period , 34 women allocated to intraoperative radiotherapy and 31 to external radiotherapy died ( p=0·59 ) . 5-year overall survival was 96·8 % ( 95 % CI 95·3 - 98·3 ) in the intraoperative radiotherapy group and 96·9 % ( 95·5 - 98·3 ) in the external radiotherapy group . In patients with data available ( n=464 for intraoperative radiotherapy ; n=412 for external radiotherapy ) we noted significantly fewer skin side-effects in women in the intraoperative radiotherapy group than in those in the external radiotherapy group ( p=0·0002 ) . INTERPRETATION Although the rate of IBTR in the intraoperative radiotherapy group was within the prespecified equivalence margin , the rate was significantly greater than with external radiotherapy , and overall survival did not differ between groups . Improved selection of patients could reduce the rate of IBTR with intraoperative radiotherapy with electrons . FUNDING Italian Association for Cancer Research , Jacqueline Seroussi Memorial Foundation for Cancer Research , and Umberto Veronesi Foundation The Danish Breast Cancer Cooperative Group ( DBCG ) conducted a r and omized trial comparing breast conservation with mastectomy in patients with invasive mammary carcinoma . From January 1983 to March 1989 , the trial accrued a total of 1153 women . Of this number , 905 patients ( 79 % ) were r and omly assigned to one of the two treatment options , whereas 248 patients ( 21 % ) did not accept r and omization . Of the r and omly assigned patients , 90 % received the surgical option to which they had been originally assigned . In the breast conservation arm the tumor was excised with the intention of obtaining free margins determined at gross examination , and radiotherapy was subsequently administered to residual breast tissue . The axilla was dissected in all instances . Patient and tumor characteristics were similar in the two r and omization arms . The median follow-up time was 40 months . At 6 years of life-table analysis the probability of recurrence-free survival was 70 % in the breast conservation arm against 66 % in the mastectomy arm . Survival figures were 79 % against 82 % , respectively In a prospect i ve r and omized clinical trial conducted by the European Organization for Research and Treatment of Cancer ( EORTC ) , mastectomy was compared with breast-conserving therapy in 903 stage I and stage II breast cancer patients entering the study between 1980 and 1986 . The main participating centers were : Guy 's Hospital , London ; The Netherl and s Cancer Institute , Amsterdam ; University Hospital , Leuven ; Radiotherapy Institute , Rotterdam ; Breast Unit , Tijgerberg , S.A. The data were collected in the EORTC Data Center , Brussels . Treatment in the study arm consisted of lumpectomy , axillary clearance , and radiotherapy to the breast ( 50 Gy external irradiation in 5 weeks followed by boost with iridium implant of 25 Gy ) . Important in this study is the large number of TNM stage II patients ( 755 ) . Most patients were stage II because of the size of the tumor ( 2 - 5 cm ) . The patient and tumor characteristics in the study and control groups were well balanced . So far the survival curves and local recurrence rates are not statistically different for the two study arms . Tumor size was found in univariate analysis to be a significant risk factor for local recurrence in the breast-conserving therapy group but not in the mastectomy group . Results of salvage treatment for local recurrence were not better for the breast-conserving therapy group compared with the mastectomy group . Measurements of quality of life and cosmesis show a clear benefit for the breast-conserving therapy group PURPOSE To report the 5-year results of a r and omized study comparing the survival and cosmetic results of breast-conserving treatment with partial breast irradiation ( PBI ) or conventional whole breast irradiation ( WBI ) . METHODS AND MATERIAL S Between 1998 and 2004 , 258 selected patients with T1 N0 - 1mi , Grade 1 - 2 , nonlobular breast cancer without presence of extensive intraductal component and resected with negative margins were r and omized after breast-conserving surgery to receive 50 Gy/25 fractions WBI ( n = 130 ) or PBI ( n = 128 ) . The latter consisted of either 7 x 5.2 Gy high-dose-rate ( HDR ) multicatheter brachytherapy ( BT ; n = 88 ) or 50 Gy/25 fractions electron beam ( EB ) irradiation ( n = 40 ) . RESULTS At a median follow-up of 66 months , the 5-year actuarial rate of local recurrence was 4.7 % and 3.4 % in the PBI and WBI arms , respectively ( p = 0.50 ) . There was no significant difference in the 5-year probability of overall survival ( 94.6 % vs. 91.8 % ) , cancer-specific survival ( 98.3 % vs. 96.0 % ) , and disease-free survival ( 88.3 % vs. 90.3 % ) . The rate of excellent to good cosmetic result was 77.6 % in the PBI group ( 81.2 % after HDR BT ; 70.0 % after EB ) and 62.9 % in the control group ( 52.2 % after telecobalt ; 65.6 % after 6 - 9-MV photons ; p(WBI/PBI ) = 0.009 ) . CONCLUSIONS Partial breast irradiation using interstitial HDR implants or EB to deliver radiation to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI . Significantly better cosmetic outcome can be achieved with carefully design ed HDR multicatheter implants compared with the outcome after WBI The TARGIT-A Trial is an international r and omized , prospect i ve trial comparing intraoperative radiotherapy ( IORT ) for equivalence to external beam radiotherapy ( EBRT ) following lumpectomy for invasive breast cancer in selected low-risk patients ; early results suggest that outcomes are similar . In addition to effectiveness data and cost considerations , the preferences of patients should help inform practice . This study was undertaken to explore and quantify preference in choosing between IORT and the current st and ard , EBRT . Eligible subjects were current or past c and i date s for breast-conserving surgery and radiation being seen at the University of California , San Francisco Breast Care Center . A trade-off technique varying the risk of local recurrence for IORT was used to quantify any additional accepted risk that these patients would accept to receive either treatment . Patients were first presented with a slideshow comparing EBRT with the experimental IORT option before being asked their preferences given hypothetical 10-year local recurrence risks . Patients were then given a question naire on demographic , social and clinical factors . Data from 81 patients were analyzed . The median additional accepted risk to have IORT was 2.3 % ( −9 to 39 % ) , mean 3.2 % . Only 7 patients chose to accept additional risk for EBRT ; 22 accepted IORT at no additional risk ; and the remaining 52 chose IORT with some additional risk . Patients weigh trade-offs of risks and benefits when presented with medical treatment choices . Our results show that the majority of breast cancer patients will accept a small increment of local risk for a simpler delivery of radiation . Further studies that incorporate outcome and side effect data from the TARGIT-A trial clarify the expected consequences of a local recurrence , and include an exp and ed range of radiation options that could help guide clinical decision making in this area PURPOSE This prospect i ve study ( Radiation Therapy Oncology Group 0319 ) examines the use of three-dimensional conformal external beam radiotherapy ( 3D-CRT ) to deliver accelerated partial breast irradiation ( APBI ) . Initial data on efficacy and toxicity are presented . METHODS AND MATERIAL S Patients with Stage I or II breast cancer with lesions < or =3 cm , negative margins and with < or =3 positive nodes were eligible . The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2x/day . Ipsilateral breast , ipsilateral nodal , contralateral breast , and distant failure ( IBF , INF , CBF , DF ) were estimated using the cumulative incidence method . Mastectomy-free , disease-free , and overall survival ( MFS , DFS , OS ) were recorded . The National Cancer Institute Common Terminology Criteria for Adverse Events , version 3 , was used to grade acute and late toxicity . RESULTS Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy . The median age of patients was 61 years with the following characteristics : 46 % tumor size < 1 cm ; 87 % invasive ductal histology ; 94 % American Joint Committee on Cancer Stage I ; 65 % postmenopausal ; 83 % no chemotherapy ; and 71 % with no hormone therapy . Median follow-up is 4.5 years ( 1.7 - 4.8 ) . Four-year estimates ( 95 % CI ) of efficacy are : IBF 6 % ( 0 - 12 % ) [ 4 % within field ( 0 - 9 % ) ] ; INF 2 % ( 0 - 6 % ) ; CBF 0 % ; DF 8 % ( 0 - 15 % ) ; MFS 90 % ( 78 - 96 % ) ; DFS 84 % ( 71 - 92 % ) ; and OS 96 % ( 85 - 99 % ) . Only two ( 4 % ) Grade 3 toxicities were observed . CONCLUSIONS Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up . However , additional patients , further follow-up , and mature Phase III data are needed to evaluate the extent of application , limitations , and value of this particular form of APBI The international r and omised targeted intraoperative radiotherapy ( TARGIT ) trial has demonstrated evidence of non-inferiority between the novel technique of TARGIT ( intra-operative radiotherapy with Intrabeam ® ) and conventional external beam radiotherapy ( EBRT ) in women with early breast cancer in terms of the primary outcome measure of risk of local relapse within the treated breast . Cosmesis is an increasingly important outcome of breast conserving treatment with both surgery and radiotherapy contributing to this . It was unknown if the single high dose of TARGIT may lead to damaging fibrosis and thus impair cosmesis further , so we objective ly evaluated the aesthetic outcome of patients within the TARGIT r and omised controlled trial . We have used an objective assessment tool for evaluation of cosmetic outcome . Frontal digital photographs were taken at baseline ( before TARGIT or EBRT ) and yearly thereafter for up to 5 years . The photographs were analysed by BCCT.core , a vali date d software which produces a composite score based on symmetry , colour and scar . 342 patients were assessed , median age at baseline 64 years ( IQR 59–68 ) . The scores were dichotomised into Excellent and Good ( EG ) , and Fair and Poor ( FP ) . There were statistically significant increases in the odds of having an outcome of EG for patients in the TARGIT group relative to the EBRT group at year 1 ( OR 2.07 , 95 % CI 1.12–3.85 , p = 0.021 ) and year 2 ( OR 2.11 , 95 % CI 1.0–4.45 , p = 0.05 ) . Following a totally objective assessment in a r and omised setting , the aesthetic outcome of patients demonstrates that those treated with TARGIT have a superior cosmetic result to those patients who received conventional external beam radiotherapy BACKGROUND We conducted 20 years of follow-up of women enrolled in a r and omized trial to compare the efficacy of radical ( Halsted ) mastectomy with that of breast-conserving surgery . METHODS From 1973 to 1980 , 701 women with breast cancers measuring no more than 2 cm in diameter were r and omly assigned to undergo radical mastectomy ( 349 patients ) or breast-conserving surgery ( quadrantectomy ) followed by radiotherapy to the ipsilateral mammary tissue ( 352 patients ) . After 1976 , patients in both groups who had positive axillary nodes also received adjuvant chemotherapy with cyclophosphamide , methotrexate , and fluorouracil . RESULTS Thirty women in the group that underwent breast-conserving therapy had a recurrence of tumor in the same breast , whereas eight women in the radical-mastectomy group had local recurrences ( P<0.001 ) . The crude cumulative incidence of these events was 8.8 percent and 2.3 percent , respectively , after 20 years . In contrast , there was no significant difference between the two groups in the rates of contralateral-breast carcinomas , distant metastases , or second primary cancers . After a median follow-up of 20 years , the rate of death from all causes was 41.7 percent in the group that underwent breast-conserving surgery and 41.2 percent in the radical-mastectomy group ( P=1.0 ) . The respective rates of death from breast cancer were 26.1 percent and 24.3 percent ( P=0.8 ) . CONCLUSIONS The long-term survival rate among women who undergo breast-conserving surgery is the same as that among women who undergo radical mastectomy . Breast-conserving surgery is therefore the treatment of choice for women with relatively small breast cancers |
2,681 | 11,406,038 | Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo .
Analysis of pooling eight r and omised clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers .
REVIEW ER 'S CONCLUSIONS Based on one low quality trial , the medicinal herb ' Jianpi Wenshen recipe ' may have an antiviral activity in asymptomatic carriers of hepatitis B virus . | BACKGROUND About 350 million people are chronically infected carriers of hepatitis B virus and are at a higher risk of serious illness and death from cirrhosis of the liver and liver cancer .
Chinese medicinal herbs have been used widely for more than 2000 years to treat chronic liver disease .
OBJECTIVES To assess whether Chinese medicinal herbs are effective and safe for treating asymptomatic carriers of hepatitis B virus . | Several drugs which react with DNA decrease hepatitis B viral ( HBV ) DNA polymerase activity in vitro . Because such an alteration of viral replication , if produced in patients with hepatitis B surface antigen (HBsAg)-positive chronic hepatitis , may lead to elimination of viral infection , we conducted a controlled trial of the use of the intercalating agent , quinacrine hydrochloride , in treatment of HBsAg-positive chronic hepatitis . No patient converted from HBsAg positive to negative during the trial and no consistent effect on HBV DNA polymerase activity was noted . Following treatment , elevated transaminase values and alterations of HBV markers were observed in several patients . Fluctuations of transaminase values and HBV markers may reflect alterations in host immunity and viral replication . Quinacrine alone is ineffective in therapy of chronic HBV infection . Additional study with intercalating agents , perhaps in conjunction with other drugs , is suggested In a preliminary study , carriers of hepatitis B virus were treated with a preparation of the plant Phyllanthus amarus for 30 days . 22 of 37 ( 59 % ) treated patients had lost hepatitis B surface antigen when tested 15 - 20 days after the end of the treatment compared with only 1 of 23 ( 4 % ) placebo-treated controls . Some subjects have been followed for up to 9 months . In no case has the surface antigen returned . Clinical observation revealed few or no toxic effects . The encouraging results of this preliminary study recommend continued evaluation of this plant and the active principles isolated from it We studied the effect of Sho-saiko-to ( Xiao-Chai-Hu-Tang ) on HBeAg clearance rate ( SN rate ) in fourteen children with chronic hepatitis B virus ( HBV ) infection and with sustained liver disease . Seven of fourteen patients ( 50.0 % ) became HBeAg negative in the average observation period of 0.47 years(0.2 - 0.9 years ) . Four of those seven patients developed anti-HBe . The annual SN rate in the She-saiko-to treated group was apparently higher than the natural annual SN rate ( 22.7 % ) of 22 untreated patients retrospectively review ed from the onset of hepatitis . Sho-saiko-to seemed to promote clearance of HBeAg in children with chronic HBV infection and with sustained liver disease . Sho-saiko-to may be a useful drug for such patients OBJECTIVE To determine whether clinical trials originating in certain countries always have positive results . DATA SOURCES Abstract s of trials from Medline ( January 1966-June 1995 ) . STUDY SELECTION Two separate studies were conducted . The first included trials in which the clinical outcome of a group of subjects receiving acupuncture was compared to that of a group receiving placebo , no treatment , or a nonacupuncture intervention . In the second study , r and omized or controlled trials of interventions other than acupuncture that were published in China , Japan , Russia/USSR , or Taiwan were compared to those published in Engl and . DATA EXTRACTION Blinded review ers determined inclusion and outcome and separately classified each trial by country of origin . DATA SYNTHESIS In the study of acupuncture trials , 252 of 1085 abstract s met the inclusion criteria . Research conducted in certain countries was uniformly favorable to acupuncture ; all trials originating in China , Japan , Hong Kong , and Taiwan were positive , as were 10 out of 11 of those published in Russia/USSR . In studies that examined interventions other than acupuncture , 405 of 1100 abstract s met the inclusion criteria . Of trials published in Engl and , 75 % gave the test treatment as superior to control . The results for China , Japan , Russia/USSR , and Taiwan were 99 % , 89 % , 97 % , and 95 % , respectively . No trial published in China or Russia/USSR found a test treatment to be ineffective . CONCLUSIONS Some countries publish unusually high proportions of positive results . Publication bias is a possible explanation . Research ers undertaking systematic review s should consider carefully how to manage data from these countries BACKGROUND In patients with chronic hepatitis B , treatment with interferon alfa and the consequent loss of hepatitis B e antigen ( HBeAg ) from the blood leads to a reduction in inflammatory activity , but the clinical benefits of this treatment have not been established . We evaluated whether HBeAg seroconversion induced by interferon alfa improves clinical outcome . METHODS We studied prospect ively a cohort of 103 patients treated with interferon alfa for chronic hepatitis B ; the mean ( + /- SD ) follow-up was 50.0 + /- 19.8 months . Fifty-three untreated patients served as controls . RESULTS After treatment with interferon alfa , 53 of 103 patients no longer had detectable HBeAg or hepatitis B virus DNA , although only 10 patients became seronegative for hepatitis B surface antigen ( HBsAg ) ( Kaplan-Meier estimates of cumulative clearance rates at five years , 56.0 percent for HBeAg and 11.6 percent for HBsAg ) . Of the 53 untreated patients , only 7 spontaneously eliminated HBeAg ( 28.1 percent at five years ) , and all remained positive for HBsAg ( p < 0.001 for the Comparison with the treated patients , by the proportional-hazards model ) . During follow-up , 6 of the 103 treated patients died of liver failure , and 2 needed liver transplantation , all 8 were persistently positive for HBeAg . In another eight treated patients , complications of cirrhosis developed ; all but one of these patients remained positive for HBeAg . Overall survival and survival without clinical complications were significantly longer in patients who were seronegative for HBeAg after therapy with interferon alfa than in those who remained seropositive ( P = 0.004 and P = 0.018 , respectively ) . In a regression analysis , clearance of HBeAg was the strongest predictor of survival . Of the 53 untreated patients , 13 had severe complications ( including 4 deaths and 1 need for liver transplantation ) ; all 13 continued to be HBeAg-positive . CONCLUSIONS In patients with chronic hepatitis B infection , the clearance of HBeAg after treatment with interferon alfa is associated with improved clinical outcomes Sixty-five adult asymptomatic chronic carriers of hepatitis B virus were enrolled to the r and omized controlled efficacy study of Phyllanthus amarus . Thirty-four received Phyllanthus amarus 600 mg per day for 30 days and 31 received placebo in identical capsules . The conversion rate of HBsAg was 6 per cent in the study group at day 30 . When 20 subjects in the Phyllanthus amarus group were given a further 30-day treatment and 22 placebo recipients given Phyllanthus amarus 1,200 mg per day for 30 days , the conversion was observed in 1 ( 5 % ) in the higher dose group . Adverse effects were not observed in all patients receiving the plant . The results indicated that Phyllanthus amarus , whole plant except root , grown in the central part of Thail and , given at the studied dosage and duration , had a very minimal effect on eradication of HBsAg from Thai adult asymptomatic chronic carriers Ninety Chinese hepatitis B surface antigen ( HBsAg ) carrier children , aged 2 - 17 years , positive for hepatitis B e antigen ( HBeAg ) and hepatitis B virus DNA on at least three occasions in 6 months , were r and omized into 3 groups . Thirty children received syrup vitamin B complex as control , 29 received 6 weeks of placebo syrup followed by 16 weeks of recombinant alpha 2b-interferon [ intron A ( rIFN2b ) ] , 5 x 10(6 ) u/m2 subcutaneously thrice weekly ; and 31 received 6 weeks of syrup prednisone ( 0.6 mg/kg tailed to 0.2 mg/kg ) followed by 16 weeks of recombinant alpha 2b-interferon as above . The placebo/prednisone syrup was given on a double-blind basis . At 24 months of follow-up , persistent loss of hepatitis B virus DNA occurred in none of the children in the control group , in one child receiving recombinant alpha 2b-interferon alone , who also seroconverted to anti-HBe and anti-HBs and in five children receiving interferon with steroid priming ( p = 0.0571 compared with controls ) , with four seroconverting to anti-HBe and one also seroconverting to anti-HBs . A rise of transaminases to above twice the upper limit of normal levels during the first 7 months of follow-up occurred in one subject in the control group , four in the group receiving alpha 2b-interferon alone and nine in the group receiving recombinant alpha 2b-interferon with steroid priming ( p = 0.0144 compared with controls ) . Side effects of the steroid were negligible ; those of recombinant alpha 2b-interferon were transient and acceptable . We conclude that 6 weeks of prednisone followed by 16 weeks of recombinant alpha 2b-interferon is of use in inducing persistent loss of hepatitis B virus DNA ( 16.1 per cent ) and e-seroconversion ( 12.9 per cent ) in a proportion of Chinese HBsAg carrier children : the prednisone probably enhances the immunomodulatory effect of recombinant alpha 2b-interferon Fifty percent of healthy hepatitis B surface antigen carriers may have histologically proven chronic hepatitis . Our aim was to study the benefit of interferon-alpha in healthy patients . Twenty-nine hepatitis B surface antigen carriers with normal liver enzymes and with serum hepatitis B virus DNA were r and omized into two groups : Group I , 14 patients treated with 9 megaunits of interferon alpha-2a thrice weekly for six months , and Group II , 15 control patients . A liver biopsy was obtained from each patient at study initiation . A second biopsy was available in nine treated patients and six controls . During treatment , a significant increase in alanine amino transferase levels was observed in treated patients as compared with the controls ( P < 0.05 ) . After treatment , transaminase levels decreased to normal values . No differences between treated and control patients were observed in clearance of hepatitis B virus markers . A significant increase in the total histological activity index between base line and final liver biopsies was observed in treated patients ( P < 0.05 ) . It is concluded that interferon alpha treatment may induce a biochemical and histological activation of liver disease . Accordingly , interferon alpha should not be administered to healthy hepatitis B surface antigen carriers , at least with the schedule used in this work Many r and omised controlled trials have been conducted in China to evaluate the effectiveness of traditional Chinese medicine , but much of the information is inaccessible to Western doctors . We estimated the total number of r and omised controlled trials published in China and identified problems in applying such methodology to the evaluation of traditional Chinese medicine , which would serve as preparatory work for systematic review and dissemination of the r and omised evidence for such medicine . We r and omly selected 28 journals using stratified sampling from a total of 100 Chinese journals of traditional Chinese medicine ( 4 national , 10 university , 10 provincial or regional , and 4 specialist journals ) . After special training , eight fifth year medical students ( working in pairs ) h and search ed all the issues of the journals published before 1 January 1997 to identify r and omised controlled trials . Discrepancies were settled by one of the principal investigators ( S-YZ ) . Data on method ological quality of r and omised controlled trials were extracted from 414 full length articles To examine the long‐term effect of interferon ( IFN ) therapy in patients with chronic hepatitis B virus ( HBV ) infection , particularly on survival and hepatocellular carcinoma ( HCC ) prevention , 101 male patients with chronic hepatitis B in a r and omized controlled trial were followed up for 1.1 to 11.5 years after the end of therapy . Of the 101 patients , 34 patients received a placebo ( control ) , and 67 patients were treated with IFN ( 31 patients were treated with IFN alone and 36 patients were treated with IFN after prednisolone priming ) . Follow‐up studies included clinical , biochemical , and virological aspects and HCC screening every 3 to 6 months . Twenty‐eight ( 42 % ) of the 67 IFN‐treated patients and 8 ( 24 % ) of the 34 untreated patients seroconverted by the end of the trial . During follow‐up , 22 ( 56 % ) of the 39 patients who did not seroconvert in the treated group and 5 ( 19 % ) of the 26 patients who did not seroconvert in the control group showed a delayed sustained response ( P < .005 ) . The cumulative incidence of sustained response was highest in the steroid priming group ( P = .049 vs. the IFN – alone group;P = .028 vs. the control group ) . HCC was detected in 1 ( 1.5 % ) of the 67 treated patients and 4 ( 12 % ) of the 34 untreated patients ( P = .043 ) . The interval between entry and HCC detection was 3.5 to 8.2 years . The cumulative incidence of HCC development was significantly higher in the control group than in the treated group ( P = .013 ) . In contrast , the cumulative survival rate was higher in the treated group than the control group ( P = .018 ) . Multivariate analysis showed that IFN therapy , preexisting cirrhosis , and the patient 's age at entry are significant independent factors for both survival and HCC development . The results suggest that IFN has long‐term beneficial effects in terms of HBV clearance , reduction of HCC , and prolonging survival BACKGROUND AND METHODS In preliminary trials , lamivudine , an oral nucleoside analogue , has shown promise for the treatment of chronic hepatitis B. We conducted a one-year , double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were r and omly assigned to receive 25 mg of lamivudine ( 142 patients ) , 100 mg of lamivudine ( 143 ) , or placebo ( 73 ) orally once daily . The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen . The primary end point was a reduction of at least two points in the Knodell necroinflammatory score . RESULTS Hepatic necroinflammatory activity improved by two points or more in 56 percent of the patients receiving 100 mg of lamivudine , 49 percent of those receiving 25 mg of lamivudine , and 25 percent of those receiving placebo ( P<0.001 and P=0.001 , respectively , for the comparisons of lamivudine treatment with placebo ) . Necroinflammatory activity worsened in 7 percent of the patients receiving 100 mg of lamivudine , 8 percent of those receiving 25 mg , and 26 percent of those receiving placebo . The 100-mg dose of lamivudine was associated with a reduced progression of fibrosis ( P=0.01 for the comparison with placebo ) and with the highest rate of hepatitis B e antigen ( HBeAg ) seroconversion ( loss of HBeAg , development of antibody to HBeAg , and undetectable HBV DNA ) ( 16 percent ) , the greatest suppression of HBV DNA ( 98 percent reduction at week 52 as compared with the base-line value ) , and the highest rate of sustained normalization of alanine aminotransferase levels ( 72 percent ) . Ninety-six percent of the patients completed the study . The incidence of adverse events was similar in all groups , and there were few serious events . CONCLUSIONS In a one-year study , lamivudine was associated with substantial histologic improvement in many patients with chronic hepatitis B. A daily dose of 100 mg was more effective than a daily dose of 25 mg BACKGROUND There have been conflicting data in literature about the value of Phyllanthus amarus in treating hepatitis B virus-related disorders . AIM To evaluate the role of Phyllanthus amarus in eradication of the virus in hepatitis B carriers . METHODS Phyllanthus amarus was administered to 30 asymptomatic carriers of hepatitis B surface antigen ( HBsAg ) in a dosage of 250 to 500 mg thrice daily for 4 to 8 weeks . RESULTS None of the 30 subjects cleared HBsAg . Phyllanthus amarus was well tolerated , with no clinical side effects or changes in the organ profiles for safety evaluation . CONCLUSION Phyllanthus amarus is not effective in clearing HBsAg in asymptomatic carriers of the antigen The therapeutic effect of Jiang Tang San ( JTS ) on 30 cases with non-insulin dependent diabetes mellitus ( NIDDM ) , was observed , whose fasting blood glucose ranged from 11 . 1 mmol/L to 13 . 8 mmol/L. The results suggested that JTS has significant effect on NIDDM patients in lowering blood glucose , blood lipid and blood pressure levels . Clinical symptoms and blood glucose improved rapidly . JTS promoted the elevation of serum insulin level 1 hour after meal . The total effective rate of lowering blood glucose reached 86.7 % . The results showed JTS is better than berberine on lowering blood glucose ( P<0.01 ) and when patients failed to respond to other hypoglycemics or on recurrence JTS was still effective . There were no marked side-effects during the course of treatment |
2,682 | 21,069,681 | These findings are consistent with the proven effectiveness of these interventions in their non-stage-based versions .
The evidence was unclear for telephone counselling , interactive computer programmes or training of doctors or lay supporters .
Providing these forms of practical support to those trying to quit appears to be more productive than not intervening .
However , the additional value of adapting the intervention to the smoker 's stage of change is uncertain .
The evidence is not clear for other types of staged intervention , including telephone counselling , interactive computer programmes and training of physicians or lay supporters .
The evidence does not support the restriction of quitting advice and encouragement only to those smokers perceived to be in the preparation and action stages | BACKGROUND The transtheoretical model is the most widely known of several stage-based theories of behaviour .
It proposes that smokers move through a discrete series of motivational stages before they quit successfully .
These are precontemplation ( no thoughts of quitting ) , contemplation ( thinking about quitting ) , preparation ( planning to quit in the next 30 days ) , action ( quitting successfully for up to six months ) , and maintenance ( no smoking for more than six months ) .
According to this influential model , interventions which help people to stop smoking should be tailored to their stage of readiness to quit , and are design ed to move them forward through subsequent stages to eventual success .
People in the preparation and action stages of quitting would require different types of support from those in precontemplation or contemplation .
OBJECTIVES Our primary objective was to test the effectiveness of stage-based interventions in helping smokers to quit . | AIMS To examine the effects of processes of change ( POC ) on forward stage movement directly , indirectly through decisional balance and temptation , and total effects as a test of the key hypothesis of the Transtheoretical Model ( TTM ) . DESIGN Prospect i ve cohort study . SETTING United Kingdom . PARTICIPANTS A total of 1160 adolescents aged 13 - 14 years who were current or former smokers at baseline . MEASUREMENTS Stage was assessed with the st and ard algorithm three times , once every 3 months . On each occasion the POC , decisional balance and temptation were measured with the st and ard question naires . Path analysis was used to examine the direct , indirectly mediated and total contribution of POC and the other constructs to stage movement 3 months later . FINDINGS Four of the 24 analyses showed evidence that the theoretically appropriate POC predicted stage transition , with statistically significant total effects . Effect sizes were small . When the POC were summarized to experiential and behavioural process means , one transition from pre-contemplation was predicted by experiential processes and , contrary to the TTM , one transition predicted by behavioural processes . There was slightly more evidence that decisional balance ( attitudes towards smoking ) and temptation ( ability to resist the urge to smoke ) was associated with stage transition . CONCLUSIONS POC use was not associated generally with stage transition and evidence that effects , if missed , must be modest , giving no support to the central tenet of the TTM BACKGROUND Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population . The intervention provides individualized feedback that guides participants through the stages of change for cessation . Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer design ed to produce nicotine fading could produce preventive programs with greater population impacts . METHODS Four interventions were compared : ( a ) the interactive expert system intervention ; ( b ) the expert system intervention plus counselor calls ; ( c ) the expert system intervention plus the stimulus control computer ; and ( d ) an assessment only condition . A 4 ( intervention ) x 4 ( occasions ) ( 0,6,12 , and 18 months ) design was used . Smokers were contacted at home via telephone or mail . The initial subject pool was the 24,178 members of a managed care company . Screening was completed for 19,236 members ( 79.6 % ) , of whom 4,653 were smokers ; 85.3 % of the smokers were enrolled . RESULTS Thirty-eight percent were in the precontemplation stage , 45 % in the contemplation stage , and only 17 % in the preparation stage . At 18 months , the expert system result ed in 23.2 % point prevalence abstinence , which was 33 % greater than that of assessment only . The counselor enhancement produced increased cessation at 12 months but not at 18 months . The stimulus control computer produced no improvement , result ing in 20 % worse cessation rates than the assessment only condition . CONCLUSIONS The enhanced conditions failed to outperform the expert system alone . The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone A longitudinal r and omized trial tested the self-determination theory ( SDT ) intervention and process model of health behavior change for tobacco cessation ( N = 1006 ) . Adult smokers were recruited for a study of smokers ' health and were assigned to intensive treatment or community care . Participants were relatively poor and undereducated . Intervention patients perceived greater autonomy support and reported greater autonomous and competence motivations than did control patients . They also reported greater medication use and significantly greater abstinence . Structural equation modeling analyses confirmed the SDT process model in which perceived autonomy support led to increases in autonomous and competence motivations , which in turn led to greater cessation . The causal role of autonomy support in the internalization of autonomous motivation , perceived competence , and smoking cessation was supported Background Online computer-tailored smoking cessation programs have not yet been compared directly . Objective To compare the efficacy of two Internet-based , computer-tailored smoking cessation programs . Methods R and omized controlled trial conducted in 2003 - 2004 . Visitors to a smoking cessation website were r and omly assigned to either an original online , interactive smoking cessation program or to a modified program . Both programs consisted of tailored , personalized counseling letters based on participants ' characteristics , followed by monthly email reminders . The original program was based on psychological and addiction theory , and on preliminary research conducted in the same population . The modified program was shorter and contained more information on nicotine replacement therapy and nicotine dependence , and less information on health risks and coping strategies . In both programs , 1 month and 2 months after entering the study , participants were invited by email to answer the same tailoring question naire again in order to receive a second counseling letter . Participants in both programs obtained , on average , 1.2 feedback counseling letters over 2.5 months , and 84 % received only 1 feedback letter . The outcome was self-reported smoking abstinence ( no puff of tobacco in the previous 7 days ) , assessed 2.5 months after entry in the program . We report results from intention-to-treat ( ITT ) analyses , where all non-respondents at follow-up were counted as smokers . Results The baseline question naire was answered by a total of 11969 current ( 74 % ) and former ( 26 % ) smokers , and the follow-up survey by 4237 people ( 35 % ) . In an ITT analysis , abstinence rates in baseline current smokers were respectively 10.9 % and 8.9 % ( odds ratio [OR]=1.24 , 95 % confidence interval [CI]1.08 - 1.43 , P=.003 ) in the original and modified programs , and 25.2 % and 15.7 % ( OR=1.81 , CI 1.51 - 2.16 , P<.001 ) in baseline former smokers . While we found statistically significant differences in quit rates in smokers in the contemplation stage favoring the original program ( OR=1.54 , CI 1.18 - 2.02 , P=.002 ) , no between-group differences in quit rates were observed in smokers in the precontemplation ( OR=1.07 , CI 0.36 - 3.14 , P=.91 ) and preparation ( OR=1.15 , CI 0.97 - 1.37 , P=.10 ) stages of change . Conclusions In smokers in the contemplation stage of change and in former smokers , the original program produced higher smoking abstinence rates than the modified program To assess the stability of intention to quit smoking , 115 US and Swedish smokers were r and omized to complete Stage of Change ( SOC ) or ladder scales of intentions to quit at either 0 , 7 , 14 and 30 days or at 0 and 30 days in the absence of intervention . The four- assessment group had more progression in intention to quit than the two- assessment group . Depending on the measure , 12 - 17 % of smokers changed their intention to quit over 7 days , 15 - 25 % changed over 14 days and 17 - 34 % changed over 30 days . Results were similar in Swedish and US participants and replicate the results of prior studies . We conclude intention to quit often spontaneously changes over short periods of time , especially with repeated testing AIMS quantitative description of adherence to motivational interviewing ( MI ) in smoking cessation sessions ; and examination of the relationships between client characteristics and adherence to MI , and between adherence to MI and future smoking status . METHODS 84 sessions were conducted during a r and omised controlled trial to test the effectiveness of a population -based smoking intervention in women during the postpartum period . Demographic and behaviour-related variables were included in a logistic regression to predict adherence to MI . MEASUREMENTS adherence was measured using the MI Treatment Integrity Scale . FINDINGS 38.1 % of sessions showed good adherence to MI . Receiving a good MI session was not related to any demographic or behavioural variables . The relationship between adherence and intervention outcome after six months was not statistically significant ( chi(2)=0.355 , p=0.551 ) . CONCLUSIONS the smoking cessation sessions examined in this study failed to adhere to MI . There was no relationship between adherence to MI and behavioural outcome six months after the intervention , indicating that women who smoke post partum may be a high-risk group for whom specific smoking cessation interventions need to be developed OBJECTIVE To evaluate a training workshop for community pharmacy personnel to improve their counselling in smoking cessation based on the stage-of-change model . DESIGN A r and omised controlled trial of community pharmacies and pharmacy customers . SETTING All 76 non-city community pharmacies registered in Grampian , Scotl and , were invited to participate . Sixty-two pharmacies ( 82 % ) were recruited . SUBJECTS All the intervention pharmacy personnel were invited to attend the training ; 40 pharmacists and 54 assistants attended . A total of 492 customers who smoked ( 224 intervention , 268 controls ) were recruited during the 12-month recruitment period ( overall recruitment rate 63 % ) . MAIN OUTCOME MEASURES The perceptions of customers and pharmacy personnel of the pharmacy support and self-reported smoking cessation rates for the two groups of customers at one , four , and nine months . RESULTS The intervention customer respondents were significantly more likely to have discussed stopping smoking with pharmacy personnel , 85 % ( 113 ) compared with 62 % ( 99 ) of the controls ( p<0.001 ) . The former also rated their discussion more highly ; 34 % ( 45 ) of the intervention customers compared with 16 % ( 25 ) of the controls rated it as “ very useful ” ( p = 0.048 ) . Assuming non-responders had lapsed , one-month point prevalence of abstinence was cl aim ed by 30 % of intervention customers and 24 % of controls ( p = 0.12 ) ; four months ’ continuous abstinence was cl aim ed by 16 % of intervention customers and 11 % of controls ( p = 0.094 ) ; and nine months ’ continuous abstinence was cl aim ed by 12 % of intervention customers and 7 % of controls ( p = 0.089 ) . These trends in outcome were not affected by potential confounders ( sex , age , socioeconomic status , nicotine dependence , and type of nicotine replacement product used ) or adjustment for clustering . CONCLUSIONS The intervention was associated with increased and more highly rated counselling , and a trend toward higher smoking cessation rates , indicating that community pharmacy personnel have the potential to make a significant contribution to national smoking cessation targets OBJECTIVES This study assessed the effectiveness of a smoking cessation program for women in public health clinics , controlling for reported exposures to 4 common intervention components ( provider advice , booklet , video segment , posters ) among smokers in the control group . METHODS After a baseline control period , 10 pair-matched clinics were r and omly assigned to study groups . A total of 1042 smokers in the combined baseline and control groups and 454 smokers in the intervention group completed a preintervention question naire and a postintervention telephone interview 5 to 8 weeks later . Eight smoking outcomes , including quitting , were analyzed for the effect of reported exposure to intervention components , experimental program , and clinic service . RESULTS Greater exposure to intervention components , being in the experimental program , and being seen in prenatal clinics independently improved smoking outcomes . CONCLUSIONS The number of interventions reported by smokers in the control group ranged from none to 4 and varied across clinic services . The experimental program we tested produced better outcomes than the minimal smoking cessation interventions already existing in the control clinics , after we controlled for whether smokers were or were not exposed to these interventions Face to face advice for smoking cessation is effective,1 but few smokers are willing to attend smoking cessation clinics , and many do not receive smoking cessation advice from their physician . Self help smoking cessation material s may not be very effective,2 but computer technology can be used to produce effective individualised self help smoking cessation material s and disseminate them widely at a low cost per participant.2 Most studies assessed the effect of computer tailored programmes on smoking cessation after one year or less.2 Only one programme was evaluated during 18 and 24 months.3 These programmes usually produced quit rates<5 % higher than in control groups who received st and ard self help material s or no intervention.2 Because over one third of ex-smokers who achieve 12 months of abstinence eventually relapse five years later,4 it is not yet known whether computer tailored programmes have a long term impact on smoking abstinence . We showed previously that a computer tailored programme doubled the odds of quitting smoking , after seven months.5 In this study , we tested whether this effect was maintained 24 months after entry in the programme — that is , 12 months after the end of the intervention . In 1998 , we sent the baseline question naire to a representative ( r and om ) sample of 20 000 residents aged 18–60 in French speaking Switzerl and . We sent out follow up question naires six and 23 months later to the 2934 baseline participants . We r and omly assigned participants to the intervention or control group ( fig 1 ) . Figure 1 Flow chart of participants in the r and omised controlled trial . The intervention consisted of personal counselling letters , written by a Smoking cessation interventions are needed for young adults . Innovative approaches to behavior change for this population should be tested . Formative research and process evaluation of those approaches would result in more effective programs . This paper presents the development process and process evaluation of a web-based smoking cessation program . A description of the stages of development is presented with formative research , development of the web-based intervention , formative evaluation , and process evaluation . The smokers reported high usage of the intervention and satisfaction with the intervention in that it helped to raise their consciousness about quitting , encouraged them to set behavioral goals , provided stages of change feedback , and offered interactivity in presenting information and strategies about quitting . The Internet may be a promising tool for patient education according to the process results Objectives : To evaluate the effectiveness in helping pregnant women stop smoking of two interventions ( Pro-Change for a healthy pregnancy ) based on the transtheoretical model of behaviour change ( TTM ) compared to current st and ard care . Design : Cluster r and omised trial . Setting : Antenatal clinics in West Midl and s , UK general practice s. Participants : 918 pregnant smokers Interventions : 100 general practice s were r and omised into the three trial arms . Midwives in these practice s delivered three interventions : A ( st and ard care ) , B ( TTM based self help manuals ) , and C ( TTM based self help manuals plus sessions with an interactive computer program giving individualised smoking cessation advice ) . Main outcome measures : Biochemically confirmed smoking cessation for 10 weeks previously , and point prevalence abstinence , both measured at 30 weeks of pregnancy and 10 days after delivery . Results : There were small differences between the TTM arms . Combining the two arms , the odds ratios at 30 weeks were 2.09 ( 95 % confidence interval ( CI ) 0.90 to 4.85 ) for 10 week sustained abstinence and 2.92 ( 95 % CI 1.42 to 6.03 ) for point prevalence abstinence relative to controls . At 10 days after delivery , the odds ratios were 2.81 ( 95 % CI 1.11 to 7.13 ) and 1.85 ( 95 % CI 1.00 to 3.41 ) for 10 week and point prevalence abstinence respectively . Conclusions : While there is a small borderline significant increase in quitting in the combined intervention arms compared with the controls , the effect of the intervention is small . At 30 weeks gestation and at 10 days postnatal , only about 3 % of the intervention groups achieved sustained cessation , with numbers needed to treat of 67 ( 30 weeks of gestation ) and 53 ( 10 weeks postnatal ) for one additional woman to achieve sustained confirmed cessation . Given also that the intervention was re source intensive , it is of doubtful benefit Objective The purpose of this study was to evaluate the effects of stage-matched repeated individual behavioral counseling as an intervention for the cessation of smoking . Methods We conducted a multisite r and omized controlled trial that enrolled smokers unselected for their readiness to quit . There were 979 smokers with hypertension or hypercholesterolemia recruited from 72 study sites and r and omly allocated to the intervention or control group . Smokers in the intervention group received stage-matched individual counseling consisting of a 40 minute initial session and four 20–30 minute follow-up sessions . Smokers in the control group received individual behavioral counseling for hypertension or hypercholesterolemia . Results The point prevalence abstinence rate at 6 months , vali date d by carbon monoxide testing , in the intervention group ( 13.6 % ) was 5.4 times higher ( p<0.001 ) than that in the control group ( 2.5 % ) . When the data were analyzed based on the baseline stage of change , there were significant differences in the abstinence rates at 6 months in smokers versus controls with each stage of change except in immotives . The odds ratio was 6.4 ( p<0.001 ) in precontemplators , 6.7 ( p<0.001 ) in contemplators , and 6.2 ( p<0.01 ) in preparators . There was a positive , consistent effect of the intervention regardless of study site ( worksite or community ) or the presence of hypertension or hypercholesterolemia . Conclusions We showed the effects of an intervention with repeated individual behavioral counseling on the cessation of smoking in smokers unselected for their readiness to quit . This result suggests that stage-matched individual counseling , based on the transtheoretical model , is effective in smokers with a lower motivation to quit as well as those ready to quit We tested the comparative efficacy of 4 interventions to increase the physical activity behavior of college personnel r and omly assigned to one condition ( N = 196 , 74 % female , M age = 43.4 years ) for 16 weeks . Stage-matched and mismatched interventions were developed based on the stages of change from the Transtheoretical Model and were contrasted with st and ard care ( action-oriented ) and control interventions to test the requirements of a true stage behavior . Repeated measures of multi-variate analyses of covariance indicated that the stage-matched and st and ard care interventions result ed in greater levels of both total and lifestyle physical activity compared with the mismatched and control interventions . The results supported the requirements of a stage behavior as defined by Weinstein , Rothman , and Sutton ( 1 ) and the superiority of the stage-matched intervention versus the mismatched intervention . However , the st and ard care intervention performed as well as the matched intervention , suggesting the need for further investigation . The results are discussed with respect to the high proportion of individuals in the action-oriented stages and previous research findings in the smoking literature Cigarette smoking is a major risk factor for head and neck cancer , and individuals who continue to smoke past diagnosis and treatment are at elevated risk for further disease . In a r and omized controlled trial , a state of the art provider-delivered smoking cessation intervention was compared to a usual care advice control condition . The intervention consisted of surgeon- or dentist-delivered advice to stop smoking , a contracted quit date , tailored written material s , and booster advice sessions . Subjects were 186 patients with newly diagnosed first primary squamous cell carcinomas of the upper aerodigestive tract who had smoked cigarettes within the past year . At r and omization , 88.2 % of subjects were current smokers . At 12-month follow-up , 70.2 % of subjects completing the trial ( n = 114 ) were continuous abstainers ; among baseline smokers alone the continuous abstinence ( CA ) rate was 64.6 % . The cotinine validation rate at 12 months was 89.6 % . Modeling techniques were utilized in order to derive expected CA rates , which included noncompleter subjects ( n = 72 ) . The CA rate expected at 1 year for the entire patient population was 64.2 % , and for smokers alone the expected CA rate was 59.4 % . Logistic regression analysis carried out on baseline smokers identified predictors of 12-month CA status . These included medical treatment , stage of change , age , nicotine dependence , and race . The intervention effect was not significant , although the sign of the effect was positive . Based on these findings , we recommend systematic brief advice to stop smoking for head and neck cancer patients , with a stepped care approach for patients less able to quit The purpose of this prospect i ve , r and omized controlled study was to determine the efficacy of an intensified , late pregnancy , smoking cessation intervention for resistant pregnant smokers ( n = 269 ) . Participants received 3 - 5 min of counseling plus a self-help booklet at their first prenatal visit and seven booklets mailed weekly thereafter ; at 28 weeks , all had been smoking in the past 28 days . The experimental group received a stage of change-based , personalized feedback letter and two telephone counseling calls using Motivational Interviewing ( MI ) strategies . The control group received care as usual . The 34th week cotinine data demonstrated no overall difference between groups . However , an implementation analysis suggested that 43 % of women who received the full intervention ( E2 ) were classified as not smoking compared to 34 % of the control group . At 6 weeks postpartum , 27.1 % of the E2 group reported being abstinent or light smokers vs. 14.6 % of the controls . No differences were detected at 3 and 6 months postpartum . Results lend preliminary but very modest support for this intervention with resistant pregnant smokers . Improvements in the intervention and implementation issues are discussed Smoking cessation treatment is now integrated into many health-care systems and a major research effort is under way to improve current success rates . Until now results from r and omized clinical trials have been reported in many different ways , leading to problems of interpretation . We propose six st and ard criteria comprising the ' Russell St and ard ' ( RS ) . These criteria are applicable to trials of cessation aids where participants have a defined target quit date and there is face-to-face contact with research ers or clinic staff , as follows . ( 1 ) Follow-up for 6 months ( RS6 ) or 12 months ( RS12 ) from the target quit date or the end of a predefined ' grace period ' ; ( 2 ) self-report of smoking abstinence over the whole follow-up period allowing up to five cigarettes in total ; ( 3 ) biochemical verification of abstinence at least at the 6-month or 12-month follow-up point ; ( 4 ) use of an ' intention-to-treat ' approach in which data from all r and omized smokers are included in the analysis unless they have died or moved to an untraceable address ( participants who are included in the analysis are counted as smokers if their smoking status at the final follow-up can not be determined ) ; ( 5 ) following-up ' protocol violators ' and using their true smoking status in the analysis ; and ( 6 ) collecting follow-up data blind to smokers ' allocation to trial group . We believe that these criteria provide the best compromise between practicability and surrogacy for long-term cessation and will enable meaningful comparison between studies . There may be good reasons why other outcome criteria would also be reported , and studies that involve interventions with special groups or where there is no design ated target quit date or face to face contact would need to adapt these criteria accordingly 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 The present study examined mechanisms underlying the effectiveness of tailored interventions for motivating smoking cessation . The study used a placebo-tailoring design to test whether the efficacy of tailoring was due , in part , to personalized features in addition to the theoretically based content . Two hundred forty adult smokers were r and omized to 1 of 3 conditions : st and ard booklet , minimally personalized booklet , or extensively personalized booklet . The interventions varied in their degree of ostensible tailoring , yet the actual smoking-related content of the booklets was identical . A dose-response relationship was hypothesized , with the greatest apparent tailoring producing the most positive outcomes . This pattern was found for evaluation of the booklets , with trends for readiness to change and self-efficacy increases . Moreover , as hypothesized , the effect of the interventions on readiness was moderated by participants ' expectancies about tailoring AIM To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline , and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation . DESIGN R and omized controlled trial comparing : ( 1 ) untailored self-help material s ; ( 2 ) computer-generated tailored advice only , and ( 3 ) computer-generated tailored advice plus callback telephone counselling . Assessment surveys were conducted at baseline , 3 , 6 and 12 months . SETTING Victoria , Australia . PARTICIPANTS A total of 1578 smokers who called the Quitline service and agreed to participate . MEASUREMENTS Smoking status at follow-up ; duration of cessation , if quit ; use of nicotine replacement therapy ; and extent of participation in the callback service . FINDINGS At the 3-month follow-up , significantly more ( chi2(2 ) = 16.9 ; P < 0.001 ) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking ( 21 % ) than in either the computer-generated advice only ( 12 % ) or the control condition ( 12 % ) . Proportions reporting not smoking at the 12-month follow-up were 26 % , 23 % and 22 % , respectively ( NS ) for point prevalence , and for 9 months sustained abstinence ; 8.2 , 6.0 , and 5.0 ( NS ) . In the telephone counselling group , those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months ( 10.2 compared with 4.0 , P < 0.05 ) . Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT , but not of computer-generated tailored advice . CONCLUSION Computer-generated tailored advice did not enhance telephone counselling , nor have any independent effect on cessation . This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice The aim of this study is to test whether subtypes exist among smokers in contemplation . Data from 194 adult smokers that participated in a r and omized controlled trial testing the effectiveness of a computer-tailored smoking cessation program in Dutch general practice s were used for secondary analysis . Cluster analysis was conducted based on baseline scores on pros and cons of quitting and self-efficacy to quit . Clusters were cross-sectionally compared for demographic variables and smoking characteristics with analyses of variance ( ANOVA ) and Chi-square tests . Logistic and multinomial regression analyses were used for longitudinal comparison for smoking behavior and stage of change at 6 months follow-up . Three clusters were identified : Early , Progressing and Disengaged Contemplators . Clusters differed significantly on all clustering variables ( P < 0.001 ) . Disengaged smokers were significantly less addicted than Early Contemplators . Cluster membership was not predictive of outcome measures . No subtype was identified representing the Classic Contemplator , scoring high on both pros and cons of quitting and low on self-efficacy , as found in previous studies among US sample s. The predictive validity of the clusters found was limited Background Smoking cessation interventions in pregnancy could influence a woman 's social behaviour and her partner 's smoking behaviour , but this has not been examined in any published r and omized trials . Method 918 women smoking at booking for antenatal care were enrolled in a cluster-r and omized trial of three interventions : st and ard care , self-help manual and enhanced stage-based counselling , or self-help manual , enhanced stage-based counselling and use of an interactive computer program . The outcomes were change in social support received by women between booking for maternity care and 30 weeks gestation and 10 days postpartum and reported cessation in the woman 's partner at these times . Results Few pregnant women 's partners stopped smoking ( 4.1 % at 30 weeks of gestation and 5.8 % at 10 days postpartum ) and the probability of quitting did not differ significantly by trial arm . Women 's scores on the Inventory of Socially Supportive Behaviors showed a slight decline from booking to 30 weeks gestation , and a slight increase to 10 days postpartum , but these changes did not differ significantly by trial arm . Conclusion The stage-based interventions tested in this trial aim ed partly to influence women 's mobilization of support and might have influenced partners ' quitting , but there was no evidence that they did so . Given that women and their partners often stopped smoking together , future interventions to prevent smoking in pregnant women could encourage both partners to quit together We evaluated whether susceptibility , the stages of smoking acquisition , and socio-environmental factors can identify adolescents who will become smokers . Our data came from a r and omized controlled trial of an intervention to prevent adolescent smoking . Subjects were adolescents ( n=1955 ) ages 14 - 17 being seen for routine medical care . The dependent variable was 30-day smoking status at 2-year follow-up ( 89.6 % response rate ) . Independent variables included susceptibility , the stages of acquisition , and socio-environmental factors . Susceptible adolescents were two to three times more likely to be smokers than non-susceptible adolescents . Compared to acquisition precontemplators , acquisition contemplators were three to five times more likely , and acquisition preparers were five to eight times more likely , to be smokers . When combined into a single measure , susceptible precontemplators were two times , contemplators were six times , and preparers were nine times more likely to be smokers than non-susceptible precontemplators . Our findings suggest that acquisition stage and susceptibility can independently predict smoking onset . They may be used together to target teens for smoking prevention efforts in the clinical setting BACKGROUND Many patients in primary care setting s present with multiple behavioral risk factors for cardiovascular disease . Research has provided little information on the most effective ways to approach multiple behavior change counseling in clinical setting s. METHODS We implemented a r and omized trial in a publicly funded primary care setting to test whether a sequential presentation of stage of change-based counseling to stop smoking , reduce dietary sodium level to less than 100 mEq/L per day , and increase physical activity by at least 10,000 pedometer steps per week would be more effective than simultaneous counseling . African Americans with hypertension , aged 45 to 64 years , initially nonadherent to the 3 behavioral goals , were r and omized to the following conditions : ( 1 ) 1 in-clinic counseling session on all 3 behaviors every 6 months , supplemented by motivational interviewing by telephone for 18 months ; ( 2 ) a similar protocol that addressed a new behavior every 6 months ; or ( 3 ) 1-time referral to existing group classes ( " usual care " ) . The primary end point was the proportion in each arm that met at least 2 behavioral criteria after 18 months . RESULTS A total of 289 individuals ( 67.3 % female ) were r and omized , and 230 ( 79.6 % ) completed the study . At 18 months , only 6.5 % in the simultaneous arm , 5.2 % in the sequential arm , and 6.5 % in the usual-care arm met the primary end point . However , results for single behavioral goals consistently favored the simultaneous group . At 6 months , 29.6 % in the simultaneous , 16.5 % in the sequential , and 13.4 % in the usual-care arms had reached the urine sodium goal ( P = .01 ) . At 18 months , 20.3 % in the simultaneous , 16.9 % in the sequential , and 10.1 % in the usual-care arms were urine cotinine negative ( P = .08 ) . CONCLUSIONS Long-term multiple behavior change is difficult in primary care . This study provides strong evidence that addressing multiple behaviors sequentially is not superior to , and may be inferior to , a simultaneous approach AIMS An innovation offered by stage models of behaviour change is that of stage-matched interventions . Match-mismatch studies are the primary test of this idea but also the primary test of the validity of stage models . This study aim ed at conducting such a test among tobacco smokers using the Social Cognitive Stage Model . DESIGN A match-mismatch field-experiment was conducted in which smokers and ex-smokers in different stages were assigned r and omly to one of three information conditions . PARTICIPANTS Smokers in the pre-contemplation stage , the contemplation stage and the preparation stage , and ex-smokers in the action stage ( n = 481 ) , who were recruited through mass media , were assigned r and omly to one of three information conditions . INTERVENTION In each of the three information conditions , participants received a four- to six-page computer-tailored letter design ed to : ( 1 ) increase the positive outcome expectations of quitting , ( 2 ) decrease the negative outcome expectations of quitting or ( 3 ) increase self-efficacy . MEASUREMENTS Forward stage transition was the primary outcome measure , which was assessed 2 months after the participants received the information . FINDINGS At the 2-month follow-up , the matched interventions were significantly more effective in stimulating forward stage transition ( 44.7 % ) than were mismatched interventions ( 25.8 % ; odds ratio = 2.78 ; confidence interval = 1.85 - 4.35 ) . CONCLUSION The present study provides experimental support for the benefits of stage-matching and for the validity of the Social Cognitive Stage Model BACKGROUND The high prevalence of behavioral risk factors for cardiovascular diseases dem and s innovative approaches to achieving behavior change . Primary care physicians are in an ideal position for offering such interventions . PURPOSE To evaluate whether training of primary care physicians in counseling skills based on the Transtheoretical Model ( TTM ) leads to motivational and behavioral changes in their patients . METHOD Seventy-four primary care physicians in Germany were r and omly assigned to either an intervention condition ( one day of training in TTM-based counseling plus brochures matched to their patients ' " stages of change " ) or a control condition ( usual care ) . Baseline and 12-month follow-up data were collected from 305 of their patients who signed up for a health check-up . OUTCOME MEASURE Patients ' movements across the stages of change for smoking , diet , exercise and stress management . RESULTS After 12 months , patients of physicians in the intervention group did not show more movement through the stages of change for any of the behaviors than did patients of control physicians . Additionally , there were no differences between groups in counseling frequency , counseling intensity , or patient satisfaction with counseling . CONCLUSIONS A high dropout rate at follow-up and result ing " power " problems limit the possible conclusions . The high numbers of patients in early stages of change and the minimal improvement over time underline the need for improving motivational counseling skills of primary care physicians in Germany . In our study the dissemination of these strategies failed . We offer lessons we feel can be learned from this outcome . Further studies should focus on ways to enhance the process of educating physicians for implementing counseling strategies in primary care setting BACKGROUND A multicomponent motivational smoking cessation intervention was evaluated in 33 prenatal , family planning , and pediatric services in 12 public health clinics . Clinic-based intervention components were implemented by clinic personnel as part of routine medical visits . METHODS The evaluation design included pre- and postintervention measurements of multiple study outcomes in a baseline ( all clinics prior to the start of the intervention ) and an experimental period ( matchedpair r and om assignment of clinics to intervention or control conditions ) . Subjects were 683 ( baseline ) and 1,064 ( experimental ) smokers with measurements of smoking outcomes at both times . Mixed-effects regressions analyzed individual outcomes clustered within clinics and services . RESULTS Control and intervention clinics had similar outcomes in the baseline period . In the experiment , outcomes improved in the intervention but not in the control clinics . Compared to controls , smokers exposed to the intervention were more likely to have quit ( 14.5 versus 7.7 % ) or take actions toward quitting and had higher mean action , stage of readiness , and motivation to quit scores . These positive effects persisted when clustering within clinics and services was controlled . CONCLUSIONS This intervention , implemented by clinic personnel as part of routine medical visits , was effective under these natural conditions across different types of clinic service OBJECTIVES 1 . Quantitative description of the adherence to the principles of Motivational Interviewing ( MI ) in smoking counseling sessions , 2 . Examination of the relation between clients ' characteristics and the adherence to the principles of MI , and between adherence to the principles of MI and future smoking status . METHODS A sample of n=163 sessions conducted during a r and omized controlled trial in testing the effectiveness of a population -based smoking intervention in women postpartum was investigated . Demographic and behavior-related variables were included in a logistic regression to predict adherence to MI . Adherence was measured using the Motivational Interviewing Treatment Integrity ( MITI ) scale . RESULTS Of the sessions , 49.4 % showed good adherence to MI . The OR of receiving a good MI session was 3.1 for non-smokers in comparison to daily smokers . No other demographic or behavioral variable gained statistical significance . The relation between adherence and intervention outcome after 6 months was statistically significant ( chi(2)=6.459 , p<0.05 ) . CONCLUSIONS This intervention study shows a satisfactory degree of adherence to and the effectiveness of MI . MI-adherence seems more likely in sessions concerned with smoking relapse prevention compared to smoking cessation sessions Community college students represent 44 % of all students enrolled in U.S. higher education facilities . To our knowledge , no previous smoking cessation intervention has targeted community college students . Previous studies suggest that a motivational smoking cessation intervention could be successful for young adult smokers . Combining motivational interviewing sessions with personalized health feedback is likely to increase participants ' motivation to quit and movement through the stages of change . The purpose of this study was to evaluate the impact of a smoking cessation program based on these premises . We design ed a computer-assisted , counselor-delivered smoking cessation program that addresses personal health risks and readiness to change smoking behavior among community college students . A group-r and omized , controlled trial was used to assess the intervention in a sample of 426 students ( 58.5 % females ; mean age , 22.8+/-4.7 years ) from 15 pair-matched campuses . At the 10-month follow-up assessment , the cotinine-vali date d smoking cessation rates were 16.6 % in the experimental condition and 10.1 % in the st and ard care condition ( p=0.07 ) . Our results indicate that our computer-assisted intervention holds considerable promise in reducing smoking among community college students Although tailored interventions consisting of only a few pages of information lead to more quitting than no intervention in the short term , the long-term efficacy of a single tailored intervention still has to be proven . In the present study smokers were reactively recruited and r and omly allocated to one of four intervention conditions : ( 1 ) outcome information , ( 2 ) self-efficacy enhancing information , ( 3 ) both sorts of information or ( 4 ) no information . Smokers in the three experimental groups received computer-generated tailored feedback containing the condition-specific information , by mail . The results from the 14 months follow-up can be summarized as follows . Compared to the no information condition , all three experimental conditions led to significantly more smokers who had engaged in 24-h quit attempts . However , no experimental condition led to more 7-day quitting than the no information condition . With regard to continuous abstinence , the experimental condition offering a combination of outcome information and self-efficacy enhancing information had a significant effect , compared to the no information condition . It is concluded that a minimal six-page tailored intervention can be beneficial in supporting smokers to quit smoking , even after 14 months BACKGROUND Health promotion interventions often contain several , conceptually diverse elements . As a result , it is often difficult to determine why interventions succeed or fail as well as which components should be retained or eliminated . One method to examine the effectiveness of individual intervention elements is process analysis . METHODS Kick It ! is a multicomponent smoking cessation intervention developed for lower socioeconomic African Americans . The intervention includes several components , including a 24-page printed cessation manual , a staged-cessation video , a quit contract , two " Quit and Win " contests , and a single telephone booster call . Using data from a r and omized intervention trial design ed to test the efficacy of the Kick It ! intervention , this article examines the use , impact , and interaction of the intervention 's subcomponents as well as possible mediating variables related to successful quitting among intervention participants ( n = 650 ) . RESULTS In univariate as well as multivariate analyses adjusting for age and stage of change , two of the five elements , watching the video and entering a Quit and Win contest , were significantly associated with 6-month point prevalence abstinence . Su bmi tting a quit contract and receiving the booster call were significantly associated with quitting in univariate analyses , while reading the Kick It ! guide was not significantly associated with quitting in either analysis . CONCLUSIONS Despite the positive effects observed for individual elements , quitting was not significantly greater among intervention relative to comparison subjects . The primary reason for this appears to be the overall lack of intervention use . Additional research examining strategies to increase use of the Kick It ! intervention components as well as the optimal sequencing and combination of components may be warranted Introduction : Family physicians ( FPs ) underuse opportunities to provide smoking cessation advice during routine consultations with patients who smoke . Distance learning is a promising approach to continuing medical education , particularly for FPs practicing in rural and remote areas . We developed a distance learning module , conducting a r and omized trial to assess its educational impact on knowledge , attitudes and skills ( “ competence ” ) , self‐rated competence , confidence , and readiness to change . Method : Volunteer FPs were r and omly allocated to receive either a distance learning module or a preventive care guideline . Self‐administered question naires were completed at baseline and post‐test . Results : Fifty‐three FPs enrolled in the study . There were no changes in knowledge or attitudes . Change in skills was limited to a reduction in use of one ineffective technique , namely “ nicotine fading . ” Change in self‐rated competence between baseline and post‐test was significantly greater for the intervention than for the control group , however ( p = .03 ) . Although self‐ratings of confidence increased significantly between baseline and post‐test in both groups , the magnitude of change was no greater in the intervention than in the control group ( p = .3 ) . Both groups demonstrated only nonsignificant shifts in readiness to change . Discussion : These modest changes are of uncertain educational value , inviting caution before recommending distance learning approaches to promote smoking cessation advice in family practice Background : In assisting the nurse 's counselling on lifestyle changes in hypertension care a behaviour model can be used . Aim : To analyse the effects of nurses ' training on the use of the stages of change model when counselling hypertensive patients to perform lifestyle changes . Methods : As part of a r and omised , controlled trial , 19 nurses belonging to the intervention group took part in video-recorded consultation training with simulated patients . To evaluate the training , the nurses audio-recorded their consultations with two patients before and after the intervention . Analysis focused on the areas of non-pharmacological treatment and the nurses ' attention to the patients ' readiness for change . Results : Patient participation in the consultations increased after the training . The importance of non-pharmacological treatment was mentioned more frequently for all areas of lifestyle behaviour , exercise , smoking , alcohol consumption , food and stress , and the nurses acquired a more distinct structure for their consultations . The mean length of the recorded consultations increased from 18 min to 20.5 min . All the criteria for fulfillment of attention to patient 's readiness to change were met in nine consultations before the training and in seven after it . After the training , attention was paid to support more frequently than before in the action and maintenance stages and a great deal of information was provided This experiment tested the transtheoretical model ( J.O. Prochaska & C.C. DiClemente , 1983 ) of smoking cessation by matching or mismatching interventions to smokers in a particular stage . The interventions were tested against a no-intervention condition with 92 college-aged daily smokers in the precontemplation stage of change . The stage-matched intervention asked smokers to think more about quitting smoking ; the stage-mismatched intervention provided action-oriented activities typically used for those ready to quit smoking . The results failed to support the value of matching interventions to a smoker 's stage of change . Instead , more smokers who received the action intervention tried to quit smoking . Matching interventions to an individual 's current stage may be less important than the transtheoretical model suggests Physicians can play a key role in smoking cessation but often fail to advise smokers effectively , mainly because they lack counseling skills . We need effective training programs starting during residency to improve physicians ’ smoking cessation interventions and smokers ’ quit rates . To achieve this goal , we developed a curriculum using active learning methods and the stages-of-change model . A r and omized trial demonstrated that this program increased the quality of physician ’s counseling and smokers ’ quit rates at 1 year . This paper describes the educational content and methods of this program . Participants learn to assess smokers ’ stage of change , to use counseling strategies matching the smoker ’s stage , and to prescribe pharmacological therapy . This 2 half-day training program includes observation of video-clips , interactive workshops , role plays , practice with st and ardized patients , and written material for physicians and patients . Participants reached learning objectives and appreciated the content and active methods of the program This prospect i ve r and omized study examined the impact of three tailored intervention approaches to increase quitting rates among African-American smokers who were clients of a community health center that serves primarily low-income and indigent persons . Smokers were r and omized to one of three groups : ( 1 ) health care provider prompting intervention alone , ( 2 ) health care provider prompting intervention with tailored print communications , and ( 3 ) health care provider prompting intervention with tailored print communications and tailored telephone counseling . Among the 160 smokers who completed the study , 35 ( 21.8 % ) had quit smoking at follow-up . Smokers who received the provider prompting intervention with tailored print material s were more likely to report having quit than smokers who received the provider intervention alone ( 32.7 % vs. 13.2 % , p < 0.05 ) . Smokers who received all three intervention components were not more likely to report having quit at follow-up than those who only received the provider intervention ( 19.2 % vs. 13.2 % ) . Smokers who at baseline were less educated , smoked less than half a pack of cigarettes per day , had a stronger desire to quit , felt more efficacious , and had thought about quitting were more likely to report having quit at follow-up . These results provide support for continued refinement of tailored communications to aid smoking cessation among African-American smokers A stage-matched expert system intervention was evaluated on 4144 smokers in a two-arm r and omized control trial with four follow-ups over 24 months . Smokers were recruited by r and om digit-dial calls , and 80.0 % of the eligible smokers were enrolled . Individualized and interactive expert system computer reports were sent at 0 , 3 , and 6 months . The reports provided feedback on 15 variables relevant for progressing through the stages . The primary outcomes were point prevalence and prolonged abstinence rates . At 24 months , the expert system result ed in 25.6 % point prevalence and 12 % prolonged abstinence , which were 30 % and 56 % greater than the control condition . Abstinence rates at each 6-month follow-up were significantly greater in the Expert System ( ES ) condition than in the comparison condition with the absolute difference increasing at each follow-up . A proactive home-based stage-matched expert system smoking cessation program can produce both high participation rates and relatively high abstinence rates Aims To test the efficacy of ( i ) computer-generated tailored letters and ( ii ) practitioner-delivered brief advice for smoking cessation against an assessment -only condition ; and to compare both interventions directly . Design Quasi-r and omized controlled trial . Setting A total of 34 r and omly selected general practice s from a German region ( participation rate 87 % ) . Participants A total of 1499 consecutive patients aged 18–70 years with daily cigarette smoking ( participation rate 80 % ) . Interventions The tailored letters intervention group received up to three individualized personal letters . Brief advice was delivered during routine consultation by the practitioner after an onsite training session . Both interventions were based on the Transtheoretical Model of behaviour change . Measurements Self-reported point prevalence and prolonged abstinence at 6- , 12- , 18- and 24-month follow-ups . Findings Among participants completing the last follow-up , 6-month prolonged abstinence was 18.3 % in the tailored letters intervention group , 14.8 % in the brief advice intervention group and 10.5 % in the assessment -only control group . Assuming those lost to follow-up to be smokers , the rates were 10.2 % , 9.7 % and 6.7 % , respectively . Analyses including all follow-ups confirmed statistically significant effects of both interventions compared to assessment only . Using complete case analysis , the tailored letters intervention was significantly more effective than brief advice for 24-hour [ odds ratio ( OR ) = 1.4 ; P = 0.047 ] but not for 7-day point prevalence abstinence ( OR = 1.4 ; P = 0.068 ) for prolonged abstinence , or for alternative assumptions about participants lost to follow-up . Conclusions The study demonstrated long-term efficacy of low-cost interventions for smoking cessation in general practice . The interventions are suitable to reach entire population s of general practice s and smoking patients . Computer-generated letters are a promising option to overcome barriers to provide smoking cessation counselling routinely Background There is a considerable body of evidence on the effectiveness of specific interventions in individuals who wish to quit smoking . However , there are no large-scale studies testing the whole range of interventions currently recommended for helping people to give up smoking ; specifically those interventions that include motivational interviews for individuals who are not interested in quitting smoking in the immediate to short term . Furthermore , many of the published studies were undertaken in specialized units or by a small group of motivated primary care centres . The objective of the study is to evaluate the effectiveness of a stepped smoking cessation intervention based on a trans-theoretical model of change , applied to an extensive group of Primary Care Centres ( PCC ) . Methods / Design Cluster r and omised clinical trial . Unit of r and omization : basic unit of care consisting of a family physician and a nurse , both of whom care for the same population ( aprox . 2000 people ) . Intention to treat analysis . Study population : Smokers ( n = 3024 ) aged 14 to 75 years consulting for any reason to PCC and who provided written informed consent to participate in the trial . Intervention : 6-month implementation of recommendations of a Clinical Practice Guideline which includes brief motivational interviews for smokers at the precontemplation – contemplation stage , brief intervention for smokers in preparation-action who do not want help , intensive intervention with pharmacotherapy for smokers in preparation-action who want help , and reinforcing intervention in the maintenance stage . Control group : usual care . Outcome measures : Self-reported abstinence confirmed by exhaled air carbon monoxide concentration of ≤ 10 parts per million . Points of assessment : end of intervention period and 1 and 2 years post-intervention ; continuous abstinence rate for 1 year ; change in smoking cessation stage ; health status measured by SF-36 . Discussion The application of a stepped intervention based on the stages of a change model is possible under real and diverse clinical practice conditions , and improves the smoking cessation success rate in smokers , besides of their intention or not to give up smoking at baseline . Trial Registration Clinical Trials.gov Identifier : Background GPs often lack time to provide intensive cessation advice for patients who smoke . This study aim ed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse . Methods Adult smokers ( n = 318 ) attending 30 GPs in South Western Sydney , Australia were r and omly allocated to usual care or referral to a telephone-based program comprising assessment and stage-based behavioural advice , written information and follow-up delivered by a nurse . Self-reported point prevalence abstinence at six and 12 months was compared between groups . Characteristics of patients who accepted and completed the intervention were investigated . Results Of 169 smokers r and omised to the intervention , 76 ( 45 % ) consented to referral . Compared with smokers in ' pre-contemplation ' , those further along the stage-of-change continuum were significantly more likely to consent ( p = 0.003 ) . Those further along the continuum also were significantly more likely to complete all four calls of the intervention ( OR 2.6 , 95 % CI : 0.8–8.1 and OR 8.6 , 95 % CI : 1.7–44.4 for ' contemplation ' and ' preparation ' respectively ) . At six months , there was no significant difference between groups in point prevalence abstinence ( intention to treat ) ( 9 % versus 8 % , p = 0.7 ) . There was no evidence of differential intervention effectiveness by baseline stage-of-change ( p = 0.6 ) or patient sex ( p = 0.5 ) . At 12 months , point prevalence abstinence in the intervention and control groups was 8 % and 6 % respectively ( p = 0.6 ) . Conclusion Acceptance of opportunistic referral for nurse delivered telephone cessation advice was low . This trial did not demonstrate improved quit rates following the intervention . Future research efforts might better focus support for those patients who are motivated to quit . Australian Clinical Trials Registry 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 see whether the stages of change are useful for targeting a brief intervention to reduce smoking based on implementation intentions . A second objective was to rule out dem and characteristics as an alternative explanation for the findings of intervention studies based on the transtheoretical model and implementation intentions . DESIGN Participants ( N = 350 ) were r and omized to a passive control condition ( question naire only ) , active control condition ( question naire plus instruction to plan to quit ) , or experimental condition ( question naire , plan to quit , form an implementation intention ) . Their behavior and psychosocial orientation to quit were measured at baseline and at 2-month follow-up . MAIN OUTCOME MEASURES Theory of planned behavior variables , nicotine dependence , and quitting . RESULTS Significantly more people quit smoking in the experimental condition than in the control conditions , and the planning instructions changed intention to quit and perceived control over quitting , but not behavior . Stage of change moderated these effects such that implementation intentions worked best for individuals who were in the preparation stage at baseline . CONCLUSION Harnessing both motivational and volitional processes seems to enhance the effectiveness of smoking cessation programs , although further work is required to clarify inconsistencies in the literature using the stages of change The Parents of Asthmatics Quit Smoking ( PAQS ) project contrasts two theory-based smoking cessation interventions for parents of children with asthma , and compares mechanisms of behavior change within and across theoretical perspectives . We hypothesize that enhancing the perception of risk to self and child will motivate smoking cessation more than st and ard approaches that emphasize building self-efficacy and coping skills for quitting in a population that is largely not motivated to quit smoking . Smokers ( n = 288 ) and their asthmatic children who receive nurse-delivered in-home asthma education ( as part of the insurance carrier 's st and ard of care ) are r and omized into one of two treatment conditions : ( 1 ) the Behavioral Action Model ( BAM ) , in which nurses emphasize goal setting and skill building to enhance self-efficacy to quit smoking , or 2 ) the Pre caution Adoption Model ( PAM ) , in which nurses tailor the intervention to the smoker 's readiness to quit and incorporate biomarker feedback [ i.e. level of carbon monoxide exposure to the smoker and level of environmental tobacco smoke ( ETS ) exposure to the child ] in order to increase risk perception in smokers . In both conditions , smokers who are ready to quit receive the nicotine patch . Analyses will examine ( 1 ) quit rates , ETS level and motivation to quit as the primary dependent variables , ( 2 ) mediators of behavior change between and within conditions , and ( 3 ) relations between parent smoking outcomes and child asthma morbidity ( i.e. ER visits and asthma symptoms ) post-treatment . Results will help tailor interventions to this population , and identify mechanisms of behavior change that result in adaptive health outcomes for smokers and their children who have asthma The incremental effects of ( a ) a self-help booklet alone , ( b ) self-help booklet with computer-generated personalized feedback , and ( c ) self-help booklet , personalized feedback , and outreach telephone counseling were evaluated in a population -based , nonvolunteer sample of smokers . Smokers ( N = 1,137 ) were identified through a telephone survey of a r and om sample of 5,903 enrollees in a health maintenance organization and r and omized to a no-treatment control group or 1 of the 3 intervention conditions . Smoking status was ascertained 3 , 12 , and 21 months postr and omization . Cotinine validation of self-reported cessation was obtained at the 12-month follow-up . Overall , the telephone counseling significantly increased smoking cessation at the 3-month follow-up , but not at 12 or 21 months . Among smokers who were precontemplative at baseline , telephone counseling significantly increased prevalent abstinence at 3 and 12 months and continuous abstinence at 21 months ( defined as self-reported abstinence at 3 , 12 , and 21 months ) PURPOSE This study examines tailored feedback letters of a smoking cessation intervention that is conceptually based on the transtheoretical model , from a content-based perspective . METHODS Data of 2 population -based intervention studies , both r and omized controlled trials , with total N=1044 were used . The procedure of the intervention , the tailoring principle for the feedback letters , and the content of the intervention material s are described in detail . Theoretical and empirical frequencies of unique feedback letters are presented . RESULTS The intervention system was able to generate a total of 1040 unique letters with normative feedback only , and almost half a million unique letters with normative and ipsative feedback . Almost every single smoker in contemplation , preparation , action , and maintenance had an empirically unique combination of tailoring variables and received a unique letter . In contrast , many smokers in precontemplation shared a combination of tailoring variables and received identical letters . CONCLUSION The transtheoretical model provides an enormous theoretical and empirical variability of tailoring . However , tailoring for a major subgroup of smokers , i.e. those who do not intend to quit , needs improvement . Conceptual ideas for additional tailoring variables are discussed This study was design ed to assess if there are consistent treatment , stage , severity , effort and demographic effects which predict long-term changes across the multiple behaviors of smoking , diet and sun exposure . A secondary data analysis integrated data from four studies on smoking cessation ( N = 3927 ) , three studies on diet ( N = 4824 ) and four studies on sun exposure ( N = 6465 ) . Across all three behaviors , behavior change at 24 months was related to treatment , stage of change , problem severity and effort effects measured at baseline . There were no consistent demographic effects . Across multiple behaviors , long-term behavior changes are consistently related to four effects that are dynamic and open to change . Behavior changes were not consistently related to static demographic variables . Future intervention research can target the four effects to determine if breakthroughs can be produced in changing single and multiple behaviors How can pregnant women be helped to stop smoking ? This was a pilot study of midwife home-based motivational interviewing . Clients were 100 consecutive self-reported smokers booking at clinics in Glasgow from March to May 1997 . Smoking guidance is routinely given at booking . In addition , intervention clients received a median of four home-based motivational interviewing sessions from one specially trained midwife . All sessions ( n = 171 ) were audio-taped and interviews ( n = 49 ) from 13 r and omly selected clients were transcribed for content analysis . Three ' experts ' assessed intervention quality using a recognized rating scale . Cotinine measurement on routine blood sample s confirmed self-reported smoking change from late pregnancy telephone interview . Postnatal telephone question naire measured client satisfaction . Focus groups of routine midwives explored acceptability , problems and disruption of normal care . Fisher exact , chi 2 and Mann-Whitney tests compared enrolment characteristics . Two- sample t-tests assessed outcome between groups . Motivational interviewing was satisfactory in more than 75 % of transcribed interviews . In this pilot study , self-reported smoking at booking ( 100 of 100 available ) corroborated by cotinine ( 93 of 100 ) compared with late pregnancy self-reports ( intervention 47 of 48 ; control 49 of 49 ) and cotinine ( intervention 46 of 48 ; control 47 of 49 ) showed no significant difference between groups . Tools have been developed to answer the question : ' Can proactive opportunistic home-based motivational interviewing help pregnant smokers reduce their habit ? ' To test the effectiveness of a low-intensity intervention program for smoking cessation targeting the worksite environment in employees who had a low readiness to quit , we conducted an intervention trial at six intervention and six control worksites in Japan . A total of 2,307 smokers at baseline who remained at their worksite throughout the three-year study period were analyzed ( 1,017 in intervention and 1,290 in control groups ) . The multi-component program at the worksites consisted of ( 1 ) presenting information on the harms of tobacco smoking and the benefits of cessation by posters , websites , and newsletters ; ( 2 ) smoking cessation campaigns for smokers ; ( 3 ) advice on design ation of smoking areas ; and ( 4 ) periodic site-visits of the design ated smoking areas by an expert research er . At baseline , the intervention and control groups each had high prevalence of immotive or precontemplation , that reflected low readiness to quit ( 71.5 % and 73.2 % , respectively ) . The smoking cessation rate , as not having smoked for the preceding six months or longer , assessed at 36 months after the baseline survey by a self-administered question naire was significantly higher in the intervention group than the control group ( 12.1 % , vs. 9.4 % , p=0.021 ) . The intervention program still had a significant effect on the smoking cessation rate after multiple logistic regression analysis adjusted for sex , age , type of occupation , age of starting smoking , quit attempts in the past , number of cigarettes per day , and readiness to quit ( odds ratio : 1.38 , 95 % confidence interval : 1.05 - 1.81 , p=0.02 ) . The cost per additional quitter due to the intervention was calculated to be Yen 70,080 . These findings indicate that this program is effective and can be implemented in similar workplaces where the prevalence of smoking is high and smokers ' readiness to cease smoking is low OBJECTIVES A key variable for the design of individual and public health interventions for smoking cessation is Stage of Change , a variable which employs past behavior and behavioral intention to characterize an individual 's readiness to change . Reactively recruited sample s distort estimates of the stage distribution in the population because such sample s attract a disproportionate number of late-stage participants . Three representative sample s are described which provide accurate estimates of the stage distribution in the population . These sample s are of adequate size to permit within- sample comparisons with respect to sex , age , Hispanic or non-Hispanic origin , race , and education level . The implication s of using stage distribution as a tool for planning intervention is discussed . METHOD The first sample of 4,144 smokers was from the state of Rhode Isl and and involved a r and om-digit-dial survey . The second sample of 9,534 smokers was from the state of California and involved a stratified r and om-digit-dial survey . The third sample of 4,785 smokers was from a total of 114 worksites located in four different geographic locations . RESULTS The stage distributions were approximately identical across the three sample s , with approximately 40 % of the sample in Precontemplation , 40 % in Contemplation , and 20 % in Preparation . The stage distribution was generally stable across age groups with the exception of the 65 years and older group . Education level did affect the stage distribution with the proportion of the sample in Precontemplation decreasing as education level increased . In all three sample s , minor differences in stage distribution were related to Hispanic origin and race , but the pattern was not consistent across the sample s. CONCLUSIONS The pattern of stage distribution has important implication s for the design of interventions . Existing interventions are most appropriate for the Preparation stage , but the majority of the three sample s were in the first two stages , result ing in a likely mismatch between the smoker and the intervention . The stability of distribution across age suggests that interventions that are appropriately matched to stage can be applied across all age groups . The differences found with respect to education , Hispanic origin , and race can serve as a guide to the tailoring of intervention material AIM To examine the population impact and effectiveness of the Pro-Change smoking cessation course based on the Transtheoretical Model ( TTM ) compared to st and ard self-help smoking cessation literature . DESIGN R and omized controlled trial . SETTING Sixty-five West Midl and s general practice s. PARTICIPANTS R and omly sample d patients recorded as smokers by their general practitioners received an invitation letter and 2471 current smokers agreed . INTERVENTIONS Responders were r and omized to one of four interventions . The control group received st and ard self-help literature . In the Manual intervention group , participants received the Pro-Change system , a self-help workbook and three question naires at 3-monthly intervals , which generated individually tailored feedback . In the Phone intervention group , participants received the Manual intervention plus three telephone calls . In the Nurse intervention group , participants received the Manual intervention plus three visits to the practice nurse . MEASUREMENTS Biochemically confirmed point prevalence of being quit and 6-month sustained abstinence , 12 months after study commencement . FINDINGS A total of 9.1 % of registered current smokers participated , of whom 83.0 % were not ready to quit . Less than half of participants returned question naires to generate second and third individualized feedback . Telephone calls reached 75 % of those scheduled , but few participants visited the nurse . There were small differences between the three Pro-Change arms . The odds ratio ( 95 % confidence intervals ) for all Pro-Change arms combined versus the control arm were 1.50 ( 0.85 - 2.67 ) and 1.53 ( 0.76 - 3.10 ) , for point prevalence and 6-month abstinence , respectively . This constitutes 2.1 % of the TTM group versus 1.4 % of the control group achieving confirmed 6-month sustained abstinence . CONCLUSIONS There was no statistically significant benefit of the intervention apparent in this trial and the high relapse of quitters means that any population impact is small In a unique approach to utilizing an existing intervention , " opportunistic " and targeted school-based strategies were used to enroll 446 adults into a tailored preventive health program featuring a health screening and smoking-cessation intervention . Implemented through a public school district serving a multi-ethnic low-to-middle income urban community , subjects in this r and omized trial were interviewed at enrollment and at three- , six- , and 12-month follow-up , and rescreened at 12 months , to assess changes in smoking-related knowledge , attitudes , and practice s. Using conservative assumptions , self-reported ever-quit rates and continuous abstinence rates of 57.5 % and 2.6 % , respectively , were achieved across groups ; point-prevalence abstinence rates were 13.2 % , 12.9 % , and 10.3 % at three , six , and 12 months . The study examines issues relevant to smoking status and stages of change in this population . The role of the school in increasing access to needed health programming in underserved communities is explored PURPOSE The purpose of this study was to test the effectiveness of a comprehensive smoking cessation program for Korean adolescents . METHOD The study design was quasi-experimental with one pre and three post-tests . The three posttests were done immediately after , three months later , and six months after the completion of the program . A total of 43 high school students who smoked participated in the study with 22 in the experimental group and 21 in the control group . The smoking cessation program consisted of 9 sessions with content on enhancement of self-efficacy , stress management , correction of distorted thoughts , consciousness raising , and assertiveness training . The study variables were urine cotinine levels , self-efficacy , stress , and stages of changed behavior . RESULTS Urine cotinine levels significantly decreased in the experimental group after the program ( F=3.02 , p=.06 ) but significantly increased in the control group ( F=6.32 , p=.004 ) . Self-efficacy and the degree of stress did not change in either group . The stages of smoking cessation behavior tended to change when compared with raw data for the experimental group . For most participants , the stages of change had been precontemplation and contemplation , but changed to action and maintenance stage among the experimental group . CONCLUSION The program was effective in smoking cessation and influencing stages of change but did not change psychosocial factors such as self-efficacy and stress . It is suggested a program should be developed to change psychosocial variables on a long-term basis . It is also desirable to involve peers and families of adolescents who smoke when planning programs to enhance social support PURPOSE Smoking cessation is an important goal for smokers with coronary artery disease ( CAD ) because it reduces cardiac morbidity and mortality . Effective interventions for cigarette smokers with CAD exist , but they often are considered to be intensive and expensive . Stepped-care interventions have been proposed as a promising way to allocate smoking cessation treatments in a cost-effective manner . Stepped care refers to the practice of initiating treatment with low-intensity intervention and then exposing treatment failures to successively more intense interventions . METHODS To address the efficacy of this approach , 254 cigarette smokers hospitalized with CAD were provided a brief cessation intervention . The participants then were assigned r and omly to either a more intensive stepped-care treatment ( counseling and nicotine patch therapy ) or no additional treatment . Outcomes were point-prevalent abstinence measured 3 months and 1 year after hospital discharge . RESULTS Stepped-care treatment increased smoking cessation rates from 42 % to 53 % during a 3-month follow-up period ( P = .05 ) , but showed little effect at the 1-year follow-up assessment , as evidence d by a cessation rate for the minimal intervention group of 36 % versus 39 % for the stepped-care group ( P = .36 ) . CONCLUSIONS A stepped-care approach to smoking cessation increased short-but not long-term point-prevalent abstinence in patients with CAD . For improvement of long-term effectiveness , refinement of the timing and content of stepped-care interventions needs to occur BACKGROUND Smoking cessation is the primary disease modifying intervention for chronic obstructive pulmonary disease ( COPD ) . SETTING A Regional Respiratory Centre ( RRC ) out-patient department in Northern Irel and . METHODS A r and omised controlled trial ( RCT ) evaluated the effectiveness of brief advice alone or accompanied by individual nurse support or group support facilitated by nurses . Smoking status was biochemically vali date d and stage of change , nicotine addiction and dyspnoea were recorded at 2 , 3 , 6 , 9 and 12 months . PARTICIPANTS Ninety-one cigarette smokers with COPD were enrolled in the study ( mean age 61 years , 47 female ) . RESULTS After 12 months cessation rates were not significantly different between groups ( p=0.7 ) , but all groups had a significant reduction in their nicotine addiction ( p=0.03 - 0.006 ) . No changes in subjects ' motivation or dyspnoea were detected over the 12 months . CONCLUSION Patients with COPD were unable to stop smoking regardless of the type of support they received . Harm reduction may be a more appropriate goal than complete cessation for intractable smokers and nurses must evaluate their role in this arena BACKGROUND Evaluate the feasibility , acceptability , and potential efficacy of a skills-training intervention for adults interested in helping someone to stop smoking ( i.e. , support persons ) . METHODS Sixty adult support persons ( 77 % female ) were directly recruited from the community and r and omly assigned to this intervention ( manual plus five weekly group-based sessions ) or a control condition ( one-page leaflet ) . All intervention and outcome assessment s occurred through the support persons . Assessment s occurred at weeks 0 ( baseline ) , 6 ( end of treatment ) , 12 , and 24 . The study was conducted from 1998 to 2001 ; data collection occurred from 1999 to 2000 . Outcomes were ratings of treatment acceptability , recruitment and retention rates , supportive behaviors provided to the smoker , and smoking behavior change in the smoker as reported by the support person . RESULTS Support persons were recruited in a timely manner and study retention rates were high . Support persons in skills training showed significant increases in their supportive behavior scores compared with control subjects at weeks 6 and 12 . Although not statistically significant , the skills-training intervention was associated with more quit attempts , greater improvement in stage of change , and higher 7-day point prevalence abstinence rates in the smokers than the control condition . CONCLUSIONS A skills training intervention for support persons is feasible and acceptable . Further studies are needed to test the efficacy of this approach for smoking cessation Counseling coupled with a stages-of-change model in cigarette smoking cessation is a useful method for physicians to help patients stop smoking . The participants were 27 physicians , r and omly assigned to three groups of nine physicians each . The first group of physicians were given two lectures on the stages-of-change model on which to base their patient counseling . The second group of physicians were not exposed to the model but a reminder reading " Ask your patients to stop smoking " was placed in their clinic . The third group of physicians were neither exposed to the model nor given any reminder . Of the 93 smokers among the patients of the 27 physicians , 39 were in the first group , 26 in the second , and 28 in the third . A survey indicated that among the three groups there was no significant difference in demographic data , cigarette smoking history , and personal attitude toward smoking cessation counseling . At the end of six months , the first group of patients accomplished a quit smoking rate of 28.6 % ; of the patients still smoking 56 % had decreased their daily cigarette consumption . The corresponding figures for the second group were 8.3 % and 9.1 % . The corresponding figures for the third group were 4.3 % and 13.6 % . These data show that counseling coupled with the concept of a stages-of-change model is feasible and effective to assist with cigarette smoking cessation OBJECTIVE To examine whether telephone counselling based on the stages of change component of Transtheoretical model of behaviour change together with educational material s could help non-motivated smoking parents of young children to cease . DESIGN R and omised controlled trial . SETTING Hong Kong Special Administrative Region , PR China . PARTICIPANTS 952 smoker fathers and mothers of Chinese children aged 5 years . INTERVENTION Participants were r and omly allocated into two groups : the intervention group received printed self-help material s and three-session telephone-based smoking cessation counselling delivered by trained counsellors ; the control group received printed self-help material s only . A structured question naire was used for data collection at baseline and at 1 , 3 and 6 month follow up . MAIN OUTCOME MEASURES The main outcome is 7 day point prevalence quit rate at 6 months ( defined as not smoking during the 7 days preceding the 6 month follow up ) determined by self reports . Other secondary outcomes were self reported 24 h point prevalence quit rate and self-reported continuous quit rate and bio-chemically vali date d quit rate at 6 months . RESULTS A total of 952 smoker fathers and mothers were r and omized to the intervention ( n = 467 ) and control ( n = 485 ) groups . Most were daily smokers ( 92.4 % ) and the mean number of cigarettes smoked per day was 14.5 ( SD = 8.9 ) . By using intention-to-treat analysis , the 7 day point prevalence quit rate at 6 month follow up was significantly greater in the intervention group ( 15.3 % ; 68/444 ) than the control group ( 7.4 % ; 34/459 ) ( P < 0.001 ) . The absolute risk reduction was 7.9 % ( 95 % confidence interval : 3.78 % to 12.01 % ) . The number needed to treat to get one additional smoker to quit was 13 ( 95 % CI : 8 - 26 ) . The crude odds ratio of quitting was 2.3(95 % CI : 1.5 - 3.5 ) . The adjusted odds ratio was 2.1 ( 95 % CI : 1.4 - 3.4 ) ( adjusted for age , number of years smoked , and alcohol dependency ) . CONCLUSION Proactive telephone counselling is an effective aid to promote smoking cessation among parents of young children AIMS To assess the effects of a smoking cessation program for recovering alcoholics on use of alcohol , tobacco and illicit drugs after discharge from residential treatment . DESIGN AND SETTING A r and omized community intervention trial design was employed in which 12 residential drug treatment centers in Iowa , Kansas and Nebraska were matched and then r and omly assigned to the intervention or control condition . PARTICIPANTS Approximately 50 adult residents ( in patients ) from each site were followed for 12 months after treatment discharge . INTERVENTION Participating residents in the six intervention centers received a 4-part , individually tailored , smoking cessation program while those in the six control sites received usual care . FINDINGS Both moderate and heavy drinking rates were reduced in the intervention group . Intervention site participants were significantly more likely than controls to report alcohol abstinence at both the 6-month ( OR = 1.59 , 95%CI : 1.09 - 2.35 ) and 12-month assessment ( OR = 1.84 , 95%CI : 1.28 - 2.92 ) . Illicit drug use rates were comparable . Effect of the intervention on tobacco quit rates was not statistically significant . CONCLUSIONS Counseling alcoholics in treatment to quit smoking does not jeopardize the alcohol recovery process . However , low-intensity tobacco interventions are unlikely to yield high tobacco quit rates BACKGROUND This study evaluated the effectiveness of three smoking cessation interventions for this population : ( 1 ) modified usual care ( UC ) ; ( 2 ) brief advice ( A ) ; and ( 3 ) brief advice plus more extended counseling during and after hospitalization ( A + C ) . METHODS Smokers ( 2,095 ) who were in- patients in four hospitals were r and omly assigned to condition . Smoking status was ascertained via phone interview 7 days and 12 months post-discharge . At 12 months , reports of abstinence were vali date d by analysis of saliva cotinine . Intent to treat analyses were performed . RESULTS At 7-day follow-up , 24.2 % of participants reported abstinence in the previous 7 days . There were no differences between conditions . At 12-month follow-up , self-reported abstinence was significantly higher in the A + C condition ( UC ( 15.0 % ) vs. A ( 15.2 % ) vs. A + C ( 19.8 % ) ) . There was no significant difference among conditions in cotinine-vali date d abstinence , however ( UC ( 8.8 % ) vs. A ( 10.0 % ) vs. A + C ( 9.9 % ) ) . CONCLUSIONS These interventions for hospital in- patients did not increase abstinence rates . Features of the study that might have contributed to this finding were the inclusiveness of the participation criteria , the fact that pharmacological aids were not provided , and a stage-matching approach that result ed in less intensive counseling for participants unwilling to set a quit date BACKGROUND Although older adults can achieve significant health benefits from smoking cessation , few programs have specifically targeted this population . This study tested the effectiveness of an office-based smoking cessation program tailored to midlife and older smokers . METHODS This paper describes a r and omized controlled trial comparing usual care with physician-delivered brief quit-smoking advice and counseling for midlife and older smokers ( ages 50 - 74 ) . Outpatient medical practice s assigned to the Immediate Intervention ( experimental ) condition were trained to deliver brief quit-smoking advice and counseling . Delayed Intervention ( control ) practice s followed usual care procedures . Thirty-nine practice s accruing five or more patients per practice were included in the analyses . RESULTS Using conservative measure of quitting , self-reported quit rates at 6-month follow-up were 15.41 % for the Immediate Intervention group versus 8.16 % of subjects in the Delayed Intervention group ( P < 0.005 ) . Baseline subject ( N = 659 ) characteristics related to 6-month abstinence included number of previous quit attempts , quitting for 24 hr in the past year , desire to quit , confidence in quitting , perceived health benefits , and lower nicotine dependence . CONCLUSIONS Smoking abstinence was significantly increased by training physicians and key office and clinical staff to intervene with older smokers . Brief interventions are tailored to this age cohort can be successfully and efficaciously integrated into routine care Background Various strategies have been used to induce lifestyle changes to reduce ischaemic heart disease ( IHD ) with various successes . The aim of Inter99 is to assess the effect on IHD incidence of individually tailored non-pharmacological intervention on lifestyle using a newly developed computer-based health educational tool . The article describes the study and baseline results . Methods From a population of 61,301 individuals two r and om sample s ( high intensity intervention group ( A ) , n = 11,708 ; low intensity intervention group ( B ) , n = 1308 ) are screened to assess their absolute risk of IHD . Those at high risk receive individual lifestyle counselling . Individuals in group A are furthermore offered lifestyle counselling in groups on smoking cessation or physical activity/diet over a 6-month period . Individuals in group B are referred to their GP . High-risk persons are re-counselled after 1 and 3 years and the whole group is re-invited after 5 years . The remaining 48,285 ( group C ) are followed by question naire . The total population is followed through central registers . Intermediate end-points are changes in lifestyle , cholesterol , blood pressure and body mass index . Final end-point is reduction in incidence of IHD . Results The r and omization leads to comparable groups . Participation rate was 52.5 % . A total of 60 % fulfilled the predetermined criteria for being at high risk for developing IHD . After an individual lifestyle counselling 41 % accepted group-based counselling . Conclusion This large r and omized population based trial discloses a noticeable need for and acceptance of lifestyle intervention in the general population . Eur J Cardiovasc Prevention Rehab 10:377 - 386 © 2003 Lippincott Williams & Wilkins The Transtheoretical Model ( TTM ) proposes that stage matching improves the effectiveness of behaviour change interventions , such as for smoking cessation . It also proposes that st and ard smoking cessation interventions are matched to the relatively few smokers in the preparation stage and will not assist the majority of smokers , who are in the precontemplation or contemplation stages . This study tested the hypothesis that stage-matched interventions increase movement through the stages relative to interventions not stage-matched . It also tested the hypothesis that the relative effectiveness of stage-matched interventions is greater for people in precontemplation or contemplation ( stage-matched for TTM but not for control ) than for people in preparation ( where both intervention and control were stage-matched ) . A total of 2471 UK adult smokers were r and omised to either control or TTM-based self-help intervention and followed up 12 months after beginning the programme . Content analysis of the intervention and control self-help interventions examined whether control interventions were action-oriented , meaning they emphasised the processes of change relevant for preparation and action . Participants in the TTM arm were slightly more likely to make a positive move in stage , but this was not significant . There was no evidence that the TTM-based intervention was more effective for participants in precontemplation or contemplation than for participants in preparation . There was no evidence that TTM-based interventions were effective in this trial . The control intervention advocated process use appropriate for all stages and was not action-orientated . Stage matching does not explain the modest effects of TTM-based interventions over control interventions observed in some trials . These effects may instead have occurred because TTM-based interventions were more intensive than control interventions Tailoring information to a target individual 's features is a promising line of development in self-help interventions . In this article , 752 smokers with explicit low intention to quit were r and omly assigned to 1 of 5 conditions : ( a ) multiple tailored letters with self-help guide , ( b ) multiple tailored letters only , ( c ) a single tailored letter with a self-help guide , ( d ) a single tailored letter only , or ( e ) a nontailored intervention . Follow-up assessment took place 4 months after the intervention . Results indicated that the single tailored intervention only had no surplus value compared with a nontailored look-alike intervention . The addition of a self-help guide to a tailored intervention was only useful in highly dependent smokers , and multiple tailoring was more effective than single tailoring . It remains important to eluci date why and for whom certain tailored interventions are more effective OBJECTIVE This study was design ed to compare the initial efficacy of Motivational Interviewing ( MI ) , Online Transtheoretical Model (TTM)-tailored communications and a brief Health Risk Intervention ( HRI ) on four health risk factors ( inactivity , BMI , stress and smoking ) in a worksite sample . METHOD A r and omized clinical trial assigned employees to one of three recruitment strategies and one of the three treatments . The treatment protocol included an HRI session for everyone and in addition either a recommended three TTM online sessions or three MI in person or telephone sessions over 6 months . At the initial post-treatment assessment at 6 months , groups were compared on the percentage who had progressed from at risk to taking effective action on each of the four risks . RESULTS Compared to the HRI only group , the MI and TTM groups had significantly more participants in the Action stage for exercise and effective stress management and significantly fewer risk behaviors at 6 months . MI and TTM group outcomes were not different . CONCLUSION This was the first study to demonstrate that MI and online TTM could produce significant multiple behavior changes . Future research will examine the long-term impacts of each treatment , their cost effectiveness , effects on productivity and quality of life and process variables mediating outcomes BACKGROUND Few smoking cessation self-help material s are available for smokers who are not planning to quit . However , computer-tailored interventions can be design ed specifically for these smokers . METHODS In a large r and omized field trial ( N = 843 ) , two different tailored smoking cessation self-help interventions ( multiple tailoring and single tailoring ) and one st and ardized smoking cessation self-help guide were compared with a no-information control group and with each other . The contents of the tailored interventions were adapted to individuals ' self-reported stage of change , outcome expectations , self-efficacy levels , and smoking behavior . RESULTS The primary outcome measure was forward stage transition . The st and ardized self-help guide had no effect . Among smokers who were not planning to quit within the next 5 years the multiple-tailored intervention was more effective than the single-tailored intervention . This pattern was supported by the cognitive changes caused by the interventions . Among smokers who were planning to quit within the next 5 years but not within the next 6 months , none of the self-help material s had any effect . CONCLUSION The present results show that the self-help material currently available in the Netherl and s , the st and ardized self-help guide , was not effective among smokers with low readiness to change . However , computer-generated tailored interventions seem a promising means of communicating information on smoking and smoking cessation to these smokers BACKGROUND Several large and well-conducted community interventions have failed to detect an effect on prevalence of smoking . METHODS Two thous and four hundred eight daily smokers in all motivational stages were actively recruited and included in a r and omised population -based intervention study in Copenhagen , Denmark . All smokers completed a question naire and underwent a health examination and a lifestyle consultation . Daily smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS The vali date d abstinence rate at 1-year follow-up was 16.3 % in the high intensity group and 12.7 % in the low intensity group compared with a self-reported abstinence rate of 7.3 % in the background population . The adjusted odds ratio of abstinence in the high intervention group was significantly higher , OR = 2.2 ( 1.6 - 3.0 ) than in the background population , also in the ' intention-to-treat ' analyses , OR = 1.5 ( 1.1 - 2.0 ) . Higher socioeconomic status , higher age at onset of daily smoking , and a higher wish to quit were predictors of success . CONCLUSION In a population -based setting , using active recruitment and offering assistance to quit , it was possible to include many smokers and to achieve a significantly higher vali date d abstinence in the high intensity intervention than in the background population , even when using ' intention-to-treat ' analyses OBJECTIVE To assess a " stage-of-change " oriented smoking cessation intervention for infertile and pregnant women , compared with st and ard of care . DESIGN R and omized controlled trial . SETTING Three university teaching hospitals in Hamilton , Ontario , Canada . PATIENT(S ) Infertile women at their first visit to a tertiary referral infertility clinic ( n = 94 ) and new patients seeking pre-natal care ( n = 110 ) who had smoked > /= 3 cigarettes in the past six months . INTERVENTION(S ) A three to five minute scripted intervention and booklet specific to the woman 's " stage-of-change " in the smoking continuum , versus st and ard of care . Exhaled carbon-monoxide ( CO ) monitoring was used to vali date exposure in both groups . MAIN OUTCOME MEASURE(S ) Delta " stage-of-change " and rate of maintained cessation at 12 months post follow-up . RESULT ( S ) Intervention and control were similarly effective for infertile women : the rate of maintained cessation rose significantly from 4 % to 24 % over twelve months , with a mean delta " stage-of-change " 0.28 . In prenatal women , neither approach was effective . Maintained cessation did not significantly change from 0 to 12 months ( 19 % to 18 % ) . Mean delta " stage-of-change " declined by -0.62 . CONCLUSION ( S ) For infertile women , basic information describing the impact of smoking on fertility , along with exhaled CO monitoring and a more intensive intervention were both highly effective . In pregnant women neither approach was beneficial , with some evidence of post-partum relapse BACKGROUND Treating multiple health behavior risks on a population basis is one of the most promising approaches to enhancing health and reducing health care costs . Previous research demonstrated the efficacy of expert system interventions for three behaviors in a population of parents . The interventions provide individualized feedback that guides participants through the stages of change for each of their risk behaviors . This study extended that research to a more representative population of patients from primary care practice and to targeting of four rather than three behaviors . METHODS Stage-based expert systems were applied to reduce smoking , improve diet , decrease sun exposure , and prevent relapse from regular mammography . A r and omized clinical controlled trial recruited 69.2 % of primary care patients ( N = 5407 ) at home via telephone . Three intervention contacts were delivered for each risk factor at 0 , 6 , and 12 months . The primary outcome measures were the percentages of at-risk patients at baseline who progressed to the action or maintenance stages at 24-month follow-up for each of the risk behaviors . RESULTS Significant treatment effects were found for each of the four behaviors , with 25.4 % of intervention patients in action or maintenance for smoking , 28.8 % for diet , and 23.4 % for sun exposure . The treatment group had less relapse from regular mammography than the control group ( 6 % vs. 10 % ) . CONCLUSION Proactive , home-based , and stage-matched expert systems can produce relatively high population impacts on multiple behavior risks for cancer and other chronic diseases Abstract Objectives : To develop and evaluate , in a primary care setting , a computerised system for generating tailored letters about smoking cessation . Design : R and omised controlled trial . Setting : Six general practice s in Aberdeen , Scotl and . Participants : 2553 smokers aged 17 to 65 . Interventions : All participants received a question naire asking about their smoking . Participants subsequently received either a computer tailored or a non-tailored , st and ard letter on smoking cessation , or no letter . Main outcome measures : Prevalence of vali date d abstinence at six months ; change in intention to stop smoking in the next six months . Results : The vali date d cessation rate at six months was 3.5 % ( 30/857 ) ( 95 % confidence interval 2.3 % to 4.7 % ) for the tailored letter group , 4.4 % ( 37/846 ) ( 3.0 % to 5.8 % ) for the non-tailored letter group , and 2.6 % ( 22/850 ) ( 1.5 % to 3.7 % ) for the control ( no letter ) group . After adjustment for significant covariates , the cessation rate was 66 % greater ( −4 % to 186 % ; P=0.07 ) in the non-tailored letter group than that in the no letter group . Among participants who smoked < 20 cigarettes per day , the cessation rate in the non-tailored letter group was 87 % greater ( 0 % to 246 % ; P=0.05 ) than that in the no letter group . Among heavy smokers who did not quit , a 76 % higher rate of positive shift in “ stage of change ” ( intention to quit within a particular period of time ) was seen compared with those who received no letter ( 11 % to 180 % ; P=0.02 ) . The increase in cost for each additional quitter in the non-tailored letter group compared with the no letter group was £ 89 . Conclusions : In a large general practice , a brief non-tailored letter effectively increased cessation rates among smokers . A tailored letter was not effective in increasing cessation rates but promoted shift in movement towards cessation ( “ stage of change ” ) in heavy smokers . As a pragmatic tool to encourage cessation of smoking , a mass mailing of non-tailored letters from general practice s is more cost effective than computer tailored letters or no letters . What is already known on this topic Brief opportunistic advice on stopping smoking that is given face to face by health professionals increases rates of cessation by 2 - 3 % Intensive , expert-led interventions increase cessation rates by up to 20 % or more but are expensive and reach only a small proportion of smokers Written advice tailored to an individual 's “ stage of change ” ( intention to stop in a particular period of time ) has been cl aim ed to be as effective as intensive interventions , but previous studies of tailored written advice did not biochemically vali date cessation What this paper adds A simple st and ard letter sent to patients of general practice s that gave brief advice on stopping smoking increased the biochemically vali date d rate of cessation by 2 % A letter tailored to the individual 's “ stage of change ” was not more effective than the non-tailored st and ard letter Although the increase in cessation result ing from the non-tailored st and ard letter was small , this intervention was highly cost Although smoking prevalence in the United States has declined markedly in recent years , prevalence among blue-collar workers remains high and few successful methods of reaching this group have been identified . The present study was design ed to test the relative efficacy of two different approaches to telephone smoking-cessation counseling for blue-collar workers . Our study built on the experience of the National Cancer Institute 's Cancer Information Service ( CIS ) and compared the past CIS smoking-cessation counseling procedure and a modified version of the present procedure . In our trial , callers to a special telephone hotline who asked for information on smoking cessation were r and omly assigned to receive counseling under one of two protocol s : 1 ) the past CIS procedure , in which general information was given and cessation material s were sent to the callers , and 2 ) a version of the present CIS stage-model procedure , adapted by us for use with blue-collar workers , in which callers were given counseling specific to their stage in the smoking-cessation process . The general-information group contained 185 subjects ; the stage-model group contained 197 . Despite extensive efforts in the present study , it was not possible to recruit the number of blue-collar workers planned for our statistical analysis . Consequently , of a total of 382 subjects recruited , 93 ( 24.3 % ) were blue-collar workers , 181 ( 47.4 % ) were white-collar workers , and 108 ( 28.3 % ) were retired persons who worked part time , student workers , or the unemployed . Our results show no statistically significant differences in either short-term or long-term nonsmoking rates between the general-information group and the stage-model group . ( ABSTRACT TRUNCATED AT 250 WORDS This study reports an experimental , r and omized controlled clinical trial comparing three treatments for smoking cessation : sustained-release bupropion , nicotine patch , and combination nicotine and bupropion , to a counseling-only control group ( N = 140 ) , for smoking sailors aboard seven Navy ships . The purpose was to determine the effectiveness of different pharmcotherapies used in smoking cessation programs . Continuous abstinence was defined as the percentage of subjects who did not smoke since the quit date assessed at 6 and 12 months and having an expired carbon monoxide concentration of < 10 ppm at educational sessions 2 , 3 , and 4 . Nine subjects dropped out of the study , and 40 subjects were lost to follow-up . Eleven percent ( 15/140 subjects ) had continuous abstinence at 12 months . The abstinence rates at 12 months were 47 % in the control group , as compared with 27 % in the nicotine patch/bupropion group , 20 % in the nicotine patch group , and 7 % in the bupropion group BACKGROUND A 2-year self-help manual smoking cessation intervention was conducted among a panel of middle-aged Finnish men ( n = 265 ) who were recruited proactively in a longitudinal cardiovascular risk factor surveillance study . METHODS Intervention utilized the stages of change concept of the transtheoretical model . The stages were assessed in the treatment condition at baseline of the cessation study and after that by mail every sixth month . Assessment s were followed by an immediate mailing of a stage-based self-help manual matching the stage of change at that time . A usual care group was assessed annually but received no treatment . RESULTS A significant time x intervention effect ( P < 0.05 ) and time x baseline stage effect ( P < 0.001 ) on quit rates were observed in the panel data over the 2-year period . An analysis of changes in the stages of change also revealed an accelerated cessation process in the treatment condition . CONCLUSIONS We conclude that mailed stage-matched self-help smoking cessation manuals were able to accelerate the smoking cessation process but manuals alone may not constitute a sufficient long-term intervention . The effects of differential exposure to intervention , subject characteristics , measurement reactivity , and secular trends are discussed as potential confounds According to the transtheoretical model of change , smoking cessation attempts are preceded by three stages : precontemplation , contemplation , and preparation . These stages have shown great utility in predicting and impacting on behavior change . This cross-cultural study examined the distribution of the stages within a 33 % r and om sample of middle-aged Finnish men . Of 490 regular smokers , 57.6 % were in precontemplation , 29.4 % in contemplation , and 13.0 % in preparation . Five conceptual clusters were used to predict the stage membership . The number of lifetime quit attempts and the number of 24-h quit attempts in the past 12 months were found to be the best discriminators among the stages . The overall correct classification rate into stages using stepwise discriminant function analysis was 64.0 % , substantially better than the chance rate . However , the analysis was successful for precontemplators only . Results showed that most smokers were precontemplators . Previous attempts to reduce smoking provided some predictive information concerning stage membership . Demographics , addiction to smoking , current smoking , smoking environment , and quit history were incomplete predictors of stage membership , as theoretically predicted This study reports the outcome of a r and omized controlled trial testing a computer-tailored smoking cessation intervention based on the transtheoretical model in a general population setting in Germany . Participants of the smoking intervention study were recruited from an existing general population health examination survey in a university hospital . The sample consisted of 611 current and former smokers at baseline , and of 485 participants in the core group of baseline daily cigarette smokers . Follow-ups were conducted 6 , 12 , 18 , and 24 months after baseline . The intervention was design ed for both current and former smokers , involved up to three individualized feedback letters , and was created using expert-system technology . Based on 7-day point-prevalence abstinence and 6-month prolonged abstinence as the outcome measures , the study identified no significant differences between the intervention and control groups . Modeling the full longitudinal data in generalized estimation equation analyses , using different nonresponse procedures , and adjusting for covariates did not alter the results . We conclude that the computer-tailored transtheoretical model-based smoking cessation intervention , as delivered in this study and in this special setting , was ineffective OBJECTIVES Examine the effectiveness of an intervention to increase fruits and vegetables ( FV ) consumption among smokers . DESIGN Cluster-r and omized trial of 20 public housing developments ; 10 r and omly assigned to an FV intervention and 10 to a smoking cessation intervention . MAIN OUTCOME MEASURES Usual ( past 7 days ) and past 30 days change in daily FV intake at 8 weeks and 6 months postbaseline . RESULTS Greater increases were seen in the FV group . At Week 8 and Month 6 , the FV group had consumed 1.58 ( p = .001 ) and 0.78 ( p = .04 ) , respectively , more daily FV servings in the past 7 days than the cessation group . At the same time points , the FV group had consumed 3.61 ( p = .01 ) and 3.93 ( p = .01 ) , respectively , more FV servings in the past 30 days than the cessation group . Completing more motivational interviewing sessions ( p = .02 ) and trying more recipes ( p = .02 ) led to significantly greater increases at Month 6 among FV participants . CONCLUSIONS Motivational interviewing counseling and lifestyle modification through trying out healthy recipes may be effective in helping a high-risk population increase their FV intake Smokers ( N = 756 ) were r and omly assigned by stage of change to ( a ) st and ardized self-help manuals ( ALA+ condition ) , ( b ) individualized manuals matched to stage ( TTT condition ) , ( c ) interactive expert-system computer reports plus individualized manuals ( ITT condition ) , or ( d ) a personalized condition with 4 counselor calls , stage manuals , and computer reports ( PITT condition ) . Over 18 months , the ITT group 's results more than doubled those of the ALA+ group on abstinence measures . The ALA+ and TTT conditions were equivalent over 12 months , but at 18 months the TTT condition was more effective . The ITT condition was the best or comparable with the best treatment at all follow-ups for smokers at all stages of change . Results suggest that an effective expert system has been developed , and discussion focuses on delivering this system to entire population s of smokers BACKGROUND The transtheoretical model ( TTM ) and computer technology are promising technologies for changing health behavior , but there is little evidence of their effectiveness among adolescents . METHOD Four thous and two hundred twenty-seven Year 9 ( ages 13 - 14 ) pupils in 26 schools were r and omly allocated to control and 4,125 in 26 schools were allocated to TTM intervention . TTM pupils received three whole class lessons and three sessions with an interactive computer program . Control pupils received no special intervention . Positive change in stage and smoking status was assessed from a question naire completed at baseline , 1 year , and 2 years . R and om effects logistic regression was used to compare the change in stage and smoking status between the arms . RESULTS Eighty-nine percent of the TTM group and 89.3 % of the control group were present at 1-year and 86.0 and 83.1 % , respectively , were present at 2-year follow-up . The adjusted odds ratio ( 95 % confidence interval ) for positive stage movement in the TTM relative to control was 1.13 ( 0.91 - 1.41 ) at 1 year and 1.25 ( 0.95 - 1.64 ) at 2 years and for regular smoking was 1.14 ( 0.93 - 1.39 ) at 1 year and 1.06 ( 0.86 - 1.31 ) at 2 years . Subgroup analysis by initial smoking status revealed no benefit for prevention or cessation . CONCLUSIONS The intervention was ineffective In the last decade , attempts have been made to improve the efficacy of minimal interventions by tailoring them to individual features . In the development of these tailored interventions , it is important to know which information in interventions is essential . Most smoking cessation interventions contain information on the outcomes of quitting and skills to be used in a quit attempt . The present study was design ed to assess the cognitive changes caused by both sorts of information . Therefore , 246 smokers who were planning to quit within 6 months were r and omly assigned to three different conditions . In the first condition , the respondents received a computer-generated tailored letter on the outcomes of smoking cessation . In the second condition , the respondents received a computer-generated tailored letter containing self-efficacy enhancing information , mainly on skills . In both conditions , the contents of the letters were based on the pre-test scores of the participants . Participants in the control condition did not receive any cessation information . The results show that information on the outcomes of quitting changed expected outcomes while information on coping skills changed self-efficacy expectations , in comparison with the control condition . Comparing both experimental conditions , information on the outcomes led to changes in expected outcomes , whereas information on coping skills did not lead to higher self-efficacy expectations than information on the outcomes of quitting . It is concluded that the hypothesized effects were partly verified Objective . To test the long-term efficacy of brief counseling plus a computer-based tobacco intervention for teens being seen for routine medical care . Methods . Both smoking and nonsmoking teens , 14 to 17 years of age , who were being seen for routine visits were eligible for this 2-arm controlled trial . Staff members approached teens in waiting rooms of 7 large pediatric and family practice departments within a group- practice health maintenance organization . Of 3747 teens invited at ≥1 visits , 2526 ( 67 % ) consented and were r and omized to tobacco intervention or brief dietary advice . The tobacco intervention was individually tailored on the basis of smoking status and stage of change . It included a 30-second clinician advice message , a 10-minute interactive computer program , a 5-minute motivational interview , and up to two 10-minute telephone or in-person booster sessions . The control intervention was a 5-minute motivational intervention to promote increased consumption of fruits and vegetables . Follow-up smoking status was assessed after 1 and 2 years . Results . Abstinence rates after 2 years were significantly higher for the tobacco intervention arm , relative to the control group , in the combined sample of baseline smokers and nonsmokers ( odds ratio [ OR ] : 1.23 ; 95 % confidence interval [ CI ] : 1.03–1.47 ) . Treatment effects were particularly strong among baseline self-described smokers ( OR : 2.42 ; 95 % CI : 1.40–4.16 ) but were not significant for baseline nonsmokers ( OR : 1.25 ; 95 % CI : 0.97–1.61 ) or for those who had “ experimented ” in the past month at baseline ( OR : 0.95 ; 95 % CI : 0.45–1.98 ) . Conclusions . Brief , computer-assisted , tobacco intervention during routine medical care increased the smoking cessation rate among self-described smokers but was less effective in preventing smoking onset 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 Health promotion interventions can not work if people do not engage with them . The aim of this study was to examine whether disengagement from an adolescent smoking prevention and cessation intervention was an independent risk factor for regular smoking 1 and 2 years later . The data were taken from a cluster r and omised controlled trial , in the West Midl and s , UK , based on the transtheoretical or stages of change model . In this trial , 8,352 13 - 14-year old school pupils enrolled , and the data in this report were based on the 7,413 and 6,782 pupils present at 1 and 2 years follow-ups , respectively . The intervention group undertook three sessions using an interactive computer programme . At the end of the programme , pupils recorded their responses to it . Pupils were classed as engaged if they thought the intervention was both useful and interesting ; all others were classed as disengaged . R and om effects logistic regression related the number of times engaged to regular smoking at 1 and 2 years follow-up , adjusted for school absences and 11 potential confounders . The majority of pupils were engaged by the intervention . For participants using the intervention three times but not engaging once , the odds ratios ( 95 % confidence intervals ) for smoking at 1 and 2 years relative to the controls were 1.83 ( 1.41 - 2.39 ) and 1.70 ( 1.38 - 2.11 ) . For those engaging three times , they were 0.79 ( 0.60 - 1.03 ) and 0.96 ( 0.75 - 1.21 ) . There was no interaction with baseline intention to smoke , classified by stage of change , but there was a borderline significant interaction with baseline smoking status , with disengagement acting as a stronger risk factor among baseline never-smokers . We conclude that disengagement from interventions is a risk factor for smoking independently of experimentation with cigarettes . The best explanation is that disengagement from school , an established risk factor for smoking , generalises to disengagement from didactic school-based health promotion programmes BACKGROUND From a public health perspective , prevention of cancer and cardiovascular diseases requires effective smoking cessation programs that can be used on a large scale . OBJECTIVE To test the effectiveness of a new computer-tailored smoking cessation program vs no intervention . METHODS R and omized controlled trial , in the French-speaking part of Switzerl and , September 20 , 1998 , to December 31 , 1999 . Potential participants were r and omly selected from a general population register and recruited by mail . Daily cigarette smokers who wished to participate ( N = 2934 ) were r and omized to either the program or no intervention . A mean of 1.5 times per 6 months , participants in the active arm received by mail a computer-tailored counseling letter based on their answers to a question naire and stage-matched booklets . The counseling letters were tailored to the participants ' stage of change ( categorized as precontemplation [ no intention of quitting smoking in the next 6 months ] , contemplation [ seriously considers quitting in the next 6 months ] , or preparation [ has decided to quit in the next 30 days ] ) , level of tobacco dependence , self-efficacy , and personal characteristics . The outcome measure was self-reported abstinence ( no puff of tobacco smoke in the past 4 weeks ) 7 months after entry into the program . RESULTS Abstinence was 2.6 times greater in the intervention group than in the control group ( 5.8 % vs 2.2 % , P<.001 ) . The program was effective in " precontemplators " who were not motivated to quit smoking at baseline ( intervention vs control , 3.8 % vs 0.8 % ; P = .001 ) and was effective regardless of perceived difficulty in quitting smoking at baseline . CONCLUSIONS The program was effective in increasing smoking cessation rates . Because it can reach a large number of smokers , this program can substantially contribute to disease prevention at a population level Abstract Objectives : To examine whether a year long programme based on the transtheoretical model of behaviour change , incorporating three sessions using an expert system computer program and three class lessons , could reduce the prevalence of teenage smoking . Design : Cluster r and omised trial comparing the intervention to a control group exposed only to health education as part of the English national curriculum . Setting : 52 schools in the West Midl and s region . Participants : 8352 students in year 9 ( age 13 - 14 years ) at those schools . Main outcome measures : Prevalence of teenage smoking 12 months after the start of the intervention . Results : Of the 8352 students recruited , 7444 ( 89.1 % ) were followed up at 12 months . The intention to treat odds ratio for smoking in the intervention group relative to control was 1.08 ( 95 % confidence interval 0.89 to 1.33 ) . Sensitivity analysis for loss to follow up and adjustment for potential confounders did not alter these findings . Conclusions : The smoking prevention and cessation intervention based on the transtheoretical model , as delivered in this trial , is ineffective in schoolchildren aged 13 - 14 . Key messages The transtheoretical model proposes that individuals move through a series of stages in behaviour change A computer programme gave 13 and 14 year old school students tailored information about what stage they were in and what to do to move to the next stage Students given this information were no more likely to move stage , refrain from smoking , or stop smoking than those exposed to ordinary classroom health education There is no evidence that the computerised expert system based on the transtheoretical model is effective in smoking prevention and OBJECTIVE Intervention effectiveness can potentially be affected by membership in different demographic subgroups ( race , ethnicity , gender , age , and education level ) or smoking behavior variables ( time to first cigarette , longest previous quit attempt , number of attempts in the past year , number of cigarettes , and stage of change ) . Previous research on these 2 sets of variables has produced mixed results . DESIGN This secondary data analysis combined data from 5 effectiveness trials ( a r and om-digit-dial sample [ N=1,358 ] , members of an HMO [ N=207 ] , parents of students recruited for a school-based study [ N=347 ] , patients from an insurance provider list [ N=535 ] , and employees [ N=175 ] ) in which smokers were all proactively recruited from a defined population and all received the same expert system intervention . The intervention produced a consistent 22 % to 26 % point prevalence cessation rate across the 5 studies . MAIN OUTCOME MEASURES The main outcome measures were 24-hr point prevalence , 7-day point prevalence , 30-day prolonged abstinence , and 6-month prolonged abstinence . RESULTS There were no significant differences in outcome across gender , race , and ethnicity subgroups . There were significant differences and small effect sizes for age and education subgroups . There were significant differences and large effect sizes for all 5 smoking behavior variables . DISCUSSION Demographic variables are static variables , whereas the smoking variables are more dynamic , that is , open to change . Given the dynamic nature of the smoking variables and the large effect sizes , interventions tailored on the smoking variables should be more successful Three stage-based expert system interventions for smoking , high-fat diet , and unsafe sun exposure were evaluated in a sample of 2,460 parents of teenagers . Eighty-four percent of the eligible parents were enrolled in a 2-arm r and omized control trial , with the treatment group receiving individualized feedback reports for each of their relevant behaviors at 0 , 6 , and 12 months as well as a multiple behavior manual . At 24 months , the expert system outperformed the comparison condition across all 3 risk behaviors , result ing in 22 % of the participants in action or maintenance for smoking ( vs. 16 % for the comparison condition ) , 34 % for diet ( vs. 26 % ) , and 30 % for sun exposure ( vs. 22 % ) . Proactive , home-based , and stage-matched expert systems can produce significant multiple behavior changes in at-risk population s where the majority of participants are not prepared to change To assess and compare the impact on quit attempts of online computer-tailored smoking cessation counseling reports and untailored reports , we performed a r and omized controlled trial on a smoking cessation website in 2007–2008 . After answering a question naire , current and former smokers were r and omly assigned to immediately receiving either an online , individually tailored counseling report or a personalized but untailored generic report . Participants were invited by e-mail to report any smoking in the previous 24 hours , 48 hours after baseline . We used an intention-to-treat analysis , where nonrespondents at follow-up were counted as smokers . There were 2,872 participants at baseline and 2,226 at follow-up ( 78 % ) . At baseline , there were 76 % of current smokers ( mean = 18 cigarettes/day ) and 24 % of recent quitters ( median = 7 days of abstinence ) . The same proportion of smokers in both study groups had made a 24-hour quit attempt at follow-up ( 12.1 % , P = 1.0 ) . In baseline recent quitters , lapse/relapse rates at follow-up were similar in both groups ( tailored : 25.1 % , untailored : 23.5 % , P = 0.64 ) . We conclude that untailored reports were as effective as tailored reports in the short term . Even though these particular computer-tailored reports were not more effective than untailored reports , meta-analyses show that computer-tailored documents are in general more effective than untailored ones This study compared interactive and noninteractive smoking cessation interventions for a population of smokers who were all members of 1 division of a managed care company . In addition , it examined whether a dose-response relationship existed . Screening was completed for 19,236 members who were contacted by telephone or mail . Of the 4,653 who were identified as smokers , 85.3 % were enrolled . A 2 Intervention ( interactive or noninteractive ) x 4 Contacts ( 1 , 2 , 3 , or 6 contacts ) x 4 Occasions ( 0 , 6 , 12 , and 18 months ) design was used . The interactive intervention was stage-matched expert-system reports plus manuals ; the noninteractive intervention was stage-matched manuals . Contact occurred in 1 of 4 series ( 1 , 2 , 3 or 6 contacts ) at 3-month intervals . The expert system outperformed the stage-matched manuals , but there was no clear dose-response relationship for either intervention Traditionally smoking cessation studies use smoker and nonsmoker categories almost exclusively to represent individuals quitting smoking . This study tested the transtheoretical model of change that posits a series of stages through which smokers move as they successfully change the smoking habit . Subjects in precontemplation ( n = 166 ) , contemplation ( n = 794 ) , and preparation ( n = 506 ) stages of change were compared on smoking history , 10 processes of change , pretest self-efficacy , and decisional balance , as well as 1-month and 6-month cessation activity . Results strongly support the stages of change model . All groups were similar on smoking history but differed dramatically on current cessation activity . Stage differences predicted attempts to quit smoking and cessation success at 1- and 6-month follow-up . Implication s for recruitment , intervention , and research are discussed Cigarette smoking by women during pregnancy continues to be a substantial contributor to poor perinatal outcomes in the United States . Decreasing tobacco smoke exposure for women and children is a lifestyle change that will improve perinatal health . A study was conducted with a sample of 74 low-income black women to evaluate the effectiveness of the Smoke Free Families intervention in moving pregnant women forward in the stages of change toward becoming a non-smoker and reducing exposure to second-h and smoke . Transtheoretical model variables were measured at intake , postintervention , and during the last month of pregnancy . There were no statistically significant differences between treatment and control group in movement forward in the stages of change . The findings raise questions about the conceptual fit of the transtheoretical model with pregnant women . We discuss additional interventions and suggest types of studies that would provide new insight into tobacco exposure issues for pregnant women AIM To assess the effectiveness of a new computer-generated tailored advice programme design ed to be used by smokers and recent quitters having problems staying stopped . DESIGN R and omized trial comparing a series of question naire assessment s leading to tailored computer-generated advice letters mailed at strategically relevant times , to a no extra treatment control sent st and ardized printed self-help material s. SETTING Victoria , Australia . PARTICIPANTS A total of 1058 smokers or recent quitters recruited from callers to the Quitline . MEASUREMENTS Smoking status and sustained abstinence at 12-month follow-up , plus extent of participation in the intervention . FINDINGS Using a conservative analysis ( missing data coded as a treatment failure ) , 6-month sustained abstinence was reported by significantly more participants in the computer-generated tailored advice ( 20 % ) than the st and ard printed material s condition ( 12 % ) at 12-month follow-up OR 1.82 ( 1.31 - 2.55 ) ) . Group differences in point prevalence abstinence ( 28 % intervention , 25 % control ) were not significant . Among participants in the tailored advice condition , 6-month sustained abstinence was associated with the number of advice letters received . CONCLUSION The provision of a series of tailored , computer-generated advice letters result ed in greater rates of sustained cessation than for controls . A dose-response relationship was found , with increased compliance with the intervention associated with improved cessation outcomes . The programme appears to have much of its effect by preventing relapse AIMS To evaluate the effect on quitting smoking at 18 months postpartum of smoking cessation interventions based on the Transtheoretical Model ( TTM ) delivered in pregnancy compared to current st and ard care . It has been cl aim ed that TTM-based interventions will continue to create quitters after the end of the intervention period . DESIGN Cluster r and omized trial . SETTING Antenatal clinics in general practice s in the West Midl and s , UK . PARTICIPANTS A total of 918 pregnant smokers originally enrolled in the trial , of which 393 women were followed-up at 18 months postpartum . INTERVENTIONS One hundred general practice s were r and omized into the three trial arms . Midwives in these practice s delivered three interventions : A ( st and ard care ) , B ( TTM-based self-help manuals ) and C ( TTM-based self-help manuals plus sessions with an interactive computer program giving individualized smoking cessation advice ) . MEASUREMENTS Self-reported continuous and point prevalence abstinence since pregnancy . FINDINGS When combined together , there was a slight and not significant benefit for both TTM arms compared to the control , with an odds ratio ( OR ) 95 % confidence interval ( CI ) of 1.20 ( 0.29 - 4.88 ) for continuous abstinence . For point prevalence abstinence , the OR ( 95%CI ) was 1.15 ( 0.66 - 2.03 ) . Seven of the 54 ( 13 % ) women who had quit at the end of pregnancy were still quit 18 months later , and there was no evidence that the TTM-based interventions were superior in preventing relapse . CONCLUSIONS The TTM-based interventions may have shown some evidence of a short-term benefit for quitting in pregnancy but no benefit relative to st and ard care when followed-up in the longer-term In the transtheoretical model ( TTM ) , the stage effect is one of the most important determinants of health behavior change . R and omly assigned to 1 of 11 treatment conditions were 4653 smokers . A total of 66 stage effects were possible with 6 for each of the 11 treatment groups . The results suggest that brief stage-matched interventions that help population s progress one stage could produce 75 % more abstinence . Interventions that help population s progress two stages could produce 300 % more abstinence . The results also support the importance of replicating the stage effects across treatment conditions and over time Brief supportive telephone counseling is a promising adjunct to self-help smoking cessation programs . This article reports rates of participation , predictors of participation , and content of telephone counseling calls with nonvolunteer smokers who were identified through health surveys administered to a r and om sample of enrollees in a health maintenance organization . Eighty-six percent of smokers accepted at least one of three counselor calls ; 66 % accepted all three calls . Baseline characteristics associated with acceptance of calls included being female and greater average length of time to the first cigarette of the day . Acceptance did not differ significantly by stage of cessation . First calls with smokers who accepted all three calls were longer and were more likely to be with smokers who were willing to take a specific next action step . Overall , 12 % of the sample reported having quit smoking by the third counseling call , with the highest quit rate ( 23 % ) among smokers who , at baseline , were planning to quit in the next month . Implication s for large-scale interventions with smokers in health care and other organizations are discussed AIM To test the efficacy of an aid to cessation/relapse prevention intervention for women postpartum . METHOD Two-armed r and omized controlled trial . Follow-ups at 6 , 12 , 18 , and 24 months , screenings on maternity wards . Intervention group received face-to-face counseling 40 days postpartum plus telephone counseling calls 4 and 12 weeks later . Control group received usual care plus self-help material for each parent . RESULTS With regard to smoking cessation , 4 week point prevalence abstinent rates were higher in the treatment group at 6 , 12 , and 18 months ( 7 % vs. 1 % , 7 % vs. 2 % , and 9 % vs. 1 % , respectively ) . Sustained abstinence was higher in the treatment group at 6 months follow-up ( 3 % vs. 0 % ) . No difference was observed with regard to relapse prevention . DISCUSSION Regarding aid to cessation we observed small effects , regarding relapse prevention no effect . In order to capitalize on the opportunity childbirth poses with regard to smoking , theories on relapse prevention in smoking cessation that guide in design ing interventions are needed OBJECTIVES Using a brief contact control , we tested the efficacy of a staged care intervention to reduce cigarette smoking among psychiatric patients in outpatient treatment for depression . METHODS We conducted a r and omized clinical trial that included assessment s at baseline and at months 3 , 6 , 12 , and 18 . Three hundred twenty-two patients in mental health outpatient treatment who were diagnosed with depression and smoked > or = 1 cigarette per day participated . The desire to quit smoking was not a prerequisite for participation . Staged care intervention participants received computerized motivational feedback at baseline and at 3 , 6 , and 12 months and were offered a 6-session psychological counseling and pharmacological cessation treatment program . Brief contact control participants received a self-help guide and referral list of local smoking-treatment providers . RESULTS As we hypothesized , abstinence rates among staged care intervention participants exceeded those of brief contact control participants at months 12 and 18 . Significant differences favoring staged care intervention also were found in occurrence of a quit attempt and stringency of abstinence goal . CONCLUSION The data suggest that individuals in psychiatric treatment for depression can be aided in quitting smoking through use of staged care interventions and that smoking cessation interventions used in the general population can be implemented in psychiatric outpatient setting BACKGROUND Until recently , Dutch general practitioners contributed little to tobacco control . This is due to several factors , among which is the lack of a feasible intervention program for adult smokers . Such a minimal contact behavioral intervention , using the Stage-of-Change concept , is now available . Effectiveness was tested in a r and omized trial . METHOD Twenty-two general practitioners and their practice assistants were trained in applying the program . In all , 530 smoking patients were enrolled , r and omly assigned to either the intervention or the usual treatment condition . Analysis of treatment effects was performed with logistic regression analysis . In a backward stepwise procedure confounding effects of baseline differences were eliminated . RESULTS At 12-month follow-up , self-reported abstinence rates ( including nonrespondents as smokers ) differed significantly between intervention subjects and controls : 13.4 vs 7.3 % point prevalence ( odds ratio 1.51 , P < 0.05 ) . An analysis of consecutive abstinence , defined as being abstinent at both 6- and 12-month follow-up , showed that 8.2 % of the intervention group compared to 3.1 % of the controls had sustained abstinence for more than 6 months ( odds ratio 3.04 , P < 0.001 ) . CONCLUSIONS Results indicate that an effective smoking cessation program for use in Dutch general practice , already shown to be feasible , is now available . Outcomes are generally consistent with recent international literature Interrelationships among key constructs of the Transtheoretical Model are examined for the first time on a large ( N = 4,144 ) representative sample of smokers . The posited relationships between the early Stages of Change ( Precontemplation , Contemplation , Preparation ) and the Processes of Change , Decisional Balance , and Situational Temptation are generally supported . Precontemplators are found to use the Processes of Change the least and those in Preparation use them the most . Precontemplators also have the least negative attitudes toward their smoking behavior . Precontemplators and Contemplators are tempted to smoke in more situations than those in Preparation . Precontemplators are also the most addicted to smoking , followed by those in Contemplation and Preparation , respectively , when examined on traditional measures of smoking behavior . The implication s for smoking cessation efforts are also discussed BACKGROUND Social cognitive theories ( e.g. , ASE-model ) propose that smoking cessation can be accomplished by changing underlying cognitive determinants such as attitudes , social influence , and self-efficacy . Others have argued that people 's preferences for a health state can also predict behavior . In this study , preferences constitute the degree to which one is willing to give up a valuable good , that is survival , to obtain a desirable behavior ( e.g. , to quit smoking ) . The aim of this study is to investigate the impact of cognitive determinants and patients ' preferences on the prediction of smoking cessation . METHODS Data were collected as part of a r and omized clinical trial . Smoking out patients ( N = 217 ) with cardiovascular disease were included . At baseline ( T0 ) , socio-demographic and clinical characteristics were measured . Social cognitions ( pros of quitting , pros of smoking , social influence , and self-efficacy ) and preferences ( using a paper time trade-off measure ( TTO ) ) were assessed at T1 ( 1 week ) . Smoking cessation was assessed at T2 ( 8 weeks ) . RESULTS Logistic regression analysis showed that socio-demographic ( P = .92 ) and clinical ( P = .26 ) factors did not predict smoking cessation , whereas social cognitions ( P = .02 ) and preferences did ( P = .00 ) . On average , quitters are willing to give up an appreciable amount of survival years in order to quit smoking . CONCLUSION Preference for quitting was the strongest single predictor of smoking cessation This study evaluated the effects of written feedback adapted to a self-help mail intervention . The efficacy of the st and ard mail intervention treatment was 37 % at the end of treatment , 22 % at the 3-month follow-up , 19 % at the 6-month follow-up , and 13 % at the 12-month follow-up . In contrast , the st and ard mail program combined with personalized written feedback result ed in an efficacy of 51 % at the end of treatment , 37 % at the 3-month follow-up , 32 % at the 6-month follow-up , and 27 % at the 12-month follow-up . Both groups were significantly different from the control group at the end of treatment ( 0 % ) , at the 3-month follow-up ( 1 % ) , and at the 6-month follow-up ( 1 % ) . There was a significant reduction in the number of cigarettes smoked daily among continuing smokers under both experimental conditions . The authors conclude that written feedback substantially increases abstinence rates when it is applied following similar guidelines to those used in clinical setting OBJECTIVES To examine whether , as predicted by the transtheoretical model ( TTM ) , stage-matched interventions will be more effective than stage-mismatched interventions . DESIGN R and omized controlled trial of smoking cessation advice to pregnant smokers . METHODS Pregnant women currently smoking at 12 weeks gestation were enrolled in a pragmatic three-arm trial of TTM-based interventions to help them stop smoking . One arm constituted st and ard midwifery advice and a self-help leaflet on stopping smoking , which is generally appropriate for women in preparation . Two arms were TTM-based . Differences in positive movement in stage towards quitting from enrolment to 30 weeks gestation and 10 days post-partum were calculated for each arm of the trial . We then examined whether , as predicted from the TTM , the relative benefit of the TTM-based intervention was greater for women in precontemplation and contemplation , for whom the control intervention was stage-mismatched , than for women in preparation , for whom the control intervention was stage-matched . RESULTS Women in the TTM-based arms were statistically significantly more likely to move forward in stage than were women in the control arm . Contrary to the TTM-derived hypothesis , the greater relative benefit of the TTM-based intervention was seen for women in preparation stage at baseline , rather than women in precontemplation and contemplation . CONCLUSIONS The TTM-based intervention was more effective in stage movement , but this could be due to its greater intensity . The failure to confirm that stage-matching was important casts doubt on the validity of the TTM in explaining smoking cessation behaviour in pregnancy Smoking markedly increases the risk of asbestos-related lung cancer . We conducted a r and omized pilot trial of a telephone-based smoking cessation intervention in asbestos workers . Fifty-nine smokers were assigned to either a control or telephone-based smoking cessation treatment group and were followed-up at 6 months . Intent-to-treat analysis revealed a 16.7 % quit rate at 6 months for the intervention group compared to 6.9 % for the control group ( P = 0.25 ) . Treatment-received quit-rates were 33 % for the intervention group and 6.9 % for the control group ( P = 0.05 ) . The intervention group was twice as likely to use smoking cessation medicines and progressed further along the stage of change continuum compared with the control group . Incorporating telephone-based smoking cessation treatment into medical screening activities for asbestos workers is feasible and the intervention is effective in increasing quit rates at 6 months 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 Aims : Potential exists for improving the impact of quit-smoking programmes , by recruiting smokers in early motivational stages , by using active recruitment strategies , and by offering professional assistance to quit . Methods : This was a r and omized population -based intervention study , in Copenhagen , Denmark . A total of 2,408 daily smokers in all motivational stages were included . All participants completed a question naire , and underwent a health examination and a lifestyle consultation . Smokers in the high-intensity intervention were offered assistance to quit smoking in smoking cessation groups . Results : Before the lifestyle consultation only 11 % of the smokers stated that they planned to quit within one month . After the lifestyle consultation 27 % accepted smoking cessation in groups and an additional 12 % planned to quit without assistance . Of the smokers who accepted smoking cessation groups 23 % had not been planning to quit before the lifestyle consultation . Being a woman , having high tobacco consumption , having a long smoking history , having tried to quit within the previous year , and having a higher motivation to quit predicted participation in smoking cessation groups . Conclusions : It was possible to recruit a large number of smokers in early motivational stages by using active recruitment strategies and by offering assistance to quit . Lifestyle consultations markedly increased the number of smokers willing to try to quit . Smokers preferred assistance to quit in a smoking cessation group to quitting on their own ; therefore , it is important to improve recruitment strategies for smoking cessation programmes OBJECTIVE Despite extremely high rates of smoking among individuals with psychotic disorders and the associated financial and health costs , few studies have investigated the efficacy of smoking cessation interventions among this group . The purpose of this study was to compare an integrated psychological and nicotine replacement therapy intervention for people with a psychotic disorder with routine care alone . METHOD The authors recruited 298 regular smokers with a psychotic disorder residing in the community and r and omly assigned them to a routine care comparison condition ( N=151 ) or an eight-session , individually administered smoking cessation intervention ( N=147 ) , which consisted of nicotine replacement therapy , motivational interviewing , and cognitive behavior therapy . Outcome variables included continuous and point-prevalence abstinence rates , smoking reduction status , and changes in symptoms and functioning . RESULTS While there were no overall differences between the treatment group and comparison group in abstinence rates , a significantly higher proportion of smokers who completed all treatment sessions stopped smoking at each of the follow-up occasions ( point-prevalence rates : 3 months , 30.0 % versus 6.0 % ; 6 months , 18.6 % versus 4.0 % ; and 12 months , 18.6 % versus 6.6 % ) . Smokers who completed all treatment sessions were also more likely to have achieved continuous abstinence at 3 months ( 21.4 % versus 4.0 % ) . There was a strong dose-response relationship between treatment session attendance and smoking reduction status , with one-half of those who completed the intervention program achieving a 50 % or greater reduction in daily cigarette consumption across the follow-ups , relative to less than one-fifth of the comparison subjects . There was no evidence of any associated deterioration in symptoms or functioning . CONCLUSIONS These findings demonstrate the utility of a nicotine replacement therapy plus motivational interviewing/cognitive behavior therapy smoking cessation intervention among individuals with a psychotic disorder . Further development of more efficacious interventions is required for those who do not respond to existing interventions INTRODUCTION The objective of this study was to test the feasibility and acceptance of an intervention using text messaging ( short message service [ SMS ] ) for continuous individual support of smoking cessation in young adults . Additionally , the optimal feedback intensity was investigated , and short-term efficacy of the intervention was explored . METHODS In a cafeteria of the University of Greifswald , 575 visitors were screened for smoking status and usage of text messaging . From these , 194 persons who fulfilled the inclusion criteria of daily smoking and weekly usage of SMS were invited for participation in an SMS-based intervention . From these , 174 ( 90 % ) consented to participate . The participants were r and omly allocated to one of three study groups : ( a ) control condition without intervention , ( b ) intervention with one weekly SMS feedback ( 1SMS ) , or ( c ) intervention with three weekly SMS feedbacks ( 3SMS ) . In study groups ( b ) and ( c ) , individualized SMS feedbacks were sent to the participants weekly , based on data from the baseline assessment and a weekly SMS assessment of the stages of change according to the transtheoretical model . Program use and acceptance were compared between the two intervention groups differing in support intensity . An exploration of the short-term efficacy of the program was conducted by comparing the three study groups at the end of the 3-month intervention program on smoking variables . RESULTS The median number of replies to the weekly SMS assessment s was 12.5 in the 1SMS group and 13.0 in the 3SMS group ( not significant ) . The acceptance of the program did not differ between the intervention groups . At post assessment , no significant differences between the three study groups emerged on the examined smoking variables . DISCUSSION The high participation and retention rates suggest that SMS-based smoking cessation interventions are attractive for young adults . Support intensity did not affect the acceptance of the program . Longer follow-up periods and larger sample s are required to obtain conclusive results about the efficacy of this intervention approach OBJECTIVE This study compared diabetes Treatment As Usual ( TAU ) with Pathways To Change ( PTC ) , an intervention developed from the Transtheoretical Model of Change ( TTM ) , to determine whether the PTC intervention would result in greater readiness to change , greater increases in self-care , and improved diabetes control . RESEARCH DESIGN AND METHODS Participants were stratified by diabetes treatment and r and omized to treatment with PTC or TAU as well as being r and omized regarding receipt of free blood testing strips . The PTC consisted of stage-matched personalized assessment reports , self-help manuals , newsletters , and individual phone counseling design ed to improve readiness for self-monitoring of blood glucose ( SMBG ) , healthy eating , and /or smoking cessation . A total of 1029 individuals with type 1 and type 2 diabetes who were in one of three pre-action stages for either SMBG , healthy eating , or smoking were recruited . RESULTS For the SMBG intervention , 43.4 % of those receiving PTC plus strips moved to an action stage , as well as 30.5 % of those receiving PTC alone , 27.0 % of those receiving TAU plus strips , and 18.4 % of those receiving TAU alone ( P < 0.001 ) . For the healthy eating intervention , more participants who received PTC than TAU ( 32.5 vs. 25.8 % ) moved to action or maintenance ( P < 0.001 ) . For the smoking intervention , more participants receiving PTC ( 24.3 % ) than TAU ( 13.4 % ) moved to an action stage ( P < 0.03 ) . In intention-to-treat ( ITT ) analysis of those receiving the SMBG intervention , PTC result ed in a greater reduction of HbA(1c ) than TAU , but this did not reach statistical significance . However , in those who moved to an action stage for the SMBG and healthy eating interventions , HbA(1c ) was significantly reduced ( P < 0 0.001 ) . Individuals who received the healthy eating intervention decreased their percentage of calories from fat to a greater extent ( 35.2 vs. 36.1 % , P = 0.004 ) , increased servings of fruit per day ( 1.89 vs. 1.68 , P = 0.016 ) , and increased vegetable servings ( 2.24 vs. 2.06 , P = 0.011 ) but did not decrease weight . However , weight loss for individuals who received the healthy eating intervention and who increased SMBG frequency as recommended was significantly greater , with a 0.26-kg loss in those who remained in a pre-action SMBG stage but a 1.78-kg loss in those performed SMBG as recommended ( P < or= 0 . 01 ) . CONCLUSIONS This study demonstrates that this intervention has the potential of positively impacting the health of broad population s of individuals with diabetes , not just the minority who are ready for change BACKGROUND Although effects of maternal smoking during pregnancy could be alleviated if women quit early in pregnancy , most do not . Relapse rates among quitters are high . OBJECTIVE To test the effects of a low-intensity , smoking-cessation/relapse-prevention intervention delivered by clinic staff and providers and based on stages-of-change constructs of the transtheoretical model and brief motivational interviewing techniques . METHODS A quasi-experimental prospect i ve cohort design employed in obstetric , in-patient , and pediatric care delivery setting s of a large health maintenance organization in Portl and , Oregon . Subjects were pregnant smokers registered for their first prenatal visit . Primary outcome measures were sustained ( self-reported ) quit rates during pregnancy and smoking abstinence between 6 and 12 months after delivery . RESULTS Regression analyses found statistically significant improvement for intervention women in sustained pregnancy quit rates ( OR=2.7 , CI=1 . 2 - 5.7 ) and on smoking abstinence between 6 and 12 months after delivery ( OR=2.4 , CI=1.1 - 5.3 ) . CONCLUSIONS While these outcomes are based on self-report only , they emerged despite variable delivery of the intervention across clinics and represent clinical ly meaningful improvements in rates of nonsmoking . The intervention supports women who want to quit smoking during pregnancy and improves the likelihood of their remaining nonsmokers for the long term BACKGROUND In a population -based sample of smokers in early motivational stages , we found a high acceptance of smoking cessation groups . METHODS Inter99 is a r and omized population -based intervention study , in Copenhagen , Denmark . Smokers in all motivational stages were included . All participants underwent a lifestyle consultation and 2,168 smokers in the high intensity intervention group were offered assistance to quit in smoking cessation groups . RESULTS Thirty-five percent were vali date d to be continuously abstinent at the end of the smoking cessation groups . Eighty-four percent of the smokers achieving sustained abstinence in our study had no serious plans to quit soon before the lifestyle consultation . Motivation to quit before the lifestyle consultation could not predict abstinence . Being a man , and having a job and at least 1 year of vocational training were predictors of abstinence in a multivariate model , whereas high nicotine dependence and living with a smoking spouse were predictors of failure . CONCLUSION High cessation rates were obtained in a population of heavy smokers with moderate nicotine dependence . It was possible to obtain sustained abstinence in smokers in early motivational stages . These smokers would probably not have been reached by traditional smoking campaigns OBJECTIVE This study reports the outcome of a smoking intervention study in a general population setting in Germany . DESIGN A r and omized , controlled trial , with a sample of 719 current daily cigarette smokers . MAIN OUTCOME MEASURE The authors tested a criterion measurement model that is related to the transtheoretical model and that proposes multivariate outcome measures with positive and negative attitudes about smoking and habit strength . The authors analyzed patterns and predictors of change in self-efficacy and in the pros and cons of nonsmoking using latent growth models . RESULTS AND CONCLUSION Participation in the intervention groups did not predict average mean levels or growth trajectories in the multivariate outcome model . Accounting for attrition in multi sample missing- data procedures and accounting for demographic and smoking behavior variables did not alter this result . Thus , the intervention was ineffective . However , endorsement of self-efficacy and the pros of nonsmoking increased linearly over time in all study groups , which may be attributable to historical or societal changes or to repeated , comprehensive smoking assessment s. In addition to reporting the outcome of a smoking intervention trial , the current study also illustrates a modeling approach to the measurement of change Telephone counseling is a popular modality for smoking cessation treatment ; however , little attention has been paid to evaluating the efficacy of different contents of calls . This study compared 2 types of proactive telephone calls following a group program . Participants were r and omized to receive either : ( a ) basic content , consisting primarily of support ; or ( b ) enhanced content , tailored to the stage of cessation ( still smoking , abstinent , or relapsed ) and targeting factors hypothesized to be related to success ( motivation , self-efficacy , and negative mood ) . There was a significant interaction between treatment condition and gender . For men , the enhanced condition produced better abstinence rates through 15 months and lower relapse rates . For women , the basic condition was better . History of depression did not interact with condition OBJECTIVE This study was undertaken to evaluate a smoking cessation intervention provided to women smokers as follow-up to cervical cancer screening . METHODS Women who had had a Pap test in the prior month ( N = 4,053 ) were called to complete a survey that assessed smoking status ; 580 identified smokers were r and omized to receive Usual care ( n = 292 ) or a Self-help intervention ( n = 288 ) that included a self-help booklet , a smoking and reproductive health information card , and three telephone counseling calls . Women were followed up at 6 and 15 months post-base line . RESULTS Cessation rates in the Usual care ( UC ) and Self-help ( SH ) groups did not differ at the 6-month ( UC 10.5 % vs SH 10.9 % , P = 0.56 ) or 15-month follow-up ( UC 15.5 % vs SH 10.6 % , P = 0.17 ) . Among women with an abnormal Pap test result there were no differences by study group in cessation rates at 6-month ( UC 9.8 % vs SH 11.0 % , P = 0.71 ) or 15-month follow-up ( UC 14.6 % vs SH 13.4 % , P = 0.96 ) . CONCLUSION Integrating interventions into the clinical setting and involving providers at the point of care may have greater potential for capitalizing on this " teachable moment . INTRODUCTION The effectiveness of low-cost smoking interventions targeted to pregnant women has been demonstrated , although few gains in absolute cessation rates have been reported in the past decade . Under conditions of typical clinical practice , this study examined whether outcomes achieved with brief counseling from prenatal care providers and a self-help booklet could be improved by adding more re source -intensive cognitive-behavioral programs . DESIGN R and omized Clinical Trial . SETTING A large-group-model managed care organization . PARTICIPANTS 390 English-speaking women 18 years of age or older who self-reported to be active smokers at their initial prenatal appointment . INTERVENTION Participants were r and omized to one of three groups : ( 1 ) a self-help booklet tailored to smoking patterns , stage of change , and lifestyle of pregnant smokers ; ( 2 ) the booklet plus access to a computerized telephone cessation program based on interactive voice response technology ; or ( 3 ) the booklet plus proactive telephone counseling from nurse educators using motivational interviewing techniques and strategies . No attempt was made to change smoking-related usual care advice from prenatal providers . MAIN OUTCOME MEASURE Biochemically confirmed abstinence measured by level of cotinine in urine sample s obtained during a routine prenatal visit at approximately the 34th week of pregnancy . RESULTS Twenty percent of participants were confirmed as abstinent with no significant differences found between intervention groups . Multivariate baseline predictors of cessation included number of cigarettes smoked per day , confidence in ability to quit , exposure to passive smoke , and educational level . No differential intervention effects were found within strata of these predictors or by baseline stage of readiness to change . Cessation rates among heavier smokers were strikingly low in all intervention groups . CONCLUSION Neither a computerized telephone cessation program nor systematic provision of motivational counseling improved cessation rates over a tailored self-help booklet delivered within the context of brief advice from prenatal providers . Innovative strategies need to be developed to increase the effectiveness of existing prenatal smoking interventions . Special attention should be paid to the needs of heavier smokers Sixty-five college-student smokers were r and omly assigned to a four-week computer-administered , stage-based smoking control program or a four-week computer-administered general health education control condition . At post-test , the percentage of students advancing to a higher stage of readiness to change was slightly higher among those in the stage-based program compared to the control condition . At seven month follow-up , both groups reported abstinence rates of approximately 30 % . Continuous abstinence for 6 months was 19 % for the stage-based group and 14 % for the control group at the final follow-up The aim of the study was to test the effectiveness of a postpartum smoking cessation and relapse prevention intervention . Structural equation modeling techniques were applied to evaluate the impact of the intervention on smoking behavior and on non-behavioral variables derived from the Transtheoretical Model ( TTM ) . Women were r and omized to an intervention ( I ) and control group ( C ) . Smoking status , TTM-variables , and control variables were assessed four weeks , six and 12 months postpartum . Membership in the intervention group significantly predicted non-smoking and higher self-efficacy six months , but not one year postpartum , after controlling for demographic , smoking , and postpartum risk variables |
2,683 | 26,495,910 | The review authors found no high- quality evidence suggesting that RF denervation provides pain relief for patients with CLBP .
Similarly , we identified no convincing evidence to show that this treatment improves function . | BACKGROUND Radiofrequency ( RF ) denervation , an invasive treatment for chronic low back pain ( CLBP ) , is used most often for pain suspected to arise from facet joints , sacroiliac ( SI ) joints or discs .
Many ( uncontrolled ) studies have shown substantial variation in its use between countries and continued uncertainty regarding its effectiveness .
OBJECTIVES The objective of this review is to assess the effectiveness of RF denervation procedures for the treatment of patients with CLBP .
The current review is an up date of the review conducted in 2003 .
RF denervation is an invasive procedure that can cause a variety of complications . | Background No proof of efficacy , in the form of a r and omized controlled trial ( RCT ) , exists to support pulsed radiofrequency ( PRF ) treatment of the dorsal root ganglion ( DRG ) for chronic lumbar radicular ( CLR ) pain . We determined the feasibility of a larger trial ( primary objective ) , and also explored the efficacy of PRF in decreasing pain on a visual analog scale ( VAS ) and improving the Oswestry Disability Index . Methods This was a single-center , placebo-controlled , triple-blinded RCT . Patients were r and omized to a placebo group ( needle placement ) or a treatment group ( PRF at 42 ° C for 120 seconds to the DRG ) . Patients were followed up for 3 months post procedure . Outcomes with regard to pain , Oswestry Disability Index score , and side effects were analyzed on an intention-to-treat basis . Results Over 15 months , 350 potential patients were identified and 56 were assessed for eligibility . Fifteen of them did not meet the selection criteria . Of the 41 eligible patients , 32 ( 78 % ) were recruited . One patient opted out before intervention . Three patients were lost to follow-up at 3 months . Mean VAS differences were not significantly different at 4 weeks ( −0.36 , 95 % confidence interval [ CI ] , −2.29 , 1.57 ) or at 3 months ( −0.76 , 95 % CI , −3.14 , 1.61 ) . The difference in mean Oswestry Disability Index score was also not significantly different at 4 weeks ( −2 % , 95 % CI , −14 % , 10 % ) or 3 months ( −7 % , 95 % CI , −21 % , 6 % ) . There were no major side effects . Six of 16 patients in the PRF group and three of 15 in the placebo group showed a > 50 % decrease in VAS score . Conclusion The recruitment rate was partially successful . At 3 months , the relative success of PRF-DRG was small . A large-scale trial to establish efficacy is not practically feasible considering the small effect size , which would necessitate recruitment of a challengingly large number of participants over a number of years . Until clear parameters for application of PRF are established , clinicians will need to use their individual judgment regarding its clinical applicability , given the present evidence Study Design . A prospect i ve double-blind r and omized trial in 28 patients . Objectives . To assess the clinical effect of percutaneous intradiscal radiofrequency thermocoagulation for reducing pain , functional disability , and physical impairment in patients with chronic discogenic low back pain . Summary of Background Data . Chronic discogenic low back pain is a challenging problem in western countries . A treatment option is radiofrequency heating of the affected disc . Its clinical efficacy has never been formally tested in a controlled trial . Methods . Twenty-eight patients with a history of at least 1 year of chronic low back pain were selected on the basis of a diagnostic anesthetization of the lower intervertebral discs . Only patients with one putative painful level were selected and r and omly assigned to one of two treatment groups . Each patient in the radiofrequency treatment group ( n = 13 ) received a 90-second 70 C lesion of the intervertebral disc . Patients in the control group ( n = 15 ) underwent the same procedure , but without use of radiofrequency current . Both the treating physician and the patients were blinded to the group assignment . Before treatment , physical impairment , rating of pain , the degree of disability , and quality of life were assessed by a blinded investigator . Results . Eight weeks after treatment , there was one success in the radiofrequency group ( n = 13 ) and two in the control group ( n = 15 ) . The adjusted and unadjusted odds ratio was 0.5 and 1.1 , respectively ( not significant ) . Also , visual analog scores for pain , global perceived effect , and the Oswestry disability scale showed no differences between the two groups . Conclusions . Percutaneous intradiscal radiofrequency thermocoagulation ( 90 seconds , 70 C ) is not effective in reducing chronic discogenic low back pain Background and aims Facet joint denervation is a frequently performed technique to treat facet joint syndrome . Most often this technique is used under fluoroscopic guidance implicating high radiation doses for both patients and surgeons . This prospect i ve study was performed to evaluate the effectiveness in reducing radiation dose during radiofrequency ablation therapy of the lumbar facet joints and to evaluate the feasibility and possibilities of the new real time image guidance system Sabre Source ™ . Material s and methods As much as 20 consecutive patients with radiofrequency ablation therapy of the facet joints L4 to S1 were included . Ten patients were treated by fluoroscopic control alone ; the following 10 patients were treated with the Sabre Source ™ image guidance system . A total of 40 thermal ablations to the facet joints were performed . Each patient was given one thermal ablation on both sides of the vertebral segment , either to the facet joints of L4–L5 or of L5–S1 . Pain , according to the visual analogue scale ( VAS ) , was documented before and 6 h after the intervention . Radiation dose , time of radiation and the number of shots needed to place the radiofrequency cannula were recorded . Results No complications occurred . Before therapy , the mean VAS in all patients was 7.6 ( range 6–10 ) . After therapy the mean VAS in all patients was 3.4 ( range 0–5 ) . Compared to the fluoroscopy-guided thermal ablation therapy the Sabre Source ™ system significantly reduced the number of fluoroscopy exposures ( reduction 23.53 % , p = 0.02 ) , the time of radiation exposure ( reduction 21.2 % , p = 0.03 ) and the mean entrance surface dose ( reduction 30.46 % , p = 0.01 ) . Conclusion The Sabre Source System reduces radiation exposure and radiation dose in the radiofrequency denervation therapy of the lumbar facet joints and can be applied for other minimally invasive techniques Research suggests that clinical examination of the lumbar spine and pelvis is unable to predict the results of diagnostic injections used as reference st and ards . The purpose of this study was to assess the diagnostic accuracy of a clinical examination in identifying symptomatic and asymptomatic sacroiliac joints using double diagnostic injections as the reference st and ard . In a blinded concurrent criterion-related validity design study , 48 patients with chronic lumbopelvic pain referred for diagnostic spinal injection procedures were examined using a specific clinical examination and received diagnostic intraarticular sacroiliac joint injections . The central isation and peripheralisation phenomena were used to identify possible discogenic pain and the results from provocation sacroiliac joint tests were used as part of the clinical reasoning process . Eleven patients had sacroiliac joint pain confirmed by double diagnostic injection . Ten of the 11 sacroiliac joint patients met clinical examination criteria for having sacroiliac joint pain . In the primary subset analysis of 34 patients , sensitivity , specificity and positive likelihood ratio ( 95 % confidence intervals ) of the clinical evaluation were 91 % ( 62 to 98 ) , 83 % ( 68 to 96 ) and 6.97(2.70 to 20.27 ) respectively . The diagnostic accuracy of the clinical examination and clinical reasoning process was superior to the sacroiliac joint pain provocation tests alone . A specific clinical examination and reasoning process can differentiate between symptomatic and asymptomatic sacroiliac Background : Sacroiliac joint pain is a challenging condition accounting for approximately 20 % of cases of chronic low back pain . Currently , there are no effective long-term treatment options for sacroiliac joint pain . Methods : A r and omized placebo-controlled study was conducted in 28 patients with injection-diagnosed sacroiliac joint pain . Fourteen patients received L4–L5 primary dorsal rami and S1–S3 lateral branch radiofrequency denervation using cooling-probe technology after a local anesthetic block , and 14 patients received the local anesthetic block followed by placebo denervation . Patients who did not respond to placebo injections crossed over and were treated with radiofrequency denervation using conventional technology . Results : One , 3 , and 6 months after the procedure , 11 ( 79 % ) , 9 ( 64 % ) , and 8 ( 57 % ) radiofrequency-treated patients experienced pain relief of 50 % or greater and significant functional improvement . In contrast , only 2 patients ( 14 % ) in the placebo group experienced significant improvement at their 1-month follow-up , and none experienced benefit 3 months after the procedure . In the crossover group ( n = 11 ) , 7 ( 64 % ) , 6 ( 55 % ) , and 4 ( 36 % ) experienced improvement 1 , 3 , and 6 months after the procedure . One year after treatment , only 2 patients ( 14 % ) in the treatment group continued to demonstrate persistent pain relief . Conclusions : These results provide preliminary evidence that L4 and L5 primary dorsal rami and S1–S3 lateral branch radiofrequency denervation may provide intermediate-term pain relief and functional benefit in selected patients with suspected sacroiliac joint pain . Larger studies are needed to confirm these results and to determine the optimal c and i date s and treatment parameters for this poorly understood disorder In this study two strategies in the treatment of Mechanical Spinal Discogenic Pain have been compared : Disc Coablation and Epidural Injection of Steroids . In 2003 50 patients treated with one or two epidural injections have been selected " ad r and om " and 50 patients treated with disc coablation . Comparison of the data indicated an improvement of average VAS when relaxed for both groups ( p < 0.01 ) , while after slight-moderate strain , this value was significant only after coablation ( p < 0.001 ) . Finally , average VAS was clearly lower ( p < 0.01 ) after coablation as compared to epidural injections STUDY DESIGN A prospect i ve audit . OBJECTIVE To establish the efficacy of lumbar medial branch neurotomy under optimum conditions . SUMMARY OF BACKGROUND DATA Previous reports of the efficacy of lumbar medial branch neurotomy have been confounded by poor patient selection , inaccurate surgical technique , and inadequate assessment of outcome . METHODS Fifteen patients with chronic low back pain whose pain was relieved by controlled , diagnostic medial branch blocks of the lumbar zygapophysial joints , underwent lumbar medial branch neurotomy . Before surgery , all were evaluated by visual analog scale and a variety of vali date d measures of pain , disability , and treatment satisfaction . Electromyography of the multifidus muscle was performed before and after surgery to ensure accuracy of the neurotomy . All outcome measures were repeated at 6 weeks , and 3 , 6 , and 12 months after surgery . RESULTS Some 60 % of the patients obtained at least 90 % relief of pain at 12 months , and 87 % obtained at least 60 % relief . Relief was associated with denervation of the multifidus in those segments in which the medial branches had been coagulated . Prelesion electrical stimulation of the medial branch nerve with measurement of impedance was not associated with outcome . CONCLUSIONS Lumbar medial branch neurotomy is an effective means of reducing pain in patients carefully selected on the basis of controlled diagnostic blocks . Adequate coagulation of the target nerves can be achieved by carefully placing the electrode in correct position as judged radiologically . Electrical stimulation before lesioning is superfluous in assuring correct placement of the electrode Objective To evaluate the effectiveness of an integrated care programme , combining a patient directed and a workplace directed intervention , for patients with chronic low back pain . Design Population based r and omised controlled trial . Setting Primary care ( 10 physiotherapy practice s , one occupational health service , one occupational therapy practice ) and secondary care ( five hospitals ) . Participants 134 adults aged 18 - 65 sick listed for at least 12 weeks owing to low back pain . Intervention Patients were r and omly assigned to usual care ( n=68 ) or integrated care ( n=66 ) . Integrated care consisted of a workplace intervention based on participatory ergonomics , involving a supervisor , and a grade d activity programme based on cognitive behavioural principles . Main outcome measures The primary outcome was the duration of time off work ( work disability ) due to low back pain until full sustainable return to work . Secondary outcome measures were intensity of pain and functional status . Results The median duration until sustainable return to work was 88 days in the integrated care group compared with 208 days in the usual care group ( P=0.003 ) . Integrated care was effective on return to work ( hazard ratio 1.9 , 95 % confidence interval 1.2 to 2.8 , P=0.004 ) . After 12 months , patients in the integrated care group improved significantly more on functional status compared with patients in the usual care group ( P=0.01 ) . Improvement of pain between the groups did not differ significantly . Conclusion The integrated care programme substantially reduced disability due to chronic low back pain in private and working life . Trial registration Current Controlled Trials IS RCT N28478651 OBJECTIVES We aim ed to prospect ively evaluate the response and safety of pulsed and continuous radiofrequecy lesioning of the dorsal root ganglion/segmental nerves in patients with chronic lumbosacral radicular pain . METHODS Seventy-six patients with chronic lumbosacral radicular pain refractory to conventional therapy met the inclusion criteria and were r and omly assigned to one of 2 types of treatment , pulsed radiofrequency lesioning of the dorsal root ganglion/segmental nerve or pulsed radiofrequency followed immediately by continuous radiofrequency . Patients were carefully evaluated for neurologic deficits and side effects . The response was evaluated at 2 months and was then tracked monthly . A Kaplan-Meier analysis was used to illustrate the probability of success over time and a Box-Whisker analysis was applied to determine the mean duration of a successful analgesic effect . RESULTS Two months after undergoing radiofrequency treatment , 70 % of the patients treated with pulsed radiofrequency and 82 % treated with pulsed and continuous radiofrequency had a successful reduction in pain intensity . The average duration of successful analgesic response was 3.18 months ( + /- 2.81 ) in the group treated with pulsed radiofrequency and 4.39 months ( + /-3.50 ) in those patients treated with pulsed and continuous radiofrequency lesioning . A Kaplan-Meier analysis illustrated that in both treatment groups the chance of success approached 50 % in each group at 3 months . The vast majority of patients had lost any beneficial effects by 8 months . There was no statistical difference between the 2 treatment groups . No side effects or neurological deficits were found in either group . CONCLUSION Pulsed mode radiofrequency of the dorsal root ganglion of segmental nerves appears to be a safe treatment for chronic lumbosacral radicular pain . A significant number of patients can derive at least a short-term benefit . The addition of heat via continuous radiofrequency does not offer a significant advantage . A r and omized controlled trial is now required to determine the effectiveness of pulsed radiofrequency STUDY DESIGN A prospect i ve double-blind r and omized trial in 31 patients . OBJECTIVES To assess the clinical efficacy of percutaneous radiofrequency denervation of the lumbar zygapophysial joints in reducing pain , functional disability , and physical impairment in patients with back pain originating from the lumbar zygapophysial joints . SUMMARY OF BACKGROUND DATA Chronic low back pain is a major health problem in the industrialized world . A treatment option is percutaneous radiofrequency denervation of the lumbar zygapophysial joints . Its clinical efficacy has never been formally tested in a controlled trial . METHODS Thirty-one patients with a history of at least 1 year of chronic low back pain were selected on the basis of a positive response to a diagnostic nerve blockade and subsequently r and omly assigned to one of two treatment groups . Each patient in the radiofrequency treatment group ( 15 patients ) received an 80 C radiofrequency lesion of the dorsal ramus of the segmental nerve roots L3 , L4 , and L5 . Patients in the control group ( n = 16 ) underwent an the same procedure but without use of a radiofrequency current . Both the treating physician and the patients were blinded to the group assignment . Before treatment , physical impairment , rating of pain , the degree of disability , and quality of life were assessed by a blinded investigator . RESULTS Eight weeks after treatment , there were 10 success patients in the radiofrequency group ( n = 15 ) and 6 in the sham group ( n = 16 ) . The unadjusted odds ratio was 3.3 ( P = 0.05 , not significant ) , and the adjusted odds ratio was 4.8 ( P < 0.05 , significant ) . The differences in effect on the visual analog scale scores , global perceived effect , and the Oswestry disability scale were statistically significant . Three , 6 , and 12 months after treatment , there were significantly more success patients in the radiofrequency group compared with the sham group . CONCLUSIONS Radiofrequency lumbar zygapophysial joint denervation results in a significant alleviation of pain and functional disability in a select group of patients with chronic low back pain , both on a short-term and a long-term basis 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 Radiofrequency neurolysis of lumbar medial branch is currently the only proven way to treat patients with chronic lumbar zygapophysial joint pain , however , in some patients it can cause transient postoperative pain due to an inflammation caused by trauma of the electrode insertion and the thermal lesion around the target nerves . The aim of this study was to assess the effectiveness of intraoperative injection of methylprednisolone or pentoxifylline in comparison with placebo ( saline ) to prevent this process . 45 consecutive patients seen by one physician at one pain management clinic were included . Patients were r and omly assigned to 3 groups of 15 patients treated with radiofrequency neurotomy procedure with an addition of methylprednisolone , pentoxifylline or saline , respectively , and were observed for 6 months . Pain intensity , summed pain intensity difference , minimum 50 % reduction of pain intensity , Patients Satisfaction Score , and local tenderness were determined . The 50 % reduction of pain intensity was achieved in 80 % of patients one week after the procedure , and at 6 months such results were reported by 60 % of patients . There was a significant reduction of pain intensity in all three groups at all time points compared to baseline , however , there were no differences between the three groups . There was a significant difference in local tenderness as a measure of postoperative pain indicating effectiveness of both , methylprednisolone and pentoxifylline . No other complications were noted in any of the patients . Radiofrequency neurotomy is a safe and effective method to treat patients with zygapophysial joint pain . An addition of pentoxifylline and methylprednisolone can reduce postoperative pain commonly appearing within a short time after the procedure , however , neither pentoxifylline nor methylprednisolone influences long-term follow-up results Background Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably result ing from single sources : facet , disc , sacroiliac joint or a combination of these . Usually , these minimal interventional procedures are an integral part of a multidisciplinary pain programme . A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown . The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic . Methods All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study . Patients with a suspected diagnosis of facet , disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis . If confirmed , they will be asked to participate in a R and omized Controlled Trial ( RCT ) . For each single source a separate RCT will be conducted . Patients with a combination of facet , disc or sacroiliac joint problems will be invited for participation in a RCT as well . An economic evaluation from a societal perspective will be performed alongside these four RCTs . Patients will complete question naires at baseline , 3 and 6 weeks , 3 , 6 , 9 and 12 months after start of the treatment . Costs will be collected using self-completed cost question naires . Discussion No trials are yet available which have evaluated the cost-effectiveness of minimal interventional procedures in patients with chronic mechanical low back pain , which emphasizes the importance of this study .Trial registration numberNational Trial Register : Objectives : Radiofrequency facet joint denervation procedures have been common practice for 2 decades in treatment of chronic low back pain . We design ed this multicenter , r and omized , double-blind , sham treatment controlled trial to determine the efficacy of radiofrequency facet joint denervation , as it is routinely performed . Methods : Inclusion criteria were low back pain , duration more than 6 months , and ≥50 % Visual Analog Scale ( VAS ) reduction on diagnostic block . Exclusion criteria were prior radiofrequency treatment , radicular syndrome , coagulopathies , specific allergies , cancer , and pregnancy . A total of 81 out of 462 patients were r and omized to undergo radiofrequency facet joint denervation or sham treatment . The first evaluation was carried out 3 months after treatment . Primary outcome was determined with a combined outcome measure comprising VAS , physical activities , and analgesic intake , from a twice-weekly recorded diary . Secondary outcome measures were the separate diary parameters , global perceived effect ( complete relief , > 50 % relief , no effect , pain increase ) , and SF-36 Quality of Life Question naire . Results : There were no dropouts before the first evaluation . The combined outcome measure showed no differences between radio- frequency facet joint denervation ( n = 40 ; success 27.5 % ) and sham ( n = 41 ; success 29.3 % ) ( P = 0.86 ) . The VAS in both groups improved ( P < 0.001 ) . Global perceived effect improved after radiofrequency facet joint denervation ( P < 0.05 ) . The other secondary outcome parameters showed no significant differences . Relevant costs were evaluated . Discussion : The combined outcome measure and VAS showed no difference between radiofrequency and sham , though in both groups , significant VAS improvement occurred . The global perceived effect was in favor of radiofrequency . In selected patients , radiofrequency facet joint denervation appears to be more effective than sham treatment OBJECTIVE The aim was to compare the efficacy of intradiscal biacuplasty ( IDB ) with that of placebo treatment for discogenic low back pain . DESIGN This is a r and omized , placebo-controlled trial . Subjects were r and omized on a 1:1 basis to IDB and sham groups . Follow-ups were conducted at 1 , 3 , and 6 months . Subjects and coordinators were blinded to r and omization until 6 months . Of the 1,894 subjects screened , 64 subjects were enrolled , and 59 were treated : 29 r and omized to IDB and 30 to sham . All subjects had a history of chronic low back pain for longer than 6 months . INTERVENTIONS Two cooled radiofrequency ( RF ) electrodes placed in a bipolar manner in affected discs to lesion the nociceptive fibers of the annulus fibrosus . The sham procedure was identical to the active treatment except that probes were not directly inserted into the disc space , and RF energy was not actively delivered . RESULTS The principal outcome measures were physical function , pain , disability , and opioid usage . Patients in the IDB group exhibited statistically significant improvements in physical function ( P = 0.029 ) , pain ( P = 0.006 ) , and disability ( P = 0.037 ) at 6-month follow-up as compared to patients who received sham treatment . Treatment patients reported a reduction of 16 mg daily intake of opioids at 6 months ; however , the results were not statistically different from sham patients . CONCLUSIONS The results suggest that the clinical benefits observed in this study are the result of non-placebo treatment effects afforded by IDB . IDB should be recommended to select the patients with chronic discogenic low back pain . ( Clinical trials.gov number , NCT00750191 . ) OBJECTIVE The objective of this study was to compare the efficacy of lateral branch neurotomy using cooled radiofrequency to a sham intervention for sacroiliac joint pain . DESIGN Fifty-one subjects were r and omized on a 2:1 basis to lateral branch neurotomy and sham groups , respectively . Follow-ups were conducted at 1 , 3 , 6 , and 9 months . Subjects and coordinators were blinded to r and omization until 3 months . Sham subjects were allowed to crossover to lateral branch neurotomy after 3 months . SUBJECTS Subjects 18 - 88 years of age had chronic ( > 6 months ) axial back pain and positive response to dual lateral branch blocks . INTERVENTIONS Lateral branch neurotomy involved the use of cooled radiofrequency electrodes to ablate the S1-S3 lateral branches and the L5 dorsal ramus . The sham procedure was identical to the active treatment , except that radiofrequency energy was not delivered . OUTCOME MEASURES The principal outcome measures were pain ( numerical rating scale , SF-36BP ) , physical function ( SF-36PF ) , disability ( Oswestry disability index ) , quality of life ( assessment of quality of life ) , and treatment success . RESULTS Statistically significant changes in pain , physical function , disability , and quality of life were found at 3-month follow-up , with all changes favoring the lateral branch neurotomy group . At 3-month follow-up , 47 % of treated patients and 12 % of sham subjects achieved treatment success . At 6 and 9 months , respectively , 38 % and 59 % of treated subjects achieved treatment success . CONCLUSIONS The treatment group showed significant improvements in pain , disability , physical function , and quality of life as compared with the sham group . The duration and magnitude of relief was consistent with previous studies , with current results showing benefits extending beyond 9 months ABSTRACT The discTRODE ™ probe applies radiofrequency ( RF ) current , heating the annulus to treat chronic discogenic low back pain . R and omized controlled studies have not been published . We assessed the long‐term effect and safety aspects of percutaneous intradiscal radiofrequency thermocoagulation ( PIRFT ) with the discTRODE ™ probe in a prospect i ve parallel , r and omized and gender stratified , double‐blind placebo‐controlled study . Twenty selected patients with chronic low back pain and a positive one‐level pressure‐controlled provocation discography were r and omized to either intra‐annular PIRFT or intra‐annular sham treatment . A blinded interim analysis was performed when 20 patients had been followed for six months . The 6‐month analysis did not reveal any trend towards overall effect or difference between active and sham treatment for the primary endpoint : change in pain intensity ( 0–10 ) . The inclusion of patients was therefore discontinued . After 12 months the overall reduction from baseline pain had reached statistical significance , but there was no significant difference between the groups . The functional outcome measures ( Oswestry Disability Index , and SF 36 subscales and the relative change in pain ) appeared more promising , but did not reach statistical significance when compared with sham treatment . Two actively treated and two sham‐treated patients reported increased pain levels , and in both groups a higher number was unemployed after 12 months . The study did not find evidence for a benefit of PIRFT , although it can not rule out a moderate effect . Considering the high number , reporting increased pain in our study , we would not recommend intra‐annular thermal therapy with the discTRODE ™ probe Abstract Background Degenerative spondylolisthesis is a well-recognized source of low back pain mainly induced by facet joint pain . Pulsed radiofrequency ( PRF ) allows heat dissipation , thus producing a temporary injury that affects only type C fibers responsible for pain conduction . Objectives We attempted to test whether PRF is a better choice for facet pain due to spondylolisthesis compared to routine steroid injection . Methods Patients were r and omly assigned to one of two groups : group one received pulsed RF , and group 2 received injection by steroids ( triamcinolone ) and bupivacaine . Outcomes assessment Multiple outcome measures were utilized which included the numeric rating scale ( NRS ) , the Oswestry Disability Index ( ODI ) , satisfaction status , and analgesic intake with assessment at 3 , 6 , and 12 months post-treatment . Significant pain relief was defined as 50 % or more , whereas significant improvement in disability score was defined as reduction of 40 % or more . Results Eighty patients were enrolled in the study and were divided into the two groups of study . PRF significantly reduced NRS at 6-month follow-up compared to steroid + bupivacaine . 75.6 ± 14.3 % at pre-treatment and 19.3 ± 9.5 % at 6 months ( p = 0.001 ) in PRF group . The mean ODI is depicted in two groups of study ( Fig. 1 ) . Interestingly , ODI% was significantly lower in PRF group at 12 weeks and 6 months compare to steroid + bupivacaine group ( p = 0.022 and 0.03 , respectively ) , but it was not significantly different at 6 weeks ( p = 0.31 ) . Proportion of patients who did not require analgesics were significantly higher in PRF group compared to other group ( p = 0.001 ) in Log-rank ( Mantel – Cox ) test . Conclusion Our results demonstrated that the application of PRF might be more effective than steroid and bupivacaine injection in decreasing back pain due to degenerative facet pain and improvement in function of patients Study Design . A critical appraisal of the literature . Objectives . To increase awareness of the importance of applicability and clinical relevance of the results of r and omized controlled trials ( RCTs ) in the field of spinal disorders by formulating a list of items for assessment of applicability and clinical relevance of results of RCTs . Summary of Background Data . In systematic review s of r and omized controlled trials ( RCTs ) , critical appraisal of method ologic quality is considered important . Less attention has been paid to the assessment of the applicability and the clinical relevance of the results . Methods . RCTs in an up date of the Cochrane review on exercise therapy for low back pain were used . Most of the trials did not score positively on the five Cochrane Back Review Group basic items describing patients : intervention and setting , outcome , effect size , and benefits related to adverse effects . Item 1 was met by 88 % of the trials , but item 2 only by 51 % , item 3 by 67 % , item 4 by 35 % , and item 5 by 0 % . Subsequently , a more comprehensive list of items for the assessment of applicability and clinical relevance of results of RCTs was developed . These criteria were pilot tested on the RCTs . After pilot testing and a subsequent consensus meeting , the list of items was drafted and circulated among the members of the Editorial Board of the Cochrane Back Review Group . Changes were made in response to comments . Results . The final list consists of 40 items . The items are ordered on two headings : Does the report enable the assessment of applicability ? Are the study results clinical ly relevant ? We present examples of informative and noninformative reporting of RCTs in order to illustrate how information on applicability and clinical relevance of results can be assessed . Conclusions . Authors of RCTs should adequately report on items that are essential to assess the applicability and clinical relevance of results . The presented list of items may help clinicians reading RCTs and authors of systematic review s to draw more balanced conclusions on applicability and clinical relevance of results BACKGROUND : Lumbar facet joint degeneration is a source of chronic low back pain , with an incidence of 15 % to 45 % among patients with low back pain . Various therapeutic techniques in the treatment of facet-related pain have been described in the literature , including intraarticular lumbar facet joint steroid injections and radiofrequency denervation . In this study , we compared the effectiveness of intraarticular facet joint steroid injections and radiofrequency denervation . METHODS : Our r and omized , double-blind , controlled study included patients who received intraarticular steroid infiltrations in the lumbar facet joints ( L3/L4–L5/S1 ) and patients who underwent radiofrequency denervation of L3/L4–L5/S1 segments . The inclusion criteria were based first on magnetic resonance imaging findings showing hypertrophy of the facet joints L3/L4–L5/S1 and a positive response to an intraarticular test infiltration of the facet joints L3/L4–L5/S1 with local anesthetics . The primary end point was the Rol and -Morris Question naire . Secondary end points were the visual analog scale and the Oswestry Disability Index . All outcome assessment s were performed at baseline and at 6 months . RESULTS : Fifty-six patients were r and omized ; 24 of 29 patients in the steroid injection group and 26 of 27 patients in the denervation group completed the 6-month follow-up . Pain relief and functional improvement were observed in both groups . There were no significant differences between the 2 groups for the primary end point ( 95 % confidence interval [ CI ] , −3 to 4 ) and for both secondary end points ( 95 % CI for visual analog scale , −2 to 1 ; 95 % CI for Oswestry Disability Index , −18 to 0 ) . CONCLUSIONS : Intraarticular steroid infiltration or radiofrequency denervation appear to be a managing option for chronic function-limiting low back pain of facet origin with favorable short- and midterm results in terms of pain relief and function improvement , but improvements were similar in both groups Background : Among patients presenting with axial low back pain , facet arthropathy accounts for approximately 10–15 % of cases . Facet interventions are the second most frequently performed procedures in pain clinics across the United States . Currently , there are no uniformly accepted criteria regarding how best to select patients for radiofrequency denervation . Methods : A r and omized , multicenter study was performed in 151 subjects with suspected lumbar facetogenic pain comparing three treatment paradigms . Group 0 received radiofrequency denervation based solely on clinical findings ; group 1 underwent denervation contingent on a positive response to a single diagnostic block ; and group 2 proceeded to denervation only if they obtained a positive response to comparative blocks done with lidocaine and bupivacaine . A positive outcome was pre design ated as ≥50 % pain relief coupled with a positive global perceived effect persisting for 3 months . Results : In group 0 , 17 patients ( 33 % ) obtained a successful outcome at 3 months versus eight patients ( 16 % ) in group 1 and 11 ( 22 % ) patients in group 2 . Denervation success rates in groups 0 , 1 , and 2 were 33 , 39 , and 64 % , respectively . Pain scores and functional capacity were significantly lower at 3 months but not at 1 month in group 2 subjects who proceeded to denervation compared with patients in groups 0 and 1 . The costs per successful treatment in groups 0 , 1 , and 2 were $ 6,286 , $ 17,142 , and $ 15,241 , respectively . Conclusions : Using current reimbursement scales , these findings suggest that proceeding to radiofrequency denervation without a diagnostic block is the most cost-effective treatment paradigm BACKGROUND Results of observational studies have shown pain reduction with percutaneous radiofrequency lesioning of dorsal root ganglia for lumbosacral radicular pain , but there are few r and omised controlled trials . We aim ed to assess the efficacy of radiofrequency lesioning of dorsal root ganglia for lumbosacral radicular pain . METHODS We screened 1001 patients , who were mostly referred by their family doctor , in four hospitals for a double-blind r and omised trial . 83 patients met inclusion criteria and thus were r and omly assigned to receive a radiofrequency lesion or control treatment of the involved dorsal root ganglion . Control treatment was done in the same way as radiofrequency lesioning , but without radiofrequency current . Preoperatively and during 3-month follow-up , patients reported visual analogue leg-pain and back-pain scores , physical impairment , and use of analgesics in a diary . Primary outcome was success or failure of treatment , defined by a multidimensional decision rule , which included median outcome variables from the diary . Post-hoc analysis for possible covariate interference with outcome variables was done . Primary outcome data were analysed on an intention-to-treat basis . FINDINGS 45 patients were assigned radiofrequency lesioning and 38 control treatment . Three patients dropped out before 3 months . After 3 months , seven ( 16 % ) of 44 patients treated with radiofrequency lesioning and nine ( 25 % ) of 36 in the control group had successful treatment ( difference -9.1 % [ 95 % CI -33.0 to 12.0 ] , p=0.43 ) . No differences between groups in side-effects were seen . INTERPRETATION Lumbosacral radiofrequency lesioning of dorsal root ganglia failed to show advantage over control treatment with local anaesthetics . Thus , its use as routine treatment in lumbosacral radicular pain should not be advocated Study design A prospect i ve cross-sectional analytic study . Objectives To assess in patients with chronic low back pain whether the presence or absence of pain originating from the lumbar zygapophysial joints correlates with changes seen on computed tomography . Summary of Background Data Results of studies have been divided as to whether or not radiologic imaging is able to predict those patients with pain originating from the zygapophysical joints . Methods Sixty-three patients with low back pain lasting for longer than 3 months underwent computed tomography and blocks of the zygapophysial joints at L5-S1,L4-L5 , and L3-L4 . The zygapophysical joints of all images were scored by three independent , masked radiologists . Results Interobserver agreement was poor with intraclass correlation coefficients of 0.34–0.66 using total joint scores for all three assessors . Using the results of a repeat assessment with two radiologists there was no statistically significant difference in joint scores between those with and those without pain originating from the zygapophysial joint . Conclusions Computed tomography has no place in the diagnosis of lumbar zygapophysial joint pain Study Design . A prospect i ve double-blind r and omized controlled trial was performed . Objective . To assess the efficacy of percutaneous radiofrequency articular facet denervation for low back pain . Summary of Background Data . Uncontrolled observational studies in patients with low back pain have reported some benefits from the use of facet joint radiofrequency denervation . Because the efficacy of percutaneous radiofrequency had not been clearly shown in previous studies , a r and omized controlled trial was conducted to assess the efficacy of the technique for improving functional disabilities and reduce pain . Methods . For this study , 70 patients with low back pain lasting of more than 3 months duration and a good response after intraarticular facet injections under fluoroscopy were assigned r and omly to receive percutaneous radiofrequency articular facet denervation under fluoroscopic guidance or the same procedure without effective denervation ( sham therapy ) . The primary outcomes were functional disabilities , as assessed by the Oswestry and Rol and -Morris scales , and pain indicated on a visual analog scale . Secondary outcomes included spinal mobility and strength . Results . At 4 weeks , the Rol and -Morris score had improved by a mean of 8.4 % in the neurotomy group and 2.2 % in the placebo group , showing a treatment effect of 6.2 % ( P = 0.05 ) . At 4 weeks , no significant treatment effect was reflected in the Oswestry score ( 0.6 % change ) or the visual analog pain score ( 4.2 % change ) . At 12 weeks , neither functional disability , as assessed by the Rol and -Morris scale ( 2.6 % change ) and Oswestry scale ( 1.9 % change ) , nor the pain level , as assessed by the visual analog scale ( −7.6 % change ) , showed any treatment effect . Conclusions . Although radiofrequency facet joint denervation may provide some short-term improvement in functional disability among patients with chronic low back pain , the efficacy of this treatment has not been established Background and objectives Radiofrequency facet denervation procedures are widely used for the treatment of chronic low-back pain . Currently , both temperature-controlled and voltage-controlled techniques are used . In this combined in vivo and in vitro study , the electrophysiologic consequences and the effects on lesion size of these techniques were determined . Methods Thirty-three patients were r and omly assigned to receive a lumbar radiofrequency facet denervation by using either temperature-controlled ( 80 ° C , 60 seconds ) or voltage-controlled ( 20 V , 60 s ) mode . Electrophysiologic parameters in both groups during radiofrequency lesioning were registered . Observed differences between electrodes were quantified and interpreted , using lesion-size data from egg-white experiments . Results Seventeen patients in the temperature group were treated with a total of 55 radiofrequency lesions , all considered technically adequate . In the voltage-controlled group , 16 patients received 63 lesions . Of these , 44 ( 69.8 % ) procedures were found to be technically inadequate . Voltage-controlled radiofrequency lesioning result ed in uncontrollable fluctuations of temperature , with result ant uncontrollable variations in lesion size . Temperature-controlled mode created reproducible lesion sizes . Conclusions There is no consistent relation between voltage and the temperature obtained during radiofrequency lumbar facet denervation . Temperature-controlled radiofrequency lesioning is preferred to create reproducible lesion sizes Many treatment options for chronic low back pain are available , including varied forms of electric stimulation . But little is known about the electricity effect between electro-acupuncture and pulsed radiofrequency . The objective of this study is to assess the difference in effectiveness of pain relief between pulsed radiofrequency and electro-acupuncture . Visual analog score ( VAS ) pain score , the Oswestry disability index ( ODI ) to measure a patient 's permanent functional disability , and Short form 36 ( SF-36 ) which is a survey used in health assessment to determine the cost-effectiveness of a health treatment , were used as rating systems to measure the pain relief and functional improvement effect of pulsed radiofrequency and electro-acupuncture , based on the method ological quality of the r and omized controlled trials , the relevance between the study groups , and the consistency of the outcome evaluation . First , the baseline status before therapy shows no age and gender influence in the SF-36 and VAS score but it is significant in the ODI question naire . From ANOVA analyses , it is apparent that radiofrequency therapy is a significant improvement over electro-acupuncture therapy after one month . But electro-acupuncture also showed functional improvement in the lumbar spine from the ODI . This study provides sufficient evidence of the superiority of pulsed radiofrequency ( PRF ) therapy for low back pain relief compared with both electro-acupuncture ( EA ) therapy and the control group . But the functional improvement of the lumbar spine was proved under EA therapy only . Both therapies are related to electricity effects STUDY OBJECTIVES To compare the efficacy of continuous radiofrequency ( CRF ) thermocoagulation with pulsed radiofrequency ( PRF ) in the treatment of lumbar facet syndrome . DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Ambulatory pain clinic at a level-I trauma center and teaching institution . PATIENTS 50 ASA physical status I , II , and III patients , at least 18 years of age , scheduled to undergo CRF or PRF for lumbar back pain . INTERVENTIONS Target facet joints were identified with oblique radiographic views . Continuous radiofrequency thermocoagulation was delivered at 80 degrees C for 75 seconds , while PRF was delivered at 42 degrees C with a pulse duration of 20 ms and pulse rate of two Hz for 120 seconds . MEASUREMENTS Visual analog scale ( VAS ) pain assessment and Oswestry Low Back Pain and Disability Question naire ( OSW ) were administered at baseline and then at three months . Comparisons between groups and within groups were made of the relative percentage improvement in VAS and OSW scores . MAIN RESULTS No significant differences in the relative percentage improvement were noted between groups in either VAS ( P = 0.46 ) or OSW scores ( P = 0.35 ) . Within the PRF group , comparisons of the relative change over time for both VAS ( P = 0.21 ) and OSW scores ( P = 0.61 ) were not significant . However , within the CRF group , VAS ( P = 0.02 ) and OSW scores ( P = 0.03 ) showed significant improvement . CONCLUSIONS Although there was no significant difference between CRF and PRF therapy in long-term outcome in the treatment of lumbar facet syndrome , there was a greater improvement over time noted within the CRF group Objective The objective of this study was to determine the efficacy of percutaneous radiofrequency ( RF ) thermocoagulation of the ramus communicans nerve in patients suffering from chronic discogenic low back pain . Methods Forty-nine patients who suffered chronic discogenic low back pain at only 1 painful vertebral level , and whose pain continued after undergoing intradiscal electrothermal annuloplasty ( IDET ) , were r and omly assigned to 1 of 2 treatment groups . The lesion group ( n = 26 ) received RF thermocoagulation of the ramus communicans nerve . Patients in the control group ( n = 23 ) received an injection of lidocaine without radiofrequency . Visual analog scale ( VAS ) pain scores , analgesic requirements , SF-36 subscales , and the overall patient satisfaction with the procedure were tabulated . Results The average follow-up period was 4 months . The patient-reported VAS pain scores were significantly lower ( P < 0.05 ) in the lesion group . The scores of the RF lesion group improved by a mean increase of 11.3 points ( P < 0.05 ) on the SF-36 bodily pain subscale , and by a mean increase of 12.4 points on the physical function subscale ( P < 0.05 ) . In a follow-up analysis within the RF lesion group , VAS pain scores improved by a mean reduction of 3.32 ( P = 0.001 ) . The scores improved by a mean increase of 14.5 points ( P = 0.005 ) on the SF-36 bodily pain subscale and 15.2 points(P = 0.002 ) on the physical function subscale within the RF lesion group . One patient in the lesion group complained of mild lower limb weakness , but he completely recovered at postoperative 15 days without any serious problems . Discussion In patients with chronic discogenic low back pain , percutaneous RF denervation of the ramus communicans nerve should be considered as a treatment option BACKGROUND : An alternative technique involving a “ distal approach ” can be used for lumbar medial branch radiofrequency denervation ( LMBRFD ) . We described and assessed this technique by comparing it with a conventional tunnel vision approach in a prospect i ve r and omized trial . METHODS : Eighty-two patients underwent LMBRFD by a distal ( n = 41 ) or a tunnel vision approach ( n = 41 ) . The primary end point was a comparison of the mean difference in the change of 11-point numeric rating scale ( NRS ) scores of low back pain from entry to the scores at 1 month ( NRS at baseline — NRS at 1 month ) and at 6 months ( NRS at baseline — NRS at 6 months ) between the distal approach group and the tunnel vision approach group . The secondary end points were a change of NRS and the Oswestry disability index over time . RESULTS : Thirty-four patients in each group had complete time courses . There were no statistically significant differences in the change of NRS scores between the groups at 1 month ( corrected P = 0.19 ; 97.5 % 2-sided confidence interval [ CI ] , −1.37 to 0.37 ) and 6 months ( corrected P = 0.53 ; 97.5 % CI , −1.36 to 0.77 ) . Patients in both groups showed a statistically significant reduction in NRS and Oswestry disability index scores from baseline to that of the scores at 1 and 6 months ( all P < 0.0001 , Bonferroni corrected ) . The procedure-related pain score was significantly lower in the distal approach group ( P = 0.001 ; 99 % CI , −2.00 to −0.23 ) . CONCLUSIONS : Patients who underwent LMBRFD by the tunnel vision or distal approaches showed significant pain relief at the 6-month follow-up . Less periprocedural pain was reported in the distal approach group . We consider that the distal approach provides an improved option for LMBRFD AIM To compare the efficacy of oxygen-ozone therapy and the combined use of oxygen-ozone therapy with percutaneous intradiscal radiofrequency thermocoagulation ( PIRFT ) for the treatment of contained lumbar disc herniation . METHODS Ninety-one adult patients with low back pain secondary to contained lumbar disc herniation were r and omly assigned into two groups . Ozone group received intradiscal oxygen-ozone therapy ( 4 to 7 mL of oxygen ozone mixture ) ; ozone-PIRFT group received a combination of oxygen-ozone therapy with PIRFT ( radiofrequency lesioning at 80 ° C for 360 s ) . OUTCOME MEASURES Primary outcome measures included a visual analog scale ( VAS ) for pain and the Oswestry disability index ( ODI ) . Secondary outcome measures included pain relief , reduction of analgesic consumption , and patient 's satisfaction . Clinical assessment of these outcome measures was performed at 2 weeks , 1 month , 3 months , 6 months , and 1 year after the procedure . RESULTS VAS scores and ODI were significantly decreased by both ozone and ozone-PIRFT when compared with the baseline values at all points of follow-up ; however , ozone-PIRFT produced a significant reduction in the VAS scores and ODI when compared to ozone at 2 weeks , 1 month , 3 months , 6 months , and 1 year follow-up . Ozone-PIRFT also result ed in a significant change in all secondary measures at all points of follow-up , as compared with the ozone group . CONCLUSION Ozone-PIRFT is more efficacious than ozone alone in reducing pain scores , analgesic consumption , improving functional outcome , and satisfaction of patients with contained lumbar disc herniation Study Design . A prospect i ve r and omized trial . Objective . To evaluate the efficacy of percutaneous intradiscal radiofrequency thermocoagulation by modifying the duration of heating , using two different time methods , for relieving pain and improving functional disability . Summary of Background Data . Lumbar discogenic pain is the major problem in lumbar degenerative disc disease that percutaneous intradiscal radiofrequency thermocoagulation has been suggested for as a nonsurgical invasive treatment technique for lumbar discogenic pain . In a previous controlled study , this method was found to be ineffective with 8 weeks of follow-up . Material s and Methods . Sixty patients with chronic low back pain were selected for provocative discography to diagnose the discogenic pain and to locate the discs to be treated . From this group , 39 patients were r and omly selected and divided into two groups . In the first group , treatment was performed for 120 seconds , and in the second group for 360 seconds , both at 80C . Patients were assessed with a visual analogue scale for pain relief and functional improvement . Evaluations were performed before , immediately after treatment , at 1 and 2 weeks , and at 1 , 3 , and 6 months after the procedure . Results . A total of 39 patients with positive provocative discographies were found to eligible for the study . There were no statistical differences in pain relief and functional improvement between two groups ( P > 0.05 ) . The immediate , 1-week and 2-week , and 1-month visual analogue scale ( VAS ) scores were decreased significantly in both groups when comparing them with the pretreatment scores ( P < 0.05 ) . However , the final values after 6 months were similar to those measured at the beginning of the study ( P > 0.05 ) . Conclusion . Percutaneous intradiscal radiofrequency thermocoagulation has been suggested and performed to relieve discogenic pain . In the previous controlled study , no effective pain relief has been obtained . In this study , the authors increased the duration of radiofrequency thermocoagulation to improve the effectiveness of this method . Yet , the authors have not found any significant differences between the application of lesioning at two different times in percutaneous intradiscal radiofrequency thermocoagulation Study Design . A r and omized controlled study of percutaneous radiofrequency neurotomy was conducted in 40 patients with chronic low back pain ( 20 active and 20 controls ) . Objective . The aim of the study was to evaluate the possible beneficial effect of percutaneous radiofrequency zygapophysial joint neurotomy in reducing pain and physical impairment in patients with pain from the lumbar zygapophysial joints , selected after repeated diagnostic blocks . Summary of Background Data . Facet or zygapophysial joint pain may be one of the causes of chronic low back pain and may be treated by a percutaneous radiofrequency denervation . Patients may possibly be identified by a positive diagnostic block . These blocks need to be repeated as false positive responses to single blocks occur . In all previous studies patients treated with radiofrequency denervation have been selected after single diagnostic blocks result ing in a varying degree of relief . Methods . All patients were examined by an orthopedic surgeon before and 6 months after the treatment ( sham or active ) . Inclusion criteria were 3 separate positive facet blocks . Denervation was achieved by multiple lesions at each level in an effort to provide effective denervation . Results . The active treatment group showed statistically significant improvement not only in back and leg pain but also back and hip movement as well as the sacro-iliac joint test . Pre operative sensory deficit and weak or absent ankle reflex normalized ( P < 0.01 ) and ( P < 0.05 ) , respectively . There was significant improvement in quality of life variables , global perception of improvement , and generalized pain . The improvement seen in the active group was significantly greater then that seen in the placebo group with regard to all the above-mentioned variables . None of our patients had any complication other than transient postoperative pain that was easily managed . Conclusion . Our study indicates that radiofrequency facet denervation is not a placebo and could be used in the treatment of carefully selected patients with chronic low back pain |
2,684 | 26,995,485 | Caveats to the use of PAL emerged , and guidelines for the use of PAL were perceived as useful .
Many student-related benefits of PAL were identified .
PAL contributes to the development of crucial skills required for a doctor in the workplace .
Vertical integration of learning and teaching skills across the curriculum and tools such as feedback checklists may be required for successful PAL in the clinical environment . | BACKGROUND Peer-assisted learning ( PAL ) is increasingly used in medical education , and the benefits of this approach have been reported .
Previous review s have focused on the benefits of peer tutoring of junior students by senior students .
Forms of PAL such as discussion groups and role-playing have been neglected , as have alternative teacher-learner configurations ( e.g. same-level PAL ) and the effects on other stakeholders , including clinician educators and patients .
This review examines the benefits of same-level PAL for students , clinician educators and patients in pre- registration clinical medical education . | Background Peer-assisted learning has many purported benefits including preparing students as educators , improving communication skills and reducing faculty teaching burden . But comparatively little is known about the effects of teaching on learning outcomes of peer educators in medical education . Methods One hundred and thirty-five first year medical students were r and omly allocated to 11 small groups for the Gastroenterology/Hematology Course at the University of Calgary . For each of 22 sessions , two students were r and omly selected from each group to be peer educators . Students were surveyed to estimate time spent preparing as peer educator versus group member . Students completed an end-of-course 94 question multiple choice exam . A paired t-test was used to compare performance on clinical presentations for which students were peer educators to those for which they were not . Results Preparation time increased from a mean ( SD ) of 36 ( 33 ) minutes baseline to 99 ( 60 ) minutes when peer educators ( Cohen 's d = 1.3 ; p < 0.001 ) . The mean score ( SD ) for clinical presentations in which students were peer educators was 80.7 % ( 11.8 ) compared to77.6 % ( 6.9 ) for those which they were not ( d = 0.33 ; p < 0.01 ) . Conclusion Our results suggest that involvement in teaching small group sessions improves medical students ' knowledge acquisition and retention BACKGROUND Medical practitioners have considerable untapped potential to assist patients in stopping smoking . However , marked deficits have been found in the amount and type of training medical practitioners receive in smoking cessation counseling with little attention paid to determination of effective training methods . METHOD A r and omized controlled trial was conducted to examine the relative effectiveness of four different educational programs in teaching smoking cessation skills to 5th-year medical students in an Australian medical school . The four programs comprised : ( a ) a traditional didactic lecture mode ( control group ) , ( b ) audio feedback through the use of audiotaped role plays , ( c ) role plays with peer feedback , and ( d ) video feedback . Students ' smoking cessation intervention skills were assessed prior to training and at the end of term via videotaped interviews with simulated patients . RESULTS Senior medical students demonstrated significantly improved skills in smoking intervention when exposed to any of the educational approaches other than traditional didactic teaching . No overall differences in smoking intervention skills were found between the three experimental training methods . CONCLUSIONS Specific training in smoking cessation techniques is necessary to increase the intervention skills of medical students . Traditional teaching methods are ineffective in developing smoking cessation intervention skills . Enhanced teaching , of an appropriate nature , at undergraduate and postgraduate levels is needed Introduction International interest in peer-teaching and peer-assisted learning ( PAL ) during undergraduate medical programs has grown in recent years , reflected both in literature and in practice . There , remains however , a distinct lack of objective clarity and consensus on the true effectiveness of peer-teaching and its short- and long-term impacts on learning outcomes and clinical practice . Objective To summarize and critically appraise evidence presented on peer-teaching effectiveness and its impact on objective learning outcomes of medical students . Method A literature search was conducted in four electronic data bases . Titles and abstract s were screened and selection was based on strict eligibility criteria after examining full-texts . Two review ers used a st and ard review and analysis framework to independently extract data from each study . Discrepancies in opinions were resolved by discussion in consultation with other review ers . Adapted models of “ Kirkpatrick ’s Levels of Learning ” were used to grade the impact size of study outcomes . Results From 127 potential titles , 41 were obtained as full-texts , and 19 selected after close examination and group deliberation . Fifteen studies focused on student-learner outcomes and four on student-teacher learning outcomes . Ten studies utilized r and omized allocation and the majority of study participants were self-selected volunteers . Written examinations and observed clinical evaluations were common study outcome assessment s. Eleven studies provided student-teachers with formal teacher training . Overall , results suggest that peer-teaching , in highly selective context s , achieves short-term learner outcomes that are comparable with those produced by faculty-based teaching . Furthermore , peer-teaching has beneficial effects on student-teacher learning outcomes . Conclusions Peer-teaching in undergraduate medical programs is comparable to conventional teaching when utilized in selected context s. There is evidence to suggest that participating student-teachers benefit academically and professionally . Long-term effects of peer-teaching during medical school remain poorly understood and future research should aim to address this OBJECTIVE Smoking is the leading cause of preventable death in the USA and reducing the number of smokers by 50 % is among the goals of the Healthy People 2010 initiative . Despite its importance , few medical students receive formal training in smoking cessation counselling . Motivational interviewing is a patient-centred , but directive , method of counselling that has been found to be more effective than giving brief advice for motivating smokers to quit . We wanted to determine whether using st and ardised patients to teach this skill to Year 3 medical students would be more effective than using student role-plays . METHODS We conducted a r and omised , controlled trial of 93 Year 3 family medicine clerkship students at our medical school between July 2003 and July 2004 . The control group ( n=46 ) practised motivational interviewing with one another and the intervention group ( n=47 ) practised with st and ardised patients trained in motivational interviewing for smoking cessation . At the end of the study all the students conducted an interview with a different st and ardised patient that was videotaped . The primary outcome was analysis by a trained masked evaluator of the quality of a final videotaped interview using the motivational interviewing treatment integrity code ( MITI ) , which assesses the quality of the interview according to 6 different criteria . RESULTS There was no significant difference between the control and intervention groups in the final analyses of the interviews . CONCLUSIONS According to MITI scores , st and ardised patient role-plays are similar in effectiveness to student role-plays when teaching basic motivational interviewing skills for smoking cessation to Year 3 medical students QUESTION What is the efficacy and acceptability of a peer-assisted learning model compared with a traditional model for paired students in physiotherapy clinical education ? DESIGN Prospect i ve , assessor-blinded , r and omised crossover trial . PARTICIPANTS Twenty-four physiotherapy students in the third year of a 4-year undergraduate degree . INTERVENTION Participants each completed 5 weeks of clinical placement , utilising a peer-assisted learning model ( a st and ardised series of learning activities undertaken by student pairs and educators to facilitate peer interaction using guided strategies ) and a traditional model ( usual clinical supervision and learning activities led by clinical educators supervising pairs of students ) . OUTCOME MEASURES The primary outcome measure was student performance , rated on the Assessment of Physiotherapy Practice by a blinded assessor , the supervising clinical educator and by the student in self- assessment . Secondary outcome measures were satisfaction with the teaching and learning experience measured via survey , and statistics on services delivered . RESULTS There were no significant between-group differences in Assessment of Physiotherapy Practice scores as rated by the blinded assessor ( p=0.43 ) , the supervising clinical educator ( p=0.94 ) or the students ( p=0.99 ) . In peer-assisted learning , clinical educators had an extra 6 minutes/day available for non-student-related quality activities ( 95 % CI 1 to 10 ) and students received an additional 0.33 entries/day of written feedback from their educator ( 95 % CI 0.06 to 0.61 ) . Clinical educator satisfaction and student satisfaction were higher with the traditional model . CONCLUSION The peer-assisted learning model trialled in the present study produced similar student performance outcomes when compared with a traditional approach . Peer-assisted learning provided some benefits to educator workload and student feedback , but both educators and students were more satisfied with the traditional model . TRIAL REGISTRATION ACTRN12610000859088 . [ Sevenhuysen S , Skinner EH , Farlie MK , Raitman L , Nickson W , Keating JL , Maloney S , Molloy E , Haines TP ( 2014 ) Educators and students prefer traditional clinical education to a peer-assisted learning model , despite similar student performance outcomes : a r and omised trial . Journal of Physiotherapy60 : 209 - 216 ] Purpose To assess the use of peer-assisted learning ( PAL ) of complex manipulative motor skills with respect to gender in medical students . Methods In 2007–2010 , 292 students in their 3rd and 4th years of medical school were r and omly assigned to two groups [ Staff group ( SG ) , PAL group ( PG ) ] led by either staff tutors or student-teachers ( ST ) . The students were taught bimanual practical and diagnostic skills ( course education module of eight separate lessons ) as well as a general introduction to the theory of spinal manipulative therapy . In addition to qualitative data collection ( Likert scale ) , evaluation was performed using a multiple-choice question naire in addition to an objective structured clinical examination ( OSCE ) . Results Complex motor skills as well as palpatory diagnostic competencies could in fact be better taught through professionals than through ST ( manipulative OSCE grade s/diagnostic OSCE score ; SG vs. PG ; male : P = 0.017/P < 0.001 , female : P < 0.001/P < 0.001 ) . The registration of theoretical knowledge showed equal results in students taught by staff or ST . In both teaching groups ( SG : n = 147 , PG : n = 145 ) , no significant differences were observed between male and female students in matters of manipulative skills or theoretical knowledge . Diagnostic competencies were better in females than in males in the staff group ( P = 0.041 ) Overall , students were more satisfied with the environment provided by professional teachers than by ST , though male students regarded the PAL system more suspiciously than their female counterparts . Conclusions The peer-assisted learning system does not seem to be generally qualified to transfer such complex spatiotemporal dem and s as spinal manipulative procedures Background Focused emergency echocardiography performed by non-cardiologists has been shown to be feasible and effective in emergency situations . During resuscitation a short focused emergency echocardiography has been shown to narrow down potential differential diagnoses and to improve patient survival . Quite a large proportion of physicians are eligible to learn focused emergency echocardiography . Training in focused emergency echocardiography usually comprises a lecture , h and s-on trainings in very small groups , and a practice phase . There is a shortage of experienced echocardiographers who can supervise the second step , the h and s-on training . We thus investigated whether student tutors can perform the h and s-on training for focused emergency echocardiography . Methods A total of 30 volunteer 4th and 5th year students were r and omly assigned to a twelve-hour basic echocardiography course comprising a lecture followed by a h and s-on training in small groups taught either by an expert cardiographer ( EC ) or by a student tutor ( ST ) . Using a pre-post- design , the students were evaluated by an OSCE . The students had to generate two still frames with the apical five-chamber view and the parasternal long axis in five minutes and to correctly mark twelve anatomical cardiac structures . Two blinded expert cardiographers rated the students ’ performance using a st and ardized checklist . Students could achieve a maximum of 25 points . Results Both groups showed significant improvement after the training ( p < .0001 ) . In the group taught by EC the average increased from 2.3±3.4 to 17.1±3.0 points , and in the group taught by ST from 2.7±3.0 to 13.9±2.7 points . The difference in improvement between the groups was also significant ( p = .03 ) . Conclusions H and s-on training by student tutors led to a significant gain in echocardiography skills , although inferior to teaching by an expert cardiographer Background To assess the student perspective on acceptability , realism , and perceived effect of communication training with peer role play ( RP ) and st and ardised patients ( SP ) . Methods 69 prefinal year students from a large German medical faculty were r and omly assigned to one of two groups receiving communication training with RP ( N = 34 ) or SP ( N = 35 ) in the course of their paediatric rotation . In both groups , training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children . Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales . Results Both forms of training were highly accepted ( RP 5.32 ± .41 , SP 5.51 ± .44 , n.s . ; 6 = very good , 1 = very poor ) and perceived to be highly realistic ( RP 5.60 ± .38 , SP 5.53 ± .36 , n.s . ; 6 = highly realistic , 1 = unrealistic ) . Regarding perceived effects , participation was seen to be significantly more worthwhile in the SP group ( RP 5.17 ± .37 , SP 5.50 ± .43 ; p < .003 ; 6 = totally agree , 1 = do n't agree at all ) . Both training methods were perceived as useful for training communication skills ( RP 5.01 ± .68 , SP 5.34 ± .47 ; 6 = totally agree ; 1 = do n't agree at all ) and were considered to be moderately applicable for future parent-physician encounters ( RP 4.29 ± 1.08 , SP 5.00 ± .89 ; 6 = well prepared , 1 = unprepared ) , with usefulness and applicability both being rated higher in the SP group ( p < .032 and p < .009 ) . Conclusions RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective . Both provide highly realistic training scenarios and warrant inclusion in medical curricula . Given the expense of SP , deciding which method to employ should be carefully weighed up . From the perspective of the students in our study , SP were seen as a more useful and more applicable tool than RP . We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective Background : Communication skills teaching is known to be effective , but students feel there are discrepancies between how communication skills are taught and how they are assessed . Aims : This study examined the effect of using st and ard assessment criteria during communication skills teaching on students ’ performance in an end-of-year summative OSCE . Method : Students attending their year 3 communication skills teaching were r and omised to one of the following three conditions : the assessment criteria were available for reference on the medical school website ; or students received the assessment criteria for use in the discussion and feedback ; or each student 's performance was grade d by him- or her- self , his or her peers , the tutor and the actor using the st and ard assessment criteria . Results : There was no significant difference in the end-of-year OSCE performance of students who received the three different conditions . Actively using st and ard assessment criteria during teaching did not therefore improve OSCE performance . There were low but significant correlations between the tutors ’ assessment and the students ’ self- assessment and between the tutors ’ assessment and the peer group 's assessment . Conclusion : The congruence between observers in the assessment s of role-played consultations using the st and ard assessment criteria indicates that the criteria may be helpful for summarizing feedback to students Background : Conducting a consultation is a core competence of medical professionals . Consultation training of medical students centers on clinical , communication , reasoning and reflection skills . The training incorporates practice with a st and ardized simulated patient and supervising physician , to prepare for real patient encounters . To meet the request for more training , while dealing with an increasing student population and limited staff availability , alternative formats of consultation training were developed and evaluated . Aim : To investigate the impact of three consultation training formats on students ’ self-efficacy beliefs and their consultation skills acquisition . The three formats comprised ( 1 ) traditional training with supervising physician , ( 2 ) autonomous training with feedback from simulated patients and peers , without direct supervision and ( 3 ) online training based on video fragments and answering guiding questions . Methods : A quasi-experimental pre/posttest study was set up , with r and om assignment of students to a training condition . The differential impact was tested on two dependent measures : self-efficacy and consultation performance . Self-efficacy was tested with a nine-item scale and the cognitive component of consultation performance was tested on the base of responses to a st and ardized video case . Results : The autonomous training has a significant positive effect on students ’ self-efficacy ( p = 0.016 ) . The traditional training and the online training did only positively influence the cognitive component of the consultation competence ( p < 0.001 and p = 0.003 ) . Conclusions : Each consultation training contributes to the learning process in a different way . In order to achieve optimum learning effects , medical educators should be aware of the particular impact of specific trainings on the cognitive and motivational side of skills and pursue a balanced mixture of instructional formats OBJECTIVES There is a need to improve competence of musculoskeletal system ( MSS ) examination in medical students and junior doctors . Peer-assisted learning ( PAL ) is a technique whereby students learn from and with each other . This study aim ed to determine whether PAL can be integrated into st and ard undergraduate medical curricula to improve MSS examination using the gait , arms , legs , spine ( GALS ) screening tool . METHODS Fifty final-year students ( trainers ) were trained using GALS for MSS examination while attending a st and ard clinical medical attachment at Glasgow Royal Infirmary . These students delivered GALS training to a further 159 students ( trainees ) . Pre/post-confidence question naire ( 100-mm visual analogue scale ) and written feedback were obtained . Final Objective Structured Clinical Examination ( OSCE ) scores from an MSS station were compared with a control group of 229 students r and omized to other hospitals for the st and ard MSS training . RESULTS Analysis of completed trainer question naires ( 30/50 ) showed increased confidence in all parts of GALS after training [ < 47 ( 19 ) cf . > 88 ( 12 ) ; P < 0.005 ] . Similarly , confidence in trainees ( 136/159 ) who answered the question naire increased [ < 43 ( 19 ) cf . > 85 ( 15 ) ; P < 0.005 ] . Written comments highlighted that students would recommend PAL . OSCE results showed 84 % ( 192/229 ) of students in the control group passed the MSS station , with 87 % ( 139/159 ) of trainees ( P = 0.3 ) and 100 % ( 50/50 ) of trainers ( P < 0.01 ) . CONCLUSIONS MSS examination skills are improved by integrating PAL into the undergraduate medical curriculum , with student confidence being increased , and higher OSCE scores Background : Video review is a valuable educational tool for teaching communication skills . Many studies have demonstrated its efficacy with individual learners , but few studies have addressed its use in a group format . Purpose : To assess the educational benefits of group versus individual video review of st and ardized patient encounters through the evaluations of 4th-year students at the Albert Einstein College of Medicine . Methods : Students ( 128 ) who participated in a 7-station , st and ardized patient , clinical competency exam were r and omly assigned to an individual or small group video review of selected segments of these encounters in 2000–2001 . Students filled out an anonymous 13-item question naire assessing the experience and provided open-ended responses . Results : With both review formats , most students had a positive learning experience ( 80 % ) , found it less stressful than they expected ( 67 % ) , and would not have preferred to do the review the other way ( 84 % ) . Students r and omized to individual review s had a significantly higher level of satisfaction with the amount of time for the session ( 91 % vs. 78 % , p < . 05 ) and the amount of feedback they received ( 95 % vs. 79 % , p = . 01 ) and were more likely to view the session as a positive learning experience ( 88 % vs. 73 % , p < . 05 ) . Students in the individual review format were more likely to choose self-assessed weak segments ( 63 % vs. 49 % , p = . 01 ) . Students ' comments indicated that they appreciated the value of peer review in a group setting . Conclusions : Although both group review s and individual review s of videotaped st and ardized patient encounters were received well by the students , there were several statistical differences in favor of the individual format OBJECTIVES This study ( a post-intervention assessment ) was design ed to assess the effectiveness of peer-assisted learning ( PAL ) using student-teachers ( STs ) with limited training to teach complicated technical skills for interpreting ultrasound images of the shoulder . METHODS Students in Years 3 and 4 of medical school were r and omly assigned to two groups . In the PAL group ( PG ) , teaching was delivered by a group of nine STs from Years 3 and 4 , who undertook a 30-minute general training and 1 week of self-teaching . In the staff-led group ( SG ) , students were taught by a group of three ultrasound-experienced doctors . Exposure took place in two separate lessons ( each of 120 minutes ) and introduced eight st and ard sectional planes ( EULAR ) using a 10-MHz Nemio XG system ( Toshiba Medical Systems GmbH ) . The theoretical and practical learning outcomes were tested using a multiple-choice question ( MCQ ) test and an objective structured clinical examination ( OSCE ) . Qualitative differences were evaluated using Likert scale-based items . RESULTS Evaluation of differences between the PG ( n = 75 ) and SG ( n = 76 ) in the theoretical ( MCQ score ; P = 0.644 ) and practical ( total OSCE score ; P = 0.133 ) outcomes showed no difference between the two groups . However , the STs themselves showed significantly better results overall ( P < 0.05 ) . Staff members were rated more highly than STs , especially on items relating to competence ( P < 0.05 ) . CONCLUSIONS Complicated technical skills can be adequately taught to students using the PAL system by STs with limited training . Self-teaching learning strategies are successful in context s of limited teacher training . However , despite positive objective results , STs still face prejudice from students with regard to competency |
2,685 | 24,558,078 | We found evidence of pharmacogenetic interactions for metformin , sulfonylureas , repaglinide , thiazolidinediones , and acarbose consistent with their pharmacokinetics and pharmacodynamics . | OBJECTIVE We performed a systematic review to identify which genetic variants predict response to diabetes medications . | AIMS The beta-cell ATP-sensitive potassium channel consists of two subunits , SUR1 and Kir6.2 . Population association studies have shown that three variants in SUR1 and one in Kir6.2 are associated with Type 2 diabetes . These polymorphisms do not result in a functional change or affect splicing , suggesting that they could be in linkage disequilibrium with a pathogenic mutation . The present study aim ed firstly to screen the promoter regions of SUR1 and Kir6.2 to determine whether mutations in linkage disequilibrium with the silent variants lie in regulatory regions , which might lead to changes in gene expression . Secondly , novel and previously described variants associated with Type 2 diabetes ( SUR1 exon 16 - 3 t , exon 18 T , and Kir6.2 E23 K ) were investigated in the UKPDS cohort . METHODS The promoter sequences of both genes were screened by single-str and ed conformational polymorphism analysis for variants associated with Type 2 diabetes . The previously reported variants were evaluated in 364 Type 2 diabetic and 328 normoglycaemic control subjects . RESULTS Two variants were detected in the SUR1 promoter , a three base insertion ( caa ) at -522 bp and a single base substitution at - 679 bp ( c-->g ) . Neither of the variants were associated with diabetes , nor were they in a sequence consensus region for transcription factors . No association with diabetes was observed for either SUR1 variant . However , in contrast , analysis of the Kir6.2 E23 K variant showed that the KK homozygosity was more frequent in Type 2 diabetic than control subjects . Variants were not associated with clinical characteristics nor did they affect response to sulphonylurea therapy CONCLUSION There is no support at present for mutations in either Kir6.2 or SUR1 promoter sequences contributing to Type 2 diabetes . However , the minimal promoter region of SUR1 has yet to be investigated . The E23 K variant of Kir6.2 is associated with Type 2 diabetes mellitus in the UKPDS cohort Common genetic variants have been recently associated with fasting glucose and insulin levels in white population s. Whether these associations replicate in pre-diabetes is not known . We extended these findings to the Diabetes Prevention Program , a clinical trial in which participants at high risk for diabetes were r and omized to placebo , lifestyle modification or metformin for diabetes prevention . We genotyped previously reported polymorphisms ( or their proxies ) in/near G6PC2 , MTNR1B , GCK , DGKB , GCKR , ADCY5 , MADD , CRY2 , ADRA2A , FADS1 , PROX1 , SLC2A2 , GLIS3 , C2CD4B , IGF1 , and IRS1 in 3,548 Diabetes Prevention Program participants . We analyzed variants for association with baseline glycemic traits , incident diabetes and their interaction with response to metformin or lifestyle intervention . We replicated associations with fasting glucose at MTNR1B ( P<0.001 ) , G6PC2 ( P = 0.002 ) and GCKR ( P = 0.001 ) . We noted impaired β-cell function in carriers of glucose-raising alleles at MTNR1B ( P<0.001 ) , and an increase in the insulinogenic index for the glucose-raising allele at G6PC2 ( P<0.001 ) . The association of MTNR1B with fasting glucose and impaired β-cell function persisted at 1 year despite adjustment for the baseline trait , indicating a sustained deleterious effect at this locus . We also replicated the association of MADD with fasting proinsulin levels ( P<0.001 ) . We detected no significant impact of these variants on diabetes incidence or interaction with preventive interventions . The association of several polymorphisms with quantitative glycemic traits is replicated in a cohort of high-risk persons . These variants do not have a detectable impact on diabetes incidence or response to metformin or lifestyle modification in the Diabetes Prevention Program AIMS We aim ed to determine whether NeuroD1/BETA2 and PAX4 polymorphisms were associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetes mellitus ( T2DM ) patients . METHODS Three hundred and sixty-eight T2DM patients and 132 healthy control subjects were genotyped by restriction fragment length polymorphism . Forty-three patients with various genotypes were r and omly selected to undergo 8 weeks of repaglinide treatment ( 3 mg day(-1 ) ) . Fasting plasma glucose , postpr and ial plasma glucose , glycated haemoglobin , fasting and postpr and ial serum insulin ( FINS , PINS ) , homeostasis model assessment for insulin resistance , serum triglyceride , total cholesterol , low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol were determined before and after repaglinide treatment . RESULTS The allelic frequency of NeuroD1/BETA2 T45 was higher in T2DM patients than in the control subjects [ 13.45 vs. 6.82 % , P < 0.01 , odds ratios = 2.342 ( 1.365 , 4.019 ) , P= 0.002 ] . Type 2 diabetes mellitus patients with the mutated allele of NeuroD1/BETA2 A45 T polymorphism showed higher FINS ( 13.46 ± 12.57 vs. 10.04 ± 7.09 mU l(-1 ) , P < 0.05 ) ( 11.67 , 14.83 vs. 8.38 , 11.37 ) and PINS ( 52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1 ) , P < 0.05 ) ( 44.89 , 58.35 vs. 55.35 , 88.87 ) than individuals with the T allele . The PAX4 R121W R allele carriers had higher PINS ( 52.11 ± 40.93 vs. 68.66 ± 43.87 mU l(-1 ) , P < 0.05 ) ( 44.89 , 58.35 vs. 55.35 , 88.87 ) than subjects with the W allele . After repaglinide treatment , patients with the T allele of NeuroD1/BETA2 A45 T polymorphisms had attenuated efficacy on fasting plasma glucose ( -2.79 ± 2.14 vs.-0.99 ± 1.80 mmol l(-1 ) , P < 0.01 ) ( -3.53 , -1.84 vs.-1.99 , -0.13 ) and postpr and ial plasma glucose ( -6.71 ± 5.90 vs.-2.54 ± 3.39 mmol l(-1 ) , P < 0.01 ) ( -9.28 , -4.62 vs.-4.34 , -0.84 ) . Patients with the RR genotype of PAX4 R121W showed better efficacy with respect to the level of postpr and ial plasma glucose than R/W genotypes ( -6.53 ± 6.52 vs.-2.95 ± 1.17 mmol l(-1 ) , P < 0.05 ) ( -8.20 , -4.89 vs.-3.92 , -1.20 ) . CONCLUSIONS The NeuroD1/BETA2 and PAX4 polymorphisms were substantially associated with plasma glucose level after repaglinide monotherapy OBJECTIVE To investigate the influence of peroxisome proliferator-activated receptor-gamma ( PPAR-gamma ) gene variants on the response rate to therapy with the thiazolidinedione ( TZD ) pioglitazone , because in vitro studies have suggested that genetic variants of the PPAR-gamma gene may influence the drug efficacy of TZD . RESEARCH DESIGN AND METHODS A total of 131 patients were treated in an open-label , r and omized , multicenter study with pioglitazone ( 45 mg o.d . ) during a course of > or=26 weeks . Response to the pioglitazone therapy was defined by either a > 20 % decrease in fasting plasma glucose or a > 15 % decrease in HbA(1c ) values after 26 weeks of pioglitazone treatment . We evaluated the association between the PPAR-gamma genotype and the response rate to pioglitazone treatment . RESULTS The Pro12Ala and the Pro12Pro variants in the PPAR-gamma gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes . However , we identified initial fasting plasma glucose level > 11.0 mmol/l , HbA(1c ) value > 9.0 % , BMI > 32 kg/m(2 ) , and fasting C-peptide concentrations at baseline > 2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment . CONCLUSIONS The Pro12Ala variant in the PPAR-gamma gene does not affect the therapy efficacy of pioglitazone , suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-gamma and its lig and pioglitazone . Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined Metformin is the most commonly used pharmacological therapy for type 2 diabetes . We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospect i ve Diabetes Study . In a combined meta- analysis , we identified a SNP , rs11212617 , associated with treatment success ( n = 3,920 , P = 2.9 × 10−9 , odds ratio = 1.35 , 95 % CI 1.22–1.49 ) at a locus containing ATM , the ataxia telangiectasia mutated gene . In a rat hepatoma cell line , inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin . We conclude that ATM , a gene known to be involved in DNA repair and cell cycle control , plays a role in the effect of metformin upstream of AMP-activated protein kinase , and variation in this gene alters glycemic response to metformin Aim : To investigate the influence of peroxisome proliferator-activated receptor γ2 ( PPAR-γ2 ) gene polymorphism rs1801282 and protein tyrosine phosphatase receptor type D ( PTPRD ) gene polymorphism rs17584499 on the occurrence of type 2 diabetes and pioglitazone efficacy in a Chinese Han population . Methods : One hundred ninety seven type 2 diabetes patients and 212 healthy controls were enrolled . Among them , 67 type 2 diabetes patients were administered pioglitazone ( 30 mg/d , po ) for 3 months . All the subjects were genotyped for genetic variants in PPAR-γ2 and PTPRD using MALDI-TOF mass spectrometry . Fasting plasma glucose , postpr and ial plasma glucose , glycated hemoglobin , serum triglyceride , total cholesterol , low-density and high-density lipoprotein-cholesterol were determined . Results : The PPAR-γ2 gene rs1801282 polymorphism was significantly associated with type 2 diabetes susceptibility ( OR=0.515 , 95 % CI 0.268–0.990 ) and the PTPRD gene rs17584499 polymorphism was also significantly associated with type 2 diabetes ( OR=1.984 , 95 % CI 1.135–3.469 ) in a dominant model adjusted for age , gender and BMI . After pioglitazone treatment for 3 months , the type 2 diabetes patients with PPAR-γ2 rs1801282 CG genotypes significantly showed higher differential values of postpr and ial plasma glucose and serum triglyceride compared with those with rs1801282 CC genotype . The patients with PTPRD rs17584499 CT+TT genotypes showed significantly lower differential value of postpr and ial plasma glucose compared to those with rs17584499 CC genotype . Conclusion : Diabetes risk alleles in PPAR-γ2 ( rs1801282 ) and PTPRD ( rs17584499 ) are associated with pioglitazone therapeutic efficacy The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor ( PPAR ) γ2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus Objective Genome-wide association studies ( GWASs ) identified that SLC30A8 genetic polymorphism was a risk of type 2 diabetes mellitus ( T2DM ) in several population s. This study aim ed to investigate whether the SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with T2DM susceptibility and repaglinide therapeutic efficacy in Chinese T2DM patients . Methods We conducted a case – control study of 443 T2DM patients and 229 healthy volunteers to identify SLC30A8 rs13266634 and rs16889462 genotypes by polymerase chain reaction – restriction fragment length polymorphism ( PCR-RFLP ) assay . Forty-eight patients were r and omly selected and underwent an 8-week repaglinide treatment ( 3 mg/d ) . Fasting plasma glucose ( FPG ) , postpr and ial plasma glucose ( PPG ) , glycated hemoglobin ( HbAlc ) , fasting serum insulin ( FINS ) , postpr and ial serum insulin ( PINS ) , homeostasis model assessment for insulin resistance ( HOMA-IR ) , serum triglyceride , total cholesterol ( TC ) , low-density lipoprotein-cholesterol ( LDL-c ) and high-density lipoprotein-cholesterol ( HDL-c ) were determined before and after repaglinide treatment . Results SLC30A8 rs13266634 risk C allele frequency was higher in T2DM patients than in healthy controls ( P < 0.05 ) . There was a better repaglinide response on FINS ( P < 0.05 ) and PINS ( P < 0.01 ) in patients with rs13266634 CT+TT genotypes compared with CC genotype carriers . Patients with rs16889462 GA genotype showed an enhanced repaglinide efficacy on FPG ( P < 0.01 ) , PPG ( P < 0.01 ) and HbAlc ( P < 0.05 ) compared with GG genotype individuals . Conclusions SLC30A8 rs13266634 and rs16889462 polymorphisms were associated with repaglinide therapeutic efficacy in Chinese T2DM patients Abstract Objective : To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes . Design : Prospect i ve observational study . Setting : 23 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Participants : 4585 white , Asian Indian , and Afro-Caribbean UKPDS patients , whether r and omised or not to treatment , were included in analyses of incidence ; of these , 3642 were included in analyses of relative risk . Outcome measures : Primary predefined aggregate clinical outcomes : any end point or deaths related to diabetes and all cause mortality . Secondary aggregate outcomes : myocardial infa rct ion , stroke , amputation ( including death from peripheral vascular disease ) , and microvascular disease ( predominantly retinal photo-coagulation ) . Single end points : non-fatal heart failure and cataract extraction . Risk reduction associated with a 1 % reduction in up date d mean HbA1c adjusted for possible confounders at diagnosis of diabetes . Results : The incidence of clinical complications was significantly associated with glycaemia . Each 1 % reduction in up date d mean HbA1c was associated with reductions in risk of 21 % for any end point related to diabetes ( 95 % confidence interval 17 % to 24 % , P<0.0001 ) , 21 % for deaths related to diabetes ( 15 % to 27 % , P<0.0001 ) , 14 % for myocardial infa rct ion ( 8 % to 21 % , P<0.0001 ) , and 37 % for microvascular complications ( 33 % to 41 % , P<0.0001 ) . No threshold of risk was observed for any end point . Conclusions : In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia . Any reduction in HbA1c is likely to reduce the risk of complications , with the lowest risk being in those with HbA1c values in the normal range ( < 6.0 % ) OBJECTIVE To investigate a potential relationship between Solute carrier family 30 ( zinc transporter ) member 8 ( SLC30A8 ) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients . METHODS A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone r and omly for 48 weeks ( 104 and 105 patients , respectively ) . Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment . An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy . RESULTS Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study . Δ value of homeostasis model assessment of beta cell function ( HOMA-B ) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups ( P=0.0149 and 0.0246 , respectively ) after rosiglitazone treatment . However , no genotype association was observed in the repaglinide or rosiglitazone group with other parameters . CONCLUSION The SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai , China Glimepiride , a sulfonylurea hypoglycemic agent , is metabolized by cytochrome P450 2C9 ( CYP2C9 ) which is known to have genetic polymorphisms . To examine the effects of CYP2C9 genetic polymorphisms on the safety and efficacy of glimepiride in patients with type 2 diabetes , the responses to the glimepiride were measured in Japanese type 2 diabetic patients with the different CYP2C9 genotype . The reduction in the HbA(1c ) was significantly larger ( P<0.05 ) among the CYP2C9 * 1/*3 subjects than among the CYP2C9 * 1/*1 subjects . The long-term observations of 2 patients with a CYP2C9 * 1/*3 suggested that subjects with a CYP2C9 * 1/*3 respond well to glimepiride during the initial phase of treatment , but 1 patient have shown the weight gain over the long-term treatment . The pharmacokinetic study showed that the area under the concentration-time curve for glimepiride in the CYP2C9 * 1/*3 subjects was approximately 2.5-fold higher than that of the CYP2C9 * 1/*1 subjects . The intrinsic clearance of glimepiride by the CYP2C9 * 3 enzyme was lower than that by the CYP2C9 * 1 enzyme . These results suggested that the lower hydroxylation activity of glimepiride in the subject with type 2 diabetes and CYP2C9 * 1/*3 led to a marked elevation in the plasma concentrations of glimepiride and a stronger pharmacological effect of glimepiride The aim of this study was to explore the impact of KCNQ1 variants on the responses to oral antidiabetic drugs in a Chinese study population . A 48‐week r and omized pharmacogenetics study compared the effects of repaglinide and rosiglitazone in 209 newly diagnosed patients with type 2 diabetes . In the repaglinide cohort , individuals who were rs2237892 TT homozygotes exhibited lower 2‐h glucose levels and significantly higher cumulative attainment rates of target 2‐h glucose levels ( Plog‐rank = 0.0383 ) than the C allele carriers ; patients with a greater number of rs2237892 C alleles showed larger augmentations in both fasting insulin and homeostasis model assessment of insulin resistance ( HOMA‐IR ) ( P = 0.0166 and 0.0026 , respectively ) ; moreover , the rs2237895 C allele was also associated with greater increments in both fasting insulin and HOMA‐IR ( P = 0.0274 and 0.0259 , respectively ) . In contrast , only an association between rs2237897 and decrease in 2‐h glucose levels was detected in the rosiglitazone cohort ( P = 0.0321 ) . Our results indicated that KCNQ1 polymorphisms are associated with repaglinide efficacy , and might also be associated with rosiglitazone response , in Chinese patients with type 2 diabetes |
2,686 | 32,145,223 | The collected data revealed distinct impairments in a range of central auditory processes in PD , including altered deviance detection of basic auditory features , auditory brainstem processing , auditory gating and selective auditory attention .
In contrast to PD , literature on central auditory processing in MSA and PSP was relatively scarce , but provided some evidence for impaired central auditory processing in MSA and PSP . | Altered auditory processing has been increasingly recognized as a non-motor feature in parkinsonian disorders .
This systematic review provides an overview of behavioral and electrophysiological literature on central auditory processing in patients with Parkinson 's disease ( PD ) , multiple system atrophy ( MSA ) and progressive supranuclear palsy ( PSP ) . | This article reports the severity and profile of neuropsychological impairment on a prevalent cohort of patients with a clinical diagnosis of either multiple system atrophy ( n=372 ) or progressive supranuclear palsy ( n=311 ) from the Neuroprotection and Natural History in Parkinson Plus Syndromes cohort . The Dementia Rating Scale and Frontal Assessment Battery were used to assess global cognition and executive dysfunction . For the Dementia Rating Scale impairment was observed in approximately 57 % of the progressive supranuclear palsy group and 20 % of the multiple system atrophy group . In the former , impairment in a single cognitive domain was observed in 40 % , with the same number showing impairment in multiple domains , while in the latter the figures were 28.6 and 13.5 % , respectively . On the Frontal Assessment Battery , impairment was observed in 62.0 % of patients with progressive supranuclear palsy and 31.8 % of those with multiple system atrophy . Although the progressive supranuclear palsy group performed worse overall , the cognitive profiles of the two groups on the Dementia Rating Scale subscales were identical , with the main impairment of the Initiation and Perseveration subscale . The impaired patients in the two groups were largely indistinguishable , qualitatively and quantitatively . Impairment was associated with greater age and clinical disability in both groups and was evident even in the early stages ( 22 % in multiple system atrophy and 50 % in progressive supranuclear palsy ) . Where a pathological diagnosis was available , the original clinical diagnosis was confirmed in the majority of cases , including those with significant cognitive impairment . The rate of impairment in those with a confirmed pathological diagnosis was comparable to that of the sample as a whole . These results demonstrate , in the largest prospect ively recruited cohort of patients with progressive supranuclear palsy and multiple system atrophy studied to date , the existence of a cognitive profile similar to that previously reported in idiopathic Parkinson 's disease . The results indicate a high level of cognitive impairment associated with progressive supranuclear palsy , but also point to comparable dysfunction in a substantial proportion of the patients with multiple system atrophy . Significant cognitive impairment appears consistent with a diagnosis of multiple system atrophy , even early in the disease , with important implication s for diagnosis , research and management Abstract Bilateral deep brain stimulation is an effective treatment for most motor signs of Parkinson 's disease ( PD ) , but the effects on cognitive functions are less clear . We therefore examined the effects of bilateral deep brain stimulation on central information processing , using the event-related auditory P300 potential as an electrophysiological index of mental chronometry . Eight PD patients with bilateral stimulators within the subthalamic nuclei ( STN ) and eight age-matched controls participated . Patients were examined after overnight withdrawal of antiparkinson medication , both “ on ” and “ off ” stimulation ( in r and om sequence ) . The P300 and reaction times were recorded using an auditory oddball paradigm . P300 latencies were prolonged in PD patients off stimulation ( 440 ± 45 ms ) compared to controls ( 397 ± 16 ms ; P < 0.05 ) . STN stimulation significantly reduced clinical disease severity ( as indexed by the Unified Parkinson 's Disease Rating Scale ) and markedly improved reaction times , but did not improve the prolonged P300 latencies in PD patients ( 429 ± 36 ms ) . These results confirm that P300 latencies are prolonged in PD . Significantly , bilateral STN stimulation did not improve this electrophysiological measure of cognitive impairment , even though motor disability was markedly reduced . This suggests that some dopa-responsive features are resistant to STN stimulation , possibly due to involvement of dopaminergic deficits outside the nigrostriatal pathway , which are not influenced by outflow from the STN In this study , individuals with Parkinson ’s disease were tested as a model for basal ganglia dysfunction to infer how these structures contribute to the processing of emotional speech tone ( emotional prosody ) . Nondemented individuals with and without Parkinson ’s disease ( n = 21/group ) completed neuropsychological tests and tasks that required them to process the meaning of emotional prosody in various ways ( discrimination , identification , emotional feature rating ) . Individuals with basal ganglia disease exhibited abnormally reduced sensitivity to the emotional significance of prosody in a range of context s , a deficit that could not be attributed to changes in mood , emotional-symbolic processing , or estimated frontal lobe cognitive re source limitations in most conditions . On the basis of these and broader findings in the literature , it is argued that the basal ganglia provide a critical mechanism for reinforcing the behavioral significance of prosodic patterns and other temporal representations derived from cue sequences ( Lieberman , 2000 ) , facilitating cortical elaboration of these events We previously reported that the P1 or P50 midlatency evoked potential underwent decreased habituation or disinhibition in patients with Parkinson 's Disease . This sleep state-dependent response appears to be generated by cholinergic elements of the reticular activating system . We attempted to determine if the decreased habituation or disinhibition of the P1 potential would be altered by bilateral pallidotomy . Twenty-three patients who met inclusion criteria for surgery underwent pre- and post-operative evaluation using a Modified United Parkinson 's Disease Rating Scale ( UPDRS ) and P1 potential recordings . Decreased habituation of the P1 potential was determined using a paired stimulus paradigm in which click stimuli were presented at 250 , 500 and 1000 msec interstimulus intervals ( ISI ) . Pre-operatively , patients showed disinhibition of the P1 potential at the 250 msec ISI ( 60 37 % vs. 21 20 % ) and 500 msec ISI ( 78 47 % vs. 43 31 % ) compared to age-matched control subjects . Post-operatively , the same patients showed a significant improvement in habituation of the P1 potential at the same ISIs ( 250 msec 37 21 % ; 500 msec 43 32 % ) . UPDRS scores for these patients pre-operatively were 59 18 and 24 11 post-operatively , result ing in a significant reduction in symptom severity . We conclude that bilateral pallidotomy result ed in a significant improvement in symptom ratings and reduced the disinhibition of the P1 midlatency evoked response To assess cortical and subcortical contributions to phonemic processing , patients with left frontal , temporal-parietal , or cerebellar lesions as well as those with Parkinson 's disease were tested on phonemic identification and production tasks . In Experiment 1 , patients and controls were asked to identify syllables on both a voicing and place of articulation continuum . Subcortical patients were relatively unimpaired at this task whereas cortical patients were less accurate at identifying the endpoints of both continua and exhibited little evidence of categorical perception . For Experiment 2 , controls and patients were asked to produce syllables . Subcortical patients were able to produce contrastive voice onset times ( VOTs ) for voicing cognates although VOT of the voiceless phoneme was more variable for cerebellar patients . Cortical patients showed greater overlap in the production of both VOT and formant transition intervals . These results are discussed in terms of the type of computations hypothesized to originate from each neural area Auditory event-related potentials were recorded using the oddball paradigm in 26 patients with Parkinson 's disease , all treated with L-Dopa . The latency of the P3 wave was significantly greater than in an age-matched controls , and was also correlated with the disease duration , but not with scores on two scales measuring cognitive deficit . One year later , when treatment with a dopaminergic agonist , bromocriptine 20 - 30 mg/day , had been added to the therapeutic regimen , N2 and P3 latencies had increased , whereas several clinical parameters had improved . Thus a longer P3 latency does not seem to be linked to a global cognitive deficit . The use of neuropsychological tests exploring more limited tasks should show the prospect i ve utility of event-related potentials in Parkinson 's disease Auditory event related potentials ( ERPs ) and visual evoked potentials ( VEPs ) were recorded from eight patients with Parkinson 's disease , before and after a single dose of apomorphine . To assess the treatment effects , the patients ' motor state , Benton visual retention test ( BVRT ) , and digit span tests were also examined . After apomorphine , although motor performance improved , the ERP latencies were delayed and the N2-P3 ERP amplitude was significantly diminished by comparison with pretreatment values . These data suggest that apomorphine induces , besides its motor effects in patients with Parkinson 's disease , a slowing down of cognitive processing . Preferential stimulation of dopamine autoreceptors in mesocortical and mesolimbic systems may represent a neural mechanism for these effects . Also , the posttreatment BVRT rotation errors significantly increased , suggesting an apomorphine induced impairment of visuospatial perception Abstract . Rationale : Cholecystokinin ( CCK ) is a neuropeptide which is colocalized with dopamine ( DA ) in neurons of the mesolimbic-frontocortical and nigrostriatal DA system . In animals CCK enhances DA activity in these systems . Objectives : The present study examined the effects of a single intranasal administration of CCK-8 on auditory brain potential ( AEP ) signs of cognitive processing and on motor performance in patients with Parkinson 's disease ( PD ) , known to originate from degeneration of DA neurons primarily in the nigrostriatal DA system . Methods : Thirteen PD patients were examined after medication withdrawal , on two occasions after administration of placebo and 25 µg CCK-8 , and compared with healthy controls matched for age and sex . AEPs were recorded while subjects performed an attention task ( oddball paradigm ) . Results : In the placebo condition , AEPs in the PD patients did not show marked alteration but were rather comparable to those in the controls . In healthy controls , CCK-8 enhanced the P3 complex ( P<0.05 ) and shortened latencies of the N2 and P3 components of the AEP evoked by task relevant target stimuli ( P<0.05 ) . Contrary to expectations , in PD patients these AEP components were distinctly delayed after CCK–8 ( P<0.05 ) . Motor performance was not changed by CCK-8 in PD patients or in controls . Conclusion : Data indicate a deleterious rather than beneficial effect of CCK on cognitive processing in PD patients that might result from a prevailing effect of the neuropeptide on transmitter systems ( e.g. GABAergic ) other than the DA system Nondemented Parkinson ’s disease ( PD ) patients showed increased amplitude of event-related potential component P3 . We recorded 18-channel spontaneous eyes-closed resting EEG and auditory oddball event-related potentials in 29 PD patients and 11 age-matched controls . Combining Mini-Mental State Examination score and oddball P3 counting performance , 15 patients were intellectually normal , 7 moderately , and 7 severely demented . P3 and N1 amplitude and latency , mean amplitude of 1,024 ms post-stimulus ( separate after rare and after frequent stimuli ) , and resting EEG total power for 40 s were computed , and linearly regressed for age , sex , and L-dopa dosage . In nondemented PD patients , increased P3 amplitude was confirmed , but N1 amplitude and mean amplitude after rare and frequent stimuli were also increased as well as – most important – resting EEG total power . With increasing dementia , amplitude and power decreased , and P3 latency increased . Task dem and s can not explain increased P3 amplitude , since similarly increased EEG total power was found during no-task resting . Prospect i ve studies must determine whether P3 amplitude and EEG power in nondemented PD patients can serve as predictors of dementia Recent evidence suggests that the frontal lobe plays an important role in an orienting response to novel events , and that frontal lobe dysfunction is linked to attentional and cognitive deficits in Parkinson 's disease ( PD ) . We tested the hypothesis that the neural network involved in novelty detection may be impaired in PD patients by study ing event-related brain potentials to target and novel stimuli and their correlation to performance in neuropsychological tests in non-demented PD patients . The PD patients showed prolonged P3 latency to novel stimuli compared with age-matched controls , whereas their P3 latency to target stimuli was not different from that in controls . The PD patients also manifested amplitude reduction and less habituation of the P3 to novel stimuli over frontal scalp sites compared with controls . The prolonged latency and frontal reduction of novelty P3 correlated with a poor performance in the Wisconsin Card Sorting Test . These results suggest that the orienting response of PD patients to novel events is impaired and that recording novelty P3 might provide a neurophysiological and quantitative measure of attentional and cognitive deficits linked to the frontal lobe in non-demented PD patients In the present study , we compared the performance of normal subjects in three age groups and of medicated Parkinson 's disease patients on auditory selective attention processes . Two tone sequences were dichotically presented . Subjects responded to deviant tones in the attended location . Event-related potentials ( ERPs ) were recorded from nine scalp electrodes . The old group showed significant decline in hit rate , increase in N1 amplitude , and reduction in P3a , P3b , target negativity , and mismatch negativity amplitude . The amplitude and duration of late Nd increased with age , reflecting modulation of both attended and unattended st and ard ERPs . Although the middle group showed a similar pattern of ERP changes , the effects were generally nonsignificant . The Parkinson 's disease group showed little further disruption of behavioral or ERP measures . However , Parkinson 's disease affected late Nd in the direction opposite of that of aging , reflecting differential modulation of unattended st and ard positivity Bradykinetic‐rigid syndromes are often accompanied by cognitive impairment . Because prominent motor involvement in these disorders may interfere with neuropsychological testing , we used event‐related potentials ( ERPs ) for the assessment of cognition and attention in 41 patients with various bradykinetic‐rigid syndromes of less than 5 years duration : idiopathic Parkinson 's disease corticobasal degeneration , Steele‐Richardson‐Olszewski syndrome ( SRO ) , and multiple system atrophy . Patients were compared with matched normals . ERP abnormalities in the auditory “ oddball ” paradigm were found only in corticobasal degeneration and SRO . ERP abnormalities in selective attention tasks were present in all patient groups , changes in SRO being the most prevalent . Abnormalities in corticobasal degeneration were present under “ less‐attention‐dem and ing ” conditions and suggested involvement of posterior parts of the brain . Multiple system atrophy and idiopathic Parkinson 's disease patient groups had minimal ERP abnormalities . However , reaction times in MSA were longer in all paradigms . The results of the study support the view that bradykinetic‐rigid syndromes involve some attentional deficits , but also have distinct reaction time and ERP characteristics , which may be helpful in differential diagnosis The P300 and regional cerebral blood flow were measured before and after intravenous injection of L-dopa in 10 patients with idiopathic Parkinson 's disease and 10 patients with vascular parkinsonism . The P300 was measured with an evoked potential recorder using an oddball paradigm and the regional cerebral blood flow was measured using the stable xenon computed tomography method . The P300 latency was significantly longer and the regional cerebral blood flow in the cerebral cortex and basal ganglia was significantly lower in the Parkinson 's disease group and the vascular parkinsonism group than in the age-matched healthy control group . The intravenous injection of L-dopa improved these abnormalities significantly in the Parkinson 's disease group but did not improve these abnormalities in the vascular parkinsonism group . Cognitive function is considered to be impaired in Parkinson 's disease and vascular parkinsonism and L-dopa is considered to improve it in Parkinson 's disease BACKGROUND Auditory feedback reflects information on multiple speech parameters including fundamental frequency ( pitch ) and formant properties . Inducing auditory errors in these acoustic parameters during speech production has been used to examine the manner in which auditory feedback is integrated with ongoing speech motor processes . This integration has been shown to be impaired in disorders such as Parkinson 's disease ( PD ) , in which individuals exhibit difficulty adjusting to altered sensory-motor relationships . The current investigation examines whether such sensorimotor impairments affect fundamental frequency and formant parameters of speech differentially . METHODS We employed a sensorimotor compensation paradigm to investigate the mechanisms underlying the control of vocal pitch and formant parameters . Individuals with PD and age-matched controls prolonged a speech vowel in the context of a word while the fundamental or first formant frequency of their auditory feedback was altered unexpectedly on r and om trials , using two magnitudes of perturbation . RESULTS Compared with age-matched controls , individuals with PD exhibited a larger compensatory response to fundamental frequency perturbations , in particular in response to the smaller magnitude alteration . In contrast , the group with PD showed reduced compensation to first formant frequency perturbations . CONCLUSIONS The results demonstrate that the neural processing impairment of PD differentially affects the processing of auditory feedback for the control of fundamental and formant frequency . The heightened modulation of fundamental frequency in response to auditory perturbations may reflect a change in sensory weighting due to somatosensory deficits associated with the larynx , while the reduced ability to modulate vowel formants may result from impaired activation of the oral articulatory musculature Auditory event-related potential ( ERP ) was studied in idiopathic Parkinson 's disease ( PD ) using our new procedures . We examined 12 non-demented patients with PD , and 9 age-matched control subjects . Ninety responses induced by rare stimulation were continuously recorded from Fz , Cz , Pz referred to linked earlobe electrode ( A1A2 ) , and were divided into nine blocks ( one block = 10 responses ) for statistical analysis . We assessed the habituation of auditory ERP to detect delicate changes related to the information processing in PD . N100 and P300 latencies were significantly longer in PD than in control subjects ( p<0.05 ) . P300 latency gradually increased with progression of recording blocks in both PD and control subjects , whereas N100 latency increased only in PD . Three way analysis of variance for P300 amplitude revealed significant effects of subject group , recording electrode site , and trial block . P300 amplitude was smaller in PD than in control subjects . Significant negative correlation between P300 amplitudes and block numbers were observed at Cz and Pz in PD , and at Fz in the control group . Previous reports as well as present results suggest that prolongation of N100 latency might be related to frontal lobe dysfunction , and abnormality of P300 to dysfunction in both the frontal lobe and hippocampus in PD OBJECTIVE Recent studies have shown that the mismatch negativity ( MMN ) , a change-specific component of the event-related potential ( ERP ) , for particular auditory features is de grade d in different clinical population s. This suggests that the MMN could , in principle , reflect the whole profile and extent of the central auditory deficit . In the present article , we tested a new MMN paradigm allowing one to obtain MMNs for several auditory attributes in a short time . METHODS MMN responses to changes in frequency , intensity , duration , location , and to a silent gap occasionally inserted in the middle of a tone were compared between the traditional ' oddball ' paradigm ( a single type of auditory change in each sequence ) and the new paradigm ( two versions ) in which all the 5 types of changes appeared within the same sequence . RESULTS The MMNs obtained in the new paradigm were equal in amplitude to those in the traditional MMN paradigm . CONCLUSIONS We propose a new paradigm that can provide 5 different MMNs in the same time in which usually only one MMN is obtained . The new paradigm enables one to objective ly determine the profile of different auditory discrimination abilities within a very short recording time Selective attention refers to the ability to focus on one channel of information in the presence of distracting other channels . For the visual modality , results on impairments of selective attention have been conflicting in patients with idiopathic Parkinson 's disease ( PD ) . Independent of possible interferences from visual or movement disturbances selective attention can be measured as the so-called ' processing negativity ' ( PN ) using auditory evoked potentials . Therefore , auditory selective attention with the PN was measured in 14 patients with PD and 16 control subjects . Subjects had to attend to tones presented to one ear ( i.e. to press a button to occasionally presented longer tones ) and ignore tones presented to the other ear . Tones were presented at a rate of 1/s ( ' slow ' ) or 2/s ( ' fast ' ) . PN was measured as the difference of the potentials evoked by attended minus ignored st and ard tones . PN was significantly smaller in the PD patients than in the controls with slow presentation . There was no difference between both groups with fast presentation . PN remained unchanged when patients had a 12-h withdrawal of their usual anti-Parkinsonian drug therapy . PD patients and controls did not differ in their P3 component evoked in the usual ' oddball ' task nor in the mismatch negativity evoked by the occasionally longer tones in the PN task . The results provide evidence for an impairment of auditory selective attention that is specific for patients with PD ( i.e. independent of the P3 component ) |
2,687 | 28,701,028 | In line with the conclusions of our previous review , there is a lack of evidence to support or refute psychological interventions in order to reduce postoperative pain in participants undergoing open heart surgery .
We found moderate- quality evidence that psychological interventions reduced mental distress in participants undergoing open heart surgery .
Given the small numbers of studies , it is not possible to draw robust conclusions on the efficacy of psychological interventions on outcomes such as analgesic use , mobility , and time to extubation respectively on adverse events or harms of psychological interventions | BACKGROUND This is an up date of a Cochrane review previously published in 2014 .
Acute postoperative pain is one of the most disturbing complaints in open heart surgery , and is associated with a risk of negative consequences .
Several trials investigated the effects of psychological interventions to reduce acute postoperative pain and improve the course of physical and psychological recovery of participants undergoing open heart surgery .
OBJECTIVES To compare the efficacy of psychological interventions as an adjunct to st and ard care versus st and ard care alone or st and ard care plus attention control in adults undergoing open heart surgery for pain , pain medication , psychological distress , mobility , and time to extubation . | 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 & 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 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 Background and Objective : Anxiety and depression are among the psychological disorders in heart surgeries . Establishing a simple communication is essential to reduce anxiety and depression . Hence , the objective of the present study was to examine the impact of Peplau therapeutic communication model on anxiety and depression in patients , who were c and i date for coronary artery bypass in Al-Zahra Heart Hospital , Shiraz during 2012 - 2013 . Methods : This is a clinical trial in which 74 patients were r and omly divided into intervention and control groups , each consisted of 37 patients . Anxiety and depression levels were assessed before , and two and four months after intervention using the Hospital Anxiety and Depression Scale ( HADS ) . Seven therapeutic communication sessions were held in four stages . Data were analyzed with the SPSS ( version 16 ) using analysis of covariance . Results : The mean anxiety and depression levels decreased in the intervention group after the therapeutic communication ( p<0.01 ) . Anxiety scores in the intervention group before and after intervention were 10.23 and 9.38 , respectively . While the corresponding scores in the control group were 10.26 and 11.62 , respectively . Depression scores in the intervention group before and after intervention were 11 and 9.13 , respectively . The corresponding scores in the control group were 11.30 and 12.08 , respectively . Conclusion : The results demonstrated the positive role of therapeutic communication in reducing anxiety and depression of the patients . Therefore , the therapeutic communication is recommended as a simple , cost effective and efficient method in this area During general anesthesia the possibility of subconscious perception of intraoperative events is a controversial subject . Some studies found that positive verbal suggestions , or music improved intraoperative relaxation and postoperative recovery . The aim of the current study was to evaluate the effect of prayer and relaxation technique applied while patients are under general anesthesia for open-heart surgery . A r and omized , controlled , double-blind trial study included 78 patients who underwent cardiac surgery . During the surgery the patients used a headphone connected to a CD player . They were r and omly divided into three groups . One group listened to prayer during the surgery , the other listened to relaxation technique and one , placebo . There was only one significant finding : the prayer group is less likely to believe that prayer would assist conventional medical treatments . Although not statistically significant , we discussed the length of stay ( LOS ) after surgery and the incidence of sternal wound infection The effectiveness of in-hospital self-care patient education , delivered to patients following heart surgery , is question able , as evidence indicates individuals are not able to absorb and /or retain information at this time . In the absence of adequate instruction , individuals will not have the relevant information to engage in specific self-care behaviors , result ing in the onset of complications and /or hospital readmissions . The purpose of this pilot study was to collect preliminary evidence to demonstrate the impact of an individualized education intervention given above and beyond usual care , delivered , at two points in time , following hospital discharge . A r and omized controlled trial was used in which 34 patients were r and omly assigned to one of two groups . Chi-square analyses to examine differences between groups on complications and hospital readmission rates were conducted . Findings point to the impact of the intervention in reducing the number of hospital readmissions and complications at 3 months following hospital discharge Background : The effect of preoperative education on anxiety and postoperative outcomes of cardiac surgery patients remains unclear . Aim : The aim of the study was to estimate the effectiveness of a nurse-led preoperative education on anxiety and postoperative outcomes . Methods : A r and omised controlled study was design ed . All the patients who were admitted for elective cardiac surgery in a general hospital in Athens with knowledge of the Greek language were eligible to take part in the study . Patients in the intervention group received preoperative education by specially trained nurses . The control group received the st and ard information by the ward personnel . Measurements of anxiety were conducted on admission-A , before surgery-B and before discharge-C by the state – trait anxiety inventory . Results : The sample consisted of 395 patients ( intervention group : 205 , control group : 190 ) . The state anxiety on the day before surgery decreased only in the intervention group ( 34.0 ( 8.4 ) versus 36.9 ( 10.7 ) ; P=0.001 ) . The mean decrease in state score during the follow-up period was greater in the intervention group ( P=0.001 ) . No significant difference was found in the length of stay or readmission . Lower proportions of chest infection were found in the intervention group ( 10 ( 5.3 ) versus 1 ( 0.5 ) ; P=0.004 ) . Multivariate linear regression revealed that education and score in trait anxiety scale on admission are independent predictors of a reduction in state anxiety . Conclusion : Preoperative education delivered by nurses reduced anxiety and postoperative complications of patients undergoing cardiac surgery , but it was not effective in reducing readmissions or length of stay Background : Patients undergoing coronary artery bypass graft surgery often experience a range of problems and symptoms such as immobility , pain and insufficient sleep . Results from trials investigating testing in-hospital physical exercise or psychological intervention have been promising . However , no r and omized clinical trials have tested a comprehensive rehabilitation programme consisting of both physical exercise and psycho-education in the early rehabilitation phase . Aims : The aims of the present SheppHeart pilot r and omized clinical trial were to evaluate the feasibility of patient recruitment , patient acceptance of the intervention , safety and tolerability of the intervention . Methods and design : Sixty patients admitted for coronary artery bypass graft were r and omized 1:1:1:1 to : 1 ) physical exercise plus usual care , or 2 ) psycho-educational intervention plus usual care , or 3 ) physical exercise and psycho-educational plus usual care , or 4 ) usual care alone during a four week period after surgery . Results : The acceptability of trial participation was 67 % during the three month recruitment period . In the physical exercise groups , patients complied with 59 % of the total expected training sessions during hospitalization . Nine patients ( 30 % ) complied with > 75 % and nine patients ( 30 % ) complied with 50 % of the planned exercise sessions . Eleven patients ( 42 % ) participated in ⩾75 % of the four consultations and six patients ( 23 % ) participated in 50 % of the psycho-educational programme . Conclusion : Comprehensive phase one rehabilitation combining physical exercise and psycho-education in coronary artery bypass graft patients shows reasonably high inclusion , feasibility and safety Background : Relevant discharge information about the use of analgesic medication and other strategies may help patients to manage their pain more effectively and prevent postoperative persistent pain . Aims : To examine patients ’ pain characteristics , analgesic intake and the impact of an educational pain management booklet intervention on postoperative pain control after cardiac surgery . Concerns about pain and pain medication prior to surgery will also be described . Methods : From March 2012 to September 2013 , 416 participants ( 23 % women ) were consecutively enrolled in a r and omized controlled trial . The intervention group received usual care plus an educational booklet at discharge with supportive telephone follow-up on postoperative day 10 , and the control group received only usual care . The primary outcome was worst pain intensity ( The Brief Pain Inventory – Short Form ) . Data about pain characteristics and analgesic use were collected at 2 weeks and at 1 , 3 , 6 and 12 months post-surgery . General linear mixed models were used to determine between-group differences over time . Results : Twenty-nine percent of participants reported surgically related pain at rest and 9 % reported moderate to severe pain at 12 months post-surgery . Many participants had concerns about pain and pain medication , and analgesic intake was insufficient post-discharge . No statistically significant differences between the groups were observed in terms of the outcome measures following surgery . Conclusion : Postoperative pain and inadequate analgesic use were problems for many participants regardless of group allocation , and the current intervention did not reduce worst pain intensity compared with control . Further examination of supportive follow-up monitoring and /or self-management strategies post-discharge is required Background : Human and animal laboratory studies have shown that stress delays healing of st and ardized punch biopsy wounds . Purpose : This 5-week prospect i ve study of 17 women who underwent elective gastric bypass surgery addressed the association between postsurgical pain intensity and subsequent healing of a st and ard 2.0-mm punch biopsy wound . Methods : Participants were assessed 1 week before surgery , within 3 hr before surgery , 1 to 3 days postsurgery , and at weekly intervals for 4 weeks following surgery . Results : Patient ratings of greater acute postsurgical pain , averaged over Days 1 and 2 postsurgery , and greater persistent postsurgical pain , averaged over 4 weekly postsurgery pain ratings , were significantly associated with subsequent delayed healing of the punch biopsy wound . Presence of depressive symptoms on the day of surgery , pre-existing persistent pain , and medical complications following initial discharge from the hospital were not related to wound healing . Depressive symptoms on the day of surgery and pre-existing persistent pain did predict persistent postsurgical pain intensity . Conclusions : These findings extend the previous laboratory models of wound healing to a surgical population , providing the first evidence that pain plays an important role in postsurgery wound healing , a key variable in postsurgical recovery AIM This study aim ed to investigate the effects of a peer education on cardiac self-efficacy ( CSE ) and readmission of the patients undergoing bypass surgery . BACKGROUND Self-efficacy is an antecedent vital factor in both initiating and maintaining healthy behaviours . It significantly improves after effects of heart attacks , anxiety and diminishes the possibility of readmission . DESIGN This study is a r and omized-controlled trial . METHOD Sixty patients undergoing bypass surgery were chosen and assigned equally into the control and intervention groups . While routine education was presented to the patients in the control group , intervention group were taught using the peer education in two sessions . CSE of all the selected patients was assessed orderly in 5 days , 4 weeks and 8 months after surgery . Moreover , their readmission was investigated after 8 months from surgery . Data was collected using demographic and the CSE scale . Data were also analysed by using χ2 , Kolmogorov-Smirnov and repeated measures analysis of variance tests . RESULTS The mean score of CSE in the intervention group was significantly different from the corresponding number in the control group in all three stages of data collecting ( p < 0·001 ) . Compared to the control group , a smaller number of the patients in the intervention group were readmitted to the hospitals after 8 months ( p = 0·011 ) . CONCLUSIONS Implementation of peer education has positive effects on CSE in patients who have bypass surgery and reduces their hospital readmission . It can be beneficial to apply this method as an educative-supportive approach in cardiac surgery fields . RELEVANCE TO CLINICAL PRACTICE Implementation of peer education has positive effects on CSE in these patients and reduces their hospital readmission 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 The purpose of this r and omized trial was to determine whether coronary artery bypass graft surgery patients and their caregivers who received telehealth follow-up had greater improvements in anxiety levels from pre-surgery to 3 weeks after discharge than did those who received st and ard care . Secondary outcomes included changes in depressive symptoms and patients ' contacts with physicians . No group differences were noted in changes in patients ' anxiety and depressive symptoms , but patients in the telehealth group had fewer physician contacts ( p = .04 ) . Female caregivers in the telehealth group had greater decreases in anxiety than those in st and ard care ( p < .001 ) , and caregivers of both genders in the telehealth group had greater decreases in depressive symptoms ( p = .03 ) Background : Some general hospitals within the German health system provide supportive interventions , psychological as well as spiritual , to their patients . It remains to be proven if these interventions are effective when used in routine clinical practice . Aim : To evaluate the effectiveness of psychological and spiritual interventions on improving recovery following bypass surgery . Methods : The BY.PASS study is a pragmatic , patient preference trial ( IS RCT N 07297983 ) . Adult patients scheduled for elective coronary bypass surgery were enrolled . Patients were assigned to study conditions according to their personal preference : preference for psychological interventions , for spiritual interventions or for no intervention . Patients who were open for any kind of intervention were r and omly assigned either to psychological or spiritual interventions . During a control period , patients were asked about their preference , but did not receive any interventions . Primary outcomes of the study were in-hospital morbidity and early mortality . Psychological measures served as secondary outcomes . Results : A total of 847 patients were enrolled . Patients of the control ( n = 260 ) and the intervention group ( n = 269 ) who explicitly wanted to have interventions were compared . No significant treatment effects either for morbidity ( d = 0.08 , 95 % CI –0.09 to 0.25 ) , or for mortality ( OR = 1.81 ; 95 % CI 0.50–6.57 ) could be found . A reduction of negative mood result ed from both interventions . Conclusions : Although the effects observed were small , the study can serve as a basis to discuss method ological as well as theoretical aspects of a pragmatic trial , based upon patients ’ preferences BACKGROUND The high incidence of symptomatic anxiety and depression in coronary artery bypass graft ( CABG ) patients may lead to impaired quality of life and increased morbidity and mortality . This prospect i ve longitudinal study on CABG patients should provide data for future preoperative and postoperative psychotherapeutic interventions . METHODS From 2009 to 2010 , 135 consecutive patients who were able and prepared were consulted by one interviewer immediately before 1 week ( early ) and 6 months ( late ) after surgery to complete the " Hospital Anxiety and Depression Scale " question naire . RESULTS Compared with the st and ard population , anxiety scores ( AS ) were preoperatively elevated in 39.3 % of the patients . Early and late after surgery , AS had decreased to 34.4 % ( not significant [ n.s . ] ) and 28.9 % ( p < 0.01 ) . Before surgery , depression scores ( DS ) were elevated in 20.7 % . Early and late after surgery , DS further increased to 24.0 % ( n.s . ) and 28.0 % (n.s.).Preoperative elevated DS appeared to correlate with increased complications . Mortality was not associated with elevated AS or DS . Both scores were not affected by on- or off-pump surgery . CONCLUSION Remarkably high AS and elevated DS late postoperatively require psychotherapeutic support even after seemingly successful CABG Post-operative fatigue is an important subjective problem for surgical patients , but its basis is unknown , and the possibility of a psychological component has been neglected . To investigate its putative physiological and psychological bases , 74 patients undergoing coronary artery bypass graft surgery were studied . Circulating catecholamine levels were measured at intervals perioperatively and question naires were used to measure fatigue , depression and anxiety up to 30 days post-operatively . We tested whether fatigue was related either to the catecholamine or to the emotional responses to surgery . The second element to the design was a controlled r and omized study : patients underwent different forms of psychological preparation or a no-treatment control procedure in an attempt to test whether post-operative fatigue was amenable to psychological manipulation . Psychological preparation had no effect . Fatigue at 30 days was greatest in patients whose noradrenaline levels were greatest perioperatively . Independently of this relationship , fatigue at 30 days correlated with concurrent levels of depression and anxiety . Post-operative fatigue has both physiological and psychological correlates 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 Research to date indicates that the number of coronary artery bypass graft ( CABG ) surgery patients affected by depression ( i.e. , major , minor , dysthymia ) approximates between 30 % and 40 % of all cases . A longst and ing empirical interest on psychosocial factors in CABG surgery patients highlights an association with increased risk of morbidity in the short and longer term . Recent evidence suggests that both depression and anxiety increase the risk for mortality and morbidity after CABG surgery independent of medical factors , although the behavioral and biological mechanisms are poorly understood . Though neither depression nor anxiety seem to markedly affect neuropsychological dysfunction , depression confers a risk for incident delirium . Following a comprehensive overview of recent literature , practical advice is described for clinicians taking into consideration possible screening aids to improve recognition of anxiety and depression among CABG surgery patients . An overview of contemporary interventions and r and omized , controlled trials are described , along with suggestions for future CABG surgery research INTRODUCTION Cardiac surgery has been the intervention of choice in many cases of cardiovascular diseases . Susceptibility to postoperative complications , cardiac rehabilitation is indicated . Therapeutic re sources , such as virtual reality has been helping the rehabilitational process . The aim of the study was to evaluate the use of virtual reality in the functional rehabilitation of patients in the postoperative period . METHODS Patients were r and omized into two groups , Virtual Reality ( VRG , n = 30 ) and Control ( CG , n = 30 ) . The response to treatment was assessed through the functional independence measure ( FIM ) , by the 6-minute walk test ( 6MWT ) and the Nottingham Health Profile ( NHP ) . Evaluations were performed preoperatively and postoperatively . RESULTS On the first day after surgery , patients in both groups showed decreased functional performance . However , the VRG showed lower reduction ( 45.712.3 ) when compared to CG ( 35.0612.09 , P<0.05 ) in first postoperative day , and no significant difference in performance on discharge day ( P>0.05 ) . In evaluating the NHP field , we observed a significant decrease in pain score at third assessment ( P<0.05 ) . These patients also had a higher energy level in the first evaluation ( P<0.05 ) . There were no differences with statistical significance for emotional reactions , physical ability , and social interaction . The length of stay was significantly shorter in patients of VRG ( 9.410.5 days vs. 12.2 1 0.9 days , P<0.05 ) , which also had a higher 6MWD ( 319.9119.3 meters vs. 263.5115.4 meters , P<0.02 ) . CONCLUSION Adjunctive treatment with virtual reality demonstrated benefits , with better functional performance in patients undergoing cardiac surgery Background Heart valve diseases are common with an estimated prevalence of 2.5 % in the Western world . The number is rising due to an ageing population . Once symptomatic , heart valve diseases are potentially lethal , and heavily influence daily living and quality of life . Surgical treatment , either valve replacement or repair , remains the treatment of choice . However , post surgery , the transition to daily living may become a physical , mental and social challenge . We hypothesise that a comprehensive cardiac rehabilitation programme can improve physical capacity and self-assessed mental health and reduce hospitalisation and healthcare costs after heart valve surgery . Methods A r and omised clinical trial , CopenHeartVR , aims to investigate whether cardiac rehabilitation in addition to usual care is superior to treatment as usual after heart valve surgery . The trial will r and omly allocate 210 patients , 1:1 intervention to control group , using central r and omisation , and blinded outcome assessment and statistical analyses . The intervention consists of 12 weeks of physical exercise , and a psycho-educational intervention comprising five consultations . Primary outcome is peak oxygen uptake ( VO2 peak ) measured by cardiopulmonary exercise testing with ventilatory gas analysis . Secondary outcome is self-assessed mental health measured by the st and ardised question naire Short Form 36 . Also , long-term healthcare utilisation and mortality as well as biochemistry , echocardiography and cost-benefit will be assessed . A mixed- method design is used to evaluate qualitative and quantitative findings encompassing a survey-based study before the trial and a qualitative pre- and post-intervention study . Discussion The study is approved by the local regional Research Ethics Committee ( H-1 - 2011 - 157 ) , and the Danish Data Protection Agency ( j.nr . 2007 - 58 - 0015).Trial registration Clinical Trials.gov ( http://NCT01558765 ) Background Single-session hypnosis has never been evaluated as a premedication technique in patients undergoing coronary artery bypass grafting ( CABG ) . The aim of the present study was to evaluate the beneficial effects of clinical hypnotherapy on perioperative anxiety , pain perception , sedation , and necessity for ventilator assistance in patients undergoing CABG . Methods Double-blind , r and omized , clinical trial was performed . Forty-four patients undergoing CABG surgery were r and omized into two groups . The patients in group A received preprocedural hypnosis by an anesthesiologist . Patients in group B ( control ) had only information on the surgical intervention by the same anesthesiologist . State-Trait-Anxiety Index-I ( STAI-I ) and Beck Depression Inventory ( BDI ) were performed preoperatively in both groups . Visual analog scale ( VAS ) and Ramsay sedation scale ( RSS ) were evaluated on 0th , 1st , 2nd , 4th , 6th , 8th , 10th , 12th , and 24th hours , postoperatively . Postoperative anxiety level , analgesic drug consumption , and duration of ventilator assistance and intensive care unit ( ICU ) stay were also documented . Results When anxiety and depression levels were compared , significantly lower STA-I and BDI values were detected in group A after hypnotherapy ( p = 0.001 , p = 0.001 , respectively ) . Significantly less total doses of remifentanil ( 34.4 ± 11.4 vs. 50.0 ± 13.6 mg ) and morphine ( 4.9 ± 3.3 vs. 13.6 ± 2.7 mg ) were administered in group A in the postoperative period . Ventilator assistance duration ( 6.8 ± 2.0 vs. 8.9 ± 2.7 hours ) was also shorter in group A when compared with that in group B ( p = 0.007 ) . Conclusion Hypnosis session prior to surgery was an effective complementary method in decreasing presurgical anxiety , and it result ed in better pain control as well as reduced ventilator assistance following CABG surgery Background Placebo effects contribute substantially to outcome in most fields of medicine . While clinical trials typically try to control or minimize these effects , the potential of placebo mechanisms to improve outcome is rarely used . Patient expectations about treatment efficacy and outcome are major mechanisms that contribute to these placebo effects . We aim ed to optimize these expectations to improve outcome in patients undergoing coronary artery bypass graft ( CABG ) surgery . Methods In a prospect i ve three-arm r and omized clinical trial with a 6 month follow-up , 124 patients scheduled for CABG surgery were r and omized to either a brief psychological pre-surgery intervention to optimize outcome expectations ( EXPECT ) ; or a psychological control intervention focusing on emotional support and general advice , but not on expectations ( SUPPORT ) ; or to st and ard medical care ( SMC ) . Interventions were kept brief to be feasible with a heart surgery environment ; “ dose ” of therapy was identical for both pre-surgery interventions . Primary outcome was disability 6 months after surgery . Secondary outcomes comprised further clinical and immunological variables . Results Patients in the EXPECT group showed significantly larger improvements in disability ( −12.6 ; −17.6 to −7.5 ) than the SMC group ( −1.9 ; −6.6 to + 2.7 ) ; patients in the SUPPORT group ( −6.7 ; −11.8 to 1.7 ) did not differ from the SMC group . Comparing follow-up scores and controlling for baseline scores of EXPECT versus SUPPORT on the variable disability only revealed a trend in favor of the EXPECT group ( P = 0.09 ) . Specific advantages for EXPECT compared to SUPPORT were found for mental quality of life and fitness for work ( hours per week ) . Both psychological pre-surgery interventions induced less pronounced increases in pro-inflammatory cytokine concentrations reflected by decreased interleukin-8 levels post-surgery compared to changes in SMC patients and lower interleukin-6 levels in patients of the EXPECT group at follow-up . Both pre-surgery interventions were characterized by great patient acceptability and no adverse effects were attributed to them . Considering the innovative nature of this approach , replication in larger , multicenter trials is needed . Conclusions Optimizing patients ’ expectations pre-surgery helps to improve outcome 6 months after treatment . This implies that making use of placebo mechanisms has the potential to improve long-term outcome of highly invasive medical interventions . Further studies are warranted to generalize this approach to other fields of medicine . Trial registration Ethical approval for the study was obtained from the IRB of the Medical School , University of Marburg , and the trial was registered at ( NCT01407055 ) on July 25 , 2011 The aim of this r and omized controlled trial was to determine the effect of jaw relaxation , music and the combination of relaxation and music on postoperative pain after major abdominal surgery during ambulation and rest on postoperative days 1 and 2 . Opioid medication provided for pain , following abdominal surgery , does not always give sufficient relief and can cause undesired side effects . Thus , additional interventions such as music and relaxation may provide more complete relief . Previous studies have found mixed results due to small sample sizes and other method ological problems . In a rigorous experimental design , 500 subjects aged 18 - 70 in five Midwestern hospitals were r and omly assigned by minimization to a relaxation , music , relaxation plus music , or control group . Interventions were taught preoperatively and tested postoperatively . The same amount of time was spent with subjects in the control group . Pain was measured with the visual analogue sensation and distress of pain scales . Demographic and surgical variables , and milligrams of parenteral or oral opioids in effect at the time of testing were not significantly different between the groups , nor did they correlate with pain scores . Controlling for pretest sensation and distress , orthogonal a priori contrasts and multivariate analysis of covariance indicated that the three treatment groups had significantly less pain than the controls , ( P = 0.028 - 0.000 ) which was confirmed by the univariate analysis of covariance ( P = 0.018 - 0.000 ) . Post hoc multivariate analysis revealed that the combination group had significantly less sensation and distress of pain than the control group on all post-tests ( P = 0.035 - 0.000 ) , and the relaxation and music groups had significantly less on all tests ( P = 0.022 - 0.000 ) except after ambulation . At post ambulation those using relaxation did not have significantly less pain than the controls on both days and those using music did not on day 1 , although there were some univariate effects . A corresponding significant decrease in mastery of the interventions from pre to post ambulation suggests the need for reminders to focus on the intervention during this increased activity . Physicians and nurses preparing patients for surgery and caring for them afterward , should encourage patients to use relaxation and music as adjuvants to medication for postoperative pain Abstract Morbidity ( i.e. , elevated anxiety and depression ) is a common feature of coronary artery bypass surgery ( CABS ) patients , pre- and postoperatively . Since hypnotherapy can possibly reduce morbidity in CABS patients , the aim of this study was to determine the feasibility of hypnotherapeutic ego strengthening ( HES ) to facilitate patient coping with concomitant anxiety and depression . Fifty patients were r and omly assigned to a non-intervention control group ( n = 25 ) and an experimental group ( n = 25 ) and exposed to a pre- and postoperative HES intervention . Anxiety and depression were assessed with the Beck Depression Inventory and Profile of Mood States , administered preoperatively , at discharge , and at 6-week follow-up . Findings confirmed large practical reductions of anxiety and depression in the experimental group and were maintained at follow-up , while a trend towards increased depression levels occurred in the control group . Although not generalizable , results suggest broadened applications of hypnotherapy with patients in cardiac centers A r and omized , single-blinded , placebo-controlled trial examined the benefits of taped therapeutic suggestions and taped music in coronary-artery-bypass patients . Sixty-six patients listened to either suggestion tapes or music tapes , intraoperatively and postoperatively ; 29 patients listened to blank tapes intraoperatively and listened to no tapes postoperatively . Half the patients who listened to a tape found it helpful . There were no significant differences between groups in length of SICU or postoperative hospital stay , narcotic usage , nurse ratings of anxiety and progress , depression , activities of daily living , or cardiac symptoms . There were no significant differences in these same outcomes between the patients who were helped by the tapes and the patients not helped . These results suggest that if taped therapeutic suggestions have a measurable effect upon cardiac surgery patients , demonstrating this effect will require more detailed patient evaluations to identify subgroups of patients responsive to this type of intervention OBJECTIVE To test the efficacy of an information intervention upon emotional recovery following coronary artery bypass surgery . METHODS R and omized trial . Video information was combined with individualized information sessions carried out by nurses at admission and at discharge from the hospital . The video was shown pre-operatively and again during the session at admission . Patients were helped to express their questions and worries and congruent information and support was provided . Control group patients received st and ardized information and no video . Recordings were made at baseline , discharge from hospital and during a 2 years follow-up period . RESULTS One hundred and nine patients were r and omized to the intervention or the control groups . A MANOVA was used to test of the variance of the outcome variables at each time point . At discharge intervention patients reported less anxiety ( p = 0.046 ) and better subjective health ( p = 0.005 ) . They reported better subjective health during the whole follow-up period ( 0.040 > or = p > or = 0.000 ) , less anxiety up to 1 year ( 0.042 > or = p > or = 0.004 ) , and less depression from 6 months to 2 years following discharge ( 0.023 > or = p > or = 0.004 ) . CONCLUSION The effects of the intervention probably relate to the combined use of the video and patient centered information sessions . PRACTICE IMPLICATION S The intervention can easily be implemented in clinical practice and nurses strongly identified with its principles For this study a r and omized clinical trial was design ed to test the effects of an early home recovery information intervention on physical functioning , psychological distress , and symptom frequency 1 month following coronary artery bypass graft surgery ( CABG ) . Recovery outcomes were compared between two groups : those receiving an audiotape of information on expected physical sensations and their management ( Cardiac Home Information Program [ CHIP ] ) in addition to the usual care , and those receiving the usual cardiac discharge information protocol . A nonprobability sample of 180 patients ( 84 women and 96 men ; mean age = 62 years ) was equally distributed between the two study groups . When controlling for age , comorbidity , and cardiac functional status , the results showed positive effects on physical functioning in women and psychological distress , vigor and fatigue in men . Consistent with other studies , women had worse physical functioning and more symptom frequency than men . These findings indicate that the CHIP intervention is an effective method to prepare CABG patients for home recovery OBJECTIVE The purpose of this study was to determine the effectiveness of an information and support telephone intervention for reducing anxiety in patients who have undergone coronary artery bypass graft surgery and their partners . DESIGN The study is a r and omized controlled trial . Intervention began at discharge ; 6 telephone calls were made to patients and partners over 7 weeks . Primary outcome was Beck Anxiety Inventory measured at baseline in hospital , at home on day 3 , week 4 , and week 8 . SAMPLE The subjects were 131 patients who have undergone elective coronary artery bypass graft surgery and their partners . RESULTS Patients ' anxiety was moderate to severe the day before discharge . It was significantly lower in the treatment group than in the control group at day 2 at home . Partners always had lower anxiety than patients . A more sustained decrease in anxiety in the partner treatment group was found at both day 2 and week 4 . CONCLUSION Intervention effect is in the early period after discharge-- the time most affected by reduced lengths of stay 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 Introduction Depression during or shortly after hospitalization elevated two to three times the risk of mortality or nonfatal cardiac events , significantly increasing the morbidity and mortality of these patients . Objective To assess the impact of revascularization on symptoms of depression in patients with coronary artery disease . Methods A prospect i ve cohort study of 57 patients of both sexes undergoing coronary artery bypass grafting between June 2010 and June 2011 . We used the SF-36 to assess quality of life , and the Beck Depression Inventory to detect depressive symptoms , applied preoperatively and six months . Results The prevalence of patients aged 60 - 69 years was 22 patients ( 38.60 % ) , 39 men ( 68.42 % ) , 26 described themselves as mixed race ( 45.61 % ) , 16 literate ( 28.07 % ) and 30 married ( 52.63 % ) . The beck depression inventory score demonstrated increased after revascularization : 15 patients mild ( 26.32 % ) at time zero to 17 ( 29.82 % ) after . And with moderate , seven patients ( 12.28 % ) before and 10 ( 17.54 % ) after . In the categories of individuals with decreased minimum degree of 32 ( 56.14 % ) to 28 ( 49.12 % ) , and severe of three ( 5.26 % ) for two ( 3.51 % ) patients . Association was observed between beck depression inventory , gender , age , lifestyle , comorbidities and quality of life . Conclusion There was a high prevalence of elevated beck depression inventory scores , lowest scores of depressive symptoms among men and association between the improvement of quality of life scores and beck depression inventory Background Approximately two thirds of adults undergoing cardiac surgery suffer from moderate to severe postoperative pain . Assisting patients with pain management is therefore critical to prevent its negative consequences . Information technologies have become part of our lifestyle and can facilitate the implementation of interventions to manage pain in a busy care setting . A computer-tailored and Web-based intervention — referred to as SOUtien à L’AutoGEstion-Traitement-Assistance Virtuelle Infirmière-Enseignement (SOULAGE-TAVIE)—for the self-management of pain was developed . Findings from a previous pilot r and omized controlled trial ( RCT ) provided some evidence of the feasibility and preliminary effectiveness of this intervention in decreasing pain interference with a few postoperative activities and by modulating pain beliefs and analgesic intake . However , its acceptability from the patient ’s perspective remains unclear . Moreover , the proportion of women is much lower in the cardiac surgical population , making it difficult to detect differences in experiences between men and women . Objective The objectives were ( 1 ) to describe SOULAGE-TAVIE ’s acceptability from the perspective of adults experiencing pain after cardiac surgery and ( 2 ) to compare the perceptions of men and women . Methods A mixed- method approach was used to capture the various attributes of patients ’ perceptions of the intervention ’s acceptability and to compare the perceptions of men and women . Quota sample s of men ( n=10 ; mean age 62.5 years , SD 7.3 ) and women ( n=10 ; mean age 64.3 years , SD 10.7 ) who had cardiac surgery in the past month were invited to view the intervention , complete a brief question naire rating its acceptability , and then to discuss each component in a 60-minute , semistructured interview . Mann-Whitney U tests were used to compare groups . The transcripts were content analyzed to generate themes based on patients ’ experiences with the intervention and reports of acceptability . The content of each category and subcategory were compared between men and women . Frequency counts were also done to vali date the emergence of a difference between the 2 subgroups . Results Participants perceived the intervention to be very acceptable in terms of content and format , and tended to describe awareness-raising and convenient support experiences . Women scored higher than men in terms of the intervention ’s appropriateness ( U=13.5 , P=.008 ) . They were willing to adhere to the intervention based on the importance and relevance of the advice provided , whereas men were more focused on the delivery mode and its flexibility . Conclusions This study underlined the acceptability of computer tailoring and persuasive communication to modulate pain beliefs and attitudes in an acute care context . Both men and women appreciated the Web-based interface and general self-guided approach of the intervention . The delivery of SOULAGE-TAVIE across the continuum of care seems to be an interesting avenue to influence the transition from acute to chronic postoperative pain 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 The final development of the Sickness Impact Profile ( SIP ) , a behaviorally based measure of health status , is presented . A large field trial on a r and om sample of prepaid group practice enrollees and smaller trials on sample s of patients with hyperthyroidism , rheumatoid arthritis and hip replacements were undertaken to assess reliability and validity of the SIP and provide data for category and item analyses . Test-retest reliability ( r = 0.92 ) and internal consistency ( r = 0.94 ) were high . Convergent and discriminant validity was evaluated using the multitrait – multi method technique . Clinical validity was assessed by determining the relationship between clinical measures of disease and the SIP scores . The relationship between the SIP and criterion measures were moderate to high and in the direction hypotheszed . A technique for describing and assessing similarities and differences among groups was developed using profile and pattern analysis . The final SIP contains 136 items in 12 categories . Overall , category , and dimension scores may be calculated Depression and anxiety are associated with increased risk of postoperative cardiac events and death in patients who have undergone coronary artery bypass graft surgery . These risks persist even several months after the procedure . Guided imagery has been used with cardiac surgery patients for some time and with numerous anecdotal reports of considerable benefit . In addition , this therapy is low-cost and easy to implement , and the literature holds ample evidence for its efficacy in symptom reduction in various patient population s. It was thus hypothesized that preoperative use of guided imagery would reduce postoperative distress in patients undergoing coronary artery bypass graft . Fifty-six patients scheduled to undergo coronary artery bypass graft at Columbia University Medical Center were r and omized into 3 groups : guided imagery , music therapy , and st and ard care control . Patients in the imagery and music groups listened to audiotapes preoperatively and intraoperatively . All patients completed psychological , complementary medicine therapies use , and other assessment s preoperatively and at 1 week and 6 months postoperatively . Only preoperative distress was predictive of postoperative distress at follow-up . Use of complementary medicine therapies was high in all groups and this fact , in addition to the small sample size , may have accounted for the lack of significant relationship between imagery and postoperative distress . Regardless , this complementary and alternative medicine therapy remains palatable to patients . Given its efficacy in other patient population s , it is worth exploring its potential utility for this population with a larger sample 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 AIM The aim of the study was to test the effect of an audiotape giving concrete objective information and strategies to reduce symptoms , psychological distress and enhance physical functioning in patients having coronary artery bypass grafts . BACKGROUND The period following hospital discharge is stressful for patients having coronary artery bypass grafts . Evident-based interventions are needed to improve outcomes in Thai population s following coronary artery bypass graft surgery . METHODS A r and omized controlled trial was conducted during 2004 - 2005 . A sample of 120 Thai patients having coronary artery bypass grafts was r and omly assigned to an intervention group or a control group . The intervention group was given an information audiotape the day prior to hospital discharge , and encouraged to listen to it as many times as necessary . Participants were interviewed using vali date d instruments predischarge and at 2 weeks and 4 weeks after discharge . FINDINGS Participants in the intervention group had statistically significantly fewer symptoms of shoulder , back or neck pain and lack of appetite , and increased physical activity after discharge , compared to the control group . This effect remained statistically significant after controlling for age , gender , co-morbidity and presurgical cardiac functional status . However , no statistically significant difference in psychological distress was observed . CONCLUSION Nurses can use an audiotape containing preparatory information to improve outcomes for patients having coronary artery bypass grafts during the few weeks after discharge from hospital . Further studies are recommended to improve its effect on psychological distress This study tested the efficacy of the Information-Motivation-Behavioral ( IMB ) skills model-based intervention to promote adherence among patients undergoing Coronary Artery Bypass Grafting ( CABG ) surgery , and evaluated the relationship of psychological variables with adherence . A total of 152 CABG patients were r and omly assigned to either an intervention group or to a st and ard care control group . Participants completed pretest measures and were reassessed one and three months later . Findings revealed that the intervention group was significantly more adherent , which showed support for the effectiveness of the IMB-based intervention . Furthermore , psychological factors played an important role in patient adherence BACKGROUND Despite high rates of postcardiac surgery depression , studies of depression treatment in this population have been limited . OBJECTIVE The aim of this study was to evaluate early cognitive behavioral therapy ( CBT ) in a home environment in patients recovering from cardiac surgery . METHODS : From July 2006 through October 2009 , we conducted a r and omized controlled trial and enrolled 808 patients who were screened for depressive symptoms using the Beck Depression Inventory ( BDI ) in the hospital and 1 month later . Patients were interviewed using the Structured Clinical Interview for DSM-IV ; those who met criteria for clinical depression ( n = 81 ) were r and omized to CBT ( n = 45 ) or usual care ( UC ; n = 36 ) . After completion of the UC period , 25 individuals were offered later CBT ( UC + CBT ) . RESULTS Main outcomes ( depressive symptoms [ BDI ] and clinical depression [ Structured Clinical Interview for DSM-IV ] ) were evaluated after 8 weeks using intention-to-treat principles and linear mixed models . Compared with the UC group , in the CBT group , there was greater decline in BDI scores ( β = 1.41 ; 95 % confidence interval [ CI ] , 0.81 - 2.02 ; P = < .001 ) and greater remission of clinical depression ( 29 [ 64 % ] vs 9 [ 25 % ] ; number need to treat , 2.5 ; 95 % CI , 1.7 - 4.9 ; P < .001 ) . Compared with the early CBT group ( median time from surgery to CBT , 45.5 days ) the later UC + CBT group ( median time from surgery to CBT , 122 days ) also experienced a reduction in BDI scores , but the group × time effect was smaller ( β = 0.79 ; 95 % CI , 0.10 - 1.47 ; P = .03 ) and remission rates between the 2 groups did not differ . CONCLUSIONS Early home CBT is effective in depressed postcardiac surgery patients . Early treatment is associated with greater symptom reduction than similar therapy given later after surgery This field experiment examined effects of a support intervention on the physical and mental health of coronary artery bypass graft ( CABG ) surgery patients . Control participants ( N = 90 ) received usual hospital care ; experimental participants ( N = 100 ) also received visits from a " similar other " while in the hospital . Similar others were Veterans Administration veterans who had CABG surgery previously and were trained in simple supportive techniques . Outcomes were assessed prior to surgery and at 1 , 6 , and 12 months afterwards . Unexpectedly , the intervention generally had no effects on participants ' well-being . Further analysis showed that participants who talked often with fellow cardiac patients in the hospital ( " de facto similar others " ) experienced improvements in their physical and emotional well-being over time BACKGROUND This study evaluated the relative effects on compliance with recommended lifestyle changes of two experimental videotapes that involved different approaches for preparing coronary artery bypass graft ( CABG ) patients for the posthospital recovery period . The tapes differed in the extent to which they portrayed the recovery period as a steady , forward progression versus a series of " ups and downs . " METHODS Two hundred sixteen male and female CABG patients were assigned r and omly either to view one of the two videotapes before discharge from the hospital or to receive only the st and ard discharge preparation provided by the hospital . All patients completed measures of anxiety and self-efficacy at discharge , 1 month and 3 months after discharge from the hospital . Patients also completed measures of dietary fat consumption and activity level 1 and 3 months after discharge . RESULTS Relative to controls , patients who viewed either of the videotapes before hospital release reported higher self-efficacy for adhering to the recommended low-fat diet both at discharge and 1 month after surgery . Viewing either of the videotapes also result ed in significantly less dietary fat intake 1 month after hospital release compared with controls . Patients who viewed the tape that portrayed the recovery period as consisting of ups and downs also reported significantly more frequent moderate exercise at 1 month and more frequent strenuous exercise 3 months after discharge . CONCLUSIONS The experimental videotapes proved to be an effective method for increasing dietary and exercise compliance during the first 3 months after CABG OBJECTIVE To determine the efficacy of a psychoeducational nursing intervention in patients who receive coronary artery bypass graft and valve repair surgery . DESIGN A cluster-r and omized controlled trial design . SETTING Two hospitals in the western United States -- a large community hospital with an active cardiovascular surgery practice and a health-sciences research center . SUBJECTS 156 patients between 25 and 75 years of age , 125 ( 81.1 % ) men , and 31 ( 19.9 % ) women , all with primary care givers . OUTCOME MEASURES Self-efficacy expectations , activities ( behavior performance ) , quality of life , mood state . INTERVENTION Supplemental in-hospital education followed by telephone contact from discharge to eighth week after discharge . RESULTS Patients in the experimental group reported significantly greater self-efficacy expectations for walking and behavior performance for walking , lifting , climbing stairs , general exertion and , where applicable , for working . CONCLUSION This trial suggests that a low-intensity psychoeducational nursing intervention can promote self-efficacy expectations for walking in recovery and is associated with more self-reported walking and lifting behavior after cardiac surgery Objective : To investigate the long-term effects of motivational interviewing on clinical outcomes , psychological outcomes , health-related quality of life among cardiac rehabilitation patients with poor motivation . Design : A r and omized controlled trial with blind data collectors . Setting : Cardiac rehabilitation centre . Subjects : A total of 146 cardiac rehabilitation patients with poor motivation . Intervention : All participants received usual care , including exercise and education , while those in the experimental group also received 10 sessions of motivational interviewing , each lasting 30–45 minutes . Main measures : Clinical and psychological outcomes and health-related quality of life were assessed at baseline and at six , nine and 12 months for both groups . Result : There was no significant difference between the two groups at baseline on demographic and clinical outcomes except for monthly family income ( p = 0.034 ) . Patients in the experimental group had higher increases in health-related quality of life ( SF-36 ) scores in bodily pain ( 88.7 SD 16.7 vs. 87.6 SD 18.7 at month 12 , p = 0.044 ) and role limitation owing to emotional problems ( 86.9 SD 19.2 vs. 78.6 SD 21.8 at month 9 , p = 0.019 ; 85.8 SD 18.9 vs. 76.9 SD 23.9 at month 12 , p = 0.022 ) . No statistically significant group difference was found among other outcomes . Conclusion : The long-term effect of motivational interviewing on clinical and psychological outcomes and health-related quality of life in studied patients is limited OBJECTIVES The purpose of this study was to determine whether vicarious experience , in which former patients exemplify the active lives they are leading , reduces anxiety and increases self-efficacy expectation and self-reported activity in patients after cardiac surgery . DESIGN A r and omized , controlled trial was used to evaluate an intervention that linked volunteers who had recovered from cardiac surgery in dyadic support with patients about to undergo similar surgery . The linking was achieved by means of visits during the hospitalization and recovery period . SUBJECTS Fifty-six first-time male patients undergoing coronary artery bypass graft ( CABG ) surgery , with a mean age of 56.5 years , were r and omly assigned to an experimental ( n = 27 ) or control group ( n = 29 ) . OUTCOME MEASURES Anxiety was measured at 48 hours and 24 hours before surgery , and again at 5 days and 4 weeks after surgery . Self-efficacy expectation and self-reported activity were both evaluated at 5 days and 4 weeks after surgery . RESULTS Only the experimental group showed a significant decrease in anxiety during hospitalization . At all measurement times after the first intervention , the experimental group reported significantly lower levels of anxiety compared with the control group . The experimental group reported significantly higher levels of self-efficacy expectation and self-reported activity for general activities , walking , and climbing stairs evaluated at 5 days , and for general activities at 4 weeks after surgery . CONCLUSIONS Vicarious experience provided through dyadic support is effective in helping patients undergoing cardiac surgery cope with surgical anxiety and in improving self-efficacy expectations and self-reported activity after surgery . Dyadic support is a valuable tool for recovery from cardiac surgery that needs to be maintained and explored through nursing practice and research Objective : To explore the long-term effect of anxiety and depression on outcome after cardiac surgery . To date , the relationship between psychosocial factors and future cardiac events has been investigated mainly in population -based studies , in patients after cardiac catheterization or myocardial infa rct ion . Methods : In total , 180 patients who underwent cardiac surgery using cardiopulmonary bypass were prospect ively studied and followed up for 4 years . Anxiety ( Spielberger State-Trait Anxiety Inventory , STAI-S/STAI-T ) , depression ( Beck Depression Inventory , BDI ) , living alone , and education level along with clinical risk factors and perioperative characteristics were assessed . Psychological self-report question naires were completed preoperatively and 6 , 12 , 24 , 36 , and 48 months after discharge . Clinical end-points were mortality and cardiac events requiring hospitalization during follow-up . Results : Average preoperative STAI-T score was 44.6 ± 10 . Kaplan-Meier analysis showed a significant effect of preoperative STAI-T > 45 points ( p = .008 ) on mortality . In multivariate models , postoperative congestive heart failure ( OR : 10.8 ; 95 % confidence interval [CI]:2.9–40.1 ; p = .009 ) and preoperative STAI-T ( score OR : 1.07 ; 95 % CI : 1.01–1.15 ; p = .05 ) were independently associated with mortality . The occurrence of cardiovascular hospitalization was independently associated with postoperative intensive care unit days ( OR : 1.41 ; 95 % CI : 1.01–1.96 ; p = .045 ) and post discharge 6th month STAI-T ( OR : 1.06 ; 95 % CI:1.01–1.13 ; p = .03 ) . Conclusions : The results of the present study suggest that the assessment of psychosocial factors , particularly the ongoing assessment of anxiety , could help in risk stratification and identification of patients at risk of mortality and cardiovascular morbidity after cardiac surgery . BDI = Beck Depression Inventory ; STAI-S = state anxiety subscale ; STAI-T = trait anxiety subscale of Spielberger State-Trait Anxiety Inventory ; CPB = cardiopulmonary bypass ; CABG = coronary artery bypass grafting ; CHF = congestive heart failure ; CHD = coronary heart disease ; ICU = intensive care unit ; MI = myocardial infa rct ion ; PTSD = posttraumatic stress disorder BACKGROUND The association of depression with cardiac events has been investigated mainly in community cohorts , in patients undergoing catheterisation , or in patients who have had myocardial infa rct ion . We have assessed the effect of depression on outcomes after coronary artery bypass graft ( CABG ) surgery . METHODS In a prospect i ve study , we followed up for 1 year 207 men and 102 women , who had undergone coronary artery bypass graft surgery . We assessed depression with a structured psychiatric interview ( diagnostic interview schedule ) and a question naire ( Beck depression inventory ) before discharge . Cardiac events included angina or heart failure that needed admission to hospital , myocardial infa rct ion , cardiac arrest , percutaneous transluminal coronary angioplasty , repeat CABG , and cardiac mortality . Non-cardiac events consisted of all other reasons for mortality or readmission . FINDINGS 63 patients ( 20 % ) met modified diagnostic statistical manual IV criteria for major depressive disorder . At 12 months , 17 ( 27 % ) of these patients had a cardiac event compared with 25 of 246 ( 10 % ) who were not depressed ( p<0.0008 ) . Five variables had significant univariate associations with cardiac events : sex , living alone , low ejection fraction ( < 0.35 ) , length of hospital stay , and depression . In a Cox proportional-hazard model with these five and two other variables of cardiac severity , major depressive disorder ( risk ratio 2.3 [ 95 % CI 1.17 - 4.56 ] ) , low ejection fraction ( 2.3 [ 1.07 - 5.03 ] ) , and female sex ( 2.4 [ 1.24 - 4.44 ] ) were associated with adverse outcomes . Depression did not predict deaths or admissions for non-cardiac events . INTERPRETATION Depression is an important independent risk factor for cardiac events after CABG 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 BACKGROUND Effects of postoperative depression on recovery from coronary artery bypass grafting have not been widely studied . OBJECTIVES To evaluate emotional and physical recovery after bypass surgery and investigate associations between depressive symptoms and infections and impaired wound healing in patients with high and low levels of depressive symptoms . METHODS A nonr and omized , comparative , longitudinal design was used to study 72 bypass surgery patients without serious noncardiac comorbidities who were available for follow-up after discharge . Patients completed question naires to assess depressive symptoms , emotional recovery , and physical recovery within 48 hours after extubation , at discharge from the hospital , and 6 weeks later and performed 6-minute walk tests at the last 2 times . Infections and impaired wound healing ( as indicated by positive cultures , antibiotic treatment , or extra treatments , such as debridements or incisions and drainage ) were identified by chart audit . RESULTS At discharge , patients with higher depressive symptom scores ( indicating more symptoms ) reported poorer emotional recovery ( P<.001 ) and poorer physical recovery ( P=.007 ) and achieved shorter walking distances ( P<.001 ) than did patients with lower scores ( indicating fewer symptoms ) . Six weeks after discharge , emotional and physical recovery remained lower in patients with more depressive symptoms ( P<.001 ) . Infections and impaired wound healing were more common among patients with higher depressive symptom scores ( 46 % ) than among patients with lower scores ( 19 % , P=.03 ) . CONCLUSIONS After bypass surgery , depressive symptoms are associated with infections , impaired wound healing , and poor emotional and physical recovery OBJECTIVES This prospect i ve study examined how preoperative depression and faith-based coping , assessed preoperatively and postoperatively , affected short-term postoperative global functioning ( SPGF ) following a major cardiac surgery . METHODS We recruited 481 patients ( male , 58 % ; mean age=62 years , range=35 - 89 ) 2 weeks before surgery for three sequential psychosocial interviews using st and ardized instruments . Of them , 426 completed the second interview , and 335 completed the postoperative follow-up . RESULTS Multiple regression analyses showed that depression predicted poor SPGF , controlling for age , preoperative illness impact , and two noncardiac chronic conditions . Preoperative positive religious coping contributed to better SPGF , controlling for preoperative depression and other confounders . However , postoperatively assessed prayer coping was associated with poor SPGF . CONCLUSION Research should distinguish the longitudinal protection of generally adaptive faith-based coping styles from the increased usage of such coping for immediate distress , mobilized by crisis AIMS AND OBJECTIVES The aim of this study was to evaluate an intervention with individualised information and emotional support before coronary artery bypass grafting in a controlled r and omised trial . BACKGROUND Anxiety is a typical phenomenon in patients who are to undergo cardiac surgery . Preoperative anxiety has been shown to correlate to adverse postoperative outcomes . Emotional support could be an effective measure to reduce preoperative anxiety . DESIGN AND METHODS Patients with planned first coronary artery bypass grafting were r and omised into an intervention group ( n = 139 ) and a control group ( n = 114 ) . The patients of the control group were routinely informed as usual . The patients of the intervention group received a dialogue with individualised information and emotional support one day before surgery in addition to st and ard care . This intervention of ~30 minutes was based on a supportive psychotherapy model and was delivered by trained nurses . The primary outcome was the change in anxiety before operation . The secondary outcomes consisted of changes in postoperative anxiety , time on intensive care unit and in-hospital mortality . RESULTS Significantly reduced anxiety was found in the intervention group patients compared to control patients before coronary artery bypass grafting ( p < 0·001 ) and five days after surgery ( p < 0·001 ) . Both groups did not differ in in-hospital mortality and duration of stay in the intensive care unit . CONCLUSIONS Our short-term psychosocial intervention in patients undergoing coronary artery bypass grafting had a beneficial effect on reducing pre- and postoperative anxiety that was better than routine information alone . RELEVANCE TO CLINICAL PRACTICE These results advocate training for nurses and physicians to provide emotional support to patients before coronary artery bypass grafting Documentation shows that conventional methods used to prepare patients for chest tube removal ( CTR ) are not effective in reducing pain associated with this procedure . The quick relaxation technique ( QRT ) was used on 24 primary aorta-coronary bypass surgical patients . Subjects rated their pain on the visual analog scale immediately following CTR and 30 minutes later . Results indicated that men > or = 70 years of age who received QRT in conjunction with analgesics reported less than half the amount of pain experienced by those who did not receive QRT . In comparison , women 70 years old or older reported much higher pain intensity scores when QRT was used . Preliminary results suggest that for most patients , the combination of analgesics and relaxation exercises is not more effective in decreasing pain during CTR than when analgesics are administered without relaxation exercises 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 & 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 BACKGROUND As coronary artery bypass grafting ( CABG ) remains an important myocardial revascularisation strategy , more attention has been paid to the role of numerous factors affecting outcomes after CABG , including depression and depressive symptoms . However , previous studies on this issue gave inconsistent results , the dynamics of depression has been seldom investigated , and only few reports have specifically addressed this problem in Pol and . AIM Prospect i ve evaluation of the effect of depressive symptoms and the dynamics of their occurrence on the incidence of cardiac events in patients after CABG during a 2-year follow-up . METHODS We studied 170 patients aged 63 ± 10 years , including 17 women and 153 men , who underwent CABG . The Beck Depression Inventory ( BDI ) was used to evaluate the severity of depressive symptoms at 2 weeks ( 0 M ) , 3 months ( 3 M ) , and 24 months ( 24 M ) after CABG . Based on the BDI findings during subsequent follow-up visits , patients were divided into three groups depending on the dynamics of depressive symptoms : Group I without depression ( 67 patients ) , Group II with incidental depression ( 72 patients ) , and Group III with chronic depression ( 31 patients ) . During the 2-year follow-up , we evaluated the incidence of three combined endpoints that included death , myocardial infa rct ion ( MI ) , coronary angioplasty or redo CABG surgery ; recurrent angina ; and hospitalisations due to arrhythmia , heart failure or other cardiac causes . We analysed the effect of demographic , clinical , perioperative end psychological parameters to identify independent risk factors for cardiac events . RESULTS Among patients with chronic depression , more cardiac events were noted compared to patients without depression or with incidental depression . All combined endpoints were significantly more common in patients with chronic depression compared to those without depression ( death , MI , coronary angioplasty or redo CABG surgery : 19.3 % in Group III vs. 5.9 % in Group I , p = 0.0437 ; recurrent angina : 45 % in Group III vs. 16.4 % in Group I , p = 0.027 ; hospitalisations due to arrhythmia , heart failure or other cardiac causes : 54.8 % in Group III vs. 31.3 % in Group I , p = 0.0287 ) . Hospitalisation rate was also higher among patients with chronic depression compared to those with incidental depression ( 54.8 % in Group III vs. 31.9 % in Group II , p = 0.031 ) . In multivariate analysis using a linear regression model , independent risk factors for hospitalisation during the 2-year follow-up included the presence of depressive symptoms in the early postoperative period ( p = 0.03 ) and the BDI score at 3 months after CABG ( p = 0.0001 ) . Use of antidepressants at baseline was an independent risk factor for recurrent angina ( p = 0.004 ) . Depressive symptoms , regardless of their dynamics , were not found to be a risk factor for the combined endpoint of death , MI , coronary angioplasty or redo CABG surgery . CONCLUSIONS During a 2-year prospect i ve follow-up of patients after CABG , cardiac events were significantly more common among patients with chronic depression ( but not incidental depression ) as compared to patients without depressive symptoms . Hospitalisation rate among patients with chronic depression was significantly higher compared to both patients without depression or with incidental depression . Both chronic and incidental depression was not shown to be to be a risk factor for the combined endpoint of death , MI , coronary angioplasty or redo CABG surgery . Severe depressive symptoms that required the use of antidepressants at baseline were an independent risk factor of recurrent angina . The presence of depressive symptoms at baseline and BDI score at 3 months were independent risk factors for rehospitalisation . This suggests that the dynamics of depressive symptoms may have an effect on rehospitalisations in patients after CABG 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 OBJECTIVE The goal of this study was to examine the feasibility , acceptability , and efficacy of a brief , tailored cognitive-behavioral intervention for patients with symptoms of preoperative depression or anxiety before undergoing a coronary artery bypass graft ( CABG ) operation . METHODS Patients were recruited from a university teaching hospital between February 2007 and May 2009 . Patients were r and omly assigned to receive treatment as usual ( TAU ) or a cognitive behavioral therapy ( CBT ) intervention called Managing Anxiety and Depression using Education and Skills ( MADES ) . A total of 100 subjects were r and omized into the study . Length of hospital stay was assessed with a 1-way analysis of variance . Depression , anxiety , and quality of life were assessed with mixed-model repeated measures analyses . RESULTS Overall , the intervention was feasible , and patients had a positive impression of the MADES . Patients in the TAU group stayed longer in the hospital than did those in the MADES group ( 7.9 days ± 2.6 vs 9.2 days ± 3.5 ; P = .049 ) . Depressive symptoms increased at time of hospital discharge for the TAU group , whereas the MADES group had a decrease in depressive symptoms at the time of discharge . Quality of life and anxiety symptoms improved in both groups at 3 to 4 weeks of follow-up . However , the MADES group had greater improvements than did the TAU group . CONCLUSIONS This study demonstrated that brief , tailored CBT targeting preoperative depression and anxiety is both feasible and acceptable for patients undergoing CABG surgery . Most important , this intervention improved depressive and anxiety symptoms , as well as quality of life . Moreover , it reduced in-hospital length of stay . This study found that a cognitive-behavioral intervention for patients undergoing CABG surgery for symptoms of preoperative depression/anxiety is both feasible and acceptable . Most important , this intervention improved depressive and anxiety symptoms , as well as quality of life . It also reduced in-hospital length of stay Background Most adults undergoing cardiac surgery suffer from moderate to severe pain for up to 6 days after surgery . Individual barriers and attitudes regarding pain and its relief make patients reluctant to report their pain and ask for analgesic medication , which results in inadequate pain management . More innovative educational interventions for postoperative pain relief are needed . We developed a Web-based nursing intervention to influence patient ’s involvement in postoperative pain management . The intervention ( SOULAGE-TAVIE ) includes a preoperative 30-minute Web-based session and 2 brief face-to-face postoperative booster sessions . The Web application generates reflective activities and tailored educational messages according to patients ’ beliefs and attitudes . The messages are transmitted through videos of a virtual nurse , animations , stories , and texts . Objective The aim of this single-blinded pilot r and omized trial was to investigate the preliminary effects of a virtual nursing intervention ( SOULAGE-TAVIE ) to improve pain relief in patients undergoing cardiac surgery . Methods Participants ( N = 60 ) were adults scheduled for their first cardiac surgery . They were r and omly assigned to the experimental group using SOULAGE-TAVIE ( n = 30 ) or the control group using usual care , including an educational pamphlet and postoperative follow-up ( n = 30 ) . Data were collected through question naires at the time of admission and from day 1 to day 7 after surgery with the help of a blinded research assistant . Outcomes were pain intensity , pain interference with daily activities , patients ’ pain barriers , tendency to catastrophize in face of pain , and analgesic consumption . Results The two groups were comparable at baseline across all demographic measures . Results revealed that patients in the experimental group did not experience less intense pain , but they reported significantly less pain interference when breathing/coughing ( P = .04 ) . A severe pain interference with breathing/coughing ( pain ranked ≥ 7/10 ) was reported on day 3 after surgery by 15 % of the patients in the experimental group ( 4/27 ) , as compared to 44 % ( 7/16 ) in the control group . On day 7 after surgery , participants in the experimental group also exhibited fewer pain-related barriers as measured by the Barriers Question naire-II ( mean 10.6 , SD 8.3 ) than patients in the control group ( mean 15.8 , SD 7.3 , P = .02 ) . No difference was found for pain catastrophizing . However , in both groups , means revealed a lower tendency to catastrophize pain before surgery as measured by the Pain Catastrophizing Scale ( control group mean 1.04 , SD 0.74 ; experimental group mean 1.10 , SD 0.95 ) and after surgery ( control group mean score 1.19 , SD 0.94 ; experimental group mean score 1.08 , SD 0.99 ) . Finally , the experimental group consumed more opioid medication ( mean 31.2 mg , SD 23.2 ) than the control group ( mean 18.8 mg , SD 15.3 , P = .001 ) . Conclusions This pilot study provides promising results to support the benefits of this new Web-tailored approach that can increase accessibility to health education and promote pain relief without generating more costs . Trial Registration Clinical trials.gov NCT01084018 ; http://www . clinical trials.gov/ct2/show/NCT01084018 ( Archived by WebCite ® at http://www.webcitation.org/6CoTBkIoT OBJECTIVE To assess the effects of phase I cardiac rehabilitation intervention on anxiety of patients hospitalized for coronary artery bypass graft ( CABG ) surgery . DESIGN Prospect i ve , quasi-experimental , r and om assignment , repeated measurements . SETTING The Veterans General Hospital Taipei , Taiwan , Republic of China . PATIENTS Seventy patients were r and omly assigned to ( 1 ) the phase I cardiac rehabilitation intervention ( experimental ) group and ( 2 ) the nonintervention ( comparison ) group . Ultimately , 60 subjects were included in the data analyses . OUTCOME MEASURES Psychological status was evaluated by the state of anxiety scores on the State-Trait Anxiety Inventory . Anxiety scores were measured 3 times : ( 1 ) after admission , before the patient underwent CABG surgery ; ( 2 ) the day before the patient underwent CABG surgery ; and ( 3 ) the day of discharge from the hospital . INTERVENTION Individual instruction in progressive exercises and daily activities according to the phase I cardiac rehabilitation program ( Chinese manual ) were used during hospitalization . RESULTS Data analysis was performed with use of generalized estimating equations ( GEE ) to assess the between- and within-group variations . The mean anxiety for all subjects before undergoing CABG surgery was 42.6 . The mean anxiety on the day before undergoing CABG surgery was 33.7 in the experimental group and 49.8 in the comparison group ; there were statistical differences , with a P < .05 level of significance between these 2 groups . The mean anxiety on the day of discharge in the experimental group was 28.6 and in the comparison group was 38.4 ; there were statistical differences , with a P < .05 level of significance between these 2 groups . CONCLUSIONS These results have been supported by similar studies . This finding suggests that application of phase I cardiac rehabilitation intervention can reduce the anxiety level during hospitalization of patients undergoing CABG surgery 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 PURPOSE To investigate postoperative pain control and analgesic use after heart surgery . METHODS 20 patients undergone heart surgery , r and omly entered the study . Each patient was asked to score his pain intensity on visual analog scale ( VAS ) at four different occasions . RESULTS 120 patients aged 59 year-old ; including 81 male were enrolled in the study . 69.2 % had coronary artery disease and 16.7 % had heart-valve problem . Main types of surgeries were coronary artery bypass surgery ( 70.5 % ) and valve repairement ( 23 % ) . Duration of ICU stay was 4.78±2.7 days and duration of intubations was 17.38 ± 36.46 hours . Pre-surgery pain relief was administrated to 42 % of the subjects and morphine and promethazine was the main pre-surgery analgesia medication . Post surgery analgesic included morphine ( injection ) , petidine ( injection ) and NSAIDS ( oral or rectal ) . According to VAS , mean pain level , 1 and 4 hours after extubation , and before and one hour after transferring to wards was 5.05±2.5 , 4.09±2.0 , 3.52±1.8 , 2.36±1.89 , respectively . Although the level of pain reported was mostly moderate , 80 % were reported satisfaction with their post-surgery pain management . CONCLUSION A closer pain management control is needed for patients after heart surgery . Introduction of newer pain management techniques , medications and dosages could reduce the pain and suffering Effects of psychological as well as spiritual interventions on outcome in cardiac surgery have mostly been studied with a focus on presurgical interventions . Systematic ally controlled analyses of the effects of psychological and spiritual interventions depending on the patients ' preference have not been performed so far , although these studies would help to assign patients to an adequate support . The By.pass study is a bi-center , controlled trial of patients undergoing coronary bypass surgery and coronary bypass surgery combined with valve replacement surgery in 2 different German hospitals . Patients are assigned to 1 of 5 conditions , mainly according to their personal therapeutic preference : preference for psychological interventions ( group 1 ) , preference for spiritual interventions ( group 2 ) , or preference for no intervention ( group 5 ) . Patients who are open for any kind of intervention are r and omly assigned either to psychological ( group 3 ) or spiritual interventions ( group 4 ) . Six months before the start and 6 months after the end of the treatment phase , patients were assigned to the control groups . These were asked about their subjective preference ( psychological , spiritual , no intervention , or no specific preference ) as well but received no interventions . Patients will be enrolled from October 2006 to December 2009 . The 6-month follow-up will be completed in July 2010 AIMS AND OBJECTIVES To investigate use of educational audiotape programme on anxiety and depression in patients undergoing coronary artery bypass graft ( CABG ) . BACKGROUND Anxiety and depression after CABG are the most common complications , having a negative impact on the prognosis of heart disease , leading to special needs according to their new physical and mental conditions . DESIGN R and omised clinical trial . METHODS This study conducted in Iran , 70 patients undergoing CABG were included and divided into two equal groups , the control group and intervention group . They were followed up for six weeks . An audiotape educational programme was given to the intervention group after surgery in addition to the routine training . But patients in the control group received only routine training . Anxiety and depression were assessed by Hospital Anxiety and Depression Scale , a st and ardised question naire for anxiety and depression . Data were collected before and six weeks after the intervention . For the comparison of mean scores between the groups , the data were analysed in spss , version 16 , using independent T-test and paired T-test . RESULTS The mean scores obtained in both anxiety and depression dimensions were significantly different between the intervention and control groups . CONCLUSIONS Audiotape educational programme used by patients undergoing CABG decreases the level of their anxiety and depression after cardiac surgery . RELEVANCE TO CLINICAL PRACTICE The most significant finding was the importance of audiotape educational programme to meet the needs of the CABG patients , which suggest that patient education through audiotape can be effective in self-care after heart surgery and nurses can use an audiotape containing preparatory information to improve outcomes and reduce anxiety and depression in patients having CABG OBJECTIVE The purpose of this study was to assess the impact of preoperative patient education on anxiety and recovery of the Lebanese patients undergoing open-heart surgery . METHODS This quasi-experimental study was conducted at a large hospital in Beirut , which is a university hospital . All patients who were admitted to the cardiac surgery unit and who met the inclusion criteria were r and omly assigned to as experimental or a control group . The patients in the experimental group ( n = 57 ) received a special educational session on their admission day and had a tour of the cardiac surgery unit . The control group ( n = 53 ) followed the routine hospital protocol , which encompassed almost no preoperative education or a tour . Anxiety was assessed using the Beck Anxiety Inventory while recovery was measured by physiological outcomes , days of hospital stay , and presence of complications . A Multivariate Analysis of Covariance ( MANCOVA ) was performed with adjustment for potential confounding variables . RESULTS Borderline statistical significance was noted for the experimental group in terms of preoperative and postoperative anxiety . The experimental group had a shorter time from awakening to extubation . CONCLUSION Unlike most studies published previously , which noted the benefits of preoperative patient education , this study with the Lebanese clients , failed to support earlier findings . PRACTICE IMPLICATION S The results suggest that patient education should not be initiated before assessing the patient 's cultural and social background The Foster Pain Intervention ( FPI ) is a 24-minute videotape of a nurse showing breathing and movement skills with four postoperative mobility activities to a patient . Its preoperative use incorporates self-efficacy concepts to teach techniques that can improve postoperative pain and mobility . This study compared the effects of the FPI on postoperative pain and mobility and the relationship with self-efficacy in 70 elective hysterectomy patients . The treatment group ( n = 35 ) received the FPI and routine information , whereas the control group ( n = 35 ) received routine information through videotaped instruction . The treatment group had significantly less pain ( p < .0001 ) , higher observed mobility ( p < .0001 ) , and higher preoperative self-efficacy and was ready to go home sooner than the control group ( p < .0001 ) . These results suggest that the FPI enhances self-efficacy , decreases pain associated with postoperative activities , and promotes earlier independent mobilization 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 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 Objective : To describe the relationship between pain and depression on recovery after coronary artery bypass grafting ( CABG ) . Methods : A secondary data analysis on 453 depressed and nondepressed post-CABG patients enrolled in a r and omized , controlled , effectiveness trial of telephone-delivered collaborative care for depression . Outcome measures were collected from March 2004 to September 2007 and included pain , physical function , and mood symptoms . Results : Depressed patients ( baseline Patient Health Question naire-9 score ≥10 ) versus those without depression reported significantly worse pain scores on the 36-Item Short Form Health Survey Bodily Pain Scale at baseline and up to 12 months post-CABG , p < .05 . Among patients with depression , those who received collaborative care reported significantly better pain scores at each time point between 2 and 12 months post-CABG versus depressed patients r and omized to the usual care control group , p < .05 . Regardless of intervention status , depressed participants with at least moderate pain at baseline reported significantly lower functional status ( measured by the Duke Activity Status Index ) at 8 and 12 months versus depressed patients with none or mild pain , p < .05 . Depressed patients with at least moderate pain at baseline were also significantly less likely to show improvement of depressive symptoms throughout the course of follow-up versus depressed patients with little or no pain , p < .05 . These findings controlled for age , gender , education , race , comorbid conditions , and baseline pain diagnosis . Conclusions : Depression and pain seem to influence functional recovery post-CABG . The relationship between these two conditions and 12-month outcomes should be considered by clinicians when planning treatment . HTN = hypertension ; CVA = cerebral vascular accident ; COPD = chronic obstructive pulmonary disease ; CHF = chronic heart failure ; PHQ = Patient Health Question naire ; HRS-D = Hamilton Rating Scale-Depression ; DASI = Duke Activity Status Index ; NSAIDs = nonsteroidal antiinflammatory drug Staying in an intensive care unit ( ICU ) is very stressful for patients after heart surgery . Although it is a general belief that support from doctors is important to reduce patients ' tension , no quantitative data are available . We investigated the stress-reducing effects of a tape-recorded message from the physician which provided information regarding the surgery and emotional support for heart surgery patients postoperatively in the ICU . Sixty patients who underwent cardiac surgery were r and omly allocated to two equal groups . The patients in the experimental group listened to a tape-recorded message from their attending surgeon soon after they recovered from anesthesia , while the control group rested during the study period . The effectiveness of the tape-recorded support program was evaluated by the influence on heart rate , blood pressure , and finger skin temperature , as well as the degree of subjective pain , tension , anxiety , depression , and anger . The pain and tension levels of the patients were measured using a visual analogue scale , while the severity of anxiety , depression , and anger was evaluated using the Brief Symptom Rating Scale . Patients ' evaluation of the usefulness of the program was also assessed . After listening to the physician 's recorded message , the mean increase in the skin finger temperature in the experimental group was higher than in the control group ( 0.44 degree C vs 0.25 degree C , p = 0.0513 ) . The experimental group had significant decreases in their mean scores of pain ( -1.11 vs 0.36 , p = 0.0043 ) , tension ( -2.26 vs -0.25 , p = 0.0001 ) , anxiety ( -1.3 vs -0.57 , p = 0.0473 ) , and depression ( -2.24 vs -0.37 , p = 0.0253 ) . The patients showed a high need for this support program ( mean need score 8.4 ) . These findings show that a physician 's tape-recorded message providing information and emotional support can reduce stress in heart surgery patients in the ICU postoperatively Background Emerging evidence indicates that the association between depression and subsequent cardiovascular events is largely mediated by health behaviors . However , it is unclear whether depression is the cause or the consequence of poor health behaviors . Purpose The purpose of the present study is to examine prospect i ve , bidirectional relationships of depressive symptoms with behavioral and lifestyle factors among patients with coronary heart disease . Methods Depressive symptoms and lifestyle behaviors ( physical activity , medication adherence , body mass index , waist to hip ratio , sleep quality , and smoking status ) were assessed at baseline and 5 years later among a prospect i ve cohort of 667 patients with stable coronary heart disease . Results Greater depressive symptoms at baseline predicted poorer lifestyle behaviors 5 years later ( less physical activity , lower medication adherence , higher body mass index , higher waist to hip ratio , worse sleep quality , and smoking ) . After adjustment for demographics , cardiac disease severity , comorbidity , and baseline lifestyle behaviors , depressive symptom severity remained predictive of subsequent worsening of physical activity ( beta = −0.08 ; 95 % confidence interval ( CI ) = −0.16 , −0.01 ; p = 0.03 ) , medication adherence ( beta = −0.16 ; 95 % CI = −0.24 , −0.08 ; p < 0.001 ) , and sleep quality ( beta = −0.19 ; 95 % CI = −0.27 , −0.11 ; p < 0.001 ) . Baseline lifestyle behaviors also predicted 5-year change in depressive symptoms , although the associations were attenuated after adjustment for baseline depressive symptoms and covariates . Conclusions Among patients with coronary heart disease , depressive symptoms were linked to a range of lifestyle risk factors and predicted further declines in physical activity , medication adherence , and sleep quality |
2,688 | 26,932,724 | Prior knowledge and belief predicted student response to the clear finding review , while years of midwifery education predicted response to the uncertain finding review .
Conclusions Abstract s with and without conclusions generated similar student responses .
PLS with conclusions gave similar results to abstract s with and without conclusions .
Removing the conclusions from a PLS with uncertain findings led to more problems with interpretation | Background Abstract s and plain language summaries ( PLS ) are often the first , and sometimes the only , point of contact between readers and systematic review s. It is important to identify how these summaries are used and to know the impact of different elements , including the authors ’ conclusions .
The trial aims to assess whether ( a ) the abstract or the PLS of a Cochrane Review is a better aid for midwifery students in assessing the evidence , ( b ) inclusion of authors ’ conclusions helps them and ( c ) there is an interaction between the type of summary and the presence or absence of the conclusions . | Background The evaluation of more than one intervention in the same r and omised controlled trial can be achieved using a parallel group design . However this requires increased sample size and can be inefficient , especially if there is also interest in considering combinations of the interventions . An alternative may be a factorial trial , where for two interventions participants are allocated to receive neither intervention , one or the other , or both . Factorial trials require special considerations , however , particularly at the design and analysis stages . Discussion Using a 2 × 2 factorial trial as an example , we present a number of issues that should be considered when planning a factorial trial . The main design issue is that of sample size . Factorial trials are most often powered to detect the main effects of interventions , since adequate power to detect plausible interactions requires greatly increased sample sizes . The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models . Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions . We also give an example of how baseline and follow-up data should be presented . Lastly , we discuss the implication s of the design , analytical and presentational issues covered . Summary Difficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient , simultaneous consideration of two or more interventions . Factorial trials can in principle be design ed to have adequate power to detect realistic interactions , and in any case they are the only design that allows such effects to be investigated Abstract Objectives : To determine how medical students apply research evidence that varies in validity of methods and importance of results to a clinical decision . Design : Students examined a st and ardised patient with a whiplash injury , decided whether to order a cervical spine radiograph , and rated their confidence in their decision . They then read one of four r and omly assigned variants of a structured abstract from a study of a decision rule that argued against such a procedure in this patient . Variants factorially combined two levels of validity of methods ( prospect i ve cohort or chart review ) with two levels of importance of results ( high sensitivity or high specificity rule ) . After reading the abstract , students repeated their choice and rated their confidence . Setting : Academic medical centre in the United States . Participants : 164 graduating medical students . Main outcome measures : Proportion of students in each group whose beliefs shifted or stayed the same . Results : When abstract s were of low importance students were more likely to shift their beliefs in favour of radiography , which was not supported by the evidence ( odds ratio 3.42 , 95 % confidence interval 1.10 to 10.66 ) . Neither method ological validity nor the interaction between validity and importance influenced decision shift . Few students acquired all necessary clinical data from the patient . Conclusions : Although the students could apply concepts of diagnostic testing , greater focus is needed on appraisal of validity and application of evidence to a particular patient . What is already known on this topic Evidence based medicine is increasingly emphasised and taught in medical schools Few studies have assessed the ability of physicians to apply literature findings to clinical decisions What this paper adds In making decisions about ordering investigations during a st and ardised patient exam students were sensitive to the importance of results This effect was not moderated by validity of the study that produced the results or whether the students had collected enough information to apply the OBJECTIVES To evaluate a new format of a summary , which presents research from synthesized evidence to patients and the public . STUDY DESIGN AND SETTING We conducted a r and omized controlled trial in 143 members of the public from five countries ( Canada , Norway , Spain , Argentina , and Italy ) . Participants received either a new summary format ( a plain language summary [ PLS ] ) or the current format used in Cochrane systematic review s. The new PLS presents information about the condition and intervention , a narrative summary of results , and a table of results with absolute numbers for effects of the intervention and quality of the evidence using Grading of Recommendations Assessment , Development , and Evaluation . RESULTS With the new PLS , more participants understood the benefits and harms and quality of evidence ( 53 % vs. 18 % , P < 0.001 ) ; more answered each of the five questions correctly ( P ≤ 0.001 for four questions ) ; and they answered more questions correctly , median 3 ( interquartile range [ IQR ] : 1 - 4 ) vs. 1 ( IQR : 0 - 1 ) , P < 0.001 ) . Better underst and ing was independent of education level . More participants found information in the new PLS reliable , easy to find , easy to underst and , and presented in a way that helped make decisions . Overall , participants preferred the new PLS . CONCLUSION This new PLS format for patients and the public is a promising tool to translate evidence from synthesized research OBJECTIVE To measure the effects of a summary -of- findings ( SoF ) table on user satisfaction , underst and ing , and time spent finding key results in a Cochrane review . STUDY DESIGN AND SETTING We r and omized participants in an evidence -based practice workshop ( r and omized controlled trial [ RCT ] I ) and a Cochrane Collaboration entities meeting ( RCT II ) to receive a Cochrane review with or without an SoF table . In RCT I , we measured user satisfaction . In RCT II , we measured correct comprehension and time spent finding key results . RESULTS RCT I : Participants with the SoF table ( n=47 ) were more likely to " agree " or " strongly agree " that it was easy to find results for important outcomes than ( n=25 ) participants without the SoF table-68 % vs. 40 % ( P=0.021 ) . RCT II : Participants with the SoF table ( n=18 ) were more likely to correctly answer two questions regarding results than ( n=15 ) those without the SoF table : 93 % vs. 44 % ( P=0.003 ) and 87 % vs. 11 % ( P<0.001 ) . Participants with the SoF table spent an average of 90 seconds to find key information compared with 4 minutes for participants without the SoF table ( P=0.002 ) . CONCLUSION In two small trials , we found that inclusion of an SoF table in a review improved underst and ing and rapid retrieval of key findings compared with review s with no SoF table Objective . To develop and obtain feedback about a summary format for Cochrane review s that is accessible to a consumer audience , without oversimplification or incorrect presentation . Methods . We developed 3 versions of a Plain Language Summary ( PLS ) format of a Cochrane Systematic Review . Using a semi-structured interview guide we tested these versions among 34 members of the public in Norway , Argentina , Canada , and Australia . The authors analyzed feedback , identified problems , and generated new solutions before retesting to produce a final version of a Plain Language Summary format . Results . Participants preferred results presented as words , supplemented by numbers in a table . There was a lack of underst and ing regarding the difference between a review and an individual study , that the effect is rarely an exact number , that evidence can be of low or high quality , and that level of quality is a separate issue from intervention effect . Participants also found it difficult to move between presentations of dichotomous and continuous outcomes . Rephrasing the introduction helped participants grasp the concept of a review . Confidence intervals were largely ignored or misunderstood . Our attempts to explain them were only partially successful . Text modifiers ( ‘ ‘ probably , ’ ’ ‘ ‘ may ’ ’ ) to convey different levels of quality were only partially understood , whereas symbols with explanations were more helpful . Participants often understood individual information elements about effect size and quality of these results , but did not always actively merge these elements . Conclusion . Through testing and iteration the authors identified and addressed several problems , using explanations , rephrasing , and symbols to present scientific concepts . Other problems remain , including how best to present confidence intervals and continuous outcomes . Future research should also test information elements in combination rather than in isolation . The new Plain Language Summary format is being evaluated in a r and omized controlled trial |
2,689 | 28,750,345 | Based on these findings , existing BAIs do not seem to be efficacious in reducing alcohol use in military population s , despite some encouraging results from one electronic intervention which was of extensive duration | BACKGROUND Rates of hazardous and harm-related drinking are higher in the military and veteran population s compared to the general population .
Brief alcohol interventions ( BAIs ) targeting alcohol use appear to reduce harmful drinking in the general population . | OBJECTIVE Veterans who served in Operation Enduring Freedom ( OEF ) and Operation Iraqi Freedom ( OIF ) commonly experience alcohol misuse and symptoms of posttraumatic stress disorder ( PTSD ) following their return from deployment to a war zone . We conducted a r and omized clinical trial to evaluate the efficacy of a newly developed , 8-module , self-management web intervention ( VetChange ) based on motivational and cognitive-behavioral principles to reduce alcohol consumption , alcohol-related problems , and PTSD symptoms in returning combat veterans . METHOD Six hundred participants , recruited through targeted Facebook ads , were r and omized to either an Initial Intervention Group ( IIG ; n = 404 ) or a Delayed Intervention Group ( DIG ; n = 196 ) that waited 8 weeks for access to VetChange . Primary outcome measures were Drinks per Drinking Day , Average Weekly Drinks , Percent Heavy Drinking Days , and PTSD symptoms . Intent-to-treat analyses compared changes in outcome measures over time between IIG and DIG as well as within-group changes . RESULTS IIG participants demonstrated greater reductions in drinking ( p < .001 for each measure ) and PTSD symptoms ( p = .009 ) between baseline and end-of-intervention than did DIG participants between baseline and the end of the waiting period . DIG participants showed similar improvements to those in IIG following participation in VetChange . Alcohol problems were also reduced within each group between baseline and 3-month follow-up . CONCLUSIONS Results indicate that VetChange is effective in reducing drinking and PTSD symptoms in OIF/OEF veterans . Further studies of VetChange are needed to assess web-based recruitment and retention methods and to determine VetChange 's effectiveness in demographic and clinical sub- population s of returning veterans 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 OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity BACKGROUND Strong evidence exists for the efficacy of screening and brief intervention for reducing hazardous drinking . However , problems have been highlighted with respect to its implementation in health-care systems , not least of which is a reluctance of some doctors to discuss alcohol proactively with their patients . AIMS To determine the efficacy of a novel web-based screening and brief intervention ( e-SBI ) to reduce hazardous drinking . DESIGN A double-blind r and omized controlled trial . SETTING A university student health service . PARTICIPANTS A total of 167 students ( 17 - 26 years ) were recruited in the reception area and completed a 3-minute web-based screen including the Alcohol Use Disorder Identification Test ( AUDIT ) question naire . Of these , 112 tested positive , and 104 ( 52 females ) who consented to follow-up were included in the trial . MEASUREMENTS Drinking frequency , typical occasion quantity , total volume , heavy episode frequency ( females > 80 g ethanol , males > 120 g ethanol ) , number of personal problems , an academic problems score . INTERVENTION Participants were r and omized to 10 - 15 minutes of web-based assessment and personalized feedback on their drinking ( intervention , n = 51 ) or to a leaflet-only control group ( n = 53 ) . FINDINGS Mean baseline AUDIT scores for control and intervention groups were 16.6 ( SD = 6.0 ) and 16.6 ( SD = 5.7 ) . At 6 weeks , participants receiving e-SBI reported significantly lower total consumption ( geometric mean ratio = 0.74 ; 95 % confidence interval : 0.56 - 0.96 ) , lower heavy episode frequency ( 0.63 ; 0.42 - 0.92 ) and fewer personal problems ( 0.70 ; 0.54 - 0.91 ) . At 6 months personal problems remained lower ( 0.76 ; 0.60 - 0.97 ) , although consumption did not differ significantly . At 6 months , academic problems were lower in the intervention group relative to controls ( 0.72 ; 0.51 - 1.02 ) . CONCLUSIONS e-SBI reduced hazardous drinking among university students , to an extent similar to that found for practitioner-delivered brief interventions in the general population . e-SBI offers promise as a strategy to reduce alcohol-related harm in a way that is non-intrusive , appealing to the target group , and capable of being incorporated into primary care . Research is required to replicate the findings , to determine the duration of intervention effects , and to investigate the mechanisms by which the intervention operates AIMS To examine patterns of drinking in the UK Armed Forces , how they vary according to gender and other demographics , and to make comparisons with the general population . DESIGN Large cross-sectional postal question naire study ( response rate 60 % ) . SETTING United Kingdom . PARTICIPANTS A r and om representative sample of the regular UK Armed Forces who were in service in March 2003 ( n = 8686 ; 7937 men , 749 women ) . Comparisons were made with the general population of Great Britain . MEASUREMENTS Alcohol consumption was assessed using the Alcohol Use Disorders Identification Test ( AUDIT ) . FINDINGS Sixty-seven per cent of men and 49 % of women in the UK Armed Forces had an AUDIT score of 8 + ( defined as hazardous drinking ) , compared to 38 % of men and 16 % of women in the general population . In both sexes , for all ages , the military have a higher prevalence of hazardous drinking . Binge drinking was associated with being younger , being in the Army , being single , being a smoker and being white . Among military men , heavy drinking ( AUDIT score 16 + ) was associated with holding a lower rank , being younger , being single , being in the Naval Service or Army , being deployed to Iraq , not having children , being a smoker , having a combat role and having a parent with a drink or drug problem . CONCLUSIONS Excessive alcohol consumption is more common in the UK Armed Forces than in the general population . There are certain socio-demographic characteristics associated with heavy drinking within the military ; for example , young age , being single and being a smoker , which may allow the targeting of preventive interventions OBJECTIVE This study sought to examine whether a web-delivered brief alcohol intervention ( BAI ) is effective for reducing alcohol misuse in U.S. military veterans presenting to primary care . METHOD Veterans ( N = 167 ) screening positive for alcohol misuse during a routine primary care visit were r and omized to receive a BAI plus treatment as usual ( TAU ) or TAU alone . An assessment of alcohol-related outcomes was conducted at baseline and 3 and 6 months after treatment . RESULTS Veterans in both study conditions showed a significant reduction in alcohol quantity and frequency and alcohol-related problems at 6-month follow-up . No differential treatment effects on outcomes were observed between the two treatment groups . CONCLUSIONS This study is the first to explore whether a web-delivered BAI using normative feedback is effective for veterans with alcohol misuse . Our findings suggest that BAIs using normative feedback may not have any additional benefit beyond TAU for older veterans with high rates of comorbid mental health concerns OBJECTIVE Research has shown that U.S. military veterans are at risk relative to the general adult population for excessive alcohol consumption , and veterans of the wars in Afghanistan and Iraq ( Operation Enduring Freedom [ OEF ] , Operation Iraqi Freedom [ OIF ] , and Operation New Dawn [ OND ] ) particularly so . The purpose of this study was to examine the efficacy of a brief personalized drinking feedback intervention tailored for veterans . METHOD All veterans who presented to the OEF/OIF/OND Seamless Transition Clinic at the Harry S. Truman Memorial Veterans ' Hospital ( Columbia , MO ) were eligible to participate . Participants were 325 veterans ( 93 % male ; 82 % White , 75 % Army , M(age ) = 32.20 years ) who were r and omly assigned to one of two conditions : personalized drinking feedback ( PDF ) or educational information ( EDU ) . Those in the PDF condition received personalized information about their alcohol use , including social norms comparisons , risks associated with reported drinking levels , and a summary of their alcohol-related problems . Follow-up assessment s were completed at 1 and 6 months after intervention ( response rates = 93 % and 86 % , respectively ) . RESULTS Results indicated a significant ( p < .05 ) Omnibus Group × Time effect for estimated peak blood alcohol concentration , although tests of simple main effects did not indicate between-group differences at the individual follow-up points . Among baseline abstainers , those in the PDF condition were more likely than those in the EDU condition to remain an abstainer at 6-month follow-up ( p < .05 ) . CONCLUSIONS These findings provide preliminary support for the efficacy of a brief , inexpensive alcohol prevention/intervention for young adult military veterans Objective : Young-adult American veterans are at risk for problematic alcohol use . However , they are unlikely to seek care and may drop out from lengthy , multicomponent treatments when they do get care . This r and omized controlled trial tested a very brief alcohol intervention delivered over the Internet to reach the population of young-adult veterans to help reduce their drinking . Method : Veterans ( N = 784 ) were recruited from Facebook and r and omized to either a control condition or a personalized normative feedback ( PNF ) intervention seeking to correct drinking perceptions of gender-specific veteran peers . Results : At immediate postintervention , PNF participants reported greater reductions in their perceptions of peer drinking and intentions to drink over the next month , compared with control participants . At 1-month follow-up , PNF participants reduced their drinking behavior and related consequences to a significantly greater extent than controls . Specifically , PNF participants drank 3.4 fewer drinks per week , consumed 0.4 fewer drinks per occasion , binge drank on 1.0 fewer days , and experienced about 1.0 fewer consequences than control participants in the month after the intervention . Intervention effects for drinks per occasion were most pronounced among more problematic drinkers . Changes in perceived norms from baseline to 1-month follow-up mediated intervention efficacy . Conclusion : Though effects were assessed after only 1 month , findings have potential to inform broader , population -level programs design ed for young veterans to prevent escalation of drinking and development of long-term alcohol problems . Given the simplicity of the PNF approach and ease of administration , this intervention has the potential for a substantial impact on public health AIM To test the efficacy of an internet-based brief intervention ( IBI ) in decreasing alcohol use among young Swiss men aged 21 years on average . DESIGN Two parallel-group r and omized controlled trial with a 1 : 1 allocation ratio containing follow-up assessment s at 1 and 6 months post-r and omization SETTING Internet-based study in a general population sample . PARTICIPANTS Twenty-one-year-old men from Switzerl and with unhealthy alcohol use ( > 14 drinks/week or ≥ 6 drinks/occasion at least monthly or Alcohol Use Disorders Identification Test ( AUDIT ) scores ≥ 8) INTERVENTION : IBI consisting of ( 1 ) normative feedback , ( 2 ) feedback on consequences of alcohol use , ( 3 ) calorific value of reported consumption , ( 4 ) computed blood alcohol concentration for reported consumption , ( 5 ) indication of risk , ( 6 ) information on alcohol and health and ( 7 ) recommendations indicating low-risk drinking limits . Control condition : no intervention ( assessment only ) . MEASUREMENTS At 1 and 6 months : quantity/frequency questions on alcohol use ( primary outcome : number of drinks/week ) and binge drinking prevalence ; at 6 months : AUDIT score , consequences of drinking ( range = 0 - 12 ) . FINDINGS Follow-up rates were 92 % at 1 month and 91 % at 6 months . At 6 months , participants in the intervention group ( n = 367 ) reported greater reductions in the number of drinks/week than participants in the control group ( n = 370 ) [ treatment × time interaction , incidence rate ratio ( RR ) = 0.86 , 95 % confidence interval ( CI ) = 0.78 ; 0.96 ] , but no significant differences were observed on binge drinking prevalence . There was a favourable intervention effect on AUDIT scores ( IRR = 0.93 , 95 % CI = 0.88 ; 0.98 ) , but not on the number of consequences ( IRR = 0.93 , 95 % CI = 0.84 ; 1.03 ) . CONCLUSIONS An internet-based brief intervention directed at harmful alcohol use among young men led to a reduction in self-reported alcohol consumption and AUDIT scores compared with a no-intervention control condition ( assessment only ) |
2,690 | 19,338,710 | The results suggest that antipsychotics act regionally rather than globally on the brain .
These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use .
Indeed , there is evidence of a specific effect of antipsychotic type on the basal ganglia , with typicals specifically increasing the volume of these structures .
Differential effects of antipsychotic type may also be present on the thalamus and the cortex , but data on these and other brain areas are more equivocal .
Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis . | BACKGROUND The potential effects of antipsychotic drugs on brain structure represent a key factor in underst and ing neuroanatomical changes in psychosis .
This review addresses two issues : ( 1 ) do antipsychotic medications induce changes in total or regional human brain volumes and ( 2 ) do such effects depend on antipsychotic type ? | We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer 's disease ( AD ) . The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions , sparing sensorimotor cortices . The shifting deficits were asymmetric ( left hemisphere > right hemisphere ) and correlated with progressively declining cognitive status ( p < 0.0006 ) . Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD ( age 68.4 ± 1.9 years ) and 14 elderly matched controls ( age 71.4 ± 0.9 years ) scanned longitudinally ( two scans ; interscan interval 2.1 ± 0.4 years ) . A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time . Cortical atrophy occurred in a well defined sequence as the disease progressed , mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy . Advancing deficits were visualized as dynamic maps that change over time . Frontal regions , spared early in the disease , showed pervasive deficits later ( > 15 % loss ) . The maps distinguished different phases of AD and differentiated AD from normal aging . Local gray matter loss rates ( 5.3 ± 2.3 % per year in AD v 0.9 ± 0.9 % per year in controls ) were faster in the left hemisphere ( p < 0.029 ) than the right . Transient barriers to disease progression appeared at limbic/frontal boundaries . This degenerative sequence , observed in vivo as it developed , provides the first quantitative , dynamic visualization of cortical atrophic rates in normal elderly population s and in those with dementia OBJECTIVE Studies have found that cau date volume increased after treatment with typical antipsychotics in patients with schizophrenia but decreased after treatment was changed to clozapine . In the current study the authors examined whether this volume decrease was related to clinical improvement . METHOD Twenty-eight patients with schizophrenia who had not responded to treatment with typical antipsychotics were included in the study ; 22 completed the study . Cau date volume was assessed by using magnetic resonance imaging during treatment with typical antipsychotics and after 24 weeks and 52 weeks of clozapine treatment . Symptoms were assessed just before clozapine treatment and once a month thereafter . RESULTS Clozapine treatment result ed in a significant reduction in left cau date volume in patients who responded to the drug but not in patients who did not respond to clozapine at 52 weeks of treatment . Overall , the degree of reduction in left cau date volume was significantly related to the extent of improvement in positive and general symptoms but not in negative symptoms . CONCLUSIONS These findings suggest that the cau date nucleus plays a role in the positive and general symptoms of schizophrenia BACKGROUND Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described . Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome . This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia . OBJECTIVE To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition . DESIGN Longitudinal , r and omized , controlled , multisite , double-blind study . Patients treated and followed up for up to 104 weeks . Neurocognitive and magnetic resonance imaging ( MRI ) assessment s performed at weeks 0 ( baseline ) , 12 , 24 , 52 , and 104 . Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI , psychopathologic , and neurocognitive outcomes . SETTING Fourteen academic medical centers ( United States , 11 ; Canada , 1 ; Netherl and s , 1 ; Engl and , 1 ) . PARTICIPANTS Patients with first-episode psychosis ( DSM-IV ) and healthy volunteers . INTERVENTIONS R and om allocation to a conventional antipsychotic , haloperidol ( 2 - 20 mg/d ) , or an atypical antipsychotic , olanzapine ( 5 - 20 mg/d ) . MAIN OUTCOME MEASURES Brain volume changes assessed by MRI . RESULTS Of 263 r and omized patients , 161 had baseline and at least 1 postbaseline MRI evaluation . Haloperidol-treated patients exhibited significant decreases in gray matter volume , whereas olanzapine-treated patients did not . A matched sample of healthy volunteers ( n = 58 ) examined contemporaneously showed no change in gray matter volume . CONCLUSIONS Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes . Haloperidol was associated with significant reductions in gray matter volume , whereas olanzapine was not . Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated . The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine OBJECTIVE Multicenter trials with the novel antipsychotic risperidone have suggested a st and ard dose of 6 mg/day . However , a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients . The aim of this positron emission tomography ( PET ) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy . METHOD Eight first-episode or drug-free schizophrenic patients were treated with risperidone , 6 mg/day , for 4 weeks and then 3 mg/day for 2 weeks . PET was performed after 4 and 6 weeks , with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy . RESULTS Seven patients completed the study and responded to treatment with risperidone . No patient had extrapyramidal side effects at the time of inclusion in the study . At the 6-mg/day dose , mean D2 receptor occupancy was 82 % ( range = 79%-85 % ) , 5-HT2A receptor occupancy was 95 % ( range = 86%-109 % ) , and six patients had developed extrapyramidal side effects . After dose reduction to 3 mg/day , D2 receptor occupancy was 72 % ( range = 53%-78 % ) , and 5-HT2A receptor occupancy was 83 % ( range = 65%-112 % ) . Three patients had extrapyramidal side effects at this time . CONCLUSIONS Treatment with risperidone , 6 mg/day , is likely to induce unnecessarily high D2 receptor occupancy , with a consequent risk of extrapyramidal side effects . High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely . The authors previously suggested an optimal interval for D2 receptor occupancy of 70%-80 % . To achieve this , resperidone , 4 mg/day , should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks , as well as early ( pre/perinatal ) and late ( usually adolescent ) developmental brain abnormalities . With the use of brain mapping algorithms , we detected striking anatomical profiles of accelerated gray matter loss in very early-onset schizophrenia ; surprisingly , deficits moved in a dynamic pattern , enveloping increasing amounts of cortex throughout adolescence . Early-onset patients were rescanned prospect ively with MRI , at 2-year intervals at three time points , to uncover the dynamics and timing of disease progression during adolescence . The earliest deficits were found in parietal brain regions , supporting visuospatial and associative thinking , where adult deficits are known to be mediated by environmental ( nongenetic ) factors . Over 5 years , these deficits progressed anteriorly into temporal lobes , engulfing sensorimotor and dorsolateral prefrontal cortices , and frontal eye fields . These emerging patterns correlated with psychotic symptom severity and mirrored the neuromotor , auditory , visual search , and frontal executive impairments in the disease . In temporal regions , gray matter loss was completely absent early in the disease but became pervasive later . Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri , deficit regions found consistently in adult studies . These emerging dynamic patterns were ( i ) controlled for medication and IQ effects , ( ii ) replicated in independent groups of males and females , and ( iii ) charted in individuals and groups . The result ing mapping strategy reveals a shifting pattern of tissue loss in schizophrenia . Aspects of the anatomy and dynamics of disease are uncovered , in a changing profile that implicates genetic and nongenetic patterns of deficits While haloperidol is still widely used in the treatment of psychoses , the optimal daily dose remains a topic of controversy , particularly in first-episode psychosis . Previous studies have suggested that doses as low as 2 mg/d may be effective , whereas others have indicated superiority for higher over lower doses . This double-blinded , r and omized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis . Both treatments were equally effective in reducing the PANSS Total and subscale scores . The low dose of haloperidol was better tolerated , with fewer extrapyramidal side-effects , less frequent use of anticholinergic medication and smaller elevations in prolactin levels . Using a low dose of haloperidol is at least as effective as , and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis OBJECTIVE A follow-up study of patients with schizophrenia was conducted to examine change in striatal volumes and extrapyramidal symptoms after a change in medication . METHOD Thirty-seven patients with schizophrenia and 23 healthy volunteers were examined . Patients at baseline receiving typical antipsychotics ( N=10 ) or risperidone but exhibiting limited response ( N=13 ) were switched to treatment with olanzapine . Patients receiving risperidone and exhibiting a good response ( N=14 ) continued treatment with risperidone . Cau date , putamen , and pallidal volumes were assessed with magnetic resonance imaging . The Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and symptoms . RESULTS At baseline , basal ganglia volumes in patients treated with typical antipsychotics were greater than in healthy subjects ( putamen : 7.0 % larger ; globus pallidus : 20.7 % larger ) . After the switch to olanzapine , putamen and globus pallidus volumes decreased ( 9.8 % and 10.7 % , respectively ) and did not differ from those of healthy subjects at the follow-up evaluation . Akathisia was also reduced . In the patients receiving risperidone at baseline , basal ganglia volumes did not differ between those exhibiting good and poor response , and no significant volume changes were observed in subjects with poor risperidone response after the switch to olanzapine treatment . CONCLUSIONS Olanzapine reversed putamen and globus pallidus enlargement induced by typical antipsychotics but did not alter volumes in patients previously treated with risperidone . Changes in striatal volumes related to typical and atypical antipsychotics may represent an interactive effect between individual medications and unique patient characteristics BACKGROUND The midbrain contains the perikarya of all the dopamine neurons in the human brain . Although other neurochemicals may well be involved , dopamine dysregulation is central in the pathophysiology of psychosis . Despite this , few imaging studies have evaluated the morphology of the midbrain . METHODS Using high-resolution magnetic resonance imaging , morphology of three posterior fossa and brain stem structures were measured : midbrain , pons , and medulla . The patient sample consisted of 50 men with schizophrenia , matched by gender and age to 50 healthy control subjects . RESULTS Patients had significantly smaller midbrain measures compared with control subjects . There were no differences between groups in measures of pons or medulla . Furthermore , midbrain size was significantly and inversely correlated with positive symptoms and cumulative neuroleptic exposure , but not with negative or disorganized symptoms . After controlling for the effect of cumulative neuroleptic exposure , the relationship between midbrain morphology and positive symptoms remained significant . CONCLUSIONS Midbrain morphology of patients with schizophrenia is abnormal , being smaller in patients compared with control subjects . Although this appears to be specifically related to psychotic symptoms , there is also a robust medication effect , with greater exposure to neuroleptics being associated with greater morphologic abnormality . We discuss the role of dopaminergic dysregulation and possible neural circuit involvement Positron Emission Tomography ( PET ) imaging of regional cerebral blood flow ( rCBF ) provides an in vivo method for sup study ing brain function . We used [15O]H2O PET to assess the effect of antipsychotic medications on rCBF in 17 subjects with schizophrenia . Each subject was scanned while receiving antipsychotic medication , and after having been withdrawn from antipsychotic medication for a 3-week period . The two scans were subtracted from one another , using a within subjects design , and the areas of difference were identified using the Montreal method . Subjects treated with antipsychotic medication had significantly higher rCBF in the left basal ganglia and left fusiform gyrus compared with the " off-medication " condition . Significantly higher relative rCBF in the anterior cingulate , left dorsolateral and inferior frontal cortex , and left and right cerebellum was observed when off antipsychotic medication . Upregulation of dopamine D2 receptors may lead to a regional increase of blood flow and metabolism in the basal ganglia , which may explain recently reported anatomical enlargement in these regions BACKGROUND Second-generation antipsychotics ( SGAs ) differ from first-generation antipsychotics ( FGAs ) with respect to induction of less extrapyramidal morbidity , partially reducing negative symptoms , and causing modest improvement in neurocognitive functioning in patients with schizophrenia . SGAs demonstrate 5-HT2a antagonism . Differential effects of SGAs and FGAs on cortical gray volumes are explored herein . METHODS Cerebral cortical gray was examined volumetrically in 19 patients with schizophrenia before and following 28 days of treatment with two SGAs ( risperidone and ziprasidone ; n = 13 ) or a FGA ( haloperidol ; n = 6 ) . Seven ( untreated ) control subjects were also assessed at a similar interval . RESULTS During treatment with the SGAs risperidone and ziprasidone , cerebral cortical gray of 13 patients with schizophrenia exp and ed 20.6 + /- 11.4 cc ( p < .0005 ) . Six patients receiving the FGA haloperidol , as well as 7 control subjects , showed no change in cortical gray volumes ( p = .983 and p = .932 , respectively ) at the time of re assessment . CONCLUSIONS Volumetric increase of cerebral cortical gray occurred early in the course of treatment with the SGAs ziprasidone and risperidone , but not with the FGA haloperidol . Such cortical gray expansion may be relevant to the reported enhanced neurocognition and quality of life associated with SGA treatment Typical antipsychotic drugs act on the dopaminergic system , blocking the dopamine type 2 ( D2 ) receptors . Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors , and a high degree of occupancy of the serotoninergic receptors 5-HT2A . Whether these different pharmacological actions produce different effects on brain structure remains unclear . We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based , nonr and omized sample of patients at the first psychotic episode . Subjects were recruited as part of a large epidemiological study ( ÆSOP : aetiology and ethnicity in schizophrenia and other psychoses ) . We evaluated 22 drug-free patients , 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics . We used high-resolution MRI and voxel-based methods of image analysis . The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes . However , typicals seem to affect more extensively the basal ganglia ( enlargement of the putamen ) and cortical areas ( reductions of lobulus para central is , anterior cingulate gyrus , superior and medial frontal gyri , superior and middle temporal gyri , insula , and precuneus ) , while atypical antipsychotics seem particularly associated with enlargement of the thalami . These changes are likely to reflect the effect of antipsychotics on the brain , as there were no differences in duration of illness , total symptoms scores , and length of treatment among the groups . In conclusion , we would like to suggest that even after short-term treatment , typical and atypical antipsychotics may affect brain structure differently BACKGROUND Atypical antipsychotics , such as risperidone , have been shown to be more effective for the treatment of the symptoms of schizophrenia and have a greater beneficial effect on neurocognition compared to the conventional antipsychotics . The present study used [(15)O]H(2)O positron emission tomography imaging of regional cerebral blood flow to examine and compare the effects of haloperidol and risperidone on brain function . METHODS Thirty-two subjects with schizophrenia participated in the study . Each subject was scanned in a medication-free state , and after being on a stable clinical ly assigned dose of either risperidone or haloperidol for 3 weeks . The off-medication scan was subtracted from the on-medication scan , using a within-subjects design . A r and omization analysis was used to determine differences between the effects of haloperidol and risperidone on regional cerebral blood flow . RESULTS Haloperidol was associated with a significantly greater increase in regional cerebral blood flow in the left putamen and posterior cingulate , and a significantly greater decrease in regional cerebral blood flow in frontal regions compared to risperidone . Risperidone was associated with a significantly greater decrease in regional cerebral blood flow in the cerebellum bilaterally compared to haloperidol . CONCLUSIONS The results show that risperidone and haloperidol have significantly different effects on brain function , which may be related to their differences in efficacy and side effects . Further work is required to more precisely determine the mechanisms by which different antipsychotic medications exert their therapeutic effects on the clinical symptoms and cognition in schizophrenia . These findings emphasize the importance of controlling for both medication status and the individual antipsychotic in neuroimaging studies The purpose of this pilot study was to : ( 1 ) determine if regional brain volume change occurs in schizophrenia patients during very short periods of withdrawal from , or stable treatment with , antipsychotics , and ; ( 2 ) compare results of region-of-interest ( ROI ) to voxel-based morphometry ( VBM ) methods . In two small groups of schizophrenic in patients , magnetic resonance imaging was performed before and after antipsychotic withdrawal , and at two time points during stable chronic antipsychotic treatment . Regional brain volumes were measured using ROI methods . Grey matter volume was measured with VBM . The medication withdrawal group showed no effect of treatment state or antipsychotic type on regional brain volumes with ROI analysis , but effects of both treatment state and antipsychotic type on grey matter volume were observed with VBM in right middle frontal , right medial frontal , right and left superior frontal , right cingulate , and right superior temporal gyrii as well as in the right and left hippocampal gyrii . The chronic stable treatment group showed an effect of time on right cau date , left hippocampal , and total cerebrospinal fluid volumes with ROI analysis , while effects of both time and antipsychotic type were observed with VBM on grey matter volume in the left superior temporal lobe . No findings survived correction for multiple comparisons . A positive correlation between regional volume change and emerging psychopathology was demonstrated using ROI methods in the medication withdrawal group . Treatment state and emergent symptoms in schizophrenia patients were associated with regional volume change over very short time periods . Longitudinal regional brain volume change in schizophrenia patients is likely physiologic and therefore potentially reversible |
2,691 | 29,047,342 | First , the use of acetylsalicylic acid ( ASA ) for primary prevention of cardiovascular disease ( CVD ) in older people can not be recommended due to an uncertainty in the risk-benefit ratio ( weak recommendation ; low quality of evidence ) .
Secondly , the combination of ASA and clopidogrel in patients without specific indications should be avoided ( strong recommendation ; moderate quality of evidence ) .
Conclusions The use of ASA for the primary prevention of CVD and the combination therapy of ASA and clopidogrel for the secondary prevention of vascular events in older people may not be justified . | Background Platelet aggregation inhibitors ( PAI ) are among the most frequently prescribed drugs in older people , though evidence about risks and benefits of their use in older adults is scarce .
The objectives of this systematic review are firstly to identify the risks and benefits of their use in the prevention and treatment of vascular events in older adults , and secondly to develop recommendations on discontinuing PAI in this population if risks outweigh benefits . | Background and Purpose — The effect of aspirin in primary prevention of stroke is controversial among clinical trials conducted in Western countries , and no data are available for Asian population s with a high risk of intracranial hemorrhage . The objective of this study was to evaluate the effect of aspirin on the risk of stroke and intracranial hemorrhage in the Japanese Primary Prevention Project ( JPPP ) . Methods — A total of 14 464 patients ( age , 60–85 years ) with hypertension , dyslipidemia , and diabetes mellitus participated and were r and omized into 2 treatment groups : 100 mg of aspirin or no aspirin . The median follow-up period was 5.02 years . Results — The cumulative rate of fatal or nonfatal stroke was similar for the aspirin ( 2.068 % ; 95 % confidence interval [ CI ] , 1.750–2.443 ) and no aspirin ( 2.299 % ; 95 % CI , 1.963–2.692 ) groups at 5 years ; the estimated hazard ratio was 0.927 ( 95 % CI , 0.741–1.160 ; P=0.509 ) . Aspirin nonsignificantly reduced the risk of ischemic stroke or transient ischemic attack ( hazard ratio , 0.783 ; 95 % CI , 0.606–1.012 ; P=0.061 ) and nonsignificantly increased the risk of intracranial hemorrhage ( hazard ratio , 1.463 ; 95 % CI ; 0.956–2.237 ; P=0.078 ) . A Cox regression adjusted by the risk factors for all stroke , which were age > 70 years , smoking , and diabetes mellitus , supported the above result . Conclusions — Aspirin did not show any net benefit for the primary prevention of stroke in elderly Japanese patients with risk factors for stroke , whereas age > 70 years , smoking , and diabetes mellitus were risk factors for stroke regardless of aspirin treatment . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00225849 OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMSTAR ) . We report on reliability ( interobserver kappas of the 11 AMSTAR items ) , intraclass correlation coefficients ( ICCs ) of the sum scores , construct validity ( ICCs of the sum scores of AMSTAR compared with those of other instruments ) , and completion times . RESULTS The interrater agreement of the individual items of AMSTAR was substantial with a mean kappa of 0.70 ( 95 % confidence interval [ CI ] : 0.57 , 0.83 ) ( range : 0.38 - 1.0 ) . Kappas recorded for the other instruments were 0.63 ( 95 % CI : 0.38 , 0.78 ) for enhanced OQAQ and 0.40 ( 95 % CI : 0.29 , 0.50 ) for the Sacks ' instrument . The ICC of the total score for AMSTAR was 0.84 ( 95 % CI : 0.65 , 0.92 ) compared with 0.91 ( 95 % CI : 0.82 , 0.96 ) for OQAQ and 0.86 ( 95 % CI : 0.71 , 0.94 ) for the Sacks ' instrument . AMSTAR proved easy to apply , each review taking about 15 minutes to complete . CONCLUSIONS AMSTAR has good agreement , reliability , construct validity , and feasibility . These findings need confirmation by a broader range of assessors and a more diverse range of review Background Multimorbidity is increasing in aging population s with a corresponding increase in polypharmacy as well as inappropriate prescribing . Depending on definitions , 25 - 50 % of patients aged 75 years or older are exposed to at least five drugs . Evidence is increasing that polypharmacy , even when guidelines advise the prescribing of each drug individually , can potentially cause more harm than benefit to older patients , due to factors such as drug-drug and drug-disease interactions . Several approaches reducing polypharmacy and inappropriate prescribing have been proposed , but evidence showing a benefit of these measures regarding clinical ly relevant endpoints is scarce . There is an urgent need to implement more effective strategies . We therefore set out to develop an evidence -based electronic decision support ( eDS ) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-r and omized controlled trial . Methods The “ Polypharmacy in chronic diseases – Reduction of Inappropriate Medication and Adverse drug events in older population s ” (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic review s and guidelines , the European list of inappropriate medications for older people , the SFINX- data base of interactions , the PHARAO- data base on adverse effects , and the RENBASE- data base on renal dosing . The tool will be evaluated in a cluster-r and omized controlled trial involving 325 general practitioners ( GPs ) and around 3500 patients across five study centres in the United Kingdom , Germany , Austria and Italy . GP practice s will be asked to recruit 11 patients aged 75 years or older who are taking at least eight medications and will be cluster-r and omized after completion of patient recruitment . Intervention GPs will have access to the PRIMA-eDS tool , while control GPs will treat their patients according to current guidelines ( usual care ) without access to the PRIMA-eDS tool . After an observation time of 2 years , intervention and control groups will be compared regarding the primary composite endpoint of first non-elective hospitalization or death . Discussion The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death . A positive result of the trial will contribute substantially to the improvement of care in multimorbidity . The trial is necessary to investigate not only whether the reduction of polypharmacy improves outcome , but also whether GPs and patients are willing to follow the recommendations of the PRIMA-eDS tool . Trial registration This trial has been registered with Current Controlled Trials Ltd. on 31 July 2014 ( IS RCT N10137559 ) CONTEXT Previous trials have investigated the effects of low-dose aspirin on primary prevention of cardiovascular events , but not in patients with type 2 diabetes . OBJECTIVE To examine the efficacy of low-dose aspirin for the primary prevention of atherosclerotic events in patients with type 2 diabetes . DESIGN , SETTING , AND PARTICIPANTS Multicenter , prospect i ve , r and omized , open-label , blinded , end-point trial conducted from December 2002 through April 2008 at 163 institutions throughout Japan , which enrolled 2539 patients with type 2 diabetes without a history of atherosclerotic disease and had a median follow-up of 4.37 years . INTERVENTIONS Patients were assigned to the low-dose aspirin group ( 81 or 100 mg per day ) or the nonaspirin group . MAIN OUTCOME MEASURES Primary end points were atherosclerotic events , including fatal or nonfatal ischemic heart disease , fatal or nonfatal stroke , and peripheral arterial disease . Secondary end points included each primary end point and combinations of primary end points as well as death from any cause . RESULTS A total of 154 atherosclerotic events occurred : 68 in the aspirin group ( 13.6 per 1000 person-years ) and 86 in the nonaspirin group ( 17.0 per 1000 person-years ) ( hazard ratio [ HR ] , 0.80 ; 95 % confidence interval [ CI ] , 0.58 - 1.10 ; log-rank test , P = .16 ) . The combined end point of fatal coronary events and fatal cerebrovascular events occurred in 1 patient ( stroke ) in the aspirin group and 10 patients ( 5 fatal myocardial infa rct ions and 5 fatal strokes ) in the nonaspirin group ( HR , 0.10 ; 95 % CI , 0.01 - 0.79 ; P = .0037 ) . A total of 34 patients in the aspirin group and 38 patients in the nonaspirin group died from any cause ( HR , 0.90 ; 95 % CI , 0.57 - 1.14 ; log-rank test , P = .67 ) . The composite of hemorrhagic stroke and significant gastrointestinal bleeding was not significantly different between the aspirin and nonaspirin groups . CONCLUSION In this study of patients with type 2 diabetes , low-dose aspirin as primary prevention did not reduce the risk of cardiovascular events . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00110448 Background — Patients with a non – ST-elevation acute coronary syndrome and prior CABG are at high risk of a recurrent ischemic event despite aspirin therapy . This trial investigated the potential benefit of secondary prevention with warfarin . Methods and Results —In a double-blind r and omized trial , 135 patients with unstable angina or non – ST-segment elevation myocardial infa rct ion , with prior CABG , and who were poor c and i date s for a revascularization procedure received therapy with aspirin and placebo+warfarin , warfarin and placebo+aspirin , or aspirin and warfarin for 12 months . Warfarin was titrated to an international normalized ratio of 2.0 to 2.5 . The primary end point ( death or myocardial infa rct ion or unstable angina requiring hospitalization 1 year after r and omization ) occurred in 14.6 % of the patients in the warfarin-alone group , in 11.5 % of patients in the aspirin-alone group , and in 11.3 % of patients r and omized to the combination therapy ( P = 0.76 ) . Subgroup analyses by risk features provided no indications that warfarin alone or in combination with aspirin could be of benefit over aspirin alone . Bleeding was more frequent in the 2 groups of patients administered warfarin . Conclusions —Moderate-intensity oral anticoagulation alone or combined with low-dose aspirin does not appear to be superior to low-dose aspirin in the prevention of recurrent ischemic events in patients with non – ST-elevation acute coronary syndromes and previous CABG OBJECTIVE We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment ( HOT ) study . DESIGN AND INTERVENTIONS The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure ( BP ) ( < or = 90 , < or = 85 or < or = 80 mmHg ) and cardiovascular ( CV ) events in hypertensive patients , and to examine the effects of 75 mg acetylsalicylic acid ( ASA ) daily versus placebo . SETTING Outpatient clinical trial in 26 countries . PATIENTS A total of 18790 patients ( mean age 61.5 years , range 50 - 80 ) were r and omized and followed for an average of 3.8 years until 71051 patient-years and 683 events had occurred . MAIN OUTCOME MEASURES CV death , myocardial infa rct ion ( MI ) and stroke . RESULTS There were significantly fewer MIs in those in the lower diastolic BP target groups ( 3.0 versus 1.2 and 1.7 MIs/1000 patient-years , P for trend = 0.034 ) in women ( n = 8883 ) , whereas the similar but smaller trend ( 4.1 versus 4.1 and 3.4 MIs/1000 patient-years ) was not statistically significant in men nor in the subgroup analysis of younger and older subjects . The effect of ASA on preventing MI was not influenced by age < 65 years ( P= 0.02 ) or age > or = 65 years ( P = 0.04 ) but was influenced by gender ( P = 0.38 in women and P = 0.001 in men , lowered by 42 % corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years ) . CONCLUSIONS The data of this HOT study sub- analysis suggest somewhat differentiated optimal gender- and age-dependent effects of anti-hypertensive and anti-platelet therapies ; lowering of diastolic BP to about 80 mmHg in hypertensive women and , in addition , the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication , i.e. myocardial infa rct ion , in patients with essential hypertension BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin Within 3 weeks of the event , 505 patients with cerebral infa rct ion , minor or major stroke , were r and omly assigned to treatment with acetylsalicylic acid ( ASA ) 1.5 g/day or placebo in a double-blind clinical trial with a follow-up of 2 years in all patients . Primary events were considered to be recurrent stroke or death ; secondary events , myocardial infa rct ion and transient ischemic attack . There was no difference in stroke recurrence rate in the ASA and placebo groups ( 12 and 13 % , respectively ) , nor was there any significant difference in the rate of recurrent stroke or death , first event counted ( 23 % in the ASA and 22 % in the placebo group ) . The risk of transient ischemic attack and myocardial infa rct ion was not reduced in the ASA group . In the present study there was no prophylactic effect of high-dose ASA after cerebral infa rct ion . A compilation of the major trials of ASA after transient ischemic attack and cerebral infa rct ion is presented BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . Cost-effective strategies to maintain healthy active lifestyle in aging population s are required to address the global burden of age-related diseases . ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals . Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed ' disability-free life ' including onset of dementia , total mortality , or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above ( ' US minorities ' ) and 70 years and above ( non-'US minorities ' ) . ASPREE is a double-blind , r and omized , placebo-controlled trial of oral 100 mg enteric-coated acetyl salicylic acid ( ASA ) or matching placebo being conducted in Australian and US community setting s on individuals free of dementia , disability and cardiovascular disease ( CVD ) events . Secondary endpoints are all-cause and cause specific mortality , fatal and non-fatal cardiovascular events , fatal and non-fatal cancer ( excluding non-melanoma skin cancer ) , dementia , mild cognitive impairment , depression , physical disability , and clinical ly significant bleeding . To 20 September 2013 14,383 participants have been recruited . Recruitment and study completion are anticipated in July 2014 and December 2018 respectively . In contrast to other aspirin trials that have largely focused on cardiovascular endpoints , ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia BACKGROUND Atrial fibrillation is a common problem in older people . The evidence base for the safety of warfarin and aspirin in atrial fibrillation is largely derived from selective research studies and secondary care . Further assessment of the safety of warfarin in older people with atrial fibrillation in routine primary care is needed . AIM To measure the complication rates and adequacy of warfarin control in a cohort of patients with atrial fibrillation managed in primary care and compare them with published data from controlled trials and community patients with atrial fibrillation not receiving warfarin . DESIGN OF STUDY Retrospective review of regional cohort . SETTING Twenty-seven general practice s in southwest Scotl and . METHOD Case note review of 601 patients previously identified as having atrial fibrillation by GPs . RESULTS The average age of our cohort was 77 years at recruitment . Two hundred and sixty-four ( 44 % ) patients died within 5 years of follow up . Three hundred and nine of the 601 ( 51 % ) patients with atrial fibrillation took warfarin at some stage during this study . INR ( international normalised ratio ) was maintained between 2 and 3 for 68 % of the time . Bleeding risk was higher in patients taking warfarin than in those on aspirin or no antithrombotic therapy ( warfarin 9.0 % per year versus aspirin 4.7 % per year versus no therapy 4.6 % per year ) . The annual risk of any bleeding complication on warfarin ( 9 % ) was similar to that recorded in r and omised trials ( 9.2 % ) whereas the annual risk of severe bleeding was approximately double ( 2.6 versus 1.3 % ) . CONCLUSION Adequacy of anticoagulant control was broadly comparable to that reported in clinical trials , whereas the risk of severe bleeding was higher , possibly reflecting the older age and the comorbidities of our unselected cohort The adverse effects of low‐dose aspirin ( 100 mg daily ) in the elderly were studied over a 12‐month period in a double‐blind , r and omized , placebo‐controlled trial of 400 subjects who were 70 years of age or older and had no preexisting major vascular diseases at the time of entry . Subjects were r and omized so that 200 subjects received low‐dose enteric‐coated aspirin ( 100 mg daily ) and 200 subjects received placebo . Compliance with medication , assessed by pill count , was 86 % . Gastrointestinal symptoms were reported by 18 % ( n = 36 ) of participants receiving aspirin and 13 % ( n = 26 ) of those receiving placebo . Clinical ly evident gastrointestinal bleeding occurred in 3 % ( n = 6 ) of subjects receiving aspirin and none receiving placebo . Aspirin‐treated subjects had a significant decrease in mean hemoglobin levels of 0.33 gm/dl during the 12‐month study period , which was significantly greater than the decrease in the placebo‐treated group ( 0.11 gm/dl ; p < 0.05 ) . These rates of unwanted symptoms are comparable with previous studies that used higher doses of aspirin . Until the risk‐benefit trade‐off from the use of low‐dose aspirin in the elderly is established with an appropriate clinical trial , caution should be exercised when this compound is used for primary prevention of cardiovascular disease in this age group STUDY OBJECTIVE To identify predictors of hospital admissions associated with adverse drug events ( ADEs ) and to determine the preventability of ADEs in patients admitted to two hospitals . DESIGN Prospect i ve observational study . SETTING Medical admission units at two British National Health Service hospitals in the United Kingdom . PATIENTS 3904 adults age 16 years or older who were admitted to the two hospitals between June 2006 and November 2007 . MEASUREMENTS AND MAIN RESULTS Clinical pharmacists identified hospital admissions associated with drug-related problems by using medical record review , supplemented by patient interview for those identified as having an ADE . The contribution of ADEs to hospital admission and the causality , severity , and preventability of the events were independently assessed by a multidisciplinary clinical team . Multivariate logistic regression was used to identify predictors of hospital admissions associated with ADEs , and a maximum-likelihood multinomial model was used to examine predictors of the preventability of ADEs . Of the 3904 patients included in the analysis , 439 ( 11.2 % ) were judged by the review panel to have experienced ADEs . Of these , 209 patients ( 47.6 % ) experienced preventable ADEs . Four independent variables were found to have significant relationships with ADE admissions and preventability of ADEs : patient age , length of time since starting new drug , total number of prescription drugs , and hospital site . Drug classes most commonly associated with preventable ADEs were antiplatelet drugs , anticoagulants , diuretics ( loop and thiazide diuretics ) , angiotensin-converting enzyme inhibitors , and antiepileptic drugs . CONCLUSION Adverse drug events are an important cause of hospital admission . Better systems for health care practitioners to identify patients at high risk of preventable hospital admissions associated with ADEs ( e.g. , age > 65 years old , receiving more than five drugs , and starting new high-risk drugs ) should be implemented in order to minimize the risks to patients and the burden on the health care system Warfarin is an established treatment for prevention of ischaemic stroke in patients with atrial fibrillation , but the value of this agent relative to aspirin in unclear . In the first Stroke Prevention in Atrial Fibrillation ( SPAF-I ) study , direct comparison of warfarin with aspirin was limited by the small number of thromboembolic events . SPAF-II aims to address this issue and also to assess the differential effects of the two treatments according to age . We compared warfarin ( prothrombin time ratio 1.3 - 1.8 , international normalised ratio 2.0 - 4.5 ) with aspirin 325 mg daily for prevention of ischaemic stroke and systemic embolism ( primary events ) in two parallel r and omised trials involving 715 patients aged 75 years or less and 385 patients older than 75 ; we sought reductions in the absolute rate of primary events by warfarin compared with aspirin of 2 % per year and 4 % per year , respectively . In the younger patients , warfarin decreased the absolute rate of primary events by 0.7 % per year ( 95 % CI-0.4 to 1.7 ) . The primary event rate per year was 1.3 % with warfarin and 1.9 % with aspirin ( relative risk [ RR ] 0.67 , p = 0.24 ) . The absolute rate of primary events in low-risk younger patients ( without hypertension , recent heart failure , or previous thromboembolism ) on aspirin was 0.5 % per year ( 95 % CI 0.1 to 1.9 ) . Among older patients , warfarin decreased the absolute rate of primary events by 1.2 % per year ( 95 % CI-1.7 to 4.1 ) . The primary event rate per year was 3.6 % with warfarin and 4.8 % with aspirin ( RR 0.73 , p = 0.39 ) . In this older group , the rate of all stroke with residual deficit ( ischaemic or haemorrhagic ) was 4.3 % per year with aspirin and 4.6 % per year with warfarin ( RR 1.1 ) . Warfarin may be more effective than aspirin for prevention of ischaemic stroke in patients with atrial fibrillation , but the absolute reduction in stroke rate by warfarin is small . Younger patients without risk factors had a low rate of stroke when treated with aspirin . In older patients the rate of stroke ( ischaemic and haemorrhagic ) was substantial , irrespective of which agent was given . Patient age and the inherent risk of thromboembolism should be considered in the choice of antithrombotic prophylaxis for patients with atrial fibrillation Several studies have established the value of anticoagulation for primary prevention of thromboembolic events in patients with non-rheumatic atrial fibrillation ( NRAF ) . However , in patients with a recent transient ischaemic attack ( TIA ) or minor ischaemic stroke the preventive benefit of anticoagulation or aspirin remains unclear . Physicians in 108 centres from 13 countries collaborated to study this question . 1007 NRAF patients with a recent TIA or minor ischaemic stroke were r and omised to open anticoagulation or double-blind treatment with either 300 mg aspirin per day or placebo ( group 1 , 669 ) . Patients with contraindications to anticoagulation were r and omised to receive aspirin or placebo ( group 2,338 ) . The measure of outcome was death from vascular disease , any stroke , myocardial infa rct ion , or systemic embolism . During mean follow-up of 2.3 years , the annual rate of outcome events was 8 % in patients assigned to anticoagulants vs 17 % in placebo-treated patients in group 1 ( hazard ratio [ HR ] 0.53 ; 95 % confidence interval [ CI ] 0.36 - 0.79 ) . The risk of stroke alone was reduced from 12 % to 4 % per year ( HR 0.34 ; 95 % CI 0.20 - 0.57 ) . Among all patients assigned to aspirin ( groups 1 and 2 ) , the annual incidence of outcome events was 15 % , against 19 % in those on placebo ( HR 0.83 ; 95 % CI 0.65 - 1.05 ) . Anticoagulation was significantly more effective than aspirin ( HR 0.60 ; 95 % CI 0.41 - 0.87 ) . The incidence of major bleeding events was low , both on anticoagulation ( 2.8 % per year ) and on aspirin ( 0.9 % per year ) . No intracranial bleeds were identified in patients assigned to anticoagulation . We conclude that anticoagulation is effective in reducing the risk of recurrent vascular events in NRAF patients with a recent TIA or minor ischaemic stroke . In absolute terms : 90 vascular events ( mainly strokes ) are prevented if 1000 patients are treated with anticoagulation for one year . Aspirin is a safe , though less effective , alternative when anticoagulation is contraindicated ; it prevents 40 vascular events each year for every 1000 treated patients OBJECTIVE To compare the therapeutic warfarin and aspirin efficacies for treatments of atrial fibrillation ( AF ) complicated with stable coronary heart disease particularly in older Chinese patients . METHODS In our prospect i ve study 101 patients with AF and stable coronary heart disease older than 80 years were r and omized into two groups . One group ( n = 51 ) basically received 1.25 mg/day warfarin per os , followed by addition of 0.5 - 1.0 mg/day from day 3 - 5 if the international normalized ratio ( INR ) was initially < 1.5 and in order to achieve a maintained INR between 1.6 and 2.5 ( warfarin group ) . The second group ( n = 50 ) received 100 mg aspirin per day ( control group ) . All patients were medicated and monitored for a period of 2 years . The primary endpoint was the occurrence of ischemic stroke or systemic embolism , and the composite secondary endpoint was non-fatal myocardial infa rct ion and all causes of death . For safety evaluation , the hemorrhage rates were recorded . RESULTS The warfarin medication was superior regarding the overall occurrence of ischemic stroke or systemic embolism as well as non-fatal myocardial infa rct ion and all causes of death outcomes compared to aspirin administration during the 2 years of medication ( 17.6 % vs. 36.0 % , p = 0.03 ) , while there was no significant difference of mild ( 5 vs. 4 ) , severe ( 2 vs. 1 ) , and fatal ( 1 vs. 1 ) hemorrhage incidences between the warfarin and aspirin groups ( p > 0.05 ) . CONCLUSION Warfarin was found to be more efficacious than aspirin for an anticoagulation therapy of older Chinese patients with AF and stable coronary heart disease |
2,692 | 26,137,968 | Conclusions Based on the evidence of few r and omised and mostly controlled series , mortality and morbidity were significantly lower after laparoscopy compared to open surgery | Purpose While definitive long-term results are not yet available , the global safety and oncologic adequacy of laparoscopic surgery for right colectomy remain controversial .
The aim of the study was to evaluate differences in safety of laparoscopic right colectomy , compared with open surgery , with particular attention to cancer patients . | Purpose sThis study aims to compare the perioperative outcomes and survival between laparoscopic-assisted right hemicolectomy ( LARH ) and open right hemicolectomy ( ORH ) for right-sided colon cancer . Methods Between July 1996 and October 2005 , 145 patients were r and omized to receive LARH ( n = 71 ) or ORH ( n = 74 ) . Results The median follow-up of living patients was 99.7 months . The demographic data of the two groups were similar . The time to resume diet ( 4 vs. 5 days , p = 0.045 ) and the hospital stay ( 7.8 vs. 10 days , p = 0.033 ) were significantly shorter in LARH group , but these benefits were at the expense of longer operating time ( 198 vs. 129 min , p = 0.002 ) and higher direct cost ( USD8745 vs. USD6293 , p < 0.001 ) . The morbidity and mortality were comparable between the two groups . After curative resection , the probabilities of survival at 5 years of the LARH and ORH groups were 74.2 % ( SE 7.4 % ) and 75 % ( SE 7.1 % ) , respectively . The probabilities of being disease free at 5 years were 82.3 % ( SE 6.9 % ) and 84.1 % ( SE 6.2 % ) , respectively . Conclusions Laparoscopic-assisted resection of right-sided colonic cancer has the advantage over open surgery in allowing earlier recovery . However this is at the expense of a longer operating time and higher direct cost ( registration number : NCT00485316 ( http://www . clinical trials.gov ) ) BACKGROUND Minimally invasive , laparoscopically assisted surgery was first considered in 1990 for patients undergoing colectomy for cancer . Concern that this approach would compromise survival by failing to achieve a proper oncologic resection or adequate staging or by altering patterns of recurrence ( based on frequent reports of tumor recurrences within surgical wounds ) prompted a controlled trial evaluation . METHODS We conducted a noninferiority trial at 48 institutions and r and omly assigned 872 patients with adenocarcinoma of the colon to undergo open or laparoscopically assisted colectomy performed by credentialed surgeons . The median follow-up was 4.4 years . The primary end point was the time to tumor recurrence . RESULTS At three years , the rates of recurrence were similar in the two groups--16 percent among patients in the group that underwent laparoscopically assisted surgery and 18 percent among patients in the open-colectomy group ( two-sided P=0.32 ; hazard ratio for recurrence , 0.86 ; 95 percent confidence interval , 0.63 to 1.17 ) . Recurrence rates in surgical wounds were less than 1 percent in both groups ( P=0.50 ) . The overall survival rate at three years was also very similar in the two groups ( 86 percent in the laparoscopic-surgery group and 85 percent in the open-colectomy group ; P=0.51 ; hazard ratio for death in the laparoscopic-surgery group , 0.91 ; 95 percent confidence interval , 0.68 to 1.21 ) , with no significant difference between groups in the time to recurrence or overall survival for patients with any stage of cancer . Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group , as reflected by a shorter median hospital stay ( five days vs. six days , P<0.001 ) and briefer use of parenteral narcotics ( three days vs. four days , P<0.001 ) and oral analgesics ( one day vs. two days , P=0.02 ) . The rates of intraoperative complications , 30-day postoperative mortality , complications at discharge and 60 days , hospital readmission , and reoperation were very similar between groups . CONCLUSIONS In this multi-institutional study , the rates of recurrent cancer were similar after laparoscopically assisted colectomy and open colectomy , suggesting that the laparoscopic approach is an acceptable alternative to open surgery for colon cancer Objective : This study aim ed to compare the outcomes of laparoscopic resection ( LR ) with open resection ( OR ) for right-sided colon cancer . Methods : During the study period from June 2000 to December 2004 , 182 patients ( 84 men ) underwent elective resection for cancer of the right colon . Laparoscopic resection was performed in 77 patients , while 105 patients had open operations . Patients who underwent operations on an emergency basis were excluded . Data on the patients ' demographics , operative details , and postoperative complications were collected prospect ively . The outcomes of patients with laparoscopic resection were compared with those of patients with open surgery . Results : There was no difference in the age , sex , presence of premorbid medical conditions , and blood loss between the 2 groups . The mean operative time for open resection was 115.4 minutes and that for laparoscopic resection was 165.1 minutes ( P<0.001 ) . Among the 77 patients who underwent laparoscopic resection , 7 ( 9 % ) required conversion to an open operation . There was no difference in postoperative surgically related complications including wound infection , leakage , intestinal obstruction , postoperative ileus . Nonsurgical-related complications were also similar . The median time to resumption of a normal diet was 3 days and 4 days in the laparoscopic and open groups , respectively . The median hospital stay in patients with laparoscopic resection was significantly shorter than in patients with open surgery ( 6.0 days vs 7.0 days , P<0.001 ) . The 2-year overall survival rates were 74 % in both groups ( P=0.904 ) . In the converted to open ( LCOR ) group , the hospital stay was significantly longer ( LR vs OR vs LCOR , 5.5 days vs 7.0 days vs 9.0 days respectively , P<0.001 ) . Conclusion : Laparoscopic right hemicolectomy is a safe option for cancers of the right colon . It is associated with a shorter hospital stay and earlier resumption of a normal diet . Mortality and morbidity are similar to that with the open approach . There is no compromise in the survival of patients BACKGROUND The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable . The multicentre COLOR ( COlon cancer Laparoscopic or Open Resection ) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon . METHODS 627 patients were r and omly assigned to laparoscopic surgery and 621 patients to open surgery . The primary endpoint was cancer-free survival 3 years after surgery . Secondary outcomes were short-term morbidity and mortality , number of positive resection margins , local recurrence , port-site or wound-site recurrence , metastasis , overall survival , and blood loss during surgery . Analysis was by intention to treat . Here , clinical characteristics , operative findings , and postoperative outcome are reported . FINDINGS Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection ( median 100 mL [ range 0 - 2700 ] vs 175 mL [ 0 - 2000 ] , p<0.0001 ) , although laparoscopic surgery lasted 30 min longer than did open surgery ( p<0.0001 ) . Conversion to open surgery was needed for 91 ( 17 % ) patients undergoing the laparoscopic procedure . Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups . Laparoscopic colectomy was associated with earlier recovery of bowel function ( p<0.0001 ) , need for fewer analgesics , and with a shorter hospital stay ( p<0.0001 ) compared with open colectomy . Morbidity and mortality 28 days after colectomy did not differ between groups . INTERPRETATION Laparoscopic surgery can be used for safe and radical resection of cancer in the right , left , and sigmoid colon PURPOSE : This study was undertaken to compare morbidity , mortality , and pathology after laparoscopically assisted right hemicolectomy ( LARHC ) or open right hemicolectomy ( ORHC ) for cancer of the right colon . METHODS : Patients undergoing either LARHC or ORHC for invasive carcinoma of the right colon during a 30-month period were studied . Data were collected from two sources . All morbidity , mortality , and pathology data were collected prospect ively in a form suitable for computer storage and analysis as part of the ongoing Concord Hospital Colorectal Cancer Registry . Data concerning in hospital course were obtained by casenote review . RESULTS : Twenty-eight patients underwent LARHC , and 33 had an ORHC during the study period . The two groups were well matched with respect to age , sex , weight , associated comorbidities , and tumor stage . Mean operating room use time was significantly higher for LARHC ( LARHC=261 minutes ; ORHC=203 minutes;P<0.001 ) . Mean hospital stay from date of resection was the same in both groups ( LARHC=12 days ; ORHC=12.2 days ) . There was no significant difference between procedures with respect to postoperative complications , return of gastrointestinal function , or narcotic analgesic requirements . There was a significant shorter distal margin of resection in the LARHC group ( ORHC=13.4 cm ; LARHC=10 cm;P=0.03 . ) . Total cost was significantly greater for LARHC ( $ 9,064vs.$7,881 (Australian);P<0.001 ) . Median follow-up was 23.4 months for the LARHC group and 23.9 months for the ORHC group . To date , there have been no local or port site recurrences . CONCLUSION : Although there is no difference in morbidity and mortality following LARHC or ORHC , there is no apparent benefit for LARHC Background The role of laparoscopic resection in the management of colon cancer is still a subject of debate . In this clinical study , we compared the perioperative results and long-term outcome for two unselected groups of patients undergoing either laparoscopic or open hemicolectomy for colon cancer . Methods This prospect i ve nonr and omized study was based on a series of 248 consecutive patients operated on by the same surgical team using the same type of surgical technique for right ( RHC ) and left ( LHC ) hemicolectomy , excluding segmental resections ; the only difference was the type of access , which was either laparoscopic or open . The choice of type of access was left up to the patient after he or she had read the informed consent form . Operative time , length of stay , complications , and long-term outcome for the two groups were compared . Follow-up time ranged between 12 and 92 months ( mean , 42 ) . Results Between March 1992 and January 2000 , 140 patients underwent a laparoscopic hemicolectomy ( 55 RHC and 86 LHC ) ; at the same time , 107 patients ( 44 RHC and 63 LHC ) were treated via an open approach . There were no conversions to open surgery in the laparoscopic RHC group , but six patients ( 7 % ) in the laparoscopic LHC group were converted . The mean operative time for laparoscopic surgery was significantly longer than the time for open surgery ( 190 vs 140 min for RHC , 240 vs 190 min for LHC ) ; however , with increasing experience , this time decreased significantly . The mean hospital stay for the patients who underwent laparoscopic procedures was significantly shorter in both the RHC and the LHC groups ( 9.2 vs 13.2 days for RHC , 10.0 vs 13.2 days for LHC ) . No statistically significant difference between the two laparoscopic and open groups was observed for the major complication rate ( 1.9 % vs 2.3 % for RHC , 7.5 % vs 6.3 % for LHC ) . The patient in the laparoscopic RHC group were lost to follow-up . The local recurrence rate was lower after laparoscopic surgery in both arms ( 5.4 % vs 9 % for RHC , 1.5 % vs 7.5 % for LHC ) , but the differences were not statistically significant . Two port site recurrences were observed in the laparoscopic groups , one after RHC ( 2.7 % ) and one after LHC ( 1.5 % ) . Metachronous metastases rates were similar for the two groups ( 16.2 % vs 15.1 % for RHC , 4.4 % vs 5.7 % for LHC ) . Cumulative survival probability at 48 months after laparoscopic RHC was 0.865 , as compared to 0.818 after open surgery , and 0.971 after laparoscopic LHC , as compared to 0.887 after open surgery . Conclusion These results suggest that laparoscopic hemicolectomy for colonic cancer can be performed safely , with morbidity , mortality , and long-term results comparable to those of open surgery Since 2001 we have conducted a prospect i ve r and omised study of right laparoscopic-assisted hemicolectomy vs open right hemicolectomy for right colon cancer in order to assess the differences in intraoperative and postoperative results as well as oncological clearance . Thirty-three patients with right colon cancer received laparoscopic-assisted right hemicolectomy ( LRH ) and were compared with 33 patients who underwent open right hemicolectomy ( ORH ) . We analysed morbidity and mortality , number of postoperative days of starving , postoperative days tolerating a liquid diet and a soft diet , duration of postoperative ileus , as well as the distance of the resection margin from the tumour ( < 5 cm or > 5 cm ) , and the number of lymph nodes found in the resected specimen . We also compared the length of operative time , blood loss , and any associated surgery . Morbidity occurred in 1 patient undergoing LRH ( 3.0 % ) as against 4 patients ( 12.1 % ) in the ORH group ( p < 0.05 ) . Postoperative ileus lasted 3.15 days ( range : 3 - 5 days ) in the LRH group vs 3.0 days ( range : 1 - 4 days ) in the ORH group . Median operative time was 251 min ( range : 130 - 360 min ) in the LRH group vs 222.9 min ( range : 135 - 360 min ) in the ORH group , while blood loss amounted to a median of 135 mi ( range : 100 - 300 ml ; SD + /- 42.9 mi ) in the LRH group vs. 404.1 ml ( range : 250 - 1000 ml ; SD + /- 159.3 ml ) in the ORH group ( p < 0.05 ) . The distance of the resection margin from the tumour was more than 5 cm in both groups . In the LRH group a median of 12.7 lymph nodes were removed ( range : 9 - 31 ; SD + /- 4.5 ) vs. 18 lymph nodes in the ORH group ( range : 8 - 29 ; SD + /- 3.9 ) ( p < 0.05 ) . Associated surgery was performed in 15.1 % of cases in both groups . In our experience LRH presents a statistically significant advantage in terms of morbidity and blood loss compared to ORH . Equivalent oncological clearance was obtained , fulfilling the stated criteria of 5 cm free resection margins and number of lymph nodes resected , though we removed fewer lymph nodes in LRH compared to ORH ( p < 0.05 ) BACKGROUND Enhanced Recovery after Surgery ( ERAS ) programs have gained popularity with potential to accelerate recovery and reduce morbidity after colectomy . We were interested in comparing recovery after open right colectomy within an ERAS program compared with laparoscopic right colectomy in a st and ard care perioperative environment . METHODS Between October 2005 and June 2009 , prospect i ve data were collected on consecutive patients undergoing elective open right colectomy within an established ERAS setting ( OpERAS ) . Similarly , between March 2008 and June 2009 , data were collected on consecutive patients undergoing laparoscopic right hemicolectomy with conventional care ( LapCon ) . Exclusion criteria for both groups were : ASA > or= 4 , formation of a stoma , and dementia or mental illness rendering the patient unable to comply with instructions . Perioperative variables were collected . The surgical recovery score ( SRS ) was used as a vali date d means to measure convalescence on d 1 , 3 , 7 , 30 , and 60 postoperatively . RESULTS There were 74 patients in the OpERAS and 39 patients in the LapCon groups . At baseline , there were no significant demographic differences except that more patients had malignancy in OpERAS group . Mean operating time was longer in the LapCon group . Median day stay was 4 ( 3 - 28 ) in OpERAS and 5 ( 2 - 18 ) in LapCon ( P = 0.032 ) . There was no statistical difference in the incidence of complications or the severity of complications . There were no significant differences in SRS after surgery at any time point . CONCLUSION When perioperative care is optimized , recovery after elective open right hemicolectomy is comparable with laparoscopic resection . Studies looking at the combination of laparoscopy and ERAS are warranted Laparoscopic right hemicolectomy has developed less markedly than rectosigmoid resection , probably because of the more complicated regional anatomy and greater difficulty in performing an adequate regional lymphectomy . The aim of the present study was to analyse our 5-year experience with laparoscopic right hemicolectomy . Twenty patients were enrolled with non-metastatic , non-infiltrating right colonic cancer , treated laparoscopically and compared to a group well matched for age , sex , comorbidity and stage of disease , treated laparotomically . The duration of the laparoscopic procedures was slightly longer , but intraoperative blood loss , passage of flatus and hospital stay were reduced compared to the laparotomic procedure . Morbidity was similar and there was no 30-day mortality in either group . Specimen length and number of harvested lymph nodes were similar and the 5-year cumulative survival curves showed no statistically significant difference ( 72.5 % versus 72.2 % ) . Our experience shows that laparoscopic right hemicolectomy is a safe , effective and oncologically adequate procedure , comparable in all respects to open hemicolectomy , but with all the advantages of the minimally invasive technique . Yet , it remains a complex surgical procedure , requiring skill and a long learning curve . Further studies , possibly prospect i ve and r and omised , are necessary to define the exact role of this technique for the treatment of non-metastatic , non-infiltrating right colonic cancer BACKGROUND Laparoscopic-assisted surgery for colorectal cancer has been widely adopted without data from large-scale r and omised trials to support its use . We compared short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer to predict long-term outcomes . METHODS Between July , 1996 , and July , 2002 , we undertook a multicentre , r and omised clinical trial in 794 patients with colorectal cancer from 27 UK centres . Patients were allocated to receive laparoscopic-assisted ( n=526 ) or open surgery ( n=268 ) . Primary short-term endpoints were positivity rates of circumferential and longitudinal resection margins , proportion of Dukes ' C2 tumours , and in-hospital mortality . Analysis was by intention to treat . This trial has been assigned the International St and ard R and omised Controlled Trial Number IS RCT N74883561 . FINDINGS Six patients ( two [ open ] , four [ laparoscopic ] ) had no surgery , and 23 had missing surgical data ( nine , 14 ) . 253 and 484 patients actually received open and laparoscopic-assisted treatment , respectively . 143 ( 29 % ) patients underwent conversion from laparoscopic to open surgery . Proportion of Dukes ' C2 tumours did not differ between treatments ( 18 [ 7 % ] patients , open vs 34 [ 6 % ] , laparoscopic ; difference -0.3 % , 95 % CI -3.9 to 3.4 % , p=0.89 ) , and neither did in-hospital mortality ( 13 [ 5 % ] vs 21 [ 4 % ] ; -0.9 % , -3.9 to 2.2 % , p=0.57 ) . Apart from patients undergoing laparoscopic anterior resection for rectal cancer , rates of positive resection margins were similar between treatment groups . Patients with converted treatment had raised complication rates . INTERPRETATION Laparoscopic-assisted surgery for cancer of the colon is as effective as open surgery in the short term and is likely to produce similar long-term outcomes . However , impaired short-term outcomes after laparoscopic-assisted anterior resection for cancer of the rectum do not yet justify its routine use |
2,693 | 19,591,680 | They calculated that due to shorter treatment periods , fewer complications and fewer inpatient episodes the initial cost of the novel biotechnology products may be offset , making the treatment cost-effective or even cost-saving .
Conclusion The study results suggest that some growth factors and tissue-engineered artificial skin products feature favourable cost-effectiveness ratios in selected patient groups with chronic wounds . | Background Tissue engineering is an emerging field .
Novel bioengineered skin substitutes and genetically derived growth factors offer innovative approaches to reduce the burden of diabetic foot and venous leg ulcers for both patients and health care systems .
However , they frequently are very costly .
Based on a systematic review of the literature , this study assesses the cost-effectiveness of these growth factors and tissue-engineered artificial skin for treating chronic wounds . | OBJECTIVE To test the safety , efficacy , and immunological impact of a cultured allogeneic human skin equivalent ( HSE ) in the treatment of venous ulcers . DESIGN Prospect i ve , r and omized study . SETTING Multicenter study in the outpatient setting . INTERVENTION Each patient with a venous ulcer received either compression therapy alone or compression therapy and treatment with HSE . The patients were evaluated for HSE safety , complete ( 100 % ) ulcer healing , time to wound closure , wound recurrence , and immune response to the HSE . OUTCOME The study was completed as planned in 293 r and omized patients . RESULTS Treatment with HSE was more effective than compression therapy in the percentage of patients healed by 6 months ( 63 % vs 49 % ; P=.02 , Fisher exact test , 2-tailed ) and the median time to complete wound closure ( 61 days vs 181 days ; P=.003 , log-rank test ) . Treatment with HSE was superior to compression therapy in healing larger ( > 1000 mm2 ; P=.02 ) and deeper ulcers ( P=.003 ) and ulcers of more than 6 months ' duration ( P=.001 ) . Occurrence of adverse events was similar in both groups . No symptoms or signs of rejection occurred in response to treatment with HSE , and no HSE-specific immune responses were detected in vitro to bovine collagen or to alloantigens expressed on keratinocytes or fibroblasts . CONCLUSIONS Treatment with HSE healed venous ulcers more rapidly and in more patients than compression therapy alone . There was no clinical or laboratory evidence of rejection or sensitization in response to HSE application . These data suggest that HSE represents a significant advance in the treatment of venous ulcers , particularly those that are difficult to heal In a prospect i ve study , 314 patients with diabetic foot ulcers were followed and 40 patients died before healing occurred . In those patients who healed , a retrospective economic analysis of the costs for topical treatment was performed . The aim of the study was to analyse the costs and discuss how different treatment strategies influence total costs . Data collected for each patient were total time to healing , treatment time for each type of dressing , and the frequency of dressing changes . Material costs for the dressings , labour , and travelling costs were calculated separately . A formula for simulation of economic consequences of different treatment strategies including the introduction of new strategies was design ed . The cost for topical treatment was strongly related to the severity of the ulcer and wound healing time . The average weekly cost per patient for topical treatment varied between 40.3 pounds and 385 pounds . The dominating costs for topical treatment were expenses for staff and transportation . The most important factor to reduce costs is the frequency of dressing changes . The study emphasizes the need for prospect i ve comparative studies of cost effectiveness in topical treatment strategies OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) . St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care OBJECTIVE To compare the efficacy and safety of topically applied recombinant human platelet-derived growth factor-BB ( rhPDGF-BB ) ( becaplermin ) with placebo gel in patients with chronic diabetic neuropathic ulcers of the lower extremities . RESEARCH DESIGN AND METHODS This multicenter double-blind placebo-controlled phase 111 trial included 382 patients with type 1 or type 2 diabetes and chronic ulcers of at least 8 weeks ' duration . After sharp debridement of the ulcer , patients were r and omized to receive becaplermin gel 30 μg/g , becaplermin gel 100 μg/g , or placebo gel , in conjunction with a st and ardized regimen of good wound care until complete wound closure was achieved or for a maximum of 20 weeks . Moist saline-soaked gauze dressings were changed twice daily with study medication applied by patients or caregivers at the evening dressing change . Safety was assessed by monitoring adverse events ( AEs ) and by clinical laboratory evaluations . RESULTS Compared with placebo gel , becaplermin gel 100 μg/g significantly increased the incidence of complete wound closure by 43 % ( 50 vs. 35 % , P = 0.007 ) and decreased the time to achieve complete wound closure by 32 % ( 86 vs. 127 days ; estimated 35th percentile , P = 0.013 ) . AEs reported during treatment or during a 3-month follow-up period were similar in nature and incidence across all treatment groups . CONCLUSIONS Becaplermin gel 100 μg/g , in conjunction with good wound care , significantly increased the incidence of complete wound closure and significantly reduced the time to complete closure of chronic diabetic neuropathic ulcers . The safety profile of becaplermin gel was similar to that of placebo gel Introduction : The effect on quality of life by healing leg ulcers is not known and no vali date d disease-specific tool is available for measuring health-related quality of life ( HRQoL ) for people with venous leg ulcers . The objective of this paper was to compare four generic instruments [ MOS 36-Item Short-Form Health Survey ( SF-36 ) ; EuroQol ( EQ ) ; McGill Short Form Pain Question naire ( SF-MPQ ) and the Frenchay Activities Index ( FAI ) ] used for measuring HRQoL in people with venous leg ulcers , and to offer guidance on the most appropriate tool for research ers . Methods : Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a r and omised controlled trial of the cost-effectiveness of community leg ulcer clinics . Subjects completed question naires containing the four instruments on three occasions ( initial assessment , 3 and 12 months ) . The discriminative and evaluative properties of the four instruments were compared . Results : All four instruments were acceptable to patients , taking a mean of 19.3 ( SD 6.3 ) min to complete . At initial assessment , the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration . The FAI was good at discriminating between the different patient groups ( at initial assessment ) in relation to age , mobility and ulcer size . At the three-month follow-up , the SF-MPQ was more responsive than the other measures and detected changes in HRQoL , whereas the EQ and SF-36 did not . At 12 months , the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage . Conclusion : In the absence of a vali date d condition-specific tool for measuring changes in general health status for patients with venous leg ulcers , we make the following recommendations . For evaluating the outcome of interventions with a short-term follow-up ( three months ) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36 , with or without the SF-MPQ The results of four multicenter , r and omized , placebo-controlled , parallel group studies of the efficacy of becaplermin gel are review ed here . The four studies included a total of 922 patients , all of whom received a st and ardized regimen of good ulcer care . Patients were r and omized to receive placebo gel , 30 or 100 microg/g becaplermin gel , or good ulcer care alone . In Studies 1 and 2 , the incidence of complete healing was significantly higher in patients receiving becaplermin gel ( 30 microg/g , Study 1 ; 100 microg/g , Study 2 ) compared with that in patients receiving placebo gel . In Study 3 , which was not powered for statistical analysis , the incidence of complete healing in patients treated with 100 microg/g becaplermin gel was approximately twice that of patients treated with good ulcer care alone . In Study 4 , there was no significant difference in the incidence of complete healing in patients treated with becaplermin gel versus good ulcer care alone The purpose of this study was to analyze long-term costs for foot ulcers in diabetic patients . Patients were treated and followed prospect ively by a foot care team . A retrospective economic analysis was performed of costs for 274 patients during 3 years from healing of an initial foot ulcer , with or without amputation . Costs were estimated for inpatient care , outpatient care , home care , and social service . The cost calculations include costs due to complications and disability related to the initial ulcer , costs related to recurrence of ulcer , and costs for prevention of new ulcers . Expected total present value cost per patient during 3 years of observation was $ 26,700 ( U.S. dollars ) for primary healed patients with critical ischemia and $ 16,100 for primary healed patients without critical ischemia . For patients who healed with an amputation , the corresponding costs were $ 43,100 after a minor amputation and $ 63,100 after a major amputation . When estimating the costs for diabetic foot ulcers , it is not sufficient to calculate short-term costs . Long-term costs are high , mainly due to the need for increased home care and social service , but also due to costs for recurrent ulcers and new amputations The results of a combined analysis and separate analyses of four multicenter , r and omized , parallel group studies that evaluated the effects of once-daily topical administration of becaplermin gel for the treatment of chronic , full thickness , lower extremity diabetic ulcers are presented . The four studies included a total of 922 patients with nonhealing lower extremity diabetic ulcers of at least 8 weeks ' duration . Following initial complete sharp debridement of the ulcer , patients were r and omized to receive a st and ardized regimen of good ulcer care alone , good ulcer care plus placebo gel , or good ulcer care plus becaplermin gel-30 microg/g , or good ulcer care plus becaplermin gel-100 microg/g , with various combinations of regimens used in the four studies . Safety was assessed by monitoring adverse events and by clinical laboratory evaluations . Meta-analytic statistical techniques were used in the combined analysis to establish homogeneity of treatment comparisons across studies . Based on an analysis of patients with baseline ulcer area common to all trials ( < /= 10 cm2 ) , representing 95 % of all patients , becaplermin gel-100 microg/g significantly increased ( p = 0.007 ) the probability of complete healing compared with placebo gel . It was determined that for the median ulcer area of these patients , which was 1.5 cm2 , the becaplermin gel-100 microg/g treatment group showed a 39 % increase in complete healing compared with that of the placebo gel treatment group ( 50 % vs. 36 % , respectively , p = 0.007 ) . Becaplermin gel-100 microg/g significantly decreased ( p = 0.01 ) the time to complete healing compared with placebo gel , with the 35th percentile of time to complete healing being reduced by 30 % ( 14.1 weeks vs. 20 . 1 weeks , respectively ) . In patients with ulcers < /= 5 cm2 at baseline ( a more homogeneous group ) , becaplermin gel-100 microg/g also significantly increased the incidence of complete healing with a similar decrease in the time to healing . Adverse events reported during treatment or during a 3-month follow-up period were not unexpected for this patient population and were similar in nature and incidence across all treatment groups . We therefore conclude that treatment with becaplermin gel at a dose of 100 microg/g once daily , in conjunction with good ulcer care , is effective and well tolerated in patients with full thickness lower extremity diabetic ulcers OBJECTIVES The objective of this study was to develop a model capable of assessing the cost-effectiveness in Sweden of treating diabetic neuropathic lower extremity ulcers with becaplermin gel ( Regranex ) plus good wound care ( GWC ) relative to treating them with GWC alone . METHODS A Markov simulation model was developed that includes six health states : Uninfected Ulcer , Infected Ulcer , Gangrene , Healed Ulcer , Healed Ulcer-History of Amputation , and Deceased . To predict clinical outcomes , information was taken from a specially design ed prospect i ve 9-month follow-up study of 183 neuropathic patients in the US treated with GWC . Cost of treatment data were taken primarily from a study of a cohort of 314 patients in Sweden . The efficacy of becaplermin was assumed equal to that achieved in a pooled analysis of four r and omized clinical trials . A model application provides expected clinical outcomes for a cohort of patients . Annual treatment costs per patient were estimated using treatment practice and unit prices from Sweden . RESULTS Due to a higher rate of healing and a shorter average healing time , treatment with becaplermin gel was predicted to increase the average number of months spent in the healed state over the first year following development of an ulcer by 24 % relative to GWC alone . In addition , the corresponding number of amputations was 9 % lower for the becaplermin-treated cohort . The average expected cost of $ 12,078 US for an individual treated with GWC alone declines to $ 11,708 US for one treated with becaplermin , in spite of $ 1262 becaplermin costs . Expenses related to topical treatment and inpatient care account for 83 % of the re sources conserved . CONCLUSIONS Our results suggest that in Sweden treatment with becaplermin in conjunction with GWC consumes fewer re sources and generates better outcomes than treatment with GWC alone for diabetic neuropathic ulcers . In light of the high and increasing incidence of such ulcers , the potential savings in costs and suffering may be important . Results are difficult to extrapolate internationally because they are strongly related to country-specific treatment practice s and price levels OBJECTIVES To perform an economic analysis of primary healing and healing with amputation in diabetic patients with foot ulcers . DESIGN A retrospective economic analysis based on a prospect i ve study of consecutively presenting diabetic patients admitted to the Department of Internal Medicine because of foot ulcer . SETTING A multidisciplinary foot-care team . SUBJECTS A total of 314 consecutively presenting diabetic patients with foot ulcers . Forty patients died before healing occurred . In those patients who healed primarily ( n = 197 ) or after amputation ( n = 77 ) , a retrospective economic analysis was performed . INTERVENTIONS All patients were treated by a multidisciplinary foot care team consisting of diabetologist , orthopaedic surgeon , diabetes nurse , podiatrist and orthotist both as in- and out- patients . The patients were followed by the team from admittance until final outcome , i.e. primary healing or healing with amputation or death . MAIN OUTCOME MEASURES Data from both the prospect ively collected patient material and from patient records were used to estimate the cost for hospital care , antibiotics , surgery , out-patient care , staff attendance , drugs and material for ulcer dressings , and orthopaedic appliances . RESULTS The total costs were SEK 51,000 ( 3000 - 808,000 ) for patients with primary healing and SEK 344,000 ( 27,000 - 992,000 ) for healing with amputation . Costs for in-patient care were 37 % of total average costs for primary healing and 82 % for patients with amputation . The costs for topical treatment of the ulcers in out-patient care were 45 % of the total average cost for primary healed and 13 % for patients who healed with amputation . The costs for products used for ulcer dressings were 21 % of total costs for topical treatment , i.e. 9 % and 3 % of total average costs for primary healing and healing with amputation , respectively . Costs for visits to the foot care team , antibiotics and orthopaedic appliances were low in relation to total costs . CONCLUSION Treatment of diabetic patients with foot ulcers in a multidisciplinary system was associated with relatively low costs . Healing with amputation was associated with high costs mainly due to multiple and extended hospitalization . These findings indicate the potential cost savings of preventive and multidisciplinary foot care |
2,694 | 20,824,859 | Overall the evidence was of poor quality regarding the analgesic effect of opioids , satisfaction with analgesia , adverse effects and harm to women and babies .
There were few statistically significant results .
Overall , findings indicated that parenteral opioids provided some pain relief and moderate satisfaction with analgesia in labour , although up to two-thirds of women who received opioids reported moderate or severe pain and /or poor or moderate pain relief one or two hours after administration .
Opioid drugs were associated with maternal nausea , vomiting and drowsiness , although different opioid drugs were associated with different adverse effects .
There was no clear evidence of adverse effects of opioids on the newborn .
We did not have sufficient evidence to assess which opioid drug provided the best pain relief with the least adverse effects .
AUTHORS ' CONCLUSIONS Parenteral opioids provide some relief from pain in labour but are associated with adverse effects .
Maternal satisfaction with opioid analgesia was largely unreported but appeared moderate at best . | BACKGROUND Parenteral opioids are used for pain relief in labour in many countries throughout the world .
OBJECTIVES To assess the acceptability , effectiveness and safety of different types , doses and modes of administration of parenteral opioids given to women in labour . | Background The minimum local analgesic concentration ( MLAC ) has been defined as the median effective local analgesic concentration ( EC50 ) in a 20-ml volume for epidural analgesia in the first stage of labor . The aim of this study was to determine the relative local anesthetic sparing efficacies of intravenous and epidural fentanyl by comparison of their effects on the MLAC of bupivacaine . Methods In this double-blind , r and omized , prospect i ve study , 84 parturients at ≤ 7-cm cervical dilation who requested epidural analgesia were allocated to one of two groups . After lumbar epidural catheter placement , 20 ml bupivacaine ( n = 44 ) or bupivacaine with 3 & mgr;g/ml ( 60 & mgr;g ) fentanyl ( n = 40 ) was administered . The plain bupivacaine group then received 60 & mgr;g intravenous fentanyl . The bupivacaine – fentanyl group received intravenous saline . The concentration of bupivacaine was determined by the response of the previous patient in that group to a higher or lower concentration using up – down sequential allocation . Analgesic efficacy was assessed using 100-mm visual analog pain scores , with ≤ 10 mm within 30 min defined as effective . Results The MLAC of bupivacaine – intravenous fentanyl was 0.064 % wt/vol ( 95 % confidence interval , 0.049–0.080 ) , and the MLAC of bupivacaine – epidural fentanyl was 0.034 % wt/vol ( 95 % confidence interval , 0.017–0.050 ) . Epidural fentanyl significantly increased the analgesic potency of bupivacaine by a factor of 1.88 ( 95 % confidence interval , 1.09–3.67 ) compared with intravenous fentanyl . The epidural fentanyl group demonstrated significantly higher dermatomal spread ( P = 0.0064 ) and increased pruritus ( P = 0.01 ) . Conclusions Epidural fentanyl significantly reduced the MLAC of bupivacaine when compared with intravenous fentanyl for the parturients in this study . The significantly enhanced local anesthetic sparing , dermatomal level , and pruritus with epidural fentanyl suggest a primarily spinal site of action BACKGROUND The pharmacokinetics of remifentanil suggests that it may be suitable for analgesia during labour . METHODS In an open pilot study , 36 women requesting meperidine for analgesia were recruited early in labour and r and omized to receive either meperidine i.m . or remifentanil given as patient-controlled analgesia ( PCA ) . Pain severity , sedation and anxiety were assessed with visual analogue scales and overall effective analgesia was assessed by the woman and midwife . RESULTS The pain scores were lower in the remifentanil group : median pain score at 60 min was 72 mm for meperidine and 48 mm for remifentanil ( P=0.004 ) and median maximum pain score during the first 2 h was 82.5 mm for the meperidine group and 66.5 mm for the remifentanil group ( P=0.009 ) . Both the midwives ' and the women 's assessment s of overall effective analgesia were higher in the remifentanil group [ Likert scale ( 5 = excellent to 1 = poor ) : chi2=12.10 , P=0.002 for mothers ' assessment ; chi2=12.80 , P=0.002 for midwives ' assessment ] . CONCLUSION In this pilot study , remifentanil by PCA gave better pain relief to mothers in labour than intramuscular meperidine . However , remifentanil is a potent respiratory depressant and adequate continuous monitoring is necessary OBJECTIVE This study was undertaken to evaluate whether the administration of meperidine decreases the length of labor in patients with a diagnosis of dystocia during the first stage of labor . STUDY DESIGN Women with term singleton pregnancies who received a diagnosis of dystocia and required an active management of labor were r and omly assigned to receive either 100 mg of meperidine or placebo . The primary outcome measure was length of labor . RESULTS Four hundred seven pregnant women were included . There were no significant statistical differences between meperidine and placebo groups in length of labor and operative delivery rates such as forceps and cesarean section by intention-to-treat analysis . Low Apgar scores , umbilical artery acidosis , and admission to neonatal care units were increased in the meperidine group . CONCLUSION Because of the absence of any benefits in patients with dystocia in labor and the presence of harmful effects on neonatal outcomes , meperidine should not be used during labor for this specific indication The aim of this quasi‐experimental study was to examine the effects of maternal pethidine during labour on the developing breast feeding behaviour in infants in the first 2 h after birth compared with infants not exposed to pethidine . Forty‐four healthy infants were observed immediately after birth . They were placed skin‐to‐skin on their mothers ' chests . The development of mouth and sucking movements as well as rooting behaviour and state of sleep/wakefulness were noted . The observer was blind as to the pain relief the mother had received during labour . Of the 44 mothers 18 had received pethidine . The main findings were that infants exposed to pethidine had delayed and depressed sucking and rooting behaviour . In addition , a smaller proportion of infants exposed to pethidine started to suckle the breast . Rooting movements which are expected to be vigorous at 30 min after birth were affected both by administration of pethidine and a longer second stage of labour . It is suggested that the differences found in sucking behaviour may be a central effect of pethidine . Depression of rooting movements in the pethidine group may be caused by exhaustion due to a longer second stage of labour and administration of pethidine . It is recommended that pethidine‐exposed mother‐infant couples stay together after birth long enough to enable the infant to make the choice to attach or not to attach to the nipple without the forceful helping h and of the health staff A sequential study of intravenous analgesic treatment during labour has shown that pentazocine 40 mg provides pain relief comparable to pethidine 100 mg alone or combined with levallorphan 1.25 mg ( Pethilorfan ) , but is significantly more effective than pethidine 50 mg . Pethilorfan gave less sustained analgesia and a high incidence of dysphoria . Emetic sequelae were much more frequent with either dose of pethidine than with pentazocine . Placebo treatment was easily identified by mother and observer . Its inclusion and early sequential exclusion may have had a significant effect on observer estimations of pain relief . The effect of the treatments on labour or on the condition of the infant at birth were not studied Preliminary observations have shown that fentanyl citrate , a potent narcotic , is helpful during labor without undue side effects . This r and omized prospect i ve investigation compared the patient-controlled administration of fentanyl with that of administration by nurses on request . Eighty healthy women beginning active labor ( cervical dilation 4 cm ) at term were assigned to receive fentanyl intravenously by either patient-controlled administration ( n=37 ) or nurse administration on dem and ( n=43 ) . Pain intensity measurements during early and late labor revealed the degree of analgesia to be the same in both groups . The delay in setting up the infusion system and the short time between requesting analgesia and vaginal delivery were limitations with self-administration . Maternal oversedation and vomiting did not occur . Neonatal naloxone therapy was used infrequently , umbilical serum levels of fentanyl were the same in both groups , and postnatal neuroadaptive testing revealed comparable results in both groups . Despite the usefulness of fentanyl during labor , administration by the patient had no advantages over administration by the nurses in significantly reducing drug use , improving pain relief , or avoiding drowsiness A single dose block r and omised double-blind study comparing intramuscular ketorolac , 50 mg of pethidine and 100 mg pethidine was carried out in multiparous women . Pain intensity and sedation effect were recorded at inclusion to the study , half hourly for the first 2 h , then hourly until 6 h after delivery . Maternal and neonatal side effects were noted including the Apgar scores and the baby 's requirements for resuscitation . All three treatments are relatively ineffective in relieving labour pain . There was no difference in the analgesic efficacy between the two doses of pethidine but both doses of pethidine were statistically more effective compared with ketorolac . There was no difference in the retrospective assessment of the three groups or when comparison was made with the previous labour . A similar number of patients required further analgesia in each group . In all three groups , no adverse effect occurred in the mother or fetus . Maternal sedation and fetal depression were statistically less in the ketorolac group . Although ketorolac had inferior analgesic effect , its use was not associated with clinical ly significant sequelae and it showed a superior safety profile compared with either dose of pethidine . The study was not powerful enough to detect a difference between 50 mg and 100 mg of pethidine Preliminary reports about patient-controlled analgesia during labor have been promising . The purpose of this investigation was to compare our experience with meperidine given intravenously by the patient versus by a nurse . Sixtyfour healthy women beginning active labor ( cervical dilation 3 cm ) at term were r and omly assigned to either self administer a 10-mg dose as often as every 20 minutes or have a nurse administer 25 - 50 mg every 3 hours as requested . The total meperidine dose and consumption rates were greater when administered by the patient than by a nurse . Maternal side effects occurred with similar frequency in both groups , and pain relief was judged to be equivalent . Maternal and umbilical serum concentrations of meperidine at delivery increased in the patient-controlled group if active labor lasted longer than 2 hours . Neonatal naloxone therapy was used more often when meperidine was administered by the patient than by a nurse ( five of 31,16 % , versus three of 33 , 10 % , respectively ) . Self-administration of intravenous meperidine by the laboring patient was not found to be advantageous over nursing administration , and may pose an increased threat to the BACKGROUND Although epidural anaesthesia has become a st and ard method for labour analgesia all over the world , it is far from being ideal because of side effects and contraindications . Many alternative techniques have therefore been proposed , including the continuous infusion of remifentanil . Encouraged by positive reports , we compared the efficacy of patient-controlled remifentanil infusion ( PCA ) with patient-controlled continuous epidural analgesia ( PCEA ) . METHODS Fifty-two ASA I and II parturients were arbitrarily allocated , without r and omisation , to two groups to receive PCEA with 0.125 % bupivacaine and 0.2 microg kg(-1 ) fentanyl ( basic infusion 1 mL h(-1 ) , bolus 4 mL , lock-out time 15 min ) or remifentanil PCA ( 0.2 microg kg(-1 ) bolus doses , without basic infusion , lock-out time 2 min ) . The intensity of pain was assessed using the VAS scale every 15 min in the PCEA group and every 10 min in the PCA group . RESULTS During the first two hours of labour , the VAS score was significantly lower in the PCEA group . Later there was no difference between the groups . The clinical status of the newborns was similar . CONCLUSION The results are difficult to interpret since there was no r and omisation and parturients participated in decisions about allocation to one of the study groups . Analgesia provided by remifentanil was assessed as highly acceptable by the patients and the drug can be regarded as a safe alternative to epidural analgesia during labour Background : We compared the efficacy and side‐effects of remifentanil with those of nitrous oxide during the first stage of labour OBJECTIVE To evaluate the association between the use of pethidine during the first stage of labor and the presence , type and timing of acidosis in the newborn at birth . STUDY DESIGN Secondary data analysis of a r and omized controlled trial , which included term singleton pregnancies diagnosed with dystocia and requiring active management of labor . Women were r and omized to receive either 100 mg of pethidine or placebo . Statistical analyses were performed using chi(2 ) or Fisher 's exact tests for proportions and multiple linear regression for continuous outcomes . RESULTS Three hundred and eighty-three pregnant women with a valid arterial blood cord sample were included in the final analysis . Lower pH and bicarbonate levels , as well as higher pCO(2 ) levels were found in the pethidide group . A higher incidence of acidosis was found in the pethidine group ( pH<7.12 OR : 8.59 95 % C.I. 3.29 , 22.46 ) . The highest frequency of acidosis was encountered when pethidine-delivery interval was 5 h. CONCLUSION Pethidine use during the first stage of labor was associated with an increased risk of acidosis at birth Two series of patients , r and omly selected , 29 of whom had pethidine and 29 of whom had a placebo , were compared in order to study the influence of intra-muscular pethidine on uterine activity and on the speed with which the cervix dilated . The experiment was a double blind one . A significant increase in the basal tone of the uterine muscle was found 40 minutes after the injection in the group that received pethidine , although there was no other significant difference in the other parameters which were intensity , frequency , length , surface of the contractions [ half the height multiplied by ( X times ) the base on the monitor recording ] , uterine activity in Montevideo and in Toulouse units and the speed of dilatation . These results do not bear out the classical hypotheses of the muscle relaxing effect of pethidine , and in particular that the uterus relaxes better between contractions , nor that there is relaxation of the cervix in labour . The indication for the use of pethidine is perhaps justified because of its analgesic effect , but as far as favouring dilatation of the cervix in labour is concerned is at best worthy of discussion OBJECTIVE To determine the effectiveness and side effects of intravenous meperidine in labour pain relief . MATERIAL AND METHOD A double blind , r and omized controlled trial was conducted in 84 parturients , using normal saline as control . Visual analogue scale , postpartum parturients ' opinion of effectiveness , sedative scores , nausea/vomiting , dizziness , delivery method , Apgar scores , and naloxone prescription were assessed . RESULT There were no statistically significant differences between the mean and median of visual analogue scale of meperidine and control group . In addition , the sedative scores , nausea/vomiting and dizziness in the meperidine group occurred more than those in the control group significantly . Even mean of the pain increment in the meperidine group was less than those in the control group ( p < 0.05 ) . The parturients ' opinion on the effectiveness of pain relief during labor within 24 hours of the first postpartum day was only 23.80 per cent in the meperidine group , however , it was statistically significantly different when compared to 7.10 per cent in the control group . CONCLUSION Intravenous meperidine exhibited the effectiveness of pain relief of only 23.80 per cent of the subjects , in addition , it may cause many side effects |
2,695 | 27,812,112 | There were no significant differences between ciclosporin and tacrolimus in terms of graft loss or AR .
CONCLUSIONS Meta- analysis of RCTs published since 2000 showed tacrolimus to be superior to ciclosporin in terms of patient mortality and hypertension , while ciclosporin was superior in terms of NODAT .
No significant differences were identified in terms of graft loss or AR .
These findings provide further evidence supporting the use of tacrolimus as the cornerstone of immunosuppressive therapy in liver transplant recipients | BACKGROUND AND AIMS Several meta-analyses comparing ciclosporin with tacrolimus have been conducted since the 1994 publication of the tacrolimus registration trials , but most captured data from r and omized controlled trials ( RCTs ) predating recent improvements in waiting list prioritization , induction protocol s and concomitant medications .
The present study comprised a systematic review and meta- analysis of ciclosporin and tacrolimus in liver transplant recipients using studies published since January 2000 . | BACKGROUND The long-term ( 5 year ) efficacy and safety of tacrolimus ( FK506 ) and cyclosporine were compared in primary liver transplant recipients who participated in a 1-year r and omized , multicenter trial and a 4-year follow-up extension study . METHODS A total of 529 patients ( 263 tacrolimus group , 266 cyclosporine group ) were r and omized to study drug . Patients were evaluated at 3-month intervals . Patient and graft survival rates , incidence of adverse events , and changes in laboratory and clinical profiles were determined . RESULTS Cumulative 5-year patient and graft survival rates were comparable for the tacrolimus ( 79.0 % , 71.8 % ) and cyclosporine ( 73.1 % , 66.4 % ) groups . However , patient half-life survival was longer for tacrolimus-treated patients ( 25.1+/-5.1 years versus 15.2+/-2.5 years ; P=0.049 ) . Improved patient survival with tacrolimus was also observed for hepatitis C-positive patients ( 78.9 % tacrolimus group versus 60.5 % cyclosporine group ; P=0.041 ) . Both treatments were associated with a low incidence of late acute rejection , late steroid-resistant rejection , and death or graft loss related to rejection . Both treatments demonstrated an acceptable safety profile with maintenance of adequate renal and liver function and a low incidence of malignancy/lymphoproliferative disease and serious infections . CONCLUSIONS Tacrolimus is a safe and effective long-term maintenance immunosuppressive agent in primary liver transplantation 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 Informing health care decision making may necessitate the synthesis of evidence from different study design s ( e.g. , r and omised controlled trials , non-r and omised/observational studies ) . Methods for synthesis ing different types of studies have been proposed , but their routine use requires development of approaches to adjust for potential biases , especially among non-r and omised studies . The objective of this study was to extend a published Bayesian hierarchical model to adjust for bias due to confounding in synthesis ing evidence from studies with different design s. Methods In this new method ological approach , study estimates were adjusted for potential confounders using differences in patient characteristics ( e.g. , age ) between study arms . The new model was applied to synthesis e evidence from r and omised and non-r and omised studies from a published review comparing treatments for abdominal aortic aneurysms . We compared the results of the Bayesian hierarchical model adjusted for differences in study arms with : 1 ) unadjusted results , 2 ) results adjusted using aggregate study values and 3 ) two methods for downweighting the potentially biased non-r and omised studies . Sensitivity of the results to alternative prior distributions and the inclusion of additional covariates were also assessed . Results In the base case analysis , the estimated odds ratio was 0.32 ( 0.13,0.76 ) for the r and omised studies alone and 0.57 ( 0.41,0.82 ) for the non-r and omised studies alone . The unadjusted result for the two types combined was 0.49 ( 0.21,0.98 ) . Adjusted for differences between study arms , the estimated odds ratio was 0.37 ( 0.17,0.77 ) , representing a shift towards the estimate for the r and omised studies alone . Adjustment for aggregate values result ed in an estimate of 0.60 ( 0.28,1.20 ) . The two methods used for downweighting gave odd ratios of 0.43 ( 0.18,0.89 ) and 0.35 ( 0.16,0.76 ) , respectively . Point estimates were robust but credible intervals were wider when using vaguer priors . Conclusions Covariate adjustment using aggregate study values does not account for covariate imbalances between treatment arms and downweighting may not eliminate bias . Adjustment using differences in patient characteristics between arms provides a systematic way of adjusting for bias due to confounding . Within the context of a Bayesian hierarchical model , such an approach could facilitate the use of all available evidence to inform health policy decisions OBJECTIVES Health decision-makers involved with coverage and payment policies are increasingly developing policies that seek information on " real-world " ( RW ) outcomes . Motivated by these initiatives , the International Society for Pharmacoeconomics and Outcomes Research ( ISPOR ) created a Task Force on Real-World Data to develop a framework to assist health-care decision-makers in dealing with RW data , especially related to coverage and payment decisions . METHODS Task Force cochairs were selected by the ISPOR Board of Directors . Cochairs selected chairs for four working groups on : clinical outcomes , economic outcomes , patient-reported outcomes , and evidence hierarchies . Task Force members included representatives from academia , the pharmaceutical industry , and health insurers . The Task Force met on several occasions , conducted frequent correspondence and exchanges of drafts , and solicited comments on three drafts from a core group of external review ers and from the ISPOR membership . RESULTS We defined RW data as data used for decision-making that are not collected in conventional r and omized controlled trials ( RCTs ) . We considered several characterizations : by type of outcome ( clinical , economic , and patient-reported ) , by hierarchies of evidence ( which rank evidence according to the strength of research design ) , and by type of data source ( supplementary data collection alongside RCTs , large simple trials , patient registries , administrative cl aims data base , surveys , and medical records ) . Our report discusses eight key issues : 1 ) the importance of RW data ; 2 ) limitations of RW data ; 3 ) the fact that the level of evidence required depends on the circumstance ; 4 ) the need for good research practice s for collecting and reporting RW data ; 5 ) the need for good process in using RW data in coverage and reimbursement decisions ; 6 ) the need to consider costs and benefits of data collection ; 7 ) the ongoing need for modeling ; and 8) the need for continued stakeholder dialogue on these topics . CONCLUSIONS Real-world data are essential for sound coverage and reimbursement decisions . The types and applications of such data are varied , and context matters greatly in determining the value of a particular type in any circumstance . It is critical that policymakers recognize the benefits , limitations , and method ological challenges in using RW data , and the need to consider carefully the costs and benefits of different forms of data collection in different situations CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective . Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) remained largely unchallenged . Five of 6 highly-cited nonr and omized studies had been contradicted or had found stronger effects vs 9 of 39 r and omized controlled trials ( P = .008 ) . Among r and omized trials , studies with contradicted or stronger effects were smaller ( P = .009 ) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact . Matched control studies did not have a significantly different share of refuted results than highly cited studies , but they included more studies with " negative " results . CONCLUSIONS Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes . The extent to which high citations may provoke contradictions and vice versa needs more study . Controversies are most common with highly cited nonr and omized studies , but even the most highly cited r and omized trials may be challenged and refuted over time , especially small ones The LIS2 T study was an open-label , multicenter study in which recipients of a primary liver transplant were r and omized to cyclosporine microemulsion ( CsA-ME ) ( Neoral ) ( n = 250 ) ( monitoring of blood concentration at 2 hours postdose ) C2 or tacrolimus ( n = 245 ) ( monitoring of trough drug blood level [ predose ] ) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months . All patients received steroids with or without azathioprine . At 12 months , 85 % of CsA-ME patients and 86 % of tacrolimus patients survived with a functioning graft ( P not significant ) . Efficacy was similar in deceased- and living-donor recipients . Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME ( 5/88 , 6 % ) than with tacrolimus ( 14/85 , 16 % ) ( P < 0.03 ) . Recurrence of hepatitis C virus in liver grafts was similar in each group . Based on biopsies driven by clinical events , the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME ( 100 + /- 50 days ) than with tacrolimus ( 70 + /- 40 days ) ( P < 0.05 ) . Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus . More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months ( 13 % vs. 5 % , P < 0.01 ) . Of patients who were diabetic at baseline , more tacrolimus-treated individuals required anti-diabetic treatment at 12 months ( 70 % vs. 49 % , P = 0.02 ) . Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups . In conclusion , the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months , and renal function is similar . More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline REFINE was a 12‐month , prospect i ve , open‐label study in 356 patients receiving de novo liver transplantation for hepatitis C virus ( HCV ) cirrhosis , r and omized to cyclosporine A ( CsA ) or tacrolimus with ( i ) no steroids , IL‐2 receptor antibody induction and mycophenolic acid , or ( ii ) slow steroid tapering . The primary analysis population based on availability of liver biopsies comprised 165 patients ( 88 CsA , 77 tacrolimus ) . There was no difference in the primary endpoint , fibrosis stage ≥2 at 12 months , which occurred in 63/88 CsA‐treated patients ( 71.6 % ) and 52/77 tacrolimus‐treated patients ( 67.5 % ) ( odds ratio [ OR ] 1.11 ; 95 % CI 0.56 , 2.21 ; p = 0.759 ) . Similarly , no significant between‐group difference occurred at month 24 ( OR 1.15 ; 95 % CI 0.47 , 2.80 ; p = 0.767 ) . Among steroid‐free patients , fibrosis score ≥2 was significantly less frequent with CsA versus tacrolimus at month 12 ( 7/37 [ 18.9 % ] vs. 16/38 [ 42.1 % ] ; p = 0.029 ) . HCV viral load was similar in both the tacrolimus‐ and CsA‐treated cohorts . Mean blood glucose was significantly higher with tacrolimus from day 15 onward . Biopsy‐proven acute rejection , graft loss and death were similar . These results showed no differences in posttransplant HCV‐induced liver fibrosis between patients treated with CsA or tacrolimus in steroid‐containing regimens , whereas CsA in steroid‐free protocol s was associated with reduced severity of fibrosis progression at 1 year posttransplant Background With effective agents available to prevent posttransplantation acute organ rejection , medication adherence becomes a key factor for successful treatment outcomes after renal transplantation . A once-daily , modified-release oral formulation of tacrolimus has been developed to simplify dosing and improve medication adherence . Methods Adherence Measurement in Stable Renal Transplant Patients Following Conversion From Prograft to Advagraf is a r and omized multicenter controlled trial to evaluate adherence between a tacrolimus once-daily regimen and a tacrolimus twice-daily regimen using an electronic monitor to document drug intake . After enrolment , all patients continued the twice-daily regimen for 3 months and then were r and omized 2:1 between the two formulations and followed for 6 months . Adherence was decomposed into patients ’ persistence and implementation of each regimen . Results Two hundred nineteen patients ( 45 % male ; 3±2 years after transplantation ) were analyzed ( 145 once daily and 74 twice daily ) . At 6 months after r and omization , 81.5 % of the once-daily group and 71.9 % of the twice-daily group remained persistent with the treatment ( P=0.0824 ) . Among patients who remained engaged with the regimen , 88.2 % of the once-daily group and 78.8 % of the twice-daily group ( P=0.0009 ) took the prescribed number of daily doses . When the patients took the twice-daily regimen , the average percentage of missed doses was 11.7 % in the morning and 14.2 % in the evening ( P=0.0035 ) . Conclusions Regimen implementation of tacrolimus once daily is significantly superior to the twice-daily regimen . There was a residual prevalence of suboptimal adherence that will have to be countered by means other than reformulation and regimen simplification . Electronically compiled dosing histories provide detailed data on patient adherence that can be used for efficient medication management Two-hour postdose cyclosporine ( C2 ) monitoring is becoming an accepted method of therapeutic drug monitoring , although it is not known whether C2 monitoring is superior to tacrolimus (FK)-based immunosuppression . The purpose of this trial was to compare the safety , efficacy , and pharmacoeconomics of cyclosporine A ( CsA ) monitored by C2 levels versus FK monitored by trough levels in de novo liver transplant recipients . After informed consent , 60 de novo liver transplant recipients were r and omized in a 1:1 fashion to receive either FK ( trough , 6 - 10 ng/mL ) or CsA ( C2 , 600 - 1200 ng/mL ) and corticosteroids . The 2 groups were similar for gender , race , indication for liver disease , and age . At 1 year , patient survival was similar ( 93 % for FK versus 90 % for C2 ) . One patient in the FK arm was retransplanted because of recurrent hepatitis C virus ( HCV ) . Early acute rejection occurred in 27 % of FK-treated patients and 23 % of CsA-treated recipients [ P = not significant ( NS ) ] . Recurrent HCV occurred in 21 % of FK-treated patients and 61 % of CsA-treated patient ( P = 0.04 ) . The incidence of other infections , new onset diabetes mellitus , requirement for antihypertensives , and requirement for cholesterol medications were similar between the groups . Annual calcineurin inhibitor costs were lower in the C2 arm ( $ 5432 + /- 2091 for C2 versus $ 8291 + /- 3948 for FK , P = 0.001 ) . Annual pretransplant drug costs ( $ 2292 + /- 2331 for C2 versus $ 2831 + /- 2358 for FK , P = NS ) and 1-year posttransplant drug costs ( $ 17,214 + /- 16,600 for C2 versus $ 15,151 + /- 11,699 for FK , P = NS ) were similar . In conclusion , immunosuppression with CsA , monitored by C2 levels , is safe , effective , and economical in liver transplant recipients and provides immunosuppression at least equivalent to that of FK Hepatitis C virus (HCV)-induced cirrhosis is the commonest indication for orthotopic liver transplantation , but HCV recurrence is nearly universal and may worsen patient / graft outcomes . The frequency and severity of HCV recurrence has apparently increased in recent years , raising concern about a possible role for newer immunosuppression regimens in this increase , including potentially tacrolimus . We r and omized 79 patients to receive tacrolimus or cyclosporine as primary immunosuppressant posttransplantation . A pathologist blinded to treatment review ed serial liver biopsies . Month 12 cumulative probabilities of histological hepatitis C recurrence for tacrolimus- and cyclosporine-treated patients were .38 and .54 ( P = .19 ) and failure / death were .25 and .28 , respectively ( P = .789 ) . Although cyclosporine-treated patients had significantly larger increases in median serum HCV RNA levels ( months 1 , 6 , and 12 ) , no significant differences were observed between the two treatment arms in histologically-diagnosed HCV recurrence / survival rates . In conclusion , choice of calcineurin inhibitors does not impact severity of recurrent HCV Studies in the USA and Japan have shown that tacrolimus ( FK506 ) is a potent immunosuppressant . To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a r and omised open trial . Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute , refractory acute , and chronic rejection episodes . The rates were , for acute rejection , tacrolimus 40.5 % vs 49.8 % cyclosporin ( p = 0.040 ; absolute difference 9.3 % [ 95 % CI 0.9 - 17.8 % ] ) . For refractory acute and chronic rejections the comparisons were 0.8 % vs 5.3 % ( p = 0.005 ) and 1.5 % vs 5.3 % ( p = 0.032 ) . There results were seen despite significantly lower corticosteroid usage . The incidence of infection was also lower in patients receiving tacrolimus . Patient and graft survival rates were not significantly different ( tacrolimus 82.9 % and 77.5 % ; cyclosporin 77.5 % and 72.6 % ) . Safety data were comparable -- the most serious events being renal impairment , disturbances of glucose metabolism , and neurological complications -- but these events were more common in the tacrolimus group . In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates , even though less concurrent immunosuppression was administered The severity of recurrent hepatitis C virus ( HCV ) is likely related to several factors . Controversial results have been reported regarding the effect of specific calcineurin-inhibitors . The aim of this research was to determine whether there are differences on posttransplantation outcome in HCV-infected patients based on initial immunosuppression . Prospect i ve r and omized trial comparing tacrolimus vs. cyclosporine-based immunosuppression in a cohort of patients undergoing primary orthotopic liver transplantation between 2001 and 2003 was used . Yearly biopsies were performed . Patients with at least 1 protocol biopsy and those with very severe recurrence despite a follow-up of less than 1 yr ( cholestatic hepatitis , progression to bridging fibrosis/cirrhosis ) were included . Baseline characteristics ( demographics , liver function at transplantation , genotype distribution , donor , surgery , immunosuppression except for the type of calcineurin inhibitor ) did not differ between the 2 groups . Severe disease ( defined as bridging fibrosis , cirrhosis , cholestatic hepatitis , and /or death due to recurrent disease in the first year ) was present in 27 in 90 ( 30 % ) , and was equally distributed in the cyclosporine and tacrolimus groups ( 15/46 vs. 12/44 , respectively ) . A total of 33 in 90 ( 37 % ) patients had no fibrosis in the first year biopsy with no difference between the cyclosporine and tacrolimus groups ( 36.5 vs. 37 % ) . The percentage of patients developing recurrent acute hepatitis was also similar ( 32 % vs 35 % ) ; time to acute hepatitis though was shorter in the tacrolimus group ( 59 days [ 35 - 185 ] vs. 92 days [ 39 - 343 ] in the cyclosporin group ; P = 0.02 ) . Cholestatic hepatitis was observed in 4 of 44 and 5 of 46 patients under cyclosporine and tacrolimus , respectively ( P = not significant ) . In conclusions , the short-term posttransplantation course of hepatitis C is not related to the calcineurin inhibitor used Corticosteroid therapy contributes significant toxicity to liver transplantation . The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A ( micro-CsA ) . The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation . From the seven Canadian adult liver transplant centers , 143 patients were r and omly allocated oral treatment with either tacrolimus ( n = 71 ) or micro-CsA ( n = 72 ) , together with corticosteroids and azathioprine . Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months , and prednisone < /=0.15 mg/kg/d . In eligible patients , the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved . At 1 year after transplantation , 75 % of the tacrolimus patients and 63 % of the micro-CsA patients were steroid-free ( P = .20 ) . Of all of the patients who became eligible for steroid withdrawal , steroid discontinuation was achieved in over 80 % . One-year patient survival was 97 % with tacrolimus and 89 % with micro-CsA ( P = .052 ) . Graft survival was 97 % and 86 % , respectively ( P = .017 ) . The overall incidence of acute rejection during the first year was 35 % with tacrolimus and 43 % with micro-CsA ( P = .26 ) . There was no difference in survival , acute rejection , or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive . Steroid-resistant rejection occurred in 5.6 % of the tacrolimus and 9.7 % of the micro-CsA patients . One patient , in the micro-CsA group , experienced refractory rejection . Chronic rejection was not observed in either group . The toxicity profiles were similar . Postoperative serum creatinine levels were similar , and dialysis was required in less than 10 % of patients in each group . Infectious complications were similar in both groups . Neurotoxicity was a serious adverse event in 13 % and 10 % of patients receiving tacrolimus and micro-CsA , respectively . Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis We evaluate 5-year results of a prospect i ve r and omized trial that compared cyclosporine microemulsion ( CsA-me ) and Tacrolimus ( Tac ) for primary immunosuppression . One hundred one adult patients undergoing liver transplantation were r and omized to receive Tac ( n = 50 ) or CsA-me ( n = 51 ) . The most frequent indication for the procedure was cirrhosis due to virus C followed by alcoholism . Survival rates at 1 , 3 , and 5 years were 86 % , 75 % , and 72 % , respectively ; there was no significant difference between CsA-me versus Tac arms . Acute rejection occurred in 30 cases ( 30 % ) , independent of the type of primary immunosuppression . Serious adverse events were reported significantly more among patients under CsA-me ( 48 episodes ) than under Tac ( 32 episodes ) . Nineteen patients were switched to the other calcineurin inhibitor . The switch was much more frequent from CsA-me to Tac ( n = 15 ; 29.4 % ) , mainly because of lack of efficacy ( n = 10 ; 19.6 % ) . There were no cases of chronic rejections in the Tac arm . Four patients were switched from Tac to CsA-me for side effects ; only 1 remains alive , after treatment was changed from CsA-me to an antimetabolite . There were no statistical differences in renal dysfunction , diabetes , hypertension , neurologic disorders , new-onset malignancies , or infections . There were no differences in survival or rejection among the intention-to-treat groups . Serious adverse events , total patients with switch of calcineurin inhibitor , as well as switches due to lack of efficacy , were statistically more frequent under CsA-me . Tacrolimus seems to be a more appropriate drug to be used for primary immunosuppression in liver transplantation CONTEXT Not all research presented at scientific meetings is subsequently published and , even when it is , there may be inconsistencies between these results and what is ultimately printed . Although late-breaking trials sessions are now integrated into several major scientific meetings and the results are often promptly and prominently communicated , no studies have examined the publication fate and degree of consistency between meeting abstract s or presentations and subsequent full-length article publications for r and omized controlled trials ( RCTs ) presented at these sessions . OBJECTIVE To compare RCT abstract s presented in the late-breaking trials session vs other sessions at a major scientific meeting and subsequent full-length publications . DESIGN RCTs were identified by h and search ing abstract proceedings booklets and related Web sites for the American College of Cardiology scientific meetings ( 1999 - 2002 ) . Subsequent full-length articles were identified via electronic data bases . MAIN OUTCOME MEASURES Publication fate and degree of consistency between meeting abstract results and subsequent full-length publication results . RESULTS The 86 late-breaking RCTs were significantly larger ( median , 2737 patients vs 896 ; P<.001 ) , were more likely to be preceded by a published design paper ( 27 [ 31 % ] vs 13 [ 13 % ] ; P = .002 ) , had higher quality scores when eventually published ( mean Jadad score 2.69 vs 2.19 ; P = .01 ) , and were less likely to report favorable results for the intervention than the 100 r and omly chosen comparison RCTs presented in other sessions ( 50 [ 58 % ] vs 75 [ 75 % ] ; P = .01 ; odds ratio 0.46 ; 95 % confidence interval , 0.24 - 0.90 ) . RCTs presented at the late-breaking trials sessions were significantly more likely to be published ( 79 [ 92 % ] vs 69 [ 69 % ] ; P<.001 ) and appeared earlier after presentation ( median 11.5 months vs 22.0 months ; P<.001 ) than RCTs presented in other sessions , an association that persisted even after adjusting for sample size , conclusion of study , and RCT design : adjusted hazard ratio , 1.80 ( 95 % confidence interval , 1.24 - 2.61 ) . Sixty ( 41 % ) of the 148 RCTs that were subsequently published exhibited discrepancies between the efficacy estimate reported in the meeting abstract vs the one reported in the full-length article for the primary outcome . The mean change in effect was 0.44 SDs and in 20 cases ( 14 % ) , the point estimate was statistically significant in only 1 member of the pair . The discrepancy rate was the same for late-breaking RCTs as for RCTs presented in other American College of Cardiology sessions ( P = .92 ) . CONCLUSIONS Late-breaking trials were larger , more likely to be preceded by a design paper , and less likely to report positive results than RCTs presented at other sessions , but discrepancies between the meeting abstract results and subsequent full-length publication results were common even for late-breaking trials BACKGROUND Tacrolimus ( FK 506 ) , a macrolide compound isolated from a bacterium , is a potent immunosuppressant with activity in solid-organ transplants . Most immunosuppressive regimens for liver transplantation are based on cyclosporine . METHODS We conducted an open-label , r and omized , multicenter trial to compare the efficacy and safety of tacrolimus-based and cyclosporine-based immunosuppressive regimens for patients receiving a first liver transplant . A total of 478 adults and 51 children ( < or = 12 years of age ) were r and omly assigned at the time of transplantation to receive tacrolimus ( n = 263 ) or cyclosporine ( n = 266 ) and were followed for one year . The primary end points were patient and graft survival at one year . The secondary end points were the incidence of acute rejection , corticosteroid-resistant rejection , and refractory rejection ( continued rejection after two courses of corticosteroids and an intervening course of muromonab-CD3 ) . RESULTS According to Kaplan-Meier analysis , actuarial patient-survival rates at day 360 were 88 percent for both the tacrolimus and cyclosporine groups ( P = 0.85 ; 95 percent confidence interval for the difference , -5.4 to 6.6 percent ) , and graft-survival rates were 82 percent and 79 percent , respectively ( P = 0.55 ; 95 percent confidence interval for the difference , -4.8 to 9.7 percent ) . Acute rejection occurred in 154 patients in the tacrolimus group and 173 patients in the cyclosporine group ( P < 0.002 ) , corticosteroid-resistant rejection occurred in 43 and 82 patients , respectively ( P < 0.001 ) , and refractory rejection occurred in 6 and 32 patients , respectively ( P < 0.001 ) . Tacrolimus was associated with a higher incidence of adverse events requiring withdrawal from the study , primarily nephrotoxicity and neurotoxicity ; 37 patients in the tacrolimus group and 13 in the cyclosporine group discontinued the study because of adverse events ( P < 0.001 ) . CONCLUSIONS After one year , immunosuppressive regimens based on tacrolimus and cyclosporine were comparable in terms of patient and graft survival . Tacrolimus was associated with significantly fewer episodes of acute , corticosteroid-resistant , or refractory rejection , but substantially more adverse events requiring discontinuation of the drug There are several case reports in the literature that describe cardiac complications in the first few weeks after orthotopic liver transplantation ( OLT ) in patients receiving tacrolimus as their primary immunosuppressive therapy . In this study , we investigated the cardiac function of patients on tacrolimus ( T ) compared with those on cyclosporin ( C ) ( Neoral ; Novartis , Basel , Switzerl and ) immunosuppression , after OLT , in a prospect i ve r and omized trial . We r and omized 40 adult patients with cirrhosis to either T or C with azathioprine and prednisolone immunosuppression and followed up on them for 3 months after OLT . All had detailed clinical , biochemical , electrocardiographic and echocardiographic assessment s at regular intervals . Abnormalities in cardiac function were common after OLT and significant deterioration in left ventricular diastolic function was demonstrable up to 3 months in both patient groups . Cardiac function was similar in the T and C arms and no significant electrocardiographic differences were observed , although reduced heart rate variability ( HRV ) and higher mean serum brain natriuretic peptide ( BNP ) levels were identified in the T group . The percentage increase in posterior wall thickness was higher in the T group . Cardiac dysfunction as shown by worsening echocardiographic measures of left ventricular diastolic function and by clinical cardiac events is common in the first 3 months after OLT in patients with cirrhosis . HRV and BNP values in the T group were worse than in the C group , but this was not translated to an increase in cardiac clinical events in this study Background . Liver transplantation ( LTX ) recipients with renal dysfunction may benefit from mycophenolate mofetil ( MMF ) and reduction or discontinuation of nephrotoxic calcineurin inhibitors ( CNI ) . The authors report the first r and omized , multicenter pilot studies of this approach ( one study for patients on cyclosporine [ CsA ] and one for those on tacrolimus [ Tac ] ) . Methods . Patients 3 to 27 months post-LTX with greater than 20 % reduced renal function since LTX , and creatinine 1.8 to 4.0 mg/dL , creatinine clearance 20 to 60 mL/min , or both , were r and omized to discontinuation ( group 1 ) or 50 % reduction ( group 2 ) of CNI dose , together with MMF 1.5 g administered twice daily and prednisone . Endpoints included measured glomerular filtration rate ( GFR ) 52 weeks after study entry and biopsy-proven rejection . Results . In the CsA and Tac trials , 15 and 12 patients , respectively , completed the 52-week follow-up . In the CsA trial , the mean GFR at baseline and week 52 were 35.0 and 57.8 mL/min ( > 15 % improvement , five of six ; unchanged , one of six ) for group 1 and 46.0 and 63.8 mL/min ( > 15 % improvement , four of nine ; unchanged , three of nine ; > 15 % deterioration , two of nine ) for group 2 . In the Tac trial , GFRs were 55.4 and 56.0 mL/min ( > 15 % improvement , two of five ; unchanged , three of five ) for group 1 and 46.7 and 60.2 mL/min ( > 15 % improvement , four of seven ; unchanged , three of seven ) for group 2 . Mild or moderate rejection occurred in 38 % and 9 % of patients in groups 1 and 2 of the CsA trial and in 14 % of each group of the patients in the Tac trial . Conclusions . These pilot studies show that in LTX recipients with renal dysfunction , MMF allows CNI dose reduction or discontinuation , improving or stabilizing GFR in most patients INTRODUCTION Modified release ( MR ) tacrolimus is an extended release formulation administered once daily . The purpose of this pharmacokinetic ( PK ) study was to evaluate tacrolimus exposure in stable liver transplant recipients converted from Prograf twice a day to MR tacrolimus once daily . METHODS This was an open-label , multicenter study with a single sequence , four-period crossover design . Eligible patients were 18 to 65 years of age , > 6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for > 2 weeks prior to enrollment . Patients received Prograf twice a day on days 1 to 14 and 29 to 42 . Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56 . Twenty-four-hour PK profiles were obtained on days 14 , 28 , 42 , and 56 . Laboratory and safety parameters were also evaluated . RESULTS Of 70 patients , 62 completed all four PK profiles . The AUC0 - 24 of tacrolimus was comparable for Prograf twice a day ( days 14 and 42 ) and MR tacrolimus once daily ( days 28 and 56 ) . The 90 % confidence intervals for MR tacrolimus versus Prograf at steady state ( days 28 and 56 vs days 14 and 42 ) was 0.85 to 0.92 for AUC0 - 24 . MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf . AUC0 - 24 was highly correlated to Cmin for Prograf ( day 14 , r = .93 ; Day 42 , r = .89 ) and for MR tacrolimus ( day 28 , r = .93 ; day 56 , r = .92 ) . Renal and liver function remained stable . One patient experienced acute rejection . CONCLUSION The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients BACKGROUND The new microemulsion formulation of cyclosporine ( Neoral ) has been developed in an effort to improve the reliability of drug absorption . The objectives of this study were to assess the efficacy , safety , and tolerability of Neoral compared to the original formulation ( S and immun ) in liver transplant recipients . METHODS In a double-blind , parallel group study conducted in 28 centers across Europe and the United States , patients receiving primary orthotopic liver allografts were r and omized within 24 hr of transplantation , 198 to Neoral and 192 to S and immun . Patients with and without T-tube biliary drainage were included . Postoperatively , all patients also received intravenous ( i.v . ) cyclosporine , together with prednisolone and azathioprine . Antibody induction was excluded . Efficacy measures were rejections , graft failure , patient survival , and the efficacy of the study medication in achieving the desired cyclosporine blood levels . Safety was assessed by reported adverse events , blood pressure , serum creatinine , and other routine laboratory measurements . RESULTS Kaplan-Meier analyses showed that the Neoral group performed better than the S and immun group , with the estimates for patients free of treated rejection and histologically confirmed rejection either showing or approaching statistical significance at the 5 % level . By 52 weeks , 5.8 % ( 95 % confidence limits : -4.4 - 15.9 % ) fewer patients required treatment of acute rejection in the Neoral group . The proportion of patients experiencing at least one treated rejection episode by 2 weeks was 29.8 % for Neoral and 43.2 % for S and immun . For histologically confirmed rejection , these proportions were 32.8 % and 44.3 % , respectively . The proportion of patients experiencing at least one steroid-resistant rejection was 2.0 % for Neoral and 6.3 % for S and immun at week 2 , and 3.0 % and 9.9 % , respectively , at week 3 . All these differences were significant at P<0.05 . By 52 weeks , graft failure was 6.3 % on Neoral and 11.4 % on S and immun , with respective patient survival figures of 85.4 % and 85.8 % . The median duration of the initial episode of i.v . cyclosporine was 4.0 days for Neoral , compared to 6.5 days for S and immun ( P<0.001 ) . Within the first 2 weeks , a larger percentage of patients in the Neoral group reached the lower target level of cyclosporine ( P < or = 0.01 ) . The weight-adjusted daily doses of study medication were lower in the Neoral group ( median dose : 4.86 vs. 5.42 mg/kg/day , P=0.001 ) , but the blood levels of cyclosporine showed no difference . For those with a T-tube , more of the patients on Neoral remained free of treated rejection throughout the study period ( P=0.042 , Wilcoxon ) . By week 2 , 44.9 % of these patients in the S and immun group required treatment for rejection compared to 30.2 % in the Neoral group ( P=0.007 ) . There was no significant difference between the groups for serum creatinine , blood pressure , other biochemical and hematological variables , or reported adverse events . CONCLUSIONS In liver transplantation in the normal clinical setting , the pharmacokinetic advantages of Neoral translate into clinical superiority over S and immun without a negative impact on safety . Recent data indicate that it is not optimal to use i.v . cyclosporine initially in this type of study , but the benefit was seen despite this . In keeping with the previous pharmacokinetic studies , patients managed by T-tube biliary drainage , and hence with no or limited bile available in the gastrointestinal tract , did particularly well with Neoral OBJECTIVES To assess how trial information reported in conference abstract s differs to their subsequent full publication . METHODS R and omized trials reported at the American Society of Clinical Oncology conference ( 1992 ) were identified . CENTRAL and PubMed ( December 2002 ) were search ed to identify corresponding full publications . A checklist ( based on CONSORT ) was used to compare abstract s for 37 trials with their full publication . RESULTS Some aspects were well reported . Ninety-five percent of study objectives , 92 % of participant eligibility , 100 % of trial interventions , and 84 % of primary outcomes were the same in both abstract and full publication . Other areas were more discrepant . Forty-six percent reported the same number of participants r and omized in the abstract and full publication ; only 22 % reported the same number analyzed ( median number analyzed per trial was 96 for abstract s and 117 for full publications ) . Eighty-two percent of trials were closed to follow-up in the full publication compared to 19 % of abstract s. Lack of information was a major problem in assessing trial quality : no abstract s reported on allocation concealment , 16 % reported on blinding and 14 % reported intention to treat analysis . These figures were 49 , 19 , and 46 % , respectively , for full publications . CONCLUSION The information given for trials in conference proceedings can be unstable , especially for trials presenting early or preliminary results , and needs to be improved |
2,696 | 17,054,191 | Hb > or = 133 g/L was not associated with a reduction in the risk of all-cause mortality compared with 120 g/L in dialysis and pre-dialysis patients .
Lower Hb targets were significantly associated with an increased risk for seizures but a reduced risk of hypertension . | BACKGROUND Anaemia affects 60 % to 80 % of patients with chronic kidney disease ( CKD ) reduces quality of life and is a risk factor for early death .
Treatment options are blood transfusion , erythropoietin ( EPO ) and darbepoetin alfa .
Recently higher haemoglobin ( Hb ) and haematocrit ( HCT ) targets have been widely advocated because of positive associations with improved survival and quality of life from observational studies .
OBJECTIVES To assess the benefits and harms of different Hb or HCT targets in CKD patients receiving any treatment for anaemia . | Anemia is one of the most serious complications in patients on dialysis . Erythropoietin improves the anemia . However , erythropoietin resistance is sometimes encountered from causes such as functional iron deficiency , secondary hyperparathyroidism , blood loss , or interaction with other drugs . To clarify the interaction between erythropoietin and the renin-angiotensin system , we studied the maintenance dose of recombinant human erythropoietin ( rHuEPO ) in patients on continuous ambulatory peritoneal dialysis ( CAPD ) with and without angiotensin converting enzyme inhibitor ( ACEIs ) , angiotensin II type I receptor blockers ( ARBs ) , and calcium channel blockers . We divided 36 hypertensive patients on CAPD into three groups -- an ACEI group ( n = 12 ) , an ARB group ( n = 12 ) , and a Ca channel blocker group ( n = 12)-- and then we compared the doses of rHuEPO required to maintain the patients ' hematocrit ( Hct ) above 30 % . In the Ca channel blocker group , the weekly dose of erythropoietin had not changed significantly at the end of the study ( 74 + /- 7 U/kg at the end vs. 76 + /- 8 U/kg at the start ) . The ( oral ) ACEI group needed a significantly higher weekly dose of erythropoietin at the end of the study ( 89 -/+ 9 U/kg at the end vs. 74 -/+ 8 U/kg at the start , p < 0.01 ) . The ( oral ) ARB group also needed a significantly higher weekly dose of erythropoietin at the end of the study ( 82 -/+ 10 U/kg at the end vs. 76 + /- 8 U/kg at the start , p < 0.05 ) . Furthermore , the weekly dose of erythropoietin required in the ACEI group was significantly larger than that required in the ARB group . We conclude that treatment with ACEIs and ARBs induces erythropoietin resistance in patients on CAPD . The inhibitory effect of ARBs on erythropoiesis is less than that of ACEIs In patients with renal anemia , iron therapy can be administered intermittently or regularly at a low dose . We performed a r and omized clinical trial in pediatric patients with end-stage renal failure on hemodialysis and absolute or functional iron deficiency . The study group received maintenance iron therapy according to the ferritin serum levels and the control group received intermittent 10-weekly doses . Success was defined as stabilization of ferritin levels between 100 and 800 μg/l and transferrin saturation ( TSAT ) between 20 % and 50 % , in addition to an increase in the hemoglobin level . The major reason for exclusion was iron overload . The study group received 6 mg/kg per month of parenteral iron [ 95 % confidence interval ( CI ) 3.3–8.8 ] and the control group 14.4 mg/kg per month ( 95 % CI 12–16.8 ) ( P<0.001 ) . After 4 months of treatment , ferritin levels increased to 66 μg/l ( 95 % CI 69–200 ) in the study group and to 334 μg/l ( 95 % CI 145–522 ) in the control group ( P=0.009 ) . Maintenance therapy and intermittent weekly doses were successful in 73 % and 38 % , respectively . After 3 months of treatment , hemoglobin levels increased to 10 g/dl , with no difference between the groups . However , in the control group the increase in hemoglobin levels was unsustained , and 3 patients needed transfusion . Patients in the control group had a higher risk of iron overload than patients in the study group ( 70 % vs. 19 % ) . Thus , the regimen based on assessment of serum ferritin levels was more efficient than the intermittent regimen because it increased and maintained the hemoglobin levels with lower iron doses and a lower risk of iron overload In a prospect i ve study , 40 maintenance hemodialysis patients , r and omized in two equal groups , were treated with recombinant human erythropoietin ( rHuEPO ) for their renal anemia , for a period of 2 years . One group was treated for 2 years , while the other was untreated control during the first year , but received rHuEPO during the second year of the study . Anemia was corrected in all treated patients and hematocrit maintained between 30 and 35 vol% by low-dose subcutaneous treatment with Recormon ( Boehringer Mannheim GmbH , Germany ) , according to the study protocol . Bone marrow biopsy ( BMB ) , from the posterior iliac crest , was taken by the method of Jamshidi from 32 patients . Fourteen patients from the control group were biopsied twice : once at baseline and the second time at 12 months of treatment , while 15 patients from the other group were biopsied only once , at 24 months of rHuEPO treatment . The biopsies were embedded in wax and in epoxy resin , and after staining for light and electron microscopy , they were semiquantitatively examined for several parameters : cellularity , myeloid : erythroid ( M : E ) ratio , megakaryocytes , fatty tissue , megaloblasts , and marrow iron . Cellularity of the bone marrow increased significantly at 12 months of treatment and it remained so at 24 months . M : E ratio was significantly reduced indicating expansion of the erythroid pool , both at 12 and 24 months of therapy . The number of megakaryocytes in the bone marrow increased significantly at 12 months and remained high at 24 months of treatment , while fatty tissue was significantly reduced at 12 and 24 months compared to the baseline values . There was no significant change in the percentage of megaloblasts in the bone marrow . Hemosiderin was reduced after treatment indicating mobilization of the bone marrow iron stores upon treatment with rHuEPO . We concluded that rHuEPO had a beneficial long-term effect on bone marrow Small-solute clearance targets for peritoneal dialysis ( PD ) have been based on the tacit assumption that peritoneal and renal clearances are equivalent and therefore additive . Although several studies have established that patient survival is directly correlated with renal clearances , there have been no r and omized , controlled , interventional trials examining the effects of increases in peritoneal small-solute clearances on patient survival . A prospect i ve , r and omized , controlled , clinical trial was performed to study the effects of increased peritoneal small-solute clearances on clinical outcomes among patients with end-stage renal disease who were being treated with PD . A total of 965 subjects were r and omly assigned to the intervention or control group ( in a 1:1 ratio ) . Subjects in the control group continued to receive their preexisting PD prescriptions , which consisted of four daily exchanges with 2 L of st and ard PD solution . The subjects in the intervention group were treated with a modified prescription , to achieve a peritoneal creatinine clearance ( pCrCl ) of 60 L/wk per 1.73 m(2 ) . The primary endpoint was death . The minimal follow-up period was 2 yr . The study groups were similar with respect to demographic characteristics , causes of renal disease , prevalence of coexisting conditions , residual renal function , peritoneal clearances before intervention , hematocrit values , and multiple indicators of nutritional status . In the control group , peritoneal creatinine clearance ( pCrCl ) and peritoneal urea clearance ( Kt/V ) values remained constant for the duration of the study . In the intervention group , pCrCl and peritoneal Kt/V values predictably increased and remained separated from the values for the control group for the entire duration of the study ( P < 0.01 ) . Patient survival was similar for the control and intervention groups in an intent-to-treat analysis , with a relative risk of death ( intervention/control ) of 1.00 [ 95 % confidence interval ( CI ) , 0.80 to 1.24 ] . Overall , the control group exhibited a 1-yr survival of 85.5 % ( CI , 82.2 to 88.7 % ) and a 2-yr survival of 68.3 % ( CI , 64.2 to 72.9 % ) . Similarly , the intervention group exhibited a 1-yr survival of 83.9 % ( CI , 80.6 to 87.2 % ) and a 2-yr survival of 69.3 % ( CI , 65.1 to 73.6 % ) . An as-treated analysis revealed similar results ( overall relative risk = 0.93 ; CI , 0.71 to 1.22 ; P = 0.6121 ) . Mortality rates for the two groups remained similar even after adjustment for factors known to be associated with survival for patients undergoing PD ( e.g. , age , diabetes mellitus , serum albumin levels , normalized protein equivalent of total nitrogen appearance , and anuria ) . This study provides evidence that increases in peritoneal small-solute clearances within the range studied have a neutral effect on patient survival , even when the groups are stratified according to a variety of factors ( age , diabetes mellitus , serum albumin levels , normalized protein equivalent of total nitrogen appearance , and anuria ) known to affect survival . No clear survival advantage was obtained with increases in peritoneal small-solute clearances within the range achieved in this study BACKGROUND Intravenous ascorbic acid ( IVAA ) administration is reported to enhance erythropoiesis in hemodialysis ( HD ) patients with functional iron deficiency . We explored the effects of IVAA on erythropoiesis and health-related quality of life ( HRQOL ) in unselected HD patients . METHODS Sixty-one HD patients were divided into two groups ; 30 patients received 100 mg of IVAA ( IVAA group ) and 31 patients did not ( control group ) after each dialysis session . Hematocrit ( Hct ) , reticulocyte hemoglobin content , transferrin saturation , ferritin , weekly recombinant human erythropoietin ( rHuEPO ) dosage , weekly intravenous iron ( IVFE ) dosage , and MOS Short Form 36 ( SF-36 ) scale scores were measured at baseline and after 6 months of treatment . RESULTS Mean changes in Hct in the IVAA and control groups were -0.5 and -0.6 mg/dL , respectively , while mean changes in SF-36 scale scores were : physical functioning -1.6 in the IVAA group and 0.38 in the controls ; role physical ( RP ) 3.8 and 9.4 ; bodily pain 9.7 and 0.81 ; general health perception 3.7 and -0.68 ; vitality 4.3 and -7.5 ; social functioning 2.7 and 0.43 ; role emotional ( RE ) 6.9 and 4.9 ; mental health 3.6 and -1.7 . The IVAA group showed significantly higher adverse events ( chest pain : n=1 , nausea : n=2 and fatigue : n=2 ) compared to the controls ( no event ) . CONCLUSIONS The beneficial effects of IVAA on erythropoiesis and HRQOL were not demonstrated in unselected HD patients . Indication of IVAA for HD patients leaves room for further study One hundred and fifty patients undergoing regular haemodialysis for end-stage renal failure entered a trial of treatment for anaemia with recombinant human erythropoietin ( r-HuEPO ) . At data cut-off 37 patients ( 24.6 % ) had dropped out for various reasons ; most of them ( n = 22 ) discontinued because of kidney transplantation ( after 3 - 17 months of treatment ) . The initial dose was 24 U/kg i.v . thrice weekly , with subsequent dose escalations after a minimum of 2 weeks if the haemoglobin ( Hb ) was less than 10 % above the pretreatment baseline . One hundred and forty-three patients who were eligible for efficacy analysis achieved an Hb increase of greater than or equal to 2 g/dl , and all 139 patients eligible for ' full response ' analysis ( Hb between 10 and 12 g/dl ) were dose titrated to reach this arbitrarily defined optimal range . Patients ' response to r-HuEPO treatment was independent of age , weight , nephric state or duration of dialysis treatment . To maintain the Hb within the range of 10 - 12 g/dl during 1 year 's treatment ( n = 96 ) a median weekly r-HuEPO dose of 200 U/kg ( range 150 - 300 ) divided into one , two , or three administrations appeared to be adequate . This maintenance dose depends slightly on the patient 's baseline Hb . The study provides evidence that long-term treatment with r-HuEPO is safe . In 48 patients ( of whom 12 had no history of hypertension ) elevation of blood pressure required additional treatment , which was effective in all but one who was withdrawn from the study . Four patients had seizures and one suffered hypertensive encephalopathy without convulsions . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The optimal haemoglobin concentration ( [ Hb ] ) for patients with end-stage renal failure is uncertain . In particular , it is unclear whether Hb normalization may be an advantage to such patients who are otherwise well . METHODS A prospect i ve , r and omized , double-blind cross-over study was completed in 14 haemodialysis patients ( 12 male ) aged between 23 and 65 years over a period of 18 months , using a variety of measures to examine the effect of epoetin at target [ Hb ] of 10 g/dl ( [Hb](10 ) ) and 14 g/dl ( [Hb](14 ) ) . Patients were r and omized to maintain one or other of the target levels for 6 weeks before being crossed over to the alternative [ Hb ] . Baseline data ( mean [ Hb ] : 8.5+/-0.2 g/dl ) were also included selectively . Six patients were known to be hypertensive . Comparisons were made between 24-h ambulatory blood pressure levels ( ABP ) , echocardiographic findings and estimates of blood volume ( BV ) , plasma volume ( PV ) and Hb mass . Quality of life estimates were obtained using the Sickness Impact Profile ( SIP ) , and epoetin dosage requirements at target [ Hb ] were assessed . RESULTS Daytime and nocturnal ABP ( systolic and diastolic ) were not different at the respective target [ Hb ] , although nocturnal diastolic levels were higher compared with baseline ( 73+/-4 mmHg ) at both [Hb](10 ) ( 83+/-3 , P:<0.01 ) and [Hb](14 ) ( 81+/-6 , P:<0.05 ) . Significant reductions in cardiac output ( 5.2+/-0.3 vs 6.6+/-0.5 l/min , P:<0.01 ) and left ventricular end-diastolic diameter ( 4.8+/-0.2 vs 5.2+/-0.2 cm , P:<0 . 001 ) were found at [Hb](14 ) compared with [Hb](10 ) . Left ventricular mass index was correlated with both PV ( P:<0.001 ) and BV ( P:<0.01 ) , but not with Hb mass . The PV decreased as the [ Hb ] rose ( P:<0.001 ) but BV remained unchanged . Quality of life was significantly improved at [Hb](14 ) compared with [Hb](10 ) for both total score ( 6 . 5+/-1.7 vs 13.4+/-3.0 , P:=0.01 ) and psychosocial dimension score ( 5 . 4+/-1.9 vs 15.4+/-4.0 , P:<0.01 ) . The maintenance weekly dose of epoetin required was 80 % higher at [Hb](14 ) compared with [Hb](10 ) ( P:<0.001 ) . CONCLUSION These data suggest there may be a significant haemodynamic and symptomatic advantage in maintaining a physiological [ Hb ] in haemodialysis patients . Although untoward effects were not identified in this study at [Hb](14 ) , a substantially higher dose of epoetin is required to maintain this level BACKGROUND This r and omized clinical trial is design ed to assess whether the prevention and /or correction of anemia , by immediate versus delayed treatment with erythropoietin alfa in patients with chronic kidney disease , would delay left ventricular ( LV ) growth . Study design and sample size calculations were based on previously published Canadian data . METHODS One hundred seventy-two patients were r and omly assigned . The treatment group received therapy with erythropoietin alfa subcutaneously to maintain or achieve hemoglobin ( Hgb ) level targets of 12.0 to 14.0 g/dL ( 120 to 140 g/L ) . The control/delayed treatment group had Hgb levels of 9.0 + /- 0.5 g/dL ( 90 + /- 5 g/L ) before therapy was started : target level was 9.0 to 10.5 g/dL ( 90 to 105 g/L ) . Optimal blood pressure and parathyroid hormone , calcium , and phosphate level targets were prescribed ; all patients were iron replete . The primary end point is LV growth at 24 months . RESULTS One hundred fifty-two patients were eligible for the intention-to-treat analysis : mean age was 57 years , 30 % were women , 38 % had diabetes , and median glomerular filtration rate was 29 mL/min ( 0.48 mL/s ; range , 12 to 55 mL/min [ 0.20 to 0.92 mL/s ] ) . Blood pressure and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were similar in the control/delayed treatment and treatment groups at baseline . Erythropoietin therapy was administered to 77 of 78 patients in the treatment group , with a median final dose of 2,000 IU/wk . Sixteen patients in the control/delayed treatment group were administered erythropoietin at a median final dose of 3,000 IU/wk . There was no statistically significant difference between groups for the primary outcome of mean change in LV mass index ( LVMI ) from baseline to 24 months , which was 5.21 + /- 30.3 g/m2 in the control/delayed treatment group versus 0.37 + /- 25.0 g/m2 in the treatment group . Absolute mean difference between groups was 4.85 g/m2 ( 95 % confidence interval , -4.0 to 13.7 ; P = 0.28 ) . Mean Hgb level was greater in the treatment group throughout the study and at study end was 12.75 g/dL ( 127.5 g/L in treatment group versus 11.46 g/dL [ 114.6 g/L ] in control/delayed treatment group ; P = 0.0001 ) . LV growth occurred in 20.1 % in the treatment group versus 31 % in the control/delayed treatment group ( P = 0.136 ) . In patients with a stable Hgb level , mean LVMI did not change ( -0.25 + /- 26.7 g/m2 ) , but it increased in those with decreasing Hgb levels ( 19.3 + /- 28.2 g/m2 ; P = 0.002 ) . CONCLUSION This trial describes disparity between observational and r and omized controlled trial data : observed and r and omly assigned Hgb level and LVMI are not linked ; thus , there is strong evidence that the association between Hgb level and LVMI likely is not causal . Large r and omized controlled trials with unselected patients , using morbidity and mortality as outcomes , are needed A study was undertaken to ascertain the effects of recombinant human erythropoietin ( r-HuEPO ) on renal function in chronic renal failure predialysis patients . The effect of improvement of anemia by r-HuEPO on the rate of decline in renal function in predialysis patients has not been previously studied prospect ively in a large number of patients using reliable measures of glomerular filtration rate ( GFR ) . To investigate the efficacy , safety , and impact of r-HuEPO therapy in chronic renal insufficiency patients , a 48-week , r and omized , open-label , multicenter study was initiated in 83 anemic , predialysis ( serum creatinine 3 to 8 mg/dL ) patients . Serial GFRs were measured using 125I-iothalamate clearance . Forty patients were r and omized to the untreated arm and 43 patients to the treatment arm ( 50 U/kg r-HuEPO subcutaneously three times weekly ) . Baseline characteristics were comparable for the r-HuEPO-treated and untreated groups . During this 48-week study , GFR , mean arterial blood pressure , and daily protein intake were not significantly different between the two groups . There was a statistically significant increase in hematocrit for the r-HuEPO-treated group that was not associated with acceleration of deterioration in residual renal function . This was demonstrated by the lack of a significant ( P = 0.376 ) between-group difference in mean change in GFR from baseline to last available value for the r-HuEPO-treated ( -2.1 + /- 3.2 mL/min ) and untreated ( -2.8 + /- 3.5 mL/min ) groups . This study concludes that r-HuEPO therapy improves anemia in predialysis patients and does not accelerate the rate of progression to end-stage renal disease Abstract A prospect i ve r and omized study of the use of recombinant human erythropoietin ( rHuEPO ) in children with chronic renal disease was conducted to assess dosing requirements and side effects . Forty-four children with chronic renal failure , aged 4 months to 21 years , were studied . Twenty-five patients were pre dialysis , 10 on peritoneal dialysis , and 9 on hemodialysis . Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin ( Hb ) was attained . Dose was then adjusted to maintain a normal Hb . Eighty-two percent of patients reached target Hb by 7.9±5.6 weeks ( mean±SD ) ; 95 % of patients in the high-dose group and 66 % in the low-dose group reached target Hb within 12 weeks . The overall median rHuEPO dose at target Hb was 150 U/kg per week . Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb ( median 250 U/kg per week ) . Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks . Iron deficiency and /or hypertension occurred in 30 % of children . In conclusion , rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease Recombinant human erythropoietin ( r-HuEpo ) is now available to correct the anaemia of end stage renal failure . The clinical consequences of increasing the haemoglobin concentration in children on dialysis are incompletely documented ; a placebo controlled study is essential when assessing subjective changes , for example in appetite or other aspects of quality of life . A single blind , placebo controlled crossover study in 11 children with end stage renal failure was performed to assess the clinical benefits result ing from correction of anaemia . Ten of the 11 children completed 36 weeks of the study and seven completed both 24 week limbs . Subcutaneous administration of r-HuEpo twice a week result ed in an increase in haemoglobin concentration , from 73 to 112 g/l . This was associated with an objective improvement in exercise tolerance , and a subjective improvement in physical performance and health , and better school attendance . No consistent effect was seen on appetite , growth , psychosocial functioning , biochemical control , or peritoneal dialysis efficiency . A small but clinical ly unimportant increase in systolic and diastolic blood pressure was seen in five children . One child on antihypertensive treatment required an increase in dosage during r-HuEpo while another child required a reduction in treatment . These findings , together with the important cardiac benefits previously described during r-HuEpo treatment , support the use of r-HuEpo in all children with end stage renal failure and anaemia The renin-angiotensin system ( RAS ) regulates BP and may affect chronic kidney disease ( CKD ) through induction of tissue growth and fibrosis . The angiotensinogen ( AGT ) promoter G(-6 ) allele lowers transcription and is inversely associated with hypertension . In white individuals , the A1166C 3'-UTR variant of angiotensin II type 1 receptor ( AT1R ) has been associated with CKD . CKD associations with these RAS genes are uncertain in high-risk black population s. A prospect i ve population -based study of CKD risk was conducted among 3706 black individuals without severe renal dysfunction at baseline ( serum creatinine > or = 177 micromol/L [ 2.0 mg/dl ] for men , > or = 159 micromol/L [ 1.8 mg/dl ] for women ) to examine associations with AGT and AT1R . Incident CKD progression was defined as kidney disease hospitalization or increase in serum creatinine level > or = 35 micromol/L ( 0.4 mg/dl ) above baseline . During mean follow-up of 10.2 yr , CKD progression incidence rate ( per 1000 person-years ) was 8.2 ( n = 312 cases ) . Risk was lower for AGT G(-6 ) carriers compared with A(-6 ) ( incidence 6.9 versus 9.0 ; log-rank P = 0.03 ) and nonsignificantly higher among AT1R C1166 carriers . Adjusting for hypertension and major CKD risk factors , AGT G(-6)decreased risk ( relative risk 0.75 ; 95 % confidence interval 0.57 to 0.98 ) . AT1R C1166 increased risk only among those with hypertension ( relative risk 1.65 ; 95 % confidence interval 1.14 to 2.39 ) . The AGT G(-6)A polymorphism may play a role in CKD progression in black individuals , consistent with in vitro effects on AGT levels and renal remodeling but independent of BP . The AT1R C1166 allele may increase susceptibility but only in the presence of hypertension The investigators evaluated the impact of recombinant human erythropoietin ( r-HuEPO ) therapy on health-related quality of life ( HRQL ) in predialysis chronic renal disease patients with anemia . Eighty-three patients were entered into a r and omized , parallel-group , open-label clinical trial with follow-up evaluations over 48 weeks . Forty-three patients were assigned to r-HuEPO treatment , and 40 patients were assigned to an untreated control group . Hematocrit levels were measured at baseline and monthly . HRQL was assessed at baseline and at weeks 16 , 32 , and 48 . The HRQL assessment included measures of physical function , energy , role function , health distress , cognitive function , social function , home management , sexual dysfunction , depression , and life satisfaction . Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group ( P < 0.0001 ) , and no changes were seen in the untreated group . Correction of anemia ( hematocrit > or = 36 ) occurred in 79 % of r-HuEPO-treated patients and 0 % of control patients . Significant improvements in assessment s of energy ( P < 0.05 ) , physical function ( P < 0.05 ) , home management ( P < 0.05 ) , social activity ( P < 0.05 ) , and cognitive function ( P < 0.05 ) were found for the r-HuEPO-treated group . No changes were observed in the control group , except for a decrease in physical function ( P < 0.05 ) . Between-group differences favoring the r-HuEPO-treated group were found for energy ( P < 0.05 ) and physical functioning ( P < 0.05 ) . In patients receiving r-HuEPO , significant improvements were seen in hemotocrit levels , and these increases result ed in improvements in HRQL BACKGROUND This study is design ed to assess the effect of early and complete correction of anemia by using recombinant human erythropoietin ( epoetin ) alfa on the progression of chronic kidney disease ( CKD ) . METHODS Patients were r and omly assigned to achieve high ( 13 to 15 g/dL [ 130 to 150 g/L ] ) or low ( 11 to 12 g/dL [ 110 to 120 g/L ] ) hemoglobin-level targets during 4 months of stabilization , followed by 36 months of maintenance . Glomerular filtration rate ( GFR ) decrease was measured by using iohexol clearance . Quality of life , nutrition , and safety also were monitored . RESULTS Because of labeling changes for subcutaneous administration of epoetin alfa ( Eprex ; Johnson and Johnson , Schaffhausen , Switzerl and ) , the study was terminated prematurely . There were 195 patients enrolled in each group ; 108 high-hemoglobin and 133 low-hemoglobin patients entered the maintenance phase . Mean maintenance duration was 7.4 months for the high-hemoglobin group and 8.3 months for the low-hemoglobin group . GFR decrease was numerically , but not statistically significantly , lower with the high-hemoglobin group ( 0.058 versus 0.081 mL/min/1.73 m2/mo [ < 0.01 mL/s/1.73 m2/mo ] ) . Physical quality -of-life measures showed trends ( Role-Physical , P = 0.055 ; Physical Function , P = 0.083 ) or statistically significant improvement ( Vitality , P = 0.042 ) with high hemoglobin levels at the end of the stabilization phase . Adverse events were similar between groups . Cardiovascular adverse events occurred in 25 % of the high-hemoglobin and 18 % of the low-hemoglobin patients ( P = 0.137 ) . Neither epoetin dosage nor hemoglobin level was associated with cardiovascular adverse events or death . CONCLUSION These data suggest that normalization of hemoglobin levels in patients with CKD is safe . Longer duration studies are needed to clarify efficacy benefits with high hemoglobin levels Renal anaemia is an independent risk factor for the development of left ventricular hypertrophy ( LVH ) , heart failure and mortality . Studies show that partial correction of anaemia leads to partial regression of LVH . However , early initiation of anaemia therapy may be the optimal way to reduce cardiac morbidity and mortality . The Cardiovascular risk Reduction by Early Anemia Treatment with Epoetin Beta ( CREATE ) trial will investigate the effect of early anaemia correction on cardiovascular risk reduction in patients not yet on renal replacement therapy . The primary objectives of this open , r and omized , multicentre trial are to investigate the effect of early anaemia correction on the change in left ventricular mass index after 1 year , and the time to first cardiovascular event . The trial comprises two treatment arms : early intervention where patients will receive epoetin beta when their haemoglobin ( Hb ) level is 11 - 12.5 g/dl and their target Hb will be 13 - 15 g/dl , and late intervention , where patients will receive epoetin beta once their Hb level is < 10.5 g/dl and their target Hb will be 10.5 - 11.5 g/dl . The study will be event-driven with a continuous evaluation and an interim analysis once every year . The inclusion of 600 patients is based on assumption of a 15 - 20 % event rate in the control group and that 200 events are needed to detect a reduction of about one-third . In conclusion , the CREATE trial will examine whether early anaemia treatment will prevent development of LVH , reduce cardiovascular morbidity and provide other benefits Abstract .Anaemia is a key component of diabetic nephropathy , but its importance has only recently been recognised . Recombinant human erythropoietin ( epoetin ) is an established treatment for renal anaemia , and may help to reduce complications associated with diabetic nephropathy , such as cardiovascular disease . The limited experience with the use of epoetin in this patient group prompts the urgent need for clinical data on anaemia correction in early diabetic nephropathy , particularly with regard to benefits on cardiovascular risk reduction . The Anaemia CORrection in Diabetes ( ACORD ) study will investigate the effects of anaemia correction on cardiac structure and function in patients with early diabetic nephropathy . This 15-month multicentre study will recruit 160 adult patients with diabetes , mild or moderate chronic kidney disease ( with creatinine clearance ≥30 ml/min at screening ) and moderate anaemia ( haemoglobin [ Hb ] , 10.5–13.0 g/dl ) . Patients will be r and omised to one of two groups : the early treatment group will receive subcutaneous epoetin beta ( NeoRecormon ) at study entry to maintain target Hb levels of 13–15 g/dl , while the control group will reflect current practice and will not receive epoetin therapy until Hb levels decline below 10.5 g/dl . The primary efficacy variable , change in left ventricular mass index , will be evaluated at 15 months following r and omisation ; secondary efficacy variables will include changes in cardiac structure and function over the study period . The ACORD study should provide valuable information on the benefits of anaemia correction in patients with early diabetic nephropathy . The study will also increase awareness of the importance of treating anaemia associated with diabetes BACKGROUND Partial correction of renal anaemia with erythropoietin improves quality of life ( QoL ) . We aim ed to examine if normalization of haemoglobin with epoetin alfa in pre-dialysis and dialysis patients further improves QoL and is safe . METHODS 416 Sc and inavian patients with renal anaemia [ pre-dialysis , haemodialysis ( HD ) and peritoneal dialysis patients ] were r and omized to reach a normal haemoglobin of 135 - 160 g/l ( n=216 ) or a subnormal haemoglobin of 90 - 120 g/l ( n=200 ) with or without epoetin alfa . Study duration was 48 - 76 weeks . QoL was measured using Kidney Disease Question naires in 253 Swedish dialysis patients . Safety was examined in all patients . RESULTS QoL improved , measured as a decrease in physical symptoms ( P=0.02 ) , fatigue ( P=0.05 ) , depression ( P=0.01 ) and frustration ( P=0.05 ) in the Swedish dialysis patients when haemoglobin was normalized . In pre-dialysis patients , diastolic blood pressure was higher in the normal compared with the subnormal haemoglobin group after 48 weeks . However , the progression rate of chronic renal failure was comparable . In the normal haemoglobin group ( N-Hb ) , 51 % had at least one serious adverse event compared with 49 % in the subnormal haemoglobin group ( S-Hb ) ( P=0.32 ) . The incidence of thrombovascular events and vascular access thrombosis in HD patients did not differ . The mortality rate was 13.4 % in the N-Hb group and 13.5 % in the S-Hb group ( P=0.98 ) . Mortality decreased with increasing mean haemoglobin in both groups . CONCLUSIONS Normalization of haemoglobin improved QoL in the subgroup of dialysis patients , appears to be safe and can be considered in many patients with end-stage renal disease BACKGROUND In patients with end-stage renal disease , anemia develops as a result of erythropoietin deficiency , and recombinant human erythropoietin ( epoetin ) is prescribed to correct the anemia partially . We examined the risks and benefits of normalizing the hematocrit in patients with cardiac disease who were undergoing hemodialysis . METHODS We studied 1233 patients with clinical evidence of congestive heart failure or ischemic heart disease who were undergoing hemodialysis : 618 patients were assigned to receive increasing doses of epoetin to achieve and maintain a hematocrit of 42 percent , and 615 were assigned to receive doses of epoetin sufficient to maintain a hematocrit of 30 percent throughout the study . The median duration of treatment was 14 months . The primary end point was the length of time to death or a first nonfatal myocardial infa rct ion . RESULTS After 29 months , there were 183 deaths and 19 first nonfatal myocardial infa rct ions among the patients in the normal-hematocrit group and 150 deaths and 14 nonfatal myocardial infa rct ions among those in the low-hematocrit group ( risk ratio for the normal-hematocrit group as compared with the low-hematocrit group , 1.3 ; 95 percent confidence interval , 0.9 to 1.9 ) . Although the difference in event-free survival between the two groups did not reach the prespecified statistical stopping boundary , the study was halted . The causes of death in the two groups were similar . The mortality rates decreased with increasing hematocrit values in both groups . The patients in the normal-hematocrit group had a decline in the adequacy of dialysis and received intravenous iron dextran more often than those in the low-hematocrit group . CONCLUSIONS In patients with clinical ly evident congestive heart failure or ischemic heart disease who are receiving hemodialysis , administration of epoetin to raise their hematocrit to 42 percent is not recommended Over the past half century there has been a vast proliferation first of r and omised trials and now of meta-analyses , both of which ( if appropriately analysed ) can avoid bias . But to get medically reliable answers to previously unanswered questions about life or death treatment decisions it is n't enough just to avoid bias . We must also ensure that we are not seriously misled by the play of chance , and often the only way to do this reliably is to get appropriate analyses of really large scale r and omised evidence .1 At present , many wrong , or at least unreliable , therapeutic answers are being generated by non-r and omised “ outcomes research , ” by small r and omised studies , by small meta-analyses , and by statistically inappropriate analyses . Moreover , even when large scale r and omised evidence is available , wrong conclusions can be drawn from unduly selective emphasis on particular trials or subgroups— and such “ selection biases ” can cause even greater errors when there is only a limited amount of evidence to review . Over the past 50 years r and omisation has already delivered reliable answers to some important questions and it offers the promise of reliable answers to many more . For that promise to BACKGROUND Erythropoietin is known to improve outcomes in patients with anemia from chronic renal disease . However , there is uncertainty about the optimal timing of initiation of erythropoietin treatment in predialysis patients with non-severe anemia . METHODS We conducted a r and omized controlled trial of early versus deferred initiation of erythropoietin in nondiabetic predialysis patients with serum creatinine 2 to 6 mg/dL and hemoglobin 9 to 11.6 g/dL. The early treatment arm was immediately started on 50 U/kg/wk of erythropoietin alpha with appropriate titration aim ing for hemoglobin of > or = 13 g/dL. The deferred treatment arm would start erythropoietin only when hemoglobin decreased to < 9 g/dL. The primary end point was a composite of doubling of creatinine , renal replacement , or death . RESULTS Eighty-eight patients were r and omized ( early treatment N= 45 , deferred treatment N= 43 ) and followed for a median of 22.5 months . During follow-up , 13 versus 23 patients reached the primary end point in the two arms , respectively ( log-rank P= 0.0078 ) . The relative hazard for reaching an end point was 0.42 ( P= 0.012 ) . Adjusting for baseline serum creatinine , the adjusted relative hazard was 0.37 ( P= 0.004 ) , while the risk increased 2.23-fold ( P < 0.001 ) per 1 mg/dL higher creatinine at baseline . The benefit was similar regardless of the baseline hemoglobin and proteinuria . No patients had any severe adverse events . CONCLUSION Early initiation of erythropoietin in predialysis patients with non-severe anemia significantly slows the progression of renal disease and delays the initiation of renal replacement therapy PURPOSE The purpose of this study was to determine the efficacy of recombinant human erythropoietin ( rHuEPO ) given subcutaneously three times/week in patients with chronic renal failure and anemia ( predialysis ) . PATIENTS AND METHODS Eleven patients with predialysis chronic renal failure participated in a double-blind , placebo-controlled study of subcutaneously administered erythropoietin . For 12 weeks , patients received either rHuEPO 100 mu/kg body weight three times/week subcutananeously or a placebo . After 12 weeks of placebo , patients now also received rHuEPO in a dose up to 150 mu/kg three times/week until target hematocrit was achieved . Throughout the study , blood pressure was monitored closely and blood work was obtained regularly for hemoglobin , hematocrit , reticulocyte count , and iron profile determinations . RESULTS At 12 weeks , the hematocrit of the treated group had risen from 29 % + /- 2 % to 35 % + /- 2 % ( p less than 0.001 ) . The placebo group baseline hematocrit was 28 % + /- 2 % and at 12 weeks 26 % + /- 2 % After 12 weeks of rHuEPO therapy , the hematocrit of the prior placebo group was 32 % + /- 2 % ( p less than 0.001 versus baseline ) . No significant change in biochemical parameters was noted . Mean blood pressure values were comparable before and after treatment . All protein ultimately required iron supplementation . In two patients , the rate of progression of renal failure appeared to increase as their hematocrit rose and rHuEPO was discontinued . CONCLUSIONS It is concluded that rHuEPO given subcutaneously is an effective and safe therapy for patients with chronic renal failure who are anemic and who are not receiving dialysis It is not known whether prevention of anemia among patients with chronic kidney disease would affect the development or progression of left ventricular ( LV ) hypertrophy . A r and omized controlled trial was performed with 155 patients with chronic kidney disease ( creatinine clearance , 15 to 50 ml/min ) , with entry hemoglobin concentrations ( [ Hb ] ) of 110 to 120 g/L ( female patients ) or 110 to 130 g/L ( male patients ) . Patients were monitored for 2 yr or until they required dialysis ; the patients were r and omized to receive epoetin alpha as necessary to maintain [ Hb ] between 120 and 130 g/L ( group A ) or between 90 and 100 g/L ( group B ) . [ Hb ] increased for group A ( from 112 + /- 9 to 121 + /- 14 g/L , mean + /- SD ) and decreased for group B ( from 112 + /- 8 to 108 + /- 13 g/L ) ( P < 0.001 , group A versus group B ) . On an intent-to-treat analysis , the changes in LV mass index for the groups during the 2-yr period were not significantly different ( 2.5 + /- 20 g/m(2 ) for group A versus 4.5 + /- 20 g/m(2 ) for group B , P = NS ) . There was no significant difference between the groups in 2-yr mean unadjusted systolic BP ( 141 + /- 14 versus 138 + /- 13 mmHg ) or diastolic BP ( 80 + /- 6 versus 79 + /- 7 mmHg ) . The decline in renal function in 2 yr , as assessed with nuclear estimations of GFR , also did not differ significantly between the groups ( 8 + /- 9 versus 6 + /- 8 ml/min per 1.73 m(2 ) ) . In conclusion , maintenance of [ Hb ] above 120 g/L , compared with 90 to 100 g/L , had similar effects on the LV mass index and did not clearly affect the development or progression of LV hypertrophy . The maintenance of [ Hb ] above 100 g/L for many patients in group B might have been attributable to the relative preservation of renal function BACKGROUND Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin ( rHuEPO ) , including a three-fold longer elimination half-life that allows for less frequent dosing . This study was aim ed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO . METHODS Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha . Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha . Patients received darbepoetin alpha by the same route of administration ( SC or IV ) as the one used for rHuEPO . The unit doses of darbepoetin alpha ( 10 - 150 microg ) were titrated to maintain haemoglobin concentration within -1.0 and + 1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks . RESULTS The mean change in haemoglobin from baseline to the evaluation period ( weeks 21 - 24 ) was statistically but not clinical ly significant [ -0.10 g/dL ( 95 % CI : -0.18 , -0.02 ] . In general , the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [ ( from 26.10 micro g/wk to 25.90 microg/wk ; percentage change -0.40 % ( 95 % CI : -3.78 , 3.10 ) ] . Overall , darbepoetin alpha was well tolerated . CONCLUSIONS The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency CONTEXT Ongoing efforts to improve the quality of reporting for r and omized controlled trials ( RCTs ) include the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement . We examined the frequency of explicit reporting of the number needed to treat ( NNT ) and the absolute risk reduction ( ARR ) in RCTs . METHODS Five frequently cited journals were investigated : Annals of Internal Medicine , BMJ , JAMA , The Lancet , and the New Engl and Journal of Medicine . For each journal , 4 years were evaluated : 1989 , 1992 , 1995 , and 1998 . All issues of each journal for each year were review ed manually . Eligible articles were those in which an RCT was conducted on the use of a medication showing a significant treatment effect . Elements abstract ed from each eligible article were the condition investigated , event being treated or prevented , intervention , study results , and reporting methods ( relative risk reduction , NNT , and ARR ) . RESULTS Of 359 eligible articles , NNT was reported in 8 articles . Six of the 8 studies were from 1998 . Absolute risk reduction was reported in 18 articles , 10 of which were from 1998 . CONCLUSIONS Despite CONSORT recommendations , few authors expressed their findings in terms of NNT or ARR . Consideration should be given to including these values in reports of RCTs In a two-way study , we treated renal anemia in chronic hemodialysis patients with recombinant human erythropoietin ( rh-EPO ) and followed heart morphology and function dynamics by echocardiography . Thirty-eight patients were r and omly divided in two equal groups : the therapy group , treated with rh-EPO for 24 months , and the control group , not treated during the first 12 months and treated with rh-EPO during the second 12 months . Anemia was corrected , and hematocrit was maintained between 30 and 35 vol% by subcutaneous rh-EPO administration . Echocardiographic assessment was performed at the end of the untreated control phase and was repeated after 12 months of rh-EPO treatment in the control group and after 12 and 24 months of treatment in the therapy group . The results revealed significant morphologic , hemodynamic , and eventually functional changes . After 12 months of rh-EPO treatment , the end-diastolic volume ( EDV ) decreased from 135.8 + /- 23.7 to 109.8 + /- 25.3 ml , p < 0.001 ; stroke volume ( SV ) from 91.9 + /- 17.6 to 71.3 + /- 12.4 ml , p < 0.001 ; left ventricular mass-Devereux ( LVMD ) from 297.2 + /- 57.8 to 218.0 + /- 50.4 g , p < 0.01 ; cardiac output ( CO ) from 7,279 + /- 1,932 to 5,711 + /- 1,276 ml/min , p < 0.002 ; total peripheral resistance ( TPR ) rose from 1,330 + /- 390 to 1,707 + /- 373 dynes x s/cm5 , p < 0.007 . After 24 months , LVMD decreased further from 224.6 + /- 43.1 to 195.7 + /- 46.3 g , p < 0.004 . The relaxation time index ( RTI ) decreased from 64.7 + /- 20.4 to 52.4 + /- 18.0 ms , p < 0.045 , suggesting improved diastolic function . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The optimal subcutaneous ( SC ) epoetin alfa strategy is unestablished . The individual variability in dose requirements needs consideration . In this study , prolonged intervals were assessed in relation to varying dose requirements . METHODS The study included 153 hemodialysis ( HD ) patients on stable SC epoetin alfa . Based on dose requirements , the patients received either 4,000 U ( group I , n=51 ) or 10,000 U ( group II , n=102 ) as whole 1 mL vials at prolonged intervals . The study comprised three 8-week periods : an initial period maintaining the basal regimens , an adjustment period where the intervals were prolonged , and a maintenance period . Alterations in hemoglobin ( Hb ) , weekly doses and intervals in each group were compared . RESULTS One hundred and thirty-seven patients completed the study ( 48 in group I and 89 in group II ) . In group I , the mean interval was prolonged from 5.4 + /- 1.9 to 7.8 + /- 3.1 days ( p=0,01 ) with stable Hb and EPO doses . In group II , prolonged intervals were associated with a reduction in mean Hb below target level and a significant increase in EPO doses ( p=0,002 ) . Iron deficiency and inflammation could explain the poor response in approximately one-third of the patients . CONCLUSIONS In HD patients , the optimal injection frequency should be individually adjusted . Prolonged intervals can be applied to patients with low-dose requirements . Observing iron status and inflammation is necessary for optimal response Transient ST-segment depression measured on ambulatory ECG monitors has been described as representing silent ischemia . Patients who demonstrate silent ischemia have been reported to show increased mortality compared to patients without silent ischemia . We undertook this study to determine if the correction of anemia in End Stage Renal Disease ( ESRD ) patients from(± = st and ard deviation ) 30 ± 3 to 42 ± 3 with the use of Epoetin alfa would result in decreased silent ischemia in patients with clinical ly evident ischemic heart disease or congestive heart failure . Methods : Thirty one ESRD patients with congestive heart failure or patients with clinical ly-evident ischemic heart disease were r and omized into one of two arms . Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42 ± 3 % and patients in Group B were maintained with a hematocrit of 30 ± 3 % throughout the course of the study . All patients had a 24 hour Holter monitor recording at baseline and at 28 weeks after r and omization ( when they had reached their target hematocrit ) . Significant silent ischemia was considered to be present if patients demonstrated at least 60 seconds of ≥ 1 mm ST segment depression . Results : Fifteen patients were r and omized to Group A and 16 patients were r and omized to Group B. The mean hematocrit increased in group A from 29.1 ± 2.4 % to 40.8 ± 5.2 % after 30 weeks . The mean hematocrit in Group B remained stable at 30 ± 3 % throughout the course of the study . Ten patients demonstrated silent ischemia at baseline . At follow up patients in group A demonstrated a mean of 1.7 ± 4.9 minutes of ischemia compared to 1.1 ± 3.4 minutes in group B. These were not significantly different . A similar number of patients in group A and Group B required adjustments in their anti-anginal medication during the course of the study . Conclusion : It is possible to increase hematocrit to near normal levels in hemodialysis with the administration of exogenous Epoetin alfa . The increase in hematocrit form 30 ± 3 % to 42 ± 3 % is not associated with a change in the level of silent ischemia these patients demonstrate In a prospect i ve cohort study of 680 incident continuous peritoneal dialysis ( PD ) patients in North America , dialysis in the United States compared with Canada was associated with a relative risk ( RR ) of death of 1.93 ( 95 % confidence interval [ CI ] , 1.14 to 3.28 ) . The 2-yr survival probability was 79.7 % in Canada and 63.2 % in the United States . This difference was not explained by race , age , gender , functional status , insulin-dependent diabetes mellitus , history of cardiovascular disease ( CVD ) , nutritional status , or adequacy of dialysis . Other potential explanatory variables were further evaluated . These included severity of CVD , residual renal function , race , differential transfer to hemodialysis or transplantation , patient compliance , modality selection bias , and incidence of endstage renal disease requiring dialysis . Cardiovascular morbidity and peritonitis probabilities were compared . The CVD severity index was not different between countries ; the RR risk associated with dialysis in the United States remained high at 1.87 ( 95 % CI , 1.09 to 3.19 ) . Residual renal function at initiation of dialysis was not different between countries . The 2-yr survival for Caucasians was 77 % in Canada and 55 % in the United States . There was no difference in the probability of transfer to hemodialysis or transplantation . The RR of a nonfatal cardiovascular event in the United States compared with Canada was 1.80 ( 95 % CI , 1.21 to 2.67 ) . There was no difference in time to first peritonitis . The observed to predicted creatinine ratio , as an estimate of compliance , was 1.13 in Canada and 1.00 in the United States . The prevalence of PD in the study centers was 48 % in Canada and 22 % in the United States . The incidence of new dialysis patients in 1992 was 100/million population in Canada compared with 211/ million in the United States . The survival difference is not explained by age , gender , insulin-dependent diabetes mellitus , nutritional status , or adequacy of dialysis . Neither is it explained by race , severity of CVD , transfer to hemodialysis , transplantation , or an estimate of compliance . The lower proportion of patients receiving PD in the United States may represent a selection bias of uncertain direction . The higher acceptance rate for dialysis in the United States may explain , in part , the greater cardiovascular morbidity and the decreased survival observed BACKGROUND Numerous prior studies have reported that a substantially higher dose of epoetin is required to maintain haemoglobin ( Hb ) concentration when patients are switched from a subcutaneous ( s.c . ) to intravenous ( i.v . ) route of administration . Many of the reported trials , however , involved patients who did not have adequate serum iron levels . It was hypothesized that patients with adequate iron stores who are switched from one route of administration to the other without a change in dose will experience substantially less change in their Hb concentration . METHODS Haemodialysis patients who were iron replete ( ferritin 300 - 800 microg/L , transferrin saturation ( TSAT ) 25 - 50 % ) participated in a prospect i ve , r and omized cross-over trial receiving epoetin for 3 months either by s.c . or i.v . injection followed by a further 3 months of epoetin via the other route . The principal aim was to determine changes in Hb concentration without altering the weekly epoetin dose . The secondary aim was to assess whether the frequency of dosing ( once , twice or thrice weekly ) influenced the Hb concentration response . RESULTS Eighty-one patients ( mean age 62 years , 60 % male ) entered the study and 15 withdrew prior to study completion . Forty-three patients began s.c . epoetin alfa administration ( group A ) and 38 on i.v . ( group B ) . Median ferritin and TSAT at entry for groups A and B were 409 and 394 microg/L ( NS ) and 31 and 32 % ( NS ) , respectively , which remained within the target range during the study . Median epoetin doses for groups A and B were similar ( 90 vs 93 IU/kg per week , NS ) . After 3 months , the mean Hb concentration rose for group A ( SC ; 118.7 - 121.9 g/L ( P = 0.03 ) ) but it fell for group B ( i.v . ; 119.1 - 116.0 g/L ( P = 0.019 ) ) . Following the change in route of administration , the Hb concentration for group A ( i.v . ) fell by 5.1 % over 3 months ( 121.9 - 115.4 , P < 0.001 ) and rose by 2.8 % for group B ( s.c . ) over 3 months ( 116.0 - 119.7 , P = 0.001 ) . Similar significant changes in the Hb concentration were seen at different dosing frequencies . CONCLUSION Subcutaneous administration of epoetin produces a significant , although slight clinical change in Hb concentration compared with i.v . administration in stable , iron replete , haemodialysis patients . A similar effect appears to prevail regardless of the frequency of injections given This study analyzed blood pressure in hemodialysis patients treated with epoetin beta in multicenter trials . Antihypertensive drugs were prescribed as usual . Placebo-controlled trials compared epoetin ( 100 to 150 U/kg ; N = 151 ) with placebo ( N = 78 ) for 82 days . Hemoglobin ( 108 + /- 18 versus 75 + /- 14 g/L ) ( mean + /- SD ) and diastolic blood pressure ( 84 + /- 14 versus 78 + /- 15 mm Hg ) were greater ( P less than 0.05 ) after epoetin . Clinical ly important increases in blood pressure ( increases in diastolic blood pressure greater than or equal to 10 mm Hg and /or drug therapy ) were more frequent with epoetin ( 58 versus 37 % ; P = 0.005 ) . A dose-response trial compared epoetin , 25 U/kg ( N = 42 ) , 100 U/kg ( N = 40 ) , and 200 U/kg ( N = 39 ) for 138 days . Increases in hemoglobin were dose dependent , but clinical ly important increases in blood pressure were not . In analyses of all patients treated with epoetin ( N = 272 ) , no baseline or final level of hemoglobin , or rate of hemoglobin rise , was a threshold for a rise in blood pressure . Patients requiring antihypertensive drugs or having uncontrolled hypertension ( diastolic blood pressure greater than 90 mm Hg ) at baseline had decreases in blood pressure ( P less than 0.05 ) with antihypertensive therapy . Thus , compared with placebo , 21 % of patients had clinical ly important increases in blood pressure during amelioration of anemia . The baseline or final levels of hemoglobin , the extent or rate of hemoglobin rise , or uncontrolled hypertension or antihypertensive drug use at baseline were not confirmed as risks . Antihypertensive drug therapy was important for blood pressure control Recombinant human erythropoietin ( r-HuEPO ) was administered in two phases to 12 patients with chronic renal insufficiency ( creatinine clearances of 0.17–0.51 ml/second [ 10–30 ml/minute ] ) and uremic anemia . In addition to the routine tests done as part of a multicenter clinical trial , our patients had serial red cell mass measurements , quantitation of bone marrow stem cells , and marrow cytogenetic analysis . During the first eight weeks ( acute phase ) , an equal number of patients was r and omized to placebo or one of three doses of r-HuEPO ( 50 , 100 or 150 unit/kg intravenously three times weekly ) . All three patients receiving 150 unit/kg responded by increasing their packed cell volume ( PCV ) to the normal range within eight weeks . There were lesser responses in PCV at the two lower doses of r-HuEPO and no response in the placebo group . The 51Cr red cell mass also increased significantly in a dose-related manner in patients receiving r-HuEPO but did not change in the placebo group . Marrow studies revealed increases in erythroid , megakaryocyte , and granulocyte-monocyte progenitor cells in those patients on r-HuEPO , but no mutagenic effects were seen . Subsequently , ten patients received open label r-HuEPO . During this maintenance phase , all ten achieved or maintained a normal PCV . Several adverse events occurred , but none were definitely linked to r-HuEPO . Recombinant human erythropoietin is an effective and potent treatment of anemia caused by renal failure BACKGROUND Hemoglobin levels below 10 g/dL lead to left ventricular ( LV ) hypertrophy , LV dilation , a lower quality of life , higher cardiac morbidity , and a higher mortality rate in end-stage renal disease . The benefits and risks of normalizing hemoglobin levels in hemodialysis patients without symptomatic cardiac disease are unknown . METHODS One hundred forty-six hemodialysis patients with either concentric LV hypertrophy or LV dilation were r and omly assigned to receive doses of epoetin alpha design ed to achieve hemoglobin levels of 10 or 13.5 g/dL. The study duration was 48 weeks . The primary outcomes were the change in LV mass index in those with concentric LV hypertrophy and the change in cavity volume index in those with LV dilation . RESULTS In patients with concentric LV hypertrophy , the changes in LV mass index were similar in the normal and low target hemoglobin groups . The changes in cavity volume index were similar in both targets in the LV dilation group . Treatment-received analysis of the concentric LV hypertrophy group showed no correlation between the change in mass index and a correlation between the change in LV volume index and mean hemoglobin level achieved ( 8 mL/m2 per 1 g/dL hemoglobin decrement , P = 0.009 ) . Mean hemoglobin levels and the changes in LV mass and cavity volume index were not correlated in patients with LV dilation . Normalization of hemoglobin led to improvements in fatigue ( P = 0.009 ) , depression ( P = 0.02 ) , and relationships ( P = 0.004 ) . CONCLUSIONS Normalization of hemoglobin does not lead to regression of established concentric LV hypertrophy or LV dilation . It may , however , prevent the development of LV dilation , and it leads to improved quality of life It is unclear whether physiologic hemoglobin targets lead to cardiac benefit in incident hemodialysis patients without symptomatic heart disease and left ventricular dilation . In this r and omized , double-blind study , lower ( 9.5 to 11.5 g/dl ) and higher ( 13.5 to 14.5 g/dl ) hemoglobin targets were generated with epoetin alpha over 24 wk and maintained for an additional 72 wk . Major eligibility criteria included recent hemodialysis initiation and absence of symptomatic cardiac disease and left ventricular dilation . The primary outcome measure was left ventricular volume index ( LVVI ) . The study enrolled 596 patients . Mean age , duration of dialysis therapy , baseline predialysis hemoglobin , and LVVI were 50.8 yr , 0.8 yr , 11.0 g/dl , and 69 ml/m2 , respectively ; 18 % had diabetic nephropathy . Mean hemoglobin levels in the higher and lower target groups were 13.3 and 10.9 g/dl , respectively , at 24 wk . Percentage changes in LVVI between baseline and last value were similar ( 7.6 % in the higher and 8.3 % in the lower target group ) as were the changes in left ventricular mass index ( 16.8 versus 14.2 % ) . For the secondary outcomes , the only between-group difference was an improved SF-36 Vitality score in the higher versus the lower target group ( 1.21 versus -2.31 ; P = 0.036 ) . Overall adverse event rates were similar in both target groups ; higher ( P < 0.05 ) rates of skeletal pain , surgery , and dizziness were seen in the lower target group , and headache and cerebrovascular events were seen in the higher target group . Normalization of hemoglobin in incident hemodialysis patients does not have a beneficial effect on cardiac structure , compared with partial correction Partial correction of anemia by erythropoietin improves hemodialysis (HD)-associated immunosuppression . It is not known whether hemoglobin normalization improves immune status further . The authors prospect ively compared the immune function of HD patients with congestive heart failure or ischemic heart disease on erythropoietin therapy r and omized to normal versus anemic blood hemoglobin concentration . HD patients were r and omized into a normal hemoglobin group ( n = 17 , target hemoglobin of 14 + /- 1 g/dl ) or an anemic hemoglobin group ( n = 18 , target hemoglobin 10 + /- 1 g/dl ) . Delayed-type hypersensitivity , CD4 and CD8 counts , anti-tetanus toxoid antibody levels , erythrocyte complement receptor 1 expression , and lymphocyte proliferative responsiveness were measured . The observation period was 1 yr , and the trial was open label . Target hemoglobin was achieved and maintained in both groups . Significantly improved cutaneous reactivity was seen in the normal hemoglobin group ( P = 0.003 ) . The prevalence of anergy decreased in the normal hemoglobin group ( from 60 to 20 % ) but increased in the anemic hemoglobin group ( from 57 to 86 % ) . The anemic hemoglobin group had higher CD8 counts compared with baseline ( P = 0.0001 ) and compared with the normal hemoglobin group ( P = 0.038 ) . Both groups had significant increases in tetanus toxoid antibody levels after vaccination but without significant differences between groups . The anemic hemoglobin group had a progressive increase in erythrocyte complement receptor 1 levels compared with baseline ( P = 0.002 ) and relative to the normal hemoglobin group ( P = 0.023 ) . There was no consistent pattern of altered proliferative responsiveness of lymphocytes . The data suggest that certain aspects of immune function , particularly delayed-type hypersensitivity , may be improved in HD patients by normalization of hemoglobin through the administration of increased doses of erythropoietin Since the earliest reports of the use of Epoetin alfa in hemodialysis patients , it has been described that Epoetin alfa may exacerbate preexisting hypertension or induce hypertension in End Stage Renal Disease ( ESRD ) patients not previously hypertensive . We undertook this study to determine if the correction of anemia in ESRD patients with cardiac disease from a hematocrit of 30 ± 3 % to 42 ± 3 % with the use of Epoetin alfa would result in increased blood pressure . This study was a sub study of the “ Normal hematocrit Study ” . Methods Thirty-one patients were r and omized into one of two arms . Patients in Group A had their hematocrit increased with the use of slowly escalating doses of Epoetin alfa to 42 ± 3 % and patients in Group B were maintained with a hematocrit of 30 ± 3 % throughout the course of the study . All patients had their blood pressure recorded with a 24 hour ambulatory BP device at study entry and at 28 weeks following r and omization when they had achieved their target hematocrit . Pre-dialysis systolic and diastolic BP was also recorded . Results The mean hematocrit increased in Group A from 29.1 ± 2.4 % to 40.8 ± 5.2 % after 30 weeks . The hematocrit in Group B remained stable at 30 ± 3 % throughout the course of the study . There was no difference in mean daytime , mean nighttime or 24 hour systolic or diastolic blood pressure between Groups A and B at either baseline or follow-up . Neither was there a difference in mean pre-dialysis systolic or diastolic BP between Groups A or B at baseline or Follow-up . Four patients in Group A and 4 patients in Group B required an increase in their antihypertensive medication during the course of the study . Conclusion It is possible to increase hematocrit to normal levels in hemodialysis with the administration of Epoetin alfa . The increase in hematocrit from 30 ± 3 % to 42 ± 3 % is not associated with increased blood pressure BACKGROUND Anemia is an important predictor of mortality and morbidity in patients with end-stage renal disease ( ESRD ) undergoing hemodialysis ( HD ) . Erythropoietin ( EPO ) is an expensive drug , which increases the cost of therapy . In addition , anemia persists in 20 - 30 % of cases despite EPO treatment . In this study , which depended on the idea that the clearance of moderate and high molecular weight erythropoiesis inhibitors leads to an improvement in terms of anemia , we aim ed to investigate the effect of high-flux dialysis on anemia and EPO requirement in patients undergoing HD . METHODS The study included 48 patients with ESRD on chronic HD treatment who could not reach the target hemoglobin ( Hb ) level , despite treatment with at least 200 IU/kg/week subcutaneous EPO . Patients were r and omized into two groups and HD was performed with polysulphone low-flux dialyzer ( Fresenius F6 HPS ) or polysulphone high-flux dialyzer ( Fresenius F60 ) for 6 months . RESULTS Although the EPO doses were significantly lower ( p<0.001 ) in the high-flux dialysis group , Hb levels showed a significant increase ( p<0.001 ) . In the low-flux dialysis group , Hb levels showed no significant increase , despite the steady increase in EPO doses . In the high-flux group , the reduction of beta2-microglobulin ( b2-MG ) and phosphorus levels during dialysis was significantly higher when compared to the low-flux group ( p<0.001 ) . During the follow-up period , while b2-MG levels decreased significantly in the high-flux group ( p<0.05 ) , there was an increase in the low-flux group ( p<0.05 ) . Kt/V(urea ) values showed no significant difference throughout the study . CONCLUSIONS Our results suggest that high-flux dialysis use is effective and this can be an alternative method in terms of controlling renal anemia and reducing the cost of therapy . These beneficial effects of high-flux dialysis are probably mediated by the improved clearance of moderate and high molecular weight toxins BACKGROUND Darbepoetin alfa is a unique molecule that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin . Due to its approximately 3-fold longer half-life and greater biological activity than recombinant human erythropoietin ( rHuEpo ) , darbepoetin alfa maintains effective haemoglobin control at extended dose intervals compared with rHuEpo . This study assessed the efficacy and safety of unit doses of darbepoetin alfa for the treatment of renal anaemia . METHODS In this multicentre , prospect i ve , open-label study , 1502 dialysis subjects maintained on stable rHuEpo treatment were switched to darbepoetin alfa at extended dose intervals by the same route of administration as previous rHuEpo therapy [ intravenous ( i.v . ) , n = 900 or subcutaneous ( s.c . ) , n = 602 ] . Subjects receiving rHuEpo two ( n = 408 , 27 % ) or three times ( n = 884 , 59 % ) a week were switched to darbepoetin alfa once a week , and those receiving rHuEpo once a week ( n = 210 , 14 % ) were switched to darbepoetin alfa once every 2 weeks . The unit doses of darbepoetin alfa ( 10 - 150 microg ) were titrated to maintain haemoglobin concentrations of 10 - 13 g/dl for 24 weeks . RESULTS Haemoglobin concentrations were maintained effectively in subjects regardless of whether they received darbepoetin alfa once a week or once every 2 weeks . The overall mean change in haemoglobin from baseline to the evaluation period ( weeks 21 - 24 ) was + 0.10 g/dl [ 95 % confidence interval ( CI ) 0.04+/- 0.17 ] . The mean haemoglobin concentration increased by 0.19 g/dl ( 95 % CI 0.11+/-0.27 ) in subjects receiving i.v . darbepoetin alfa , and was unchanged ( -0.02 g/dl ; 95 % CI -0.12 to 0.07 ) in patients treated with s.c . darbepoetin alfa . Subjects with baseline haemoglobin < 11 g/dl experienced a clinical ly relevant increase in mean haemoglobin concentration of 0.67 g/dl ( 95 % CI 0.56+/-0.77 ) from baseline to the evaluation period . The mean weekly i.v . and s.c . darbepoetin alfa dosage requirements during the evaluation period were 19.9 microg/week ( 95 % CI 19.02+/-20.87 ) and 21.6 microg/week ( 95 % CI 20.36+/- 22.94 ) , respectively . Darbepoetin alfa was well tolerated and the safety profile was consistent with previous trials with darbepoetin alfa in dialysis subjects . CONCLUSIONS Treating renal anaemia with darbepoetin alfa administered at extended dose intervals is both effective and well tolerated . Moreover , administration of darbepoetin alfa by both the i.v . and s.c . route is associated with stable haemoglobin concentrations STUDY OBJECTIVE To determine the efficacy and safety of recombinant human erythropoietin ( r-HuEPO ) in predialysis renal patients . DESIGN R and omized , double-blind , placebo-controlled trial for 8 weeks . SETTING Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital . PATIENTS Fourteen adult subjects with renal insufficiency ( mean serum creatinine , 473 mumol/L + /- 61 [ 6.2 + /- 0.8 mg/dL ] ) and anemia ( mean hematocrit , 0.27 + /- 0.01 ) . INTERVENTIONS Recombinant human erythropoietin , 50 , 100 , or 150 IU/kg body weight or placebo given intravenously three times per week . MEASUREMENTS AND MAIN RESULTS Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit ; mean hematocrit increased 41 % from 0.27 + /- 0.01 to 0.38 + /- 0.01 . At the same time , erythrocyte mass rose 43 % from 13.7 + /- 0.6 mL/kg in the baseline state to 19.6 + /- 1.0 mL/kg after treatment . Maximal oxygen consumption during exercise increased 9 % from 16.0 mL/min.kg + /- 1.8 to 17.5 mL/min.kg + /- 1.9 . CONCLUSIONS Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients We have explored the consequences of setting different thresholds and ceilings for erythropoietin dose changes in two r and omized controlled studies of renal anaemia management based on an established algorithm . STUDY 1 : A large ( n=236 ) unselected haemodialysis cohort was r and omized to monthly intervention ( increased erythropoietin ( Epo ) ) at haemoglobin ( Hb ) levels falling below either 10.5 g/dl ( group A ) or 11.5 g/dl ( group B ) and followed for 6 months . The mean Hb was 0.6 g/dl higher in the 11.5 g/dl threshold group ( 11.1 g/dl vs 11.7 g/dl ) at 6 months ( P=0.001++ ) . The Epo dose did not differ between them ( median 133 IU/kg/week , Interquartile range ( IQR ) 86 - 217 and 140 , IQR 74 - 227 respectively ) ( P = NS ( * * ) ) . STUDY 2 : A large ( n=211 ) unselected haemodialysis cohort was r and omized to a reduction in Epo dose at Hb levels above either 12.0 g/dl ( group C ) or 13.0 g/dl ( group D ) . The Hb outcome at 8 months differed between group C ( mean 11.5 g/dl , SD 1.4 ) and group D ( 12.2 , SD 2.1 ) ( P=0.03++ ) . The Epo dose did not significantly differ between groups C and D ( median 60 IU/kg/week , IQR 32 - 142 and 71 , IQR 38 - 117 respectively ) ( P = NS ( * * ) ) . Study 1 showed that an intervention threshold of 11.0 g/dl with a mean Hb outcome of 11.6 g/dl and SD 1.6 g/dl would produce the desired UK Renal Association St and ards outcome of 85 % Hb > or = 10.0 g/dl . Study 2 demonstrated that a ceiling of 12.0 g/dl narrowed the range of Hb values ( P:<0.001 # # ) , achieving a SD of 1.37 g/dl , and reduced the number of patients with a Hb > 13.0 g/dl from 25 to 12 % . This narrowing of the distribution has cost implication s for reaching minimum st and ards in a haemodialysis population . Formal use of threshold and ceiling values for intervention within an anaemia management system enabled the haemodialysis population outcome mean and SD to be literally prescribed The limitation to exercise capacity in hemodialysis patients has been attributed to anemia . We report the effects of normalization of hematocrit levels by using r-hu-recombinant erythropoietin and exercise training on exercise capacity and self-reported physical functioning in hemodialysis patients . Sixty-five patients were r and omized into 1 of 4 groups : usual hematocrit ( 30%-33 % ) with no exercise training ( UH ) ; usual hematocrit ( 30%-33 % ) plus exercise training ( UHX ) ; normalized hematocrit ( 40%-42 % ) with no exercise training ( NH ) ; and normalized hematocrit ( 40%-42 % ) plus exercise training ( NHX ) . Treadmill exercise testing was conducted at baseline and at 5 months after the initiation of the interventions . Analysis was performed on the data collapsed for 48 patients who met the criteria for hematocrit and exercise adherence and completed both baseline and post intervention ( 5.6 + /- 1.6 months ) testing . Significant effects of exercise were found in peak oxygen uptake measurements ( P = 0.03 ) and in self-reported physical functioning as measured by the Short Form-36 question naire ( P = 0.01 ) . There was a significant effect of hematocrit on the General Health scale on the SF-36 ( P = 0.03 ) . The changes in peak oxygen uptake with exercise training were small and levels remained lower than age-predicted values at the end of the study . These results indicate that there are other physiologic limitations to exercise capacity that are not overcome by exercise training or normalization of hematocrit . The effects of exercise training on self-reported physical functioning may be of clinical importance because these scores have been shown to be highly predictive of outcomes such as hospitalizations and mortality in hemodialysis patients This report describes the approach the National Kidney Foundation-Dialysis Outcomes Quality Initiative ( NKF-DOQI ) used to assess the strength of published evidence pertinent to individual NKF-DOQI Clinical Practice Guidelines , as well as the relationship between that approach and methods used by the US Preventive Services Task Force , the Cochrane Collaboration , and the Agency for Health Care Policy and Research to rate the quality and /or strength of evidence . We also present the results of an analysis of the strength of evidence underlying the NKF-DOQI Guidelines showing that one can not infer the quality of evidence reported in a study ( rated either on a 0-to-1 scale or categorically as excellent , very good , good , fair , or poor ) simply by knowing the type of study design used ( r and omized trial , nonr and omized trial , natural experiment , cohort study , cross-sectional study , case-control study , case report ) . Issues related to assessment of the strength of evidence underlying a practice guideline opposed to that reported in an individual study are highlighted This study suggests that both the quality of life and exercise capacity of anaemic hemodialysis patients is improved with EPO therapy . This was seen most convincingly in the dimensions of fatigue and physical symptoms . There was no difference in improvement in quality of life or exercise capacity between patients with a mean hemoglobin level of 102 g/L and those with a mean hemoglobin level of 117 g/L. There was an increase in diastolic blood pressure in the EPO-treated patients , especially those r and omized to the high EPO group Fourteen nondialyzed patients with chronic renal insufficiency ( serum creatinine 265 to 972 mumol/L [ 3.0 to 11.0 mg/dL ] ) and severe anemia ( hematocrit less than 30 % ) were r and omized to receive either recombinant human erythropoietin ( r-HuEPO ) or a placebo subcutaneously thrice weekly for 12 weeks or until reaching a hematocrit of 38 % to 40 % . Anemia was significantly ameliorated in the treated patients . No acceleration in the progression of renal failure ( 1/serum creatinine v time ) or change in serum potassium was noted for either the placebo or treated group over the 12-week period . Six of seven treated patients had a significant decrease in serum ferritin and percent transferrin saturation ( plasma iron/total iron-binding capacity ) . This result ed in functional iron deficiency and the requirement for iron supplementation . The average systolic and diastolic blood pressure did not differ significantly between the two groups of patients during the study . Quality of life was improved in all r-HuEPO-treated patients but not in those in the placebo group . This study demonstrates the safety and efficacy of r-HuEPO in the correction of anemia in predialysis patients without adverse effects on renal function over a 12-week period . Improved patient well-being as a result of the correction of anemia result ed in one patient refusing appropriate initiation of dialysis therapy Aim : This multicenter , open-label study determined safety and efficacy of once-every-other-week administration of darbepoetin alfa for anemia of chronic kidney disease in erythropoietin-naive patients not on dialysis . Methods : Participants with hemoglobin levels < 11.0 g/dl at baseline were administered darbepoetin alfa at an initial dosage of 0.75 µg/kg once every other week . The dose was titrated to achieve and maintain a hemoglobin response , defined as a hemoglobin range of between 11.0 and 13.0 g/dl for up to 24 weeks . The primary end point was the dose of darbepoetin alfa at initial hemoglobin response . Results : Six hundred and eight patients were enrolled , and 463 completed the study ; 95 % ( 95 % confidence interval : 0.93 , 0.97 ) of the patients who completed treatment achieved a hemoglobin response . The mean darbepoetin alfa dose at the time of response was 63.5 ± ( SD ) 16.9 µg , and the mean time to hemoglobin response was 5.7 ± ( SD ) 4.5 weeks . Oral iron therapy was administered to 60 % and intravenous iron to 16 % of the participants . Darbepoetin alfa was well tolerated , and adverse events were consistent with those expected in patients with chronic kidney disease . Conclusion : Darbepoetin alfa administered once every other week is effective and safe for achieving and maintaining target hemoglobin levels in anemic patients with chronic kidney disease BACKGROUND Patients on chronic hemodialysis often suffer from severe anemia , the outcome of iron deficiency and inadequate response to erythropoietin . Antihypertensive treatment with captopril worsens anemia , erythropoietin production and iron balance in hemodialysis patients . We investigated the possibility that iron chelation by captopril in the blood may result in elimination of iron-captopril complexes during hemodialysis , thus minimizing the effect of both medications . METHODS Twelve hypertensive hemodialysis patients ( group 1 ) were treated with 12.5 mg/day captopril , while their 12 counterparts received 1.25 mg/day ramipril . Following two weeks of treatment and two weeks of " washout " , captopril in group 1 was substituted with ramipril and ramipril in group 2 was replaced by captopril for an additional two week period . Blood and dialysate sample s were procured at the beginning and the end of the dialysis , for iron , aluminum , transferin , ferritin , hemoglobin ( Hb ) and hematocrit ( Htc ) determination . RESULTS Iron , ferritin , transferin , Hb and Htc were decreased in the captopril-treated group 1 . They similarly decreased in group 2 following replacement of ramipril by captopril for an additional period of two weeks . Significant amounts of iron were detected in dialysates of captopril , but not ramipril-treated patients . At the end of the dialysis , iron content was further increased in dialysates of the captopril-treated groups . CONCLUSIONS 1 ) Captopril-chelated iron is eliminated in dialysis fluid during the dialysis session , apparently contributing to captopril-related anemia in patients on chronic hemodialysis . 2 ) Antihypertensive treatment with angiotensin converting enzyme ( ACE ) inhibitors other than captopril might prove advantageous for this patient category BACKGROUND Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein that functions by the same mechanism as recombinant human erythropoietin ( rHuEPO ) , but has a three-fold longer serum half-life . Reduction in the frequency of darbepoetin alfa administration would be beneficial to patients with renal disease and their healthcare providers . This study evaluated the effect of extending the darbepoetin alfa dosing interval to once monthly in patients with chronic kidney disease ( CKD ) not receiving dialysis . METHODS This study was a multicenter , open-label study of 97 patients with CKD not on dialysis . Patients receiving stable subcutaneous doses of darbepoetin alfa once every two weeks were converted to darbepoetin alfa once monthly for 29 weeks . The proportion of patients who successfully maintained hemoglobin concentrations between 10.0 and 12.0 g/dl and the mean darbepoetin alfa dose were evaluated . Safety measurements ( e.g. adverse events , laboratory parameters , blood pressure ) and seroreactivity were assessed . RESULTS Hemoglobin concentration was maintained within the target range in 79 % ( 95 % confidence interval ( CI ) = 71 % to 87 % ) of all patients receiving darbepoetin alfa and in 85 % ( 95 % Cl = 78 % - 93 % ) of patients who completed the study period . The mean + /- st and ard deviation monthly darbepoetin alfa dose was similar between baseline ( 88.7 + /- 49.9 microg ) and the evaluation period ( 86.6 + /- 78.8 microg ) . The safety profile for monthly darbepoetin alfa administration was comparable with that previously observed with more-frequent administration . CONCLUSION Patients with CKD who are clinical ly stable on darbepoetin alfa administered once every two weeks can be safely and effectively converted to darbepoetin alfa administered once monthly BACKGROUND Hypertension is a recognized complication of partial correction of anemia with recombinant human erythropoietin ( epoetin ) in hemodialysis patients . We used interdialytic ambulatory blood pressure ( ABP ) monitoring to study the effects of partially corrected anemia versus normal hematocrit ( hct ) on BP in hemodialysis patients . METHODS Repeated interdialytic ABP monitoring was performed for up to one year in 28 chronic hemodialysis patients with cardiac disease who were r and omized to achieve and maintain normal hct levels ( 42 + /- 3 % , group A ) or anemic hct levels ( 30 + /- 3 % , group B ) with epoetin . Routine BP measurements obtained at dialysis treatments were also evaluated . RESULTS Mean hct levels were 30.7 + /- 0.7 % in group A and 30.6 + /- 0.7 % in group B at baseline , then 39.3 + /- 1.2 % ( group A ) and 33.5 + /- 0.6 % ( group B ) at four months , and 42.0 + /- 1.1 % ( group A ) and 30.4 + /- 1.0 % ( group B ) at 12 months . Baseline ABP and routine dialysis unit BP levels were not different between the groups . At 2 , 4 , 8 , and 12 months of follow-up , there were no statistically significant differences in any BP parameters between groups or increases in any BP parameters in either group A or group B patients compared with baseline . At 12 months , the mean nighttime diastolic BP ( DBP ) in group A patients was slightly but significantly lower than the mean daytime DBP ( daytime DBP 76.6 + /- 1.9 mm Hg vs. nighttime DBP 72.9 + /- 2.1 mm Hg , P < 0.05 ) . The mean daytime and nighttime BPs were not different from each other at two , four , and eight months in group A or at any time in group B , and in both groups , most patients had little diurnal change in BP . CONCLUSION Correction of hct to normal with epoetin in chronic hemodialysis patients with cardiac disease did not cause increased BP as assessed by interdialytic ABP monitoring or by the measurement of routine predialysis and postdialysis BP . There was little diurnal change in systolic or diastolic BP at baseline or after correction of anemia to normal levels , and although mean nighttime DBP was lower than mean daytime DBP at 12 months in group A , the maintenance of normal hct levels did not affect the abnormal diurnal BP pattern seen at moderately anemic hct levels in most patients Therapy with human recombinant erythropoietin ( EPO ) has been accepted as effective for renal anemia in dialysis patients . However , studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction . In humans , however , the effect of EPO on residual renal function is a matter of controversy . We , therefore , investigated whether the long-term administration of EPO to predialysis patients influences residual renal function . Anemic patients at the predialysis stage with a serum creatinine ( Cr ) concentration ranging from 2 to 4 ( average 2.9 ) mg/dl and a hematocrit ( Ht ) of less than 30 % were r and omly assigned to two groups which consisted of anemic patients not treated with EPO ( group I , untreated anemic controls , n = 31 ) and anemic patients treated with EPO ( group II , treated anemics , n = 42 ) . Patients with nonsevere or moderate anemia ( Ht > 30 % ) with a Cr ranging from 2 to 4 ( average 2.6 ) mg/dl were also recruited as nonanemic controls ( group III , untreated nonanemic controls , n = 35 ) . Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors . All patients were kept strictly on a low-protein ( 0.6 g/kg/day ) and a low-salt ( 7 g/day ) diet . The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups . The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time . Ht rose significantly from 27.0+/-2.3 to 32.1+/-3.2 % in group II ( n = 42 , p < 0.001 ) with a rate of increase of 0.4+/-0.06%/week . However , it declined from 27.9+/-1.8 to 25.3+/-1.9 % in group I ( n = 31 , p < 0.001 ) and from 35.9+/-3.5 to 32.2+/-3.9 % in group III ( n = 35 , p < 0.001 ) . Cr doubled in 26 patients ( 84 % ) in group I as compared with 22 ( 52 % ) in group II and 21 ( 60 % ) in group III . The cumulative renal survival rates in groups II and III were significantly better than that in group I : p = 0.0003 ( group I vs. group II ) and p = 0.0024 ( group I vs. group III ) . However , there was no difference in the renal survival rate between groups II and III ( p = 0.3111 ) . The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group . The present study suggests that anemia , per se , is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure , especially in nondiabetic patients , provided that blood pressure control , rate of increase in Ht , and dietary protein restriction are appropriate Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients . We examined the effects of erythropoietin ( EPO ) treatment in 12 predialytic uremic patients ( EPO group : mean age 46 + /- 12 years ; 6 men , 6 women ) with a mean glomerular filtration rate ( GFR ) of 10 + /- 4 ml/min x 1.73 m2 . These patients were compared to a control group of 8 patients ( 5 men , 3 women ) . The observation period was 3 months . The EPO group received 300 U/kg body weight i.v . once a week . The EPO group increased their total hemoglobin ( THb ) from 323 + /- 89 to 466 + /- 128 g ( p less than 0.001 ) and their hemoglobin concentration from 86 + /- 8 to 117 + /- 11 milligrams ( p less than 0.001 ) . Their exercise capacity , measured by a st and ardized exercise test on a bicycle ergometer , increased from 128 + /- 45 to 147 + /- 57 W ( p less than 0.01 ) . The control group did not change their THb ( 349 + /- 124 and 357 + /- 131 g ) , hemoglobin ( 93 + /- 8 and 94 + /- 10 milligrams ) or exercise capacity ( 98 + /- 49 and 101 + /- 50 W ) during the observation period . There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group ( r = 0.81 , p less than 0.005 ) . The GFR was unchanged in both groups ( EPO group : 10 + /- 4 and 10 + /- 6 ml/min x 1.73 m2 ; control group : 8 + /- 3 and 8 + /- 3 ml/min x 1.73 m2 ) . ( ABSTRACT TRUNCATED AT 250 WORDS |
2,697 | 23,612,509 | Conclusion : Better characterisation in behaviour-change interventions will reduce potential confounding and enhance generalisability of such studies | Background / objective : To investigate the extent of baseline psychosocial characterisation of subjects in published dietary r and omised controlled trials ( RCTs ) for weight loss . | OBJECTIVE : To reveal whether baseline body mass index ( BMI ) , and psychobehavioral and nutritional markers were significant predictors of the change in BMI observed after 4 and 12 months in obese women enrolled in a weight reduction program , including low-energy diet , increased physical activity , cognitive behavior therapy and sibutramine . The impact of changes in psychobehavioral and nutritional markers observed after 4 and 12 months of treatment on BMI changes was also investigated . DESIGN : During a double-blind placebo-controlled 4-month period , subjects received either sibutramine ( 10 mg/day ) or placebo . Then , an open phase with sibutramine administered to all patients continued until month 12.SUBJECTS : In total , 80 obese women ( age : 43.9±10.6 y , BMI : 36.7±4.8 kg/m2 ) . MEASUREMENTS : The dependent variable was change in BMI while baseline BMI , mode of treatment , the Beck depression score , the three items ( dietary restraint , disinhibition and perceived hunger ) of the Eating Inventory ( EI ) , energy and macronutrient intakes were independent variables . At 1-week dietary records were analyzed using a computer software for assessing energy and macronutrient intake . RESULTS : Multiple regression analysis revealed that the BMI loss at month 4 was significantly influenced by mode of treatment and initial BMI , whereas a borderline negative relationship was observed with the baseline restraint score . Baseline BMI , depression score , restraint score and total energy intake predicted weight loss at month 12 . These predictive variables accounted for 43.8 % of the variance in BMI loss at 12 months . When relationships between the BMI loss and changes in all included psychobehavioral and nutritional parameters were considered after 12 months of treatment , a drop in the disinhibition score of the EI appeared the only significant factor affecting the BMI decrease . CONCLUSIONS : Our results suggest that psychobehavioral and nutritional characteristics can be used as predictors of weight loss in response to a comprehensive weight management program including pharmacological treatment with sibutramine BACKGROUND Cognitive behavioral therapy ( CBT ) teaches behavioral and cognitive strategies that focus on achieving and maintaining lifestyle changes . OBJECTIVE We examined the effectiveness of a CBT program ( CHOOSE HEALTH ) for improving body composition , diet , and physical activity in overweight and obese adolescents . DESIGN Adolescents [ 16 male , 31 female ; aged 14.5 + /- 1.6 y ; body mass index ( BMI ; in kg/m(2 ) ) 30.9 + /- 4.2 ] were block-matched into 2 groups by age , sex , Tanner stage , BMI , and hip and waist circumferences and were r and omly assigned to CBT or no treatment ( control ) . CBT consisted of 10 weekly sessions , followed by 5 fortnightly telephone sessions . RESULTS Compared with the control , over 20 wk , CBT improved ( significant group x time interactions ) BMI ( CBT , -1.3 + /- 0.4 ; control , 0.3 + /- 0.3 ; P = 0.007 ) , weight ( CBT , -1.9 + /- 1.0 kg ; control , 3.8 + /- 0.9 kg ; P = 0.001 ) , body fat ( CBT , -1.5 + /- 0.9 kg ; control , 2.3 + /- 1.0 kg ; P = 0.001 ) , and abdominal fat ( CBT , -124.0 + /- 46.9 g ; control , 50.1 + /- 53.5 g ; P = 0.008 ) . CBT showed a greater reduction in intake of sugared soft drinks as a percentage of total energy ( CBT , -4.0 + /- 0.9 % ; control , -0.3 + /- 0.9 % ; P = 0.005 for group x time interaction ) , which was related to reductions in weight ( r = 0.48 , P = 0.04 ) , BMI ( r = 0.53 , P = 0.02 ) , and waist circumference ( r = 0.54 , P = 0.02 ) . Physical activity did not change significantly . CONCLUSIONS A 10-wk CBT program followed by 10 wk of fortnightly phone contact improved body composition in overweight and obese adolescents . Changes in soft drink consumption may have contributed to this benefit BACKGROUND Obesity is associated with many chronic diseases , and weight loss can reduce the risk of developing these diseases . Obesity is highly prevalent among Black women , but weight loss treatment for black women has been understudied until recently . The Obesity Reduction black Intervention Trial ( ORBIT ) is a r and omized controlled trial design ed to assess the efficacy of a culturally proficient weight loss and weight loss maintenance program for black women . This paper describes the design of the trial , the intervention , and baseline characteristics of the participants . METHODS Two hundred thirteen obese black women aged 30 - 65 years were r and omized to the intervention group or a general health control group . The intervention consists of a 6-month weight loss program followed by a 1-year maintenance program . Weight , dietary intake , and energy expenditure are measured at baseline , 6 months , and 18 months . RESULTS More than 40 % of participants had a baseline body mass index ( BMI ) > 40 kg/m(2 ) ( class III obesity ) . Intake of fat and saturated fat was higher and consumption of fruit , vegetables , and fiber was lower than currently recommended guidelines . Self-reported moderate to vigorous physical activity was high ( median 85 min/day ) . However , objective ly measured physical activity among a subgroup of participants was lower ( median 15 min/day ) . CONCLUSIONS Weight loss among obese black women has received inadequate attention in relation to the magnitude of the problem . Factors that contribute to successful weight loss and more importantly , weight loss maintenance need to be identified OBJECTIVE A transition G to A at codon 54 of FABP2 was associated with high insulin resistance and different dietary response . The aim of our study was to investigate the influence of this polymorphism on weight loss and metabolic changes secondary to two hypocaloric diets . SUBJECTS AND METHODS A sample of 204 obesity patients was analyzed . Before and after 2 months of hypocaloric diet , a nutritional evaluation was performed . Patients were r and omly allocated to diet I ( low-fat diet ) or II ( low carbohydrate diet ) . RESULTS With diet Type I and in the wild group ( Ala54/Ala54 ) , BMI , weight , fat mass , waist circumference , waist to hip ratio , systolic and diastolic blood pressures , total cholesterol , triglyceride and insulin levels decreased . In the mutant group ( Ala54/Thr54 and Thr54/Thr54 ) , BMI , weight , waist circumference and fat mass decreased . In the wild group with diet Type II , the same parameters that group I decreased and glucose levels , too . In the mutant group , BMI , weight , waist circumference and fat mass decreased . Only leptin levels have a significant decrease in the wild group with both diets ( diet I : 30.7 % ; p<0.05 and diet II : 15.85 % ; p<0.05 ) . CONCLUSION Similar weight loss is associated with different changes , depending on the FABP genotype with both diets . Weight loss is associated with a more deep decrease in serum leptin concentration with low-fat diet Background We investigated whether macronutrient composition of energy-restricted diets influences the efficacy of a telemedically guided weight loss program . Methods Two hundred overweight subjects were r and omly assigned to a conventional low-fat diet and a low-carbohydrate diet group ( target carbohydrate content : > 55 % energy and < 40 % energy , respectively ) . Both groups attended a weekly nutrition education program and dietary counselling by telephone , and had to transfer actual body weight data to our clinic weekly with added Bluetooth ® technology by mobile phone . Various fatness and fat distribution parameters , energy and macronutrient intake , and various biochemical risk markers were measured at baseline and after 6 , and 12 months . Results In both groups , energy intake decreased by 400 kcal/d compared to baseline values within the first 6 months and slightly increased again within the second 6 months . Macronutrient composition differed significantly between the groups from the beginning to month 12 . At study termination , weight loss was 5.8 kg ( SD : 6.1 kg ) in the low-carbohydrate group and 4.3 kg ( SD : 5.1 kg ) in the low-fat group ( p = 0.065 ) . In the low-carbohydrate group , triglyceride and HDL-cholesterol levels were lower at month 6 and waist circumference and systolic blood pressure were lower at month 12 compared with the low-fat group ( P = 0.005–0.037 ) . Other risk markers improved to a similar extent in both groups . Conclusion Despite favourable effects of both diets on weight loss , the carbohydrate-reduced diet was more beneficial with respect to cardiovascular risk factors compared to the fat-reduced diet . Nevertheless , compliance with a weight loss program appears to be even a more important factor for success in prevention and treatment of obesity than the composition of the diet . Trial registration Clinical trials.gov as Overweight or obesity is an established negative prognostic factor in breast cancer . Co-morbidities associated with obesity , including cardiovascular disease ( CVD ) , may negatively impact quality of life and survival in this population . Our purpose was to determine the effect of a cognitive behavioral therapy ( CBT ) intervention for weight loss through exercise and diet modification on risk factors for recurrence of breast cancer , and risks for CVD associated with obesity . Eighty-five overweight or obese breast cancer survivors were r and omly assigned to a once weekly , 16-week intervention or wait-list control group . The intervention incorporated elements of CBT for obesity , addressing a reduction in energy intake , as well exercise , with a goal of an average of 1 h a day of moderate to vigorous activity . Body weight , total and regional body fat ( by dual energy X-ray absorptiometry ) , waist and hip circumference , and blood lipids were assessed at baseline and following 16 weeks of intervention . Results : Seventy six women ( 89.4 % ) completed the intervention . Independent t-test to evaluate group differences at 16 weeks showed significant differences in weight , body mass index , percent fat , trunk fat , leg fat , as well as waist and hip circumference between intervention and control groups ( P ≤ 0.05 ) . Furthermore , levels of triglycerides and total cholesterol/high density lipoprotein cholesterol levels were also significantly reduced following the intervention . These results indicate that 16 weeks of a CBT program for weight management may reduce obesity and CVD risk in overweight breast cancer survivors BACKGROUND Although the DASH ( Dietary Approaches to Stop Hypertension ) diet has been shown to lower blood pressure ( BP ) in short-term feeding studies , it has not been shown to lower BP among free-living individuals , nor has it been shown to alter cardiovascular biomarkers of risk . OBJECTIVE To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension ( systolic BP , 130 - 159 mm Hg ; or diastolic BP , 85 - 99 mm Hg ) . DESIGN AND SETTING R and omized , controlled trial in a tertiary care medical center with assessment s at baseline and 4 months . Enrollment began October 29 , 2003 , and ended July 28 , 2008 . PARTICIPANTS Overweight or obese , unmedicated out patients with high BP ( N = 144 ) . INTERVENTIONS Usual diet controls , DASH diet alone , and DASH diet plus weight management . OUTCOME MEASURES The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring . Secondary outcomes included pulse wave velocity , flow-mediated dilation of the brachial artery , baroreflex sensitivity , and left ventricular mass . RESULTS Clinic-measured BP was reduced by 16.1/9.9 mm Hg ( DASH plus weight management ) ; 11.2/7.5 mm ( DASH alone ) ; and 3.4/3.8 mm ( usual diet controls ) ( P < .001 ) . A similar pattern was observed for ambulatory BP ( P < .05 ) . Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity , baroreflex sensitivity , and left ventricular mass ( all P < .05 ) . CONCLUSION For overweight or obese persons with above-normal BP , the addition of exercise and weight loss to the DASH diet result ed in even larger BP reductions , greater improvements in vascular and autonomic function , and reduced left ventricular mass . CLINICAL TRIAL REGISTRATION clinical trials.gov Identifier : NCT00571844 Objective : To investigate the effect of dietary restraint with or without exercise during weight maintenance after energy restriction . Subjects and methods : In total , 40 obese male subjects ( mean BMI 32.3 kg/m2 ; mean age 39 y ) were recruited and r and omly divided into a diet ( D ; n=20 ) and a diet plus exercise ( DE ; n=20 ) group . Both groups participated in an energy restriction programme ( ER ) , which was followed by a weight maintenance phase ( WM ) . Subjects in the DE also participated in an exercise programme . Body mass ( BM ) and the scores on the three factor eating question naire ( TFEQ ) were measured before and after the ER and after WM . Results : No significant differences between both groups were found . All data taken together showed that BM loss during ER was explained by initial BM ( r 2=0.3 , P<0.0005 ) and inversely by initial cognitive restraint ( F1 ) ( r 2=0.4 , P<0.0005 ) in a stepwise regression . BM regain during WM was explained by BM loss ( r 2=0.5 , P<0.001 ) and by increase in F1 during ER ( r 2=0.6 , P<0.001 ) , while the exercise intervention did not contribute further to the explained variation . Subjects with a relatively high diet frequency prior to the study had relatively significant higher initial F1 scores ( P<0.05 ) . During ER , increase in F1 was associated with decrease in general hunger ( F3 ) . Conclusion : Successful BM loss was associated with higher initial BM and lower initial F1 . Successful WM was explained by BM loss and increase in F1 during ER , irrespective of possible exercise training effects . Successful WM was reduced when F1 scores reach their limit , due to diet-frequency Background Psychological and behavioral characteristics that predict success or failure with weight-loss treatments are poorly understood . Purpose The purpose of this study was to assess whether social cognitive theory-based factors discriminate between women who are successful and unsuccessful at weight loss . Method Obese women ( BMI = 30 to 45 kg/m2 ) who participated in a treatment of behavioral exercise support counseling and nutrition education were divided into quartiles based on percentage of body weight lost over 6 months . Factors based on social cognitive theory , both at baseline and change over 6 months , and exercise attendance were used to discriminate between the successful ( highest quartile , Mchange in body weight = −9.3 % ; n = 40 ) and unsuccessful ( lowest quartile , Mchange in body weight = 1.9 % ; n = 37 ) groups . Results Stepwise discriminant analyses indicated that body satisfaction and tension ( anxiety ) scores at baseline , and changes over 6 months in self-regulatory efficacy and body satisfaction , made significant contributions to predicting group membership ( 64 % and 69 % of cases were correctly classified , respectively ) . Attendance percentage of exercise sessions was significantly greater for the successful weight-loss group , and when added as a predictor , changes in self-regulatory efficacy and attendance made a significant contribution to predicting group membership ( 81 % of cases were correctly classified ) . Conclusion Further research may enable psychological determinants to better guide weight loss theory and treatments Background : Data are limited as to whether participants in diet trials truly adhere to their assigned diet and the factors that affect their adherence . Methods : We evaluated success and adherence in a two-year dietary intervention r and omized controlled trial ( DIRECT ) in which 322 moderately obese participants ( mean age 52 yrs , mean body-mass-index ( BMI ) 31 kg/m2 , 86 % men ) were r and omized to one of three groups : low-fat , Mediterranean , or low-carbohydrate diets . Results : Overall compliance at month-24 was 85 % , with 90 % in low-fat , 85 % in Mediterranean , and 78 % in low-carbohydrate diet ( p = .042 between groups ) . Attrition was higher in women ( 29 % vs. 14 % men , p = .001 ) and current smokers ( 25 % vs. 14 % among maintainers , p = 0.04 ) . In a multivariate model , independent predictors of dropping-out were : higher baseline BMI ( OR = 1.11 ; CI : 1.03–1.21 ) and less weight loss at month-6 ( OR = 1.20 ; CI : 1.1–1.3 ) . In a multivariate model , greater weight loss achieved at month-6 was the main predictor associated with success in weight loss ( > 5 % ) over 2 years ( OR = 1.5 ; CI : 1.35–1.67 ) . Self-reported complete adherence score to diet was greater on low-carbohydrate diet ( p < .05 compared to low-fat ) until month-6 , but dropped overall from 81 % at month-1 to 57 % at month-24 . Holidays were a trigger to a significant decrease in adherence followed by a partial rebound . Changes in diet composition from month-1 to month-12 were more pronounced in the multi-stage low-carbohydrate diet-group ( p < .05 ) . Generally , the most irresistible restricted food items were cookies ( 45 % of dieters ) and fruits ( 30 % ) . Among the physically active ( n = 107 ) , 44 % reported a tendency to eat less after exercising compared to 10 % who tended to eat more . Conclusion : Initial 6-month reduction in weight is the main predictor of both long-term retention and success in weight loss . Special attention is needed for women , current smokers , and during holidays . Physical activity is associated with subsequent reduction in energy intake OBJECTIVE The treatment of obesity is universally disappointing ; although usually some weight loss is reported directly after treatment , eventual relapse to , or even above , former body weight is common . In this study it is tested whether the addition of cognitive therapy to a st and ard dietetic treatment for obesity might prevent relapse . It is argued that the addition of cognitive therapy might not only be effective in reducing weight and related concerns , depressed mood , and low self-esteem , but also has an enduring effect that lasts beyond the end of treatment . METHODS Non-eating-disordered overweight and obese participants in a community health center ( N=204 ) were r and omly assigned to a group dietetic treatment+cognitive therapy or a group dietetic treatment+physical exercise . RESULTS Both treatments were quite successful and led to significant decreases in BMI , specific eating psychopathology ( binge eating , weight- , shape- , and eating concerns ) and general psychopathology ( depression , low self-esteem ) . In the long run , however , the cognitive dietetic treatment was significantly better than the exercise dietetic treatment ; participants in the cognitive dietetic treatment maintained all their weight loss , whereas participants in the physical exercise dietetic treatment regained part ( 25 % ) of their lost weight . CONCLUSION Cognitive therapy had enduring effects that lasted beyond the end of treatment . This potential prophylactic effect of cognitive therapy is promising ; it might be a new strategy to combat the global epidemic of obesity Background : Dietary adherence has been implicated as an important factor in the success of dieting strategies ; however , studies assessing and investigating its association with weight loss success are scarce . Objective : We aim ed to document the level of dietary adherence using measured diet data and to examine its association with weight loss success . Design : Secondary analysis was performed using data from 181 free-living overweight/obese women ( mean±s.d . age=43±5 years , body mass index=31±4 kg m−2 ) participating in a 1-year r and omized clinical trial ( the A TO Z study ) comparing popular weight loss diets ( Atkins , Zone and Ornish ) . Participants ' dietary adherence was assessed as the difference between their respective assigned diet 's recommended macronutrient goals and their self-reported intake . Association between dietary adherence and 12-month weight change was computed using Spearman 's correlations . Differences in baseline characteristics and macronutrient intake between the most and least adherent tertiles for diet groups were compared using t-tests . Results : Within each diet group , adherence score was significantly correlated with 12-month weight change ( Atkins , rs=0.42 , P=0.0003 ; Zone , rs=0.34 , P=0.009 and Ornish , rs=0.38 , P=0.004 ) . Twelve-month weight change in the most vs least adherent tertiles , respectively , was −8.3±5.6 vs −1.9±5.8 kg , P=0.0006 ( Atkins ) ; −3.7±6.3 vs −0.4±6.8 kg , P=0.12 ( Zone ) and −6.5±6.8 vs −1.7±7.9 kg , P=0.06 ( Ornish ) . Conclusions : Regardless of assigned diet groups , 12-month weight change was greater in the most adherent compared to the least adherent tertiles . These results suggest that strategies to increase adherence may deserve more emphasis than the specific macronutrient composition of the weight loss diet itself in supporting successful weight loss To evaluate the efficacy of adding cognitive behavioural treatment ( CBT ) to either a low-carbohydrate ( LC ) diet or a low-fat ( LF ) diet in the treatment of weight loss of obese women , a r and omised clinical intervention study was performed . A total of 105 healthy non-pregnant obese women ( average age and BMI of 45.4 ( sd 10.4 ) years and 36 ( sd 4.3 ) kg/m2 ) were r and omly allocated to the CBT or control ( C ) groups ; within each group , women were r and omly selected to receive either the LC or LF diet during 6 months . The pre-planned primary trial end-point was the weight loss . Differences between the groups were assessed using one-way ANOVA . There were three women ( 2.8 % ) who dropped out , all of them in the CBT group . No differences in the anthropometric and laboratory characteristics at baseline were noted between women in the CBT ( n 52 ) and control groups ( n 50 ) . Intention-to-treat analysis showed that weight loss in the CBT-LC ( 90 ( sd 12.3 ) to 82.1 ( sd 12.1 ) kg ) and C-LC ( 89.4 ( sd 10.0 ) to 85.8 ( sd 9.8 ) kg ) groups reached 8.7 and 4.0 % , respectively ( P < 0.0001 ) , and in the CBT-LF ( 87.9 ( sd 11.4 ) to 79.4 ( sd 11.8 ) kg ) and C-LF ( 88.8 ( sd 14.5 ) to 85.3 ( sd 14.3 ) kg ) groups it was 9.7 and 3.9 % , respectively ( P < 0.05 ) . Weight loss was higher in the CBT-LF group than in the CBT-LC groups ( P = 0.049 ) . The present results showed that adding CBT to either the LF or LC diet produced significantly greater short-term weight loss in obese women compared with diet alone . These finding support the efficacy of CBT in breaking previous dietary patterns and in developing healthier attitudes that reinforce a healthier lifestyle OBJECTIVE To study the effects of a 12-week weight loss strategy involving increased physical activity , self-selected hypocaloric diet , and group support on psychological well-being , quality of life , and health practice s in moderately obese women . METHODS Eighty women aged 20 - 49 years weighing between 20 - 50 % above 1983 Metropolitan Life Insurance Tables were r and omly assigned to a weight loss intervention ( 6279 kJ/week of physical activity , 33,258 - 41,462 kJ/week diet and weekly meetings ) or served as controls . Subjects were tested pre and post 12-weeks . RESULTS The intervention group lost significant ( p<0.001 ) body weight ( kg ) and body fat ( % ) compared to controls ( -6.07+/-4.01 kg vs. 1.31+/-1.28 kg ; 36.8%-32.5 % vs. 36.2%-36.0 % ) . Intervention subjects vs. controls achieved significant improvements ( p<0.001 ) in body cathexis ( X Change 18.6+/-16.7 vs. 0.7+/-8.6 ) and estimation of ability to achieve physical fitness ( X Change 8.1+/-7.1 vs. 0.9+/-5.9 ) . Various quality of life indices also improved ( p<0.01 ) in the intervention group compared to controls ( physical function : X Change 13.5.2+/-16.7 vs. 1.4+/-9.5 ; vitality : X change 21.7+/-17.9 vs. 2.9+/-20.8 ; mental health : X change 10.4+/-16.0 vs. 2.3+/-10.1 ) . Similarly , physical activity levels also improved significantly ( p<0.0001 ) in the intervention group ( 4.4+/-2.3 vs. 0.6+/-1.3 ; on NASA 0 - 7 scale ) . CONCLUSIONS Practical weight loss practice s such as increased activity , self-selected hypocaloric diet , and group support are effective for weight loss and yield significant health and psychological benefits in moderately obese females BACKGROUND AND AIMS In a cross-European study it was recently shown that consumption of cod increases weight loss in men and also has other positive health effects . The aim of this study was to investigate whether cod consumption increases weight loss and improves cardiovascular risk factors in a dose dependent manner during an 8-week energy restriction diet in young overweight and obese healthy adults . METHODS AND RESULTS In this dietary intervention 126 subjects ( 20 - 40 years , BMI 27.5 - 32.5 kg/m(2 ) ) comprised the group given energy-restricted diets ( -30 % ) ; they were prescribed an identical macronutrient composition but different amounts of cod : the control group were given no seafood ; group 1 were given 150 g cod 3 times a week ; and group 2 were given 150 g cod 5 times a week . Anthropometric measurements and cardiovascular risk factors were assessed at baseline and endpoint . Body weight decreased after 8-weeks ( 5.0+/-2.9 kg , P<0.001 ) , also waist circumference ( 5.0+/-3.2 cm , P<0.001 ) , BMI ( 1.65+/-0.95 kg , P<0.001 ) , systolic ( 3.4+/-8.9 mmHg , P=0.001 ) and diastolic blood pressure ( 2.4+/-6.9 mmHg , P<0.001 ) , triglycerides ( 1.26+/-0.567 mmol/L , P=0.030 ) and insulin ( 1.21+/-5.31 mU/L , P=0.025 ) . The prevalence of the metabolic syndrome dropped from 29 to 21 % . According to linear models weight loss was 1.7 kg greater among subjects consuming 150 g 5x/week compared to the control group ( P<0.015 ) . The trend analysis supported a dose-response relationship between cod consumption and weight loss ( P<0.001 ) , but changes of other measured cardiovascular risk factors were similar between the groups . CONCLUSION A dose-response relationship between cod consumption and weight loss during an 8-week energy restriction diet is found and 5 x 150 g cod/week results in 1.7 kg greater weight loss in young overweight or obese adults than a isocaloric diet without seafood Objective : To investigate the impact of current mental disorders on weight loss with special consideration of depressive and /or anxiety disorders as well as binge eating behavior in obese individuals undergoing different weight loss treatments . Methods : Three different sample s of obese individuals were investigated in a prospect i ve , longitudinal study : participants in a conventional weight loss treatment program ( CONV TREAT ; n = 250 ) , obesity surgery patients ( OBES SURG ; n = 153 ) , and obese control individuals ( OC ; n = 128 ) . Current mental disorders and BMI were assessed at baseline and at 4-year follow-up . Results : OBES SURG patients with a depressive and /or anxiety disorder lost significantly less weight compared with those without a comorbid mental diagnosis . This result was not detected for CONV TREAT participants . A trend to gain weight was seen in OC participants with a depressive and /or anxiety disorder , whereas OC participants without current mental disorders at baseline lost some weight . Binge eating behavior at baseline did not predict weight loss at 4-year followup . Conclusions : These results underline the importance of addressing current depressive and anxiety disorders in obese patients , especially when such patients are undergoing obesity surgery Background : The effectiveness of high-protein ( HP ) diets in reducing body weight and adiposity and potentially improving clinical outcomes in heart failure ( HF ) is not known . Objective : This feasibility study was conducted to evaluate the impact of 3 dietary interventions on body weight and adiposity , functional status , lipid profiles , glycemic control , and quality of life ( QOL ) in overweight and obese patients with HF and type 2 diabetes mellitus . Design : Fourteen patients with HF with a body mass index greater than 27 kg/m2 were r and omized to an HP diet , a st and ard protein diet , or a conventional diet . Data were obtained at baseline and 12 weeks . Results : There were no significant differences in age ( 59 ± 10 years ) , sex ( 78 % male ) , New York Heart Association class ( 43 % class II , 57 % class III ) , and HF etiology or left ventricular ejection fraction ( 26 ± 7 ) between the groups at baseline . Patients on the HP diet demonstrated significantly greater reductions in weight ( P = .005 ) , percent body fat ( P = .036 ) , total cholesterol ( P = .016 ) , triglyceride concentrations ( P = .034 ) , and low-density lipoprotein cholesterol ( P = .041 ) and greater improvements in functional status ( 6-minute walk [ P = .010 ] and VO2 peak [ P = .003 ] ) , high-density lipoprotein cholesterol ( P = .006 ) , and physical QOL scores ( P = .022 ) compared with those on st and ard protein and conventional diets . Conclusion : A 12-week HP diet result ed in moderate weight loss and reduced adiposity in a small sample of overweight and obese patients with HF that were associated with improvements in functional status , lipid profiles , glycemic control , and QOL . However , these preliminary findings must be confirmed in studies with more participants and long-term follow-up BACKGROUND Treatment-resistant major depressive disorder ( MDD ) is a complex condition , with very low remission rates . Physical exercise has been used , with some encouraging results , as an alternative therapy in other depressive disorders . This study assessed the impact on depression and functioning parameters of a moderate intensity exercise program , as an adjuvant to pharmacotherapy , in treatment-resistant MDD patients . METHODS 150 individuals with treatment-resistant MDD , defined as taking combined therapy in doses considered adequate for 9 - 15 months , without showing clinical remission , were initially screened . 33 were r and omized to one of two groups : usual pharmacotherapy ( N = 11 ) and usual pharmacotherapy plus aerobic exercise ( N = 22 ) . The exercise program consisted of home-based 30 - 45 min/day walks , 5 days/week , for 12 weeks , being 1 walk per week supervised . RESULTS The exercise group showed improvement of all depression and functioning parameters , as indicated by lower HAMD17 , BDI and CGI-S and higher GAF ( p < 0.05 ) at last observation compared both to baseline values and to control group . At the end of the study none of the participants in the control group showed response or remission , whilst in the exercise group 21 % of participants showed response and 26 % remission , although these differences were not statistically significant . CONCLUSION A 12 week , home-based exercise program of 30 - 45 min/day walks , 5 days/week , improved depression and functioning parameters in treatment-resistant MDD patients , and contributed to remission of 26 % of these patients . Moderate intensity exercise may be a helpful and effective adjuvant therapy for treatment-resistant MDD |
2,698 | 21,435,054 | Specific interventions require further research but there is emerging evidence that specialised intervention for people in the early phase of psychotic illness is achievable and possibly essential .
It is within the scope of practice of mental health nurse-practitioners to ensure patient and carer education and support , adherence to medication and other treatments , promotion of social inclusion and social connectedness . | AIMS AND OBJECTIVES The aim of this paper is to examine high-level evidence in early intervention in psychosis and scope the potential role of the mental health nurse-practitioner in the treatment of management of early psychosis .
BACKGROUND Psychosis imposes complex symptoms that impact on the individual and their social network , often result ing in long-term disability .
As specialised early intervention in psychosis is emerging , the nurse-practitioner role in mental health is also gaining momentum .
The background literature highlights several critical synergies between nurse-practitioners ' scope of practice and needs of patients with early psychosis .
RELEVANCE TO CLINICAL PRACTICE Mental health nurse-practitioners have the potential to provide specialist support to meet the needs of this complex group . | Abstract Objectives To evaluate the effects of integrated treatment for patients with a first episode of psychotic illness . Table 2 Clinical outcomes and user satisfaction of patients with a first episode of psychotic illness who received integrated treatment or st and ard treatment . Values are means ( SD ) unless stated otherwise 1 year follow-up ( n=419 ) 2 year follow-up ( n=369 ) Integrated treatment ( n=227 ) St and ard treatment ( n=192 ) Estimated mean difference ( 95 % CI ) P value of difference Integrated treatment ( n=205 ) St and ard treatment ( n=164 ) Estimated mean difference ( 95 % CI ) P value of difference Psychopathology * : Psychotic dimension 1.09 ( 1.27 ) 1.35 ( 1.39 ) -0.31 ( −0.55 to −0.07 ) 0.02 1.06 ( 1.26 ) 1.27 ( 1.40 ) -0.32 ( −0.58 to −0.06 ) 0.02 Negative dimension 1.68 ( 1.10 ) 2.02 ( 1.12 ) -0.36 ( −0.54 to −0.17 ) < 0.001 1.41 ( 1.15 ) 1.82 ( 1.23 -0.45 ( −0.67 to −0.22 < 0.001 Disorganised dimension 0.40 ( 0.59 ) 0.42 ( 0.56 ) -0.04 ( −0.14 to 0.07 ) 0.5 0.37 ( 0.56 ) 0.50 ( 0.73 ) -0.12 ( −0.25 to 0.00 ) 0.06 GAF , symptom 48.2 ( 14.9 ) 44.9 ( 16.0 ) 3.00 ( 0.37 to 5.63 ) 0.03 51.18 ( 15.01 ) 48.67 ( 15.92 ) 2.45 ( −0.32 to 5.22 ) 0.08 GAF , function 51.7 ( 15.1 ) 49.4 ( 14.6 ) 2.61 ( 0.11 to 5.15 ) 0.04 55.16 ( 15.15 ) 51.13 ( 15.92 ) 3.12 ( 0.37 to 5.88 ) 0.03 User satisfaction† 24.9 ( 4.5 ) 23.0 ( 7.2 ) 1.88 ( 0.73 to 3.02 ) 0.001 26.1 ( 3.7 ) 22.9 ( 5.2 ) 3.09 ( 2.10 to 4.04 ) < 0.001 GAF = global assessment of functioning . * Estimated mean differences are based on a repeated measurements model with treatment site , sex , substance misuse , diagnosis at baseline , and baseline values of the scale included as covariates ( see text for details ) . † Based on client satisfaction question naire score . Estimated mean differences calculated by analysis of variance with treatment site as covariate . Design R and omised clinical trial . Setting Copenhagen Hospital Corporation and Psychiatric Hospital Aarhus , Denmark . Participants 547 patients with first episode of schizophrenia spectrum disorder . Interventions Integrated treatment and st and ard treatment . The integrated treatment lasted for two years and consisted of assertive community treatment with programmes for family involvement and social skills training . St and ard treatment offered contact with a community mental health centre . Main outcome measures Psychotic and negative symptoms ( each scored from 0 to a maximum of 5 ) at one and two years ' follow-up . Results At one year 's follow-up , psychotic symptoms changed favourably to a mean of 1.09 ( st and ard deviation 1.27 ) with an estimated mean difference between groups of −0.31 ( 95 % confidence interval −0.55 to −0.07 , P = 0.02 ) in favour of integrated treatment . Negative symptoms changed favourably with an estimated difference between groups of −0.36 ( −0.54 to −0.17 , P < 0.001 ) in favour of integrated treatment . At two years ' follow-up the estimated mean difference between groups in psychotic symptoms was −0.32 ( −0.58 to −0.06 , P = 0.02 ) and in negative symptoms was −0.45 ( −0.67 to −0.22 , P < 0.001 ) , both in favour of integrated treatment . Patients who received integrated treatment had significantly less comorbid substance misuse , better adherence to treatment , and more satisfaction with treatment . Conclusion Integrated treatment improved clinical outcome and adherence to treatment . The improvement in clinical outcome was consistent at one year and two year follow-ups Some studies in first-episode schizophrenia correlate shorter duration of untreated psychosis ( DUP ) with better prognosis , suggesting that timing of treatment may be important . A three-site prospect i ve clinical trial in Norway and Denmark is underway to investigate the effect of the timing of treatment in first-episode psychosis . One health care sector ( Rogal and , Norway ) is experimental and has developed an early detection ( ED ) system to reduce DUP . Two other sectors ( Ullevål , Norway , and Roskilde , Denmark ) are comparison sectors and rely on existing detection and referral systems for first-episode cases . The study ultimately will compare early detected with usual detected patients . This paper describes the study 's major independent intervention variable , i.e. a comprehensive education and detection system to change DUP in first onset psychosis . System variables and first results from the four-year inclusion period ( 1997 - 2000 ) are described . It includes targeted information towards the general public , health professionals and schools , and ED teams to recruit appropriate patients into treatment as soon as possible . This plus easy access to psychiatric services via ED teams systematic ally changed referral patterns of first-episode schizophrenia . DUP was reduced by 1.5 years ( mean ) from before the time the ED system was instituted ( to 0.5 years ) . The ED strategies appear to be effective and to influence directly the community 's help-seeking behaviour Abstract Objective To evaluate the effectiveness of a service for early psychosis . Design R and omised controlled clinical trial . Setting Community mental health teams in one London borough . Participants 144 people aged 16 - 40 years presenting to mental health services for the first or second time with non-organic , non-affective psychosis . Interventions Assertive outreach with evidence based biopsychosocial interventions ( specialised care group ) and st and ard care ( control group ) delivered by community mental health teams . Primary outcome measures Rates of relapse and readmission to hospital . Results Compared with patients in the st and ard care group , those in the specialised care group were less likely to relapse ( odds ratio 0.46 , 95 % confidence interval 0.22 to 0.97 ) , were readmitted fewer times ( β 0.39 , 0.10 to 0.68 ) , and were less likely to drop out of the study ( odds ratio 0.35 , 0.15 to 0.81 ) . When rates were adjusted for sex , previous psychotic episode , and ethnicity , the difference in relapse was no longer significant ( odds ratio 0.55 , 0.24 to 1.26 ) ; only total number of readmissions ( β 0.36 , 0.04 to 0.66 ) and dropout rates ( β 0.28 , 0.12 to 0.73 ) remained significant . Conclusions Limited evidence shows that a team delivering specialised care for patients with early psychosis is superior to st and ard care for maintaining contact with professionals and for reducing readmissions to hospital . No firm conclusions can , however , be drawn owing to the modest sample size With the emerging global focus on early psychosis , indicated prevention in schizophrenia has increasingly become a focus of psychiatric research interests . It has been argued that CBT may have some advantages compared with antipsychotics regarding this issue . According to MEDLINE , EMBASE and Psycinfo two completed r and omised controlled trials ( RCTs ; PACE , Melbourne , Australia ; EDIE , Manchester , United Kingdom ) and one ongoing RCT with only preliminary results published so far ( FETZ , Cologne/Bonn , Germany ) on indicated prevention in schizophrenia including manualised and st and ardised psychological treatment can be identified . The aims of the present paper are to present and discuss the three approaches with regard to ( I ) inclusion , exclusion and exit criteria , ( II ) characteristics of interventions and ( III ) evaluations . All interventions use intake , exclusion and exit criteria , which have been evaluated in prospect i ve follow-along studies . The approaches are based on the general structure and principles of cognitive behavioural therapy which have been developed , applied and evaluated in a wide range of mental health problems . Despite several method ological limitations , the first evaluations indicate some effects with regard to three possible aims of early intervention : ( 1 ) improvement of present possible pre-psychotic symptoms , ( 2 ) prevention of social decline/stagnation and ( 3 ) prevention or delay of progression to psychosis . Even though the first results are promising , we conclude that several ethical issues have to be taken into consideration and further predictive and therapeutic research is needed to judge whether psychological intervention is a realistic option for the treatment of people at risk of psychosis Abstract . Background : Despite considerable interest in early intervention in psychosis , the evidence base for its effectiveness is sparse . We aim ed to evaluate a new service in South London , UK , Croydon Outreach and Assertive Support Team ( COAST ) using a r and omised controlled trial ( RCT ) during its first year . Method : Referrals were taken from local adult community mental health teams of those with documented first service contact in the last 5 years and a diagnosis of any functional psychosis . Those who consented ( N = 59 ) were r and omised to COAST or treatment as usual ( TAU ) . COAST offered a range of interventions , including optimum atypical medication , psychological interventions ( individual cognitive behavioural therapy and family intervention if appropriate ) and a range of vocational and welfare help according to need . Whole team training was used to be able to offer these kinds of interventions . Results : Outcomes were evaluated at baseline , 6 months and 9 months on a range of st and ardised clinical and social measures . Overall both COAST and TAU clients improved over time , but there were no significant improvements for COAST clients ; a lack of significant results in the time x treatment interaction . There was a trend for COAST carers ’ quality of life to increase . Bed days were also less in COAST , but not significantly so . Conclusions : The lack of clearly demonstrated improvements for COAST is consistent with the published literature so far . The fact that both groups improved in symptoms and functioning over the year suggests that while access to early intervention is helpful , community adult mental health teams should aim to offer high quality input at any stage of psychosis in order to meet client and carer needs BACKGROUND Little is known about the early phases of bipolar disorders ( BPAD ) and most of current knowledge derives from putative " high-risk " studies conducted in population s of bipolar off-spring ; such information may therefore be relevant only to a sub-group of at-risk subjects . METHODS Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania . The collected data was used mainly to generate hypotheses . RESULTS Before onset of a first episode of psychotic mania , patients go through a phase of change from previous mental state where they present mood symptoms , sleep disruption and general functional decline . These clinical manifestations are however likely to have low specificity . However , their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample , may be an indicator of impending first episode mania . LIMITATIONS This is a retrospective study , in a small sample of patients presenting with psychotic mania . Criteria identified need therefore to be vali date d in larger prospect i ve studies . CONCLUSIONS Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone . However , the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD could be a sign of impending first episode mania |
2,699 | 29,971,241 | Inhibiting rumen methanogenesis tended to associate positively with milk production efficiency , although the relationship was influenced by individual experiments .
Likewise , a positive relationship between methanogenesis inhibition and growth and fattening efficiency depended on the inclusion and weighting of individual experiments .
Inhibiting rumen methanogenesis negatively associated with dry matter intake . | Methane ( CH4 ) formed in the rumen and released to the atmosphere constitutes an energy inefficiency to ruminant production .
Redirecting energy in CH4 to fermentation products with a nutritional value to the host animal could increase ruminant productivity and stimulate the adoption of CH4-suppressing strategies .
The hypothesis of this research was that inhibiting CH4 formation in the rumen is associated with greater ruminant productivity .
The primary objective of this meta- analysis was to evaluate how inhibiting rumen methanogenesis relates with the efficiencies of milk production and growth and fattening . | The objective was to evaluate whether long-term addition of 3-nitrooxypropanol ( NOP ) to a beef cattle diet results in a sustained reduction in enteric CH4 emissions in beef cattle . Eight ruminally cannulated heifers ( 637 ± 16.2 kg BW ) were used in a completely r and omized design with 2 treatments : Control ( 0 g/d of NOP ) and NOP ( 2 g/d of NOP ) . Treatments were mixed by h and into the total mixed ration ( 60 % forage , DM basis ) at feeding time . Feed offered was restricted to 65 % of ad libitum DMI ( slightly over maintenance energy intake ) and provided once per day . The duration of the experiment was 146 d , including an initial 18-d covariate period without NOP use ; a 112-d treatment period with NOP addition to the diet , divided into four 28-d time intervals ( d 1 to 28 , 29 to 56 , 57 to 84 , and 85 to 112 ) ; and a final 16-d recovery period without NOP use . During the covariate period and at the end of each interval and the end of the recovery period , CH4 was measured for 3 d using whole animal metabolic chambers . The concentration of VFA was measured in rumen fluid sample s collected 0 , 3 , and 6 h after feeding , and the microbial population was evaluated using rumen sample s collected 3 h after feeding on d 12 of the covariate period , d 22 of each interval within the treatment period , and d 8 of the recovery period . Average DMI for the experiment was 7.04 ± 0.27 kg . Methane emissions were reduced by 59.2 % when NOP was used ( 9.16 vs. 22.46 g/kg DMI ; P < 0.01 ) . Total VFA concentrations were not affected ( P = 0.12 ) ; however , molar proportion of acetate was reduced and that for propionate increased when NOP was added ( P < 0.01 ) , which reduced the acetate to propionate ratio ( 3.0 vs. 4.0 ; P < 0.01 ) . The total copy number of the 16S rRNA gene of total bacteria was not affected ( P = 0.50 ) by NOP , but the copy number of the 16S rRNA gene of methanogens was reduced ( P < 0.01 ) and the copy number of the 18S rRNA gene of protozoa was increased ( P = 0.03 ) . The residual effect of NOP for most of the variables studied was not observed or was minimal during the recovery period . These results demonstrated that the addition of NOP to a diet for beef cattle caused a sustained decrease of methanogenesis , with no sign of adaptation , and that these effects were reversed once NOP addition was Significance Methane from enteric fermentation in the ruminant digestive system is a major contributor to anthropogenic greenhouse gas emissions in the United States and worldwide . Methane is also a net loss of feed energy to the animal . This study was undertaken to investigate the effect of a methane inhibitor on enteric methane emissions from lactating dairy cows . The experiment demonstrated that , under industry-relevant conditions , the inhibitor persistently decreased by 30 % enteric methane emissions , without negatively affecting animal productivity . The spared methane energy was partially used for tissue synthesis , which led to a greater body weight gain by the inhibitor-treated cows . If adopted , this mitigation practice could lead to a substantial reduction of greenhouse gas emissions from the ruminant livestock sector . A quarter of all anthropogenic methane emissions in the United States are from enteric fermentation , primarily from ruminant livestock . This study was undertaken to test the effect of a methane inhibitor , 3-nitrooxypropanol ( 3NOP ) , on enteric methane emission in lactating Holstein cows . An experiment was conducted using 48 cows in a r and omized block design with a 2-wk covariate period and a 12-wk data collection period . Feed intake , milk production , and fiber digestibility were not affected by the inhibitor . Milk protein and lactose yields were increased by 3NOP . Rumen methane emission was linearly decreased by 3NOP , averaging about 30 % lower than the control . Methane emission per unit of feed dry matter intake or per unit of energy-corrected milk were also about 30 % less for the 3NOP-treated cows . On average , the body weight gain of 3NOP-treated cows was 80 % greater than control cows during the 12-wk experiment . The experiment demonstrated that the methane inhibitor 3NOP , applied at 40 to 80 mg/kg feed dry matter , decreased methane emissions from high-producing dairy cows by 30 % and increased body weight gain without negatively affecting feed intake or milk production and composition . The inhibitory effect persisted over 12 wk of treatment , thus offering an effective methane mitigation practice for the livestock industries This study evaluated if 3-nitrooxypropanol reduces enteric methane ( CH4 ) emissions when added to the diet of beef cattle . The effects of 3-nitrooxypropanol on related variables including diet digestibility , ruminal fermentation , and ruminal microorganisms were also investigated . Eight ruminally cannulated Angus heifers ( 549 ± 64.3 kg [ mean BW ± SD ] ) were fed a high forage diet ( background ing diet ) supplemented with 4 levels of 3-nitrooxypropanol ( 0 , 0.75 , 2.25 and 4.50 mg/kg BW ) . The experiment was design ed as a duplicated 4 × 4 Latin square with 2 groups of heifers and four 28-d periods . Methane emissions were measured during 3 consecutive days using metabolic chambers . Up to a 5.8 % reduction in ad libitum DMI was observed when 2.5 mg/kg BW of 3-nitrooxypropanol was fed ( P = 0.03 ) . Increasing level of 3-nitrooxypropanol linearly ( P < 0.001 ) reduced CH4 , with 33 % less CH4 ( corrected for DMI ) at the highest level of supplementation compared with the control . Feed energy lost as CH4 was also reduced when 3-nitrooxypropanol was supplemented ( P < 0.001 ) . Molar proportion of acetate was reduced ( P < 0.001 ) and that for propionate increased ( P < 0.001 ) with increasing dose of 3-nitrooxypropanol , which in turn led to a reduction in the acetate to propionate ratio ( P < 0.001 ) . Total copy numbers of 16S ribosomal RNA ( rRNA ) genes for bacteria , methanogens , and 18S rRNA genes for protozoa in ruminal contents were not affected by 3-nitrooxypropanol supplementation ( P ≥ 0.31 ) . There was no effect of 3-nitrooxypropanol on DM ( P = 0.1 ) digestibility in the total tract . The use of 4.5 mg/kg BW of 3-nitrooxypropanol in beef cattle consuming a background ing diet was effective in reducing enteric CH4 emissions without negatively affecting diet digestibility It has been suggested that the rumen microbiome and rumen function might be disrupted if methane production in the rumen is decreased . Furthermore concerns have been voiced that geography and management might influence the underlying microbial population and hence the response of the rumen to mitigation strategies . Here we report the effect of the dietary additives : linseed oil and nitrate on methane emissions , rumen fermentation , and the rumen microbiome in two experiments from New Zeal and ( Dairy 1 ) and the UK ( Dairy 2 ) . Dairy 1 was a r and omized block design with 18 multiparous lactating cows . Dairy 2 was a complete replicated 3 x 3 Latin Square using 6 rumen cannulated , lactating dairy cows . Treatments consisted of a control total mixed ration ( TMR ) , supplementation with linseed oil ( 4 % of feed DM ) and supplementation with nitrate ( 2 % of feed DM ) in both experiments . Methane emissions were measured in open circuit respiration chambers and rumen sample s were analyzed for rumen fermentation parameters and microbial population structure using qPCR and next generation sequencing ( NGS ) . Supplementation with nitrate , but not linseed oil , decreased methane yield ( g/kg DMI ; P<0.02 ) and increased hydrogen ( P<0.03 ) emissions in both experiments . Furthermore , the effect of nitrate on gaseous emissions was accompanied by an increased rumen acetate to propionate ratio and consistent changes in the rumen microbial population s including a decreased abundance of the main genus Prevotella and a decrease in archaeal mcrA ( log10 copies/ g rumen DM content ) . These results demonstrate that methane emissions can be significantly decreased with nitrate supplementation with only minor , but consistent , effects on the rumen microbial population and its function , with no evidence that the response to dietary additives differed due to geography and different underlying microbial population The study objective was to evaluate the effects of sustained reduction of enteric methane ( CH ) emissions with dietary supplementation of the inhibitor 3-nitrooxypropanol ( NOP ) on growth rate and feed conversion efficiency of growing and finishing beef cattle . Eighty-four crossbred steers were used in a 238-d feeding study and fed a background ing diet for the first 105 d ( background ing phase ) and transition diets for 28 d followed by a finishing diet for 105 d ( finishing phase ) with 3 doses of NOP ( 0 , 100 , and 200 mg/kg DM ) . The experiment was a completely r and omized design using 21 pens ( 4 cattle/pen ) with 7 pens per treatment . When cattle were fed the background ing diet , pen DMI was reduced ( < 0.01 ) whereas G : F tended to improve ( = 0.06 ) with increasing dose of NOP supplementation . During the finishing phase , DMI ( = 0.06 ) and ADG ( = 0.07 ) tended to decrease with increasing dose of NOP supplementation . Although both levels of NOP were effective in reducing CH emissions from the background ing diet ( < 0.01 ) , only NOP supplemented at the highest dose was effective in reducing total CH emissions from the finishing diet ( < 0.01 ) . Methane yield ( g/kg DMI ) was reduced whereas hydrogen emissions were increased at the highest dose of NOP supplementation with both background ing and finishing diets ( < 0.01 ) . Overall , these results demonstrate efficacy of NOP in reducing enteric CH emissions from cattle fed background ing and finishing diets , and these effects were negated once NOP supplementation was discontinued Strategies to manage metabolic hydrogen ( [ H ] ) in the rumen should be considered when reducing ruminant methane ( CH4 ) emissions . However , little is known about the use of dietary treatments to stimulate rumen microorganisms capable of capturing the [ H ] available when CH4 is inhibited in vivo . The effects of the phenolic compound phloroglucinol on CH4 production , [ H ] flows and subsequent responses in rumen fermentation and microbial community composition when methanogenesis is inhibited were investigated in cattle . Eight rumen fistulated Brahman steers were r and omly allocated in two groups receiving chloroform as an antimethanogenic compound for 21 days . Following that period one group received chloroform + phloroglucinol for another 16 days , whilst the other group received only chloroform during the same period . The chloroform treatment result ed in a decrease in CH4 production and an increase in H2 expelled with a shift in rumen fermentation toward higher levels of propionate and formate and lower levels of acetate at day 21 of treatment . Bacterial operational taxonomic units ( OTUs ) assigned to Prevotella were promoted whilst Archaea and Synergistetes OTUs were decreased with the chloroform treatment as expected . The shift toward formate coincided with increases in Ruminococcus flavefaciens , Butyrivibrio fibrisolvens , and Methanobrevibacter ruminantium species . The addition of chloroform + phloroglucinol in the rumen result ed in a decrease of H2 expelled ( g ) per kg of DMI and moles of H2 expelled per mol of CH4 decreased compared with the chloroform only treated animals . A shift toward acetate and a decrease in formate were observed for the chloroform + phloroglucinol-treated animals at day 37 . These changes in the rumen fermentation profile were accompanied by a relative increase of OTUs assigned to Coprococcus spp . , which could suggest this genus is a significant contributor to the metabolism of this phenolic compound in the rumen . This study demonstrates for the first time in vivo that under methanogenesis inhibition , H2 gas accumulation can be decreased by redirecting [ H ] toward alternative sinks through the nutritional stimulation of specific microbial groups . This results in the generation of metabolites of value for the host while also helping to maintain a low H2 partial pressure in the methane-inhibited rumen Volatile fatty acid concentrations ( [ VFA ] , mM ) have long been used to assess the effect of dietary treatments on ruminal fermentation in vivo . However , discrepancies in statistical results between [ VFA ] and VFA pool size ( VFAmol ) possibly related to ruminal digesta liquid amount ( LIQ , kg ) indicate potential issues with the use of [ VFA ] . We investigated relationships among [ VFA ] , VFAmol , and LIQ measured 2 h postfeeding using individual lactating cow data ( n=175 ) from 7 separate feeding studies . Regression analyses were performed using mixed models with " study " as a discrete r and om variable . The mean across studies and average range of values within studies , respectively , were 151 and 75 for [ VFA ] , 11.2 and 9.8 for VFAmol , 73.3 and 41.0 for LIQ , and 289 and 83 mmol/kg for rumen fluid osmolality . Liquid amount changed with VFAmol ( 3.76 VFAmol+31.2 ; average within- study R2=0.69 ) , but the relationship was weak between [ VFA ] and LIQ ( 0.524 LIQ+112.8 ; average within- study R2=0.12 ) . The relationship between LIQ and VFAmol was likely a function of the osmotic gradient between rumen liquid and blood . The VFA are a major ruminal solute ; VFAmol amounts can affect water flux in the rumen as similar tonicities of rumen fluid and blood are maintained . This also has a damping effect on ruminal solute concentration , creating the weak relationship between [ VFA ] and LIQ . Within studies , similar [ VFA ] were found in LIQ differing by 30 kg or more . The difference between minimum and maximum LIQ within cow within study was 12.7 kg ( st and ard deviation=7.1 ) , so inclusion of " cow " in analyses did not correct for the variation in LIQ . To allow valid comparisons of experimental treatments , responses must be on an equivalent basis ; concentrations in different LIQ are not on an equivalent basis and so are not valid to use for comparing treatment effects . The [ VFA ] changed with VFAmol ( 5.80 VFAmol+86.3 ; average within- study R2=0.56 ) . However , the ratio of [ VFA ] to VFAmol ranged from 9.0 to 24.1 as a function of 1,000/LIQ ; this reflects the inherent calculated relationship among the variables . The varying relationship of [ VFA ] to VFAmol further indicates that [ VFA ] is not an appropriate measure to evaluate the progress or effect of treatments on ruminal fermentation . Predictions of LIQ and VFAmol using cow and ruminal measures were insufficiently precise to be used in research . Previously drawn conclusions based on [ VFA ] need to be reevaluated , and alternate evaluations for in vivo ruminal fermentation are needed Nitrate can be a source of NPN for microbial growth at the same time that it reduces ruminal methane production . The objective of this study was to evaluate the effects of 2 encapsulated nitrate products used as urea replacers on blood and rumen constituents , methane emission , and growth performance of lambs . Eighteen Santa Inês male lambs ( 27 ± 4.9 kg ) were individually allotted to indoor pens and assigned to a r and omized complete block design with 6 blocks and 3 dietary treatments : control ( CTL ) = 1.5 % urea , ENP = 4.51 % encapsulated nitrate product ( 60.83 % NO3(- ) in the product DM ) , and ENP+CNSL = 4.51 % ENP containing cashew nut shell liquid ( 60.83 % NO3(- ) and 2.96 % cashew nut shell liquid [ CNSL ] in the product DM ) . Diets were isonitrogenous with 60:40 concentrate : forage ( Tifton 85 hay ) ratio . The experiment lasted for 92 d and consisted of 28 d for adaptation ( a weekly 33 % stepwise replacement of CTL concentrate by nitrate-containing concentrates ) and 64 d for data collection . The ENP and ENP+CNSL showed greater ( P < 0.05 ) red blood cell counts than CTL . Blood methemoglobin ( MetHb ) did not differ ( P > 0.05 ) among treatments , with mean values within normal range and remaining below 1.1 % of total hemoglobin . There was an increase ( P < 0.05 ) in total short-chain fatty acids concentration at 3 h postfeeding for ENP , with an additional increase ( P < 0.05 ) observed for ENP+CNSL . No treatment effects ( P > 0.05 ) were observed on acetate to propionate ratio . Methane production ( L/kg DMI ) was reduced ( P < 0.05 ) with nitrate inclusion , recording 28.6 , 19.1 , and 19.5 L/kg DMI for CTL , ENP , and ENP+CNSL , respectively . Addition of CNSL did not result ( P > 0.05 ) in further reduction of methane production when compared with ENP . Final BW , DMI , ADG , and feed efficiency were similar ( P > 0.05 ) among treatments . Values for DMI were 1.11 , 1.03 , and 1.04 kg/d and for ADG were 174 , 154 , and 158 g for CTL , ENP , and ENP+CNSL , respectively . In conclusion , encapsulated nitrate products showed no risks of toxicity based on MetHb formation . The products persistently reduced methane production without affecting performance . Inclusion of cashew nut shell liquid in the product formulation had no additional benefits on methane mitigation The objective of this study was to determine the effect of dietary nitrate on methane emission and rumen fermentation parameters in Nellore × Guzera ( Bos indicus ) beef cattle fed a sugarcane based diet . The experiment was conducted with 16 steers weighing 283 ± 49 kg ( mean ± SD ) , 6 rumen cannulated and 10 intact steers , in a cross-over design . The animals were blocked according to BW and presence or absence of rumen cannula and r and omly allocated to either the nitrate diet ( 22 g nitrate/kg DM ) or the control diet made isonitrogenous by the addition of urea . The diets consisted of freshly chopped sugarcane and concentrate ( 60:40 on DM basis ) , fed as a mixed ration . A 16-d adaptation period was used to allow the rumen microbes to adapt to dietary nitrate . Methane emission was measured using the sulfur hexafluoride tracer technique . Dry matter intake ( P = 0.09 ) tended to be less when nitrate was present in the diet compared with the control , 6.60 and 7.05 kg/d DMI , respectively . The daily methane production was reduced ( P < 0.01 ) by 32 % when steers were fed the nitrate diet ( 85 g/d ) compared with the urea diet ( 125 g/d ) . Methane emission per kilogram DMI was 27 % less ( P < 0.01 ) on the nitrate diet ( 13.3 g methane/kg DMI ) than on the control diet ( 18.2 g methane/kg DMI ) . Methane losses as a fraction of gross energy intake ( GEI ) were less ( P < 0.01 ) on the nitrate diet ( 4.2 % of GEI ) than on the control diet ( 5.9 % of GEI ) . Nitrate mitigated enteric methane production by 87 % of the theoretical potential . The rumen fluid ammonia-nitrogen ( NH(3)-N ( ) ) concentration was significantly greater ( P < 0.05 ) for the nitrate diet . The total concentration of VFA was not affected ( P = 0.61 ) by nitrate in the diet , while the proportion of acetic acid tended to be greater ( P = 0.09 ) , propionic acid less ( P = 0.06 ) and acetate/propionate ratio tended to be greater ( P = 0.06 ) for the nitrate diet . Dietary nitrate reduced enteric methane emission in beef cattle fed sugarcane based diet Feeding nitrate to dairy cows may lower ruminal methane production by competing for reducing equivalents with methanogenesis . Twenty lactating Holstein-Friesian dairy cows ( 33.2±6.0 kg of milk/d ; 104±58 d in milk at the start of the experiment ) were fed a total mixed ration ( corn silage-based ; forage to concentrate ratio 66:34 ) , containing either a dietary urea or a dietary nitrate source [ 21 g of nitrate/kg of dry matter ( DM ) ] during 4 successive 24-d periods , to assess the methane-mitigating potential of dietary nitrate and its persistency . The study was conducted as paired comparisons in a r and omized design with repeated measurements . Cows were blocked by parity , lactation stage , and milk production at the start of the experiment . A 4-wk adaptation period allowed the rumen microbes to adapt to dietary urea and nitrate . Diets were isoenergetic and isonitrogenous . Methane production , energy balance , and diet digestibility were measured in open-circuit indirect calorimetry chambers . Cows were limit-fed during measurements . Nitrate persistently decreased methane production by 16 % , whether expressed in grams per day , grams per kilogram of dry matter intake ( DMI ) , or as percentage of gross energy intake , which was sustained for the full experimental period ( mean 368 vs. 310±12.5 g/d ; 19.4 vs. 16.2±0.47 g/kg of DMI ; 5.9 vs.4.9±0.15 % of gross energy intake for urea vs. nitrate , respectively ) . This decrease was smaller than the stoichiometrical methane mitigation potential of nitrate ( full potential=28 % methane reduction ) . The decreased energy loss from methane result ed in an improved conversion of dietary energy intake into metabolizable energy ( 57.3 vs. 58.6±0.70 % , urea vs. nitrate , respectively ) . Despite this , milk energy output or energy retention was not affected by dietary nitrate . Nitrate did not affect milk yield or apparent digestibility of crude fat , neutral detergent fiber , and starch . Milk protein content ( 3.21 vs. 3.05±0.058 % , urea vs. nitrate respectively ) but not protein yield was lower for dietary nitrate . Hydrogen production between morning and afternoon milking was measured during the last experimental period . Cows fed nitrate emitted more hydrogen . Cows fed nitrate displayed higher blood methemoglobin levels ( 0.5 vs. 4.0±1.07 % of hemoglobin , urea vs. nitrate respectively ) and lower hemoglobin levels ( 7.1 vs. 6.3±0.11 mmol/L , urea vs. nitrate respectively ) . Dietary nitrate persistently decreased methane production from lactating dairy cows fed restricted amounts of feed , but the reduction in energy losses did not improve milk production or energy balance |
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